DNB

Pediatrics
NOTES
BASED ON

1
 INDEX

TOPIC PAGE
1. ACUTELY ILL CHILD 3
2. ADOLESCENCE 30
3. ALLERGY 33
4. BEHAVIOUR 42
5. CNS 53
6. CVS 104
7. ENDOCRINE 118
8. ENVIRONMENT 127
9. EYE, EAR, SKIN, RHEUMATOLOGY 131
10. METABOLIC 162
11. GENETIC 167
12. GIT 174
13. GROWTH 234
14. HEMATOLOGY 245
15. INFECTIOUS DISEASE 272
16. IMMUNOLOGY 321
17. NEPHROLOGY 330
18. ONCOLOGY 348
19. PULMONOLOGY 357
20. UROLOGY 413
21. NUTITION 417
22. FLUID AND ELECTROLYTES 435
23. MISCELLANEOUS 451
1.Developmental anomalies of lung
2.Cystic adenomatoid malformation
3.Epistaxis
4.Pulmonary function tests
5.Diaphragmatic hernia
6.PEDIATRIC INTERSTITIAL
LUNG DISEASES
7.Genetic Counselling
8.Cytogenetics
9.Dialysis/ renal replacement therapy
10.ADHD
11.PALS
12.HIGH RISK PREGNANCY

2
 ACUTELY ILL CHILD

1. BRAIN DEATH:
2. Shock:
3. INTERNATIONAL CONSENSUS DEFINITIONS FOR PEDIATRIC SEPSIS
4. RESPIRATORY FAILURE:
5. DROWNING:
6. BURNS:
7. Electrical burns:
8. Cold injury:
9. PEDIATRIC PAIN MANAGEMENT:
10. Heat injuries
11. RSI
12. Outcome measurement

3
1. BRAIN DEATH:
Brain death is the irreversible cessation of all functions of the entire brain, including the brainstem.
It is also known as the determination of death using neurologic criteria.
Clinical Manifestations:
Brain death is primarily a clinical diagnosis.
The 3 key components of clinical brain death diagnosis are demonstrations of
Irreversible coma/unresponsiveness
Absence of brainstem reflexes and Apnea.
Irreversible coma/unresponsiveness:
Before a determination of brain death may be made, it is of utmost importance that the cause of the
coma be determined through the use of historical, radiologic, and laboratory data to rule out a
reversible condition.
Potentially reversible causes of coma include metabolic disorders, toxins, sedative drugs, paralytic
agents, hypothermia, hypoxia, hypotension/shock, hypoglycemia/hyperglycemia,
hyponatremia/hypernatremia, hypercalcemia, hypermagnesemia, nonconvulsive status epilepticus,
hypothyroidism, hypocortisolism, hypercarbia, liver or renal failure, sepsis, meningitis, encephalitis,
SAH, and surgically remediable brainstem lesions.
Some complex spinal movements may be particularly pronounced following removal of the
ventilator like Lazarus sign, which consists of extension of the upper extremities followed by flexion
of the arms with the hands reaching to midsternal level.
The apnea test assesses the function of the medulla in driving ventilation.
 It is performed by first ensuring the adequacy of hemodynamics and temperature and the
absence of apnea-producing drug effects or significant metabolic derangements.
 The test is performed by first preoxygenating the patient with 100% oxygen for
approximately 10 min and adjusting ventilation to achieve a Pco2 of about 40 mm Hg.
 A baseline blood gas result documents the starting values. During the test, oxygenation must
be maintained. Throughout the test, the child is assessed for breathing efforts through
observation and auscultation.
 A blood gas sample is obtained approximately 10 min into the test and every 5 min thereafter
until the target Pco2 is surpassed; ventilatory support is resumed at that time.
 If at any point during the test the patient becomes hypoxic or hypotensive, the test is aborted
and ventilatory support is resumed.
 Absence of respiratory efforts with a Pco2 > 60 mm Hg or more that 20 mm Hg above an
elevated baseline value is consistent with brain death.

BRAINSTEM REFLEX TESTING TO DETERMINE BRAIN DEATH (total 5)

BRAINSTEM HOW TO PERFORM THE What happens What happens in brain
REFLEX EXAM normally death
Pupillary light Shine a light into the eyes Constriction of pupils on Midposition (4-6 mm) or
reflex while closely observing stimulation with light fully dilated pupils that are
4
BRAINSTEM HOW TO PERFORM THE What happens What happens in brain
REFLEX EXAM normally death
pupillary size not reactive to light are
consistent with brain death.
Pinpoint pupils, even if
nonreactive, are not
consistent with brain death.
Manually rotate the patient's In an intact patient, the
head side to side and closely eyes remain fixed on a
In a result consistent with
Oculocephalic watch the position of the distant spot, as if
brain death, the eyes move
reflex (doll's eyes. maintaining eye contact
in concert with the patient's
eyes reflex) (Should not be performed in a with that spot.
head movement.
patient with a cervical spine
injury.)
In the intact patient, the
In a result consistent with
Touch the patient's cornea touch results in eyelid
Corneal reflex brain death, there is no
with a cotton swab. closure, and the eye may
response.
rotate upward.
Irrigate the tympanic Cold water same side
Absence of eye movement
Oculovestibular membrane with iced water or deviation of eye
is consistent with brain
reflex saline and look for eye
death.
movement.
Touch the posterior pharynx cough is initiated
with a tongue depressor or a immediately
cotton-tipped swab to Absence of both a cough
Gag and cough
stimulate a gag. Advance a and a gag is consistent with
reflex
suction catheter through the brain death.
endotracheal tube to the
carina to stimulate a cough.

Observation Periods:
To establish the diagnosis of brain death, the findings must remain consistent over a period of
observation.
For children aged 7 days to 2 mo, 2 examinations separated by at least 48 hr are recommended.
For children aged 2 mo to 1 yr, 2 examinations separated by at least 24 hr are recommended.
For children older than 1 yr the recommendation is a 12-hr observation period between exams.
Confirmatory Tests:
The 2 most commonly used confirmatory tests are EEG and studies to confirm the absence of CBF,
such as nuclear medicine cerebral flow scans.
Supportive Care:

Following a diagnosis of brain death, supportive care may continue for hours to days as the family
makes decisions about potential organ donation and comes to terms with the diagnosis.

2. Shock:

Def: Shock is an acute syndrome characterized by the body's inability to deliver adequate oxygen to
meet the metabolic demands of vital organs and tissues.

Initially, shock may be well compensated, but it may rapidly progress to an uncompensated state
5
requiring more aggressive therapies to achieve clinical recovery or improvement. Untreated shock
causes irreversible tissue and organ injury (i.e., irreversible shock) and, ultimately, death.

TYPES OF SHOCK
DISTRIBUTI OBSTRUCTIV
HYPOVOLEMIC CARDIOGENIC SEPTIC
VE E
Encompasses
multiple forms of
shock Decreased
Hypovolemic: third cardiac output
Abnormalities spacing of fluids into secondary to
Decreased preload of vasomotor the extracellular, direct
Cardiac pump failure interstitial space
secondary to tone due to impediment to
secondary to poor
internal or external loss of venous Distributive: early right or left
myocardial function
losses and arterial shock with decreased heart outflow or
capacitance afterload restriction of all
Cardiogenic: cardiac
depression of chambers
myocardial function
by endotoxins
POTENTIAL ETIOLOGIES
Anaphylaxis Tension
Neurologic: pneumothorax
Blood loss: Congenital heart
disease loss of Pericardial
hemorrhage; Bacterial
sympathetic tamponade
Plasma loss: Cardiomyopathies: vascular Viral
infectious or Pulmonary
burns, nephrotic tone Fungal
acquired, dilated embolism
syndrome; secondary (immunocompromised
or restrictive Anterior
Water/electrolyte to spinal patients are at
Ischemia mediastinal
loss: vomiting, cord or increased risk)
masses
diarrhea Arrhythmias brainstem
injury Critical
coarctation of
Drugs the aorta

Algorithm for decompensated shock:

6
CLINICAL FEATURES:

SIGNS OF DECREASED PERFUSION

ORGAN SYSTEM ↓↓↓ PERFUSION

Central nervous system Agitated/confused, stuporous, coma
Respiration ↑↑ Ventilation
Metabolism Uncompensated metabolic acidemia
Gut Ileus

Kidney Oliguria/anuria

Skin Mottled, cyanotic, cold extremities

Cardiovascular system ↑↑ Heart rate ↓ Blood pressure, central pulses only

7
Pathophysiology of septic shock:

8
INTERNATIONAL CONSENSUS DEFINITIONS FOR PEDIATRIC SEPSIS
Suspected or proven infection or a clinical syndrome associated with high
Infection
probability of infection
2 out of 4 criteria, 1 of which must be abnormal temperature or abnormal
leukocyte count:
1 Core temperature >38.50C or <360C (rectal, bladder, oral, or central
catheter)
2 Tachycardia:
Mean heart rate >2 SD above normal for age in absence of
\ external stimuli, chronic drugs or painful stimuli
OR
Systemic inflammatory Unexplained persistent elevation over 0.5-4 hr
response syndrome OR
(SIRS)
In children <1 year old, persistent bradycardia over 0.5 hour
(mean heart rate <10th percentile for age in absence of vagal
stimuli, β-blocker drugs, or congenital heart disease)
3 Respiratory rate >2 SD above normal for age or acute need for
mechanical ventilation not related to neuromuscular disease or general
anesthesia
4 Leukocyte count elevated or depressed for age (not secondary to
chemotherapy) or >10% immature neutrophils
Sepsis SIRS plus a suspected or proven infection
Sepsis plus 1 of the following:
1 Cardiovascular organ dysfunction, defined as:
• Despite >40 mL/kg of isotonic intravenous fluid in 1 hour:
Hypotension <5th percentile for age or systolic blood pressure <2
SD below normal for age
OR
• Need for vasoactive drug to maintain blood pressure
OR
• 2 of the following:
Severe sepsis • Unexplained metabolic acidosis: base deficit > 5 mEq/L
• Increased arterial lactate: >2 times upper limit of normal
• Oliguria: urine output <0.5 mL/kg/hr
• Prolonged capillary refill: >5 sec
• Core to peripheral temperature gap >30C
2 Acute respiratory distress syndrome (ARDS) as defined by the
presence of a Pao2/Fio2 ratio ≤300 mm Hg, bilateral infiltrates on chest
radiograph, and no evidence of left heart failure
OR
9
 Sepsis plus 2 or more organ dysfunctions (respiratory, renal,
neurologic, hematologic, or hepatic)
Septic shock Sepsis plus cardiovascular organ dysfunction as defined above
Multiple organ
Presence of altered organ function such that homeostasis cannot be
dysfunction syndrome
maintained without medical intervention
(MODS)

TREATMENT: GOAL-DIRECTED THERAPY OF ORGAN SYSTEM DYSFUNCTION IN

SHOCK (6)

SYSTEM DISORDERS THERAPIES

Acute respiratory distress
Oxygen
syndrome
Early endotracheal intubation and mechanical
Respiratory muscle fatigue
ventilation
Respiratory
Positive end-expiratory pressure (PEEP)
Permissive hypercapnia
Central apnea
High-frequency ventilation
Extracorporeal membrane oxygenation (ECMO)
Judicious fluid resuscitation
Low-dose dopamine
Prerenal failure
Establishment of normal urine output and blood
Renal Renal failure pressure for age
Furosemide (Lasix)
Dialysis, ultrafiltration, hemofiltration
Vitamin K
Coagulopathy (disseminated
Fresh frozen plasma
intravascular coagulation)
Hematologic Platelets
Heparinization
Thrombosis
Activated protein C
Histamine H2 receptor–blocking agents or proton
Stress ulcers pump inhibitors
Gastrointestinal Nasogastric tube
Ileus
Early enteral feedings
Bacterial translocation

Adrenal insufficiency, Stress-dose steroids in patients previously given

Endocrine primary or secondary to steroids
chronic steroid therapy Physiologic dose for presumed primary
10
SYSTEM DISORDERS THERAPIES
insufficiency in sepsis
Treatment of hypovolemia (fluids), poor cardiac
function (fluids, inotropic agents)
Metabolic Metabolic acidosis
Low-dose (0.5-2 mEq/kg) sodium bicarbonate if
the patient is not showing response, pH < 7.1,
and ventilation (CO2 elimination) is adequate

CARDIOVASCULAR DRUG TREATMENT OF SHOCK

DOSING
DRUG EFFECT(S) COMMENT(S)
RANGE
3-20 ↑ Risk of arrhythmias at high
↑ Cardiac contractility
mcg/kg/min doses
Dopamine Significant peripheral
vasoconstriction at >10
mcg/kg/min
↑ Heart rate and ↑ cardiac May ↓ renal perfusion at high
contractility 0.05-3.0 doses
Epinephrine
mcg/kg/min ↑ Myocardial O2 consumption
Potent vasoconstrictor
Risk of arrhythmia at high doses
↑ Cardiac contractility 1-10
Dobutamine —
Peripheral vasodilator mcg/kg/min
↑ Blood pressure secondary to ↑
Potent vasoconstriction
0.05-1.5 systemic vascular resistance
Norepinephrine
No significant effect on cardiac mcg/kg/min
↑ Left ventricular afterload
contractility
0.5-2.0 Can cause sudden hypertension
Phenylephrine Potent vasoconstriction
mcg/kg/min ↑ O2 consumption

VASODILATORS/AFTERLOAD REDUCERS
DOSING
DRUG EFFECT(S) COMMENT(S)
RANGE
Rapid effect
0.5-4.0
Nitroprusside Vasodilator (mainly arterial) Risk of cyanide toxicity with
mcg/kg/min
prolonged use (>96 hours)

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 DOSING
DRUG EFFECT(S) COMMENT(S)
RANGE
Rapid effect
1.0-20
Nitroglycerin Vasodilator (mainly venous) Risk of increased intracranial
mcg/kg/min
pressure
Vasodilator Can lead to hypotension
Prostaglandin Maintains an open ductus 0.01-0.2
E1 arteriosus in the newborn with mcg/kg/min
Risk of apnea
ductal-dependent congenital heart
disease
Phosphodiesterase
Load 50
inhibitor—slows cyclic
Milrinone Increased cardiac contractility mcg/kg over 15
adenosine monophosphate
min
breakdown
Improves cardiac diastolic 0.5-1
function mcg/kg/min
Peripheral vasodilatation

ALGORITHM FOR SHOCK:

12
13
3. RESPIRATORY FAILURE:

Respiratory failure occurs when oxygenation and ventilation are insufficient to meet the metabolic
demands of the body.

Respiratory failure may result from an abnormality in lung disease or respiratory pump failure

Lung disease Respiratory pump failure

1. Central airway obstruction 1. Chest wall deformity
Croup, epiglottitis, FB Flial chest, kyphoscoliosis
2. Peripheral airway obstruction 2. Brainstem
Bronchiolitis, Bronchial asthma Trauma, sleep apnea, poisoning
3. Diffuse alveolar damage 3. Spinal cord - SMA, trauma
Pneumonia, ILD, aspiration 4. Neuromuscular- GBS, myasthenia,

SIMPLIFIED CONSENSUS DEFINITION OF ACUTE LUNG INJURY

• Acute onset (<7 days)
• Severe hypoxemia (Pao2/Fio2 < 300 for acute lung injury, or <200 for acute respiratory distress
syndrome)
• Diffuse bilateral pulmonary infiltrates on frontal radiograph consistent with pulmonary edema
(these can be patchy and asymmetric, and pleural effusions can be present)
• Absence of left atrial hypertension (pulmonary artery wedge pressure <18 mm Hg if measured)

Pathophysiology of Respiratory Failure

Respiratory failure can be classified into 2 categories:

Type 1 hypoxic respiratory failure (failure of oxygenation) and

Type 2 hypercarbic respiratory failure (failure of ventilation).

The two entities may coexist as a combined failure of oxygenation and ventilation.

The main function of the respiratory system is to move atmospheric gases into the alveolar capillary
units of the lung and to move alveolar gas back out into the atmosphere.

The arterial gas composition depends on the (doc put one diagram here indicating all four things)

1. Gas composition of the atmosphere (inhalational injury)

2. Effectiveness of alveolar ventilation (pneumonia, aspiration pneumonia, severe trauma)

3. Pulmonary capillary perfusion (reperfusion injury, DIC, burns, sepsis, pancreatitis, drug overdose,)

4. Diffusion across the alveolar capillary membrane (drowning)

Abnormality at any of these steps can result in respiratory failure.

Monitoring:

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Clinical examination Pulse oximetry Chest x ray Capnography

Blood gases DLCO

MANAGEMENT:

1. Control of causative factors.

2. Careful fluid administration.

3. Oxygen administration: nasal cannula, SFM, bubble humidifier, venturi and NRM.

4. Air way adjuncts: oropharyngeal and nasopharyngeal air way

5. Inhaled gases: heliox, nitric oxide

6. Surfactant, corticosteroids and other nsiads.

7. Positive pressure respiratory support: CPAP and BiPAP

8. Endotracheal intubation and ventilation.

9. Positioning (prone ventilation)

10. HFOV, liquid ventilation

11. Supportive therapy: analgesia, sedation, nutrition and psychological support

5. DROWNING:

Drowning is a leading cause of childhood morbidity and mortality in the world.

“Drowning is the process of experiencing respiratory impairment from submersion/immersion in

liquid.”

The outcome should be denoted as fatal or nonfatal drowning.

Epidemiology:

The risk of drowning and the circumstances leading to it vary by age.

Drowning risk also relates to male gender, exposure to water, and supervision.

Children Younger than 1 Year

Most (71%) drowning deaths in children younger than 1 yr occur in the bathtub, when an infant is
left alone or under the “supervision” of an older sibling.

Children 1-4 Years

Drowning rates are consistently highest in 1 to 4 yr old children, likely because of their curious but
unaware nature coupled with the rapid progression of their physical capabilities. In rural areas,
15
children in this age group often drown in irrigation ditches or nearby ponds and rivers.

School-aged Children:

School-aged children are at increased risk of drowning in natural bodies of water such as lakes,
ponds, rivers, and canals.

Underlying Conditions:

Alcohol Use
Substance abuse
Sports and Recreation

Pathophysiology:

Once submersion occurs, all organs and tissues are at risk for hypoxia. In minutes, hypoxia leads to
coma and then cardiac arrest, adding ischemia to the succession of events.

1. Anoxic-Ischemic Injury:

After submersion small amounts of water enter the hypopharynx, triggering laryngospasm.

There is a progressive decrease in arterial blood oxygen saturation (Sao2), and soon loses
consciousness from hypoxia.

Profound hypoxia and medullary depression lead to terminal apnea.

At the same time, the cardiovascular response leads to progressively decreasing cardiac output and
oxygen delivery.

2. Pulmonary Injury:

Pulmonary aspiration occurs in a majority of drowning victims, but the amount aspirated is usually
small. Aspirated water does not obstruct airways and is readily moved into the pulmonary circulation
with positive pressure ventilation. It can wash out surfactant and cause alveolar instability,
ventilation-perfusion mismatch, and intrapulmonary shunting.

3. Hypothermia:

Hypothermia is common after submersion. It is often categorized, according to core body

temperature measurement, as mild (34-360C), moderate (30-340C), or severe (<300C).

Most often hypothermia is a poor prognostic sign, and a neuroprotective effect has not been
demonstrated. As core temperature drops to <350C, cognition, coordination, and muscle strength
become progressively impaired.

The likelihood of self-rescue decreases at this point.

With progressive hypothermia, there may be loss of consciousness, water aspiration, decreases in
heart rate and cardiac output, ineffective breathing, and cardiac arrest.

Management:

1. Initial Evaluation and Resuscitation:

16
Initial resuscitation must focus on rapidly restoring oxygenation, ventilation, and adequate circulation.
Abdominal thrusts should not be used. Once a submersion has occurred, immediate institution of
CPR efforts at the scene is imperative. The goal is to reverse the anoxia from submersion and prevent
secondary hypoxic injury after submersion.

2. Hospital-Based Evaluation and Treatment:

Pediatric drowning victims probably should be observed for at least 6-8 hr, even if they are
asymptomatic on presentation to the ED. At a minimum, serial monitoring of vital signs (respiratory
rate, heart rate, blood pressure, and temperature) and of oxygenation by pulse oximetry, repeated
pulmonary examination, and neurologic assessment should be performed in all drowning victims.

3. Renal: Diuretics, fluid restriction, and dialysis are occasionally needed to treat fluid overload or
electrolyte disturbances.

4. GI: Bowel rest, nasogastric suction, and gastric pH neutralization.

5. Hypothermia Management:

Damp clothing should be removed from all drowning victims. The goal is to prevent or treat
moderate or severe hypothermia. Rewarming measures are generally categorized as passive, active
external, or active internal. Passive rewarming measures include the provision of dry blankets, a
warm environment, and protection from further heat loss.

PROGNOSIS:

The outcomes for drowning victims are remarkably bimodal: The great majority of victims either
have a good outcome (intact or mild neurologic injury) or a bad outcome (persistent vegetative state
or death), with very few exhibiting intermediate neurologic injury. Of hospitalized pediatric
drowning victims, 15% die and as many as 20% survive with severe permanent neurologic damage.

APPROACH TO DROWNING-PREVENTION
STRATEGIES
HOME RECREATION NEIGHBOURHOOD
Swimming pools Swimming Irrigation ditches
Water Ponds pools
hazards Bathtubs Water drainage
Large buckets

Lapse in supervision

Lapse in supervision
Delayed discovery of child
Common Risky behavior when with
risks Reliance on water wings or
peers
pool toys
Reliance on sibling or bath
seat for bathing supervision

17
 HOME RECREATION NEIGHBOURHOOD
Provide constant
adult supervision
Educate families on hazards
and risks Swim in
lifeguarded areas
Provide constant adult
supervision of infants and
small children Avoid alcohol and
other drugs Provide constant adult
Install isolation fencing of
supervision
pools
Teach children Fence, cover, or fill in ditches
Prevention Install rescue equipment and
about water safety to prevent access to water
strategies phone at poolside
Recognize Provide fenced-in “safe area”
Learn swimming and water
limitations of for children to play
survival skills
swimming ability
Individuals with epilepsy
should shower and avoid Be aware of
bathtubs current weather
and water
Learn first aid and CPR conditions
Learn first aid and
CPR

6. BURNS:

Burns are a leading cause of unintentional death in children, second only to motor vehicle crashes.

CATEGORIES OF BURN DEPTH

2ND-DEGREE, OR
1ST-DEGREE 3RD-DEGREE, OR
PARTIAL-THICKNESS,
BURN FULL-THICKNESS, BURN
BURN
Dry, no
blisters Moist blebs, blisters
Underlying tissue is mottled Dry, leathery eschar
Minimal or no
Surface edema pink and white, with fair soot-stained
appearance capillary refill. No blanching or bleeding
Erythematous
Bleeds
Blanches,
bleeds
Pain Very painful Very painful Insensate
Epidermis, papillary, and
reticular layers of dermis Down to and may include fat,
Histologic Epidermal layers
subcutaneous tissue, fascia,
depth only May include domes of muscle, and bone
subcutaneous layers

18
 2ND-DEGREE, OR
1ST-DEGREE 3RD-DEGREE, OR
PARTIAL-THICKNESS,
BURN FULL-THICKNESS, BURN
BURN
Superficial: 5-21 days with
no grafting
Large areas require grafting, but
2-5 days with no Deep partial: 21-35 days small areas may heal from the
Healing time
scarring with no infection; edges after wks
if infected, converts to
full-thickness burn

Estimation of Body Surface Area for a Burn:

The rule of nines used in adults may be used only in children older than 14 yr or as a very rough
estimate to institute therapy before transfer to a burn center.

In small burns, <10% of BSA, the rule of palm may be used, especially in outpatient settings: The
area from the wrist crease to the finger crease (the palm) in the child equals 1% of the child's BSA.
The variable growth rate of the head and extremities throughout childhood makes it necessary to use
BSA charts, such as that modified by Lund and Brower.

INDICATIONS FOR HOSPITALIZATION FOR BURNS

1. Burns affecting >15% of body surface area
2. 3rd-degree burns
3. Electrical burns caused by high-tension wires or lightening
4 Chemical burns
5 Inhalation injury, regardless of the amount of body surface area burned
6 Inadequate home or social environment
7 Suspected child abuse or neglect
8 Burns to the face, hands, feet, perineum, genitals, or major joints
9 Burns in patients with preexisting medical conditions that may complicate the acute recovery
phase
10 Associated injuries (fractures)

19
 11 Pregnancy

ACUTE TREATMENT OF BURNS:

1. Fluid Resuscitation

For most children, the Parkland formula is an appropriate starting guideline for fluid resuscitation
(4 mL lactated Ringer solution /kg/% BSA burned). Half of the fluid is given over the 1st 8 hr,
calculated from the time of onset of injury; the remaining fluid is given at an even rate over the next
16 hr.

A 5% albumin infusion may be used to maintain the serum albumin levels at a desired 2 g/dL.

Infusion of packed red blood cells is recommended if the hematocrit falls to <24% (hemoglobin = 8
g/dL).

Fresh frozen plasma may be used for volume resuscitation within 72 hr of injury in patients younger
than 2 yr with burns over 20% of BSA and associated inhalation injury.

2. Nutritional Support: Calories are provided at approximately 1.5 times the basal metabolic rate,
with 3-4 g/kg of protein/day. Multivitamins, particularly the B vitamin group, vitamin C, vitamin A,
and zinc, are also necessary.

3. Pain Relief and psychological adjustment:

It is important to provide adequate analgesia, anxiolytics, and psychologic support to reduce early
metabolic stress, decrease the potential for post-traumatic stress syndrome, and allow future
stabilization as well as physical and psychologic rehabilitation.

4. Control of bacterial wound flora.

5. Use of biologic and synthetic dressings to close the wound (0.5% silver nitrate solution, silver
sulfadiazine cream, or mafenide acetate) (porcine xerograft, biobrane, hydrocolloid dressings).

BURN PROPHYLAXIS

PREVENT FIRES
1. Install and use smoke detectors
2. Control the hot water thermostat
3. Keep fire, matches, and lighters out of the reach of children
4. Avoid cigarette smoking, especially in bed
5. Do not leave lit candles unattended
6. Use flame retardant–treated clothing
7. Use caution when cooking, especially with oil
8. Keep cloth items off heaters

PREVENT INJURY
1. Roll, but do not run, if clothing catches fire;
2. wrap in a blanket
3. Practice escape procedures
4. Crawl beneath smoke if a fire occurs indoors
5. Use educational materials and fire extinguishers.
20
7. Electrical burns: 3 types

1. Minor electrical burns usually occur as a result of biting on an extension cord. These injuries
produce localized burns to the mouth, which usually involve the portions of the upper and lower lips
that come in contact with the extension cord. Because these are nonconductive injuries (do not extend
beyond the site of injury), hospital admission is not necessary and care is focused on the area of the
injury visible in the mouth. Treatment with topical antibiotic creams is sufficient until the patient is
seen in a burn unit outpatient department or by a plastic surgeon.

2. A more serious category of electrical burn is the high-tension electrical wire burn, for which
children must be admitted for observation, regardless of the extent of the surface area burn. Deep
muscle injury is typical and cannot be readily assessed initially. Such injuries have a mortality rate of
3-15% for children who arrive at the hospital for treatment. The electrical path, from entrance to exit,
takes the shortest distance between the 2 points and may produce injury in any organ or tissue in the
path of the current.

3. Lightning burns occur when a high-voltage current directly strikes a person (most dangerous) or
when the current strikes the ground or an adjacent (in-contact) object. Lightning burns depend on 1.
the current path, 2. the type of clothing worn, 3. the presence of metal, and 4. cutaneous moisture.
Feathering or an arborescent pattern is characteristic of lightning injury.

ELECTRICAL INJURY: CLINICAL

CONSIDERATIONS

CLINICAL MANIFESTATIONS MANAGEMENT

Extricate the patient; perform
ABCs of resuscitation;
immobilize the spine
History: voltage, type of current
1. General
Complete blood count with
platelets, electrolytes, blood urea
nitrogen (BUN), creatinine,
glucose
Treat dysrhythmias
Cardiac monitor,
Dysrhythmias: asystole, ventricular fibrillation,
electrocardiogram, and
sinus tachycardia, sinus bradycardia, premature
radiographs with suspected
2. Cardiac atrial contractions (PACs), premature
thoracic injury
ventricular contractions (PVCs), conduction
defects, atrial fibrillation, ST-T wave changes Creatinine phosphokinase with
isoenzyme measurements if
indicated
Protect and maintain the airway
acute respiratory distress, aspiration syndrome, Mechanical ventilation if
3. Pulmonary
Respiratory arrest. indicated, chest radiograph,
arterial blood gas levels
4. Renal Acute renal failure, myoglobinuria Provide aggressive fluid
21
 management unless a central
nervous system injury is present
Maintain adequate urine output,
>1 mL/kg/hr
Consider central venous or
pulmonary artery pressure
monitoring
Measure urine myoglobin;
perform urinalysis; measure
BUN, creatinine
Immediate: loss of consciousness, motor Treat seizures
paralysis, visual disturbances, amnesia, Provide fluid restriction if
agitation; intracranial hematoma indicated
5. Neurologic Secondary: pain, paraplegia, brachial plexus
injury, syndrome of inappropriate antidiuretic Consider spine radiographs,
hormone secretion (SIADH), autonomic especially cervical
disturbances, cerebral edema
Delayed: paralysis, seizures, headache, CT scan of the brain if indicated
Search for the entrance/exit
wound
Oral commissure burns, tongue and dental Treat cutaneous burns;
6. Cutaneous/oral injuries; skin burns resulting from ignition of determine the tetanus status
clothes, entrance and exit burns, and arc burns
Obtain a plastic surgery of ear,
nose, and throat consultation if
needed
Place a nasogastric tube if the
patient has airway compromise
or ileus
Viscus perforation and solid organ damage;
7. Abdominal Obtain SGOT, SGPT, amylase,
ileus.
BUN, and creatinine
measurements and, CT scans as
indicated
Compartment syndrome from subcutaneous Monitor the patient for possible
necrosis limb edema and deep burns compartment syndrome
8.Musculoskeletal Obtain radiographs and
Long bone fractures, spine injuries orthopedic/general surgery
consultations as indicated
Visual changes, optic neuritis, cataracts, Obtain an ophthalmology
9. Ocular
extraocular muscle paresis consultation as indicated

8. Cold injury:
Cold injury may produce either local tissue damage, with the injury pattern depending on exposure to

1. Damp cold (frostnip, immersion foot, or trench foot), 2. Dry cold (which leads to local
frostbite),
3. Generalized systemic effects (hypothermia) 4. Others (chill blains,
22
panniculitis).

Pathophysiology:
Ice crystals may form between or
within cells,

interfering with the sodium pump,

lead to rupture of cell membranes.

Blood may be shunted away from an affected area

damage to injured part

secondary neurovascular responses

clumping of red blood cells or platelets, causing
microembolism or thrombosis.

Clinical manifestations:

Frostnip: firm, cold, white areas on the face, ears, or extremities. Blistering and peeling may occur.
Treatment consists of warming the area with an unaffected hand or a warm object.

Immersion Foot (Trench Foot): Immersion foot occurs in cold weather when the feet remain in
damp or wet, poorly ventilated boots. The feet become cold, numb, pale, edematous, and clammy.
Tissue maceration and infection are likely. The treatment is largely prophylactic and consists of using
well-fitting, insulated, waterproof, nonconstricting footwear.
Frostbite: initial stinging or aching of the skin progresses to cold, hard, white aesthetic
and numb areas. On rewarming, the area becomes blotchy, itchy, and often red, swollen, and painful.

Treatment consists of

1. Warming the damaged area.

2. Anti-inflammatory agents and an analgesic agent is necessary.

3. Freeze and rethaw cycles are most likely to cause permanent tissue injury.

4. The affected area should be immersed in warm water (approximately 420C), with care taken not
to burn the anesthetized skin.

5. Vasodilating agents, such as prazosin and phenoxybenzamine, may be helpful.

6. Surgical sympathectomy has also been equivocal.

Chilblain (Pernio):

Chilblain (pernio) is a form of cold injury in which erythematous, vesicular, or ulcerative lesions
occur. They are often itchy, may be painful, and result in swelling and scabbing. The lesions are most
often found on the ears, the tips of the fingers and toes, and exposed areas of the legs. Treatment
consists of prophylaxis: avoiding prolonged chilling and protecting potentially susceptible areas with
a cap, gloves, and stockings. Prazosin and phenoxybenzamine. For significant itching, local
corticosteroid preparations may be helpful.

23
Cold-Induced Fat Necrosis (Panniculitis)

A common, usually benign injury, cold-induced fat necrosis occurs upon exposure to cold air, snow,
or ice and manifests in exposed (or, less often, covered) surfaces as red (or, less often, purple to blue)
macular, papular, or nodular lesions. Treatment is with nonsteroidal anti-inflammatory agents. The
lesions may last 10 days to 3 wk.

9. PEDIATRIC PAIN MANAGEMENT:

Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant
sensory and emotional experience associated with actual or potential tissue damage or described in
terms of such damage.

PAIN CATEGORIES AND

CHARACTERISTICS
PAIN DEFINITION AND
CHARACTERISTICS
CATEGORY EXAMPLES
Pain resulting from
injury to or
inflammation of tissues
In skin and superficial structures: sharp; pulsatile;
(skin, muscle, tendons,
well-localized
bone, joints, fascia,
Somatic vasculature, etc.) In deep somatic structures: dull; aching; pulsatile;
not well-localized
Examples: burns,
lacerations, fractures,
infections, inflammatory
conditions
Pain resulting from
injury to or
inflammation of viscera Aching and cramping; nonpulsatile; poorly localized
(e.g., appendiceal pain perceived around umbilicus) or
Visceral Examples: angina, bowel referred to distant locations (e.g., angina perceived
distention or in shoulder)
hypermobility,
pancreatitis
Pain resulting from
injury to, inflammation Spontaneous; burning; lancinating or shooting;
of, or dysfunction of the dysesthesias (pins and needles, electrical sensations);
peripheral or central hyperalgesia (amplification of noxious stimuli);
nervous systems. hyperpathia (widespread pain in response to a discrete
Neuropathic
Examples: complex noxious stimulus); allodynia (pain in response to
regional pain syndrome nonpainful stimulation); pain may be perceived distal or
(CRPS), phantom limb proximal to site of injury, usually corresponding to
pain, Guillain-Barre innervation pathways (e.g., sciatica)
syndrome, sciatica

24
Pain pathway:

Injury through A delta and C fibres dorsal horn of spinal cord

spinothalamic tract thalamus

From thalamus through dorsolateral pontine tegmentum to the site of injury.

PAIN MEASUREMENT
TOOLS (vasu likes BF HA)
AGE
NAME FEATURES ADVANTAGES LIMITATIONS
RANGE
Cannot be used in
younger children or in
Horizontal 10-cm those with cognitive
line; subject marks a limitations
spot on the line Good psychometric Requires language
Visual Analog between anchors of 6-8 yr and properties; validated skills and numerical
Scale (VAS) “no pain” (or neutral older for research processing; upper
face) and “most pain purposes anchor of “most pain”
imaginable” (or sad requires an
face) experiential reference
point that is lacking in
many children
Integers from 0 to
Good psychometric
10, inclusive,
6-8 yr and properties; validated
Likert Scale corresponding to a Same as for VAS
older for research
range from no pain
purposes
to most pain
Faces Scales Subjects rate their
Choice of “no pain” face
(e.g., FACES-R, pain by identifying Can be used at
4 yr and affects responses
Wong-Baker, with line drawings younger ages than
older (neutral vs smiling); not
Oucher, Bieri, of faces, or photos VAS and Likert
culturally universal
McGrath scales) of children
Behavioural or Some work Nonspecific; some
combined Scoring of observed for any ages; measures are convenient,
behavioural-phys behaviors (e.g., some work but others require
May be used in both
iologic scales facial expression, for specific videotaping and complex
infants and
(e.g., FLACC, limb movement) age groups, processing; vital sign
nonverbal children
N-PASS, heart rate and blood including changes unrelated to
CHEOPS, OPS, pressure preterm pain can occur and may
FACS, NIPS) infants affect total score
Autonomic Scores changes in
Can be used at all Nonspecific; vital sign
measures (e.g., heart rate, blood
ages; useful for changes unrelated to
heart rate, blood pressure, or
All ages patients receiving pain may occur, and may
pressure, heart measures of heart
mechanical artifactually increase or
rate spectral rate variability (e.g.,
ventilation decrease score
analyses) “vagal tone”)
25
 AGE
NAME FEATURES ADVANTAGES LIMITATIONS
RANGE
Plasma or salivary Nonspecific; changes
sampling of “stress” unrelated to pain can
Hormonal-metab Can be used at all
hormones (e.g., All ages occur; inconvenient;
olic measures ages
cortisol, cannot provide
epinephrine) “real-time” information;

Treatment:

Pharmacological Non pharmacological

Non opiod acetaminophen, aspirin, ibubrofen Relaxation techniques
ketorolac
Opiod codeine fentanyl methadone morphine Distraction
Local anesthetics lidocaine bupivacaine cocaine Hypnotherapy
Unconventional- antidepressants AED, neurotropic drugs Biofeedback
Invasive interventions: celiac plexus block stellate Iyengar yoga, psychotherapy
ganglion block
Intra thecal analgesia Massage therapy acupuncture
Nerve ablation and destruction Music and art therapy aroamtherapy

4.INVASIVE
THERAPY-INTRACTABLE PAIN
3.PARENTERAL POTENT OPIOD.MODERATE
-SEVERE PAIN
2.WEAK OPIODS.MILD-MODERATE
PAIN
1.NON-OPIOD
ANALGESICS.MILD PAIN
WHO LADDER FOR PAIN MANAGEMENT

10. Heat injuries:

In human beings a group of reflex responses that are primarily integrated in the hypothalamus
operate to maintain body temperature within a narrow range inspite of wide fluctuations in
environmental temperature.

Temperature regulating mechanisms:

Mechanisms activated by cold Mechanisms activated by heat

26
Increasing heat production Increase heat loss
Shivering Cutaneous vasodilatation
Hunger Shivering
Increased activity Increased respiration
Increased secretion of epinephrine and
Norepinephrine Decrease heat production
Decreased heat loss Anorexia
Cutaneous vasoconstriction Apathy and inertia
Curling up
Horripulation

Why children are more vulnerable to heat illness than adults:

1. They have greater ratio of surface area to body mass than adults

2. Produce greater heat per kilogram of body weight than adults during activity.

3. The sweat rate is lower in children and the temperature at which sweating occurs is higher.

4. Children can take longer to acclimatize to warmer, more humid environments.

5. Children also have a blunted thirst response compared to adults and might not consume enough
fluid during exercise to prevent dehydration.

Categories:

Three categories for heat illness are generally used: heat cramps, heat exhaustion, and heat stroke.

1. Heat cramps are the most common heat injury and usually occur in mild dehydration and or salt
depletion, usually affecting the calf and hamstring muscles. They tend to occur later in activity, as
muscle fatigue is reached and water loss and sodium loss worsen. They respond to oral rehydration
with electrolyte solution and with gentle stretching. Heat syncope is fainting after prolonged exercise
attributed to poor vasomotor tone and depleted intravascular volume, and it responds to fluids,
cooling, and supine positioning. Heat edema is mild edema of the hands and feet during initial
exposure to heat; it resolves with acclimatization. Heat tetany is carpopedal tingling or spasms
caused by heat-related hyperventilation. It responds to moving to a cooler environment and
decreasing respiratory rate (or rebreathing by breathing into a bag).

2. Heat exhaustion is a moderate illness with core temperature 100-103?F (37.7-39.4?C).

Performance is obviously affected, but central nervous system (CNS) dysfunction is mild, if present.
It is manifested as headache, nausea, vomiting, dizziness, orthostasis, weakness, piloerection, and
possibly syncope. Treatment includes moving to a cool environment, cooling the body with fans,
removing excess clothing, and placing ice over the groin and axillae. If a patient is not able to
tolerate oral rehydration, IV fluids are indicated. If rapid improvement is not achieved, transport to
an emergency facility is recommended.

3. Heat stroke is a severe illness manifested by CNS disturbances and potential tissue damage. It is
a medical emergency; the mortality rate is 50%. Sports-related heat stroke is characterized by
profuse sweating and is related to intense exertion, whereas “classic” heatstroke with dry, hot skin is
of slower onset (days) in elderly or chronically ill persons. Rectal temperature is usually >104?F
(40?C). Significant damage to the heart, brain, liver, kidneys, and muscle occurs with possible fatal
consequences if untreated. Treatment is immediate whole-body cooling via cold water immersion.
27
Airway, breathing, circulation, core temperature, and CNS status should be monitored constantly.
Rapid cooling should be ceased when core temperature is ~101-102?F (38.3-38.9?C). IV fluid at a
rate of 800 mL/m2 in the first hour with normal saline or lactated Ringer solution improves
intravascular volume and the body's ability to dissipate heat. Immediate transport to an emergency
facility is necessary.

Prevention:

1. Athletes are advised to be well hydrated before exercise and should drink every 20 min during
exercise.

2. Free access to cold water should be advocated to coaches.

3. Practices and competition should be scheduled in the early morning or late afternoon to avoid the
hottest part of the day.

4. Proper clothing such as shorts and t-shirts without helmets can improve heat dissipation.

5. Prepractice and postpractice weight can be helpful in determining the amount of fluid necessary to
replace (8 oz for each pound of weight loss).

6. Salt pills should not be used because of their risk of causing hypernatremia and delayed gastric
emptying.

11. RAPID SEQUENCE INTUBATION

STEP PROCEDURE COMMENT/EXPLANATION

Obtain a brief history
Rule out drug allergies; examine the airway anatomy (e.g.,
1 and perform an
micrognathia, cleft palate)
assessment
Assemble equipment,
2 See lists below
medications, etc.
Preoxygenate the
3 With bag/mask, nasal cannula, hood or blow-by
patient
Lidocaine minimizes the ICP rise with intubation and can be applied
Premedicate the patient topically to the airway mucosa for local anesthesia
4
with lidocaine, atropine Atropine helps blunt the bradycardia associated with upper airway
manipulation and reduces airway secretions
Sedatives:
Thiopental (2-5 mg/kg): Very rapid onset; can cause hypotension.
Diazepam (0.1 mg/kg): Onset 2-5 min; elimination in 30-60 min or
more.
Induce sedation and Ketamine (2 mg/kg): Onset 1-2 min; elimination in 30-40 min. May
5 cause hallucinations if used alone; causes higher ICP, mucous
analgesia
secretions, increased vital signs, and bronchodilation.
Analgesics:
Fentanyl (3-10 mcg/kg, may repeat 3-4mins): Rapid administration
risks “tight chest” response, with no effective ventilation. Effects
wear off in 20-30 min.

28
STEP PROCEDURE COMMENT/EXPLANATION
Morphine (0.05-0.1 mg/kg dose): May last 30-60 min; may lead to
hypotension in hypovolemic patients.
Pretreat with Small dose of a nondepolarizing paralytic agent (see below), with
6 nondepolarizing intent of diminishing the depolarizing effect of succinylcholine,
paralytic agent which is administered next
Succinylcholine dose is 1-2 mg/kg; causes initial contraction of
muscles, then relaxation. This depolarization can, however, raise ICP
and blood pressure. Onset of paralysis in 30-40 sec; duration is 5-10
Administer muscle min.
7
relaxants Increased use of pretreatment with a nondepolarizing muscle
relaxant, especially rocuronium (1 mg/kg), which has a very rapid
onset and short duration. Other nondepolarizing agents include
vecuronium and pancuronium, both dosed at 0.1 mg/kg.
Perform a Sellick Pressure on the cricoid cartilage, to occlude the esophagus and
8
maneuver prevent regurgitation or aspiration
ET: Select the proper size for the age and weight of the child
Perform endotracheal Laryngoscope blades: A variety of Miller and the Macintosh blades
9
intubation Patient supine; the neck is extended moderately to the “sniffing”
position
Secure the tube and
ET secured with tape to the cheeks and upper lip or to an adhesive
10 verify the position with
patch applied to the skin near the mouth.
a roentgenogram
Begin mechanical Verify tube placement before ventilating with positive pressure; if an
11
ventilation ET tube is in one bronchus, barotraumas may occur

12. Outcome measures in paediatrics

Scores used in icu-
APACHE (Acute Physiology And Chronic Health Evaluation) system for adults and the
PRISM (Pediatric Risk of Mortality) score for pediatric patients.
Scores used in pediatric emergency medicine-
The second-generation Pediatric Risk of Admission (PRISA II) score and
The Revised Pediatric Emergency Assessment Tool (RePEAT).
ELEMENTS OF THE RePEAT SCORE
• Age
• Chief complaint
• Triage category
• Current use of prescription medications
• Arrival via EMS (ground/air)
• Heart rate
• Respiratory rate
• Temperature

29
 ADOLESCENCE MEDICINE

INDEX
1. SMR
2. Adolescent health problems

SMR
Adolescence is defined as a period of development.
Puberty is the biologic process in which a child becomes an adult.
Once the onset of puberty has begun, the resulting sequence of somatic and physiologic changes
gives rise to the sexual maturity rating (SMR) or Tanner stages
CLASSIFICATION OF SEXUAL MATURITY STATES IN GIRLS
SMR
PUBIC HAIR BREASTS
STAGE
1 Preadolescent Preadolescent
Sparse, lightly pigmented, straight, medial Breast and papilla elevated as small
2
border of labia mound; diameter of areola increased
Breast and areola enlarged, no contour
3 Darker, beginning to curl, increased amount
separation
Coarse, curly, abundant, but less than in
4 Areola and papilla form secondary mound
adult
Adult feminine triangle, spread to medial Mature, nipple projects, areola part of
5
surface of thighs general breast contour

CLASSIFICATION OF SEX MATURITY STATES IN BOYS

SMR
PUBIC HAIR PENIS TESTES
STAGE
1 None Preadolescent Preadolescent
Minimal Enlarged scrotum,
2 Scanty, long, slightly pigmented
change/enlargement pink, texture altered
Darker, starting to curl, small
3 Lengthens Larger
amount
Resembles adult type, but less Larger; glans and breadth
4 Larger, scrotum dark
quantity; coarse, curly increase in size
Adult distribution, spread to medial
5 Adult size Adult size
surface of thighs

HORMONAL CHANGES:
Adrenal production of androgen may occur as early as 6 yr of age, with development of underarm
odor and faint genital hair (adrenarche).
Levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rise progressively
throughout middle childhood without dramatic effect.
Rapid pubertal changes begin with increased sensitivity of the pituitary to gonadotropin-releasing

30
hormone (GnRH);
Pulsatile release of GnRH, LH, and FSH during sleep; and corresponding increases in gonadal
androgens and estrogens.
The triggers for these changes are incompletely understood, but may involve ongoing neuronal
development throughout middle childhood and adolescence.

2. Adolescent health problems:

History should include HEADS/SF/FIRSTV
Home. Space, privacy, frequent geographic moves, neighbourhood.
Education/School. Frequent school changes, repetition of a grade/in each subject, teachers’ reports,
vocational goals, after-school educational clubs (language, speech, math, etc.), learning disabilities.
Abuse. Physical, sexual, emotional, verbal abuse; parental discipline.
Drugs. Tobacco, alcohol, marijuana, inhalants, “club drugs,” “rave” parties, others. Drug of choice,
age at initiation, frequency, mode of intake, rituals, alone or with peers, quit methods, and number of
attempts.
Safety. Seat belts, helmets, sports safety measures, hazardous activities, driving while intoxicated.
Sexuality/Sexual Identity. Reproductive health (use of contraceptives, presence of sexually
transmitted infections, feelings, pregnancy)
Family and Friends. Family: Family constellation, genogram,
single/married/separated/divorced/blended family, family occupations and shifts; history of addiction
in 1st- and 2nd-degree relatives, parental attitude toward alcohol and drugs, parental rules;
chronically ill physically or mentally challenged parent.
Friends: peer cliques and configuration (cheerleaders), gang or cult affiliation.
Image. Height and weight perceptions, body musculature and physique, appearance (including dress,
jewellery, tattoos, body piercing as fashion trends or other statement).
Recreation. Sleep, exercise, organized or unstructured sports, recreational activities (television,
video games, computer games, Internet and chat rooms, church or community youth group activities
[e.g., Boy/Girl Scouts; Big Brother/Sister groups, campus groups]). How many hours per day, days
per week involved?
Spirituality and Connectedness. Use HOPE or FICA acronym; adherence, rituals, occult practices,
community service or involvement.
Threats and Violence. Self-harm or harm to others, running away, cruelty to animals, guns, fights,
arrests, stealing, fire setting, and fights in school.

Common problems in girls

a. Dysmenorrhoea and dysfunctional uterine bleeding
b. Premenstrual syndrome
c. Acne
d. Breast disorders- asymmetry, hypoplasia, breast enlargement, and galactorrhea.
e. Hirsutism and voiding dysfunction
f. STDI, PID and pregnancy (vulvovaginitis- history, etiology- candida, trichomonas vaginalis,
staphylococci, hemophilus, shigella, pin worm. proper perineal hygiene, broad spectrum
antifungals and metronidazole, adhesive tapes for pin worm).

Common problems in boys

a. penile problems- anomalies, infections, genital herpes
b. scrotal- hydrocele, cryptorchidism, varicocele, torsion testes

31
c. voiding dysfunction
d. acne
e. substance abuse
Common to both genders:
a. depression
b. suicidal attempts and suicide
c. risk taking behaviour
d. violent behaviour
e. juvenile delinquency
f. obesity and eating disorder
To reach out to the maximum number of adolescents, FAMILY LIFE EDUCATION for adolescents
should be imparted through high schools. Following are the components
a. adolescent nutrition b. Personal hygiene c. Understanding ones emotions
d. awareness on one’s own sexuality, HIV/ AIDS and substance abuse e. Teenage care clinic
g. Teen clubs- awareness, personality guidance, medical check up and carrier guidance.

32
 ALLERGY

1. Anaphylaxis
2. Allergic rhinitis
3. Uricaria
4. Serious drug eruptions
5. Food allergy flow chart
6. Immunotherapy
7. Skin prick tests
8. Cmpi
9. Atopic dermatitis

1. Anaphylaxis: Anaphylaxis is defined as a serious allergic reaction that is rapid in onset and may
cause death.
Etiology: HAVELI DMF
COMMON CAUSES OF ANAPHYLAXIS IN CHILDREN
Food: peanuts, nuts, milk, eggs, fish, shellfish, fruits, grains
Drugs: Penicillin, cephalosporins, sulfonamides, nonsteroidal
anti-inflammatory agents
Hymenoptera venom: honeybee, yellow jacket, wasp, hornet, fire ant
Latex
Allergen immunotherapy
Exercise
Vaccinations: tetanus, measles, mumps, influenza
Miscellaneous: radiocontrast media, gamma globulin, blood products,
Idiopathic
Clinical features:
It occurs when there is a sudden release of potent biologically active mediators from mast cells and
basophils, leading to
 Cutaneous - urticaria, angioedema, flushing, pruritis
 Respiratory - bronchospasm, wheeze, dyspnea, laryngeal edema, deep cough
 Cardiovascular - hypotension, dysrhythmias, myocardial ischemia
 Gastrointestinal - nausea, colicky abdominal pain, vomiting, diarrhea.
 Cns: syncope, incontinence, death
Lab findings:

Plasma histamine is elevated for a brief period but is unstable and difficult to measure in a clinical
setting.

Plasma β-tryptase is more stable and remains elevated for several hours but often is not elevated,
especially in food-induced anaphylactic reactions.

DIAGNOSIS OF ANAPHYLAXIS
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled:

33
 1 Acute onset of an illness (minutes to several hours) with involvement of the skin and/or mucosal tissue
(e.g., generalized hives, pruritus or flushing, swollen lips/tongue/uvula)
AND AT LEAST ONE OF THE FOLLOWING:
a Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced peak PEF,
hypoxemia)
b Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse],
syncope, incontinence)
2 Two or more of the following that occur rapidly after exposure to a likely allergen for that patient
(minutes to several hours):
a Involvement of the skin/mucosal tissue (e.g., generalized hives, itch/flush, swollen
lips/tongue/uvula)
b Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
c Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence)
d Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3 Reduced BP following exposure to known allergen for that patient (minutes to several hours):
a Infants and children: low systolic BP (age-specific) or >30% drop in systolic BP
b Adults: systolic BP <90 mm Hg or >30% drop from patient's baseline

Treatment: The initial assessment should ensure an adequate airway

with effective respiration, circulation, and perfusion.

Anaphylaxis is a medical emergency requiring aggressive management with

1. intramuscular or intravenous epinephrine, 0.01ml/kg/dose 1: 1000 (max 0.5

ml)
2. high flow oxygen
3. lay patient flat and legs elevated
4. Secure an IV line with a wide bore needle and start intravenous fluids (bolus 20ml/kg rapid
push if hypotensive)
5. Intramuscular or intravenous H1 and H2 antihistamine antagonists.
6. inhaled β-agonists, nebulised salbutamol
7. Corticosteroids (IV mps or oral prednisone).
8. Epinephrine can be repeated after 3-5 minutes if required.
9. Post emergency management continue cetrizine and steroids for 3 days.

Preventive Treatment
Follow-up evaluation to determine/confirm etiology
Immunotherapy for insect sting allergy
Prescription for adrenaline and antihistamine
Provide written plan outlining patient emergency management

Patient Education
34
Instruction on avoidance of causative agent
Information on recognizing early signs of anaphylaxis
Stress early treatment of allergic symptoms to avoid systemic anaphylaxis

2. Allergic rhinitis:

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa characterized by nasal
congestion, rhinorrhea, and itching, often accompanied by sneezing and conjunctival irritation.

Classification:

AR is currently classified as seasonal (SAR) or perennial (PAR), although these terms may soon be
replaced by intermittent allergic rhinitis (IAR) and persistent rhinitis (PER).

Pathogenesis:

Lab findings:
1. Epicutaneous skin tests provide the best method for detection of allergen-specific IgE.
They are inexpensive and sensitive, and the risks and discomfort are minimal. To avoid false-negative
results, montelukast should be withheld for 1 day, most sedating antihistamine preparations for 3-4
days, and nonsedating antihistamines for 5-7 days.
2. Serum immunoassays for IgE to allergens provide a suitable alternative.

35
Clinical features:
Symptoms signs
1. Nasal itching brings on grimacing, twitching, and Signs on physical exam include
picking of the nose that may result in epistaxis. 1. dental malocclusion,
2. Allergic salute, an upward rubbing of the nose with an
2. “allergic gape”
open palm or extended index finger.
3. Typical complaints include intermittent nasal 3. “allergic shiners” (dark circles
congestion, itching, sneezing, clear rhinorrhea, and under the eyes),
conjunctival irritation.
4. The patients may lose their senses of smell and taste. 4. the transverse nasal crease.
5. Some experience headaches, wheezing, and coughing.
6. Nasal congestion is often more severe at night, causing 5. Conjunctival edema.
6. A nasal exam reveal bluish
mouth-breathing and snoring, interfering with sleep,
mucus membranes and
and inciting irritability. swollen turbinates
Treatment:
Non pharmacological Pharmacological
1. Sealing the patient's mattress, pillow, and 4. Second generation antihistamines:
covers in allergen-proof encasings Cetirizine, levocetirizine, loratidine,
reduces the exposure to mite allergen. fexofenadine.

5. Intra nasal steroids:

2. Bed linen and blankets should be washed Beclomethasone, fluticasone and
every week in hot water. mometasone

3. The only effective measure for avoiding 6. Other nasal sprays:

animal allergens in the home is the Ipratropium, cromolyn sodium and
removal of the pet and outdoor molds. oxymetazoline
7. Specific allergen immunotherapy

3. Urticaria: Urticaria is transient, pruritic, erythematous, raised wheals, with flat tops
and edema that may become tense and painful.
Types:
Episodes of hives that last for <6 wk are considered acute.
Those that occur at least twice a week for >6 wk are designated chronic.
ETIOLOGY OF ACUTE URTICARIA
Foods Egg, milk, wheat, peanuts, tree nuts, soy, shellfish, fish, strawberries
Medications Suspect all medications, even over-the-counter or homeopathic
Insect stings honeybee, wasp, fire ants
Bacterial (streptococcal pharyngitis, Mycoplasma, sinusitis);
viral (hepatitis, Epstein-Barr virus, coxsackievirus A and B);
Infections
parasitic (Ascaris, Ancylostoma, Echinococcus);
fungal (dermatophytes, Candida)
Contact allergy Latex, pollen
Transfusion reactions Blood, blood products, or IV immunoglobulin administration
Etiology of chronic Urticaria:
Idiopathic 75- 90% of chronic Urticaria are idiopathic
Physical Cholinergic, cold,
Rheumatologic SLE, JRA
Endocrine Hypothyroidism, hyperthyroidism
36
Neoplastic Mastocytosis. leukemia
Angioedema Hereditary, acquired and ACE inhibitors

DIAGNOSTIC TESTING FOR URTICARIA AND

ANGIOEDEMA
DIAGNOSIS DIAGNOSTIC TESTING
Elimination of offending agent, skin testing, and challenge
Food and drug reactions
with suspected foods
Autoimmune urticaria Autologous serum skin test; anti-thyroid antibodies
Thyroiditis Thyroid-stimulating hormone; anti-thyroid antibodies
Infections Appropriate cultures or serology, stool for parasites
Collagen vascular diseases and cutaneous Skin biopsy, immunofluorescence of tissues, antinuclear
vasculitis antibodies, cryoglobulins
Dermatographism Stroking with narrow object (e.g., tongue blade, fingernail)
Pressure urticaria Application of pressure for defined time and intensity
Vibratory urticaria Vibration for 4 min
Aquagenic urticaria Challenge with tap water at various temperatures
Urticaria pigmentosa Skin biopsy, test for dermographism
Hereditary angioedema C4, C2, CH50, C1-INH testing by protein and function
Skin biopsy, immunofluorescence (negative result), autologous
Chronic idiopathic urticaria
skin test
Treatment:
Type H1 Type H2 Leukotriene receptor Immunomodulatory
antihistaminic antihistaminic antagonist drugs
Cetrizine Cyclosporine
Loratidine Cimitidine Montelukast Tacrolimus
Desloratidine Ranitidine zafirlukast IVIG
Fexofenadine famotidine immunotherapy

4. SERIOUS DRUG ERUPTIONS

TYPICAL
DRUGS MOST
MUCOSAL TYPICAL PRODROMAL/SIGNS TIME TO
DIAGNOSIS OFTEN
LESIONS SKIN LESIONS AND SYMPTOMS ONSET
IMPLICATED
(WK)
Severe
Phenytoin,
exanthematous fever,
phenobarbital,
rash (could lymphadenopathy,
Drug
become hepatitis,
hypersensitivity carbamazepine,
Infrequent edematous, nephritis, 1-6
syndrome sulfonamides,
pustular, carditis,
(DHS)
purpuric), eosinophilia,
allopurinol,
exfoliative atypical lymphocytes
terbinafine
dermatitis
Stevens-Johnso Erosions at Crops of lesions High fever, sore throat, Sulfonamides,
1-3
n syndrome ≥2 sites on skin, rhinorrhea, cough phenytoin,
37
 TYPICAL
DRUGS MOST
MUCOSAL TYPICAL PRODROMAL/SIGNS TIME TO
DIAGNOSIS OFTEN
LESIONS SKIN LESIONS AND SYMPTOMS ONSET
IMPLICATED
(WK)
(SJS) conjunctivae, carbamazepine,
mouth, and barbiturates,
genitalia; allopurinol,
detachment of aminopenicillins,
≤10% of body nonsteroidal
surface area anti-inflammatory
drugs
Lesions similar
Sulfonamides,
to those with
Fever, headache, sore phenytoin,
SJS; confluent
throat; nearly all cases carbamazepine,
epidermis
Toxic epidermal involve fever, “acute skin barbiturates,
Erosions at separates readily
necrolysis failure,” leukopenia, allopurinol, 1-3
≥2 sites with lateral
(TEN) lesions of the respiratory aminopenicillins,
pressure;
and/or gastrointestinal nonsteroidal
detachment of
tracts anti-inflammatory
≥30% of body
drugs
surface area

5. Food allergy: Adverse reactions to foods consist of any untoward reaction

following the ingestion of a food or food additive and are classically divided into

Food intolerances, which are adverse physiologic responses.

Food hypersensitivities, which include adverse immunologic responses and allergies.
Food intolerance:
Host factors- enzyme deficiencies, GI disorders, psychologic and migrane
Food factors- infectious organisms, toxins, drugs
Symptoms elicited during acute IgE-mediated reactions can affect the
Skin- urticaria, angioedema, flushing, atopic dermatitis
Gastrointestinal tract- oral pruritus, angioedema, nausea, abdominal pain, vomiting, diarrhea
Respiratory tract- nasal congestion, rhinorrhea, nasal pruritus, sneezing, laryngeal edema, dyspnea,
wheezing.
Cardiovascular system- dysrhythmias, hypotension, loss of
consciousness.

38
 Food allergy

IgEmediated Non IgE mediated Mixed

1.oral allergy syndrome 1.allergic proctocolitis 1.Allergic eosinophilic esophagitis

2.food induced enterocolitis 2.Allergic eosinophilic gastritis
2.GI anaphylaxis
3.food induced enteropathy 3.allergic eosinophilic
4.celiac gastroenterocolitis

Investigations:
1. Unfortunately, there are no laboratory studies to help identify foods responsible for cell-mediated
reactions. Consequently, elimination diets followed by food challenges are the only way to establish
the diagnosis.
2. Skin prick tests
3. RAST
4. Specific IgE levels
Treatment:
1. Appropriate identification and elimination of foods responsible for food hypersensitivity
reactions are the only validated treatments for food allergies.
2. Children with asthma and IgE-mediated food allergy, peanut or nut allergy, or a history of a
previous severe reaction should be given self-injectable epinephrine (EpiPen) and a written
emergency plan in case of accidental ingestion.
3. Sublingual immunotherapy.

4. In addition, other forms of therapy, such as anti-IgE immunoglobulin therapy, engineered

recombinant food protein vaccines, and herbal formulations, are being evaluated.

5. In addition, tolerance may be generated by heating (cooking) the food (milk).

6. Exclusive breast feeding till 6 months or use of hydrolyzed milk-based formulas for the first 4-6
months of life, introduction of milk after 12 months, egg after 18 months and nuts after 24 months.

6. Allergin specific immunotherapy:

Allergen immunotherapy involves administering gradually increasing doses of allergens to a person
with allergic disease for the purpose of reducing or eliminating the patient's adverse clinical response
to subsequent natural exposure to those allergens.
indications Contra indications
1. insufficient response to pharmacotherapy 1. age less than 5 years
2. significant side effects to medical therapy 2. on β blocker therapy
3. poor compliance to medical regimen 3. severe asthma
4. patients who have perennial disease 4. immunodeficiency/ autoimmune diseases

39
5. insufficient response to environmental control 5. ABPA
6. asthma triggered by allergen exposure 6. pregnancy
7. insect venom sensitivity 7. severe psychiatric patients

Routes of administration:
1. Sub Cutaneous 2. Oral (OIT) 3. Intranasal 4. Sublingual
(SLIT) 5. Intrabronchial

Adverse reactions:
1. Allergen immunotherapy should be offered in only medical settings where a physician with access
to emergency equipment and medications required for the treatment of anaphylaxis is available.
2. Wheals, induration and urticaria.
3. Severe anaphylaxis. Alum precipitated extracts have less severe chances of anaphylaxis.
RUSH immunotherapy: Rush
immunotherapy is the administration of multiple injections either in a single day or over several days
in an attempt to reach maintenance dose more rapidly. The risk of adverse reactions, including
systemic reactions, is higher than with traditional allergen immunotherapy schedules. Patients to
undergo rush immunotherapy are often pretreated with antihistamines and corticosteroids.
Pre-administration of omalizumab has been shown to reduce the incidence of systemic reactions
associated with the use of this form of immunotherapy.

7. Skin prick tests:

Invivo tests Invitro tests
Widely used, Costly.
simple to perform, Not influenced by skin disease or medications.
less cost, Results correlate well with those obtained by skin
rapidity of performance testing and provocation challenges.
Skin tests
Patch test Eosinophilia
Prick/ puncture test Nasal and bronchial secretions for eosinophils
Intradermal test Serum Ig E levels
Provocation tests RAST(radioallergosorbent test)
Oral food challenge ELISA
Methacholine challenge test FAST (fluorescent immunoassay)
Conjunctival challenge test CLIA (chemiluminescent immunoassay)
Sub lingual challenge test Immunocap system

Medications that interfere with the tests are

1. Antihistaminies 2. TCA 3. Steroids (topical and oral)
4. Benzodiazepines.

8. CMPI:
CMPI is the most common food allergy in young infants often mistaken as lactose intolerance.
Incidence: 2-6% in non breast fed infants and 5% breast fed infants

IMMUNE-MEDIATED REACTIONS TO COW’S MILK

Cow’s milk protein:

 Cow’s milk constitutes =casein + whey proteins.
40
  The coagulum (casein proteins) accounts for about 80% of the total protein content in cow’s
milk and the lactoserum (whey) for the rest.

IgE-mediated CMP-induced reactions:

 When the introduction of breast feeding is delayed or not possible post partum, it is common
practice to offer a CMP-based formula to newborn infants. This early feed may represent the
index “sensitising-event”,  B cell class switching and specific-IgE production with
subsequent exposure to even minute amounts of bovine milk protein in human milk acting as
a “booster sensitising dose” or even elicit allergic reactions in a significant proportion of
breastfed CMPA neonates.

Clinical presentations:
Immediate: Ig E mediated- vomiting, pallor, shock, urticaria and swollen lips.
Late onset: T cell mediated- few hours or days, diarrhea, FTT, anemia and skin manifestations
Diagnosis:
1. High index of suspicion 2. Family history of atopy or allergy 3. Positive Ig E against
cow’s milk protein
4. Modified goldmans criteria includes clinical suspicion of CMA and abnormal histology reverting
back to normal once cow’s milk is withdrawn from diet.
5. UGIE reveals lymphoid hyperplasia with apthoid ulcerations
Management: (flow charts)
1. Removal of cow’s milk and milk products from diet.
2. Permit soy or hydrolysed formula.
3. Home available vegetable milk like amylase rich feeds, cereals with rice and dhal.
4. Parenteral counselling and education.
9. Atopic dermatitis:
Atopic dermatitis (AD), or eczema, is the most common chronic relapsing skin disease seen in
infancy and childhood. Frequently occurs in families with other atopic diseases, such as asthma,
allergic rhinitis, and food allergy.
Etiology: AD is a complex genetic disorder that results in a defective skin
barrier, reduced skin innate immune responses, and exaggerated T-cell responses to
environmental allergens and microbes that lead to chronic skin inflammation.

Pathogenesis:

Two forms of AD have been identified. Atopic eczema is associated with IgE-mediated sensitization
(at onset or during the course of eczema) and occurs in 70-80% of patients with AD. Nonatopic
eczema is not associated with IgE-mediated sensitization and is seen in 20-30% of patients with AD.
Both forms of AD are associated with eosinophilia.

Clinical features:

AD is diagnosed on the basis of 3 major features: pruritus, an eczematous dermatitis that fits into a
typical presentation, and a chronic or chronically relapsing course. Associated features,
such as a family history of asthma, hay fever, elevated IgE, and immediate skin test reactivity, are
variably present.

Triggering factors: Foods (cow milk, egg, peanut, soy, wheat, fish, shellfish), inhalant allergens,
bacterial infection, reduced humidity, excessive sweating, and irritants (wool, acrylic, soaps, toiletries,
fragrances, detergents) can exacerbate (trigger) pruritus and scratching.

Laboratory Findings:
41
There are no specific laboratory tests to diagnose AD. Many patients have peripheral blood
eosinophilia and increased serum IgE levels. Serum IgE measurement or prick skin testing can
identify the allergens to which patients are sensitized

Treatment: The treatment of AD requires a systematic and multifaceted approach.

1. Bathing and moisturization - Lukewarm soaking baths for 15-20 min followed by the application
of an occlusive emollient to retain moisture provide symptomatic relief.

2. Topical Corticosteroids-- Topical corticosteroids are the cornerstone of anti-inflammatory

treatment.

3. Topical Calcineurin inhibitors—Pimecrolimus in mild to moderate AD and Tacrolimus in mod to

severe AD.

4. Tar preparations 5. Antihistamines 6. Systemic steroids 7. avoid triggering factors 8. treat

superinfection

9. Phototherapy Natural sunlight is often beneficial to patients with AD as

long as sunburn and excessive sweating are avoided. Many phototherapy modalities are effective for
AD, including ultraviolet A-1, ultraviolet B (UVB), narrow-band UVB, and psoralen plus ultraviolet
A (PUVA). Phototherapy is generally reserved for patients in whom standard treatments fail.

10. Other- omalizumab, interferon γ, allergen immunotherapy, Probiotics, Chinese herbal medicines
and antimetabolites.

Prevention:
1. Breast-feeding or a feeding with a hypoallergenic hydrolyzed formula may be beneficial.

2. Avoid/ eliminate triggering factors 3. Maintain adequate hydration of skin.

42
 BEHAVIOUR
1. Pica
2. Rumination
3. Habit disorders
4. Temper tantrums
5. Anxiety disorders
6. Suicide
7. Pervasive developmental disorder
8. Autism
9. Biopsychosocial Models of Development

Behavioural problems in childhood:

Vegetative disorders Habit and tic disorders Disruptive and behavioural disorders
1. Rumination Thumb sucking Oppositionalism
2. Pica Bruxism Temper tantrum
3. Enuresis Nail biting Breath holding spells
4. Encopresis Tics Lying
3 & 4 – elimination Trichotillomania Head banging
disorders Head banging
Skin picking

1.Pica:
Pica involves the persistent eating of non nutritive substances (e.g.,
plaster, charcoal, clay, wool, ashes, paint, and earth). The eating behavior is inappropriate to the
developmental level (e.g., the normal mouthing and tasting of objects in infants and toddlers) and not
part of a culturally sanctioned practice.
Epidemiology:
Pica appears to be more common in children with intellectual disability,
pervasive developmental disorders, obsessive-compulsive disorders, and other neuropsychiatric
disorders. (DON) Children with pica are at increased risk for lead poisoning, iron-deficiency anemia,
obstruction, dental injury, and parasitic infections. (Pneumonic DIPLOI)
Etiology:
1. Nutritional deficiencies (e.g., iron, zinc, and calcium) 2. Low socioeconomic factors
3. Child abuse and neglect 4. Family disorganization (e.g., poor
supervision) 5. Psychopathology
6. Learned behavior
7. Underlying (but undetermined) biochemical disorder 8. Cultural and familial factors.

Treatment:
1. A combined medical and psychosocial approach is generally indicated for pica.
2. The sequelae related to the ingested item can require specific treatment (e.g., lead toxicity,
iron-deficiency anemia, parasitic infestation).
3. Ingestion of hair can require medical or surgical intervention for a gastric bezoar.
4. Nutritional education, cultural factors, psychologic assessment, and behavior interventions are
important in developing an intervention strategy for this disorder.
2. RUMINTAION:
Rumination disorder is defined as the repeated regurgitation and rechewing of food for a period of
at least 1 mo following a period of normal functioning. The rumination is not due to an associated
43
gastrointestinal illness or other general medical condition (e.g., esophageal reflux). Malnourishment
with resultant weight loss or growth delay is a hallmark of this disorder.
Epidemiology :
Rumination is a rare disorder that is potentially fatal, and some reports indicate that 5-10% of
affected children die. In otherwise healthy children, this disorder typically appears in the 1st yr of
life, generally between the ages of 3 and 6 months. The disorder is more common in infants with
severe intellectual disability than in those with mild or moderate intellectual disability.
Etiology and Differential Diagnosis:
Proposed causes of rumination disorder include a disturbed relationship with primary caregivers;
lack of an appropriately stimulating environment. The differential diagnosis includes congenital
gastrointestinal system anomalies, pyloric stenosis, Sandifer's syndrome, increased intracranial
pressure, diencephalic tumours, adrenal insufficiency, and inborn errors of metabolism.
Treatment:
1. Treatment begins with a behavioural analysis to determine if the disorder serves as
self-stimulation or is socially motivated.
2. Treatment is generally directed at reinforcing correct eating behavior and minimizing
attention to rumination.
3. Aversive conditioning techniques (e.g., withdrawal of positive attention) are useful when a
child's health is jeopardized.
4. Successful treatment requires the child's primary caregivers to be involved in the
intervention.
5. The caretakers need counselling around responding adaptively to the child's behavior as well
as altering any maladaptive responses.
6. There is no current evidence supporting a psychopharmacologic response to these disorders.

3. Habit Disorders:
The Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) defines stereotypic movement
disorders (habit disorders) as repetitive, seemingly driven, and non functional motor behavior
that markedly interferes with normal activities or results in self-inflicted bodily injury that
requires medical treatment. The behavior persists for 4 wk or longer and is not better accounted
for by a compulsion, a tic, a stereotypy that is part of a pervasive developmental disorder, or hair
pulling (as in trichotillomania).
Clinical Manifestations: A child's
presentation depends on the nature of the habit and level of the child's awareness of the behavior.
1. Teeth grinding, or bruxism, is common, can begin in the first 5 yr of life, and may be associated
with daytime anxiety. Untreated bruxism can cause problems with dental occlusion. Helping the child
find ways to reduce anxiety might relieve the problem; bedtime can be made more relaxing by
reading or talking with the child and allowing the child to discuss fears. Praise and other emotional
support are useful. Persistent bruxism requires referral to a dentist and can manifest as muscular or
temporomandibular joint pain.
2. Thumb sucking is normal in infancy and toddlerhood. Like other rhythmic patterns of behavior,
thumb sucking is self-soothing. Basic behavioural management, including encouraging parents to
ignore thumb sucking and instead focus on providing the child with praise for substitute behaviors, is
often effective treatment. Simple reinforces, such as giving the child a sticker for each block of time
that he or she does not suck the thumb, can also be considered. Although some literature suggests that
the use of noxious agents (bitter salves) may be effective in controlling thumb sucking, this approach
should rarely be necessary. Problems of thumb sucking- A) dental problems – anterior open bite,
44
decreased alveolar bone growth, mucosal trauma, malocclusion. B) Digit problems- paronychia,
thumb callus.
3. Trichotillomania is the repetitive pulling of hair resulting in loss and strand breakage of hair. The
usual age of onset of trichotillomania is around 13 yr, although preschoolers have been described
with this disorder. Children with trichotillomania have an increasing sense of tension immediately
before pulling or when resisting the behavior, followed by pleasure or relief when pulling out the hair.
The prevalence of trichotillomania in children is not well known but is believed to be 1-2% in
college students. Although trichotillomania often remits spontaneously, treatment of those whose
disorder has been present for >6 mo is unlikely to remit and requires behavioural treatment.
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine have some success as adjuncts.
Etiology:
Brain regions implicated are those involved in navigating human
experience through unpredictable, anxiety-provoked emotional states (e.g., amygdala and
hippocampus) as well as regions related to pleasure and reward seeking (e.g., nucleus accumbens).
The latter involves the hypothesis that individuals experience some level of gratification from
performing the habit behavior.
Diagnosis and Differential Diagnosis:
The child should be screened for current and past psychiatric symptoms (particularly anxiety,
obsessions, compulsions, and depression) along with any accompanying functional limitations. The
child should be examined for any significant physical injury from habit behaviors.
The differential diagnosis includes the stereotypic movements associated with mental retardation and
pervasive developmental disorders. Compulsions with obsessive-compulsive disorder (OCD) and
tic disorders as well as involuntary movements associated with neurologic conditions must be
considered.
Treatment:

 Often the initial approach to helping children with habit behaviors is for the parents to ignore
the behavior and not convey worry to their children.
 Generally these behaviors disappear with time and elimination of attention.
 If distress in the child or family, social isolation, and/or physical injury is occurring, then
treatment is indicated.
 Behavior therapy is the mainstay of treatment using a variety of strategies including habit
reversal, relaxation training, self-monitoring, reinforcement, competing responses,
negative practice, (HR SR CN) and, rarely, the use of aversive-tasting substances (for thumb
sucking or nail biting).
 SSRIs are helpful in reducing repetitive behaviors, and they might play a role in particularly
disabling and problematic behaviors, particularly those co-occurring with anxiety and
obsessive-compulsive behaviors.
4. Temper tantrum:
Seen between 18 months- 3 years
At this age child begins to develop autonomy from primary caregivers and tries to develop
negativism. Do things oppositely to what they are requested to do.
They show physical aggression and resistance like biting, kicking, thumping objects, hitting, head
banging. These kinds of activities are called as temper tantrums.
Reaches peak at 2 years of age and subside by 3-6 years when child learns to control negativism.
Treatment:
1. Child should be protected from injury.
2. Deviation of attention or change of environment helps.
3. Parents should be calm, loving firm and consistent.
4. Punishment is negative stimulus- to be avoided.
5. Time out - removal of positive reinforcements.
45
 6. Rule of thumb for length of time out is 1 min/1 year.

5. Anxiety disorders:
Anxiety disorders are characterized by pathologic anxiety in which anxiety becomes disabling,
interfering with social interactions, development, and achievement of goals or quality of life, and can
lead to low self-esteem, social withdrawal, and academic underachievement.
Anxiety disorders are the most common psychiatric disorders of childhood; they occur in 5-18%
of all children and adolescents, prevalence rates comparable to physical disorders such as asthma and
diabetes.
Types: total 7
Separation anxiety disorder (SAD), childhood-onset social phobia or social
anxiety disorder,
Generalized anxiety disorder (GAD), Obsessive-compulsive disorder (OCD),
phobias,
Post-traumatic stress disorder (PTSD), and panic disorder.

6. Suicide:
Youth suicide is a major and preventable public health problem. It ranks as the 3rd and 4th leading
causes of death among young people ages 15-24 yr and 10-14 yr, respectively.
Epidemiology: Each year, there are approximately, an estimated 12 suicides every day. It is
estimated that for every completed youth suicide, as many as 200 suicide attempts are made.
Males complete suicide at a rate 4 times that of females and represent 79.4% of all suicides where as
attempts are more common in girls.
Risk Factors:
In addition to age, race and ethnicity, and a history of a previous suicide attempt, there are multiple
risk factors that predispose youths to suicide.
1. Pre-existing Psychiatric Illness:
The great majority (estimated at 90%) of youths who complete suicide have a pre-existing psychiatric
illness, most commonly major depression. Among girls, chronic anxiety, especially panic
disorder, also is associated with suicide completion.
2. Cognitive Distortions:
Many suicidal youth hold negative views of their own competence, have poor self-esteem, and have
difficulty identifying sources of support or reasons to live. Many youngsters lack the coping
strategies necessary to manage strong emotions and instead tend to catastrophize and engage in
all-or-nothing thinking.
3. Social, Cultural, and Environmental Factors:
Of children and adolescents who attempt suicide, 65% can name a precipitating event for their action.
Most adolescent suicide attempts are precipitated by stressful life events, such as academic or social
problems, being bullied, trouble with the law, family instability, questioning one's sexual
orientation, a newly diagnosed medical condition, or a recent or anticipated loss. Suicide may also
be precipitated by exposure to news of another person's suicide or by reading about or viewing a
suicide portrayed in a romantic light in the media. Physical and sexual abuse can also increase one's
risk of suicide.

Management:

 Youth with these risk factors generally require inpatient level of care to ensure safety,
clarify diagnosis, and comprehensively plan treatment.
 For those youth suitable for treatment in the outpatient setting, an appointment should be
scheduled within a few days with a mental health professional.
 A procedure should be in place to contact the family if the family fails to complete the
46
 referral.
 Therapies that have been found to be helpful with suicidal youth include
cognitive-behavioural therapy, dialectical behavioural therapy and interpersonal
therapy.
 Psychotropic medications are used adjunctively to treat underlying psychiatric disorders.

Prevention:

 At present there is insufficient evidence to either support or refute universal suicide

prevention programs.
 Peer helpers have not been shown to be efficacious.
 Students are taught to recognize the signs of suicide and depression in themselves and others,
and they are taught the specific action steps necessary for responding to these signs.

7. Pervasive Developmental Disorders and Childhood Psychosis:

PERVASIVE DEVELOPMENTAL DISORDERS AND AUTISM SPECTRUM DISORDERS

PERVASIVE
CHILDHOOD DEVELOPMENTAL
ASPERGER'S RETT'S
AUTISM DISINTEGRATIVE DISORDER—NOT
SYNDROME SYNDROME
DISORDER OTHERWISE
SPECIFIED
Delayed and
disordered Similar to autism Clinically significant
Almost always
communication except language regression in skills
affects girls Features of 1 of the other
Atypical social skills relatively (language, social skills,
Regression in autism spectrum
interaction intact bowel and bladder
skills between 6 disorders, but insufficient
Restricted range Usually not control, play motor
and 18 mo of for a specific diagnosis
of interests cognitively skills) before 10 yr of
age
Onset before 3 delayed age
yr of age

Autistic Disorder:

DSM-IV-TR DIAGNOSTIC CRITERIA FOR AUTISTIC DISORDER

A A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from
(2) and (3):
1 Qualitative impairment in social interaction, as manifested by at least two of the following:
a Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze,
facial expression, body postures, and gestures to regulate social interaction
b Failure to develop peer relationships appropriate to developmental level
c A lack of spontaneous seeking to share enjoyment, interests, or achievements with other
people (e.g., by a lack of showing, bringing, or pointing out objects of interest)
d Lack of social or emotional reciprocity
2 Qualitative impairments in communication as manifested by at least one of the following:
a Delay in, or total lack of, the development of spoken language (not accompanied by an
attempt to compensate through alternative modes of communication such as gesture or
47
 mime)
b In individuals with adequate speech, marked impairment in the ability to initiate or
sustain a conversation with others
c Stereotyped and repetitive use of language or idiosyncratic language
d Lack of varied, spontaneous make-believe play or social imitative play appropriate to
developmental level
3 Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as
manifested by at least one of the following:
a Encompassing preoccupation with one or more stereotyped and restricted patterns of
interest that is abnormal either in intensity or focus
b Apparently inflexible adherence to specific, nonfunctional routines or rituals
c Stereotyped and repetitive motor manners (e.g., hand or finger flapping or twisting, or
complex whole-body movements)
d Persistent preoccupation with parts of objects
B Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3
years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or
imaginative play.
C The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder.

MEDICAL AND GENETIC EVALUATION OF CHILDREN WITH PERVASIVE

DEVELOPMENTAL DISORDERS

REQUIRED EVALUATIONS
Careful physical examination to identify dysmorphic physical features
Macrocephaly
Wood's lamp examination for tuberous sclerosis
Formal audiologic evaluation
Lead test; repeat periodically in children with pica
High-resolution karyotype
CONSIDER IF RESULTS OF ABOVE EVALUATIONS ARE NORMAL, AND IN CHILDREN WITH
COMORBID MENTAL RETARDATION
FISH test for region 15q11q13 to rule out duplications in Prader-Willi /Angelman's syndrome
region
FISH test for telomeric abnormalities
Test for mutations in MECP2 gene (Rett's syndrome)
DNA testing for fragile X syndrome
METABOLIC TESTING TO CONSIDER BASED ON OTHER CLINICAL FEATURES
Fasting blood glucose Plasma amino acids
Ammonia and lactate

Fatty acid profile Carnitine Acylcarnitine

Homocysteine

48
 Urine amino acids Urine organic acids Urine testing for purines and
pyrimidines

OTHER TESTING TO CONSIDER BASED ON CLINICAL FEATURES

Liver enzymes Biotinidase Thyroxine,
thyroid-stimulating hormone

Complete blood cell count Ceruloplasmin and

serum copper

ELECTROENCEPHALOGRAPHY IF THE FOLLOWING CLINICAL FEATURES ARE NOTED

Clinically observable seizures
History of significant regression in social or communication functioning

Early Identification:

Early identification and intervention of PDD are associated with better outcomes. Several instruments
have been developed for screening of PDD in primary care settings including the Checklist for
Autism in Toddlers (CHAT), the Modified Checklist for Autism in Toddlers (M-CHAT), and the
Pervasive Developmental Disorders Screening Test (PDDST).

Treatment:

The primary goals of treatment are to maximize the child's ultimate functional independence and
quality of life by minimizing the core features of the disorder, facilitating development and learning,
promoting socialization, reducing maladaptive behaviors, and educating and supporting families.

Educational interventions, including behavioral and habilitative (speech, occupational, and physical)
therapies, are the cornerstones of treatment for the PDDs.

Pharmacotherapy can increase the ability of persons with AD to benefit from educational and other
interventions and to remain in less-restrictive environments.

Target symptom clusters Selected medication

OCD, anxiety, depression SSRI
ADHD Stimulants, Atomoxetine, mood stabilizers
Sleep dysfunction Melatonin

49
Biopsychosocial Models of Development
CLASSIC STAGE THEORIES
SCHOOL ADOLESCE
INFANCY TODDLERHOO PRESCHOO
AGE (6-12 NCE (12-20
(0-1 YR) D (2-3 YR) L (3-6 YR)
YR) YR)
Freud:
psychosex Oral Anal Phallic/oedipal Latency Genital
ual
Erikson:
Basic trust Autonomy vs Initiative vs Industry vs Identity vs role
psychosoci
vs mistrust shame and doubt guilt inferiority diffusion
al
Piaget: Sensorimot Concrete Formal
Sensorimotor Preoperational
cognitive or operations operations
Preconventional:
avoid Conventional: Conventional: Postconventio
Kohlberg:
— punishment/obtain conformity law and order nal: moral
moral
rewards (stages 1 (stage 3) (stage 4) principles
and 2)

2. Psychoanalytic Theories
At the core of Freudian theory is the idea of body-centered (or, broadly, “sexual”) drives
stages age description
Oral phase 1-2yrs The focus of the drives shifts
with maturation from oral
satisfactions (sucking in the
1st yr of life)
Anal phase 2-4yrs anal sensations
Anal zone is the primary
zone of pleasure.
Gratification is derived from
expelling or withholding
faeces/urine
Phallic phase 5-10yrs oedipal drives
(possessiveness f boys
toward a parent in the
preschool years) electra
drives(similarly girls with her
father)
Genital phase in puberty and beyond

At each stage, the child's drive can potentially conflict with the rules of society. The emotional health
of both the child and the adult depends on adequate resolution of these conflicts.
Moreover, the effectiveness of psychoanalytic therapy has been difficult to demonstrate empirically.
Erikson's
Chief contribution was to recast Freud's stages in terms of the emerging personality.
The child's sense of basic trust develops through the successful negotiation of infantile needs,
corresponding to Freud's oral period. As children progress through these psychosocial stages,
different issues become salient.
Thus, it is predictable that a toddler will be preoccupied with establishing a sense of autonomy,
whereas a late adolescent may be more focused on establishing meaningful relationships and an
occupational identity.
Erikson's work calls attention to the intrapersonal challenges facing children at different ages in a
50
way that facilitates professional intervention.
Cognitive Theories:
Cognitive development is best understood through the work of Piaget. During the sensorimotor stage,
an infant's thinking is tied to immediate sensations and a child's ability to manipulate objects. Piaget
described how children actively construct knowledge for themselves through the linked processes of
 Assimilation (taking in new experiences according to existing schemata) and
 Accommodation (creating new patterns of understanding to adapt to new information). In this
way, children are continually and actively reorganizing cognitive processes.
Challenges have included questions about the timing of various stages and the extent to which
context may affect conclusions about cognitive stage.
Piaget's work is of special importance to pediatricians for 3 reasons:
(1) It helps make sense of many puzzling behaviors of infancy, such as the common exacerbation of
sleep problems at 9 and 18 mo of age.
(2) Piaget's observations often lend themselves to quick replication in the office, with little special
equipment.
(3) Open-ended questioning, based on Piaget's work, can provide insights into children's
understanding of illness and hospitalization.
Based on cognitive development, Kohlberg developed a theory of moral development in 6 stages
from early childhood through adulthood.
Preschoolers’ earliest sense of right and wrong is egocentric, motivated by externally applied
controls.
In later stages, children perceive equality, fairness, and reciprocity in their understanding of
interpersonal interactions through perspective-taking.
Most youth will reach stage 4, conventional morality, by mid to late adolescence. Whereas moral
thinking considers interpersonal interactions, justice, and human welfare, social conventions are the
agreed-on standards of behavior particular to a social or cultural group. Within each stage of
development, children are guided by the basic precepts of moral behavior, but also may take into
account local standards, such as dress code, classroom behavior, and dating expectations.
Behavioral Theory
This theoretical perspective distinguishes itself by its lack of concern with a child's inner experience.
Its sole focus is on observable behaviors and measurable factors that either increase or decrease the
frequency with which these behaviors occur. No stages are implied; children, adults, and indeed
animals all respond in the same way. In its simplest form, the behaviorist orientation asserts that
behaviors that are positively reinforced occur more frequently; behaviors that are negatively
reinforced or ignored occur less frequently. The strengths of this position are its simplicity, wide
applicability, and conduciveness to scientific verification. A behavioral approach lends itself to
interventions for various common problems, such as temper tantrums and aggressive preschool
behavior, in which behaviors are broken down into discrete units. In cognitively limited children and
children with autism spectrum disorders, behavioral interventions using applied behavior analysis
(ABA) approaches have demonstrated their ability to teach new, complex behaviors. ABA has been
particularly useful in the treatment of early diagnosed autism. However, in cases in which
misbehavior is symptomatic of an underlying emotional, perceptual, or family problem, an exclusive
reliance on behavior therapy risks leaving the cause untreated. Behavioral approaches can be taught
to parents to apply at home.
Theories Commonly Employed in Behavioral Interventions
During the past few decades an increasing number of programs (within and outside of the physician's
office) designed to influence behavior have been based on theoretical models of behavior. Some of
these models are based on behavioral or cognitive theory or in cases have attributes of both. The most
commonly employed models are the Health Belief Model, Theory of Reasoned Action, Theory of
Planned Behavior, Social Cognitive Theory, and the Transtheoretical Model, also known as Stages of
Change Theory. Pediatricians should be aware of these models; similarities and differences between
these models are shown in Table 6-3. Motivational interviewing is less a theory of behavior and
more a technique to bring about behavior change. The goal in using the technique is to enhance an
individual's motivation to change behavior by exploring and removing ambivalence. This may be
51
practiced by an individual practitioner and is being taught in some pediatric residency programs.
Motivational interviewing emphasizes the importance of the therapist (pediatrician) understanding
the client's perspective and displaying unconditional support. The therapist is a partner rather than an
authority figure and recognizes that ultimately the patient has control over his or her choices.

52
 CNS
1. HEADACHE

2. PSEUDOTUMORE CEREBRI

3. GLOSCOW COMA SCALE

4. BREATH HOLDING SPELL

5. CEREBRAL ABSCESS

6. HYDROCEPAHLUS

7. PEDIATRIC STROKE SYNDROMES:

8. VIRAL MENINGOENCEPAHALITIS

9. NEURAL TUBE DEFECTS

10. MENINGITIS

11. SEIZURES/ febrile seizure

12. MICROCEPHALY

13. HMSN: PERONEAL MUSCULAR ATROPHY

(CHARCOT-MARIE-TOOTH DISEASE; HMSN TYPE I)

14. PATTERN OF WEAKNESS AND LOCALIZATION IN THE FLOPPY INFANT

15. DISTINGUISHING FEATURES OF DISORDERS OF THE

MOTOR SYSTEM

16. BELLS PALSY

17. MOVEMENT DISORDERS/ chorea/ rheumatic chorea

18. ATAXIA

19. MYASTHENIA GRAVIS

20. Cerebral palsy

21. ADEM

22. Mitochondrial encephalopathies

23. DMD

24. Aseptic meningitis

53
 25. encephalitis

26. Neurophysiology – article ijpp 03 volume 2

27. Intractable epilepsy 08 vol 3 28. Circle of willis 29.

1. Headache:
Headache is a common complaint in children and teenagers.
Types:
Primary: migrane and tension type headache.
Secondary: due to an underlying illness.

Migrane: Migraine is the most frequent type of recurrent headache that is brought to the
attention of parents and primary care providers.
Classification:
1. migrane without aura 2. migrane with aura 3. childhood periodic
syndromes that are
commonly precursors of
migrane
4. retinal migrane 5. complications of migrane 6. probable migrane

Criteria:
All these features can be with or without aura
I At least 5 attacks fulfilling B-D
II Headaches lasting 4-72 hr (untreated or unsuccessfully treated)
III Headaches with at least two characteristics (UPMA)
A U unilateral location
B P pulsating quality
C M moderate of severe pain intensity
D A aggravation by or causing avoidance of routine physical
activity
IV During the headache have at least 1 of the following:
A Nausea and/or vomiting
B Photophobia and phonophobia
V Not attributed to another disorder

In addition to the classifying features, there may additional markers of a migraine disorder. These
include such things as triggers (skipping meals, inadequate or irregular sleep, dehydration and
weather changes are the most common), pattern recognition (associated with menstrual periods in
adolescents or Monday morning headaches due to change in sleep patterns over the weekend), and
prodromes (a feeling of irritability, tiredness, and food cravings prior to the start of the headache).

INDICATIONS FOR NEUROIMAGING IN A CHILD WITH HEADACHES

54
 1. Abnormal or focal neurologic signs or symptoms

2. Seizures or very brief auras (<5 min)

3. Unusual headaches in children
4. Headache in children <6 yr old or any child that cannot adequately describe their
headache
5. Brief cough headache in a child or adolescent
6. Headache worst on first awakening or that awakens the child from sleep
7. Migrainous headache in the child with no family history of migraine or its equivalent

Treatment:
Acute treatment: This mainly includes 2 groups of medicines: nonsteroidal antiinflammatory
drugs (NSAIDs) and triptans. Ibuprofen has been the most well documented at a dose of 7.5-10
mg/kg. The most effective way to administer the NSAIDs and triptans is to use the NSAIDs first,
restricting their use to fewer than 2-3 times per wk, and adding the triptan for moderate to severe
attacks. Fluid hydration should be integrated into the acute treatment plan.
Preventive therapy: The most commonly used preventive therapy for headache and migraine is
amitriptyline usually given for at least 4-6 months at an adequate dose and then weaned over several
weeks time. Antiepileptic medications are more recently commonly used for migraine prophylaxis.
Biobehavioral therapy: Biobehavioral evaluation and therapy is essential for effective
migraine management. This should include adequate fluid intake without caffeine, regular exercise,
not skipping meals and making healthy food choices, and adequate (8-9 hr) sleep on a regular basis.
Biofeedback-assisted relaxation therapy has been demonstrated to be effective for both acute and
preventive therapy.

Secondary headache: By definition, a secondary headache has a specific cause and

should resolve once this cause is treated. If the headache persists, the diagnosis and treatment should
be questioned because either the diagnosis may be incorrect, the headache may be a primary
headache, and/or the treatment chosen may have been incorrect.

Causes of secondary headache

1. Headache attributed to head and/or neck trauma
2. Acute post-traumatic headache
3. Medication-overuse headaches
4. Headache attributed to Rhinosinusitis
5. Headache attributed to psychiatric disorder
6. Headache attributed to nonvascular intracranial disorder

2. PSEUDOTUMOR CEREBRI:
Pseudotumor cerebri, also known as idiopathic intracranial hypertension, is a clinical syndrome
that mimics brain tumors and is characterized by increased intracranial pressure, with a normal
cerebrospinal fluid (CSF) cell count and protein content and normal ventricular size, anatomy, and
position documented by MRI.
Causes: C D HEROIN
HEMATOLOGIC INFECTIONS DRUGS RENAL
Wiskott-Aldrich Acute Tetracyclines
syndrome sinusitis Sulfonamides
Iron deficiency Otitis media Nalidixic acid
55
 anemia Mastoiditis Corticosteroid
therapy and Nephrotic syndrome
Aplastic anemia Tonsillitis
Sickle cell disease Measles withdrawal
Nitrofurantoin Chronic renal insufficiency

Post–renal transplant

NUTRITIONAL OTHER CONNECTIVE ENDOCRINE

TISSUE
Hypovitaminosis A Dural sinus Menarche
DISORDERS
Vitamin A thrombosis
intoxication Obesity Antiphospholipid Polycystic ovarian syndrome
Hyperalimentation Head trauma antibody
in malnourished syndrome Hypo /hyperparathyroidism
Superior
patient vena cava Systemic lupus
erythematosus Congenital adrenal
Vitamin syndrome hyperplasia
D–dependent Behcet disease
rickets

Clinical features and Investigations:

The most frequent symptom is headache, although vomiting also occurs.
Infant with pseudotumor cerebri characteristically reveals a bulging fontanel and a “cracked pot
sound” or MacEwen sign (percussion of the skull produces a resonant sound) due to separation of
the cranial sutures.
Papilledema with an enlarged blind spot is the most consistent sign in a child beyond infancy.
Orbit ultrasonography- for optic nerve edema. Tanget screen testing- for visual field defect.

Visual-evoked potentials. MRA/MRV should be considered in patients suspected of dural sinus

thrombosis.

Treatment : 1. The key objective in management is recognition and treatment of the underlying
cause.

2. Obese patient should be treated with a weight loss regimen.

3. Lumbar tap.

4. Acetazolamide, is an effective regimen. Corticosteroids are not routinely administered.

5. Optic nerve sheath fenestration to prevent visual loss.

3. GLASGOW COMA SCALE

EYE OPENING (TOTAL POSSIBLE POINTS 4)
Spontaneous 4
To voice 3
To pain 2
None 1
56
VERBAL RESPONSE (TOTAL POSSIBLE POINTS 5)
OLDER CHILDREN INFANTS AND YOUNG CHILDREN
Oriented 5 Appropriate words; smiles, fixes, and follows 5
Confused 4 Consolable crying 4
Inappropriate 3 Persistently irritable 3
Incomprehensible 2 Restless, agitated 2
None 1 None 1
MOTOR RESPONSE (TOTAL POSSIBLE POINTS 6)
Obeys 6
Localizes pain 5
Withdraws 4
Flexion 3
Extension 2
None 1

The Munro-Kellie doctrine describes intracranial dynamics in the setting of an expanding mass
lesion (i.e., hemorrhage, tumor) or brain edema. In the normal state, the brain parenchyma, arterial
blood, cerebrospinal fluid (CSF), and venous blood occupy the cranial vault at a low pressure,
generally <10 mm Hg. With an expanding mass lesion or brain edema, initially there is a
compensated state as a result of reduced CSF and venous blood volumes, and intracranial pressure
(ICP) remains low. Further expansion of the lesion, however, leads to an uncompensated state when
compensatory mechanisms are exhausted and intracranial hypertension results.

4. Breath-Holding Spells:

This term has been applied to 2 types of spells.

The 1st is the pallid breath-holding spell, which is the vasovagal reflex usually triggered by
dehydration, heat, standing for a long time without movement, hot showers, the sight of blood, pain,
or sudden stress.

57
The 2nd is the cyanotic or, “blue,” breath-holding spell.

Pathophysiology: Spells usually begin between 6 and 18 mo of age.

Triggering factors like Injury, anger, and frustration, particularly with surprise, dehydration, heat,
stress and pain.

An episode starts with a cry following a trigger

Prolonged expiratory apnea and reflex vagal cardiac bradycardia

Cyanosis resulting from intrapulmonary shunting

Blurring of vision, Syncope, loss of consciousness and even reflex anoxic seizures may follow.

Management: 1. Education and reassurance of the parents is usually all that is needed, as these
episodes are, as a rule, self-limited and outgrown within a few years.

2. Treat coexisting iron deficiency.

3. Anticholinergic drugs (atropine sulfate)

4. Instructing parents in basic cardiopulmonary resuscitation (CPR), or antiepileptic drug therapy

for anoxic seizures that are recurrent and not responding to other measures.

PREVENTION: Education of the parents on how to handle more severe spells by first-aid measures
is important.

All parents should be taught not to provide secondary gain when the episodes occur, because this
can reinforce the episodes.

Also, preparation for unpleasant experiences (such as receiving a shot) rather than surprising the
child with them can help limit the number of spells.

5. Cerebral abscess:

Brain abscesses can occur in children of any age but are most common in children between 4 and 8 yr
and neonates. Most brain abscesses are single, but 30% are multiple.

Causes:

1. CHD rt to lt shunt esp TOF 6. soft tissue infections of the face and scalp
2. meningitis 7. dental infections
3. chronic otitis media and mastoiditis 8. penetrating injury
4.sinusitis 9. immunodeficiency states
5.orbital cellulitis 10. infection of VP shunts

Etiology:

The responsible bacteria include streptococci (Streptococcus pyogenes group A or B, Streptococcus

pneumoniae, Enterococcus faecalis)

anaerobic organisms (Bacteroides spp., Fusobacterium spp., Prevotella spp., Actinomyces spp.)

58
gram-negative aerobic bacilli (Haemophilus influenzae, Enterobacter, Escherichia coli, Proteus)

Citrobacter is most common in neonates.

Fungal abscesses (Aspergillus, Candida) are more common in immunosuppressed patients.

Clinical features:

The early stages of cerebritis and abscess As the inflammatory process proceeds,
formation are associated with nonspecific vomiting, severe headache, seizures,
symptoms, including low-grade fever, papilledema, focal neurologic signs
headache, and lethargy. The significance of (hemiparesis), and coma may develop. If
these symptoms is generally not recognized, the abscess ruptures into the ventricular
and an oral antibiotic is often prescribed with cavity, overwhelming shock and death
resultant transient relief. usually ensue.

Diagnosis:

1. CBC – leukocytosis or normal counts

2. Blood culture- positive in 10 % of cases
3. CSF examination is usually avoided as it may cause herniation
4. Aspiration of the abscess.
5. EEG shows corresponding focal slowing.
6. RADIONUCLIDE brain scan indicates an area of enhancement.
7. MRI is the diagnostic test of choice. MRI also demonstrates an abscess capsule with gadolinium
administration.
8. An abscess cavity shows a ring-enhancing lesion by contrast CT.

TREATMENT: The duration of antibiotic therapy depends on the organism and response to
treatment, but is usually 4-6 wk.

Organism/ site of infection drugs

Unknown/ otitis media/ mastoiditis Vanco + 3 rd gen cephalosporin + metro
rd
Penetrating head injury/ head trauma Vanco + 3 gen cephalosporin
Cyan heart disease Ampicillin- sulbactum
VP shunt inf Vanco + ceftazidime
citrobacter 3 rd gen cephalosporin +
aminoglycoside
immunocompromised Broad spectrum + Amphotericin B

Surgery is indicated when the abscess is >2.5 cm in diameter, gas is present in the abscess, the lesion
is multiloculated, the lesion is located in the posterior fossa, or a fungus is identified.

6. HYDROCEPAHLUS:

59
COMMUNICATING NONCOMMUNICATING
Achondroplasia Aqueductal stenosis
Basilar impression Infectious*
X-linked
Choroid plexus papilloma
Chiari malformation
Meningeal malignancy Dandy-Walker malformation
Meningitis Klippel-Feil syndrome
Posthemorrhagic Mass lesions
Abscess
HYDRANENCEPHALY Hematoma
Holoprosencephaly Tumors and neurocutaneous
disorders
Massive hydrocephalus
Vein of Galen malformation
Porencephaly

*Inf- toxoplasmosis, mumps neurocysticercosis

CSF pathway: formed by choroid plexus of lateral ventricles (small quantity by brain parenchyma
of third ventricle) enters third ventricle thru foramen of manro passes thru aqui
duct of silvius enters the fourth ventricle escapes mainly thru foramen of
lushka and megendie occupies the subarachinoid space

1.Distributed all over the brain. 2.Small part enters central

canal

Normal rate of production: 18-20ml/hr. Normal volume in infants 50ml and in adults 150ml.

Clinical features:

Infant: In an infant, an accelerated rate of enlargement of the head is the most prominent sign. In
addition, the anterior fontanel is wide open and bulging, and the scalp veins are dilated. The
forehead is broad, and the eyes might deviate downward because of impingement of the dilated
suprapineal recess on the tectum, producing the setting-sun eye sign. Long-tract signs including
brisk tendon reflexes, spasticity, clonus (particularly in the lower extremities), and Babinski sign are
common. Serial measurements of the head circumference often indicate an increased velocity of
growth. Percussion of the skull might produce a cracked pot sound or MacEwen's sign, indicating
separation of the sutures.

Children: Irritability, lethargy, poor appetite, and vomiting are common to both age groups, and
headache is a prominent symptom in older patients. A gradual change in personality and
deterioration in academic productivity suggest a slowly progressive form of hydrocephalus.

60
Chiari malformation consists of two major subgroups. Type I typically produces symptoms during
adolescence or adult life and is usually not associated with hydrocephalus. Patients complain of
recurrent headache, neck pain, urinary frequency, and progressive lower extremity spasticity. The
deformity consists of displacement of the cerebellar tonsils into the cervical canal. Although the
pathogenesis is unknown, a prevailing theory suggests that obstruction of the caudal portion of the
4th ventricle during fetal development is responsible. Other theories include tethering of the cord or
additional anomalies (syrinx). (ccc= chiari, cerebellar tonsils, into cervical canal)

The type II Chiari malformation is characterized by progressive hydrocephalus with a

myelomeningocele. This lesion represents an anomaly of the hindbrain, probably owing to a failure
of pontine flexure during embryogenesis, and results in elongation of the 4th ventricle and kinking
of the brainstem, with displacement of the inferior vermis, pons, and medulla into the cervical canal.
Approximately 10% of type II malformations produce symptoms during infancy, consisting of stridor,
weak cry, and apnea, which may be relieved by shunting or by decompression of the posterior fossa.
A more indolent form consists of abnormalities of gait, spasticity, and increasing incoordination
during childhood.

The Dandy-Walker malformation consists of a cystic expansion of the 4th ventricle in the posterior
fossa and midline cerebellar hypoplasia, which results from a developmental failure of the roof of
the 4th ventricle during embryogenesis. Approximately 90% of patients have hydrocephalus, and a
significant number of children have associated anomalies, including agenesis of the posterior
cerebellar vermis and corpus callosum. Infants present with a rapid increase in head size and a
prominent occiput. Transillumination of the skull may be positive. Most children have evidence of
long-tract signs, cerebellar ataxia, and delayed motor and cognitive milestones, probably due to the
associated structural anomalies. The Dandy-Walker malformation is managed by shunting the cystic
cavity (and on occasion the ventricles as well) in the presence of hydrocephalus.

Treatment:

Medical: acetazolamide/ glycerol/ hypertonic saline

Surgical: vp shunt

Complications: Eye- optic atrophy, strabismus

Cognitive impairement gait abnormalities

metabolic acidosis following medical treatment.

Increase icp. Hematoma, shunt infection, failure, peritonitis, meningitis and seizures following
surgery

61
7. Pediatric stroke syndromes:

Stroke has emerged as an important cause of acquired brain injury in newborns and children.

Types

Ischemic: arterial ischemic stroke (AIS) cerebral sinovenous thrombosis (CSVT)

Hemorrhagic: hemorrhagic stroke and cerebrovascular disease.

Causes for arterial ischemic stroke:

Arteriopathic Cardiac Haematological Genetic

Sickle cell anemia
Focal cerebral Complex cyanotic Hereditary
arteriopathy heart disease Iron deficiency anemia dyslipoproteinemia
Inherited prothrombotic
Transient Cardiac procedures Heritable disorders of
(factor V Leiden, prothrombin
cerebral connective tissue
gene mutation)
arteriopathy Arrhythmias
Organic acidemias
Acquired prothrombotic (e.g.,
Moyamoya Endocarditis
protein C/S deficiency,
Mitochondrial
antithrombin III deficiency,
Arterial infection cardiomyopathy encepahalomyoapthies
lipoprotein [a], antiphospholipid
antibodies, oral contraceptives,
migrane
pregnancy)

Causes of hemorrhagic stroke

Vascular disorders Blood disorder Trauma

Arteriovenous malformations Idiopathic thrombocytopenic Middle meningeal

purpura artery injury
Cavernous malformations
(cavernomas) Bridging vein injury
Hemolytic uremic syndrome (subdural hematoma)
Venous angiomas
Hepatic disease/failure Subarachnoid
Hereditary hemorrhagic coagulopathy
telangiectasia hemorrhage
Vitamin K deficiency
Intracranial aneurysm (hemorrhagic disease of the Hemorrhagic
newborn) contusions (coup and
Choroid plexus angiomas
contrecoup)
Drugs/ toxins Disseminated intravascular
coagulation Non accidental trauma
Iatrogenic
(neurosurgical
procedures,
angiography)

62
Clinical Arterial ischemic stroke (AIS) Hemorrhagic stroke (HS)
features:

The acute onset of a focal Clinical presentations vary according to

neurologic deficit in a child is location, cause, and rate of bleeding.
stroke until proven otherwise. Acute hemorrhages may feature
instantaneous or thunderclap
The most common focal headache, loss of consciousness, and
presentation is hemiparesis but acute nuchal rigidity focal neurologic
visual, speech, sensory, or balance deficits and seizures.
deficits also occur.
HS can be rapidly fatal.
Children with these presentations
require urgent neuroimaging and In bleeds associated with vascular
consultation with a child neurologist malformations, pulsatile tinnitus,
as emergency interventions may be cranial bruit and high-output heart
indicated. failure may be present.
Investigati
ons
lumbar puncture may be required to
CT imaging can demonstrate larger exclude subarachnoid hemorrhage.
mature AIS and exclude CT is highly sensitive to acute HS.
hemorrhage. MRI is highly sensitive to even small
MRI identifies early and small amounts of acute hemorrhage.
infarcts and is therefore required to Angiography by CT, MR, or
exclude ischemic stroke. conventional means is often required to
Diffusion weighted MRI (DWI) exclude underlying vascular
can demonstrate AIS within minutes abnormalities.
of onset.
MR angiography can confirm
vascular occlusion

Treatment 1.antithrombotic statergies-

heparin, aspirin The same principles of
neuroprotection as in AIS.
2. neuroprotective statergies
Control of seizures, blood glucose
and temperature. Reversal of anticoagulant therapy
may be required (e.g., vitamin K, fresh
3. disease specific frozen plasma) but the role of factor
Transfusion in sickle cell and iron VII are unstudied.
def anemia
Immunosupression – vasculitis
Surgery in moyamoya Emergent neurosurgical intervention
for large or rapidly expanding lesions.
4. Sec stroke prevention

5. Rehabilitation

63
Neuroimaging findings:
1. CT: hyperdense region surrounded by edema, intraventicular hemorrhages
2. CT Venography: filling defects
3. MRI: Focal increased diffusion, multifocal and restricted diffusion. Demyelination. Follow
up MRI may show atrophy/ gliosis.
4. MR Angiogram: occlusion, stenosis, decreased flow, puffed smoke appearance (moya moya),
aneurysms, vascular malformations
5. MR Spectroscopy: increased lactate in MELAS
6. Gradient ECHO: can show presence of blood products

DIFFERENTIAL DIAGNOSIS OF STROKELIKE EPISODES IN

CHILDREN
CLINICAL DISTINCTION FROM IMAGING DISTINCTION
DISORDER
STROKE FROM STROKE

Evolving or “marching” symptoms, short

Typically normal
Migraine duration, complete resolution, headache,
Migrainous infarction is rare
personal or family history of migraine

Normal or may identify source of

Positive symptoms, Todd paralysis is
Seizure seizures (e.g., malformation, old
postseizure and limited
injury)

Normal or signs of
Fever, encephalopathy, gradual onset, encephalitis/cerebritis, which are
Infection
meningismus typically diffuse and bilateral

Gradual onset, multifocal symptoms, Multifocal lesions, typical

Demyelination encephalopathy Accompanying optic appearance (e.g., patchy in ADEM,
neuritis ovoid in MS),
Risk factor (e.g., insulin therapy), related to Bilateral, symmetric
Hypoglycemia
meals, additional systemic symptoms Posterior dominant pattern

Watershed Bilateral, symmetric restricted

Risk factor (e.g., hypotension, sepsis, heart
infarction due to diffusion in border zones between
disease), bilateral deficits
global HIE major arteries (watersheds)

Hypertensive Posterior dominant, bilateral,

Documented hypertension, bilateral visual
encephalopathy patchy lesions involving gray and
symptoms, encephalopathy
(PRES) white matter
64
 CLINICAL DISTINCTION FROM IMAGING DISTINCTION
DISORDER
STROKE FROM STROKE

Inborn errors of Pre-existing delays/regression, multisystem MR spectroscopy changes (e.g.,

metabolism disease, abnormal biochemical profiles high lactate in MELAS)

Symptoms limited to vertigo, imbalance

Vestibulopathy Normal
(i.e., no weakness) Gradual onset

Acute cerebellar Sudden onset bilaterally symmetric ataxia

Normal
ataxia postviral

Syndromic cluster of symptoms not

Channelopathy localizing to single lesion Normal
Gradual onset, progressive evolution

Alternating History contralateral events

Normal
hemiplegia Choreoathetosis/dystonia
ADEM, acute disseminated encephalomyelitis; HIE, hypoxic-ischemic encephalopathy; MELAS,
mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; MR, magnetic
resonance; MS, multiple sclerosis; PRES, posterior reversible leukoencephalopathy syndrome.

MIS W HAD A/C HIV (mis world had acute on chronic hiv) migrane, infections, seizure,
watershed infarcts due to HIE, hypoglycemia, ataxia, demyelination, alternating hemiplegia,
channelopathies, HTN, IEM, vestibulopathy.
MSC WAHIDA HIV (MSC chadivey WAHIDA ki HIV vachindi)
8. Viral meningoencepahalitis:
Viral meningoencephalitis is an acute inflammatory process involving the meninges and, to a variable
degree, brain tissue.

Etiology:
Enteroviruses are the most common cause of viral meningoencephalitis.

Arboviruses are arthropod-borne agents, responsible for some cases of meningoencephalitis during
summer months.

Several members of the herpes family of viruses can cause meningoencephalitis. (HSV-1) (HSV-2)
(VZV) (CMV) (EBV) (HHV-6).

Other viruses – mumps and occasionally by respiratory viruses (adenovirus, influenza virus,
parainfluenza virus), rubeola, rubella, or rabies.

Pathogenesis and pathology:

Neurologic damage is caused by direct invasion and destruction of neural tissues by actively
multiplying viruses or by a host reaction to viral antigens.

Temporal lobe - HSV Entire brain – Arbovirus Basal structures - Rabies

Clinical features:
Fever, nausea and vomiting, photophobia, and pain in the neck, back, and legs are common. The
presenting manifestations in older children are headache and hyperesthesia, and in infants, irritability
65
and lethargy. Headache is most often frontal or generalized; adolescents frequently complain of
retrobulbar pain. As body temperature increases, there may be mental dullness, progressing to
stupor in combination with bizarre movements and convulsions. Exanthems often precede or
accompany the CNS signs.

Investigations: The diagnosis of viral encephalitis is usually made on the basis of the clinical
presentation of nonspecific prodrome followed by progressive CNS symptoms. The diagnosis is
supported by examination of the CSF, which usually shows a mild mononuclear predominance. EEG
typically shows diffuse slow-wave activity, usually without focal changes. Neuroimaging studies (CT
or MRI) may show swelling of the brain parenchyma. Isolation of the virus from the CSF. PCR for
entero and HSV.

Treatment: With the exception of the use of acyclovir for HSV encephalitis, treatment of
viral meningoencephalitis is supportive. Treatment of mild disease may require only symptomatic
relief. More severe disease may require hospitalization and intensive care. If cerebral edema or
seizures become evident, vigorous treatment should be instituted.

Prevention:
1. Widespread use of effective viral vaccines for polio, measles, mumps, rubella, and varicella.
2. The availability of domestic animal vaccine programs against rabies has reduced the frequency of
rabies encephalitis.
3. Control of encephalitis due to arboviruses has been less successful because specific vaccines for
the arboviral diseases are not available.
4. Control of insect vectors by suitable spraying methods and eradication of insect breeding sites.
5. Furthermore, minimizing mosquito bites through the application of DEET-containing insect
repellents on exposed skin and wearing long-sleeved shirts, long pants, and socks when outdoors,
especially at dawn and dusk, reduces the risk of arboviral infection.

9. Neural tube defects:

Neural tube defects (NTDs) account for the largest proportion of congenital anomalies of the CNS
and result from failure of the neural tube to close spontaneously between the 3rd and 4th wk of in
utero development.

Causes:
Abnormal maternal Exposure to Drugs
nutritional state radiation before (valproate)
conception Unknown etiology
Hyperthermia
Malnutrition Maternal obesity Mutations in the
Chemicals and diabetes folate pathway

Types
Spina bifida Meningocele Myelomenigocele Anencephaly
occulta
Caudal regression Dermal sinus Tethered cord Syringomyelia
syndrome
encephalocele Diastematomyelia Lipoma involving iniencepahly
the conus

Embryology: The human nervous system originates from the primitive ectoderm that also develops
into the epidermis. The endoderm, particularly the notochordal plate and the intraembryonic
mesoderm, induces the overlying ectoderm to develop the neural plate in the 3rd wk of development.

66
Failure of normal induction is responsible for most of the NTDs.

Investigations:
1. Prenatal screening of maternal serum for AFP in the 16th-18th wk of gestation is an effective
method for identifying pregnancies at risk for fetuses with NTDs in utero.
2. A spine roentgenogram in simple spina bifida occulta shows a defect in closure of the posterior
vertebral arches and laminae, typically involving L5 and S1.
3. Ultrasonography is most helpful in determining the contents of the sac.
4. MRI or CT further helps define the spectrum of the lesion.

Prevention:

1. All women of childbearing age and who are capable of becoming pregnant take 0.4 mg of folic
acid daily.
2. If, however, a pregnancy is planned in high-risk women (previously affected child),
supplementation should be started with 4 mg of folic acid daily, beginning 1 mo before the time of
the planned conception.
3. The modern diet provides about half the daily requirement of folic acid. To increase folic acid
intake, fortification of flour, pasta, rice, and cornmeal with 0.15 mg folic acid per 100 g is usually
recommended.
4. Avoid anti folate drugs.
5. Screening pregnant women at for NTD with AFP.
6. Informative educational programs regarding folic acid vitamin supplementation during
pregnancy.
10. MENINGITIS:

PROTEI
PRESSURE LEUKOCYTES GLUCOSE
CONDITION N
(mm H2O) (mm3) (mg/dL)
(mg/dL)
COMMENTS
>50 (or 75%
<5, ≥75%
Normal 50-80 20-45 Serum
Lymphocytes
Glucose)
COMMON FORMS OF MENINGITIS
Decreased,
Organisms usually
Usually 100-10,000 or usually <40
Acute bacterial Usually seen on Gram stain
elevated more; PMNs (or <50%
meningitis 100-500 and recovered by
(100-300) predominate serum
culture
glucose)

67
 PROTEI
PRESSURE LEUKOCYTES GLUCOSE
CONDITION N
(mm H2O) (mm3) (mg/dL)
(mg/dL)
COMMENTS
>50 (or 75%
<5, ≥75%
Normal 50-80 20-45 Serum
Lymphocytes
Glucose)
HSV encephalitis is
suggested by focal
Generally
seizures or by focal
normal; may
Rarely >1,000 findings on CT or
be decreased
Normal or cells. PMNs early MRI scans or EEG.
Viral meningitis or to <40 in some
slightly but mononuclear Usually Enteroviruses and
meningoencephaliti viral diseases,
elevated cells predominate 50-200 HSV infrequently
s particularly
(80-150) through most of recovered from CSF.
mumps
the course HSV and
(15-20% of
enteroviruses may be
cases)
detected by PCR of
CSF

Acute Bacterial Meningitis Beyond the Neonatal Period:

Bacterial meningitis is one of the most potentially serious infections occurring in infants and older
children.

Etiology:

The most common cause of bacterial meningitis in children 1 mo to 12 yr of age in the developed
countries is Neisseria meningitidis. Bacterial meningitis caused by Streptococcus pneumoniae and
Haemophilus influenzae type b has become much less common in developed countries since the
introduction of universal immunization against these pathogens beginning at 2 mo of age. Other less
common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative
staphylococci, Salmonella spp., and Listeria monocytogenes.

1. Defects of the complement system (C5-C8) associated with recurrent meningococcal infection

2. Defects of the properdin system associated with a significant risk of lethal

meningococcal disease
3. Splenic dysfunction (sickle cell anemia) or is associated with an increased risk of
asplenia (due to trauma, or congenital pneumococcal, H. influenzae type b (to some
defect) extent), and, rarely, meningococcal sepsis and
meningitis.
4. T-lymphocyte defects (congenital or Are associated with an increased risk of L.
acquired by chemotherapy, AIDS, or monocytogenes infections of the CNS.
malignancy)

5. Congenital or acquired CSF leak increased risk of pneumococcal meningitis

6. Lumbosacral dermal sinus and Staphylococcal and gram-negative enteric bacterial

68
 meningomyelocele meningitis.

Epidemiology:

A major risk factor for meningitis is the lack of immunity to specific pathogens associated with
young age. Additional risks include recent colonization with pathogenic bacteria, close contact
(household, daycare centers, college dormitories, military barracks) with individuals having invasive
disease caused by N. meningitidis and H. influenzae type b, crowding, poverty, black or Native
American race, and male gender.

Clinical Manifestations

The onset of acute meningitis has 2 predominant patterns.

The more dramatic and, fortunately, less common presentation is sudden onset with rapidly
progressive manifestations of shock, purpura, disseminated intravascular coagulation (DIC), and
reduced levels of consciousness often resulting in progression to coma or death within 24 hr.

Nonspecific findings include fever, anorexia and poor feeding, headache, symptoms of upper
respiratory tract infection, myalgias, arthralgias, tachycardia, hypotension, and various cutaneous
signs, such as petechiae, purpura, or an erythematous macular rash.

Meningeal irritation is manifested as nuchal rigidity, back pain, Kernig sign (flexion of the hip 90
degrees with subsequent pain with extension of the leg), and Brudzinski sign (involuntary flexion of
the knees and hips after passive flexion of the neck while supine).

Seizures (focal or generalized) due to cerebritis, infarction, or electrolyte disturbances occur in

20-30% of patients with meningitis. Seizures that persist after the 4th day of illness and those that
are difficult to treat may be associated with a poor prognosis.

Diagnosis:

A. Lumbar Puncture: The diagnosis of acute pyogenic meningitis is confirmed by analysis of the CSF,
which typically reveals microorganisms on Gram stain and culture, a neutrophilic pleocytosis,
elevated protein, and reduced glucose concentrations. Hypoglycorrhachia (reduced CSF glucose
levels) is due to decreased glucose transport by the cerebral tissue.

Contraindications for an immediate LP include

(1) Evidence of increased ICP (other than a bulging fontanel), such as 3rd or 6th cranial nerve palsy
with a depressed level of consciousness, or hypertension and bradycardia with respiratory
abnormalities

(2) severe cardiopulmonary compromise requiring prompt resuscitative measures for shock or in
patients in whom positioning for the LP would further compromise cardiopulmonary function; and

(3) Infection of the skin overlying the site of the LP.

(4) Thrombocytopenia is a relative contraindication for LP.

B. Blood cultures should be performed in all patients with suspected meningitis. Blood cultures
69
reveal the responsible bacteria in up to 80-90% of cases of meningitis.

C. CT scan: for evidence of a brain abscess, basal skull fractures, cribriform bone abnormalities or
increased ICP.

D. ultrasound abdomen- Splenic malformations

E. MRI- myelomeningocele

F. Complement levels

G. blood- complete counts, renal function tests, SGOT, SGPT, PT, PTT

H. urine- microscopy, culture and osmolality.

Treatment:

1. Antibiotics:

Based on the substantial rate of resistance of S. vancomycin (60 mg/kg/24 hr, given every 6 hr)
pneumoniae to β-lactam drugs, for 10- 14 days
S. pneumoniae, N. meningitidis, and H. influenzae cefotaxime (200 mg/kg/24 hr, given every 6 hr) or
type b, ceftriaxone (100 mg/kg/24 hr administered once per
day or 50 mg/kg/dose, given every 12 hr) for 7- 10
days
If L. monocytogenes infection is suspected, as in ampicillin (200 mg/kg/24 hr, given every 6 hr)
young infants or those with a T-lymphocyte
deficiency Intravenous trimethoprim-sulfamethoxazole is an
alternative treatment for L. monocytogenes
If a patient is immunocompromised and initial therapy might include ceftazidime and an
gram-negative bacterial meningitis is suspected, aminoglycoside.

2. Corticosteroids

Rapid killing of bacteria in the CSF effectively sterilizes the meningeal infection but releases toxic
cell products after cell lysis (cell wall endotoxin) that precipitate the cytokine-mediated
inflammatory cascade. Therefore, agents that limit production of inflammatory mediators may be of
benefit to patients with bacterial meningitis.

Data support the use of intravenous dexamethasone, 0.15 mg/kg/dose given every 6 hr for 2 days,
in the treatment of children older than 6 wk with acute bacterial meningitis caused by H. influenzae
type b.

3. Glycerol:Glycerol increases plasma osmolality, reducing CNS edema and enhancing cerebral
circulation.

4. Supportive Care

a) Pulse rate, blood pressure, and respiratory rate should be monitored frequently.
70
b) Neurologic assessment, including pupillary reflexes, level of consciousness, motor strength,
cranial nerve signs, and evaluation for seizures, should be made frequently in the 1st 72 hr, when the
risk of neurologic complications is greatest.

c) Patients should initially receive nothing by mouth.

d) If a patient is judged to be normovolemic, with normal blood pressure, intravenous fluid

administration should be restricted to one half to two thirds of maintenance.

e) Patients with shock, a markedly elevated ICP, coma, and refractory seizures require intensive
monitoring with central arterial and venous access and frequent vital signs, necessitating admission to
a pediatric intensive care unit.

f) Seizures are common during the course of bacterial meningitis. Immediate therapy for seizures
includes intravenous diazepam (0.1-0.2 mg/kg/dose) or lorazepam (0.05-0.10 mg/kg/dose). Phenytoin
is preferred to Phenobarbital.

Complications:

1. During the treatment of meningitis, acute CNS complications can include seizures, increased ICP,
cranial nerve palsies, stroke, cerebral or cerebellar herniation, and thrombosis of the dural venous
sinuses.

2. SIADH occurs in some patients with meningitis, resulting in hyponatremia and reduced serum
osmolality. This may exacerbate cerebral edema or result in hyponatremic seizures (Chapter 52).

3. Prolonged fever (>10 days) is noted in about 10% of patients. Prolonged fever is usually due to
intercurrent viral infection, nosocomial or secondary bacterial infection, thrombophlebitis, or drug
reaction.

4. Nosocomial infections are especially important to consider in the evaluation of these patients.

5. Pericarditis or arthritis may occur in patients being treated for meningitis, especially that caused
by N. meningitidis.

6. Anemia may be due to hemolysis or bone marrow suppression.

7. DIC is most often associated with the rapidly progressive pattern of presentation and is noted most
commonly in patients with shock and purpura.

8. The combination of endotoxemia and severe hypotension initiates the coagulation cascade; the
coexistence of ongoing thrombosis may produce symmetric peripheral gangrene.

9. Severe neurodevelopmental sequelae may occur in 10-20% of patients recovering from bacterial
meningitis.

10. Sensorineural hearing loss is the most common sequela of bacterial meningitis

Prevention: Vaccination and antibiotic prophylaxis of susceptible at-risk contacts represent the 2
available means of reducing the likelihood of bacterial meningitis.

71
11. Seizures: A seizure is a transient occurrence of signs and/or symptoms resulting from
abnormal excessive or synchronous neuronal activity in the brain.

Types:
SELF-LIMITED SEIZURE TYPES CONTINUOUS SEIZURE TYPES
Focal Seizures Generalized Status Epilepticus
Focal sensory seizures Generalized tonic-clonic status
Focal motor seizures epilepticus
Gelastic seizures Clonic status epilepticus
Absence status epilepticus
Generalized Seizures
Tonic status epilepticus
Tonic-clonic seizures
Myoclonic status epilepticus
Clonic seizures
Focal Status Epilepticus

Epilepsia partialis continua

Typical absence seizures Hemiconvulsive status with hemiparesis
Atypical absence seizures
Myoclonic absence seizures
Tonic seizures

Simple febrile seizure:

Febrile seizures are seizures that occur between the age of 6 and 60 mo with a temperature of 38C or
higher, that are not the result of central nervous system infection or any metabolic imbalance, and
that occur in the absence of a history of prior afebrile seizures.

A simple febrile seizure is a primary generalized, usually tonic-clonic, attack associated with fever,
lasting for a maximum of 15 min, and not recurrent within a 24-hour period.

A complex febrile seizure is more prolonged (>15 min), is focal, and/or recurs within 24 hr.

Febrile status epilepticus is a febrile seizure lasting >30 min.

RISK FACTORS FOR RECURRENCE OF FEBRILE SEIZURES:

MAJOR MINOR Ppt stimuli for

seizures
Family history of febrile seizures Visual stimuli
Age <1 yr
Family history of epilepsy Thinking
Duration of fever <24 hr Complex febrile seizure Music
Day care Male gender Eating
Fever 38-390C
Reading
Hot water
Lower serum sodium

72
 RISK FACTORS FOR OCCURRENCE OF SUBSEQUENT EPILEPSY
RISK FACTOR RISK FOR SUBSEQUENT EPILEPSY
Simple febrile seizure 1%
Neurodevelopmental abnormalities 33%
Focal complex febrile seizure 29%
Family history of epilepsy 18%
Fever <1 hr before febrile seizure 11%
Complex febrile seizure, any type 6%
Recurrent febrile seizures 4%

Genetic: FEB 1-7 gene

Syndromes starting as febrile seizures: dravet syndrome, temporal lobe epilepsy secondary to
mesial temporal sclerosis and generalised epilepsy with febrile seizures plus.

Investigations:

1. Lumbar puncture: Lumbar puncture is recommended in children <12

mo of age after their first febrile seizure to rule out meningitis. A child between 12 and 18 mo of age
should also be considered for lumbar puncture. For children >18 mo of age, a lumbar puncture is
indicated in the presence of clinical signs and symptoms of meningitis.

2. EEG If the child is presenting with his

or her first simple febrile seizure and is otherwise neurologically healthy, an EEG need not normally
be performed as part of the evaluation. If an EEG is indicated as in intermediate or high risk child it
is delayed until or repeated after >2 wk have passed.

3. BLOOD STUDIES: Blood studies (serum electrolytes, calcium,

phosphorus, magnesium, and complete blood count [CBC]) are not routinely recommended in the
work-up of a child with a first simple febrile seizure.

4. Neuroimaging: A CT or MRI is not recommended in evaluating the

child after a first simple febrile seizure.

TREATMENT:

In general, antiepileptic therapy, continuous or intermittent, is not recommended for children with
one or more simple febrile seizures.

Parents should be counselled about the relative risks of recurrence of febrile seizures and recurrence
of epilepsy, educated on how to handle a seizure acutely, and given emotional support.

If seizures last for more than 5 minutes intranasal midazolam may be used.

Intermittent prophylaxis: diazepam, cloabazam and clonazeapam may be used.

Chronic antiepileptic therapy may be considered for children with a high risk for later epilepsy.

Prognosis:

1. Between 2% and 5% of neurologically healthy infants and children experience at least 1,

73
 usually simple, febrile seizure.
2. Febrile seizures recur in approximately 30% of those experiencing a first episode, in 50%
after 2 or more episodes, and in 50% of infants <1 yr old at febrile seizure onset.
3. Only 2-7% of children who experience febrile seizures proceed to develop epilepsy later in
life.

12. Microcephaly:

Def: Microcephaly is defined as a head circumference that measures more than 3 standard deviations
below the mean for age and sex.

Causes:
Primary Secondary
Familial Cong inf - cmv, rubella, toxoplasma
Autosomal dominant Drugs - fetal alcohol, fetal hydantoin
Genetic downs, Edwards, cri du chat Others - radiation, malnutrition, HIE

Diagnosis:
1. Thorough family history
2. Serial head circumference
3. Head circumference of the parents.
4. Mothers serum phenyalanine if the cause of Microcephaly not found
5. Karyotyping if abnormal facies, short stature
6. CT scan to detect calicifiactions
7. MRI to detect structural anomalies
8. TORCH titers and urine culture for CMV.
9. HIV testing for both mother and the child.
10. single gene mutation study

13. CONDITIONS THAT MIMIC SEIZURES ACCORDING TO AGE OF

PRESENTATION
GENERALIZE ABNORMAL
OCULOMOTOR SLEEP
AGE D MOVEMENTS AND
ABNORMALITIES DISORDERS
PAROXYSMS POSTURES
Apnea Paroxysmal tonic up
Benign neonatal
Hyperekplexia gaze
Jitteriness sleep myoclonus
Jitteriness
Neonate Paroxysmal dystonic
Paroxysmal Alternating
choreoathetosis Sleep transition
extreme pain hemiplegia of
disorders
disorder childhood

74
 GENERALIZE ABNORMAL
OCULOMOTOR SLEEP
AGE D MOVEMENTS AND
ABNORMALITIES DISORDERS
PAROXYSMS POSTURES
Hyperekplexia
Reflex anoxic Jitteriness
seizures Benign myoclonus of Non-REM partial

Breath-holding early infancy Paroxysmal tonic up arousal disorders

spells Shuddering attacks gaze
Infants
Opsoclonus REM sleep
Pathologic startle Alternating hemiplegia myoclonus syndrome
Paroxysmal of childhood disorders

extreme pain Drug reactions Narcolepsy

disorder

Tics
Non-REM partial
Benign Tremor
paroxysmal arousal disorders
vertigo Benign paroxysmal
REM sleep
Pathologic startle torticollis
Compulsive disorders
valsalva Episodic ataxia
Narcolepsy
Alternating Episodic rage
Children
hemiplegia of Sleep transition
and Psychologic disorders Daydreaming
childhood
adolescen Drug reactions disorders
Familial including Munchausen
ts
hemiplegic (somnambulism,
migraine syndrome by proxy,
somniloquy)
Syncope malingering
Psychogenic Sleep myoclonus
seizures Masturbation
Restless legs
Hyperventilation head banging
spells syndrome
Drug reactions

14. HMSN: Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease; HMSN

Type I)

The hereditary motor-sensory neuropathies (HMSNs) are a group of progressive diseases of

peripheral nerves. Motor components generally dominate the clinical picture, but sensory and
autonomic involvement is expressed later.

Clinical Manifestations:

Asymptomatic until late childhood.

75
The peroneal and tibial nerves are the earliest and most severely affected. Children with the disorder
are often described as being clumsy, falling easily, or tripping over their own feet.
Muscles of the anterior compartment of the lower legs become wasted, and the legs have a
characteristic stork-like contour. The muscular atrophy is accompanied by progressive weakness of
dorsiflexion of the ankle and eventual footdrop. Pes cavus and claw hand are also seen.

Axial muscles, spincter control and Cranial nerves are not involved.

Sensory involvement mainly affects large myelinated nerve fibers that convey proprioceptive
information and vibratory sense. Because the muscle mass is reduced, the nerves are more vulnerable
to trauma or compression. Nerves often become palpably enlarged. Autonomic neuropathy does
not affect the heart, gastrointestinal tract, or bladder. Intelligence is normal.

Laboratory Findings and Diagnosis:

Motor and sensory nerve conduction velocities are greatly reduced, sometimes as slow as 20% of
normal conduction time.
Electromyography (EMG) and muscle biopsy are not usually required for diagnosis, but they show
evidence of many cycles of denervation and reinnervation. Serum creatine kinase level is normal.
Sural nerve biopsy is diagnostic. Large- and medium-sized myelinated fibers are reduced in
number, collagen is increased, and characteristic onion bulb formations of proliferated Schwann
cell cytoplasm surround axons. The definitive molecular genetic diagnosis may be made in blood.

Treatment:

Stabilization of the ankles is a primary concern.

In early stages, stiff boots that extend to the mid-calf often suffice. As the dorsiflexors of the ankles
weaken further, lightweight plastic splints may be custom made to extend beneath the foot and
around the back of the ankle. Surgical fusion of the ankle may be considered in some cases.

The leg should be protected from traumatic injury. In advanced cases, compression neuropathy
during sleep may be prevented by placing soft pillows beneath or between the lower legs. Burning
paresthesias of the feet are not common but are often abolished by phenytoin or carbamazepine.
No medical treatment is available to arrest or slow the progression.

15. PATTERN OF WEAKNESS AND LOCALIZATION IN THE FLOPPY INFANT

ANATOMI
C REGION CORRESPONDI
OF NG PATTERN OF WEAKNESS AND INVOLVEMENT
HYPOTON DISORDERS
IA

76
ANATOMI
C REGION CORRESPONDI
OF NG PATTERN OF WEAKNESS AND INVOLVEMENT
HYPOTON DISORDERS
IA
Chromosomal
disorders
Inborn errors of Central hypotonia
Central metabolism Axial hypotonia more prominent
nervous Cerebral
system Hyperactive reflexes
dysgenesis
Cerebral, spinal
cord trauma

Generalized weakness;
Motor Spinal
often spares the diaphragm, facial muscles, pelvis, and
neuron muscular atrophy
sphincters

Peripheral Distal muscle groups involved

Nerve Weakness with wasting
neuropathies

Myasthenia
Neuromuscu syndromes Bulbar, oculomotor muscles exhibit greater degree of
lar junction Infantile botulisminvolvement

Congenital
myopathies
Metabolic Weakness is prominent
myopathies Proximal musculature
Muscle CMD Hypoactive reflexes
Congenital Joint contractures
myotonic
dystrophy

DISTINGUISHING FEATURES OF DISORDERS OF THE MOTOR SYSTEM

conditions MUSCLE
WEAKNESS DTR EMG OTHER
LOCUS OF BIOPSY
LESION Proxima
Face
l-Distal
Cerebral Seizures,
Norma dysgenesis hemiparesis, and
Central 0 > or = Normal Normal
l or ↑ delayed
development

77
 conditions MUSCLE
WEAKNESS DTR EMG OTHER
LOCUS OF BIOPSY
LESION Proxima
Face
l-Distal

Ventral horn Fasciculations SMA Denervati Fasciculations

Late > or = 0
cell and fibrillations on pattern (tongue)
HMSN Sensory
deficit, elevated
Peripheral Denervati cerebrospinal
0 < ↓ Fibrillations
nerve on pattern fluid protein,
depressed
nerve biopsy

Decremental Myastheni Response to

response a neostigmine or
(myasthenia); edrophonium
Neuromuscul Norma
+++ = incremental Normal (myasthenia);
ar junction l
response and constipation
BSAP and fixed pupils
(botulism) (botulism)

Short duration, Myopathie

small-amplitud s
Variabl e motor unit Elevated
Myopathic
Muscle e (+ to > ↓ potentials and muscle enzyme
pattern
++++) myopathic levels (variable)
polyphasic
potentials
BSAP, brief duration, small amplitude, overly abundant motor unit potentials

16. Bells palsy:

Bell palsy is an acute unilateral facial nerve palsy that is not associated with other cranial
neuropathies or brainstem dysfunction. It is a common disorder at all ages from infancy through
adolescence and usually develops abruptly about 2 wk after a systemic viral infection.

Causes:
Common: herpes simplex type 1 varicelle zoster virus
Uncommon: EBV, CMV, HSV6, MUMPS, MYCOPLASMA, Trauma, tumour, ribavarin,
interferon α

78
Clinical features: The upper and lower portions of the face are paretic, and the corner of the
mouth droops. Patients are unable to close the eye on the involved side and can develop an exposure
keratitis at night. Taste on the anterior 2/3 of the tongue is lost on the involved side in about 50% of
cases. Several grading systems have been devised for Bell palsy, including the Sunnybrook,
House-Brackmann, and Yanagihara systems.

Treatment:

Oral prednisone (1 mg/kg/day for 1 wk, followed by a 1-wk taper) started within the first 3-5 days
results in improved outcome and is a traditional treatment. Some also recommend adding oral
acyclovir or valacyclovir to the prednisone therapy.
Surgical decompression of the facial canal, is not of value.
Physiotherapy to the facial muscles.
Protection of the cornea with methylcellulose eyedrops or an ocular lubricant is especially important
at night.

17. Movement disorders:

Selected types of involuntary movements
Hypokinetic parkinsonism
Hyperkinetic tics, tremors, chorea, athetosis, ballismus, myoclonus and restless leg syndrome.

CHOREA:

Chorea, meaning “dance-like” in Greek, refers to rapid, chaotic movements that seem to flow from
one body part to another.

Classification: Chorea can be divided into primary (i.e., disorders in which chorea is
the dominant symptom and the etiology is presumed to be genetic) and secondary forms, with the
vast majority of pediatric cases falling into the latter category

79
 STRUCTUR PARAINFECTI INFECTIOU METABOLIC OR Drugs
GENETIC CHOREAS AL OUS AND S CHOREA TOXIC
BASAL-GA AUTOIMMUN ENCEPHALOPAT
HIV Phenothia
Huntington diseaseNGLIA E DISORDERS HIES
encephalop
LESIONS
(rarely presents with zines
Sydenham athy Acute intermittent
chorea in childhood)Vascular chorea Toxoplasm porphyria l-Dopa
chorea in Systemic osis
Neuroacanthocytosisstroke Hypo/hypernatremia
phenytoin
lupus Cysticercos
Ataxia telangiectasiaMass erythematosus Hypocalcemia
is valproic
Hyperthyroidism
Benign hereditarylesions Antiphospholi Diphtheria acid
chorea (e.g., CNS pid antibody Hypoparathyroidism
lymphoma Bacterial amphetam
syndrome endocarditi Hepatic/renal failure
Spinocerebellar ,
Postinfectious
ataxia (types 2, 3, ormetastatic
s Mercury poisoning ines
or
brain Scarlet
17) postvaccinal Organophosphate verapamil
tumors) fever
encephalitis poisoning lithium
Multiple Viral
Paraneoplasti encephalitis TCA
sclerosis c choreas
plaques (mumps,
theophylli
measles,
varicella) ne

Sydenham chorea (SC, St. Vitus dance) is the most common acquired chorea of childhood. It
occurs in 10% to 20% of patients with acute rheumatic fever, typically weeks to months after a
group A β-hemolytic streptococcal infection. Peak incidence is at age 8 to 9 yr, with a female
predominance of 2: 1.

Pathophysiologically, antibodies against the N-acetyl-β-d-glucosamine epitope (GlcNAc) of

streptococcal group A carbohydrate have been shown to cause the neurologic manifestations of SC by
increasing dopamine release into the synapse.

The clinical hallmarks of SC are chorea, hypotonia, and emotional lability. Hypotonia manifests
with the “pronator sign” (arms and palms turn outward when held overhead) and the “choreic
hand” (spooning of the extended hand by flexion of the wrist and extension of the fingers). When
chorea and hypotonia are severe, the child may be incapable of feeding, dressing, or walking.
Affected individuals exhibit motor impersistence, with difficulty keeping the tongue protruded
80
(“darting tongue”) or maintaining grip (“milkmaid grip”). Chorea tends to occur both at rest and
with action. Chorea increases with stress and disappears in sleep.

Diagnosis: Sydenham chorea is a clinical diagnosis; however, a combination of acute and

convalescent serum antistreptolysin O titers may help to confirm an acute streptococcal infection.
Negative titers do not exclude the diagnosis.

Treatment: All patients with SC should be evaluated for carditis and started on long-term
antibiotic prophylaxis (e.g., penicillin G benzathine 1.2 million units IM every 2-3 weeks) to
decrease the risk of rheumatic heart disease. For patients with chorea that is impairing, treatment
options include valproate, carbamazepine, and/or dopamine receptor antagonists. Although
phenothiazines, haloperidol, and pimozide are also effective, their side effects limit their utility.

18. Ataxia:
Ataxia is the inability to make smooth, accurate, and coordinated movements, usually due to a
dysfunction of the cerebellum, its inputs or outputs, sensory pathways in the posterior columns of the
spinal cord, or a combination of these.

Causes of acute or recurrent ataxia

Brain tumor
Conversion reaction Postinfectious/immune
Drug ingestion Acute disseminated encephalomyelitis
Encephalitis (brainstem) Acute postinfectious cerebellitis
Genetic disorders (varicella)
Episodic ataxia type 1 Miller Fisher syndrome
Episodic ataxia type 2 Multiple sclerosis
Hartnup disease Pseudoataxia (epileptic)
Maple syrup urine disease Trauma
Hematoma
Hereditary ataxia Postconcussion
Ataxia telangiectasia Vertebrobasilar occlusion
Friedrich ataxia Vascular disorders
Abetalipoprotinemia
Cerebellar hemorrhage
Migraine
Kawasaki disease
Basilar
Benign paroxysmal vertigo

19. Myasthenia gravis:

Myasthenia gravis is a chronic disease characterized by rapid fatigability of striated muscle. The most
common cause is an immune-mediated neuromuscular blockade. The release of acetylcholine (ACh)
into the synaptic cleft by the axonal terminal is normal, but the postsynaptic muscle membrane or
81
motor endplate is less responsive than normal. A decreased number of available ACh receptors are
due to circulating receptor-binding antibodies in most cases of acquired myasthenia.

Clinical Manifestations:

Three clinical varieties are distinguished in childhood: juvenile myasthenia gravis in late infancy
and childhood, congenital myasthenia, and transient neonatal myasthenia.

In the juvenile form, ptosis and some degree of extraocular muscle weakness are the earliest and
most constant signs. Dysphagia and facial weakness are also common, and in early infancy, feeding
difficulties are often the cardinal sign of myasthenia.

Rapid fatigue of muscles is a characteristic feature of myasthenia gravis that distinguishes it from
most other neuromuscular diseases.

Patients are more symptomatic late in the day or when tired. Dysphagia can interfere with eating,
and the muscles of the jaw soon tire when an affected child chews.

Left untreated, myasthenia gravis is usually progressive and can become life threatening

Investigations:

EEG- characteristic decremental response.

Anti Ach antibodies

Thyroid profile and CPK

Muscle biopsy may show lymphorrhages

A clinical test for myasthenia gravis is administration of a short-acting cholinesterase inhibitor,

usually edrophonium chloride. Ptosis and ophthalmoplegia improve within a few seconds, and
fatigability of other muscles decreases.

Treatment:

Cholinesterase inhibiting drugs neostigmine and physostigmine

Steroid treatment

Thymectomy

Plasmapheresis/ IVIG/ rituximab

20. Cerebral palsy:

Cerebral palsy (CP) is a diagnostic term used to describe a group of permanent disorders of
movement and posture causing activity limitation that are attributed to non progressive disturbances
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in the developing fetal or infant brain.

CLASSIFICATION OF CEREBRAL PALSY AND MAJOR CAUSES

MOTOR SYNDROME
NEUROPATHOLOGY/MRI MAJOR CAUSES
(APPROX % OF CP)
Prematurity
Periventricular leukomalacia Ischemia
Periventricular cysts or scars in
Spastic diplegia (35%)
White matter, enlargement of ventricles, Infection
squared of posterior ventricles
Endocrine/metabolic (e.g.,
thyroid)
Periventricular leukomalacia Ischemia, infection
Spastic quadriplegia
(20%) Multicystic encephalomalacia Endocrine/metabolic,
Cortical malformations genetic/developmental
Thrombophilic disorders
Stroke: in utero or neonatal Infection
Focal infarct or cortical, subcortical
Hemiplegia (25%) Genetic/developmental
damage
Cortical malformations
Periventricular hemorrhagic
infarction
Asphyxia
Asphyxia: symmetric scars in putamen and
thalamus Kernicterus
Kernicterus: scars in globus pallidus,
Extrapyramidal (athetoid, Mitochondrial
hippocampus
dyskinetic) (15%)
Mitochondrial: scaring globus pallidus,
caudate, putamen, brainstem
Genetic/metabolic
No lesions: ? dopa-responsive dystonia

Diagnosis:

A thorough history and physical examination should preclude a progressive disorder of the CNS,
including degenerative diseases, metabolic disorders, spinal cord tumor, or muscular dystrophy.

An MRI scan of the brain is indicated to determine the location and extent of structural lesions or
associated congenital malformations; MRI with diffusion tensor imaging (DTI) is being used to
map white matter tracks more precisely.

Additional studies may include tests of hearing and visual function.

Genetic evaluation should be considered in patients with congenital malformations (chromosomes)

or evidence of metabolic disorders (e.g., amino acids, organic acids, MR spectroscopy).

Tests to detect inherited thrombophilic disorders may be indicated in patients in whom an in utero
or neonatal stroke is suspected as the cause of CP.

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Treatment:

1. Because CP is usually associated with a wide spectrum of developmental disorders, a

multidisciplinary approach is most helpful in the assessment and treatment of such children.

2. A team of physicians from various specialties, as well as occupational and physical therapists,
speech pathologists, social workers, educators, and developmental psychologists provide important
contributions to the treatment of those children who develop CP.

3. Several drugs have been used to treat spasticity, including the benzodiazepines and baclofen.

4. ophthalmologist should be included in the initial assessment.

5. Lower urinary tract dysfunction should receive prompt assessment and treatment.

6. Surgery-- rhizotomy, tenotomy of Achilles tendon, Botulinum toxin injected into specific
muscle groups for the management of spasticity shows a very positive response in many patients and
intrathecal baclofen delivered with an implanted pump has been used successfully.

21. ADEM: ADEM is an initial inflammatory, demyelinating event

with multifocal neurologic deficits, typically accompanied by encephalopathy.
Mean age between 5 and 8 yr with a slight male predominance.

Etiopathogenesis: Molecular mimicry induced by infectious exposure or vaccine

may trigger production of CNS autoantigens. Many patients experience a transient febrile illness in
the month prior to ADEM onset. Preceding infections associated with ADEM include influenza,
Epstein-Barr virus, cytomegalovirus, varicella, enterovirus, measles, mumps, rubella, herpes simplex,
and Mycoplasma pneumoniae. Postvaccination ADEM has been reported following immunizations
for rabies, smallpox, measles, mumps, rubella, Japanese encephalitis B, pertussis,
diphtheria-polio-tetanus, and influenza.

Clinical Manifestations: Initial symptoms of ADEM may include lethargy,

fever, headache, vomiting, meningeal signs, and seizure, including status epilepticus.
Encephalopathy is a hallmark of ADEM and common neurologic signs in ADEM include visual loss,
cranial neuropathies, ataxia, motor and sensory deficits, plus bladder/bowel dysfunction with
concurrent spinal cord demyelination.

Neuroimaging: Head CT may be normal or show

hypodense regions. Cranial MRI, the imaging study of choice, typically exhibits large, multifocal

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and sometimes confluent or tumefactive T2 lesions with variable enhancement within white and
often gray matter. Serial MRI imaging 3-12 mo following ADEM shows improvement and often
complete resolution of T2 abnormalities although residual gliosis may remain.

Laboratory Findings: There is no biologic marker for

ADEM and laboratory findings can vary widely. CSF studies often exhibit pleocytosis. CSF protein
can be elevated. Up to 10% of ADEM have oligoclonal bands in the CSF . Electroencephalograms
(EEG) often show generalized slowing, consistent with encephalopathy.

Differential Diagnosis: Follow-up MRI examinations 3-12 mo

after ADEM should show improvement; new or enlarging T2 lesions should prompt re-evaluation for
other etiologies such as MS, leukodystrophies, tumor, vasculitis, or mitochondrial, metabolic, or
rheumatologic disorders.

Treatment: High dose intravenous steroids

are commonly employed (typically methylprednisolone 20-30 mg/kg per day for 5 days with a
maximum dose of 1,000 mg per day). An oral prednisone taper over 1 mo may prevent relapse. Other
treatment options include intravenous immune globulin (IVIG; usually 2 g/kg administered over 2-5
days) or plasmapheresis (typically 5-7 exchanges administered every other day).

Prognosis: Many children experience full

recovery after ADEM but some are left with residual motor and/or cognitive deficits. ADEM is
usually a monophasic illness but demyelinating symptoms can fluctuate for several months.

CLINICAL AND MRI FEATURES THAT MAY DISTINGUISH FROM FIRST ATTACK OF
MS
MS
ADEM
Age <10 yr >10 yr
Stupor/coma + −
Fever/vomitin
+ −
g
Family history No 20%
Sensory
+ +
complaints
Optic neuritis Bilateral Unilateral
Manifestations Polysymptomatic Monosymptomatic
85
 MS
ADEM
Widespread lesions: basal ganglia, Isolated lesions: periventricular white
MRI imaging
thalamus, cortical gray-white junction matter, corpus callosum
CSF Pleocytosis (lymphocytosis) Oligoclonal bands
Response to
+ +
steroids
Follow-up No new lesions New lesions

Oligoclonal bands are also found in:

• Multiple sclerosis, Devic's disease, Systemic lupus erythematosus, Neurosarcoidosis, SSPE
Subarachnoid hemorrhage, Syphilis, CNS Lymphoma.

22. Mitochondrial Encephalomyopathies:

Def: Mitochondrial encephalomyopathies are a heterogeneous group of clinical

syndromes caused by genetic lesions that impair energy production through oxidative
phosphorylation.

Clinical features: Signs of brain and muscle dysfunction (seizures, weakness, ptosis, external
ophthalmoplegia, psychomotor regression, hearing loss, movement disorders, and ataxia) in
association with lactic acidosis are prominent features of mitochondrial disorders. Cardiomyopathy
and diabetes mellitus can also result from mitochondrial disorders. Children with mitochondrial
disorders often have multifocal signs that are intermittent or relapsing-remitting, often in association
with intercurrent illness.

mtDNA is distinct from nDNA for the following reasons:

(1) Its genetic code differs from nDNA,

(2) It is tightly packed with information because it contains no introns,

(3) It is subject to spontaneous mutations at a higher rate than nDNA,

(4) It has less efficient repair mechanisms, and

(5) It is present in hundreds or thousands of copies per cell and is transmitted by maternal
inheritance.

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mtDNA is contributed only by the oocyte in the formation of the zygote.

Mitochondrial diseases can be caused by mutations of nuclear DNA (nDNA) or mtDNA.

Diseases of mitochondrial oxidative phosphorylation can be divided into 3 groups: (1) defects of
mtDNA, (2) defects of nDNA, and (3) defects of communication between the nuclear and
mitochondrial genome.

Mitochondrial diseases caused by defects in nDNA include

a) defects in substrate transport (plasmalemmal carnitine transporter, carnitine palmitoyltransferase I

and II, carnitine acylcarnitine translocase defects),

b) defects in substrate oxidation (pyruvate dehydrogenase complex, pyruvate carboxylase,

intramitochondrial fatty acid oxidation defects),

c) defects in the Krebs cycle (α-ketoglutarate dehydrogenase, fumarase, aconitase defects), and

d) defects in the respiratory chain (complexes I-V) including defects of oxidation/phosphorylation

coupling (Luft syndrome) and defects in mitochondrial protein transport.

Diseases caused by defects in mtDNA can be divided into those

a) associated with point mutations that are maternally inherited (e.g., LHON, MELAS, MERRF,
and NARP syndromes) and

b) those due to deletions or duplications of mtDNA that reflect altered communication between the
nucleus and the mitochondria (KSS; Pearson syndrome and progressive external ophthalmoplegia
[PEO]).

1. Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike Episodes (Melas):

Children with MELAS may be normal for the 1st several years, but they gradually display
delayed motor and cognitive development and short stature.

The clinical syndrome is characterized by

(1) recurrent strokelike episodes of hemiparesis or other focal neurologic signs with lesions most
commonly seen in the posterior temporal, parietal, and occipital lobes (CT or MRI evidence of focal
brain abnormalities);

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(2) lactic acidosis, ragged red fibers (RRF), or both; and

(3) at least 2 of the following: focal or generalized seizures, dementia, recurrent migraine headaches,
and vomiting.

Investigations: Regional cerebral hypoperfusion can be detected by single-photon emission

CT (SPECT) studies and MR spectroscopy can detect focal areas of lactic acidosis in the brain.
Neuropathology may show cortical atrophy. Muscle biopsy specimens usually show RRF.

Treatment: The prognosis in patients with the full syndrome is poor. Therapeutic trials
reporting some benefit have included corticosteroids, coenzyme Q10, nicotinamide, riboflavin,
and L-arginine and preclinical studies reported some success with resveratrol.

2. Reversible Infantile Cytochrome C Oxidase Deficiency Myopathy:

A reversible form of severe neuromuscular weakness and hypotonia in infants was recently
characterized and found to be due to a maternally inherited homoplasmic m.14674T>C
mt-tRNAGlu mutation associated with a deficiency of cytochrome c oxidase (COX) in 17 patients
from 12 families. Affected children presented within the 1st few weeks of life with hypotonia,
severe muscle weakness and very elevated serum lactate levels, and they often required
mechanical ventilation. Muscle biopsies taken from these children in the neonatal period show
ragged red fibers and deficient COX activity, but these findings disappeared within 5-20 mo when
the infants recovered spontaneously. This reversible disorder has been observed only in COX
deficiency associated with the 14674T>C mt-tRNAGlu mutation, so it has been suggested that infants
with this type of severe weakness in the neonatal period be tested for this mutation to help with
prognosis.

3. Myoclonus Epilepsy and Ragged Red Fibers (MERRF):

This syndrome is characterized by progressive myoclonic epilepsy, mitochondrial myopathy, and

cerebellar ataxia with dysarthria and nystagmus. Pathologic findings include elevated serum lactate
concentrations, RRF on muscle biopsy, and marked neuronal loss and gliosis. Targeted mutation
analysis or mutation analysis after sequencing of the mitochondrial genome are used to diagnosis
MERRF. There is no specific therapy, although coenzyme Q10 appeared to be beneficial in a
mother and daughter with the MERRF mutation. The anticonvulsant levetiracetam has been reported
to help reduce myoclonus and myoclonic seizures in this disorder.

4. Leigh Disease (Subacute Necrotizing Encephalomyopathy):

There are several known genetically determined causes of Leigh disease: pyruvate dehydrogenase
88
complex deficiency, complex I or II deficiency, complex IV (COX) deficiency, complex V (ATPase)
deficiency, and deficiency of coenzyme Q10.

Clinical features: Leigh disease is a progressive degenerative disorder, and most cases become
apparent during infancy with feeding and swallowing problems, vomiting, and failure to thrive.
Delayed motor and language milestones may be evident, and generalized seizures, weakness,
hypotonia, ataxia, tremor, pyramidal signs, and nystagmus are prominent findings. Intermittent
respirations with associated sighing or sobbing are characteristic and suggest brainstem dysfunction.

Investigations: Abnormal results on CT or MRI scan consist of bilaterally symmetric

areas of low attenuation in the basal ganglia and brainstem as well as elevated lactic acid on MR
spectroscopy. Microscopically, these spongiform lesions show cystic cavitation with neuronal loss,
demyelination, and vascular proliferation.

Treatment: The overall outlook is poor, but a few patients experience prolonged periods of
remission. There is no definitive treatment for the underlying disorder, but a range of vitamins
including riboflavin, thiamine, and coenzyme Q are often given to try to improve mitochondrial
function. Biotin, creatine, succinate, and idebenone as well as a high-fat diet have also been used, but
phenobarbital and valproic acid should be avoided due to their inhibitory effect on the
mitochondrial respiratory chain.

5. Leber Hereditary Optic Neuropathy (LHON):

LHON is characterized acute or subacute visual loss caused by severe bilateral optic atrophy. The
classic ophthalmologic features include circumpapillary telangiectatic microangiopathy and
pseudoedema of the optic disc. Variable features may include cerebellar ataxia, hyperreflexia,
Babinski sign, psychiatric symptoms, peripheral neuropathy, or cardiac conduction abnormalities
(pre-excitation syndrome). Lactic acidosis and RRF tend to be conspicuously absent in LHON.

6. Kearns-Sayre Syndrome (KSS):

The criteria for KSS include a triad of

(1) onset before age 20 yr,

(2) progressive external ophthalmoplegia (PEO) with ptosis, and

(3) pigmentary retinopathy.

There must also be at least 1 of the following: heart block, cerebellar syndrome, or cerebrospinal
fluid protein >100 mg/dL.

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The prognosis is guarded, despite placement of a pacemaker, and progressively downhill, with death
resulting by the 3rd or 4th decade. Muscle biopsy shows RRF and variable COX-negative fibers.
Patients should be monitored closely for endocrine abnormalities, which can be treated. Coenzyme Q
has been reported anecdotally to have some beneficial effect and positive effects of folinic acid for
low folate levels has been reported.

7. Reye Syndrome:

This encephalopathy, which has become uncommon, is associated with pathologic features
characterized by fatty degeneration of the viscera (microvesicular steatosis) and mitochondrial
abnormalities and biochemical features consistent with a disturbance of mitochondrial metabolism.

23. DMD:

Definition: The term dystrophy means abnormal growth, derived from the Greek trophe,
meaning “nourishment.”

A muscular dystrophy is distinguished from all other neuromuscular diseases by four obligatory
criteria: It is a primary myopathy, it has a genetic basis, the course is progressive, and degeneration
and death of muscle fibers occur at some stage in the disease.

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease
affecting all races and ethnic groups. This disease is inherited as an X-linked recessive trait.

Its characteristic clinical features are progressive weakness, intellectual impairment, hypertrophy of
the calves, and proliferation of connective tissue in muscle.

Clinical Manifestations:

1. Infant boys are only rarely symptomatic at birth or in early infancy.

2. Poor head control in infancy may be the first sign of weakness.
3. Distinctive facies are not an early feature because facial muscle weakness is a late event; in
later childhood, a “transverse” or horizontal smile may be seen.
4. Walking is often accomplished at the normal age of about 12 mo, but hip girdle weakness
may be seen in subtle form as early as the 2nd year. Toddlers might assume a lordotic
posture when standing to compensate for gluteal weakness. Scoliosis often becomes rapidly
progressive after confinement to a wheelchair.
5. An early Gowers sign is often evident by age 3 yr and is fully expressed by age 5 or 6 yr. A
Trendelenburg gait, or hip waddle, appears at this time.
6. Common presentations in toddlers include delayed walking, falling, toe walking and trouble
running or walking upstairs, developmental delay, and, less often, malignant hyperthermia
after anesthesia.
7. Respiratory muscle involvement is expressed as a weak and ineffective cough, frequent
pulmonary infections, and decreasing respiratory reserve. The thoracic deformity further

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 compromises pulmonary capacity and compresses the heart.
8. Pharyngeal weakness can lead to episodes of aspiration, nasal regurgitation of liquids, and
an airy or nasal voice quality.
9. The function of the extraocular muscles remains well preserved. Incontinence due to anal and
urethral sphincter weakness is an uncommon and very late event.
10. Contractures most often involve the ankles, knees, hips, and elbows.
11. Enlargement of the calves (pseudohypertrophy) and wasting of thigh muscles are classic
features. After the calves, the next most common site of muscular hypertrophy is the tongue,
followed by muscles of the forearm. Fasciculations of the tongue do not occur.
12. Cardiomyopathy, including persistent tachycardia and myocardial failure, is seen in 50-80%
of patients with this disease.
13. Intellectual impairment occurs in all patients, although only 20-30% have an IQ <70.
14. Epilepsy is slightly more common than in the general pediatric population.
15. Death occurs usually at about 18-20 yr of age. The causes of death are respiratory failure in
sleep, intractable heart failure, pneumonia, or occasionally aspiration and airway obstruction.

Laboratory Findings:

1. The serum CK level is consistently greatly elevated in DMD, even in presymptomatic stages,
including at birth.
2. Cardiac assessment by echocardiography, electrocardiography (ECG), and radiography of the
chest is essential and should be repeated periodically.
3. Electromyography (EMG) shows characteristic myopathic features but is not specific for
DMD. No evidence of denervation is found. Motor and sensory nerve conduction velocities
are normal.

Diagnosis:

1. Polymerase chain reaction (PCR) for the dystrophin gene mutation is the primary test, if the
clinical features and serum CK are consistent with the diagnosis.
2. If the blood PCR is diagnostic, muscle biopsy may be deferred, but if it is normal and clinical
suspicion is high, the more specific dystrophin immunocytochemistry performed on muscle
biopsy sections detects the 30% of cases that do not show a PCR abnormality.
3. The muscle biopsy is diagnostic and shows endomysial connective tissue proliferation,
scattered degenerating and regenerating myofibers.

Genetic Etiology and Pathogenesis:

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Despite the X-linked recessive inheritance in DMD, about 30% of cases are new mutations, and the
mother is not a carrier. Symptomatic girls are explained by the Lyon hypothesis in which the normal
X chromosome becomes inactivated and the one with the gene deletion is active. The asymptomatic
carrier state of DMD is associated with elevated serum CK values in 80% of cases. The level of
increase is usually in the magnitude of hundreds or a few thousand but does not have the extreme
values noted in affected males.

A 427-kd cytoskeletal protein known as dystrophin is encoded by the gene at the Xp21.2 locus.

The molecular defects in the dystrophinopathies vary and include intragenic deletions, duplications,
or point mutations of nucleotides.

Analysis of the dystrophin protein requires a muscle biopsy and is demonstrated by Western blot
analysis or in tissue sections by immunohistochemical methods using either fluorescence or light
microscopy of antidystrophin antisera. In classic DMD, levels of <3% of normal are found.

Prenatal diagnosis is possible as early as the 12th wk of gestation by sampling chorionic villi for
DNA analysis by Southern blot or PCR and is confirmed in aborted fetuses with DMD by
immunohistochemistry for dystrophin in muscle.

Treatment:

1. There is neither a medical cure for this disease nor a method of slowing its progression. Much
can be done to treat complications and to improve the quality of life of affected children.
2. Cardiac decompensation often responds initially well to digoxin.
3. Pulmonary infections should be promptly treated. Patients should avoid contact with
children who have obvious respiratory or other contagious illnesses. Immunizations for
influenza virus and other routine vaccinations are indicated.
4. Preservation of a good nutritional state is important. Adequate calcium intake is important
to minimize osteoporosis in boys confined to a wheelchair.
5. Physiotherapy delays but does not always prevent contractures. Excessive exercise can
actually accelerate the process of muscle fiber degeneration.
6. Other treatment of patients with DMD involves the use of prednisone, prednisolone,
deflazacort, or other steroids.
7. Research areas: Another potential treatment still under investigation is the intramuscular
injection of antisense oligonucleotide drugs that induce exon skipping during mRNA
splicing to restore the open reading frame in the DMD gene.
8. Stem cell implantation or activation in muscle was theoretically plausible but has not

92
 proved practical.

24. Aseptic meningitis:

Viruses BACTERIA Bacterial Fungi Parasites
Entero viruses Parameningeal Strongyloides
Arboviruses M. tuberculosis Focus Coccidiomycosis Toxocara canis
EBV Leptospirosis Blastomycosis Taenia solium
CMV Rickettsia Sinusitis Cyptococcosis Schistosoma
Varicella-zoster rickettsii Mastoiditis Histoplasmosis Acanthamoeba
Measles M. pneumoniae Brain abscess Candida Naegleria fowleri
Mumps C. pneumoniae Subdural
rubella empyema
Cranial
osteomyelitis
Post infectious Systemic Malignancy Drugs Miscellaneous
Intrathecal
Vaccines: rabies, Endocarditis Leukemia infections Post migrane state
influenza, measles Kawasaki disease Lymphoma NSAIDS Post ictal state
SLE CNS tumours OKT3 monoclonal
Rheumatoid antibodies
artritis IvIg

Determining the specific cause of CNS infection is facilitated by careful examination of the CSF with

1. specific stains Kinyoun carbol fuchsin for mycobacteria, India ink for fungi,
2. cytology
3. antigen detection (Cryptococcus)
4. serology (syphilis, West Nile virus, arboviruses)
5. viral culture (enterovirus)
6. polymerase chain reaction (herpes simplex, enterovirus, and others).
7. Other potentially valuable diagnostic tests include blood cultures, CT or MRI of the brain,
serologic tests, and, rarely, brain biopsy.

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CLASSIFICATION OF ENCEPHALITIS BY CAUSE AND SOURCE

I INFECTIONS: VIRAL
A Spread: person to person only
1 Mumps, Measles Enteroviruses Rubella Herpesvirus group Pox group

2 : Parvovirus Influenza A and B Adenovirus

3 : Other: reoviruses, respiratory syncytial, parainfluenza, hepatitis B

B Arthropod-borneagents
Arboviruses: spread to humans by mosquitoes or ticks
Dengue
West Nile

C Spread by warm-blooded mammals Rabies:

94
II INFECTIONS: NONVIRAL
A Rickettsial: in Rocky Mountain spotted fever and typhus
B Mycoplasma pneumoniae:
C Bacterial: tuberculous and other bacterial meningitis;
D Spirochetal: syphilis, congenital or acquired; leptospirosis; Lyme disease
E Fungal: immunologically compromised patients at special risk: cryptococcosis;
histoplasmosis; aspergillosis; mucormycosis; candidosis; coccidioidomycosis
F Protozoal: Plasmodium, Trypanosoma, Naegleria, and Acanthamoeba species;
Toxoplasma gondii
G Metazoal: trichinosis; echinococcosis; cysticercosis; schistosomiasis

III PARAINFECTIOUS: POSTINFECTIOUS, ALLERGIC, AUTOIMMUNE

A Associated with specific diseases (these agents may also cause direct CNS damage; see I and II
Measles Rickettsial infections Influenza A and B
Rubella Mumps Varicella-zoster Mycoplasma pneumoniae

B Associated with vaccines

Rabies Measles

Vaccinia Yellow fever

C Autoimmune
Paraneoplastic
Idiopathic

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 IV HUMAN SLOW-VIRUS DISEASES
A Subacute sclerosing panencephalitis; measles; rubella?
B Creutzfeldt-Jakob disease (spongiform encephalopathy)
C Progressive multifocal leukoencephalopathy
D Human immunodeficiency virus

V UNKNOWN: COMPLEX GROUP.

32. Neurodegenerative Disorders of Childhood:

Neurodegenerative disorders of childhood encompass a large, heterogeneous group of diseases that

result from specific genetic and biochemical defects, chronic viral infections, and varied unknown
causes.

The hallmark of a neurodegenerative disease is regression and progressive deterioration of

neurologic function.

Upper motor neuron signs and progressive spasticity are the hallmarks of white matter disorders;

Convulsions, intellectual, and early visual impairment are the hallmarks of grey matter disorders.

NEUROMETABOLIC CONDITIONS ASSOCIATED WITH DEVELOPMENTAL

REGRESSION
AGE AT
CONDITIONS COMMENTS
ONSET (yr)
Vomiting, hypoglycemia, poor feeding,
Fructose intolerance
failure to thrive (when given fructose)
Lethargy, hypotonia, icterus, cataract,
Galactosemia
hypoglycemia (when given lactose)
<2, with Glycogenosis (glycogen storage
Hypoglycemia, cardiomegaly (type II)
hepatomegaly disease) types I-IV
Mucopolysaccharidosis types I and
Coarse facies, stiff joints
II
Niemann-Pick disease, infantile
Gray matter disease, failure to thrive
type

96
AGE AT
CONDITIONS COMMENTS
ONSET (yr)
Seizures, cherry red macula, edema,
Tay-Sachs disease
coarse facies
Zellweger syndrome Hypotonia, high forehead, flat facies
Gaucher disease (neuronopathic
Extensor posturing, irritability
form)
Irritability, extensor posturing, optic
Krabbe disease
atrophy and blindness
Girls with deceleration of head growth,
Rett syndrome loss of hand skills, hand wringing,
<2, without impaired language skills, gait apraxia
hepatomegaly Poor feeding, tremors, myoclonus,
Maple syrup urine disease
opisthotonos
Phenylketonuria Light pigmentation, eczema, seizures
MRK Likes
MPC Hypertonia, irritability, seizures,
Menkes kinky hair disease
abnormal hair
Subacute necrotizing
White matter disease
encephalopathy of Leigh
Canavan disease White matter disease, Macrocephaly
Niemann-Pick disease types III and
Hepatosplenomegaly, gait difficulty
IV
Liver disease, Kayser-Fleischer ring;
Wilson disease
deterioration of cognition is late
Gangliosidosis type II Gray matter disease
Neuronal ceroid lipofuscinosis Gray matter disease
Mitochondrial encephalopathies
2-5 (e.g., myoclonic epilepsy with Gray matter disease
ragged red fibers [MERRF])
Ataxia-telangiectasia Basal ganglia disease
Huntington disease (chorea) Basal ganglia disease
Metachromatic leukodystrophy White matter disease
White matter disease, behavior
Adrenoleukodystrophy problems, deteriorating school
performance, quadriparesis
Same as for adrenoleukodystrophy in 2
Adrenoleukodystrophy
to 5 yr olds
Multiple sclerosis White matter disease
Neuronal ceroid lipofuscinosis,
5-15 juvenile and adult (Spielmeyer-Vogt Gray matter disease
and Kufs disease)
Peripheral neuropathy, ataxia, retinitis
Refsum disease
pigmentosa
Subacute sclerosing panencephalitis Diffuse encephalopathy, myoclonus;
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AGE AT
CONDITIONS COMMENTS
ONSET (yr)
may occur years after measles

Metachromatic Leukodystrophy (MLD)

This disorder of myelin metabolism is inherited as an autosomal recessive trait and is characterized
by a deficiency of arylsulfatase A (ARSA) activity. The absence or deficiency of arylsulfatase A
leads to accumulation of cerebroside sulfate within the myelin sheath of the central nervous system
(CNS) and peripheral nervous system.

Late infantile MLD begins with insidious onset of gait disturbances between 1 and 2 yr of age. The
child initially appears awkward and frequently falls, but locomotion is gradually impaired
significantly and support is required in order to walk. The extremities are hypotonic, and the deep
tendon reflexes are absent or diminished. Within the next several months, the child can no longer
stand, and deterioration in intellectual function becomes apparent. Visual fixation is diminished,
nystagmus is present, and examination of the retina shows optic atrophy. Feeding and swallowing
are impaired due to pseudobulbar palsies, and a feeding gastrostomy is required. Patients ultimately
become stuporous and die of aspiration or bronchopneumonia by age 5-6 yr.

Investigations:

1. Neurophysiologic evaluation shows slowing of peripheral nerve conduction velocities (NCVs) and
progressive changes in the VEPs, ABRs, and somatosensory-evoked potentials (SSEPs).

2. CT and MRI images of the brain indicate diffuse symmetric attenuation of the cerebellar and
cerebral white matter.

3. Examination of the CSF shows an elevated protein content.

4. Cresyl violet applied to tissue specimens produces metachromatic staining of the sulfatide
granules, giving the disease its name.

Treatment: Bone marrow transplantation is a promising experimental therapy.

Prenatal diagnosis of MLD is made by assaying of ARSA activity in chorionic villi or cultured
amniotic fluid cells.

Juvenile MLD has many features in common with late infantile MLD, but the onset of symptoms is
delayed to 5-10 yr of age. Deterioration in school performance and alterations in personality may
herald the onset of the disease. In the terminal stages, generalized tonic-clonic convulsions are
prominent and are difficult to control. Patients rarely live beyond mid-adolescence.

Adult MLD occurs from the 2nd to 6th decade. Abnormalities in memory, psychiatric disturbances,
and personality changes are prominent features.

Adrenoleukodystrophy:

The adrenoleukodystrophies consist of a group of CNS degenerative disorders that are often
associated with adrenal cortical insufficiency and are inherited by X-linked recessive transmission.
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Classic adrenoleukodystrophy (ALD), also called cerebral ALD (CERALD) is considered to be the
most common leukodystrophy.
Boys present between 5 and 15 yr of age with evidence of academic difficulties, behavioral
disturbances, and gait abnormalities.
ALD is caused by accumulation of very long chain fatty acids in neural tissue and adrenals due to
mutations in the ABCD1 gene coding for the ALD protein.

CERALD:

Clinical features: Generalized seizures are common in the early stages. Upper motor
neuron signs include spastic quadriparesis and contractures, ataxia, and marked swallowing
disturbances secondary to pseudobulbar palsy. Adrenal insufficiency characterized by abnormal
skin pigmentation (tanning without exposure to sun) may precede the onset of neurologic symptoms.
Death occurs within 10 yr of the onset of the neurologic signs.

Investigations: CT scans and MRI studies of patients indicate periventricular

demyelination beginning posteriorly. ABRs, VEPs, and SSEPs may be normal initially but
ultimately show prolonged latencies and abnormal waveforms.

Treatment: Lorenzo's oil (LO), a mixture of glyceryl trioleate and glyceryl trierucate,
lowers very long chain fatty acid (VLCFA) levels by inhibiting synthesis. LO may be effective in
slowing onset of cerebral disease when given to asymptomatic boys with no clinical or MRI findings.
Bone marrow transplant can prevent the progression of the disease when done at an early stage
before clinical signs develop.

Adrenomyeloneuropathy and Neonatal ALD are the other varieties in ALD.

Investigation for neurodegenerative conditions in school-age children :

 Blood
o Liver function tests
o Copper, ceruloplasmin
o Lactate
o Amino acids
o Very long chain fatty acids
o Immunoglobulin’s
o Thyroid function tests
o Autoantibodies, including antinuclear antibodies
o White cell enzymes (targeted for conditions being considered)
o Appropriate genetic tests, esp. DNA studies for specific disorders
 Urine
o Amino acids/organic acids
o Renal epithelial
o Metachromatic granules
 CSF
o Immunoglobulin’s
o Electrophoresis
99
 o Cells (cytospin)
o Measles IgG
o Lactate
o Neurotransmitters
 Neurophysiology
o EEG
o ERG
o VEP
 Neuroimaging : CT scan, MRI

Differentiating features White Matter disease Gray matter disease

1 Age of onset Usually late Early
2 Head size May have Megalencephaly Usually Microcephaly
3 Seizures Late,rare Early ,Severe
4 Cognitive function Initially normal Progressive dementia
5 Peripheral neuropathy Early demyelination Late, Axonal loss
6 Spasticity Early severe Late,Progressive
7 Reflexes Absent(Neuropathy) Normal or Exaggarated
Exaggerated(Long tracts)
8 Cerebellar signs Early prominent Late

9 Fundus examination May show optic atrophy Retinal degeneration

10 EEG Diffuse Delta slowing Epileptiform discharges

11 EMG Slowing nerve conduction Usually normal

velocity
12 Evoked potentials(VEP,ABR) Prolonged / Absent Usually normal

13 ERG normal abnormal

Childhood epileptic syndromes with good prognosis:

1. Benign neonatal familial convulsions

2. Infantile familial convulsions
3. Febrile convulsions plus syndromes
4. Benign myoclonic epilepsy of infancy
5. Juvenile myoclonic epilepsy
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 6. Partial idiopathic epilepsy with rolandic spikes
7. Idiopathic occipital partial epilepsy
8. Petit mal absence epilepsy

Absence Seizures:

Age: Typical absence seizures usually start at 5-8 yr of age and are often overlooked by parents for
many months even though they can occur up to hundreds of times per day.

Clinical features: Unlike complex partial seizures they do not have an aura, usually last for only a
few seconds, and are accompanied by flutter or upward rolling of the (absence seizures can have
simple automatisms like lip-smacking or picking at clothing and the head can minimally fall
forward).

Absence seizures do not have a postictal period and are characterized by immediate resumption of
what the patient was doing before the seizure.

Hyperventilation for 3-5 min can precipitate the seizures.

EEG findings: 3 Hz spike–and–slow wave discharges.

DOC- ethosuximide, valproate.

Atypical absence seizures have associated myoclonic components and tone changes of the head and
body and are also usually more difficult to treat. They are precipitated by drowsiness and are usually
accompanied by 1-2 Hz spike–and–slow wave discharges.

Juvenile absence seizures are similar to typical absences but occur at a later age and are
accompanied by 4-6 Hz spike–and–slow wave and polyspike–and–slow wave discharges.

Mechanisms of Seizures:

One can distinguish in the pathophysiology of epilepsy four distinct, often sequential, mechanistic
processes.

1. First is the underlying etiology, which is any process that can disrupt neuronal function and
connectivity and that eventually leads to the process of making the brain epileptic (epileptogenesis).

The underlying etiologies of epilepsy are diverse and include, among other things, brain tumors,
strokes, scarring, or mutations of specific genes. In many other epileptic conditions, a clear
etiology is still lacking and in others the etiology may be known, but it is still not known how the
identified underlying genetic etiology or brain insult results in epilepsy.

2. Second, epileptogenesis is the mechanism during which the brain turns epileptic. Kindling is an
animal model for human temporal lobe epilepsy in which repeated electrical stimulation of selected
areas of the brain with a low-intensity current initially causes no apparent changes but with repeated
stimulation results in epilepsy. Mossy fibers are shown to underlie increased excitability in medial
temporal lobe epilepsy resulting from mesial temporal sclerosis in humans and in animal models.

3. The third process is the resultant epileptic state of increased excitability that is present in all
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patients irrespective of the underlying etiology or mechanism of epileptogenesis.

4. The fourth process is seizure-related neuronal injury as demonstrated by MRI in patients after
prolonged febrile and afebrile status epilepticus. Many such patients show acute swelling in the
hippocampus and long-term hippocampal atrophy with sclerosis on MRI.

Infantile spasms (west syndrome):

Age- 4 mon to 8 mon

Types:

Flexor- occurs in clusters, salam attack

Extensor – least common

Mixed- Mc type

Infantile spasms grouped into 2

Crytogenic: only 10%, antenatal, natal, post natal, dev h/o, development h/o, imaging all are normal

Symptomatic: triad of infantile spasms, hypsarrthymias, psychomotor retardation.ususally associated

with malformation of brain, neurocutaneous syndromes and chromosomal anomalies.

Pathogenesis:

CRH a putative neurotransmitter

CRH acts on ant pituitary to release ACTH

ACTH suppresses the metabolism and secretion of CRH by negative feed back mechanism

Any prenatal/ perinatal/ post natal insult results in loss of negative feed back mechanisms

Leading to increased CRH

Neuronal hyperexcitability and seizures

EEG: hypsarrthymias

Treatment: ACTH,prednisolone, pyridoxine, vigabatrin , IVIG and sodium valproate.

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An approach to the child with a suspected convulsive disorder.

103
 CVS
1. SVT
2. PULMONARY VASCULAR DISEASE (EISENMENGER SYNDROME)
3. PDA- new born notes
4. HYPERTENSION:
5. CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS
6. CLINICAL EVALUATION OF CONFIRMED HYPERTENSION
7. HYPERTENSIVE EMERGENCY:
8. ANTIARRYTHMIC DRUGS: VAUGHAN WILLIAMS CLASSIFICATION
9. Cardiomyopathy
10. Chest pain
11. syncope
12. Cardiac intervention procedures
13. Ccf
14. Levosimendan articles
15. Rheumatic fever
16. Second heart sound - notes
17. Tof/ cyanotic spell
18. Long qt syndrome

SVT:
Supraventricular tachycardia (SVT) is a general term that includes essentially all forms of
paroxysmal or incessant tachycardia except ventricular tachycardia. The category of SVT can be
divided into 3 major subcategories:
1. re-entrant tachycardias using an accessory pathway,
2. re-entrant tachycardias without an accessory pathway, and
3. ectopic or automatic tachycardias.
Atrioventricular reciprocating tachycardia (AVRT) involves an accessory pathway and is the most
common mechanism of SVT in infants.
CAUSES:
 Idiopathic- more common in young infants.
 WPW pre excitation in 10 to 20% of cases.
 Congenital heart diseases: Ebsteins anomaly, single ventricle
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  May occur following cardiac surgeries
Clinical features:
1. Many infants tolerate SVT well.
2. SVT may decrease cardiac output and result in CHF.
3. Clinical features of CHF include irritability, tachypnea, poor feeding and pallor.
4. Older children may complain of chest pain, palpitations, shortness of breath and fatigue.
5. Children with WPW have a small real risk of sudden death.
Investigations:
ECG: In neonates, SVT is usually manifested as a narrow QRS complex (<0.08 sec). AV
reciprocating tachycardia uses a bypass tract that may either be able to conduct bidirectionally
(Wolff-Parkinson-White [WPW] syndrome) or retrograde only (concealed accessory pathway).
For risk stratification 24 hr holter monitoring, exercise study and catheter ablation.

Schematic representation of the heart with a right-sided accessory pathway (Wolff-Parkinson-White

syndrome). The asterisk indicates initiation of the sinus beat. The arrows indicate the direction and
spread of excitation. The electrocardiographic complex shown represents a fusion beat that combines
activation over the normal (n) and accessory (a) pathways. The latter inscribes the delta wave. NSR,
normal sinus rhythm.

Management:

Vagal stimulatory manoeuvres: Vagal stimulation by placing of the face in ice water (in older
children) or by placing an ice bag over the face (in infants) may abort the attack. To terminate the
attack, older children may be taught vagal maneuvers such as the Valsalva maneuver, straining,
breath holding, or standing on their head.

Drugs:

1. Adenosine is considered the drug of choice. Other drugs like esmolol, verapamil and digoxin
have been tried. ADENOSINE 0.1 – 0.2 mg/kg rapid push. Adenosine breaks SVT by producing
block at the AV node.

2. Iv Amiodarone for resistant and recurrent SVT.

3. If in severe CHF emergency cardioversion.

4. Transoesophageal pacing.

5. Radiofrequency catheter ablation

6. Surgical interruption of accessory pathways should be considered.

Prevention of recurrence of SVT:

105
1. In infants without WPW pre excitation – propranolol is useful.

2. In infants with WPW pre excitation – digoxin is used

3. Parents should be taught to measure the heart rate in their infants, so that prolonged unapparent
episodes of SVT may be detected before heart failure occurs.

2. Pulmonary Vascular Disease (Eisenmenger Syndrome)

Pathophysiology

The term Eisenmenger syndrome refers to patients with a ventricular septal defect in which blood is
shunted partially or totally from right to left as a result of the development of pulmonary vascular
disease. This physiologic abnormality can also occur with atrioventricular septal defect, ventricular
septal defect, patent ductus arteriosus or any other communication between the aorta and pulmonary
artery.

In Eisenmenger syndrome, pulmonary vascular resistance after birth either remains high or, after
having decreased during early infancy, rises thereafter because of increased shear stress on
pulmonary arterioles.

Factors playing a role in the rapidity of development of pulmonary vascular disease include

 Increased pulmonary arterial pressure,

 Increased pulmonary blood flow, and
 The presence of hypoxia or
 Hypercapnia.

Early in the course of disease, pulmonary hypertension (elevated pressure in the pulmonary arteries)
is the result of markedly increased pulmonary blood flow (hyperkinetic pulmonary hypertension).
This form of pulmonary hypertension decreases with the administration of pulmonary vasodilators
such as nitric oxide, or oxygen, or both.

With the development of Eisenmenger syndrome, pulmonary hypertension is the result of pulmonary
vascular disease (obstructive pathologic changes in the pulmonary vessels). This form of pulmonary
hypertension is usually only minimally responsive to pulmonary vasodilators or oxygen or not at
all.

Histological grading: The pathologic changes of

Eisenmenger syndrome occur in the small pulmonary arterioles and muscular arteries and are graded
on the basis of histologic characteristics (Heath-Edwards classification):

Grade I changes involve medial hypertrophy alone,

grade II consists of medial hypertrophy and intimal hyperplasia,

grade III involves near obliteration of the vessel lumen,

grade IV includes arterial dilatation, and

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 grades V and VI include plexiform lesions, angiomatoid formation, and fibrinoid necrosis.

Grades IV-VI indicate irreversible pulmonary vascular obstructive disease.

Clinical Manifestations:

Symptoms do not usually develop until the 2nd or 3rd decade of life, although a more fulminant
course may occur. Intracardiac or extracardiac communications that would normally shunt from left
to right are converted to right-to-left shunting as pulmonary vascular resistance exceeds systemic
vascular resistance.

Cyanosis becomes apparent, and dyspnea, fatigue, and a tendency toward dysrhythmias begin to
occur. In the late stages of the disease, heart failure, chest pain, headaches, syncope, and
hemoptysis may be seen.

Physical examination reveals a right ventricular heave and a narrowly split 2nd heart sound with a
loud pulmonic component. Palpable pulmonary artery pulsation may be present at the left upper
sternal border.

Diagnosis:

Cyanotic patients have various degrees of polycythemia that depend on the severity and duration of
hypoxemia.

Roentgenographically, the heart varies in size from normal to greatly enlarged. The main
pulmonary artery is generally prominent, similar to primary pulmonary hypertension.

The electrocardiogram shows marked right ventricular hypertrophy. The P wave may be tall and
spiked.

The echocardiogram shows a thick-walled right ventricle and demonstrates the underlying
congenital heart lesion.

Cardiac catheterization usually shows a bidirectional shunt at the site of the defect.
Systolic pressure is generally equal in the systemic and pulmonary circulations.

Treatment:
Medical treatment of Eisenmenger syndrome is primarily symptomatic. Many patients benefit
substantially from either oral (calcium channel blocker, endothelin antagonist, phosphodiesterase
inhibitors) or chronic intravenous (prostacyclin) therapy.

The best management for patients who are at risk for the development of late pulmonary vascular
disease is prevention by early surgical elimination of large intracardiac or great vessel
communications during infancy.

Combined heart-lung or bilateral lung transplantation is the only surgical option for many of
these patients.

HYPERTENSION
DEFINITIONS:
Normal BP: systolic or diastolic BP < 90th percentile for age, sex and height.
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Pre- hypertension: defined as average SBP or DBP that are ≥90th percentile but <95th percentile.
Hypertension: hypertension as average systolic blood pressure (SBP) and/or diastolic blood pressure
(DBP) that is ≥95th percentile for age, sex, and height on ≥3 occasions.
Stage 1 HTN: Children with BP between the 95th and 99th percentile plus 5 mm Hg
Stage 2 HTN: children with BP above the 99th percentile plus 5 mm Hg.
White coat hypertension: A child with BP levels ≥95th percentile in a medical setting but normal BP
outside of the office.
CAUSES OF HTN:
Neonate Infancy to 6 years of age
Renal malformation
Coarctation of aorta Renal parenchymal disease
Renovascular hypertension following Renal artery stenosis
umbilical artery catheterisation Coarctation of aorta
Bronchopulmonary dysplasia

6-10 years of age Adolescent hypertension

Renal parenchymal disease
Renal artery stenosis Renal parenchymal disease
Endocrine causes Essential hypertension
Primary or essential HT

CLINICAL EVALUATION OF CONFIRMED HYPERTENSION (total 14)

STUDY OR PROCEDURE PURPOSE

1. Evaluation for identifiable causes

(4)
History, including sleep history, family
history, risk factors, diet, and habits History and physical examination help focus
such as smoking and drinking alcohol; subsequent evaluation
physical examination

BUN, creatinine, electrolytes,

R/O renal disease and chronic pyelonephritis
urinalysis, and urine culture

CBC R/O anemia, consistent with chronic renal disease

Renal U/S R/O renal scar, congenital anomaly, or disparate renal size

2. Evaluation of co morbid
conditions(3)

Fasting lipid panel, fasting glucose Identify hyperlipidemia, identify metabolic abnormalities

Drug screen Identify substances that might cause hypertension

108
STUDY OR PROCEDURE PURPOSE

1. Evaluation for identifiable causes

(4)

Polysomnography Identify sleep disorder in association with hypertension

3. Evaluation of target organ

damage (2)

Echocardiogram Identify LVH and other indications of cardiac involvement

Retinal exam Identify retinal vascular changes

4. Additional evaluation as
indicated(5)

Identify white coat hypertension,

ABPM (ambulatory BP monitoring)
abnormal diurnal BP pattern

Identify low renin,

Plasma renin determination
suggesting mineralocorticoid-related disease

Renovascular imaging
Isotopic scintigraphy (renal scan)
MRA Identify Renovascular disease
Duplex Doppler flow studies
3-Dimensional CT

Plasma and urine steroid levels Identify steroid-mediated hypertension

Plasma and urine catecholamines Identify catecholamine-mediated hypertension

Treatment:
Non pharmacological:
1. The mainstay of therapy for children with asymptomatic mild hypertension without evidence of
target organ damage is therapeutic lifestyle modification with dietary changes and regular
exercise.
2. Weight loss is the primary therapy in obesity-related hypertension.
3. It is recommended that all hypertensive children have a diet increased in fresh fruits, fresh
vegetables, fiber, and non fat dairy reduced in sodium.
4. In addition, regular aerobic physical activity for at least 30-60 min on most days along with a
reduction of sedentary activities to less than 2 hr per day is recommended.

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Classification of antihypertensive drugs:

1.ACE inhibitors Captopril enalapril lisinopril, Inhibits the action of ACE

perindopril ramipril
2. Angiotensin(AT1) Losartan AT1 antagonists
antagonists
3. CCB Nifedipine, verapamil, diltiazem, Lower the BP by decreasing
amlodine the peripheral vascular
resistance without
compromising the cardiac

110
 output

4. diuretics Thiazide Hydrochlorthiazide Diuresis decreases the t.p.r

High ceiling - Furosemide
K sparing spirinolactone Decreases the c.o by diuresis
5. Beta adrenergic Propranolol atenolol
blockers
6. Beta + alpha adrenergic Labetalol, carvedilol
blockers
7. Alpha adrenergic Prazosin, terazosin phentoloamine, Dilates both resistance and
blockers pheonxybenzamine capacitance vessels
8. Central sympatholytics Clonidine methyl dopa Stimulation of α2 receptors
9. Vasodilators Arteriolar hydralazine
Venodilator nitroglycerine
Arteriolar+ venous sodium
nitroprusside

Hypertensive emergency:

Hypertensive emergency is a Severe, symptomatic hypertension that is often accompanied by cardiac

failure, retinopathy, renal failure, encephalopathy, and seizures.

Intravenous administration is often preferred so that the fall in BP can be carefully titrated. Because
too rapid a reduction in BP may interfere with adequate organ perfusion, a stepwise reduction in
pressure should be planned.

In general, the pressure should be reduced by 10% in the 1st hour, and 15% more in the next 3-12 hr,
but not to normal during the acute phase of treatment.

Hypertensive urgencies, usually accompanied by few serious symptoms such as severe headache or
vomiting, can be treated either orally or intravenously.

ANTIHYPERTENSIVE DRUGS FOR MANAGEMENT OF SEVERE HYPERTENSION

Code (H- LENS)
DRUG CLASS DOSE ROUTE COMMENTS
USEFUL FOR SEVERELY HYPERTENSIVE PATIENTS WITH LIFE-THREATENING
SYMPTOMS
Very short-acting—constant infusion
β-adrenergic 100-500 µg/kg per IV
Esmolol preferred. May cause profound
blocker min infusion
bradycardia
Direct 0.2-0.6 mg/kg per Should be given every 4 hr when
Hydralazine IV, IM
vasodilator dose given IV bolus
Bolus: 0.20-1.0
α- and mg/kg per dose,
IV bolus or Asthma and overt heart failure are
Labetalol β-adrenergic up to 40 mg per
infusion relative contraindications
blocker dose
Infusion: 0.25-3.0
111
DRUG CLASS DOSE ROUTE COMMENTS
mg/kg/hr
Bolus: 30 µg/kg
Calcium
up to 2 mg/dose IV bolus or
Nicardipine channel May cause reflex tachycardia
Infusion: 0.5-4 infusion
blocker
µg/kg per min
Monitor cyanide levels with
Sodium Direct 0.5-10 µg/kg per IV prolonged (>72 hr) use or in renal
nitroprusside vasodilator min infusion failure, or co-administer with sodium
thiosulfate

Antiarrythmic drugs: VAUGHAN WILLIAMS Classification

Clas Action Drugs

s
1 Membrane stabilising agents (Na channel blockers)

A Moderately decrease dv/dt of 0 phase Quinidine, procainamide, disopyramide

B Little decrease in dv/dt of 0 phase Lidociane, mexiletine, tocainide
C Marked decrease in dv/dt of 0 phase flecainide, encainide, Propafenone

2 Anti adrenergic drugs ( β blockers) Propranolol, esmolol, sotalol, acebutalol

3 Agents widening AP (prolong repolarization) Amiodarone, bretylium, ibutilide
(k channel blockers)
4 CCB Verapamil, diltiazem, bepridil

Amiodarone: class 3 drug, iodine containing highly lipophilic

Uses 1. Ventricular and supra ventricular arrhythmias 2. WPW

syndrome

Interactions can increase the level of digoxin and warfarin by decreasing their renal
clearance.

Adverse effects: Dose related and increases with the duration of the therapy.

General nausea, vomiting

Eye corneal opacities - reversible on stopping the drug

Skin photosensitivity and depigmentation

Endocrine interferes with thyroid functions – goiter, hypothyroidism and rarely hyper

Resp pulmonary alveolitis and fibrosis is the most serious toxicity

Cns peripheral neuropathy

112
 Cardiomyopathy
Dilated Hypertrophic Restrictive
Overview ↑ Ventricular size, Hypertrophied LV and/or Myocardial fibrosis with
↓contractility (systolic RV, commonly asymmetric stiff ventricular walls and
dysfunction), MR is septal hypertrophy and impaired diastolic filling
common LVOT obstruction, stiff LV (diastolic dysfunction),
(diastolic dysfunction) atrial enlargement
Prevalence 55% 35% 5%
Etiology Primarily idiopathic, 30% AD inheritance in 50% due Myocardial fibrosis,
familial, can occur post to sarcomere mutations, hypertrophy or infiltration
myocarditis, secondary to others with sporadic (amyloidosis, sarcoidosis,
toxins/meds (doxorubicin) mutations mucopolysaccharidosis)
or metabolic disturbances
Clinical Signs and symptoms ofVaries—can be Exercise intolerance, chest
manifestationsCHF, S3 gallop, murmur
asymptomatic, dizziness, pain, dyspnea, JVD, gallop
of MR palpitations, syncope, chest
pain, sudden death, S4
gallop, SEM due to LVOT
obstruction
CXR—cardiomegaly, CXR—LV enlargement, CXR—cardiomegaly,
pulmonary congestion globular-shaped heart pulmonary congestion
EKG—tachycardia, LVH, EKG—LVH, deep Q waves, EKG—atrial hypertrophy,
ST-T waves changes ST-T wave changes atrial arrhythmias
Diagnosis
Echocardiogram—bivent Echocardiogram—thickene Echocardiogram—biatrial
ricular dilatation, atrial d LV (± RV) wall, small LV enlargement, normal
enlargement, poor chamber size, ↑ LV ventricular volume and
ventricular function, apical contractility function, atrial thrombus
thrombus
Treatment CHF treatment—diuretics,  Activity restriction  Diuretics
ACE-I, β -blockers  β-Blockers and CCB (congestive
 Anticoagulation to improve symptoms)
 Antiarrhythmic ventricular filling  CCB(increased
 ± ICD  Antiarrhythmic diastolicc
 Cardiac transplant  ICD placement compliance)
 Myomectomy  Anticoagulants
 Cardiac transplant

Digoxin and diuretics are

contraindicated
Prognosis Progressive; 50% of Variable from asymptomatic Poor; 5–year survival rate is
patients die within 5 years to progressive symptoms. <30%
of diagnosis Sudden death in 5% of
patients per year (secondary
to arrhythmias), 10%–20%
develop DCM

113
 Chest pain is a common complaint in children that usually has a benign etiology and is only rarely
associated with underlying cardiac disease.

Etiologies of Cardiac Chest Pain and Associated Clinical Manifestations sitaacc

Cardiac Causes Associated Signs and Symptoms Examination Findings
Severe obstructive Pain associated with exercise, and is often Loud harsh systolic murmur
lesions (aortic or recurrent. Anginal pain may be present
pulmonary stenosis)
Cardiomyopathy Pain may be ischemic or arrhythmic in Normal or SEM
origin. Syncope or palpitations may also be
present.
Coronary artery History of Kawasaki disease, pain with Normal, possible gallop, or SEM
disease (anomalous intense physical activity, anginal pain, of mitral insufficiency
origin, vasospasm) diaphoresis, nausea, dyspnea, syncope
Aortic dissection or Severe tearing pain with radiation to the Stigmata of associated syndrome
aneurysm back. Patients with Marfan syndrome,
Turner syndrome, and Noonan's syndromes
are at risk.
Inflammatory Sharp, stabbing precordial pain, improved Pericardial friction rub,
(pericarditis, with upright position or leaning forward, tachycardia, muffled heart sounds
myocarditis) signs of tamponade, evidence of fever, or
recent illness
Arrhythmias Sensation of “heart pounding,” palpitations, Tachycardia, irregular rhythm
syncope, abrupt onset, and termination
Toxins (cocaine, Social history of use or abuse, anginal pain, Tachycardia, hypertension
methamphetamines, possible palpitations related to arrhythmia,
sympathomimetic may present similar to coronary artery
decongestants) disease
SEM, systolic ejection murmur
Noncardiac Chest Pain crpgm
Examination
Causes Associated Signs and Symptoms Findings Treatment
Costochondritis Anterior chest pain, usually unilateral Reproducible pain Rest, NSAIDs or
with tenderness at the costochondral with palpation acetaminophen
joint. May follow respiratory illnesses or
physical activity.
Musculoskeletal Secondary to stain of chest wall muscles Tenderness of the Rest, NSAIDs or
(related to exercise or coughing) or chest wall, signs of acetaminophen
trauma. trauma (bruises)
Respiratory Chest tightness or pain may occur with Tachypnea, crackles, Asthma—inhaled
(Exercise-induced exercise induced bronchospasm. Other wheezing, or β-agonists;
asthma, pneumonia, complaints include shortness of breath, increased work of pneumonia and
bronchitis) decreased exercise tolerance, or cough. breathing. Fever with bronchitis—appr
pneumonia. opriate
antimicrobial
therapy
114
Psychogenic More common in children older than 12 Normal or Reassurance,
years and girls. Often related to anxiety nonspecific address life
or stressful events. Vague associated stressors
somatic complaints include headache
and abdominal pain.
Gastrointestinal Burning substernal pain, relief or Epigastric tenderness Antacids,
(GER, esophageal exacerbation with eating, worse when in hydrogen ion
spasm, foreign supine position inhibitors, or
body, or ingestion) proton pump
inhibitors.
GER, gastroesophageal reflux; NSAID, nonsteroidal anti-inflammatory drugs.

Etiologies of Syncope and Associated Clinical Manifestations (2+4+2+2 = 10)

Differential Diagnosis Clinical Manifestations

Autonomic (2) Orthostatic Vasovagal syncopeProdrome of dizziness, lightheadedness, nausea,
Intolerance pallor, palpitations, visual changes, headache,
and shortness of breath.
May be precipitated by acute illness or noxious
stimuli (pain, fear).
Heart rate and blood pressure drop acutely with
symptoms.

Orthostatic ≥20/10 mmHg drop in blood pressure after

hypotension assuming an upright position Lightheadedness
without extensive prodrome
Exacerbated by dehydration and prolonged bed
rest.

Postural Orthostatic symptoms (fatigue, lightheadedness,

orthostatic recurrent near syncope) associated with 30 bpm
tachycardia increase in heart rate with upright positioning.
syndrome (POTS) Associated with chronic fatigue syndrome.

Related to breathholding spells, cough,

Situational syncope micturition, defecation.

Suggested by occurrence of events in a supine

Arrhythmias (SVT, VT) or sitting position, can be provoked by exercise.

Cardiac (2) obstructive lesions (AS, PS, May be accompanied by chest pain or
HCM) palpitations.
Myocardial dysfunction
(Coronary artery anomalies,
Kawasaki disease)

115
 Unnoticed apprehension and deep sighing
Hyperventilation respirations
Associated with emotional disturbances
Reproducible with intentional hyperventilation

Seizure Unusual eye or limb movements

Neuropsychiat Postictal confusion
ric (4) Prolonged duration of unconsciousness (>1
minute)

Migraine Headache, nausea, vomiting, photophobia, relief

by sleep
Hysteria Prolonged episode occurring only in the
presence of others; rare before age 10 years
Hypoglycemia Symptoms may include pallor, perspiration,
lightheadedness; duration of onset and recovery
are gradual
Metabolic(2)
Electrolyte disturbances Varied dependant on the underlying etiology

Cardiac intervention procedures:

These procedures can

1. open the things that are closed

2. widen the things that are too small

3. close things that are open.

A) Balloon and blade atrial septostomy:

In balloon atrial septostomy, a special balloon tipped catheter is placed in LA from the RA through a
patent foramen ovale or an existing ASD. The balloon is inflated with diluted contrast material, and
the catheter is rapidly pulled back to the RA, thereby creating a large opening in the atrial septum.
In infants older than 6 to 8 weeks, the atrial septum may be too thick to allow an effective balloon
septostomy, in such cases blade atrial septostomy can be used.

B) Balloon valvuloplasty: The balloons used in

these interventional procedures are made of plastic polymers and retain their predetermined
diameters. A long guide wire is advanced far beyond the valve of interest, and the balloon catheter is
placed over the wire. The balloon is then inflated with contrast material to relieve obstruction at the
valve.

Used in Pulmonary valve stenosis, aortic valve stenosis, mitral stenosis and stenosis of prosthetic
conduits.

C) Balloon angioplasty: Appropriate guide wires are placed

116
beyond the point of narrowing, and the balloon catheter is placed over the guide wires. The mid
portion of the balloon is positioned at the point of narrowing, and the balloon is inflated with diluted
contrast material to relieve the narrowing of vascular structures. Following balloon procedure, some
blood vessels recoil and do not maintain the dilated caliber of the vessel. Endovascular stents are
used to maintain vessel patency in such cases.

Used in recoarctation of aorta, native COA, branched pulmonary artery stenosis and systemic artery
stenosis.

D) Closure techniques: Various procedures have been used for

nonsurgical closure of ASD, patent ductus arteriosus, and muscular VSD. The nonsurgical devices
( like amplatzer device and, occlusion coils) have the advantage of a short life stay, rapid recovery
and no surgical scar.

117
 ENDOCRINE
1. Pituitary hormones
2. functions of adrenal hormones
3. thyroid hormone
4. PCOD
5.
6.
7.
8.
9.
10.

Pituitary hormones:

The pituitary's central role in this hormonal system and its ability to interpret and respond to a
variety of signals has led to its designation as the “master gland.” The pituitary gland is
connected to the hypothalamus by the pituitary stalk. The pituitary gland is composed of an
anterior (adenohypophysis) and a posterior (neurohypophysis) lobe.
I. Anterior pituitary hormones:

Five cell types in the anterior pituitary produce 6 peptide hormones.

1. Somatotropes produce growth hormone (GH),

2. lactotropes produce prolactin (PRL),

3. thyrotropes make thyroid-stimulating hormone (TSH),

4. corticotropes express pro-opiomelanocortin (POMC), the precursor of adrenocorticotropic

hormone (ACTH), and

5. gonadotropes express luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

1. Growth Hormone:

GH is secreted in a pulsatile fashion under the regulation of hypothalamic hormones. The

alternating secretion of growth hormone–releasing hormone (GHRH), which stimulates GH
release, and somatostatin, which inhibits GH release, accounts for the rhythmic secretion of GH.
Sleep, exercise, physical stress, trauma, acute illness, puberty, fasting, ghrelin, and
hypoglycemia stimulate the release of GH whereas hyperglycemia, hypothyroidism, and
glucocorticoids inhibit GH release.

The biological effects of GH include increases in linear growth, bone thickness, soft tissue
growth, protein synthesis, fatty acid release from adipose tissue, insulin resistance, and blood
glucose. The mitogenic actions of GH are mediated through increases in the synthesis of
insulin-like growth factor-1 (IGF-1).

2. Prolactin:

118
PRL is a 199-amino-acid peptide made in pituitary lactotropes. Dopamine antagonists, states of
primary hypothyroidism, administration of thyrotropin-releasing hormone (TRH), and pituitary
tumors result in increased serum levels of PRL. Dopamine agonists and processes causing
destruction of the pituitary cause reduced levels of PRL.

The primary physiologic role for PRL is the initiation and maintenance of lactation. PRL
prepares the breasts for lactation and stimulates milk production postpartum.

3. Thyroid-Stimulating Hormone:

TSH consists of 2 glycoprotein chains (α, β) linked by hydrogen bonding; the α-subunit, which
is composed of 89 amino acids and is identical to other glycoproteins (FSH, LH, and human
chorionic gonadotropin [hCG]), and the β-subunit, composed of 112 amino acids, that is
specific for TSH.

TSH is stored in secretory granules and released into circulation primarily in response to
thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus. TSH stimulates
release of thyroxine (T4) and triiodothyronine (T3) from the thyroid gland. In addition to the
negative feedback inhibition by T3, the release of TRH and TSH are inhibited by dopamine,
somatostatin, and glucocorticoids.

4. Adrenocorticotropic Hormone:

ACTH is a 39-amino-acid single-chain peptide that is derived by proteolytic cleavage from

POMC.

Secretion of ACTH is regulated by corticotropin-releasing hormone (CRH). ACTH is

secreted in a diurnal pattern. It acts on the adrenal cortex to stimulate cortisol synthesis and
secretion. ACTH and cortisol levels are highest in the morning at the time of waking, are low
in the late afternoon and evening, and reach their nadir an hour or two after beginning sleep.
ACTH also appears to be the principal pigmentary hormone in humans. Physiologic
conditions such as stress, fasting, and hypoglycemia also stimulate release of CRH and ACTH.

119
 5. Luteinizing Hormone and Follicle-Stimulating Hormone:

Gonadotropic hormones include two glycoproteins, LH and FSH. Receptors for FSH on the
ovarian Granulosa cells and on testicular Sertoli cells mediate FSH stimulation of follicular
development in the ovary and of gametogenesis in the testis. On binding to specific receptors
on ovarian theca cells and testicular Leydig cells, LH promotes luteinization of the ovary
and Leydig cell function of the testis.

Secretion of LH is inhibited by androgens and estrogens, and secretion of FSH is suppressed

by gonadal production of inhibin, produced by the Sertoli cells.

II. Posterior Pituitary hormones:

The posterior lobe of the pituitary is part of a functional unit, the neurohypophysis, that consists
of the neurons of the supraoptic and paraventricular nuclei of the hypothalamus.
Arginine vasopressin (AVP; antidiuretic hormone [ADH]) and oxytocin are the 2 hormones
produced by neurosecretion in the hypothalamic nuclei and released from the posterior
pituitary. They are octapeptides and differ by only 2 amino acids.

1. Antidiuretic Hormone:

ADH regulates water conservation at the level of the kidney by increasing the permeability of
the renal collecting duct to water through its interaction with vasopressin 2 receptors in the
collecting duct. ADH has a short half-life and responds quickly to changes in hydration. The
stimuli for its release are increased plasma osmolality, perceived by osmoreceptors in the
hypothalamus, and decreased blood volume, perceived by baroreceptors in the carotid sinus of
the aortic arch.

2. Oxytocin:

Oxytocin stimulates uterine contractions at the time of labor and delivery in response to
distention of the reproductive tract and stimulates smooth muscle contraction in the breast
during suckling, which results in milk letdown.

2. Functions of adrenal hormones:

I. Actions of Glucocorticoids: Glucocorticoids are essential for survival. The term
glucocorticoid refers to the glucose-regulating properties of these hormones. In stress situations,
glucocorticoid secretion can increase up to 10-fold. This increase is believed to enhance survival
through increased cardiac contractility, cardiac output, sensitivity to the pressor effects of
catecholamines and other pressor hormones, work capacity of the skeletal muscles, and capacity to
mobilize energy stores.
A) Metabolic Effects: The primary action of the glucocorticoids on carbohydrate
metabolism is to increase glucose production by increasing hepatic gluconeogenesis.
Glucocorticoids also increase cellular resistance to insulin, thereby decreasing entry of glucose into
the cell. Glucocorticoid excess can cause hyperglycemia, and glucocorticoid deficiency can cause
hypoglycemia.

Glucocorticoids increase free fatty acid levels by enhancing lipolysis, decreasing cellular glucose
uptake, and decreasing glycerol production, which is necessary for re-esterification of fatty acids. In
the patient with glucocorticoid excess, fat is lost in the extremities, but it is increased in the trunk
(centripetal obesity), neck, and face (moon facies).
120
Glucocorticoids generally exert a catabolic or antianabolic effect on protein metabolism.
Proteolysis in fat, skeletal muscle, bone, lymphoid, and connective tissue increases amino acid
substrates that can be used in gluconeogenesis. Cardiac muscle and the diaphragm are almost entirely
spared from this catabolic effect.

B) Circulatory and Renal Effects: Glucocorticoids have a positive inotropic influence on

the heart, increasing the left ventricular work index. In the absence of glucocorticoids, decreased
cardiac output and shock can develop; in states of glucocorticoid excess, hypertension is often
observed.

C) Growth: In excess, glucocorticoids inhibit linear growth and skeletal

maturation in children, apparently through direct effects on the epiphyses. Glucocorticoids are often
given to pregnant women at risk for delivery of premature infants in an effort to accelerate these
maturational processes.

D) Immunologic Effects: Glucocorticoids play a major role in immune regulation. They

inhibit synthesis of glycolipids and prostaglandin precursors and the actions of bradykinin. They also
block secretion and actions of histamine and proinflammatory cytokines (tumor necrosis
factor[TNF]-α, interleukin[IL]-1, and IL-6), thus diminishing inflammation.

Glucocorticoids increase circulating polymorphonuclear cell counts, mostly by preventing their

egress from the circulation. Glucocorticoids decrease diapedesis, chemotaxis, and phagocytosis of
polymorphonuclear cells. High levels of glucocorticoids decrease inflammatory and cellular
immune responses and increase susceptibility to certain bacterial, viral, fungal, and parasitic
infections.

E) Effects on Skin, Bone, and Calcium: Glucocorticoids inhibit fibroblasts, leading to increased
bruising and poor wound healing through cutaneous atrophy. This effect explains the thinning of the
skin and striae that are seen in patients with Cushing syndrome. Glucocorticoids have the overall
effect of decreasing serum calcium and have been used in emergency therapy for certain types of
hypercalcemia. The most significant effect of long-term glucocorticoid excess on calcium and bone
metabolism is osteoporosis.

F) Central Nervous System Effects: Glucocorticoids readily penetrate the blood-brain barrier
and have direct effects on brain metabolism. They stimulate appetite and cause insomnia with a
reduction in rapid eye movement (REM) sleep. Glucocorticoid excess produces psychosis in some
patients.

II. Actions of Mineralocorticoids: Mineralocorticoids have more-limited actions than

glucocorticoids. Their major function is to maintain intravascular volume by conserving sodium
and eliminating potassium and hydrogen ions. Thus, patients with mineralocorticoid deficiency can
develop weight loss, hypotension, hyponatremia, and hyperkalemia, whereas patients with
mineralocorticoid excess can develop hypertension, hypokalemia, and metabolic alkalosis.

III. Actions of the Adrenal Androgens: Many actions of adrenal androgens are exerted through
their conversion to active androgens or estrogens such as testosterone, dihydrotestosterone, estrone,
and estradiol. In men, <2% of the biologically important androgens are derived from adrenal
production, whereas in women approximately 50% of androgens are of adrenal origin. Adrenal
androgens contribute to the physiologic development of pubic and axillary hair during normal
puberty. They also play an important role in the pathophysiology of congenital adrenal hyperplasia,
premature adrenarche, adrenal tumors, and Cushing syndrome.

121
ADRENAL MEDULLA: The proportions of epinephrine and norepinephrine in the
adrenal gland vary with age. In early fetal stages, there is practically no epinephrine; at birth,
norepinephrine remains predominant. Both epinephrine and norepinephrine raise mean arterial
blood pressure, but only epinephrine increases cardiac output. By increasing peripheral vascular
resistance, norepinephrine increases systolic and diastolic blood pressures with only a slight
reduction in the pulse rate. Epinephrine increases the pulse rate and, by decreasing the
peripheral vascular resistance, decreases the diastolic pressure.

3. Thyroid hormones:

T4 levels in sick intensive care nursery (ICN) infants,

healthy term infants, and normal adults. (TSH) levels in healthy
preterm infants

122
 Circulating TSH and T4 levels are minimal until approximately 18 to 20 weeks. After 20 weeks,
there is a progressive increase in TSH and free T4 level.
 There is an increase in the T4:TSH ratio, suggesting maturation of the negative feedback control
of the HPT axis
 T3 levels also progressively increase, although later, after approximately 30 weeks of gestation.

4. Hirsutism:

Hirsutism

Hirsutism is defined as abnormally increased terminal (mature, heavy, dark) hair growth in areas of
the body where hair growth is normally androgen dependent. Hirsutism as an isolated finding is to
be distinguished from masculinization. The latter includes alteration in muscle mass, clitoral
enlargement, and voice change, generally manifesting as a rapid evolution (over months).

CAUSES OF HIRSUTISM
PERIPHERAL
Idiopathic
Partial androgen insensitivity (5α-reductase deficiency)
HAIR-AN syndrome (hirsutism, androgenization, insulin resistance, and acanthosis
nigricans)
Hyperprolactinemia
GONADAL
Polycystic ovary syndrome (polycystic ovaries, chronic anovulation)
Ovarian neoplasm (Sertoli-Leydig cell, granulosa cell, thecoma, gynandroblastoma, lipoid
cell, luteoma, hypernephroma, Brenner tumor)
Gonadal dysgenesis (Turner mosaic with XY or H-Y antigen positive)
ADRENAL
Cushing syndrome
123
 Adrenal hyper-responsiveness
Congenital adrenal hyperplasia (classic, cryptic, adult onset)
21-Hydroxylase deficiency
11-Hydroxylase deficiency
3β-Hydroxysteroid deficiency
17β-Hydroxylase deficiency
Adrenal neoplasm (adenoma, cortical carcinoma)
EXOGENOUS
Minoxidil
Dilantin
Cyclosporine
Anabolic steroids
Acetazolamide (Diamox)
Penicillamine
Oral contraceptives with androgenic progestins
Danazol
Androgenic steroids
Psoralens
Hydrochlorothiazide
Phenothiazines
CONGENITAL ANOMALIES
Trisomy 18 (Edwards syndrome)
Cornelia de Lange syndrome
Hurler syndrome
Juvenile hypothyroidism

Estrogen and progestin suppression of ovarian function, with or without added antiandrogen
treatment, is the mainstay of therapy for these patients. Patients should therefore be advised that the
effects of medical therapy accrue slowly, over many months.

Idiopathic hirsutism (without evidence of androgen excess) usually responds to antiandrogen or

androgen suppression therapy similarly to hirsutism associated with elevated androgens and
anovulation (PCOS), and benign hyperandrogenism not associated with PCOS.

4. PCOD:

Polycystic ovary syndrome (PCOS) is a common disorder of reproductive hormone dysfunction,

often with associated metabolic abnormalities, that affects 5-8% of women of reproductive age.

It is characterized by the triad of (the Rotterdam criteria)

1. oligo-ovulation or anovulation,

124
 2. clinical or biochemical hyperandrogenism, and
3. ovarian cysts (≥12 immature follicles)

Pathophysiology:

Schematic of pathophysiology of polycystic ovary syndrome and mechanism of therapeutic drugs.

DHT, dihydrotestosterone; LH, luteinizing hormone; SHBG, sex hormone binding globulin; OCPs,
oral contraceptive pills

LIFELONG HEALTH COMPLICATIONS

PRENATAL OR ADOLESCENCE, REPRODUCTIVE

POSTMENOPAUSAL
CHILDHOOD YEARS
REPRODUCTIVE
Menstrual irregularity
Hirsutism
Premature adrenarche
Acne
Early menarche Delayed menopause
Infertility
Endometrial cancer
Miscarriage

125
 PRENATAL OR ADOLESCENCE, REPRODUCTIVE
POSTMENOPAUSAL
CHILDHOOD YEARS
Pregnancy complications
METABOLIC
Obesity Obesity
Impaired glucose tolerance Impaired glucose
Insulin resistance tolerance
Abnormal fetal growth
Dyslipidaemia Insulin resistance
Type 2 diabetes Dyslipidaemia
Type 2 diabetes
OTHER
Sleep apnea
Fatty liver Cardiovascular disease
Depression

Investigations:
s. androgens, free T4, TSH, Prolactin. Fasting glucose, insulin. USG

Treatment:

Life style modifications:

OCP
Metformin
Antiandrogens

126
 ENVIRONMENT

1. Radiation
2. Environmental pollution
3. Bioterrorism
4. Biomedical waste
5. Disaster management

1. Radiation:
Radiation exposure may be natural (50%) or environmental (man-made) (50%).
The contribution of man-made radiation has dramatically increased to 50% from 15% in the
mid-1980s.
Sources with %
Radon and thoron 37%
CT 24%
Nuclear medicine 12%
Interventional fluoroscopy 7%
Biological effects:
1. Deterministic effects (determined by the dose) are characterized by a threshold dose: For example,
cataracts occur with an acute exposure to > 200 rad or with long-term exposure to > 500 rad.
Deterministic effects never occur from the doses generally used in diagnostic radiation.
2. Stochastic (random) effects are of greater concern because they can occur at any dose; that is,
there is no threshold, with the probability of an effect increasing with rising dose.
3. Syndromes associated with increased exposure to radiation:
Ataxia telangiectasia, downs, ushers, fanconi’s anemia and basal cell nevoid syndrome.
Side effects Early:
The acute effects of therapy (occurring less than 3 months after therapy begins) are usually related
to the area of the body being irradiated (except fatigue, which can begin during this time period).
These acute effects include radiation-caused pneumonitis, dermatitis, mucositis and esophagitis,
cerebral edema, and swelling of the organ irradiated.
Late:
LATE EFFECTS OF RADIATION THERAPY IN CHILDREN TREATED FOR CANCER

SYSTEM LATE EFFECT

Muscular hypoplasia
Musculoskeletal Scoliosis, kyphosis, lordosis
Osteocartilaginous exostosis
Impaired growth hormone
Adrenocorticotropic hormone deficiency
Neuroendocrine (cranial or cranial spinal) Thyrotropin-releasing deficiency
Precocious puberty (females mostly)
Gonadotropin deficiency
Ovarian failure
Gonad failure
Testicular failure
Structured changes
Central nervous system dysfunction
Cognitive changes

127
SYSTEM LATE EFFECT
Pulmonary fibrosis
Nephropathy
Liver failure
Arteritis
Other
Eye impairment
Ear impairment
Bone marrow dysfunction
Cardiac impairment

Treatment: (rbcde)
The most effective treatment requires knowledge of both the radionuclide and the chemical form.
Treatment must be instituted quickly to be effective.
1. Removal treatment involves cleaning a contaminated wound and performing stomach lavage
or administration of cathartics in the case of ingestion. Administration of alginate-containing
antacids also usually helps in removal by decreasing absorption in the gastrointestinal tract.
2. Blocking therapy is the administration of potassium iodine or other stable iodine-containing
compounds to patients with known internal contamination with radioactive iodine.
3. Chelation therapy: Cases of internal contamination with transuranic elements (americium and
plutonium) may require chelation therapy with calcium diethylene triamine pentaacetic acid (DTPA)
and ZINC.
4. Dilution therapy is used in cases of tritium (radioactive hydrogen as water) contamination.
Forcing fluids promotes excretion.
5. Enhancing elimination: Prussian blue has been approved for internal contamination with
cesium or thallium. It can speed fecal elimination of radioactive cesium from the body. Prussian blue
can be given days after ingestion, unlike potassium iodine.
Prevention:
1. No exposure during pregnancy.
2. Radon exposure can be minimised by increasing ventilation at home.
3. Sealing of cracks in the foundation.
4. Creating negative pressure under the basement floor.
5. Prohibiting the use of building materials containing radium may help.
6. Window glass blocks all the ultraviolet rays.
7. Use of sunscreen lotions though controversial has some benefits.
8. Wearing a hat and using sunglasses is advisable.
9. Health education and improving literacy levels.
10. Active role of media in educating people.

2. Environmental pollution:
Can be caused by
1. Air a) gases b) particulate like dust, smoke, smog, fumes, aerosols, industrial stack
emissions. c) Chemical and gaseous substances
2. Water pollution – contamination by industrial wastes, agricultural wastes, domestic wastes
and pathogenic organisms.
3. Soil pollution - improperly disposed excreta, waste materials from industries dumped on
land, fertilisers, pathogenic organisms, parasites and radioactive materials.
4. Food contamination- milk, meat, ice, fruits and vegetables.

128
 5. House hold hazards- medicine, kitchen gas connection and sharps.
Prevention:
1. Control population explosion.
2. Monitoring of pollution levels frequently especially near industrial areas.
3. Educating the public on the causes and effects of pollutants and how best these can be minimised.
4. Building of factories away from the living areas.
5. Careful planning of factory stacks to prevent health hazards.
6. Enforcement of rigorous controls on emission including transport vehicles.
7. Adequate vector control.
8. Conservation of forest and wild life.
9. Health education and improvement of literacy levels.
10. Active role by media.

3. CRITICAL BIOLOGIC AGENTS OF TERRORISM (TAP SVB)

ISOLATION INITIAL
CLINICAL I Period PROPHYLAX
DISEASE PRECAUTIO TREATMEN
FINDINGS (DAYS) IS
NS T
Anthrax
(inhalational)
Febrile
Patients who
prodrome with Ciprofloxacin
are clinically
rapid OR
stable after 14 Ciprofloxacin
progression to doxycycline
d can be 10-15 mg/kg
mediastinal AND
switched to a 1-5 Standard PO q12h OR
lymphadenitis clindamycin
single oral doxycycline 2.2
and
agent mg/kg PO q12h
mediastinitis, AND
(ciprofloxacin
sepsis, shock, penicillin
or doxycycline)
and meningitis
to complete a
60-d course.
Febrile
prodrome with
rapid
Doxycycline 2.2
progression to Gentamicin
mg/kg PO q12h
fulminant Droplet (for OR
Plague OR
pneumonia, 2-3 first 3 d of doxycycline
(pneumonic) Ciprofloxacin
hemoptysis, therapy) OR
20 mg/kg PO
sepsis, ciprofloxacin
q12h
disseminated
intravascular
coagulation

129
 ISOLATION INITIAL
CLINICAL I Period PROPHYLAX
DISEASE PRECAUTIO TREATMEN
FINDINGS (DAYS) IS
NS T
Pneumonic:
abrupt onset of
fever with
fulminant Same as for Same as for
Tularemia 2-10 Standard
pneumonia plague plague
Typhoidal:
fever, malaise,
abdominal pain
Vaccination
Febrile
may be
prodrome with
effective if
synchronous, Airborne Supportive
Smallpox 7-17 given within the
centrifugal, (+ contact) care
first several
vesiculopustula
days after
r exanthema
exposure
Supportive
Afebrile
care;
descending
antitoxin
symmetric
may halt the
Botulism flaccid 1-5 Standard None
progression of
paralysis with
symptoms but
cranial nerve
is unlikely to
palsies
reverse them
Febrile
prodrome with Contact Supportive
rapid (consider care;
Viral
progression to airborne in ribavirin
hemorrhagic 4-21 None
shock, cases of may be
fevers
purpura and massive beneficial in
bleeding hemorrhage) select cases
diatheses

DISEASES CAUSED BY AGENTS OF CHEMICAL AND BIOLOGIC TERRORISM,

CLASSIFIED BY SYNDROME
NEUROMUSCULAR RESPIRATORY DERMATOLOGIC
SYMPTOMS SYMPTOMS FINDINGS
PROMINENT PROMINENT PROMINENT

Chlorine
Sudden-o Mustard
Nerve agents Phosgene
nset Lewisite
Cyanide

Tularemia
Delayed-
Botulism Anthrax Smallpox
onset
Plague

130
 EYE, EAR, SKIN, RHEUMATOLOGY
1. Acne:
2. Seborrheic dermatitis
3. Developmental dysplasia of hip
4. Osteogenesis imperfecta
5. Achondroplasia
6. Jia/ mas
7. Kawasaki
8. Heat injuries
9. Performance enhancing drugs
10. Hearing impairment
11. AOM
12. Cutaneous reactions to Sunlight
13. Osteomyelitis
14. Torticollis
15. Hypopigmented patch
16. Childhood vasculitis
17. Cutaneous manifestations of systemic diseases
18. Atopic dermatitis
19. Differential diagnosis for limping gait
20. Bowing of legs
21. Hyperpigmentation
22. HSP
23. Impetigo
24. Scabies
Acne:
It is a common chronic inflammation of pilosebacious units that mainly affect adolescents during
puberty.
Etiology: multifactorial
1. Genetic 2. Emotional stress 3. Endocrine factors-
androgens
4. Exposure to acnegenic mineral oils, hair preparations and greasy cosmetics.
5. Drugs- lithium, steroids
6. Triggered by menstruation, pressure on the skin by leaning face on hands.
7. Proliferation of Propionibacterium acnes within the follicle.
8. Increased production of sebum by sebaceous glands.
9. Diet – little evidence that particular foods can trigger acne.
10. Climate - flaring during winter and remission during summer.
Clinical features:
 Acne vulgaris is characterized by 4 basic types of lesions:
open and closed comedones, papules, pustules and nodulocystic lesions.
 Sites of predilection include face, chest, upper back and deltoid.
 Acne can also be classified by mild, moderate, moderately severe and severe.
CLASSIFICATION OF ACNE
SEVERITY DESCRIPTION
Comedones (noninflammatory lesions) are the main lesions. Papules and pustules
Mild
may be present but are small and few in number (generally < 10).
Moderate numbers of papules and pustules (10-40) and comedones (10-40) are
Moderate
present. Mild disease of the trunk may also be present.

131
 SEVERITY DESCRIPTION
Numerous papules and pustules are present (40-100), usually with many
Moderately
comedones (40-100) and occasional larger, deeper nodular inflamed lesions (up to
severe
5). Widespread affected areas usually involve the face, chest, and back.
Nodulocystic acne and acne conglobata with many large, painful nodular or
Severe pustular lesions are present, along with many smaller papules, pustules, and
comedones.
Treatment:
A) General measures:
 No evidence shows that early treatment, with the exception of isotretinoin, alters the course of
acne.
 Therapy must be individualized and aimed at preventing microcomedone formation through
reduction of follicular hyperkeratosis, sebum production, the P. acnes population in follicular
orifices, and free fatty acid production.
 It is also important to address the potentially severe emotional impact of acne on adolescents.
 Diet: Little evidence shows that ingestion of particular foods can trigger acne flares. When a
patient is convinced that certain dietary items exacerbate acne, it is prudent for him or her to
omit those foods.
 Climate: Climate appears to influence acne, in that improvement frequently occurs in
summer and flares are more common in winter. Emotional tension and fatigue seem to
exacerbate acne in many individuals.
 Cleansing: Cleansing with soap and water removes surface lipid and renders the skin less
oily in appearance, but no evidence shows that surface lipid has a role in generating acne
lesions. Only superficial drying and peeling are achieved by cleansing, and almost any mild
soap or astringent is adequate. Repetitive cleansing can be harmful because it irritates and
chaps the skin. Greasy cosmetic and hair preparations must be discontinued because they
exacerbate pre-existing acne and cause further plugging of follicular pores. Manipulation and
squeezing of facial lesions only ruptures intact lesions and provokes a localized inflammatory
reaction
B) Topical
1. Topical antibiotics (Clindamycin, erythromycin)
2. Benzoyl peroxide gels (2%, 5%) - antimicrobial
3. Topical retinoids (tretinoin, adapalene, tazarotene)- gradual increase in conc and frequency, over a
period of over 2 to 5 months.
4. Combination of any of the above three.
C) Sytemic:1. Tetracycline, minocycline, doxycycline and erythromycin.
2. Hormonal agents: OCP (only in females) and spironolactone.
3. Oral 13- cis- retinoic acid --Birth defects; adherence to pregnancy prevention program.
hypertriglyceridemia, elevated results on liver function tests, abnormal night vision, benign
intracranial hypertension are possible common or important side effects; laboratory testing of lipid
profiles and liver function tests monthly should be performed monthly until dose is stabilized.
D) Surgery for scars: intralesional steroids, intralesional 5-FU, intralesional bleomycin and vascular
laser
2. Seborrheic dermatitis:
Seborrheic dermatitis is a chronic inflammatory disease most common in infancy and adolescence
that .
The cause is unknown, as is the role of the sebaceous glands in the disease. Malassezia furfur has
been implicated as a causative agent.

Clinical features:

 The disorder may begin in the 1st mo of life and may be most troublesome in the 1st yr.
132
  Diffuse or focal scaling and crusting of the scalp, sometimes called cradle cap, may be the
initial and at times the only manifestation.
 A greasy, scaly, erythematous papular dermatitis, which is usually nonpruritic, may
involve the face, neck, retroauricular areas, axillae, and diaper area.
 In adolescents-

Histopathology is not diagnostic but most characteristic feature is neutrophils at the tips of the
dilated follicular opening.

Differntial diagnosis

Treatment:

For scalp: Scalp lesions should be controlled with an antiseborrheic shampoo (selenium sulfide,
sulfur, salicylic acid, zinc pyrithione, tar), used daily if necessary. Inflamed lesions usually respond
promptly to low- to medium-potency topical corticosteroid therapy.

Face: Topical antifungal agents (ketoconazole, bifonazole) effective against Malassezia

Intertrigenous areas: castellanis paint
Wet compressions in fissured areas.
3.Developmental dysplasia of hip:
Developmental dysplasia of the hip (DDH) refers to a spectrum of pathology in the development of
the immature hip joint.
Classification:
1. Acetabular dysplasia
2. Hip subluxation – partial contact b/n hip and acetabulum
3. Hip dislocation- no contact
4. DDH
(a) typical in normal children
(b) teratologic – have identifiable genetic cause

Etiology and risk factors:

Exact etiology is unknown usually multi factorial including genetic, intra uterine and environmental
factors.
1. Antenatal: oligohydramnios, large baby and first pregnancy supporting the theory of crowding
phenomenon
2. Increased laxity of hip capsule probably the result of hormonal, mechanical and genetic factors.
3. Risk factors- breech presentation, family history and torticollis.
4. Female sex. 5. Left hip is more involved.
Clinical features and treatment:
Age Clinical features treatment
Neonate DDH in the neonate is asymptomatic and must Braces- pavlik, frejka pillow and
be screened for by specific maneuvers. von rosen splint
The Barlow provocative maneuver assesses the By maintaining hip in a Pavlik
potential for dislocation of a nondisplaced hip. harness on a full-time basis for 6
The Ortolani test is the reverse of Barlow test wk, hip instability resolves in 95%
of cases
Infant apparent shortening of the thigh, The goals in the management of
proximal location of the greater trochanter, DDH are to obtain and maintain a
asymmetry of the gluteal or thigh folds concentric reduction of the
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 Limitation of abduction is the most reliable femoral head within the
sign of a dislocated hip in this age group. acetabulum to provide the optimal
Galeazzi test environment for the normal
Klisic test examiner places the 3rd finger over development of both the femoral
the greater trochanter and the index finger of the head and acetabulum. The later the
same hand on the anterior superior iliac spine. In diagnosis of DDH is made, the
a normal hip, an imaginary line drawn between more difficult it is to achieve these
the two fingers points to the umbilicus. In the goals.
dislocated hip, the trochanter is elevated, and the 6months to 2 years:
line projects halfway between the umbilicus and Surgery either open or closed
the pubis reduction
Older than 2 years
Pelvic osteotomy by open
reduction
Walking The walking child often presents to the physician Complications
child after the family has noticed a limp, a waddling Redislocation
gait, or a leg-length discrepancy. Residual subluxation
Trendelenburg sign is positive. Avascular necrosis of femoral
Excessive lordosis. epiphysis
Post op complications- infection
Investigations:
Ultrasonography: Because it is superior to radiographs for evaluating cartilaginous structures,
ultrasonography is the diagnostic modality of choice for DDH before the appearance of the femoral
head ossific nucleus.
Radiographs: Radiographs are recommended for an infant once the proximal femoral epiphysis
ossifies, usually by 4-6 months. Shenton line is broken. Acetabular index is less than 30 degrees
by 4 months in normal infant.
Perkins line, hilgenreiner line are also disrupted.
4. Osteogenesis imperfecta:
Osteogenesis imperfecta (OI) (brittle bone disease), the most common genetic cause of osteoporosis,
is a generalized disorder of connective tissue.
Etiology: Type I collagen is the primary component of the extracellular matrix of bone and skin.
Structural or quantitative defects in type I collagen cause the full clinical spectrum of OI.
Clinical Manifestations:

OI has the triad of fragile bones, blue sclera and early deafness.

Other features: Recurrent fractures, easy bruising, joint laxity, short stature, bowing of
extremities, scoliosis, vertebral compression and respiratory insufficiency.

Types: The Sillence classification divides OI into four types based on clinical and
radiographic criteria. Additional types have been proposed based on histologic distinctions.

Type1- mild OI
Type 2- perinatal - lethal

Type 3- progressive deforming

Type 4- moderately severe

Diagnosis:

1. Clinical features 2. Blood normal /increased

SAP

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3. X ray a.osteoporotic bones
b. metaphyseal flaring

c. popcorn formation of growth plates

d. vertebral compression

4. Dual energy x-ray absorptiometry (DEXA) L1-L2 z-score in the −6 to −7 range.

5. Collagen biochemical studies 6. Gel

electrophoresis for collagen

7. Antenatal: fetal ultra sound and cvs biopsy

8. Spirometry: decreased pulmonary functions

Complications:

Neuro- Basilar invagination, brainstem compression, hydrocephalus, and syringohydromyelia.

Resp- Recurrent pneumonias and declining pulmonary function occur in childhood.

Treatment:

 There is no cure for OI.

 Active physical rehabilitation in the early years.
 Psychologic support with body image issues.
 Orthopedic- fracture management and correction of deformity to enable function.
 Bisphosphonates (IV pamidronate or oral olpadronate) confers some benefits.
 Growth hormone improves bone histology in growth-responsive children.

Add a note on prognosis and genetic counselling.

5. Achondroplasia:
Mode of inheritance- AD
Genetics- typical achondroplasia have mutations at FGFR3.
Clinical Manifestations:

1. Infants usually exhibit delayed motor milestones, often not walking alone until 18-24 mo.
2. Intelligence is normal unless central nervous system complications develop.
3. As the child begins to walk, the gibbus usually gives way to an exaggerated lumbar lordosis.
4. Virtually all infants and children with achondroplasia have large heads, although only a
fraction has true hydrocephalus.
5. The spinal canal is stenotic and spinal cord compression can occur at the foramen magnum
and in the lumbar spine.
6. Other common problems include dental crowding, articulation difficulties, obesity, and
frequent episodes of otitis media, which can contribute to hearing loss.
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Diagnosis:

Skeletal radiographs confirm the diagnosis.

1. The calvarial bones are large, whereas the cranial base and facial bones are small.
2. The vertebral pedicles are short throughout the spine as noted on a lateral radiograph.
3. The interpedicular distance, which normally increases from the 1st to the 5th lumbar vertebra,
decreases in achondroplasia.
4. The iliac bones are short and round and the acetabular roofs are flat.
5. The fibula is disproportionately long compared with the tibia.

Treatment: Supportive. Prenatal diagnosis is available.

6. Juvenile idiopathic arthritis:

Juvenile idiopathic arthritis (JIA) (formerly juvenile rheumatoid arthritis) is the most common
rheumatic disease in children and one of the more common chronic illnesses of childhood. JIA
represents a heterogeneous group of disorders all sharing the clinical manifestation of arthritis.
INTERNATIONAL LEAGUE OF ASSOCIATIONS FOR RHEUMATOLOGY
CLASSIFICATION OF JUVENILE IDIOPATHIC ARTHRITIS (JIA)
CATEGORY DEFINITION
Arthritis in ≥1 joints with, or preceded by, fever of at least 2 wk in
duration that is documented to be daily for at least 3 days and
accompanied by ≥1 of the following:
Systemic-onset JIA 1 Evanescent (nonfixed) erythematous rash.
2 Generalized lymph node enlargement.
3 Hepatomegaly or splenomegaly or both.
4 Serositis.

Arthritis affecting 1-4 joints during the 1st 6 mo of disease. Two

subcategories are recognized:
1 Persistent oligoarthritis—affecting ≤4 joints throughout the disease
Oligoarticular JIA course.
2 Extended oligoarthritis—affecting >4 joints after the 1st 6 mo of
disease.
Polyarthritis Arthritis affecting ≥5 joints during the 1st 6 mo of disease; a test for RF is
(RF-negative) negative.
Polyarthritis Arthritis affecting ≥5 joints during the 1st 6 mo of disease; ≥2 tests for RF at
(RF-positive) least 3 mo apart during the 1st 6 mo of disease are positive.
Arthritis and psoriasis, or arthritis and at least 2 of the following: POND
1. Dactylitis.
Psoriatic arthritis
2. Nail pitting and onycholysis.
3. Psoriasis in a 1st-degree relative.
Enthesitis-related Arthritis and enthesitis, or arthritis or enthesitis with at least 2 of the
arthritis following:
1 Presence of or a history of sacroiliac joint tenderness or inflammatory

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CATEGORY DEFINITION
lumbosacral pain or both.
2 Presence of HLA-B27 antigen.
3 Onset of arthritis in a male > 6 yr old.
4 Acute (symptomatic) anterior uveitis.
5 History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis
with inflammatory bowel disease, Reiter syndrome, or acute anterior
uveitis in a 1st-degree relative.
Undifferentiated
Arthritis that fulfills criteria in no category or in ≥2 of the above categories
arthritis

Macrophage activation syndrome (MAS) is a rare but potentially fatal complication of SoJIA that
can occur at anytime during the disease course. It is also referred to as secondary hemophagocytic
syndrome or hemophagocytic lymphohistiocytosis (HLH).

MAS classically manifests as acute onset of profound anemia associated with thrombocytopenia or
leukopenia with high, spiking fevers, lymphadenopathy, and hepatosplenomegaly.

PRELIMINARY DIAGNOSTIC GUIDELINES FOR MACROPHAGE ACTIVATION

SYSTEM (MAS) COMPLICATING SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
(JIA)
LABORATORY CRITERIA
1 Decreased platelet count (≤262 ? 109/L).
2 Elevations of aspartate aminotransferase (>59 U/L).
3 Decreased white blood cell count (≤4.0 ? 109/L).
4 Hypofibrinogenemia (≤2.5 g/L).

CLINICAL CRITERIA
1 Central nervous system dysfunction (headache, lethargy, disorientation, irritability, seizures,
coma).
2 Hemorrhages (purpura, easy bruising, mucosal bleeding).
3 Hepatomegaly (edge of liver ≥3 cm below the costal arch).
HISTOPATHOLOGIC CRITERION
• Evidence of macrophage hemophagocytosis in the bone marrow aspirate
DIAGNOSTIC RULE
• The diagnosis of MAS requires the presence of any 2 or more laboratory criteria or of any 2 or 3
or more clinical and/or laboratory criteria. A bone marrow aspirate for the demonstration of
hemophagocytosis may be required only in doubtful cases.

Emergency treatment with high-dose intravenous methylprednisolone, cyclosporine, or anakinra may

be effective. Severe cases may require therapy similar to that for primary HLH.

Laboratory tests: 1. ANA seropositivity

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2. Elevated white blood cell and platelet counts and a microcytic anemia. ESR elevated except in
MAS.
3. Anti–cyclic citrullinated peptide (CCP) antibody, like RF, is a marker of more aggressive
disease.
4. Ferritin values are typically elevated.
5. Radiographic changes: soft tissue swelling, Periarticular osteoporosis, erosions and bony
destruction.
6. MRI is more sensitive than radiography to early changes.
7. Ophthal slit lamp examination : for uveitis
Treatment: Dmards Biological agents
Nsaids Methotrexate Anti TNF α- etanercept, infliximab, adalimumab
Naproxen Sulfasalazine Anti-Cytotoxic T Lymphocyte–Associated Antigen-4
Ibubrofen leflunomide Immunoglobulin- abatacept
meloxicam Anti CD 20 – rituximab
Interlukin 1 receptor antagonist- ankinra
Non pharmacological:
1. Dietary advice with appropriate calcium, vitamin D, protein and calorie intake.
2. Physical therapy and occupational therapy.
Differential diagnosis:
1. Rheumatic and inflammatory diseases: juvenile idiopathic arthritis, SLE, Behcet, Kawasaki,
HSP
2. Seronegative spondyloarthropathies: juvenile AS, IBD, psoriatic arthritis
3. Infectious illness: bacterial (staphy, pneumo), lyme disease, viral (mumps, EBV, rubella),
fungal
4. Reactive arthritis: acute rheumatic fever, reactive arthritis
5. Immunodeficiency: HIV, hypogammaglobulinemia
6. Congenital and metabolic disorders: gout, pseudogout, scurvy, hypo/hyperthyroidism
7. Bone and cartilage disorders: trauma, avascular necrosis, benign bone tumours
8. Neuropathic disorders: peripheral neuropathies, carpal tunnel syndrome
9. Neoplastic disorders: leukemia, lymphoma, bone tumours
10. Haematological disorders: hemophilia
11. Miscellaneous: raynaud phenomenon, fibromyalgia, growing pains.

7. Kawasaki: Kawasaki disease (KD), formerly known as mucocutaneous lymph node

syndrome and infantile polyarteritis nodosa.
Etiology:
Unknown infectious origin genetic predisposition
Clinical and laboratory features of Kawasaki:
EPIDEMIOLOGIC CASE DEFINITION (CLASSIC CLINICAL CRITERIA)
1.Fever persisting at least 5 days
2. Presence of at least 4 principal features:
Changes in extremities:
Acute: Erythema of palms, soles; edema of hands, feet
Subacute: Periungual peeling of fingers, toes in weeks 2 and 3
Polymorphous exanthem
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 Bilateral bulbar conjunctival injection without exudate
Changes in lips and oral cavity: Erythema, lip cracking, strawberry tongue, diffuse
injection of oral and pharyngeal mucosa
Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral
3. Exclusion of other diseases with similar findings

Other clinical and laboratory evidence:

Cvs- myocarditis, ccf, coronary artery aneurysms
Cns- extreme irritability, aseptic meningitis, hearing loss
Git- nausea, vomiting, diarrhoea, abdominal pain and hepatic dysfunction
Musculo skeletal- arthritis, arthralgia
Genitourinary – urethritis, meatitis
Skin: erythema and induration at BCG site and desquamating rash in groin
eye: Anterior uveitis

In the absence of treatment, KD can be divided into 3 clinical phases.

The acute febrile phase is characterized by fever and the other acute signs of illness and usually lasts
1-2 wk.
The subacute phase is associated with desquamation, thrombocytosis, the development of coronary
aneurysms, and the highest risk of sudden death in patients in whom aneurysms have developed,
and generally lasts about 2 wk.
The convalescent phase begins when all clinical signs of illness have disappeared and continues
until the erythrocyte sedimentation rate (ESR) returns to normal, typically about 6-8 wk after the
onset of illness.
Laboratory findings:
Blood- leukocytosis, anemia, elevated CRP, ESR, hypoalbuminemia, hyponatremia, thrombocytosis
(2 nd week), increased Transaminases
Urine- sterile pyuria
CSF- pleocytosis and leukocytosis
Echo- pericarditis, pericardial effusion, mitral regurgitation, coronary aneurysms > 8 mm pose
greater risk.
Predictors of poor outcome:
Male gender, young age and (3 increase and 3 decrease)
lab evidence of neutrophilia, thrombocytopenia, hepatic transaminase elevation,
hyponatremia, hypoalbuminemia and elevated CRP.

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 Supplemental laboratory criteria include albumin ≤3.0 g/dL, anemia for age, elevation of alanine
aminotransferase, platelet count after 7 days ≥450,000/mm3, white blood cell count ≥15,000/mm3,
and urine white blood cell count ≥10 /high-power field

TREATMENT OF KAWASAKI DISEASE

ACUTE STAGE
• Intravenous immunoglobulin 2 g/kg over 10-12 hr
AND
• Aspirin 80-100 mg/kg/day divided every 6 hr orally until patient is afebrile for at least 48 hr
CONVALESCENT STAGE
• Aspirin 3-5 mg/kg once daily orally until 6-8 wk after illness onset
LONG-TERM THERAPY FOR PATIENTS WITH CORONARY ABNORMALITIES
• Aspirin 3-5 mg/kg once daily orally
• Clopidogrel 1 mg/kg/day (max 75 mg/day)
• Most experts add warfarin or low-molecular-weight heparin for those patients at particularly
high risk of thrombosis
ACUTE CORONARY THROMBOSIS
• Prompt fibrinolytic therapy with tissue plasminogen activator or other thrombolytic agent
under supervision of a pediatric cardiologist

Ivig resistant KD: Defined by persistent or

recrudescent fever 36 hr after completion of the initial IVIG infusion. Patients with IVIG resistance
are at increased risk for coronary artery abnormalities. Typically, another dose of IVIG at 2 g/kg is
administered to patients with IVIG resistance. Other therapies that have been used to date include

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intravenous methylprednisolone and, less often, cyclophosphamide and plasmapheresis. A tumor
necrosis factor inhibitor, infliximab, has also been tried.

DIFFERENTIAL DIAGNOSIS OF KAWASAKI DISEASE

VIRAL INFECTIONS
• Adenovirus
• Enterovirus
• Measles
• Epstein-Barr virus
BACTERIAL INFECTIONS
• Scarlet fever
• Rocky Mountain spotted fever
• Leptospirosis
• Bacterial cervical lymphadenitis
RHEUMATOLOGIC DISEASE
• Systemic-onset juvenile idiopathic arthritis
OTHER
• Toxic shock syndrome
• Staphylococcal scalded skin syndrome
• Drug hypersensitivity reactions
• Stevens-Johnson syndrome

8. Heat injuries:

In human beings a group of reflex responses that are primarily integrated in the hypothalamus
operate to maintain body temperature within a narrow range inspite of wide fluctuations in
environmental temperature.

Temperature regulating mechanisms:

Mechanisms activated by cold Mechanisms activated by heat

Increasing heat production Decrease heat production

Shivering Hunger Anorexia
Increased activity Apathy and inertia
Increased secretion of epinephrine and
Norepinephrine Increase heat loss
Decreased heat loss Cutaneous vasodilatation
Cutaneous vasoconstriction Shivering
Horripulation Curling up Increased respiration

Why children are more vulnerable to heat illness than adults:

1. They have greater ratio of surface area to body mass than adults.
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2. Produce greater heat per kilogram of body weight than adults during activity.

3. The sweat rate is lower in children and the temperature at which sweating occurs is higher.

4. Children can take longer to acclimatize to warmer, more humid environments.

5. Children also have a blunted thirst response compared to adults and might not consume enough
fluid during exercise to prevent dehydration.

Categories:

Three categories for heat illness are generally used: heat cramps, heat exhaustion, and heat stroke.

1. Heat cramps are the most common heat injury and usually occur in mild dehydration and or salt
depletion, usually affecting the calf and hamstring muscles. They tend to occur later in activity, as
muscle fatigue is reached and water loss and sodium loss worsen. They respond to oral rehydration
with electrolyte solution and with gentle stretching. Heat syncope is fainting after prolonged exercise
attributed to poor vasomotor tone and depleted intravascular volume, and it responds to fluids,
cooling, and supine positioning. Heat edema is mild edema of the hands and feet during initial
exposure to heat; it resolves with acclimatization. Heat tetany is carpopedal tingling or spasms
caused by heat-related hyperventilation. It responds to moving to a cooler environment and
decreasing respiratory rate (or rebreathing by breathing into a bag).

2. Heat exhaustion is a moderate illness with core temperature 100-103?F (37.7-39.4?C).

Performance is obviously affected, but central nervous system (CNS) dysfunction is mild, if present.
It is manifested as headache, nausea, vomiting, dizziness, orthostasis, weakness, piloerection, and
possibly syncope. Treatment includes moving to a cool environment, cooling the body with fans,
removing excess clothing, and placing ice over the groin and axillae. If a patient is not able to
tolerate oral rehydration, IV fluids are indicated. If rapid improvement is not achieved, transport to
an emergency facility is recommended.

3. Heat stroke is a severe illness manifested by CNS disturbances and potential tissue damage. It is
a medical emergency; the mortality rate is 50%. Sports-related heat stroke is characterized by
profuse sweating and is related to intense exertion, whereas “classic” heatstroke with dry, hot skin is
of slower onset (days) in elderly or chronically ill persons. Rectal temperature is usually >104?F
(40?C). Significant damage to the heart, brain, liver, kidneys, and muscle occurs with possible fatal
consequences if untreated.

Treatment is immediate whole-body cooling via cold water immersion. Airway, breathing,
circulation, core temperature, and CNS status should be monitored constantly. Rapid cooling should
be ceased when core temperature is ~101-102?F (38.3-38.9?C). IV fluid at a rate of 800 mL/m2 in
the first hour with normal saline or lactated Ringer solution improves intravascular volume and the
body's ability to dissipate heat. Immediate transport to an emergency facility is necessary.

Prevention:
1. Athletes are advised to be well hydrated before exercise and should drink every 20 min during
exercise.
2. Free access to cold water should be advocated to coaches.
3. Practices and competition should be scheduled in the early morning or late afternoon to avoid the
hottest part of the day.
4. Proper clothing such as shorts and t-shirts without helmets can improve heat dissipation.
5. Prepractice and postpractice weight can be helpful in determining the amount of fluid necessary to
replace (8 oz for each pound of weight loss).
6. Salt pills should not be used by most people because of their risk of causing hypernatremia and
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delayed gastric emptying.
9. Performance enhancing drugs: AAG - CDE
GOALS OF
ERGOGENIC DRUG CATEGORY ADVERSE EFFECTS
USE

Multiple organ systems:

infertility, gynecomastia, female
Anabolic-androgenic Controlled Gain muscle
virilization, hypertension,
steroids substance mass, strength
atherosclerosis, physeal closure,
aggression, depression

Increase
Increase estrogens in men;
Controlled testosterone to
Androstenedione overlaps systemic risks with
substance gain muscle
steroids
mass, strength

Increase
Dehydroepiandrosterone Nutritional testosterone to Increase estrogens in men;
(DHEA) supplement gain muscle impurities in preparation
mass, strength

Increase muscle Acromegaly effects: increased

Controlled
Growth hormone mass, strength, lipids, myopathy, glucose
substance
and definition intolerance, physeal closure

Dehydration, muscle cramps,

Nutritional Gain muscle
Creatine gastrointestinal distress,
supplement mass, strength
compromised renal function

Cerebral vascular accident,

Possibly returning Increase weight
arrhythmia, myocardial infarction,
Ephedra alkaloids as nutritional loss, delay
seizure, psychosis, hypertension,
supplement fatigue
death

10. Hearing loss:

Types of Hearing Loss and causes:

Hearing loss can be peripheral or central in origin.

A. Peripheral hearing loss can be conductive, sensorineural, or mixed.

Conductive hearing loss (CHL) the most common type is caused by dysfunction in the transmission
of sound through the external or middle ear or by abnormal transduction of sound energy into neural
activity in the inner ear and the 8th nerve. Common causes of CHL in the ear canal include atresia or
stenosis, impacted cerumen, or foreign bodies. In the middle ear, perforation of the tympanic
membrane (TM), discontinuity or fixation of the ossicular chain, otitis media (OM) with effusion,
otosclerosis, LCH and cholesteatoma can cause CHL.

Sensorineural hearing loss (SNHL) - damage to or maldevelopment of structures in the inner ear.
Causes include genetic (waardenberg, pendred and usher), infections (CMV,EBV, rubella, varicella,
H. influenza), trauma and also can occur secondary to exposure to toxins, chemicals, and
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 antimicrobials.

A combination of CHL and SNHL is considered a mixed hearing loss.

B. Central (or retrocochlear) hearing loss - an auditory deficit originating along the central
auditory nervous system pathways from the proximal 8th nerve to the cerebral cortex. Tumors or
demyelinating disease of the 8th nerve and cerebellopontine angle.

Screening techniques: The recommended hearing screening techniques are either

otoacoustic emissions (OAE) testing or auditory brainstem evoked responses (ABR).

1. The ABR test, an auditory evoked electrophysiologic response that correlates highly with
hearing, has been used successfully and cost-effectively to screen newborns and to identify
further the degree and type of hearing loss. The ABR test does not assess “hearing.” A normal
ABR result only suggests that the auditory system, up to the level of the midbrain, is responsive to
the stimulus used.

2. OAE tests, used successfully in most universal newborn screening programs, are quick, easy to
administer, and inexpensive, and they provide a sensitive indication of the presence of hearing
loss. Results are relatively easy to interpret.

3. Behavioural observation audiometry

Clinical audiological evaluation:

Audiometry
Speech- recognition threshold
Play audiometry
Visual reinforcement audiometry
Tympanometry

Treatment:
1. Once a hearing loss is identified, a full developmental and speech and language evaluation is
needed.
2. Counselling and involvement of parents are required in all stages of the evaluation and
treatment or rehabilitation.
3. A conductive hearing loss often can be corrected through treatment of a middle-ear effusion
(i.e., ear tube placement) or surgical correction of the abnormal sound-conducting mechanism.

4. Children with SNHL should be evaluated for possible hearing aid use by a pediatric
audiologist.
5. Infants and young children with profound congenital or prelingual onset of deafness have
benefited from multichannel cochlear implants.
6. Total communication approach; depending on the individual child's needs, this technique uses
a mixture of sign language, lip-reading, hearing aids, and speech.

11. AOM: It is the most common cause of hearing loss in children.

The term otitis media has 2 main categories:
acute infection, which is termed suppurative or acute otitis media (AOM); and
Inflammation accompanied by effusion, termed nonsuppurative or secretory OM, or otitis
media with effusion (OME).

Factors believed to affect the occurrence of OM include (total 11 points)

age, gender, race, genetic background, socioeconomic status,
type of milk used in infant feeding, degree of exposure to tobacco smoke, season of the year,
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degree of exposure to other children, presence or absence of respiratory allergy,
and vaccination status.

Etiology: (4 + 3)
S.pneumoniae, H.influenza Moraxella catarrhalis S. Aureus
rhinovirus RSV influenza

Diagnosis:
(1) a history of acute onset of signs and symptoms,
(2) the presence of MEE (bulging of TM, absent or diminished mobility of TM, otorrhea, air fluid
level)
(3) signs and symptoms of middle-ear inflammation.(distinct erythema and otalgia)

Inv – Tympanometry, tympanogram

Treatment: 1. Medical:

AGE CERTAIN DIAGNOSIS UNCERTAIN DIAGNOSIS

<6 mo Antibacterial therapy Antibacterial therapy
6 mo-2 Antibacterial therapy if severe illness;
Antibacterial therapy
yr observation option* if non severe illness
Antibacterial therapy if severe illness;
≥2 yr observation option* if nonsevere Observation option*
illness

*
Non severe illness is mild otalgia and fever <39?C in the past 24 hr.
Severe illness is moderate to severe otalgia or fever ≥39?C.

Drugs and duration:

First line: amoxicillin 80-90 mg/kg/day for 10 days
Second line drugs: amoxiclav, cefdinir, ceftriaxone cefuroxime
Add antifungal if no
improvement.

2. Surgical: myringotomy with tympanocentesis or myringotomy with tympanostomy tube

insertion

Complications:
Intratemporal: dermatitis, tympanic membrane perforation, chronic suppurative OM (CSOM),
hearing loss, facial nerve paralysis, cholesteatoma formation, mastoiditis and labyrinthitis.

Intracranial : Meningitis, epidural abscess, subdural abscess, brain abscess, focal encephalitis,
sigmoid sinus thrombosis (also called lateral sinus thrombosis), and otitic hydrocephalus.

12. Cutaneous reactions to sunlight:

Sun burn

Photo allergic eruptions

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Phototoxic drug eruptions

Genetic disorders with photosensitivity- xeroderma pigmentosa, bloom syndrome

Inborn errors of metabolism—porphyrias, hartnup disease

Infectious diseases associated with photosensitivity- recurrent herpes

Skin diseases precipitated or exacerbated by light- lichen planus, lupus erythematosus, psoriasis

Deficient protection due to lack of pigment- vitiligo, oculocutaneous albinism.

13. Osteomyelitis:

Bone infections in children are relatively common and important because of their potential to cause
permanent disability. Early recognition of osteomyelitis in young patients before extensive infection
develops and prompt institution of appropriate medical and surgical therapy minimize permanent
damage.

MOST COMMON CLINICAL

MICROORGANISM
ASSOCIATION
Frequent microorganism in any type of Staphylococcus aureus (susceptible or resistant to
osteomyelitis methicillin)
Coagulase-negative staphylococci, other skin flora,
Foreign body–associated infection
atypical mycobacteria
Enterobacteriaceae, Pseudomonas aeruginosa,
Common in nosocomial infections
Candida spp.
Salmonella spp., S. aureus, or Streptococcus
Sickle cell disease
pneumoniae
Aspergillus spp., Candida albicans, or Mycobacteria
Immunocompromised patients
spp.
Populations in which tuberculosis is
Mycobacterium tuberculosis
prevalent

Clinical features:

1. The earliest signs and symptoms of osteomyelitis, often subtle and nonspecific, are generally
highly dependent on the age of the patient.
2. Neonates might exhibit pseudoparalysis or pain with movement of the affected extremity
(e.g., diaper changes). Half of neonates do not have fever and might not appear ill.
3. Older infants and children are more likely to have fever, pain, and localizing signs such as
edema, erythema, and warmth. With involvement of the lower extremities, limp or refusal to

146
 walk is seen in approximately half of patients.
4. Focal tenderness over a long bone can be an important finding.
5. Long bones are principally involved in osteomyelitis.
6. Conditions causing pseudoparalysis include unrecognized trauma, transient (toxic) synovitis,
acute osteomyelitis, acute rheumatic fever, scurvy, and congenital syphilis (pseudoparalysis of
Parrot).

Diagnosis:

1. The diagnosis of osteomyelitis is clinical; blood cultures should be performed in all suspected
cases.
2. There are no specific laboratory tests for osteomyelitis.
3. The white blood cell count and differential, erythrocyte sedimentation rate (ESR), or
C-reactive protein (CRP) are generally elevated in children with bone infections but are
nonspecific.
4. Monitoring elevated ESR and CRP may be of value in assessing response to therapy or
identifying complications.
5. Depending on the results of imaging studies aspiration or biopsy of bone or subperiosteal
abscess for Gram stain, culture, and possibly bone histology provides the optimal specimen
for culture to confirm the diagnosis.

Imaging:

1. Plain radiograph - Within 72 hr of onset of symptoms of osteomyelitis, plain radiographs of the

involved site using soft-tissue technique and compared to the opposite extremity, if necessary, can
show displacement of the deep muscle planes from the adjacent metaphysis caused by deep-tissue
edema.
2. MRI is more sensitive than CT or radionuclide imaging in acute osteomyelitis and is the best
radiographic imaging technique for identifying abscesses and for differentiating between bone and
soft-tissue infection.
3. Radionuclide imaging can be valuable in suspected bone infections, especially early in the course
of infection and/or if multiple foci are suspected or an unusual site is suspected, as in the pelvis.

Antibiotic therapy:
The initial empirical antibiotic therapy is based on knowledge of likely bacterial pathogens at various
ages, the results of the Gram stain of aspirated material, and additional considerations.

In neonates, an antistaphylococcal penicillin, such as nafcillin or oxacillin (150-200 mg/kg/24 hr

divided q6h IV), and a broad-spectrum cephalosporin, such as cefotaxime (150-225 mg/kg/24 hr
147
divided q8h IV), provide coverage for the S. aureus, group B streptococcus, and gram-negative
bacilli.
If methicillin-resistant Staphylococcus is suspected, vancomycin is substituted for nafcillin.

Duration of antibiotic therapy is individualized depending on the organism isolated and clinical
course. For most infections including those caused by S. aureus, the minimal duration of antibiotics is
21-28 days, provided that the patient shows prompt resolution of signs and symptoms and the CRP
and ESR have normalized.

Surgical Therapy When frank pus is obtained from subperiosteal or

metaphyseal aspiration or is suspected based on MRI findings, a surgical drainage procedure is
usually indicated. Surgical intervention is also often indicated after a penetrating injury and when a
retained foreign body is possible.

Physical Therapy: The affected extremity should be kept in extension with

sandbags, splints, or, if necessary, a temporary cast. Casts are also indicated when there is a
potential for pathologic fracture. After 2-3 days, when pain is easing, passive range of motion
exercises are started and continued until the child resumes normal activity.

14. DIFFERENTIAL DIAGNOSIS OF TORTICOLLIS NACO-I

CONGENITAL
Osseous anomalies (Hemivertebra, unilateral atlanto-occipital fusion, Klippel-Feil
syndrome)
Soft tissue abnormalities (unilateral absence of sternocleidomastoid, pterygium colli)
ACQUIRED
Positional deformation or congenital muscular torticollis
Trauma (muscular injury, fractures)
Cervical instability (atlanto-occipital subluxation, atlantoaxial subluxation, subaxial
subluxation)
Atlantoaxial rotatory displacement
INFLAMMATION
Cervical lymphadenitis
Retropharyngeal abscess
Diskitis or vertebral osteomyelitis
Rheumatoid arthritis

NEUROLOGIC
Visual disturbances (nystagmus, superior oblique paresis)
Dystonic drug reactions (phenothiazines, haloperidol, metoclopramide)
Neoplasia (cervical spinal cord or posterior fossa tumor)
Chiari I malformation and/or syringomyelia
148
 Wilson disease
Dystonia
Spasmus nutans (nystagmus, head bobbing, head tilting)
OTHER

Sandifer syndrome (gastroesophageal reflux, hiatal hernia)

Benign paroxysmal torticollis of infancy
Bone tumors (eosinophilic granuloma)
Soft tissue tumor
Hysteria

15. Approach to hypopigmented patch

hypopigmented
lesions

Hypopigmention without surface Hypopigmention with surface with organ involvment

changes
changes

vitilligo p.Alba hypomelanosis of ito

nevus depigmentosus P.versicolor Tuberous sclerosus
topical steroid Hansen
PLE
post infla.

Congenital and Acquired Disorders of Hypopigmentation and Depigmentation:

149
Disorder Cong vs acq Hypo vs dep Clinical features
Piebaldism Cong dep Autosomal dominant inheritance

Leukoderma of frontal scalp, White forelock

Special variants includes Waardenburg syndrome,

associated with sensorineural deafness

Within areas of depigmentation, may have areas

of normal or hyperpigmentation
Nevus Cong hypo Well-circumscribed hypopigmented patch (not
depigmentosis depigmented as the name suggests)

Usually present at birth or early infancy

Wood lamp examination may aid in diagnosis

Hypomelanosis Cong hypo Whorls or streaks of hypopigmentation that
of Ito follow lines of blaschko
No evidence
Both sexes of genetic Usually present at birth or manifests within first
equally transmission year of life
affected
Possible systemic associations include CNS,
eye and musculoskeletal abnormalities
Nevus Cong hypo Asymptomatic. Often unilateral on trunk
anemicus
Rubbing or temperature change causes erythema
of surrounding skin
Ash leaf spot Cong hypo Often present at birth

Wood lamp examination may aid in the diagnosis

Atleast 3 must be present to meet one criteria for

tuberous sclerosis

Full examination for other signs of tuberous

sclerosis
Pityriasis alba Acq Hypo Post inflammatory hypopigmentation

Poorly demarcated, hypopigmented, slightly

scaly patches often located on the cheeks

Repigmentation usually occurs

Vitiligo Acq Dep Complete loss of pigment in involved areas

Symmetric May be segmental/ non segmental in

lesions distribution
Puva
Topical therapy Hyperpigmentation may be present at borders of
steroids, lesion
topical Avoid
tacrolimus sunexposure Infrequently associated with autoimmune
pimercolimus disorders, including hypothyroidism
150
albinism

16. CLASSIFICATION OF CHILDHOOD VASCULITIS

I. PREDOMINANTLY LARGE VESSEL VASCULITIS

• Takayasu arteritis
II. PREDOMINANTLY MEDIUM VESSEL VASCULITIS
• Childhood polyarteritis nodosa
• Cutaneous polyarteritis nodosa
• Kawasaki disease
III. PREDOMINANTLY SMALL VESSEL VASCULITIS
A Granulomatous:
• Wegener granulomatosis
• Churg-Strauss syndrome
B Nongranulomatous:
• Microscopic polyangiitis
• Henoch-Schonlein purpura
• Isolated cutaneous leukocytoclastic vasculitis
• Hypocomplementemic urticarial vasculitis
IV. OTHER VASCULITIDES
• Behcet disease
• Vasculitis secondary to infection (including hepatitis B–associated polyarteritis nodosa),
malignancies, and drugs, including hypersensitivity vasculitis
• Vasculitis associated with connective tissue disease
• Isolated vasculitis of the central nervous system
• Cogan syndrome
• Unclassified

17. CHARACTERISTICS OF CUTANEOUS SIGNS OF SYSTEMIC DISEASES

DIAGNOSTIC ASSOCIATED
AGE OF SKIN DISTRIBUT
DISEASE EVALUATION(S) SYMPTOMS/SI
ONSET LESIONS ION
AND FINDINGS GNS
Erythematous
ANA panel
patches;
palpable Anti–double-strand
purpura; livedo ed DNA Arthritis
Systemic Leukopenia/lymph Nephritis
reticularis; Photodistribut
lupus openia
Any Raynaud ion; “malar” Cerebritis
erythematos
phenomenon; face Thrombocytopenia Serositis
us
thrombocytopen Complement levels
ic and
Urinalysis
nonthrombocyto
penic purpura
Discoid Adolesce Annular, scaly Photodistribut ANA Scarring

151
 DIAGNOSTIC ASSOCIATED
AGE OF SKIN DISTRIBUT
DISEASE EVALUATION(S) SYMPTOMS/SI
ONSET LESIONS ION
AND FINDINGS GNS
lupus nce plaques; ion
atrophy;
dyspigmentation
Annular, Photodistribut ANA Heart block
Neonatal Newborn
erythematous, ion; Anti-Ro Thrombocyto
lupus to 6 mo
scaly plaques head/neck penia
Periocular ANA Proximal
Erythematous to
face; shoulder Jo-1 antibody muscle
violaceous scaly,
Juvenile girdle; weakness
macules; Aldolase
dermatomyo Any extensor
discrete papules Creatine kinase Calcifications
sitis extremities;
overlying Lactate Vasculopathy
knuckles;
knuckles dehydrogenase
palms
Urinalysis
Childhoo Abdominal
Henoch-Sch Buttocks; Blood urea pain
d and Purpuric papules
onlein lower nitrogen/creatinine
adolescen and plaques Arthritis
purpura extremities ratio
ce
Skin biopsy
Erythematous Strawberry
maculopapular Leukocytosis tongue
to urticarial ESR Conjunctivitis
Infancy,
Kawasaki plaques; acral
childhoo Diffuse C-reactive protein Lymphadenopa
disease and groin
d Thrombocytosis thy
erythema,
edema, Cardiovascular
desquamation complications
Aphthae; Abdominal
erythema ESR pain
Childhoo
Inflammator nodosum; Oral ulcers; Thrombocytosis Diarrhea
d and
y bowel pyoderma perianal Radiographic
adolescen Cramping
disease gangrenosum; fissures abnormalities
ce Arthritis
thrombophlebiti
s Conjunctivitis
Infiltrated Skin biopsy Fever
Sweet erythematous, Leukocytosis Flulike illness
Any Diffuse
syndrome edematous
plaques ESR Conjunctivitis
Acute: Head and Skin biopsy Fever
Graft versus erythema, neck; Mucositis
Any Liver function
host disease papules, palms/soles;
vesicles, bulla diffuse Hepatitis

Erythema; Liver function Perioral edema

Hypersensiti urticarial Eosinophilia Lymphadenopa
Any Diffuse
vity reaction macules and Atypical thy
plaques lymphocytosis Fever
152
 DIAGNOSTIC ASSOCIATED
AGE OF SKIN DISTRIBUT
DISEASE EVALUATION(S) SYMPTOMS/SI
ONSET LESIONS ION
AND FINDINGS GNS
Hepatitis
Fever
Serum Lymphadenopa
Edematous,
sickness–lik Any Acral; diffuse ESR thy
purpuric plaques
e reaction Arthritis,
nephritis
ANA, antinuclear antibodies; ESR, erythrocyte sedimentation rate

18. Atopic dermatitis:

Atopic dermatitis (AD), or eczema, is the most common chronic relapsing skin disease seen in
infancy and childhood. Frequently occurs in families with other atopic diseases, such as asthma,
allergic rhinitis, and food allergy.
Etiology:

AD is a complex genetic disorder that results in a defective skin barrier, reduced skin innate
immune responses, and exaggerated T-cell responses to environmental allergens and microbes that
lead to chronic skin inflammation.

Pathogenesis:

Two forms of AD have been identified. Atopic eczema is associated with IgE-mediated sensitization
(at onset or during the course of eczema) and occurs in 70-80% of patients with AD. Nonatopic
eczema is not associated with IgE-mediated sensitization and is seen in 20-30% of patients with AD.
Both forms of AD are associated with eosinophilia.

Clinical features:

AD is diagnosed on the basis of 3 major features: pruritus, an eczematous dermatitis that fits into a
typical presentation, and a chronic or chronically relapsing course. Associated features,
such as a family history of asthma, hay fever, elevated IgE, and immediate skin test reactivity, are
variably present.

Triggering factors: Foods (cow milk, egg, peanut, soy, wheat, fish, shellfish), inhalant allergens,
bacterial infection, reduced humidity, excessive sweating, and irritants (wool, acrylic, soaps, toiletries,
fragrances, detergents) can exacerbate (trigger) pruritus and scratching.

Laboratory Findings:

There are no specific laboratory tests to diagnose AD. Many patients have peripheral blood
eosinophilia and increased serum IgE levels. Serum IgE measurement or prick skin testing can
identify the allergens to which patients are sensitized

Treatment: The treatment of AD requires a systematic and multifaceted approach.

1. Bathing and moisturization - Lukewarm soaking baths for 15-20 min followed by the application
of an occlusive emollient to retain moisture provide symptomatic relief.

2. Topical Corticosteroids-- Topical corticosteroids are the cornerstone of anti-inflammatory

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treatment.

3. Topical Calcineurin inhibitors—Pimecrolimus in mild to moderate AD and Tacrolimus in mod to

severe AD.

4. Tar preparations 5. Antihistamines 6. Systemic steroids

7. avoid triggering factors 8. treat superinfection

9. Phototherapy Natural sunlight is often beneficial to patients with AD as

long as sunburn and excessive sweating are avoided. Phototherapy is generally reserved for patients
in whom standard treatments fail.

10. Other- omalizumab, interferon γ, allergen immunotherapy, Probiotics, Chinese herbal medicines
and antimetabolites.

Prevention:
1. Breast-feeding or a feeding with a hypoallergenic hydrolyzed formula may be beneficial.

2. Avoid/ eliminate triggering factors

3. Maintain adequate hydration of skin.

19. Approach to a limping child:

Most cases of limp are transient and may improve with time without any specific treatment.
Diseases causing tenderness, weakness or asymmetry of the weight bearing apparatus, result in a
limping gait.

Common conditions resulting in a limp:

1. NEUROMUSCULAR diseases:

 Paralysis of muscles- poliomyelitis and traumatic neuritis

 Hemiplegia
 Myopathies and muscular dystrophies
 Hemi hypertrophy of muscles
 Cerebral palsy

2. Disorders of bones and joints:

 HIP - CDH, pyogenic arthritis, transient synovitis, trauma, rickets, slipped epiphysis, perthes
disease

 KNEE and ANKLE: Tb, rheumatoid arthritis, transient synovitis, trauma and osteochondritis

 FOOT- painful lesions of the nail, toes and soles (warts, corns, blisters, paronychial, fracture)
Ill fitting shoes, osteochondritis

 SPINE- Tb, scoliosis and congenital defects

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3. Bone tumours both benign and malignant

Approach:
History should include the following

CHARACTERIZATION OF PAIN AND PRESENTING SYMPTOM

Age of presentation
Location: Whether pain is localized to a particular segment or involves a larger area.
Intensity: Usually on a pain scale of 1 to 10.
Quality: Tumor pain is often unrelenting, progressive, and often present during the night.
Pain at night particularly suggests osteoid osteoma. Pain in inflammation and infection is
usually continuous.
Onset: Was it acute and related to specific trauma or was it insidious? Acute pain and
history of trauma are more commonly associated with fractures.
Duration: Whether transient, only lasting for minutes, or lasting for hours or days. Pain
lasting for longer than 3-4 wk suggests a serious underlying problem.
Progress: Whether static, increasing, or decreasing.
Radiation: Pain radiating to upper or lower extremities or complaints of numbness, tingling,
or weakness require appropriate work-up.
Aggravating factors: Relationship to any activities such as swimming or diving or any
particular position.
Alleviating factors: Is the pain relieved by rest, heat, and/or medication?
Gait and posture: Disturbances associated with pain.

Examination should help to localise the cause of limp:

1. Child with painful knee will try to walk with extended knee.
2. In spinal disease, trunk is held rigidly.
3. With septic arthritis one would refuse to walk
4. In legg calve perthes disease- trendlenburg gait
5. In neuromuscular disorders look for atrophy, asymmetry and torsion of muscles

20. DIFFERENTIATION OF LEG BOWING

PHYSIOLOGIC BOWING BLOUNT DISEASE

Gentle and symmetric deformity Asymmetric, abrupt, and sharp angulation

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PHYSIOLOGIC BOWING BLOUNT DISEASE

Metaphyseal-diaphyseal angle <11 degrees Metaphyseal-diaphyseal angle >11 degrees

Medial sloping of the epiphysis
Normal appearance of the proximal
Widening of the physis
tibial growth plate
Fragmentation of the metaphysis
No significant lateral thrust Significant lateral thrust

Classification of genu varum - bow legs

1. Physiologic
2. Asymmetric growth
 Tibia vara (blount disease)
 Focal fibrocartilagenous dysplasia
 Trauma
 Infection
 Tumour
 Physeal injury
3. Metabolic disorders
 Nutritional (vit D deficiency) rickets
 Vitamin D resistant rickets
 Hypophosphatasia
4. Skeletal dysplasia
 Metaphyseal dysplasia
 Achondroplasia
 Enchondromatosis

Causes of back pain:

1. Inflammatory/ infectious- diskitis, vertebral osteomyelitis, spinal epidural abscess,
pyelonephritis, pancreatitis
2. Rheumatological- juvenile rheumatoid arthritis, reiter syndrome, ankylosing spondylitis,
psoriatic arthritis
3. Developmental- spondylolysis, spondylolisthisis, scoliosis
4. Traumatic
5. Neoplastic – benign and malignant tumours of verterbra

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 6. Spinal cord, ganglia and nerve roots
7. Others- following LP
21. Hyperpigmentation
Freckles Acquired Small, tan to brown, 1- to 5-mm macules
Increase in number and pigmentation in summer and spring
during exposure to sunlight
Seen in fair-skinned individuals in sun-exposed areas
Lentigines Acquired Uniform, dark, brown/black 2- to 5-mm macules
No seasonal variation or change with sun exposure
Involve any part of the body, including mucous membranes
Café au lait Congenital/ May be seen at birth or later in life
acquired
spots Tan to brown discrete macules or patches; usually round or oval
Six or more lesions larger than 5 mm in prepubertal persons and
larger than 15 mm in postpubertal persons to meet criteria for
neurofibromatosis
Neurofibromatosis lesions: smooth, well-demarcated borders
resembling “coast of California”
McCune-Albright syndrome: larger lesions with more jagged,
not as well-demarcated borders resembling “coast of Maine”
Mongolian Congenital Brown, blue-gray patches often seen in the lower trunk and
spot lumbosacral area.
Usually fades later in life
Benign with no known extracutaneous findings
Nevus of Ota Congenital/ 50% present at birth, 50% during second decade
acquired Unilateral blue-gray pigmentation in trigeminal nerve
distribution
May increase in size and color with time
Nevus of Ito Congenital/ Patchy blue-gray pigmentation of shoulder, supraclavicular area
acquired and deltoid areas
May increase in size and color with time
Nevus spilus Congenital/ Well-demarcated, hyperpigmented patch with smaller, darker
Patch within acquired macules and papules within larger patch
May look like a “chocolate chip cookie”
a patch
Small risk of malignant transformation; follow clinically
Congenital Congenital Tan, brown/dark brown macules, patches, or plaques seen at
melanocytic birth or early infancy
Variable color and texture

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nevus Small (<2 cm), medium (2-20 cm), large (>20 cm)
Large or multiple (>3) nevi carry risk of neurocutaneous
melanosis or melanoma
Acquired Acquired May start as hyperpigmented macules
melanocytic Peaks in number during 2nd-3rd decade of life
Abnormalities in color, borders, size, symmetry may suggest
nevi
malignant transformation
Melanoma Acquired Variegation in color, texture or border of congenital and acquired
melanocytic nevus
Rare in childhood; risk correlated with family history and sun
exposure in childhood

AUTOANTIBODY SPECIFICITY AND DISEASE ASSOCIATIONS

ANTIBODY DISEASE SPECIFICITY

Associated with increased risk of
uveitis in JIA and psoriatic
SLE, juvenile rheumatoid arthritis,
Antinuclear antibody arthritis
dermatomyositis, scleroderma,
(ANA) Up to 30% of children testing
psoriatic arthritis, MCTD
positive for ANAs have no
underlying rheumatic disease
Double-stranded DNA High specificity for SLE;
SLE
(dsDNA) associated with lupus nephritis
Highly specific for SLE;
Smith (Sm) SLE
associated with lupus nephritis
Smooth muscle (Sm) Autoimmune hepatitis —
Pm-Scl
(polymyositis-sclerode Sclerodermatomyositis —
rma)
Associated with neonatal lupus
SSA (Ro) SLE, Sjogren syndrome
syndrome,
SSB (La) SLE, Sjogren syndrome
Ribonuclease protein
MCTD, SLE
(RNP)
Histone Drug-induced lupus, SLE —
Centromere Limited cutaneous systemic sclerosis
Topoisomerase I
Systemic sclerosis
(Scl-70)
158
 ANTIBODY DISEASE SPECIFICITY
Antineutrophil
cytoplasmic antibodies Vasculitis —
(ANCAs):
Cytoplasmic cANCAs associated with
(cANCAs) Wegener granulomatosus,
pANCAs associated with
Perinuclear (pANCAs) microscopic polyangiitis,
polyarteritis nodosa, SLE,
READ ALSO 2 TABLES IN NELSON REGARDING MULTIDISCIPLANRY APPROACH AND
VARIOUS DRUGS USED IN CTD

Henoch-Schonlein Purpura:
Henoch-Schonlein purpura (HSP) is the most common vasculitis of childhood and is characterized
by leukocytoclastic vasculitis and immunoglobulin (Ig) A deposition in the small vessels in the
skin, joints, gastrointestinal tract, and kidney.
Epidemiology:
HSP affects males more than females. Approximately 90% of HSP cases occur in children, usually
between the ages of 3 and 10 yr. HSP is more common in the fall, winter, or spring and is unusual
in summer months. Many cases of HSP follow a documented upper respiratory infection.

Pathogenesis:
The exact pathogenesis of HSP remains unknown. Given the frequency of preceding upper
respiratory infections, including group A streptococcal infections, an infectious trigger is suspected.
Skin biopsies demonstrate vasculitis of the dermal capillaries and postcapillary venules. In all tissues,
immunofluorescence identifies IgA deposition in walls of small vessels, accompanied to a lesser
extent by deposition of C3, fibrin, and IgM.

Clinical Manifestations:
1. The hallmark of HSP is its rash: palpable purpura starting as pink macules or wheals and
developing into petechiae, raised purpura, or larger ecchymoses. The skin lesions are usually
symmetric and occur in gravity-dependent areas (lower extremities) or on pressure points
(buttocks). The skin lesions often evolve in groups, typically lasting 3-10 days, and may recur up to
4 mo after initial presentation. Subcutaneous edema localized to the dorsa of hands and feet,
periorbital area, lips, scrotum, or scalp is also common.
2. Musculoskeletal involvement, including arthritis and arthralgias. The arthritis tends to be
self-limited and oligoarticular, with a predilection for the lower extremities, and does not lead to
deformities.

159
3. Gastrointestinal manifestations of HSP occur in up to 80% of children with HSP. They include
abdominal pain, vomiting, diarrhea, paralytic ileus, melena, intussusception, and mesenteric ischemia
or perforation.
4. Renal involvement occurs in up to 50% of children with HSP, manifesting as hematuria,
proteinuria, hypertension, frank nephritis, nephrotic syndrome, and acute or chronic renal failure.
5. Neurologic manifestations of HSP, due to hypertension or central nervous system (CNS) vasculitis,
may also occur. They include intracerebral hemorrhage, seizures, headaches, and behavior changes.
6. Other less common potential manifestations of HSP are orchitis, carditis, inflammatory eye
disease, testicular torsion, and pulmonary hemorrhage.

Diagnosis:CLASSIFICATION CRITERIA FOR HENOCH-Schonlein PURPURA

AMERICAN COLLEGE OF RHEUMATOLOGY CLASSIFICATION CRITERIA
Two of the following criteria must be present:
• Palpable purpura
• Age at onset ≤20 yr
• Bowel angina (postprandial abdominal pain, bloody diarrhea)
• Biopsy demonstrating intramural granulocytes in small arterioles and/or venules
Differential diagnosis: acute hemorrhagic edema (The younger age, the nature of the lesions,
absence of other organ involvement, and a biopsy may help distinguish AHE from HSP)
Laboratory diagnosis:
1. No laboratory finding is diagnostic of HSP.
2. Common but nonspecific findings include leukocytosis, thrombocytosis, mild anemia, and
elevations of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
3. Occult blood is frequently found in stool specimens.
4. Assessment of renal involvement with blood pressure, urinalysis, and serum creatinine is
necessary.
5. Ultrasound is often used in the setting of gastrointestinal complaints to look for bowel wall
edema or the rare occurrence of an associated intussusception.
6. Barium enema can also be used to both diagnose and treat intussusception.
7. Although often unnecessary in typical HSP, biopsies of skin and kidney can provide
important diagnostic information, particularly in atypical or severe cases, and
characteristically show IgA deposition in affected tissues.
Treatment:
Treatment of HSP is supportive, with an emphasis on assuring adequate hydration,
nutrition, and analgesia.

 Steroids are most often used to treat significant gastrointestinal involvement or other
160
 life-threatening manifestations. Empiric use of prednisone (1 mg/kg/day for 1 to 2 wk,
followed by taper) reduces abdominal and joint pain but does not alter overall prognosis nor
prevent renal disease.
 Other drugs: IVIG, plasma exchange, immunosuppressants, including azathioprine,
cyclophosphamide, and mycophenolate mofetil.

Complications:

GIT- Intestinal perforation

Renal- Renal disease is the major long-term complication, occurring in 1-2% of children with
HSP. It is recommended that children with HSP undergo serial monitoring of blood pressure
and urinalyses for 6 mo after diagnosis, especially those who presented with hypertension or
urinary abnormalities. End-stage renal disease develops in up to 8% of children with HSP
nephritis.

Prognosis:

Overall, the prognosis for childhood HSP is excellent, and most children experience an acute,
self-limited course. About 30% of children with HSP experience one or more recurrences, typically
within 4-6 mo of diagnosis. With each relapse, symptoms are usually milder than at presentation.

161
 METABOLIC
1. Carbohydrate metabolism
a.FEATURES OF THE DISORDERS OF CARBOHYDRATE METABOLISM
i. Liver glycogenoses
ii. Muscle glycogenoses
2. Type I Glycogen Storage Disease (Glucose-6-Phosphatase or Translocase Deficiency, Von
Gierke Disease)

3. MPS

4. gout

1. FEATURES OF THE DISORDERS OF CARBOHYDRATE METABOLISM

Liver glycogenoses (1 3 4 6)

DISORDERS BASIC DEFECTS CLINICAL PRESENTATION

Glucose-6-phosphata Growth retardation, hepatomegaly, hypoglycemia; elevated
Ia/Von Gierke se in liver, kidney blood lactate, cholesterol, triglyceride, and uric acid levels.
and intestine Intermittent diarrhea, PCOD in females
Glucose-6-phosphate Same as type Ia, with additional findings of neutropenia and
Ib
translocase impaired neutrophil function
Childhood: hepatosplenomegaly, growth retardation, muscle
Liver and muscle weakness, hypoglycemia, hyperlipidemia, elevated
IIIa/Cori or
debrancher transaminase levels;
Forbes
deficiency liver symptoms can progress to liver failure later in life. Liver
biopsy shows fibrosis
Liver debrancher
deficiency; normal
IIIb Liver symptoms same as in type IIIa; no muscle symptoms
muscle enzyme
activity
IV/Andersen so Failure to thrive, hypotonia, hepatosplenomegaly, progressive
remember 4 Branching enzyme cirrhosis (death usually before 5th yr), elevated transaminase
features levels. No hypoglcemia
Hepatomegaly, typically mild hypoglycemia, hyperlipidemia, and
VI/Hers Liver phosphorylase
ketosis

Muscle glycogenoses: (2 5 7)
Cardiomegaly, hypotonia, hepatomegaly; onset: birth to 6 mo. Specific
II/Pompe Acid α-glucosidase
enzyme replacement therapy (ERT) with recombinant human acid
Infantile (acid maltase)
α-glucosidase (alglucosidase alfa, [Myozyme]) is available

Acid α-glucosidase
Juvenile Myopathy, variable cardiomyopathy; onset: childhood
(acid maltase)

Acid α-glucosidase
Adult Myopathy, respiratory insufficiency; onset: adulthood
(acid maltase)

162
V/McArdle Myophosphorylase Exercise intolerance, muscle cramps, increased fatigability
Exercise intolerance, muscle cramps, hemolytic anemia,
VII/Tarui Phosphofructokinase
myoglobinuria

2. Type I Glycogen Storage Disease (Glucose-6-Phosphatase or Translocase Deficiency, Von

Gierke Disease)

Type I GSD an autosomal recessive disorder, is caused by the absence or deficiency of

glucose-6-phosphatase activity in the liver, kidney, and intestinal mucosa.

Clinical Manifestations:

1. GENERAL: These children often have doll-like faces (cherubic appearance) with fat
cheeks, relatively thin extremities, short stature, and a protuberant abdomen that is due to
massive hepatomegaly; the kidneys are also enlarged, whereas the spleen and heart are normal
2. GIT: Intermittent diarrhea.
3. BLOOD: Easy bruising and epistaxis may occur in GSD I.
4. OVARIES: Virtually all females have ultrasound findings consistent with polycystic ovaries;
5. Symptoms of gout usually start around puberty from long-term hyperuricemia.
6. PANCREAS: Secondary to the lipid abnormalities, there is an increased risk of pancreatitis.
7. BONE: Frequent fractures and radiographic evidence of osteopenia are common.
8. LIVER: By the 2nd or 3rd decade of life, most patients with type I GSD exhibit hepatic
adenomas that can hemorrhage and, in some cases, become malignant.
9. LUNG: Pulmonary hypertension has been seen in some long-term survivors of the disease.
10. KIDNEY: Renal disease is another complication, and most patients with type I GSD who are
>20 yr of age have proteinuria. Many also have hypertension, renal stones,
nephrocalcinosis, and altered creatinine clearance.

Diagnosis:
1. The diagnosis of type I GSD is suspected on the basis of clinical presentation and the
laboratory findings of hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia.
Neutropenia is noted in GSD Ib patients, typically after the 1st 2-3 yr of life.

2. Gene-based mutation analysis provides a noninvasive way of diagnosis for most patients
with types Ia and Ib disease.
3. The histologic appearance of the liver is characterized by a universal distention of
hepatocytes by glycogen and fat. The lipid vacuoles are particularly large and prominent.
There is little associated fibrosis.

Treatment: Treatment is designed to maintain normal blood glucose levels and is achieved
by continuous nasogastric infusion of glucose or oral administration of uncooked cornstarch.

1. Frequent feedings with high-carbohydrate content are given during the day.
2. Uncooked cornstarch acts as a slow-release form of glucose and can be introduced at a dose
of 1.6 g/kg every 4 hr for infants <2 yr of age. The response of young infants is variable. As
the child grows older, the cornstarch regimen can be changed to every 6 hr at a dose of
1.75-2.5 g/kg of body weight.
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 3. Restrict fructose, sorbitol, sucrose, lactose and galactose.
4. For hyperuricemia -allopurinol
5. For
hyperlipidemia- HMG-CoA reductase inhibitors and fibrate.
6. Microalbuminuria-is treated with angiotensin-converting enzyme (ACE) inhibitors.
7. Growth hormone should be used with extreme caution.
8. In patients with type Ib GSD, granulocyte and granulocyte-macrophage colony–stimulating
factors.
9. Smaller adenomas (<2 cm) percutaneous ethanol injection or transcatheter arterial
embolization.
10. Large adenomas (>2 cm) may require partial hepatic resection.
11. Orthotropic liver transplantation is a potential cure of type I GSD.

Prognosis:
1. Previously, the prognosis was guarded for those who survived.
2. Early diagnosis and effective treatment have improved the outcome.
3. Renal disease and formation of hepatic adenomas with potential risk for malignant
transformation remain serious complications.

3. Mucopolysacchridosis:

Defective
eponym Clinical features Stored material
enzyme
C corneal clouding
H hearing loss,
I- hydrocephalus
H U dysostosis multiplex
Pfaundler-Hurl α-L-Iduronida Derman sulfate
R oar shaped ribs and
er Severe form se heparan sulfate
Ovoid shaped vertebral bodies
L limited learning
E enlarged ventricles
R recurrent URI
S Joint Stiffness
O onset after > 5 years of
age
I- Scheie N normal intelligence α-L-Iduronida Derman sulfate
S Milder form and stature se heparan sulfate
E (eye) corneal clouding,
glaucoma
A aortic valve disease
Hurler-Scheie M micrognathia
I-
intermediate S spondylolisthisis α-L-Iduronida Derman sulfate
H
type D dysostosis multiplex se heparan sulfate
S
C cord compression

164
 Defective
eponym Clinical features Stored material
enzyme
C corneal clouding
H hearing loss,
I- hydrocephalus
H U dysostosis multiplex
Pfaundler-Hurl α-L-Iduronida Derman sulfate
R oar shaped ribs and
er Severe form se heparan sulfate
Ovoid shaped vertebral bodies
L limited learning
E enlarged ventricles
R recurrent URI
Severe course similar to I-H but
clear corneas. Mild course: less
pronounced features, later
manifestation, survival to
Hunter Iduronate
adulthood with mild or no Derman sulfate
II X- linked sulfate
mental deficiency. heparan sulfate
recessive sulfatase
C chronic diarrhoea
C carpal tunnel syndrome
Grouped skin papules are present
in some patients
AB aggressive behavior
CC coarse hair, clear corneas
D D progressive dementia,
III mild Heparan-S-sul
Sanfilippo A Heparan sulfate
-A dysmorphism, famidase
S S sleeping disorder,
survival to
adulthood possible
Heparan sulfate
III N-Ac-α-gluco
Sanfilippo B
-B saminidase

Heparan sulfate
Ac-CoA-gluco
III
Sanfilippo C saminide-N-ac
-C
etyltransferase

Heparan sulfate
N-Ac-glucosa
III
Sanfilippo D minine-6-sulfa
-D
te sulfatase

C fine corneal opacities

S short-trunk dwarfism
N-Ac-galactos
IV F final height <125 cm
Morquio A amine-6-sulfat Keratin sulfate
-A B characteristic bone
e sulfatase
dysplasia
P Preservation of intelligence
Same as IV-A, but milder;
IV β-Galactosida
Morquio B adult height >120 cm Keratin sulfate
-B se
Preservation of intelligence

165
 Defective
eponym Clinical features Stored material
enzyme
C corneal clouding
H hearing loss,
I- hydrocephalus
H U dysostosis multiplex
Pfaundler-Hurl α-L-Iduronida Derman sulfate
R oar shaped ribs and
er Severe form se heparan sulfate
Ovoid shaped vertebral bodies
L limited learning
E enlarged ventricles
R recurrent URI
Hurler phenotype but normal N-Ac-galactos
intelligence -amine-α-4-su
Maroteaux-La
VI 4c corneal clouding cardiac lfate sulfatase Dermatan sulfate
my
disease, cord compression (arylsulfatase
communicating hydrocephalus B)
Varying from fetal hydrops to
VI β-Glucuronida Derman sulfate
Sly(seven) mild dysmorphism; dense
I se heparan sulfate
inclusions in granulocytes

Hyaluronidase Periarticular masses, normal

IX Hyaluronidase
def intelligence

4. GOUT:
Gout is associated with hereditary disorders in three different enzyme disorders that result in
hyperuricemia. These include the severe form of hypoxanthine-guanine phosphoribosyltransferase
(HPRT) deficiency (Lesch-Nyhan disease) and partial HPRT deficiency and glycogen storage disease
type I (glucose-6-phosphatase deficiency).

166
 GENETICS
1. Genetic counselling
2. Cytogenetics/ fish
3. Dysmorphology – sagar sir notes endocrinology
4. Modes of inheritance
5. Gene therapy and also my notes (black and white crane classmate note book)
6. Enzyme replacement
7. Mitochondrial inheritance
8. Chromosomal abnormalities--------iap text book
9. Mutations iap text book
10. Downs syndrome------ muthuram sir notes
11.

1. Genetic counselling:
Genetic counselling is a communication process in which the genetic contribution to health is
explained, along with specific risks of transmission of a trait and options to manage the condition and
its inheritance.
INDICATIONS FOR GENETIC COUNSELING
1. Advanced parental age
• Maternal age ≥35 yr
• Paternal age ≥50 yr
2. Previous child with or family history of
• Congenital abnormality
• Dysmorphology
• Mental retardation
• Isolated birth defect
• Metabolic disorder
• Chromosome abnormality
• Single-gene disorder
3. Adult-onset genetic disease (pre symptomatic testing)
• Cancer
• Huntington disease
4. Consanguinity
5. Teratogen exposure (occupational, abuse)
6. Repeated pregnancy loss or infertility
7. Pregnancy screening abnormality
• Maternal serum α-fetoprotein
• Maternal triple or quad screen or variant of this test
• Fetal ultrasonography
• Fetal karyotype
8. Heterozygote screening based on ethnic risk
• Sickle cell anemia
• Tay-Sachs, Canavan, Gaucher
167
 diseases
• Thalassemia
9. Follow-up to abnormal neonatal genetic testing

Genetic Counselling (remember total 9 points)

Providing accurate information to families requires
A) Specific Condition or Conditions
If a specific diagnosis is made and confirmed, that should be discussed with the family and
information should be provided in writing. However, often the disorder fits into a spectrum (e.g., one
of many types of arthrogryposis) or the diagnosis is clinical rather than laboratory based. In those
situations, the family needs to understand the limits of present knowledge and that additional
research will probably lead to better information in the future.
B) Knowledge of the Diagnosis of the Particular Condition
Although it is not always possible to make an exact diagnosis, having a diagnosis as accurate as
possible is important. When a specific diagnosis cannot be made (as in many cases of multiple
congenital anomalies), the various possibilities in the differential diagnosis should be discussed
with the family and empirical information should be provided.
C) Natural History of the Condition
It is very important to discuss the natural history of the specific genetic disorder in the family.
Affected persons and their families have questions regarding the prognosis and potential therapy
that can be answered only with knowledge of the natural history. If there are other possible diagnoses,
their natural history may also be discussed. If the disorder is associated with a spectrum of clinical
outcomes or complications, the worst and best scenarios, as well as treatment and referral to the
appropriate specialist, should be addressed.
D) Genetic Aspects of the Condition and Recurrence Risk
The genetic aspects and risk of recurrence are important because all family members need to be
aware of their reproductive choices. The genetics of the disorder can be explained with visual aids
(e.g., diagrams of chromosomes). It is important to provide accurate occurrence and recurrence
risks for various members of the family, including unaffected individuals. Counselling should give
patients the necessary information to understand the various options and let the patients make their
own informed decisions regarding pregnancy, adoption, artificial insemination, prenatal diagnosis,
screening, carrier detection, and termination of pregnancy. It may be necessary to have more than 1
counselling session.
E) Prenatal Diagnosis and Prevention
Many different methods of prenatal diagnosis are available, depending on the specific genetic
disorder. The use of ultrasonography allows prenatal diagnosis of anatomic abnormalities such as
congenital heart defects. Amniocentesis and chorionic villous sampling are used to obtain fetal
tissue for analysis of chromosomal abnormalities, biochemical disorders, and DNA studies.
Maternal blood or serum sampling is used for some types of screening. Fetal cells can be retrieved
from the umbilical cord or from maternal blood (free fetal DNA) for testing, although mothers might
harbour cells from all previous pregnancies.
F) Therapies and Referral
A number of genetic disorders require the care of a specialist. Girls with Turner syndrome usually
need to be evaluated by an endocrinologist. Prevention of known complications is a priority. The
psychologic adjustment of the family might require specific intervention. When to discuss the
diagnosis of a chronic disease with the patient is always a difficult decision. The decision to do so
should always involve the parents and an assessment of the maturity and capacity of the child or
adolescent.
Alternative medicines or non-traditional therapies are often brought to attention by parents after
exhaustive Internet searches. Such treatments should not necessarily be dismissed out of hand
because the physician and counsellor should serve as an important resource for helping parents
navigate the maze of nonstandard treatments. Instead, the relative merits of treatments should be

168
framed in the context of cost and benefit, scientific rationale, evidence from controlled and/or
observational studies, the placebo effect, safety of the treatment, and the gaps on our own scientific
knowledge base.
G) Support Groups
A large number of community lay support groups have been formed to provide information and to
fund research on specific genetic and non genetic conditions. An important part of genetic
counselling is to give information about these groups to patients and to suggest a contact person for
the families. Many groups have established websites with very helpful information.
H) Follow-up
Families should be encouraged to continue to ask questions and keep up with new information about
the specific disorder. New developments often influence the diagnosis and therapy of specific
genetic disorders. Lay support groups are a good source of new information.
I) Nondirective Counselling
Genetic counselling is usually nondirective; choices about reproduction are left to the family to
decide what is right for them. The role of the counsellor (physician, genetic counsellor, nurse,
medical geneticist) is to provide information in understandable terms and outline the range of options
available.

2. Cytogenetics: Clinical cytogenetics is the study of chromosomes: their structure, function,

inheritance, and abnormalities.
Chromosome analyses are indicated in persons presenting with
1. Multiple congenital anomalies, dysmorphic features, and/or mental retardation with or without
associated anatomic abnormalities.
2. Advanced maternal age (>35 yr)
3. Multiple abnormalities on fetal ultrasound (prenatal testing), multiple congenital anomalies,
unexplained growth retardation in the fetus.
4. Postnatal problems in growth and development
5. Ambiguous genitalia
6. Primary amenorrhea or infertility, recurrent miscarriages (≥3) or prior history of stillbirths and
neonatal deaths
7. A 1st-degree relative with a known or suspected structural chromosome abnormality
8. Clinical findings consistent with a known anomaly, some malignancies, and chromosome breakage
syndromes (Bloom syndrome, Fanconi anemia).
Cytogenetic studies are usually performed on
1. Peripheral blood lymphocytes, although cultured fibroblasts may also be used.
2. Prenatal (fetal) chromosome studies are performed with cells obtained from the amniotic fluid,
chorionic villus tissue, and fetal blood.
3. Preimplantation diagnosis, by analysis of a blastomere.
4. Cytogenetic studies of bone marrow have an important role in tumor surveillance, particularly
among patients with leukemia.
Methods:
Karyotyping - Banding (G, Q, C, R)
Molecular cytogenic techniques: FISH, Genomic array hybridization studies, Spectral
karyotyping (SKY), multicolour FISH (M-FISH), RFLP, Linkage analysis and Comparative genomic
hybridization (CGH).
FISH:

169
Fluorescence in situ hybridization (FISH) involves

Denaturation of double-stranded DNA as present in metaphase chromosomes or interphase nuclei on

cytogenetic slide preparations (A) into single-stranded DNA (B).

The slide-bound (in situ) DNA is then renatured or reannealed in the presence of excess copies of a
single-stranded, fluorochrome-labeled DNA base-pair sequence or probe (C).

The probe anneals or “hybridizes” to sites of complementary DNA sequence (D) within the
chromosomal genome.

Probe signal is visualized and imaged on the chromosome by fluorescent microscopy.

Advantages: FISH can reliably detect deletions as small as 50 to 200 kb of

DNA. This has allowed the clinical characterization of a number of microdeletion syndromes.

Disadvantages: FISH requires the clinical

knowledge and tests only 1 area at a time. Needs cell culture to generate sufficient DNA.

Applications:

1. Preimplantation chromosomal analysis

2. Pre and post natal diagnosis

3. Chromosomal microdeletion syndromes

170
4. Age related losses

5. Oncology

6. Chromosomal structure study

7. Specific probe preparation

RECOGNIZABLE POISON SYNDROMES

SIGNS
Poison
Mental Bowel Possible Toxins
Syndrome Vital Pupils Skin Other
Status Sounds
Amphetamines,
Hypertensio
cocaine,
n, Agitated,
Sympathomim Dilate Diaphore Normal to ecstasy,
tachycardia, psychosis,
etic d tic increased pseudoephedrin
hyperthermi delirium
e, caffeine,
a
theophylline
Antihistamines,
Hypertensio
Agitation, tricyclic
n,
Anticholinergi delirium, Dilate Decrease antidepressants,
tachycardia, Dry
c mumbling d d atropine, jimson
hyperthermi
speech weed,
a
phenothiazines
Bradycardia
Diarrhea,
(though
urination,
may show Confusion, Organophospha
bronchorrhea,
tachycardia coma, Diaphore Hyperacti tes, nerve gases,
Cholinergic Small bronchospasm
), BP and fasciculatio tic ve Alzheimer
, emesis,
temp ns medications
lacrimation,
typically
salivation
normal
Vitals:
Respiratory
depression
(hallmark Methadone,
of toxicity), suboxone,
Depression Pinpoi Normal to
Opioids bradycardia Normal morphine,
, coma nt decreased
, oxycodone,
hypotension heroin, etc.
,
hypothermi
a
Respiratory
depression,
HR normal
Barbiturates,
Sedative-Hypn to Somnolenc
Small Normal Normal benzodiazepine
otics decreased, e, coma
s, ethanol
BP normal
to
decreased,
171
 SIGNS
Poison
Mental Bowel Possible Toxins
Syndrome Vital Pupils Skin Other
Status Sounds
temp
normal to
decreased

Neuromuscula
Hypertherm
r
ia,
hyperexcitabil SSRIs, lithium,
tachycardia,
Agitation, ity: clonus, MAOIs,
Serotonin hypertensio Dilate Diaphore
confusion, Increased hyperreflexia linezolid,
syndrome n or d tic
coma (lower tramadol,
hypotension
extremities > meperidine
(autonomic
upper
instability)
extremities)
Nausea,
vomiting,
Aspirin,
Tachypnea, tinnitus, ABG
bismuth
hyperpnea, Agitation, with primary
Norma Diaphore subsalicylate
Salicylates tachycardia, confusion, Normal respiratory
l tic (Pepto-Bismol),
hyperthermi coma alkalosis and
methyl
a primary
salicylates
metabolic
acidosis

Tachycardia Withdrawal
Lethargy,
, tachypnea, Dilate Diaphore from opioids,
Withdrawal confusion, Increased
hyperthermi d tic sedative-hypnot
delirium
a ics, ethanol

Enzyme Replacement

Enzyme replacement therapy (ERT) is a component of the treatment of cystic fibrosis to manage
intestinal malabsorption. Pancreatic enzymes are easily administered orally, because they must be
delivered to the gastrointestinal tract.

Enzyme replacement strategies are effective for some lysosomal storage disorders. Enzymes are
targeted for the lysosome by modification with mannose-6-phosphate, which binds to a specific
receptor. This receptor is also present on the cell surface, so lysosomal enzymes with exposed
mannose-6-phosphate residues can be infused into the blood and are taken into cells and transported
to lysosomes. Enzyme replacement therapies are available for Gaucher disease and Fabry disease,
some mucopolysaccharidoses (I, II, VI), Niemann-Pick disease type C, and Pompe disease.

One complication of ERT is antibody response to the enzyme. The magnitude of this response is
172
not always predictable and varies depending on the enzyme preparation and the disease. In most
cases, the patient's antibody response does not affect the treatment's efficacy (e.g, in Gaucher disease),
but in other situations it may be a significant hurdle (e.g., in Pompe disease).

173
 GIT
1. DENTAL CARIES
2. Wilsons disease
3. Pancreatic function tests
4. Chronic diarrhea
5. Malabsorption
6. Peptic ulcer disease and H. pylori
7. Liver transplantation
8. Liver abscess
9. Viral markers in hepatitis
10. c/f of metabolic liver disease
11. autoimmune hepatitis
12. Reyes syndrome
13. portal hypertension
14. Hypertrophic pyloric stenosis
15. mechanisms of diarrhea
16. constipation
17. achalasia
18. duodenal obstruction
19. Hirschsprungs disease
20. Celiac disease
21. Ascites/ SAAG
22. vomiting
23. chronic abdominal pain
24. short bowel syndrome
25. upper GI bleed
26. intussusception
27. antibiotic associated diarrhea
28. GSD
29. portal venous system
30. acute fulminant hepatic failure
31. GERD
32. Pancreatitis (acute, chronic)
33. Indian childhood cirrhosis
34. Liver function tests
35. Neonatal cholestasis approach notes
36. Neonatal hepatitis approach
37. Tracheosophageal fistula
38. Diarrhea – acute and persistent
39. GI bleed (upper and lower)
40. Pre- probiotics
41. gall stones (article)
42.

1. DENTAL CARIES

ETIOLOGY: The development of dental caries depends on interrelationships among the

174
tooth surface, dietary carbohydrates, and specific oral bacteria. The initial demineralization
appears as an opaque white spot lesion on the enamel, and with progressive loss of tooth mineral,
cavitation of the tooth occurs. The group of microorganisms Streptococcus mutans are associated
with the development of dental caries.

CLINICAL FEATURES: Dental caries of the primary dentition usually begins in the pits and
fissures. Small lesions may be difficult to diagnose by visual inspection, but larger lesions are
evident as darkened or cavitated lesions on the tooth surfaces. Rampant dental caries in infants and
toddlers is usually referred as early childhood caries (ECC). Children who develop caries at a young
age are known to be at high risk for developing further caries as they get older.

Complications:

1.Pulpitis 2. Pulp necrosis 3. Dental abscess sepsis

infection of the facial space cerebral abscess.

Treatment:
1. Oral analgesics, such as ibuprofen, are usually adequate for the pain control.
2. Oral antibiotics are indicated for dental infections associated with fever, cellulitis, and facial
swelling, or if it is difficult to anesthetize the tooth in the presence of inflammation.
3. Dental treatment, using silver amalgam, plastic composite, or stainless steel crowns, can restore
most teeth affected with dental caries. If caries involves the dental pulp, a partial removal of the pulp
(pulpotomy) or complete removal of the pulp (pulpectomy) may be required.
4. Dental infection localized to the dentoalveolar unit can be managed by local measures (extraction,
pulpectomy).

Prevention: 1. Fluoride: The most effective preventive measure against dental

caries is communal water supplies optimized to 1 ppm fluoride.

SUPPLEMENTAL FLUORIDE DOSAGE SCHEDULE

FLUORIDE IN HOME WATER (ppm)

AGE
<0.3 0.3-0.6 >0.6
6 mo-3 yr 0.25* 0 0
3-6 yr 0.50 0.25 0
6-16 yr 1.00 0.50 0
*
Milligrams of fluoride per day

2. Fluoridated toothpaste
3. Fluoride varnish is ideal for professional applications in preschool children.

4. Oral hygiene: Daily brushing, especially with fluoridated toothpaste, atleast twice daily helps
prevent dental caries.
5. Diet: Frequent consumption of fruit juice is not generally recognized by parents for its high
cariogenic potential. Special efforts must be made to instruct parents that their child should only
consume juices at meal times and not exceed 6 oz per day.

6. Dental Sealant: Sealants are most effective when placed soon after teeth erupt and used in
175
children with deep grooves and fissures in the molar teeth.

2. Wilson Disease (also read notes for management in siblings with Wilson’s disease)

Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder that can be

associated with degenerative changes in the brain, liver disease, and Kayser-Fleischer rings in the
cornea.

The incidence is 1/50,000 to 1/100,000 births. It is progressive and potentially fatal if

untreated.

Pathogenesis: The abnormal gene for Wilson disease is localized to the

long arm of chromosome 13.
The Wilson disease gene encodes a copper transporting P-type ATPase, ATP7B, which is critical for
biliary copper excretion and for copper incorporation into ceruloplasmin. Absence or malfunction of
ATP7B results in decreased biliary copper excretion and diffuse accumulation of copper in the
cytosol of hepatocytes. With time, liver cells become overloaded and copper is redistributed to other
tissues, including the brain and kidneys, causing toxicity, primarily as a potent inhibitor of enzymatic
processes.

Clinical Manifestations (Total 8 points)

Forms of Wilsonian hepatic disease include

176
1. Asymptomatic hepatomegaly (with or without splenomegaly),

2. Subacute or chronic hepatitis

3. Acute hepatic failure (with or without hemolytic anemia).

4. Cryptogenic cirrhosis, portal hypertension, ascites, edema, variceal bleeding, or other effects of
hepatic dysfunction (delayed puberty, amenorrhea, and coagulation defect) can be manifestations of
Wilson disease.

The younger the patient, the more likely hepatic involvement will be the predominant manifestation.
Girls are 3 times more likely than boys to present with acute hepatic failure.

5. After 20 yr of age, neurologic symptoms predominate. Neurologic disorders can develop

insidiously or precipitously, with intention tremor, dysarthria, rigid dystonia, parkinsonism,
choreiform movements, lack of motor coordination, deterioration in school performance, or
behavioral changes. Kayser-Fleischer rings may be absent in young patients with liver disease but
are always present in patients with neurologic symptoms.

6. Psychiatric manifestations include depression, personality changes, anxiety, or psychosis.

7. Coombs-negative hemolytic anemia may be an initial manifestation, possibly related to the

release of large amounts of copper from damaged hepatocytes; this form of Wilson disease is usually
fatal without transplantation.

8. Unusual manifestations include arthritis, infertility or recurrent miscarriages, cardiomyopathy,

and endocrinopathies (hypoparathyroidism).

Pathology: All grades of hepatic injury occur with steatosis, heptocellular ballooning and
degeneration, glycogen granules, minimal inflammation, and enlarged Kupffer cells. The lesion
may be indistinguishable from that of autoimmune hepatitis. With progressive parenchymal damage,
fibrosis and cirrhosis develop.

Diagnosis:

1. Wilson disease should be considered in children and teenagers with 1. Unexplained acute or
chronic liver disease, 2. Neurologic symptoms of unknown cause, 3. Acute hemolysis, 4.
Psychiatric illnesses, behavioral changes, 5. Fanconi syndrome or 6. Unexplained bone
(osteoporosis, fractures) or muscle disease (Myopathy, arthralgia).
2. Most patients with Wilson disease have decreased Ceruloplasmin levels (<20 mg/dL).
3. The serum copper level may be elevated in early Wilson disease.
4. Urinary copper excretion (usually <40 µg/day) is increased to >100µ g/day and often up to
1,000 µg or more per day.
5. d- Penicillamine challenge test: In equivocal cases, the response of urinary copper output to
chelation may be of diagnostic help. During the 24 hr urine collection patients are given two
500 mg oral doses of d-penicillamine 12 hr apart; affected patients excrete >1,600 µg/24 hr.
6. Demonstration of Kayser-Fleischer rings, requires a slit-lamp examination by an
ophthalmologist.
177
 7. Liver biopsy is of value for determining the extent and severity of liver disease and for
measuring the hepatic copper content (normally <10 µg/g dry weight). In Wilson disease,
hepatic copper content exceeds 250 µg/g dry weight.
8. Screening: Family members of patients with proven cases require screening for pre
symptomatic Wilson disease.
9. Genetic screening by either linkage analysis or direct DNA mutation analysis is possible.

Treatment:

A major attempt should be made to restrict dietary copper intake to <1 mg/day.

Foods such as liver, shellfish, nuts, and chocolate should be avoided.

Demineralise the water if necessary.

The initial treatment in symptomatic patients is the administration of copper-chelating agents,

which leads to rapid excretion of excess deposited copper.

d- penicillamine 10 -50% of patients have worsening of their

condition.

hypersensitivity reactions.
20 mg/kg/day for pediatric
patients deficiency of other elements such as zinc.

aplastic anemia and nephrosis

antimetabolite of vitamin B6 tujhfv

Triethylene tetramine Few side effects

dihydrochloride
20 mg/kg/day for children
Ammonium 120 mg/day (20 mg anemia, leukopenia, thrombocytopenia, and
tetrathiomolybdate between meals tid and 20 mild elevations of transaminases.
mg with meals tid)
Side effects are mostly limited to gastric
upset.
Zinc 25 mg 3 times a day in
children >5 yr of age. Zinc has also been used as adjuvant
therapy, maintenance therapy, or primary
therapy in presymptomatic patients,
owing to its unique ability to impair the
gastrointestinal absorption of copper

Prognosis:

Untreated patients with Wilson disease can die of hepatic, neurologic, renal, or hematologic
complications. The prognosis for patients receiving prompt and continuous penicillamine is variable
178
and depends on the time of initiation of and the individual response to chelation.

Liver transplantation should be considered for patients with fulminant liver disease, decompensated
cirrhosis, or progressive neurologic disease.

In asymptomatic siblings of affected patients, early institution of chelation or zinc therapy can
prevent expression of the disease.

Approach to evaluation and treatment of asymptomatic siblings (or other first-degree relatives) of a
patient with Wilson’s disease. Illustrated are both a “phenotype” and a “genotype” approach to
evaluation

179
3. Pancreatic Function Tests:

Pancreatic function can be measured by direct and indirect methods.

1. An indirect test, the measurement of fecal elastase, which has become the standard screening test
for pancreatic insufficiency, has a sensitivity and specificity >90%.

2. A 72-hr stool collection for quantitative analysis of fat content is the gold standard for the
diagnosis of malabsorption. Normal fat absorption is >93% of intake.

3. Qualitative examination of the stool for microscopic fat globules can give false-positive and
false-negative results.

4. Pancreatic function can also be measured by a breath test using 13C-triolein as the substrate.

5. Serum trypsinogen estimation- a good screening test for pancreatic insufficiency.

6. Bentiromide test (NBT- PABA test): Bentiromide a synthetic non absorbable peptide is degraded
by pancreatic chymotrypsin, releasing PABA that is absorbed by the normal intestinal mucosa,
conjugated and excreted in urine. Thus, a low serum or urine PABA indicated pancreatic
insufficiency.

Direct test:

1. Pancreozymin- Secretin test: The gold standard test for exocrine pancreatic function is direct
analysis of duodenal aspirate for volume, bicarbonate, trypsin and lipase upon secretin and
pancreozymin /cholecystokinin stimulation. This involves duodenal intubation, and only a few
180
centers perform this test.

2. Lundh meal test:

Pancreatic functions:

1. The acinar cell synthesizes, stores, and secretes >20 enzymes, which are stored in zymogen

granules, some in inactive forms.

2. The main enzymes involved in digestion include amylase, which splits starch into maltose,

isomaltose, maltotriose; dextrins;

3. Trypsin, chymotrypsin, and endopeptidases are secreted by the pancreas as inactive

proenzymes.

4. Trypsin can then activate trypsinogen, chymotrypsinogen, and procarboxypeptidase into their

respective active forms.

5. Pancreatic lipase liberates fatty acids from the 1 and 3 positions of triglycerides, leaving a

monoglyceride.

6. The stimuli for exocrine pancreatic secretion are neural and hormonal. Acetylcholine

mediates the cephalic phase; cholecystokinin (CCK) mediates the intestinal phase.

4. Chronic diarrhea:

Chronic diarrhea is defined as a diarrheal episode that lasts for ≥14 days.

Pathophysiology

181
Etiology: ab n esi mind

INFECTIOUS ETIOLOGIES DIARRHEA ASSOCIATED ABNORMAL DIGESTIVE

WITH EXOGENOUS PROCESSES:
Bacterial SUBSTANCES
Cystic fibrosis
Excessive intake of Isolated pancreatic enzyme
Viral and protozoan agents carbonated fluid deficiency
Dietetic foods containing Chronic pancreatitis
sorbitol, mannitol, or
Tropical sprue Chronic cholestasis
xylitol
Use of bile acids sequestrants
Excessive intake of
Whipple disease antacids or laxatives Primary bile acid
containing lactulose or malabsorption
Mg(OH)2
Excessive intake of
drinks containing
methylxanthines (cola,
tea, coffee)

NUTRIENT IMMUNE AND STRUCTURAL DEFECTS

MALABSORPTION INFLAMMATORY
Food allergy (cow's milk Microvillus inclusion disease
Congenital or acquired lactase
lactase deficiency or soy proteins, others)
Celiac disease Tufting enteropathy
Congenital or acquired
sucrase-isomaltase deficiency Eosinophilic
gastroenteritis Lymphangiectasia
Glucose-galactose malabsorption Inflammatory bowel
Fructose malabsorption disease
Autoimmune enteropathy

DEFECTS OF MOTILITY DISORDERS NEOPLASTIC DISEASES

ELECTROLYTE AND
Hirschsprung disease Neuroendocrine
METABOLITE TRANSPORT
hormone-secreting tumors
Congenital chloride diarrhea Chronic (APUDomas such as
Congenital sodium diarrhea intestinalpseudo-obstruction VIPoma)
Acrodermatitis (neurogenic and myopathic) Zollinger-Ellison
enteropathica Mastocytosis
Thyrotoxicosis
Selective folate deficiency Pheochromocytoma
Abetalipoproteinemia Lymphoma

Management:

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STEP 1 STEP 2
Intestinal microbiology Intestinal morphology
• Stool cultures • Standard jejunal/colonic histology
• Microscopy for parasites • Morphometry
• Viruses • PAS staining
• Stool electrolytes • Electron microscopy
• H2 breath test
STEP 3
Screening test for celiac
disease (transglutaminase 2 Special investigations
autoantibodies) • Intestinal immunohistochemistry
Noninvasive tests for: • Anti-enterocyte antibodies
• Intestinal function •
Serum catecholamines
• Pancreatic function and
sweat test • 75SeHCAT measurement
• Intestinal inflammation • Brush border enzymatic activities
Tests for food allergy •
Motility and electrophysiological studies
• Prick/patch tests

Treatment: 1Q2AZC (typed by my little daughter)

Treatment includes

1. General supportive measures Replacement of fluid and electrolyte losses is the most
important early intervention.

2. Nutritional rehabilitation is often essential and is based on clinical and biochemical assessment.
In moderate to severe malnutrition, caloric intake may be progressively increased to 50% or more
above the recommended dietary allowances.

Clinical nutrition includes enteral or parenteral nutrition. Enteral nutrition may be delivered via
nasogastric or gastrostomy tube and is indicated in a child who cannot be fed through the oral route,
either because of primary intestinal diseases or because of extreme weakness. In extreme wasting,
enteral nutrition might not be sufficient, and parenteral nutrition is required.

Micronutrient and vitamin supplementation are part of nutritional rehabilitation and prevent further
problems, especially in malnourished children from developing countries. Zinc supplementation is an
important factor in both prevention and therapy of chronic diarrhea, because it promotes ion
absorption, restores epithelial proliferation, and stimulates immune response.

3. Elimination diet

A lactose-free diet should be started in all children with chronic diarrhea, as is recommended by the
World Health Organization.

A sucrose-free formula is indicated in sucrase-isomaltase deficiency. .

4. Drug therapy includes

A) Anti-infectious drugs, Trimethoprim-sulfamethoxazole, metronidazole or albendazole, and

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nitazoxanide have a broad pattern of targets, including parasites.

B) Immune suppression- In Rotavirus-induced severe and protracted diarrhea, oral administration of

human immunoglobulins (300 mg/kg) should be considered.

Immune suppression should be considered in selected conditions such as autoimmune enteropathy.

C) Drugs that can inhibit fluid loss and promote cell growth. Severe ion secretion may be reduced by
pro-absorptive agents, such as the enkephalinase inhibitor racecadotril. In diarrhea due to
neuroendocrine tumors, microvillus inclusion disease, and enterotoxin-induced severe diarrhea, a trial
with the somatostatin analog octreotide may be considered. Zinc or growth hormone promote
enterocyte growth and ion absorption and may be effective when intestinal atrophy and ion secretion
are associated.

When other attempts have failed, the only option may be parenteral nutrition or intestinal
transplantation.

5. Malabsorption:

Malabsorption can result from a defect in the nutrient digestion in the intestinal lumen or from
defective mucosal absorption.

Malabsorption disorders can be categorized into

generalized mucosal malabsorption of specific

abnormalities nutrients

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1. Mucosal disorders CARBOHYDRATE
Gluten-sensitive enteropathy (celiac disease) MALABSORPTION
Cow's milk and other protein-sensitive Lactose malabsorption
enteropathies Congenital lactase deficiency
Eosinophilic enteropathy Secondary lactase deficiency
2. Protein-losing enteropathy Congenital sucrase- isomaltase
Lymphangiectasia (congenital and acquired) deficiency
Disorders causing bowel mucosal inflammation,
Crohn disease
3. Congenital bowel mucosal defects FAT MALABSORPTION
Microvillous inclusion disease
Abetalipoproteinemia
Tufting enteropathy
Lymphangiectasia
Cystic fibrosis
Shwachman-Diamond syndrome
Enterokinase deficiency
4. Immunodeficiency disorders Trypsinogen deficiency
Congenital immunodeficiency disorders Lipase/co-lipase deficiency
Selective IgA deficiency Chronic pancreatitis
Severe combined immunodeficiency Bile acid malabsorption (terminal
Agammaglobulinemia ileal disease)
X-linked hypogammaglobulinemia

Acquired immune deficiency

HIV infection
Immunosuppressive therapy and post-bone
marrow transplantation
5. Autoimmune enteropathy
IPEX (immune dysregulation, polyendocrinopathy,
enteropathy, X-linked inheritance)
6. Miscellaneous AMINO ACID MALABSORPTION
Immunoproliferative small intestinal disease
Lysinuric protein intolerance
Short bowel syndrome
Hartnup disease
Chronic malnutrition
Blue diaper syndrome (isolated
Radiation enteritis
tryptophan malabsorption)

MINERAL AND VITAMIN

MALABSORPTION
Congenital chloride diarrhea
Congenital sodium absorption
defect

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 Acrodermatitis enteropathica (zinc
malabsorption)
Menkes disease (copper
malabsorption)
Vitamin D–dependent rickets
Folate malabsorption
Vitamin B12 malabsorption

DRUG INDUCED

Clinical approach:

The clinical features depend on the extent and type of the malabsorbed nutrient.

The common presenting features are diarrhea, abdominal distention, and failure to gain weight, with
a fall in growth chart percentiles.

Physical findings include muscle wasting and the disappearance of the subcutaneous fat, with
subsequent loose skin folds.

A) Specific findings on examination can guide toward a specific disorder;

1. edema is usually associated with protein-losing enteropathy,

2. digital clubbing with cystic fibrosis and celiac disease,

3. perianal excoriation and gaseous abdominal distention with carbohydrate malabsorption,

4. perianal and circumoral rash with acrodermatitis enteropathica,

5. abnormal hair with Menkes syndrome, and

6. The typical facial features diagnostic of the Johanson-Blizzard syndrome.

B) The nutritional assessment is an important part of clinical evaluation in children with

malabsorptive disorders.

1. calcium and vitamin D malabsorption can lead to reduced bone mineral density with increased risk
186
of bone fractures.

2. Vitamin K malabsorption can result in Coagulopathy.

3. Severe protein-losing enteropathy causes hypoalbuminemia and edema.

4. Iron malabsorption causing microcytic anemia and low reticulocyte count,

5. low serum folate levels in conditions associated with mucosal atrophy, and

6. low serum vitamin A and vitamin E concentrations in fat malabsorption.

C) Onset of diarrhea

Onset of diarrhea in early infancy suggests a congenital defect.

Onset of symptoms after introduction of a particular food into a child's diet such as with sucrose in
sucrase-isomaltase deficiency.

D) The nature of the diarrhea may be helpful:

Explosive watery diarrhea suggests carbohydrate malabsorption.

Loose, bulky stools are associated with celiac disease.

Pasty and yellowish offensive stools suggest an exocrine pancreatic insufficiency.

Green stool with undigested “peas and carrots” can suggest rapid intestinal transit in toddler's
diarrhea

Evaluation of Malabsorption:

Initial work-up should include:

Stool microscopy for ova and parasites such as Giardia.

Stool occult blood and leukocytes to exclude inflammatory disorders.
Stool cultures and antibody tests for parasites.
A complete blood count including peripheral smear for microcytic anemia, lymphopenia
(lymphangiectasia), neutropenia (Shwachman syndrome), and acanthocytosis (abetalipoproteinemia)
is useful.

A. Investigations for Carbohydrate Malabsorption:

1. Measurement of carbohydrate in the stool, using a Clinitest reagent that identifies reducing
substances, is a simple screening test.
2. Breath hydrogen test is used to identify the specific carbohydrate that is malabsorbed.
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3. Small bowel mucosal biopsies can measure mucosal disaccharidase (lactase, sucrase, maltase)
concentrations directly.

B. Investigations for Fat Malabsorption:

The presence of fat globules in the stool suggests fat malabsorption.

Quantitative determination of fat malabsorption requires a 3-day stool collection for
evaluation of fat excretion and determination of the coefficient of fat absorption.
When bile acid deficiency is suspected the evaluation of bile acid levels in duodenal fluid aspirate
may be useful.
Fat malabsorption and exocrine pancreatic insufficiency are usually associated with deficiencies of
fat-soluble vitamins A, D, E, and K.

C. Investigations for Protein Losing Enteropathy:

Excessive bowel protein loss usually manifests as hypoalbuminemia.

Measurement of stool α1-antitrypsin is a useful screening test for protein-losing enteropathy.

D. Investigations for Exocrine Pancreatic Function:

Cystic fibrosis is the most common cause of exocrine pancreatic insufficiency in children; therefore,
a sweat chloride test must be performed before embarking on invasive tests to investigate possible
exocrine pancreatic insufficiency.
Fecal elastase-1 estimation is a sensitive test to assess exocrine pancreatic function in chronic cystic
fibrosis and pancreatitis.
Serum trypsinogen concentration can also be used as a screening test for exocrine pancreatic
insufficiency.
The gold standard test for exocrine pancreatic function is direct analysis of duodenal aspirate for
volume, bicarbonate, trypsin and lipase upon secretin and pancreozymin/cholecysto-kinin
stimulation.

E. Investigations for Intestinal Mucosal Disorders:

Establishing a specific diagnosis for malabsorption often requires histologic examination of small
bowel mucosal biopsies. Periodic acid–Schiff (PAS) staining of mucosal biopsies and electron
microscopy are necessary in congenital diarrhea to assess congenital microvillus atrophy. During
endoscopy, mucosal biopsies can be obtained to measure mucosal disaccharidase activities.
Duodenal aspirates can be performed to measure pancreatic enzyme concentration as well as
quantitative bacterial cultures. Aspirates to demonstrate other infections and infestations such as
Giardia may be useful.

F. Imaging Procedures:

Plain radiographs and barium contrast studies might suggest a site and cause of intestinal motility
disorders.

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6. Peptic ulcer disease:

Peptic ulcer disease, the end result of inflammation due to an imbalance between cytoprotective and
cytotoxic factors in the stomach and duodenum, manifests with varying degrees of gastritis or frank
ulceration.

Classification:

Primary: Secondary Acute and more

often gastric

Chronic and moreoften Result from stress due to sepsis, shock, or an intracranial lesion
duodenal (Cushing ulcer) or in response to a severe burn injury (Curling
ulcer).
Most often associated with
H.pylori Often the result of using aspirin or nonsteroidal anti-inflammatory
drugs (NSAIDs)
Idiopathic ulcers
Hypersecretory states like Zollinger-Ellison syndrome, short
bowel syndrome, and systemic mastocytosis

Pathogenesis:

Acid Secretion: Excessive acid secretion is associated with a large parietal cell mass,
hypersecretion by antral G cells, and increased vagal tone, resulting in increased or sustained acid
secretion in response to meals and increased secretion during the night. Mediators that decrease
gastric acid secretion and enhance protective mucin production include prostaglandins.

Mucosal Defense: A continuous layer of mucous gel that serves as a diffusion barrier to
hydrogen ions and other chemicals covers the gastrointestinal (GI) mucosa. Mucus production and
secretion are stimulated by prostaglandin E2. Another important function of epithelial cells is to
secrete chemokines when threatened by microbial attack. Secretion of bicarbonate into the mucous
coat, which is regulated by prostaglandins, is important for neutralization of hydrogen ions.

Clinical features: The presenting symptoms of peptic ulcer disease vary with the age of the
patient. Hematemesis or melena is reported in up to half of the patients with peptic ulcer disease.
School-aged children and adolescents more commonly present with epigastric pain and nausea,
presentations generally seen in adults. Dyspepsia, epigastric abdominal pain or fullness, is seen in
older children. Infants and younger children usually present with feeding difficulty, vomiting,
crying episodes, hematemesis, or melena. In the neonatal period, gastric perforation can be the
initial presentation.

Rarely, in patients with acute or chronic blood loss, penetration of the ulcer into the abdominal cavity
or adjacent organs produces shock, anemia, peritonitis, or pancreatitis. If inflammation and edema
are extensive, acute or chronic gastric outlet obstruction can occur.

Investigations: 1. Esophagogastroduodenoscopy is the method of choice to establish the

diagnosis of peptic ulcer disease. 2. Biopsy specimens must be obtained from the esophagus,
stomach, and duodenum for histologic assessment as well as to screen for the presence of H. pylori
infection. 3. Fecal enzyme immunoassay tests for H. pylori are available and have varying utility in
189
children.

Treatment:

ANTISECRETORY THERAPY WITH PEDIATRIC DOSAGES

MEDICATION PEDIATRIC DOSE

H2 RECEPTOR ANTAGONISTS
20-40mg/kg/day mg/kg/day
Cimetidine
Divided 2 to 4 x a day
4-10 mg/kg/day
Ranitidine
Divided 2 or 3 x a day
1-2 mg/kg/day
Famotidine
Divided twice a day
10 mg/kg/day
Nizatidine
Divided twice a day

PROTON PUMP INHIBITORS

1-3 mg/kg/day
<20 kg: 10 mg/day
Omeprazole
>20 kg: 20 mg/day
Approved for use in those >2 yr old
1-4 mg/kg/day
<30 kg: 15 mg/day
Lansoprazole
>30 kg: 30 mg/day
Approved for use in those >1 yr old
Rabeprazole Adult dose: 20 mg/day
Pantoprazole Adult dose: 40 mg/day
Sucralfate 40-80 mg/kg/day

H.pylori: spiral gram negative bacilli, highly motile with unipolar flagella. Group I carcinogen.

Epidemiology: Atleast half of the world is infected with H. pylori and most of them are
asymptomatic. Man is the only reservoir. Mainly spread through feco oral route.

Pathogenesis:

190
 cytotoxin associated urease, catalase,
gene A (cagvirulence
A) factors of cytotoxin, LPS
vacoulating toxin A,
organism
(vac A)

IL- 1 B .
SEstatus

Clinical features:
Asymptomatic gastritis
Acute active gastritis
Chronic gastritis, duodenitis and duodenal ulcer
Chronic recurrent abdominal pain
Extra gastric manifestations: anemia, short stature, sids and ITP.

Diagnosis:
Endoscopy and biopsy urea breath test serology (Ig G antibody) H. pylori
antigens in feces

Treatment:
1. amoxicillin + clarithromycin (both for twice daily 14 days) + PPI (1 month)
2. amoxicillin + metronidazole (both for twice daily 14 days) + PPI (1 month)
3. metronidazole + clarithromycin (both for twice daily 14 days) + PPI (1 month)

Amox 50 mg/ kg/day bd clarithromycin 15 mg/kg/day bd metronidazole

20mg/kg/day bd

7. Liver Transplantation –

TYPES:

a) Split liver transplantation: in response to shortage of donor organs. One liver is split into two and
used for 2 recipients. There is a need for extensive construction of segment vessels and biliary
system.

b) Living related donor: parent/ relative provide a portion, commonly left lateral segment.

c) Cadaveric organ donation: unrealistic in pediatric sub group.

d) Macro segment liver Tx: segment 2 of couinouds anatomy

191
 e) Auxillary partial liver Tx: left lobe of patients liver is replaced with a similar portion from donor.
Recovery is rapid.

f) Orthotropic liver Tx:

Indications:

1. Obstructive biliary tract disease: biliary atresia, sclerosing cholangitis, traumatic or post-surgical injury
2. Metabolic disorders: glycogen storage disease type IV, Wilson disease, neonatal hemochromatosis,
tyrosinemia type I, α1-Antitrypsin deficiency.
3. Acute hepatitis: fulminant hepatic failure, viral, toxin, or drug induced
4. Chronic hepatitis with cirrhosis: hepatitis B or C, autoimmune
5. Intrahepatic cholestasis: idiopathic neonatal hepatitis, Alagille syndrome, familial intrahepatic cholestasis
6. Miscellaneous: cryptogenic cirrhosis, congenital hepatic fibrosis, Caroli disease, cystic fibrosis (4 c’s)
7. Primary liver tumors: benign tumors (hamartomas, hemangioendothelioma), unresectable hepatoblastoma,
and hepatocellular carcinoma

Contraindications to liver transplantation include uncontrolled infection of extrahepatic origin,

uncontrolled extrahepatic malignancies, and severely disabling and uncorrectable disease in other
organ systems, principally the heart and lungs.

Pre-treatment evaluation:

Donor assessment Nutritional immunization

rehabilitation
Age < 65 Avoid pre op Routine immunization
Same blood group malnutrition MMR, DTaP, Polio, HiB,
HIV/CMV/EBV/Hep B, C/ DM Fat 50% Pneumococcal, Influenza,
have been excluded 150% RDA Hep B, Hep C
Adequate left lobe of liver size Vitamins and mineral
assessed supplementation

Complications:

Post-transplant complications can be related to the

192
 1. Pretransplant condition of the recipient and the donor match and type.

2. Immunologic responses to the graft.

3. The need for immunosuppressive drug therapy, and toxicity effects of these drugs or

4. Infections from over-Immunosupression.

They can occur at varying specific frequencies over a fairly well-defined time course (early, late, remote).

The early complications are generally related to the condition of the patient at the time of transplant and
are reflected in the patient's PELD (pediatric end stage liver disease) score, and also to the type of
graft received as it relates to the donor type,

ischemic time (primary non function of the graft), and

technical complications (hepatic artery thrombosis, portal vein thrombosis, vena cava stenosis, and
biliary complications).

Rejection usually occurs after the first 2 wk after transplant, with the highest incidence within the
first 90 days. The need to treat rejection can place the patient at a higher risk of drug toxicity or infection.

The most common transplant-related infections are cytomegalovirus (CMV) and Epstein-Barr virus (EBV)

infections, for which there are well-developed algorithms of prophylaxis.

LATE COMPLICATIONS:

Tx ass infection Post Tx Chronic Developmental Expenditure

lymphoproiferative rejection retardation
disorders
Growth failure Post Tx Psychological School Retransplantation
Immunosupression morbidity attendance
state

The diseases for which liver transplantation is indicated can be categorized into the following groups:

8. Liver abscess:

Etiology:

Pyogenic liver abscesses are rare in children, with an incidence of 10/100,000 hospitalizations.

1. Pyogenic hepatic abscesses can be caused by bacteria entering the liver via the portal circulation
193
in cases of omphalitis, portal vein pylephlebitis, intra-abdominal infection, or abscess secondary to

appendicitis or inflammatory bowel disease.

2. A primary bacteremia (sepsis, endocarditis).

3. Ascending cholangitis associated with biliary tract obstruction caused by gallstones or sclerosing

cholangitis.

4. After a Kasai procedure, or secondary to choledochal cysts.

5. Contiguous infection or penetrating trauma;

6. Protozoans: E. Histolytica and E. Dispar

7. Multiple abscess: Candida, cat scratch disease.

Organisms: In children with pyogenic liver abscesses, the most common pathogenic organisms

include Staphylococcus aureus, Streptococcus spp; Escherichia coli, Klebsiella pneumoniae,

Salmonella, and anaerobic organisms; Entamoeba histolytica or Toxocara canis–associated liver

abscesses have also been reported in developing countries or in highly endemic areas.

Clinical features: Signs and symptoms are nonspecific and can include fever, chills, night sweats,

malaise, fatigue, nausea, abdominal pain with right upper quadrant tenderness, and hepatomegaly;

jaundice is uncommon.

Diagnosis: A high index of suspicion is necessary in children with risk factors. Serum

aminotransferase and more often the alkaline phosphatase levels are elevated. The erythrocyte

sedimentation rate is high, and leukocytosis is common. The results of blood cultures are positive in

50% of patients. Chest x-rays might show elevation of the right hemidiaphragm with decreased

mobility or a right pleural effusion. Ultrasound or CT can confirm diagnosis.

Treatment:

Medical: Empirical initial antibiotic regimens include ampicillin/sulbactam or

piperacillin/tazobactam. Others recommend a combination of a third-generation cephalosporin

plus metronidazole. Antibiotic therapy for pyogenic abscess is intravenous for 2-3 wk followed by

194
oral therapy to complete a 4-6 wk course.

Amebic abscesses are treated with metronidazole or tinidazole plus paromomycin.

Surgical: Treatment requires percutaneous ultrasound- or CT-guided needle

aspiration and less often open surgical drainage, particularly if multiple or large abscesses are

present. Some treat empirically without aspiration or drainage. If amebic disease is present, most do

not attempt aspiration.

9. DIAGNOSTIC BLOOD TESTS: SEROLOGY AND VIRAL PCR

HAV HBV HCV HDV HEV

ACUTE INFECTION

Anti-HAV Anti-HDV Anti-HEV

Anti-HBc IgM+ Anti-HCV+
IgM+ IgM+ IgM+
HBsAg+ Blood PCR
Blood PCR
Blood PCR Anti-HBs HCV RNA+ positive
positive
positive* HBV DNA+ (PCR) HBsAg+
(PCR) Anti-HBs−

PAST INFECTION
(RECOVERED)
Anti-HDV Anti-HEV
+ Anti-HCV−
Anti-HAV Anti-HBs IgG+ IgG+
+ Blood PCR
IgG+ Anti-HBc IgG Blood PCR Blood PCR
negative
negative negative
CHRONIC INFECTION

Anti-HBc IgG+ Anti-HDV

HBsAg+ Anti-HCV+ IgG+
N/A Anti-HBs Blood PCR Blood PCR N/A
PCR positive positive negative
or negative HBsAg+
VACCINE RESPONSE

Anti-HAV Anti-HBs+
N/A N/A N/A
IgG+ Anti-HBc−

195
10. CLINICAL MANIFESTATIONS THAT SUGGEST THE POSSIBILITY OF METABOLIC
DISEASE

Clinical features: Recurrent vomiting, failure to thrive, short stature, dysmorphic features,
edema/Anasarca
GI clinical features: Jaundice, hepatomegaly (? splenomegaly), fulminant hepatic failure,
bleeding (Coagulopathy)
Metabolic features: Hypoglycemia, organic acidemia, lactic acidemia, hyperammonemia,
unusual odors, rickets, cataracts
Neurological: Developmental delay/psychomotor retardation, hypotonia, progressive
neuromuscular deterioration, seizures
Cardiac features: Cardiac dysfunction/failure

11. Autoimmune hepatitis:

Def: Autoimmune hepatitis is a chronic hepatic inflammatory process manifested by elevated

serum aminotransaminase concentrations, liver-associated serum autoantibodies, and/or
hypergammaglobulinemia. Important negative features include the absence of viral markers
(hepatitis B, C, D) of infection, absence of a history of drug or blood product exposure.

Classification:

CLASSIFICATION OF AUTOIMMUNE HEPATITIS

TYPE 1 AUTOIMMUNE TYPE 2 AUTOIMMUNE

VARIABLE
HEPATITIS HEPATITIS
Antibody against liver-kidney
Antinuclear antibody
microsome 1
Smooth-muscle antibody
Characteristic Antiactin antibody Antibody against liver cytosol 1
autoantibodies Autoantibodies against soluble liver
antigen and liver-pancreas antigen
Atypical perinuclear antineutrophil
cytoplasmic antibody
Geographic variation Worldwide Worldwide
Predominantly childhood and
Age at presentation Any age
young adulthood
Sex of patients Female in ~75% of cases Female in ~95% of cases
Association with other
Common Common
autoimmune diseases
Clinical severity Broad range Generally severe
Histopathologic features at
Broad range Generally advanced
presentation

196
 TYPE 1 AUTOIMMUNE TYPE 2 AUTOIMMUNE
VARIABLE
HEPATITIS HEPATITIS
Treatment failure Infrequent Frequent
Relapse after drug
Variable Common
withdrawal
Need for long-term
Variable ~100%
maintenance

Etiology:

In autoimmune hepatitis (AIH) a dense portal mononuclear cell infiltrate invades the surrounding
parenchyma and comprises T and B lymphocytes, macrophages, and plasma cells.

Triggering factors can include infections, drugs, and the environment (toxins) in a genetically
susceptible host.

Variable necrosis, fibrosis, and zones of parenchymal collapse between a portal triad and central vein
(bridging necrosis) and variable degrees of bile duct epithelial injury.

Clinical Manifestations:

 The clinical features and course of autoimmune hepatitis are extremely variable.
 Signs and symptoms at the time of presentation comprise a wide spectrum of disease
including a substantial number of asymptomatic patients and some who have an acute, even
fulminant, onset.
 Patients can be asymptomatic or have fatigue, malaise, behavioral changes, anorexia, and
amenorrhea, sometimes for many months before jaundice or stigmata of chronic liver disease
are recognized.
 Extrahepatic manifestations can include arthritis, vasculitis, nephritis, thyroiditis,
Coombs-positive anemia, and rash.
 There is usually mild to moderate jaundice. Spider telangiectasias and palmar erythema may
be present.
 The liver is often tender and slightly enlarged but might not be felt in patients with cirrhosis.
 The spleen is commonly enlarged. Edema and ascites may be present in advanced cases.

Diagnosis and Laboratory investigations:

Moderately increased liver transaminases, liver-associated serum autoantibodies,

hypergammaglobulinemia and absence of viral markers, history of drug or blood products.

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An ultrasonogram should be done to identify a choledochal cyst or other structural disorders of the
biliary system.

Differential diagnosis: Wilsons disease and alpha 1 antitrypsin.

Treatment and prognosis:

Prednisone, with or without azathioprine or 6-mercaptopurine, improves the clinical, biochemical,

and histologic features in most patients with autoimmune hepatitis and prolongs survival in most
patients with severe disease.

The choleretic agent ursodeoxycholic acid may be particularly useful in patients with biliary features
of their disease.

The initial response to therapy in autoimmune hepatitis is generally prompt, with a >75% rate of
remission.

Transaminases and bilirubin fall to near-normal levels, often in the 1st 1-3 mo.

When present, abnormalities in serum albumin and prothrombin time respond over a longer period
(3-9 mo).

12. Reyes syndrome:

 Secondary mitochondrial hepatopathies are caused by a hepatotoxic metal, drug, toxin, or

endogenous metabolite.
 One should consider the diagnosis of a mitochondrial disorder in a patient of any age, who
presents with progressive, multisystem involvement that cannot be explained by a specific
diagnosis.
 Gastrointestinal (GI) complaints include vomiting, diarrhea, constipation, failure to thrive
(FTT), and abdominal pain. In the past, the most common secondary mitochondrial
hepatopathy was Reye syndrome.
 It is precipitated in a genetically susceptible person by the interaction of a viral infection
(influenza, varicella) and salicylate use.
 Liver dysfunction is invariably present when vomiting develops, with Coagulopathy and
elevated serum levels of AST, ALT, and ammonia. Importantly, patients remain anicteric and
serum bilirubin levels are normal.
 Liver biopsies show microvesicular steatosis without evidence of liver inflammation or
necrosis.
 Death is usually secondary to increased intracranial pressures and herniation.

CLINICAL STAGING OF REYE SYNDROME AND REYE-LIKE DISEASES

I Usually quiet, lethargic and sleepy, vomiting, laboratory evidence of liver dysfunction
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 II Deep lethargy, confusion, delirium, hyperventilation, hyperreflexia
III Obtunded, light coma seizures, decorticate rigidity, intact pupillary light reaction
IV Seizures, deepening coma, decerebrate rigidity, loss of oculocephalic reflexes, fixed pupils
V Coma, loss of deep tendon reflexes, respiratory arrest, fixed dilated pupils,
flaccidity/decerebration, isoelectric EEG.

Diseases resembling reye syndrome: Organic aciduria, urea cycle defects, cns
infections and hemorrhagic shock with encephalopathy.

13. Portal hypertension: (7+5+12)

Portal hypertension, defined as an elevation of portal pressure >10-12 mm Hg or hepatic wedge

venous pressure > 4 mm of Hg above IVC pressure. The normal portal venous pressure is ∼7 mm

Hg.

Causes:

EXTRAHEPATIC PORTAL HYPERTENSION

Portal vein agenesis, atresia, stenosis
Portal vein thrombosis or cavernous transformation
Splenic vein thrombosis
Increased portal flow
Arteriovenous fistula

Intrahepatic portal hypertension:

Hepatocellular disease
Acute and chronic viral Biliary tract disease
hepatitis Idiopathic portal
Cirrhosis hypertension
Extrahepatic biliary
Congenital hepatic fibrosis atresia
Postsinusoidal obstruction
Wilson disease Cystic fibrosis
α1-Antitrypsin deficiency Budd-Chiari syndrome
Choledochal cyst
Glycogen storage disease
type IV Sclerosing cholangitis Veno-occlusive disease
Hepatotoxicity
Methotrexate Intrahepatic bile duct
Parenteral paucity
nutrition

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Pathogenesis:

1. Cirrhosis

 Resistance to portal blood flow

 Rise in portal pressures
 Development of portosystemic collaterals
 Hyperdynamic circulation

2. Forward flow theory

Splanchnic vasodilatation + decreased resistance due to collaterals + increased cardiac output

Will lead to increased portal flow.

Clinical manifestations:

1. Bleeding from esophageal varices is the most common presentation. Hemorrhage, particularly in
children with portal vein obstruction, can be precipitated by minor febrile, intercurrent illness and
drugs like aspirin or other nonsteroidal anti-inflammatory.

Gastrointestinal (GI) hemorrhage can also originate from portal hypertensive gastropathy or from
gastric, duodenal, peristomal, or rectal varices.

2. In patients with underlying hepatic disease, physical examination might show jaundice, palmar
erythema and vascular telangiectasias.

3. Ascites may be present in patients with intrahepatic causes of portal hypertension and can
transiently occur with portal vein obstruction.

4. Splenomegaly, sometimes with hypersplenism, is the next most common presenting feature in

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portal vein obstruction.

5. Long-term follow-up of patients with portal vein obstruction has revealed a variety of
complications including variceal hemorrhage, hypersplenism, biliary obstruction, growth and
development retardation, and neuropsychiatric dysfunction.

6. Blood in the intestinal lumen can promote bacterial translocation, leading to peritonitis.

7. Another serious complication of portal hypertension is the hepatopulmonary syndrome, which

develops in ≥10% of patients with cirrhosis.

Diagnosis:

Non invasive – ultrasound, Doppler, CT and MRI

Invasive- angiography, contrast enhanced echocardiography, endoscopy

1. Doppler flow ultrasonography can demonstrate the direction of flow within the portal system.
Reversal of portal vein blood flow (hepatofugal flow) is more likely to be associated with variceal
bleeding.

2. Ultrasonography is also effective in detecting the presence of esophageal varices. Another

important feature of extrahepatic portal vein obstruction is cavernous transformation of the portal
vein.

3. Contrast-enhanced CT and magnetic resonance angiography provide information similar to

ultrasonography.

4. In a patient with hypoxia (hepatopulmonary syndrome), intrapulmonary microvascular dilatation is

demonstrated with contrast-enhanced echocardiography that shows delayed appearance in the left
heart of micro bubbles from a saline bolus injected into a peripheral vein.

5. Endoscopy is the most reliable method for detecting esophageal varices and for identifying the
source of GI bleeding. Red spots apparent over varices at the time of endoscopy are a strong
predictor of imminent hemorrhage.

Treatment:

The therapy of portal hypertension can be divided into

I. Emergency treatment of potentially life-threatening hemorrhage and

II. Prophylaxis directed at prevention of initial or subsequent bleeding.

1. ABC- Treatment of patients with variceal hemorrhage must focus on fluid resuscitation, initially
in the form of crystalloid infusion, followed by the replacement of red blood cells. Care should be
taken in fluid resuscitation of children after bleeding to avoid producing an excessively high venous
pressure and increasing risk for further bleeding.

2. Correction of coagulopathy by administration of vitamin K and/or infusion of platelets or fresh

frozen plasma may be required.
201
3. A nasogastric tube should be placed to document the presence of blood within the stomach and to
monitor for ongoing bleeding.

3. An H2 receptor blocker or proton pump inhibitor should be given intravenously to reduce the
risk of bleeding from gastric erosions.

4. Vasopressin or one of its analogs has been commonly used and is thought to act by increasing
splanchnic vascular tone and thus decreasing portal blood flow.

5. Nitroglycerin, usually given as a portion of a skin patch, has also been used to decrease portal
pressure and, when used in conjunction with vasopressin, can ameliorate some of its untoward
effects.

6. The somatostatin analog octreotide is more commonly used, and it decreases splanchnic blood
flow with fewer side effects.

7. After an episode of variceal hemorrhage or in patients in whom bleeding cannot be controlled,

endoscopic sclerosis or elastic band ligation of esophageal varices are important options.

8. In patients who continue to bleed despite pharmacologic and endoscopic methods to control
hemorrhage, a Sengstaken-Blakemore tube may be placed to stop hemorrhage by mechanically
compressing esophageal and gastric varices. It poses a particularly high risk for pulmonary
aspiration.

9. Various surgical procedures have been devised to divert portal blood flow and to decrease portal
pressure. (portacaval shunt mesocaval or distal splenorenal shunt)

10. A transjugular intrahepatic portosystemic shunt (TIPS), in which a stent can aid in the
management of portal hypertension in children, especially in those needing temporary relief before
liver transplantation. The TIPS procedure can precipitate hepatic encephalopathy and is prone to
thrombosis.

11.Orthotopic liver transplantation represents a much better therapy for portal hypertension
resulting from intrahepatic disease and cirrhosis.

II. Long-term treatment with nonspecific β-blockers such as propranolol has been used extensively
in adults with portal hypertension. These agents might act by lowering cardiac output and portal
perfusion.

Prognosis:

Portal hypertension secondary to intrahepatic disease has a poor prognosis.

Portal hypertension is usually progressive in these patients and is often associated with deteriorating
liver function.

14. Congenital hypertrophic pyloric stenosis:

Males (especially first-borns) are affected approximately 4 to 6 times as often as females. The
offspring of a mother and, to a lesser extent, the father who had pyloric stenosis are at higher risk for
pyloric stenosis. The incidence of pyloric stenosis is increased in infants with B and O blood
groups.

Etiology:
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 The cause of pyloric stenosis is unknown, but many factors have been implicated.

1. Pyloric stenosis has been associated with eosinophilic gastroenteritis, Apert syndrome,
Zellweger syndrome, trisomy 18.
2. An association has been found with the use of erythromycin in neonates with highest risk if
the medication is given within the 1st 2 wk of life.
3. Abnormal muscle innervation,
4. Elevated serum levels of prostaglandins,
5. Reduced nitric oxide and
6. Infant hypergastrinemia have been implicated.

Clinical Manifestations: Nonbilious

vomiting is the initial symptom of pyloric stenosis. The vomiting may or may not be projectile
initially but is usually progressive, occurring immediately after a feeding. The vomiting usually
starts after 3 wk of age. After vomiting, the infant is hungry and wants to feed again. As vomiting
continues, a progressive loss of fluid, hydrogen ion, and chloride leads to hypochloremic metabolic
alkalosis. Hyperbilirubinemia is the most common clinical association of pyloric stenosis, also
known as icteropyloric syndrome.

Diagnosis:

The diagnosis has traditionally been established by palpating the pyloric mass. The mass is firm,

movable, ∼2 cm in length, olive shaped, hard, best palpated from the left side, and located above and

to the right of the umbilicus in the mid-epigastrium beneath the liver's edge. The olive is easiest
palpated after an episode of vomiting. After feeding, there may be a visible gastric peristaltic wave
that progresses across the abdomen.

Ultrasound examination confirms the diagnosis in the majority of cases. Criteria for diagnosis
include pyloric thickness 3-4 mm, an overall pyloric length 15-19 mm, and pyloric diameter of
10-14 mm.

Contrast tests: When contrast studies are performed, they

demonstrate an elongated pyloric channel (string sign), a bulge of the pyloric muscle into the antrum
(shoulder sign), and parallel streaks of barium seen in the narrowed channel, producing a “double
tract sign”.

Differential Diagnosis: 1.Gastroesophageal reflux, with or without

a hiatal hernia, 2. adrenal insufficiency from the adrenogenital syndrome can simulate pyloric
stenosis, 3. inborn errors of metabolism 4. pyloric membrane or pyloric duplication 5. Duodenal
stenosis proximal to the ampulla of Vater

Treatment:

1. The preoperative treatment is directed toward correcting the fluid, acid-base, and electrolyte
losses.

2. The surgical procedure of choice is Ramstedt pyloromyotomy. Endoscopic balloon dilatation

has been successful in infants with persistent vomiting secondary to incomplete pyloromyotomy.

3. Conservative management with nasodudodenal feedings is advisable in patients who are not good
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surgical candidates. Oral and intravenous atropine sulfate (pyloric muscle relaxant) has also been
described when surgical treatment is not available.

15. Mechanisms of diarrhea:

PRIMARY
STOOL
MECHANI DEFECT EXAMPLES COMMENT
EXAMINATION
SM
Cholera, toxigenic
Escherichia coli;
carcinoid, VIP,
Persists during
Decreased absorption, Watery, normal neuroblastoma,
fasting;
Secretory increased secretion, osmolality with ion congenital chloride
no stool
electrolyte transport gap <100 mOsm/kg diarrhea, Clostridium
leukocytes
difficile,
cryptosporidiosis
(AIDS)
Stops with
Maldigestion, Watery, acidic, and Lactase deficiency, fasting;
transport defects, reducing substances; glucose-galactose increased breath
Osmotic ingestion of increased osmolality malabsorption, hydrogen with
unabsorbable with ion gap >100 lactulose, laxative carbohydrate
substances mOsm/kg abuse malabsorption; no
stool leukocytes
Irritable bowel
Loose to
syndrome, Infection can also
Increased normal-appearing
Decreased transit time thyrotoxicosis, contribute to
motility stool, stimulated by
postvagotomy increased motility
gastrocolic reflex
dumping syndrome
Defect in Loose to
Decreased Pseudo-obstruction, Possible bacterial
neuromuscular normal-appearing
motility blind loop overgrowth
unit(s) stasis stool
Short bowel Might require
Decreased Decreased functional syndrome, celiac elemental diet
Watery
surface area capacity disease, rotavirus plus parenteral
enteritis alimentation
Salmonella, Shigella,
Inflammation, Dysentery
infection; amebiasis;
Mucosal decreased colonic Blood and increased evident in blood,
Yersinia,
invasion reabsorption, WBCs in stool mucus, and
Campylobacter
increased motility WBCs
infections

16. Constipation: (also see flow chart in notes)

A hard stool passed with difficulty every 3rd day should be treated as constipation.

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Constipation can arise from defects either in filling or emptying the rectum.

Causes:

Non organic (functional) - retentive

Organic

Anatomic Intestinal nerve or Drugs Intestinal disorders

Anal stenosis, muscle Anticholinergics Celiac disease
atresia with fistula abnormalities Narcotics Cow's milk
Imperforate anus Hirschsprung Methylphenidate protein
disease intolerance
Anteriorly Phenytoin
displaced anus Pseudo-obstructi Cystic fibrosis
on Antidepressants
Intestinal stricture (meconium ileus
(post necrotizing Intestinal equivalent)
enterocolitis) neuronal Lead Inflammatory
dysplasia Vitamin D bowel disease
Anal stricture
intoxication (stricture)
Tumor
Abnormal Spinal cord Metabolic disorders Connective tissue
musculature defects Hypokalemia disorders
Prune-belly Tethered cord Hypercalcemia Systemic lupus
syndrome Spinal cord erythematosus
Hypothyroidism
Gastroschisis trauma Scleroderma
Diabetes mellitus,
Down syndrome Spina bifida diabetes insipidus Psychiatric
Muscular diagnosis
dystrophy Anorexia nervosa

Clinical features: Defective rectal filling occurs when colonic peristalsis is

ineffective

The resultant colonic stasis leads to excessive drying of stool and a failure to initiate reflexes from
the rectum that normally trigger evacuation.

Constipation tends to be self-perpetuating, whatever its cause. Hard, large stools in the rectum
become difficult and even painful to evacuate; thus, more retention occurs and a vicious circle
ensues.

Eventually, watery content from the proximal colon might percolate around hard retained stool and
pass per rectum unperceived by the child. This involuntary encopresis may be mistaken for diarrhea.

CHRONIC CONSTIPATION: ROME III CRITERIA

CHILDREN WITH A DEVELOPMENTAL
INFANTS AND TODDLERS
AGE OF 4-18 YEARS
At least 2 of the following: At least 2 of the following:

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 • ≤2 defecations per week
• ≥1 episode of incontinence after • ≤2 defecations per week
the acquisition of toilet training
skills • ≥1 episode of fecal incontinence per week
• History of excessive stool • History of retentive posturing or excessive
retention volitional stool retention
• History of painful or hard bowel • History of painful or hard bowel movements
movements • Presence of a large fecal mass in the rectum
• Presence of a large fecal mass in • History of a large-diameter stool that might
the rectum obstruct the toilet
• History of a large-diameter stool
that might obstruct the toilet

Investigations:

1. Barium enema: for hirschsprungs disease and anatomical abnormalities.

2. Colonic transit time: normally it is 5- 7 days if it is more than 7 days, then colonic motility is
decreased.

3. Anorectal manometry: In hirschsprungs the anorectal inhibitory reflex is absent. In functional

constipation there is decreased rectal sensitivity to distension and elevated rectal sphincter pressures

4. Pelvic floor electromyography:

Management:

1. Prevention: diet, toilet training and provision of clean toilets

2. Treatment: five parts

a. Education

b. Softening of retained faeces: increase fluid intake and use lactulose.

c. Evacuation of retained faeces: seena, sodium picosulphate, polyethylene glycol, enema and manual
evacuation.

d. Prevention of further faecal retention.

e. Treat the underlying causes like hypothyroidism and surgical correction of tethered cord.

17. Achalasia:

Achalasia is a primary esophageal motor disorder of unknown etiology characterized by loss of

LES relaxation and loss of esophageal peristalsis, both contributing to a functional obstruction of
the distal oesophagus.

Possible Etiology:

206
1. Degenerative

2. Autoimmune (antibodies to Auerbach plexus)

3. Infectious (Chagas disease due to Trypanosoma cruzi) factors are possible causes.

4. In rare cases, achalasia is familial or part of the achalasia, alacrima, and corticotropin insensitivity,
known as Allgrove syndrome.

Pseudoachalsia refers to achalasia caused by various forms of cancer via obstruction of the
gastroesophageal junction, infiltration of the submucosa and muscularis of the LES, or as part of the
paraneoplastic syndrome with formation of anti-Hu antibodies.

Pathogenesis: Pathologically, in achalasia, inflammation surrounds ganglion cells, which

are decreased in number. There is selective loss of postganglionic inhibitory neurons that normally
lead to sphincter relaxation, leaving postganglionic cholinergic neurons unopposed. This imbalance
produces high basal LES pressures and insufficient LES relaxation. The loss of esophageal
peristalsis can be a secondary phenomenon.

Clinical features: Achalasia manifests with regurgitation and dysphagia for solids and
liquids and may be accompanied by undernutrition or respiratory symptoms; retained esophageal
food can produce esophagitis.

Investigations:

1. Chest radiograph shows an air-fluid level in a dilated esophagus.

2. Barium fluoroscopy reveals a smooth tapering of the lower esophagus leading to the closed LES,
resembling a bird's beak. Loss of primary peristalsis in the distal esophagus with retained food and
poor emptying are often present.

3. Manometry is the most sensitive diagnostic test; it reveals the defining features of aperistalsis in
the distal esophageal body and incomplete or absent LES relaxation, often accompanied by high
pressure LES and low-amplitude esophageal body contractions.

Management:

Medical: Calcium channel blockers (nifedipine) and phosphodiesterase inhibitors offer temporary
relief of dysphagia.

Surgical: The 2 most effective treatment options are pneumatic dilatation and surgical (Heller)
myotomy.

Pneumatic dilatation is the initial treatment of choice.

Endoscopic injection of the LES with botulinum toxin may be an effective therapy.

18. Duodenal obstruction:

In most cases, it is caused by atresia, an intrinsic defect of bowel formation. It can also result from
extrinsic compression by abnormal neighbouring structures (e.g., annular pancreas, preduodenal

207
portal vein), duplication cysts, or congenital bands associated with malrotation.

Types: In contrast to more-distal atresias, which likely arise from prenatal vascular
accidents, duodenal atresia results from failed recanalization of the intestinal lumen during
gestation.

Duodenal atresia can take several forms, including a 1. Thin membrane that occludes the lumen is
most common 2. A short fibrous cord that connects 2 blind duodenal pouches, or 3. a gap that spans
2 nonconnecting ends of the duodenum. In rare cases, the membrane is distensible and is referred to
as a windsock web. This unusual form of duodenal atresia causes obstruction several centimeters
distal to the origin of the membrane.

Associations: Approximately 50% of infants with duodenal atresia are premature.

Concomitant congenital anomalies are common and include congenital heart disease (30%),
malrotation (20-30%), annular pancreas (30%), renal anomalies (5-15%), esophageal atresia with or
without tracheoesophageal fistula (5-10%), skeletal malformations (5%), and anorectal anomalies
(5%). Nearly half of patients with duodenal atresia have chromosome abnormalities; trisomy 21 is
identified in up to one third of patients.

Clinical Manifestations: The hallmark of duodenal obstruction is bilious vomiting without

abdominal distention, which is usually noted on the 1st day of life. Peristaltic waves may be
visualized early in the disease process. A history of polyhydramnios is present in half the
pregnancies and is caused by inadequate absorption of amniotic fluid in the distal intestine.

Diagnosis: The diagnosis is suggested by the presence of a “double-bubble” sign on a

plain abdominal radiograph. The appearance is caused by a distended and gas-filled stomach and
proximal duodenum, which are invariably connected. Contrast studies are occasionally needed to
exclude malrotation and volvulus because intestinal infarction can occur within 6-12 hr if the
volvulus is not relieved.

Echocardiography, renal ultrasound, and radiology of the chest and spine should be performed
to evaluate for associated anomalies. Prenatal diagnosis of duodenal atresia is readily made by fetal
ultrasonography, which reveals a sonographic double-bubble.

Treatment: The initial treatment of infants with duodenal atresia includes nasogastric
or orogastric decompression and intravenous fluid replacement. The typical surgical repair for
duodenal atresia is duodenoduodenostomy. Postoperatively, a gastrostomy tube can be placed to
drain the stomach and protect the airway. Long-term prognosis is excellent, approaching 90%
survival in most series.

19. Congenital Aganglionic Megacolon (Hirschsprung Disease):

Hirschsprung disease, or congenital

aganglionic megacolon, is a developmental disorder (neurocristopathy) of the enteric nervous
system, characterized by the absence of ganglion cells in the submucosal and myenteric plexus. It is

208
the most common cause of lower intestinal obstruction in neonates.

The male: female ratio for Hirschsprung disease is 4 : 1 for short-segment disease and closer to 1 : 1
as the length of the involved segment increase.

There is an increased familial incidence in long-segment disease. Hirschsprung disease may be

associated with other congenital defects, including Down, Smith-Lemli-Opitz, Shah-Waardenburg,
and congenital hypoventilation (Ondine's curse) syndromes and urogenital or cardiovascular
abnormalities.

Pathology: Hirschsprung disease is the result of an absence of ganglion cells in the bowel
wall, extending proximally and continuously from the anus for a variable distance. The absence
of neural innervation is a consequence of an arrest of neuroblast migration from the proximal to
distal bowel. Without the myenteric and submucosal plexus, there is inadequate relaxation of the
bowel wall and bowel wall hypertonicity, which can lead to intestinal obstruction. The aganglionic
segment is limited to the rectosigmoid in 80% of patients.

Observed histologically is an 1. absence of Meissner and Auerbach plexus and 2. hypertrophied

nerve bundles 3. with high concentrations of acetylcholinesterase between the muscular layers and in
the submucosa.

Clinical Manifestations: Hirschsprung disease is usually diagnosed in the neonatal period secondary
to a distended abdomen, failure to pass meconium, and/or bilious emesis or aspirates with feeding
intolerance. As the bowel dilates, intraluminal pressure increases, resulting in decreased blood
flow and deterioration of the mucosal barrier. Stasis allows proliferation of bacteria, which can lead
to enterocolitis (Clostridium difficile, Staphylococcus aureus, anaerobes, coliforms) with associated
diarrhea, abdominal tenderness, sepsis and signs of bowel obstruction.

DISTINGUISHING FEATURES OF HIRSCHSPRUNG DISEASE AND FUNCTIONAL

CONSTIPATION (5+5+3)

FUNCTIONAL HIRSCHSPRUNG DISEASE

HISTORY
Onset of constipation After 2 yr of age At birth
Encopresis Common Very rare
Failure to thrive Uncommon Possible
Enterocolitis None Possible
Forced bowel training Usual None
EXAMINATION
Abdominal distention Uncommon Common
Poor weight gain Rare Common
Rectum Filled with stool Empty
Rectal Examination Stool in rectum Explosive passage of stool
Malnutrition None Possible
INVESTIGATIONS
Anorectal manometry Relaxation of internal anal Failure of internal anal sphincter
209
 FUNCTIONAL HIRSCHSPRUNG DISEASE
sphincter relaxation
No ganglion cells, increased
Rectal biopsy Normal
acetylcholinesterase staining
Massive amounts of stool, no Transition zone, delayed evacuation
Barium enema
transition zone (>24 hr)

In neonates, Hirschsprung disease must be differentiated from meconium plug syndrome, meconium
ileus, and intestinal atresia. In older patients, the Currarino triad must be considered, which
includes anorectal malformations (ectopic anus, anal stenosis, imperforate anus), sacral bone
anomalies (hypoplasia, poor segmentation), and presacral anomaly (anterior meningoceles,
teratoma, cyst).

Diagnosis: 1. Rectal suction biopsy is the gold standard for diagnosing Hirschsprung
disease.

2. Anorectal manometry measures the

pressure of the internal anal sphincter while a balloon is distended in the rectum.

3. An unprepared contrast enema is

most likely to aid in the diagnosis in children older than 1 mo because the proximal ganglionic
segment might not be significantly dilated in the first few weeks of life. Classic findings are based on
the presence of an abrupt narrow transition zone between the normal dilated proximal colon and a
smaller-caliber obstructed distal aganglionic segment.

Treatment: Once the diagnosis is established, the definitive treatment is operative

intervention. Currently, many infants undergo a primary pull-through procedure except if there is
associated enterocolitis or other complications, when a decompressing ostomy is usually required.

There are 3 basic surgical options. Swenson, Duhamel and Soave. The prognosis of surgically
treated Hirschsprung disease is generally satisfactory; Long-term postoperative problems include
constipation, recurrent enterocolitis, stricture, prolapse, perianal abscesses, and fecal soiling. Some
children require myectomy or a redo pull-through procedure.

20. Gluten sensitive enteropathy (celiac disease):

Celiac disease is an immune-mediated disorder elicited by the ingestion of gluten in genetically

susceptible persons and characterized by chronic inflammation of the small intestine. It is
considered an autoimmune condition because of the presence of anti–TG2 antibodies and the
association with other autoimmune diseases (thyroid, liver, diabetes, adrenal).

Genetics and Pathogenesis:

210
Pathogenesis:

T cell–mediated chronic inflammatory disorder with an autoimmune component and genetic

predisposition.

Gliadin-specific T-cell responses are enhanced by the action of TG2

higher affinity of these gliadin peptides for HLA-DQ2 or HLA-DQ8.

activation of cytokines interferon-γ (IFN-γ).

A complex remodeling of the mucosa then takes place leading to the classic flat mucosa.

CLINICAL MANIFESTATIONS OF CELIAC DISEASE IN CHILDREN

SYSTEM MANIFESTATION (POSSIBLE) CAUSE
Diarrhea
Distended abdomen
Vomiting Atrophy of the small bowel mucosa
Gastrointestinal
Anorexia Malabsorption
Weight loss
Failure to thrive
211
SYSTEM MANIFESTATION (POSSIBLE) CAUSE
Aphthous stomatitis
Hematologic Anemia Iron malabsorption
Rickets
Skeletal Osteoporosis Calcium/vitamin D malabsorption
Enamel hypoplasia of the teeth
Muscular Atrophy Malnutrition
Peripheral neuropathy
Neurologic Epilepsy Thiamine/vitamin B12 deficiency
Irritability
Short stature Malnutrition
Endocrinologic
Secondary hyperparathyroidism Calcium/vitamin D malabsorption
Dermatitis herpetiformis
Dermatologic Alopecia areata Autoimmunity
Erythema nodosum
Idiopathic pulmonary
Respiratory
hemosiderosis

RISK GROUPS FOR CELIAC DISEASE CASE-FINDING

(DATA) code

1st-degree relatives
Dermatitis herpetiformis
Unexplained iron deficiency anaemia
Autoimmune thyroiditis
Type 1 diabetes
Dental enamel hypoplasia
Short stature
Delayed puberty

Down, Williams, and Turner syndromes

Irritable bowel syndrome

Epilepsy with occipital calcifications
Selective IgA deficiency

CLINICAL SPECTRUM OF CELIAC DISEASE

212
SYMPTOMATIC
Frank malabsorption symptoms: chronic diarrhea, failure to thrive, weight loss
Extraintestinal manifestations: anemia, fatigue, hypertransaminasemia, neurologic disorders, short
stature, dental enamel defects, arthralgia, aphthous stomatitis
SILENT
No apparent symptoms in spite of histologic evidence of villous atrophy
In most cases identified by serologic screening in at-risk groups
LATENT
Subjects who have a normal histology, but at some other time, before or after, have shown a
gluten-dependent enteropathy
POTENTIAL
Subjects with positive celiac disease serology but without evidence of altered jejunal histology
It might or might not be symptomatic

Non-Hodgkin lymphoma is the main cause of death.

Diagnosis:

CBC- anemia

Serologic tests have a crucial role in the diagnosis of celiac disease; sensitivity of the IgA anti-TG2
is 61-100% (mean, 87%), and specificity is 86-100% (mean, 95%). Antibodies against
gliadin-derived deamidated peptides (D-AGA) have a greater sensitivity and specificity.

Genetic tests have an increasing role in the diagnosis. the measurement of HLA DQ2 and/or DQ8
has a strong negative predictive value

According to The European Society for Pediatric Gastroenterology, Hepatology and Nutrition
(ESPGHAN) current criteria, the 2 requirements mandatory for the diagnosis of celiac disease are

1. The finding of villous atrophy with

2. Hyperplasia of the crypts and abnormal surface epithelium

3. While the patient is eating adequate amounts of gluten, and a full clinical remission after
withdrawal of gluten from the diet.

Treatment: The only treatment for celiac disease is lifelong strict adherence to a
gluten-free diet. This requires a wheat-, barley-, and rye-free diet.

It is important that an experienced dietician with specific expertise in celiac disease counselling
educates the family and the child about dietary restriction.

Iron supplementation if anemic.

It is recommended that children with celiac disease be monitored with periodic visits for assessment
of symptoms, growth, physical examination, and adherence to the gluten-free diet.

Complications:
213
Celiac crisis- shock, acidosis and dehydration

Refractory sprue

Ulceration and strictures

NHL

21. Ascites:

Def: ascites is a clinical condition characterised by the presence of free fluid in the peritoneal cavity.

Etiology:

214
 I. Ascites in II. ascites in older
neonates children

1. ascites with hydrops a) liver- decompensated cirrhosis, subacute hepatic

failure, venoocclusive disease, budd chiari
a) cardiac- congenital heart block, ebsteins syndrome
anomaly and HLHS
b) peritoneal- Tb, malignant infiltration
b) blood- alpha thalassemia, hemolytic anemia
c) renal- NS
c) chromosomal- trisomy 21, 13, 18 and 45XO
d) cardiac- cardiomyopathy, constrictive
d) inf- TORCH, cong syphilis pericarditis, chronic CCF

e) renal- cong NS, PUV e) hypoalbuminemia- protein losing enteropathy,

PEM, NS
f) git- intestinal atresias and neonatal
haemocromatosis f) endocrine- myxoedema

g) malignancies- wilms, neuroblastoma g) ovarian- meig’s syndrome, struma ovarii

2. ascites without hydrops h) misc- chylous, pseudochylous, pancreatic and

lymphatic obstruction
Chylous, biliary and urinary

Pathogenesis:

According to starling’s hypothesis, the exchange of fluids between the blood and tissue spaces is
controlled by the balance between two factors

a) the capillary blood pressure, which forces fluid into the tissue spaces.

b) the osmotic pressure of plasma proteins, which retain fluid within the vascular compartment

I. In cirrhotic ascites:

The hepatic architecture is distorted by fibrosis and nodule formation, which compress the sinusoids.

In cirrhosis, the splanchnic blood flow is increased, hence increase in hydrostatic pressure.

Increased sinusoidal pressure drives protein rich fluid from the sinusoids into the space of disse and
then into hepatic lymphatics

The excess hepatic lymph enters the peritoneal cavity directly and ultimately ascites

Fluid into the interstitium resulting in edema

Decreased albumin synthesis

Decompensated liver disease

215
II. Renal factors:

a) Under fill theory: hypovolemia in cirrhosis stimulates JGA renin aldosterone

increased absorption of sodium and water

Ascites

ADH and aldosterone are not metabolised properly due to decompensated liver disease, hence
increased circulating levels

b) Over fill theory: combination of portal hypertension and circulating hypervolemia results in over
flow from the congested portal system to the peritoneal cavity, to produce ascites

III. Nitric oxide theory (peripheral arterial vasodilatation theory)

When the portal pressure increases above a critical threshold, nitric oxide levels increase, leading to
vasodilatation. As the state of vasodilatation worsens, plasma levels of vasoconstrictor, sodium
retentive hormones increase and renal functions deteriorates, resulting in ascites.

Types: High grade ascites (SAAG > 1.1) Chylous ascites

Tb ascites
Exudative vs vs Pseudochylous ascites
transudative Pancreatic ascites
Low grade ascites (SAAG < 1.1) Urinary ascites
Chlamydial ascites

features Exudative ascites Transudative ascites

Protein in gm% >3 <3

Specific gravity > 1015 < 1015
LDH High low
Fibronectin Elevated in malignant ascites Low
Cholesterol Elevated in malignant ascites Low
Hyaluronic acid Increased in mesothelioma Low
ADA(adenosine deaminase) High in Tb Normal

High grade ascites (SAAG > 1.1)/ Low grade ascites (SAAG < 1.1)/ exudative
transudative ascites/ low gradient ascites/ high gradient

Cirrhosis, veno occlusive disease, budd Tuberculosis ascites, nephrotic syndrome,

chiari syndrome, fulminant hepatic failure pancreatic, biliary and chylous ascites

SAAG: serum ascites albumin gradient: calculated by subtracting the albumin concentration of
ascitic fluid from that of serum.

Chylous ascites:

216
Chylous ascites can result from an anomaly, injury, or obstruction of the intra-abdominal portion of
the thoracic duct.

Causes include congenital malformations, peritoneal bands, generalized lymphangiomatosis, chronic

inflammatory processes of the bowel, tumors, enlarged lymph nodes, previous abdominal surgery,
and trauma. Congenital anomalies of the lymphatic system are associated with Turner, Noonan,
yellow nail, and Klippel-Trenaunay-Weber syndromes.

Clinical features: In neonates, rapidly progressing abdominal distention is noted, along with poor
weight gain and loose stools. Peripheral edema is common. Massive chylous ascites can result in
scrotal edema, inguinal and umbilical herniation, and respiratory embarrassment.

Diagnosis of chylous ascites depends on the demonstration of milky ascitic fluid obtained via
paracentesis after a fat-containing feeding. Fluid analysis reveals a high protein content, elevated
triglycerides, positive staining by sudan red for fat and lymphocytosis. Hypoalbuminemia,
hypogammaglobulinemia, and lymphopenia are common in these patients.

Treatment includes a high-protein, low-fat diet supplemented with medium-chain triglycerides

that are absorbed directly into the portal circulation.

Octreotide, a somatostatin analog, has been used.

Paracentesis should be repeated only if abdominal distention causes respiratory distress.

Laparotomy may be indicated to search for the site of the leak if a trial of dietary management has
been unsuccessful.

Pseudochylous ascites: usually secondary to neoplasm or inflammatory diseases.

Pancreatic ascites: abdominal trauma, severe acute pancreatitis and chronic pancreatitis. High levels
of amylase. May resolve spontaneously, respond to stomatostatin and require endoscopic stenting.

Urinary ascites: male neonates with high grade urinary tract obstruction due to PUV, rupture of
bladder diverticula and ureteroperitoneal fistula following surgery.

Diagnosis: 1.ascitic fluid examination for

Cell count Culture

N- <250 cells/cc Amylase Grams staining Cytology

Wbc > 500 and PMN > Inc in pancreatic Monomicrobial inf- prim pH
250/cc indicate SBP ascites and SBP
perforation of gut
High wbc count with Multiple bacteria- sec SBP
lymphocytosis s/o Tb
M. Tb in Tb
Increased RBC- trauma. Tb
and malignancy
Low Glucose, inc LDH and Triglycerides Fibronectin, cholesterol, ADA
multiple organisms on gram hyaluronic acid
staining inc in chylous Inc in Tb
ascites Increased in malignancy
s/o peritonitis
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2. Plain X ray abdomen:

Lateral liver edge is medially displaced from the thoracoabdominal wall - HELLMER sign

Fluid in the para vesical fossa bilaterally – DOG’S EAR SIGN or MICKEY MOUSE appearance

3. Ultra sound abdomen:

4. CT scan: more useful than ultrasound in determining hepatic lesions

5. MRI: rarely needed

6. Endoscopy for varices and gastropathy

7. Peritoneal biopsy

Treatment:

1. Bed rest
2. Salt restriction
3. Fluid restriction
4. Diuretics- mainstay of treatment and should be used liberally but carefully.
5. Beta blockers- lower the portal pressures and inhibits the renin secretion resulting in
natriuresis.
6. Paracentesis
7. Refractory ascites- chronic outpatient paracentesis, ascites ultrafiltration and reinfusion,
LeVeen shunt, TIPSS and Liver transplantation.

Complications:

1. Spontaneous bacterial peritonitis (SBP)

2. Hydrothorax
3. Gastro-esophageal reflux
4. Respiratory distress and atelectasis due to elevation of diaphragm
5. Inguinal hernia
6. Umbilical hernia
7. Scrotal edema

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DRA: Diuretic Resistant Ascites (even after maximal dosage of both diuretics for atleast 1wk)
DIA: Diuretic Intractable Ascites (side effects of diuretics appear before maximal doses can be
tolerated)

TREATMENT OF SBP :

 Treatment should be started empirically if SBP is suspected clinically, regardless of the

availability of laboratory results.
 Organisms : In community-acquired SBP and in patients not on SBP prophylaxis, Escherichia
coli and Klebsiella pneumoniae are seen in up to 60% of isolates. About 25% are Gram-positive
cocci, mostly streptococcal species, usually pneumococci. Anerobes are rarely seen
 Intravenous Cefotaxime (or a similar third generation cephalosporin) is the empiric antibiotic of
choice as it covers 95% of the flora and has been shown to cure SBP episodes in 85% of patients.

219
 Patients who develop SBP while on norfloxacin prophylaxis are more likely to have infections
caused by Gram-positive cocci or quinolone resistant Gram-negative bacilli. Cefotaxime is
effective even in these latter cases.
 The weight adjusted pediatric dosage would be 50 mg/kg/dose to a maximum of 2 g/ dose every
8 hrly.
 Optimal duration of treatment is 5 days.
 Once culture results are available, antibiotic modifications may be necessary, but
aminoglycosides should still be avoided because of the risk of renal failure.
 Alternatively oral ofloxacin in hospitalized patients without septic shock, encephalopathy (grade
II or higher), azotemia (serum creatinine greater than 3 mg/dL), gastrointestinal bleed, or ileus
has been shown to be effective in SBP treatment.

Prevention of SBP:

 Risk factors for development of SBP are ascitic fluid protein concentration <1 g/dL, variceal
hemorrhage and prior episode of SBP.
 Long-term administration of oral norfloxacin 5-7.5 mg/Kg once a day in cirrhotic patients with
ascitic fluid protein content of <1g/dL or prior episode of SBP is recommended for prevention of
SBP.
 Patients having cirrhosis and upper gastrointestinal hemorrhage should be given short-term (7
days) norfloxacin 5-7.5 mg/Kg/dose orally twice a day, however, during active bleeding
intravenous ofloxacin should be prescribed.

22. Vomiting:

Def: Violent descent of the diaphragm and constriction of the abdominal muscles with relaxation of
the gastric cardia actively force gastric contents back up the oesophagus.

Causes:

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ESOPHAGUS STOMACH COLON
SMALL INTESTINE
Congenital
Congenital Congenital
Congenital Meconium plug
Esophageal atresia Antral webs Duodenal atresia Hirschsprungs disease
Vascular rings Pyloric stenosis Annular pancreas Colonic atresia,
Acquired Malrotation/Volvulus stenosis
Schatzki ring
Malrotation/Ladd Imperforate anus
Tracheobronchial Bezoar, foreign body bands Rectal stenosis
remnant Ileal atresia
Pyloric stricture (ulcer) Pseudo-obstruction
Acquired Meconium Ileus Volvulus
Meckel diverticulum Colonic duplication
Esophageal stricture Chronic with Volvulus or
granulomatous disease intussusception Acquired
Foreign body of childhood
Inguinal hernia Ulcerative colitis
Achalasia (toxic megacolon)
Eosinophilic Intestinal duplication
Chagas disease gastroenteritis Chagas disease
Acquired
Crohn disease
Collagen vascular Crohn disease Postsurgical
disease adhesions Fibrosing colonopathy
Epidermolysis bullosa (cystic fibrosis)
Crohn disease
Intussusception
Distal ileal
obstruction syndrome
(cystic fibrosis)
Duodenal hematoma
Superior mesenteric
artery syndrome

Investigations:

Screening tests Specific tests

1. CBC, urine analysis, 1. X ray abdomen- intestinal obstruction, FB
urine culture 2. USG- duodenal atresia, annular pancreas
2. Stool- parasites, and 3. Barium studies- GOR, malrotation
occult blood 4. Endoscopy- GOR, Peptic ulcer disease, Biopsy for H. pylori
3. SGPT- hepatitis 5. CT scan
4. BUN- CRF 6. IEM work up
7. For motility disorders- electrogastrography, radionuclide
gastric emptying studies

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 COMPLICATIONS OF VOMITING
HISTORY, PHYSICAL
COMPLICATION PATHOPHYSIOLOGY EXAMINATION, AND
LABORATORY STUDIES
Metabolic Fluid loss in emesis Dehydration
HCl loss in emesis Alkalosis; hypochloremia
Na, K loss in emesis Hyponatremia; hypokalemia
Alkalosis →
• Na into cells
• HCO3 loss in urine Urine pH 7-8
• Na and K loss in urine Urine Na ↑, K ↑
Hypochloremia → Cl conserved by kidneys Urine Cl ↓
Emesis of calories and nutrients
Nutritional Malnutrition; “failure to thrive”
Anorexia for calories and nutrients
Retching → tear at lesser curve of
Mallory-Weiss tear Forceful emesis → hematemesis
gastroesophageal junction
Esophagitis Chronic vomiting → esophageal acid exposure Heartburn; hemoccult + stool
Aspiration of vomitus, especially in context of
Aspiration Pneumonia; neurologic dysfunction
obtundation
Severe fluid loss in emesis or in accompanying Dehydration (accompanying diarrhea
Shock
diarrhea can explain acidosis?)
Severe blood loss in hematemesis Blood volume depletion
Pneumomediastinum,
Increased intrathoracic pressure Chest x-ray
pneumothorax
Petechiae, retinal
Increased intrathoracic pressure Normal platelet count
hemorrhages

Treatment:

Reflux: dopamine antagonist Cyclical vomiting syndrome: 3. Prophylactic:

(metachlopramide)
1. Supportive: 1. Antimigrane, β
Gastroparesis: dopamine
adrenergic blocker:
antagonist, motilin agonist 1. Child kept in dark, non
(erythromycin) propranolol
stimulating environment
2. Antimigrane,
Chemotherapy: dopamine 2. Correct dehydration
antagonist, serotonergic 5-HT3 antihistamine:
3. Avoid triggering factors –
antagonist, phenothiazines,
cyproheptadine
steroids diet, psychological stress
3. Antimigrane, TCA:
4. Analgesic: meperidine
Motion sickness, vestibular
amitriptyline
disorders: Antihistamine, 5. Anxiolytics, sedative:
anticholinergic (scopolamine) 4. Antimigrane,
lorazepam

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Adrenal crisis: steroids 6. Antihistamine, sedative: antiepileptic:
Diphenhydramine phenobarbitone,
7. Family support- erythromycin
education, counselling 5. Low estrogen OCP

2. Abortive:

1. serotonergic 5-HT3
antagonist: ondansetron
2. NSAIDS
3. serotonergic 5-HT1D
agonist: sumatriptan

Cyclical vomiting syndrome:

4 stages: Prodrome, episode, recovery and inter episodic phase

CRITERIA FOR CYCLICAL VOMITING SYNDROME

All of the criteria must be met for the consensus definition of cyclical vomiting syndrome:
• 1. At least 5 attacks in any interval, or a minimum of 3 attacks during a 6-month
period
• 2. Episodic attacks of intense nausea and vomiting lasting 1 hr to 10 days and
occurring at least 1 wk apart
• 3. Stereotypical pattern and symptoms in the individual patient
• 4. Vomiting during attacks occurs ≥4 times/hr for ≥1 hr
• 5. Return to baseline health between episodes
• 6. Not attributed to another disorder

Investigations:

During the episode before starting IV fluids When the child is well

1. urine analysis, urine organic acids, amino acids, UGI scopy/ small bowel follow through
porphobilinogen
Abdominal USG/ CT
2. blood- RFT, ammonia, lactate, Carnitine, LFT,
amylase, lipase

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23. Chronic abdominal pain:

DISORDER DEFINITION
Chronic Long-lasting intermittent or constant abdominal pain that is functional or organic
abdominal pain (disease based)
Abdominal pain without demonstrable evidence of pathologic condition, such as
anatomic, metabolic, infectious, inflammatory or neoplastic disorder. Functional
Functional
abdominal pain can manifest with symptoms typical of functional dyspepsia,
abdominal pain
irritable bowel syndrome, abdominal migraine or functional abdominal pain
syndrome.
Functional
Functional abdominal pain or discomfort in the upper abdomen
dyspepsia
Irritable bowel
Functional abdominal pain associated with alteration in bowel movements
syndrome
Functional abdominal pain with features of migraine (paroxysmal abdominal pain
Abdominal
associated with anorexia, nausea, vomiting or pallor as well as maternal history of
migraine
migraine headaches)
Functional
Functional abdominal pain without the characteristics of dyspepsia, irritable bowel
abdominal pain
syndrome, or abdominal migraine.
syndrome

CHILDHOOD FUNCTIONAL GI DISORDERS: CHILD / ADOLESCENT (CATEGORY H)

H1 Vomiting and aerophagia

H1a Adolescent rumination syndrome
H1b Cyclic vomiting syndrome
H1c Aerophgia
H2 Abdominal pain—–related FGIDs
H2a Functional dyspepsia
H2b Irritable bowel syndrome
H2c Abdominal migraine
H2d Childhood functional abdominal pain
H2d1 Childhood functional abdominal pain
syndrome
H3 Constipation and incontinence
H3a Functional constipation
H3b Non-Retentive fecal incontinence

ROME III CRITERIA

H2d. CHILDHOOD FUNCTIONAL ABDOMINAL PAIN

Diagnostic criteria* must include all of the following:

224
 • Episodic or continuous abdominal pain
• Insufficient criteria for other FGIDs
• No evidence of an inflammatory, anatomic, metabolic or neoplastic process that explains the
subject's symptoms
H2d1. CHILDHOOD FUNCTIONAL ABDOMINAL PAIN SYNDROME
Diagnostic criteria* must satisfy criteria for childhood functional abdominal pain and have at least 25%
of the time one or more of the following:
• Some loss of daily function
• Additional somatic symptoms such as headache, limb
pain, or difficulty sleeping.

Pathophysiology:

1. The symptoms of FGIDs may be the result of dysfunctions of the intestinal sensory and motor
systems. The pathophysiology of functional abdominal pain is complex and not fully understood.
Visceral hypersensitivity and motility disturbances are thought to be involved in functional
abdominal pain.

2. The child's response to pain can be influenced by stress, personality type, and the reinforcement
of illness behavior within the family.

3. A normal functioning enteric nervous system (ENS) is important for coordination of intestinal
motility, secretion and blood flow. Abnormalities of the enteric nervous system may be an underlying
factor for functional abdominal pain. Altered intestinal permeability enabling passage of food
antigens into the mucosa leading to prolonged stimulation of the intestinal mucosal immune system
and the ENS is also a possible cause for functional abdominal pain.

ALARM SYMPTOMS USUALLY NEEDING ALARM SIGNS USUALLY NEEDING

FURTHER INVESTIGATIONS FURTHER INVESTIGATIONS

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 Pain that wakes up the child from sleep Localized tenderness in the right upper
Persistent right upper or right lower quadrant pain quadrant
Significant vomiting (bilious vomiting, protracted Localized tenderness in the right lower
vomiting, cyclical vomiting or worrisome pattern to quadrant
the physician)
Localized fullness or mass
Unexplained fever
Hepatomegaly
Genitourinary tract symptoms
Splenomegaly
Dysphagia
Chronic severe diarrhea or nocturnal diarrhea Jaundice

Gastrointestinal blood loss Costovertebral angle tenderness

Involuntary weight loss Arthritis

Deceleration of linear growth Spinal tenderness

Delayed puberty Perianal disease

Family history of inflammatory bowel disease, Abnormal or unexplained physical findings

celiac disease, and peptic ulcer disease

Investigations:

1. Laboratory studies may be unnecessary if the history and physical examination lead to a diagnosis
of functional abdominal pain.

2. A complete blood cell count, sedimentation rate, C-reactive protein, basic chemistry panel, celiac
panel, stool culture, stool test for ova and parasites, and urinalysis are reasonable screening studies.

3. Elevated stool calprotectin levels usually suggest an inflammatory etiology.

4. An upper GI x-ray series is indicated if one suspects a disorder of the stomach or small intestine.

5. If indicated, an ultrasound examination of the abdomen can give information about kidneys,
gallbladder, and pancreas;

6. Helicobacter pylori infection does not seem to be associated with chronic abdominal pain, but in
patients with symptoms suggesting gastritis or ulcer, an H. pylori test (fecal H. pylori antigen) may
be performed.

7. Breath hydrogen testing is done for ruling out lactose or sucrose malabsorption.

8. Esophagogastroduodenoscopy is indicated with symptoms suggesting persistent upper GI

pathology.

Treatment:

1. The most important component of the treatment is reassurance and education of the child and
family. The child and family need to be reassured that no evidence of a serious underlying disorder is
present.

2. The parents should be instructed to avoid reinforcing the symptoms with secondary gain.
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 VARIOUS TREATMENT OPTIONS FOR ABDOMINAL PAIN IN CHILDREN

CAP – FALL

THERAPY DEFINITION OF DISORDER

Cognitive behavioral (family) therapy Recurrent abdominal pain
Famotidine Recurrent abdominal pain and dyspeptic symptoms
Added dietary fiber Recurrent abdominal pain
Lactose-free diet Recurrent abdominal pain
Peppermint oil Irritable bowel syndrome
Amitriptyline Functional GI disorders, Irritable bowel syndrome
Lactobacillus GG Irritable bowel syndrome using Rome II criteria

24. Short bowel syndrome:

Loss of >50% of the small bowel, with or without a portion of the large intestine, can result in
symptoms of generalized malabsorption disorder or in specific nutrient deficiencies, depending on
the region of the bowel resected.

Causes: CONGENITAL BOWEL RESECTION

Necrotizing enterocolitis
Congenital short bowel Volvulus with or without malrotation
syndrome
Long segment Hirschsprungs disease
Multiple atresias Meconium peritonitis
Crohn disease
Gastroschisis
Trauma

Effects of short bowel:

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Treatment:

1. DIET: After bowel resection, treatment of short bowel syndrome is

initially focused on repletion of the massive fluid and electrolyte losses while the bowel initially
accommodates to absorb these losses. Nutritional support is often provided via parenteral nutrition.

2. BOWEL REHABILTATION: After the initial few weeks following resection, fluid
and electrolyte losses stabilize, and the focus of therapy shifts to bowel rehabilitation with the
gradual reintroduction of enteral feeds. Continuous small-volume trophic enteral feeding should
be initiated with a protein hydrolysate and medium-chain triglyceride–enriched formula to
stimulate gut hormones and promote mucosal growth.

3. VITAMIN SUPPLIMENTATION: After achieving the maximal increase in bowel

absorptive capacity, management of specific micronutrient and vitamin deficiencies and treatment of
transient problems such as post infectious mucosal malabsorption are required.

4. DRUGS:

a) In patients with large stool outputs, the addition of soluble fiber and antidiarrheal agents such as
loperamide and anticholinergics can be beneficial, although these drugs can increase the risk of
bacterial overgrowth.

b) Cholestyramine can be beneficial for patients with distal ileal resection, but its potential depletion
of the bile acid pool can increase steatorrhea.

c) Empirical treatment with metronidazole or other antibiotics is often useful.

d) Diets high in fat and lower in carbohydrate may be helpful in reducing bacterial overgrowth as
well as enhancing adaptation.

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5. SURGERY: In patients who are unable to achieve full enteral feeding after
several years of nutritional rehabilitation, surgical bowel lengthening procedures may be
considered.

6. In some children with complications of parenteral nutrition, especially impending liver failure,
small intestinal and liver transplantation may be considered.

Complications:

1. Long-term complications of short bowel syndrome include those of parenteral nutrition: central
catheter infection, thrombosis, hepatic cholestasis and cirrhosis, and gallstones.

2. Long-term monitoring for deficiencies of vitamin B12, folate, iron, fat-soluble vitamins, and trace
minerals such as zinc and copper is important.

3. Renal stones can occur as a result of hyperoxaluria secondary to steatorrhea (calcium binds to the
excess fat and not to oxalate, so more oxalate is reabsorbed and excreted in the urine).

4. Bloody diarrhea secondary to patchy, mild colitis can develop during the progression of enteral
feedings. The pathogenesis of this “feeding colitis” is unknown, but it is usually benign and can
improve with a hypoallergenic diet or treatment with sulfasalazine.

Manifestations of upper GI bleed:

Haematemesis: vomiting of fresh blood

Malena: passage of black, tarry, sticky, offensive loose stools

Manifestations of Lower GI bleed:

Haematochezia: passage of fresh blood in the stools

Occult blood in the stools.

229
Upper GI bleed:

230
1. ABC- Treatment of patients with upper GI hemorrhage must focus on fluid resuscitation, initially
in the form of crystalloid infusion, followed by the replacement of red blood cells. Care should be
taken in fluid resuscitation of children after bleeding to avoid producing an excessively high venous
pressure and increasing risk for further bleeding.

2. Correction of coagulopathy by administration of vitamin K and/or infusion of platelets or fresh

frozen plasma may be required.

3. A nasogastric tube should be placed to document the presence of blood within the stomach and to
monitor for ongoing bleeding.

3. An H2 receptor blocker or proton pump inhibitor should be given intravenously to reduce the
risk of bleeding from gastric erosions.

4. Vasopressin or one of its analogs has been commonly used and is thought to act by increasing
splanchnic vascular tone and thus decreasing portal blood flow. Vasopressin is administered
initially with a bolus of 0.33 U/kg over 20 min, followed by a continued infusion of the same dose
on an hourly basis or a continuous infusion of 0.2 U/1.73 m2/min.

5. Nitroglycerin, usually given as a portion of a skin patch, has also been used to decrease portal
pressure and, when used in conjunction with vasopressin, can ameliorate some of its untoward
effects.

6. The somatostatin analog octreotide is more commonly used, and it decreases splanchnic blood
flow with fewer side effects. It may be administered by continuous intravenous infusion of 1.0-5.0
µg/kg/hr.

7. After an episode of variceal hemorrhage or in patients in whom bleeding cannot be controlled,

endoscopic sclerosis or elastic band ligation of esophageal varices are important options. Treatments
may be associated with further bleeding, bacteremia, esophageal ulceration, and stricture formation.

8. In patients who continue to bleed despite pharmacologic and endoscopic methods to control
hemorrhage, a Sengstaken-Blakemore tube may be placed to stop hemorrhage by mechanically
compressing esophageal and gastric varices. It poses a particularly high risk for pulmonary
aspiration. The tube is not well tolerated in children without significant sedation.

9. Various surgical procedures have been devised to divert portal blood flow and to decrease portal
pressure. (portacaval shunt mesocaval or distal splenorenal shunt)

10. A transjugular intrahepatic portosystemic shunt (TIPS), in which a stent is placed by an

interventional radiologist between the right hepatic vein and the right or left branch of the portal vein,
can aid in the management of portal hypertension in children, especially in those needing temporary
relief before liver transplantation. The TIPS procedure can precipitate hepatic encephalopathy and is
prone to thrombosis.

11. Orthotopic liver transplantation represents a much better therapy for portal hypertension
resulting from intrahepatic disease and cirrhosis.

II. Long-term treatment with nonspecific β-blockers such as propranolol has been used extensively
in adults with portal hypertension. These agents might act by lowering cardiac output and portal
perfusion.

26. Intussusception:

231
Intussusception occurs when a portion of the alimentary tract is telescoped into an adjacent segment.

It is the most common cause of intestinal obstruction between 3 mo and 6 yr of age and the most
common abdominal emergency in children <2 yr.

Sixty percent of patients are <1 yr of age.

The male: female ratio is 3: 1

Etiology

Approximately 90% of cases of intussusception in children are idiopathic.

In 2-8% of patients, recognizable lead points for the intussusception are found, such as a Meckel
diverticulum, intestinal polyp, neurofibroma, intestinal duplication cysts, hemangioma, or malignant
conditions such as lymphoma.

Other risk factors- HSP, hemophilia and cystic fibrosis

Pathology:

 Intussusceptions are most often ileocolic.

 The upper portion of bowel, the intussusceptum, invaginates into the lower, the
intussuscipiens, pulling its mesentery along with it into the enveloping loop.
 Constriction of the mesentery obstructs venous return,
 Engorgement of the intussusceptum follows, with edema, and bleeding from the mucosa
leads to a bloody stool.
 If left unrecognised then eventuate in intestinal gangrene, peritonotis and shock.

Clinical features:

 In typical cases, there is sudden onset, in a previously well child, of severe paroxysmal
colicky pain that recurs at frequent intervals and is accompanied by straining efforts with legs
and knees flexed and loud cries.
 At times, the lethargy is out of proportion to the abdominal signs.
 Eventually, a shock like state, with fever, can develop.
 Vomiting occurs in most.
 Pass a stool containing red blood and mucus, the currant jelly stool.
 The classic triad of pain, a palpable sausage-shaped abdominal mass, and bloody or currant
jelly stool is seen in <15% of patients with intussuscpetion.
 On rare occasions, the advancing intestine prolapses through the anus.
 Recurrent intussusception is noted in 5-8% and is more common after hydrostatic than
surgical reduction.

232
  Chronic intussusception, in which the symptoms exist in milder form at recurrent intervals,
is more likely to occur with or after acute enteritis and can arise in older children as well as in
infants.

Diagnosis:

 A plain abdominal radiograph might show a density in the area of the intussusception.
 The diagnostic findings of intussusception on ultrasound include a tubular mass in
longitudinal views and a doughnut or target appearance in transverse images.
 Contrast enemas demonstrate a filling defect or cupping in the head of the contrast media
where its advance is obstructed by the intussusceptum. A central linear column of contrast
media may be visible in the compressed lumen of the intussusceptum, and a thin rim of
contrast may be seen trapped around the invaginating intestine in the folds of mucosa within
the intussuscipiens (coiled-spring sign), especially after evacuation.

Treatment:

 Radiologic hydrostatic reduction under fluoroscopic or ultrasonic guidance.

 If manual operative reduction is impossible or the bowel is not viable, resection of the
intussusception is necessary, with end-to-end anastomosis.
 Corticosteroids can reduce the frequency of recurrent intussusception.

Complications: if left untreated, most lead to intestinal infarction, perforation, peritonitis, and death.

27. Antibiotic associated diarrhea: (from ip june 2009)

Def: Antibiotic associated diarrhea (AAD) is unexplained diarrhea occurring between2 hours to 2
months after starting antibiotics, where diarrhea is defined as more than 2 unformed stools for > 2
days.

Pathophysiology:

 Disruption of normal enteric flora caused by the antibiotic may lead to overgrowth of
pathogens, functional disturbances of the intestinal carbohydrates and bile acids metabolism
resulting in osmotic diarrhea.

 .Erythromycin accelerates the rate of gastric emptying.

 Amoxycillin-clavunate stimulates small bowel motility.

 Other drugs might affect the intestinal mucosa and the motility.

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Clinical features and investigations:

The mild illness and AAD would present with only watery stools, occur sporadically and resolve on
withdrawal of the antibiotic. They are usually C. difficile toxin negative and do not need any further
treatment.

Severe diarrhea, liquid stool with mucus and blood, fecal leucocytes >5/high power field, altered
flora and presence of Gram-positive bacilli with oval subterminal spores were sensitive predictors
for diagnosis of clostridium difficile infection. Detection of toxin A and B by ELISA and detection
of toxin B by tissue culture form the mainstay in the diagnosis of C. difficile.

Pseudomembranous colitis usually presents with abdominal cramps, fever, leucocytosis, fecal
leucocytes, hypoalbuminemia, colonic thickening on CT and widely spread punctate yellow plaques
seen on endoscopic examination. This form of colitis follows administration of antibiotics including
clindamycin, cephalosporins and penicillin.

Treatment:

 Discontinue or change implicated antibiotic and give supportive management with fluid and
electrolytes, if required.

 Most of the AAD would respond to only discontinuation or change of the antibiotic.

 Avoid usage of any anti-peristaltic drug.

 Control the infection in the patient with other antibiotics.

 Oral metronidazole or oral vancomycin is drug of choice for CDI (clostridium difficile
infection) for 10 days. Vancomycin should be reserved for those with severe illness, or
intolerance or failure to metronidazole.

 Treatment regimens may also include probiotics, bile-acid sequestrants and intravenous
immunoglobulin (IVIG). Most recurrences also respond to this line of management.

 A prolonged treatment with low dose vancomycin is preferred for the repeated recurrences.

Prevention:

 Hand washing, isolation and environmental decontamination are the factors which can
prevent recurrences and reinfection.

 Avoiding usage of rectal thermometers, usage of vinyl gloves and hospital antibiotic policies
are other factors which can help in prevention.

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 GROWTH & DEVELOPMENT

1. Sleep hygiene
2. Eating disorders
3. Intellectual Disability

BASIC PRINCIPLES OF sleep hygiene FOR CHILDREN

1 Have a set bedtime and wake time routine for your child.
2 Bedtime and wake-up time should be about the same time on school nights and non-school
nights. There should not be more than about an hour difference from one day to another.
3 Make the hour before bed shared quiet time. Avoid high-energy activities, such as rough play, and
stimulating activities, such as watching television or playing computer games, just before bed.
4 Don't send your child to bed hungry. A light snack (such as milk and cookies) before bed is a good
idea. Heavy meals within an hour or two of bedtime, however, may interfere with sleep.
5 Avoid products containing caffeine for at least several hours before bedtime. These include
caffeinated sodas, coffee, tea, and chocolate.
6 Make sure your child spends time outside every day whenever possible and is involved in regular
exercise.
7 Keep your child's bedroom quiet and dark. A low-level night light is acceptable for children who
find completely dark rooms frightening.
8 Keep your child's bedroom at a comfortable temperature during the night.
9 Don't use your child's bedroom for time-out or punishment.
10 Keep the television set out of your child's bedroom. Children can easily develop the bad habit of
“needing” the television to fall asleep. It's also much more difficult to control your child's viewing if
the set is in the bedroom

BASIC PRINCIPLES OF sleep hygiene FOR ADOLESCENTS

1 Wake up and go to bed at about the same time every night. Bedtime and wake-up time should not
differ from school to non-school nights by more than approximately an hour.
2 Avoid sleeping in on weekends to “catch up” on sleep. This makes it more likely that you will have
problems falling asleep.
3 If you take naps, they should be short (no more than an hour) and scheduled in the early to
midafternoon. However, if you have a problem with falling asleep at night, napping during the day
may make it worse and should be avoided.
4 Spend time outside every day. Exposure to sunlight helps to keep your body's internal clock on track.
5 Exercise regularly. Exercise may help you fall asleep and sleep more deeply.
6 Use your bed for sleeping only. Don't study, read, listen to music, watch television, etc., on your bed.
7 Make the 30-60 minutes before a quiet or wind-down time. Relaxing, calm, enjoyable activities, such
as reading a book or listening to calm music, help your body and mind slow down enough to let you
get to sleep. Don't study, watch exciting/scary movies, exercise, or get involved in “energizing”
activities just before bed.
8 Eat regular meals and don't go to bed hungry. A light snack before bed is a good idea; eating a full
meal in the hour before bed is not.
9 Avoid eating or drinking products containing caffeine from dinner time on. These include caffeinated
sodas, coffee, tea, and chocolate.

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 10 Do not use alcohol. Alcohol disrupts sleep and may cause you to awaken throughout the night.
11 Smoking disturbs sleep. Don't smoke at least one hour before bed (and preferably, not at all!).
12 Don't use sleeping pills, melatonin, or other over-the-counter sleep aids to help you sleep unless
specifically recommended by your doctor. These can be dangerous, and the sleep problems often
return when you stop taking the medicine

To evaluate sleep problems, it is important to have an understanding of what constitutes “normal”

sleep in children and adolescents. Sleep disturbances, as well as many characteristics of sleep itself,
have some distinctly different features in children from sleep and sleep disorders in adults. In
addition, changes in sleep architecture and the evolution of sleep patterns and behaviors reflect the
physiologic/chronobiologic, developmental, and social/environmental changes that are occurring
across childhood.
These trends may be summarized as the gradual assumption of more adult sleep patterns as children
mature:
• A decline in the average 24 hr sleep duration from infancy through adolescence, which involves a
decrease in both diurnal and nocturnal sleep amounts. There is a dramatic decline in daytime sleep
(scheduled napping) by 5 yr, with a less marked and more gradual continued decrease in nocturnal
sleep amounts into late adolescence.
• A dramatic decrease in the proportion of REM sleep from birth (50% of sleep) through early childhood
into adulthood (25-30%), and a similar initial predominance of SWS that peaks in early childhood,
drops off abruptly after puberty (40-60% decline), and then further decreases over the life span. This
SWS preponderance in early life has clinical significance; the high prevalence of partial arousal
parasomnias (sleepwalking and sleep terrors) in preschool and early school-aged children is related to
the relative increased proportion of SWS in this age group.
• Due to the lengthening of the nocturnal ultradian sleep cycle, a concomitant decrease in the number of
end-of-cycle arousals across the nocturnal sleep period occurs.
• A gradual shift to a later bedtime and sleep onset time that begins in middle childhood and accelerates
in early to mid-adolescence.
• Irregularity of sleep/wake patterns characterized by increasingly larger discrepancies between school
night and non–school night bedtimes and wake times, and increased weekend oversleep that typically
begins in middle childhood and peaks in adolescence.

NORMAL DEVELOPMENTAL CHANGES IN

CHILDREN'S SLEEP
AGE
SLEEP DURATION AND SLEEP PATTERNS
CATEGORY
Total sleep: 10-19 hr per 24 r (average = 13-14.5 hr), may be higher in premature
babies
Bottle-fed babies generally sleep for longer periods (2-5 hr bouts) than
breast-fed babies (1-3 hr)
Newborn (0-2 mo)
Sleep periods are separated by 1-2 hr awake.
No established nocturnal/diurnal pattern in the 1st few wk; sleep is evenly
distributed throughout the day and night, averaging 8.5 hr at night and 5.75 hr
during the day
Total sleep: average is 12-13 hr (note that there is great individual variability in
sleep times during infancy)
Infant (2-12 mo)
Nighttime: average is 9-10 hr
Naps: average is 3-4 hr

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 AGE
SLEEP DURATION AND SLEEP PATTERNS
CATEGORY
Total sleep: average is 11-13 hr
Toddler (1-3 yr) Nighttime: average is 9.5-10.5 hr
Naps: average is 2-3 hr; decrease from 2 naps to 1 at average age of 18 mo

Nighttime: average is 9-10 hr

Preschool (3-5 yr) Naps decrease from 1 nap to no nap

Middle childhood
9-11 hr
(6-12 hr)

Average sleep duration 7-7.5 hr; only 20% of adolescents overall get the
Adolescence (>12 recommended 9-9.25 hr of sleep
yr) Later bedtimes; increased discrepancy sleep patterns weekdays/weekends

Common Sleep Disorders

Most sleep problems in children may be broadly conceptualized as
 Resulting from either inadequate duration of sleep for age and sleep needs (insufficient sleep
quantity) or
 Disruption and fragmentation of sleep (poor sleep quality) as a result of frequent, repetitive,
and brief arousals during sleep.
Less common types:
Inappropriate timing of the sleep period (as occurs in circadian rhythm disturbances), or
Primary disorders of excessive daytime sleepiness (central hypersomnias such as narcolepsy).
Difficulty initiating (delayed sleep onset) and/or maintaining sleep (prolonged night wakings).

Causes of sleep disorders:

 Primarily behavioral factors (bedtime resistance resulting in shortened sleep duration) and/or
medical causes (obstructive sleep apnea causing frequent, brief arousals).
 Children with medical problems including chronic illnesses, such as cystic fibrosis, asthma,
and rheumatoid arthritis, and acute illnesses, such as otitis media; children taking medications
or ingesting substances with stimulant (e.g., psychostimulants, caffeine), sleep-disrupting (e.g.,
corticosteroids), or daytime sedating (some anticonvulsants, α-agonists) properties;
hospitalized children; and children with a variety of psychiatric disorders, including
attention-deficit/hyperactivity disorder (ADHD), depression, bipolar disorder, and anxiety
disorders.
 Children with neurodevelopmental disorders may be more prone to nocturnal seizures, as
well as other sleep disruptions, and children with blindness, mental retardation, some
chromosomal syndromes (Smith-Magenis, fragile X), and autism spectrum disorders are at
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 increased risk for severe sleep onset difficulty and night wakings, as well as circadian rhythm
disturbances.

Insomnia of Childhood:
Definition: Insomnia may be broadly defined as repeated difficulty initiating and/or maintaining
sleep that occurs despite age-appropriate time and opportunity for sleep.
Clinical features: These sleep complaints must also result in some degree of impairment in daytime
functioning for the child and/or family, which may range from fatigue, irritability, lack of energy, and
mild cognitive impairment to effects on mood, school performance, and quality of life.
Duration: Insomnia complaints may be of a short-term and transient nature (usually related to an
acute event), or may be characterized as long-term and chronic.

Etiology: Insomnia is a set of symptoms with a large number of possible etiologies (e.g., pain,
medication, medical and psychiatric conditions, learned behaviors) and not as a diagnosis per se.
Insomnia, like many behavioral issues in children, is often primarily defined by parental concerns
rather than by objective criteria, and therefore should be viewed in the context of family (i.e.,
maternal depression, stress), child (i.e., temperament, developmental level), and environmental (i.e.,
cultural practices, sleeping space) considerations.
Types: One of the most common sleep disorders found in infants and toddlers is behavioral
insomnia of childhood, sleep onset association type. In this disorder, the child learns to fall asleep
only under certain conditions or associations which typically require parental presence, such as being
rocked or fed, and does not develop the ability to self-soothe. During the night, when the child
experiences the type of brief arousal that normally occurs at the end of a sleep cycle (every 60-90
minutes in infants) or awakens for other reasons, he or she is not able to get back to sleep without
those same conditions being present. The infant then “signals” the parent by crying (or coming into
the parents' bedroom, if the child is no longer in a crib) until the necessary associations are provided.
The problem is one of prolonged night waking resulting in insufficient sleep (for both child and
parent).
Management:
 Management of night wakings should include establishment of a set sleep schedule and
bedtime routine, and implementation of a behavioral program.
 The treatment approach typically involves a program of rapid withdrawal (extinction) or
more gradual withdrawal (graduated extinction) of parental assistance at sleep onset and
during the night.
 The goal is to allow the infant or child to develop skills in self-soothing during the night, as
well as at bedtime.
 In older infants, the introduction of more appropriate sleep associations that will be readily
available to the child during the night (transitional objects, such as a blanket or toy), in
addition to positive reinforcement (i.e., stickers for remaining in bed), is often beneficial.
 If the child has become habituated to awaken for nighttime feedings, then these feedings
should be slowly eliminated.
 Older children may benefit from being taught relaxation techniques to help themselves fall

238
 asleep more readily.
 Following the principles of sleep hygiene for children is essential.

2. EATING DISORDERS:
Eating disorders (EDs) are characterized by body dissatisfaction related to overvaluation of a thin
body ideal associated with dysfunctional patterns of cognition and weight control behaviours that
results in significant biologic, psychologic, and social complications.
Classification:
Anorexia nervosa (AN) involves significant overestimation of body size and shape, with a relentless
pursuit of thinness that typically combines excessive dieting and compulsive exercising in the
restrictive subtype; in the binge-purge subtype, patients might intermittently overeat and then
attempt to rid themselves of calories by vomiting or taking laxatives, still with a strong drive for
thinness .
Bulimia nervosa (BN) is characterized by episodes of eating large amounts of food in a brief period,
followed by compensatory vomiting, laxative use, and exercise or fasting to rid the body of the
effects of overeating in an effort to avoid obesity.
The Eating Disorder Not Otherwise Specified category is for disorders of eating that do not meet
the criteria for any specific Eating Disorder.
Binge eating disorder (BED), in which binge eating is not followed regularly by any compensatory
behaviours, is included in ED.
Primary care management:
Close monitoring of the response of the patient and the family to suggested interventions is required
to determine which patients can remain in primary care treatment (patients with early, mildly
disordered eating), which patients need to be referred to individual specialists for co-management
(mildly progressive disordered eating), and which patients need to be referred for interdisciplinary
team management .
Between the initial and subsequent visits, the patient can record daily caloric intake (food, drink,
amount, time, location), physical activity (type, duration, intensity), and emotional state (e.g., angry,
sad, worried) in a journal that is reviewed jointly with the patient in follow-up. In addition, a
targeted physical examination focused on hypometabolism, cardiovascular stability, and mental
status, as well as any related symptoms, should occur at each visit to monitor progress (or
regression).
3. Intellectual disability:
Definition
Three criteria must be met to establish the diagnosis of intellectual disability:
1. Significantly subaverage intellectual function,
2. Significant impairments in adaptive function, and
3. Onset before 18 years of age.

IDENTIFICATION OF CAUSE IN CHILDREN WITH SEVERE INTELLECTUAL

DISABILITY
CAUSE EXAMPLES
Trisomies 21, 18, 13,
1.Chromosomal disorder
Deletion 1p36

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CAUSE EXAMPLES
Klinefelter's syndrome

Fragile X syndrome
2.Genetic syndrome Prader-Willi syndrome
Rett syndrome
3.Nonsyndromic autosomal mutations
4.Developmental brain abnormality Hydrocephalus, meningomyelocele, lissencephaly
5.Inborn errors of metabolism or
PKU, Tay-Sachs, various storage diseases
neurodegenerative disorder
HIV, toxoplasmosis, rubella, CMV, syphilis, herpes
6.Congenital infections
simplex
7.Familial intellectual disability Environment, syndromic, or genetic
8.Perinatal causes HIE, meningitis, IVH, PVL, fetal alcohol syndrome
9.Postnatal causes Trauma (abuse), meningitis, hypothyroidism
10.Unknown Cerebral palsy

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Diagnostic strategy for identifying and assessing children with developmental delay. *Metabolic
evaluation includes serum amino acids, serum and urine organic acids, serum lactate, and ammonia.
†
Genetic evaluation includes karyotype, microarray analysis, and dysmorphology consultation if
indicated.

EMERGING PATTERNS OF BEHAVIOR DURING THE 1ST YEAR OF LIFE*

NEONATAL PERIOD (1ST 4 WK)
Prone: Lies in flexed attitude; turns head from side to side; head sags on ventral suspension
Supine: Generally flexed and a little stiff
Visual: May fixate face on light in line of vision; “doll's-eye” movement of eyes on turning of the body
Reflex: Moro response active; stepping and placing reflexes; grasp reflex active
Social: Visual preference for human face
AT 1 MO
Prone: Legs more extended; holds chin up; turns head; head lifted momentarily to plane of body on
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 ventral suspension
Supine: Tonic neck posture predominates; supple and relaxed; head lags when pulled to sitting position
Visual: Watches person; follows moving object
Social: Body movements in cadence with voice of other in social contact; beginning to smile
AT 2 MO
Prone: Raises head slightly farther; head sustained in plane of body on ventral suspension
Supine: Tonic neck posture predominates; head lags when pulled to sitting position
Visual: Follows moving object 180 degrees
Social: Smiles on social contact; listens to voice and coos
AT 3 MO
Prone: Lifts head and chest with arms extended; head above plane of body on ventral suspension
Supine: Tonic neck posture predominates; reaches toward and misses objects; waves at toy
Head lag partially compensated when pulled to sitting position; early head control with bobbing
Sitting:
motion; back rounded
Typical Moro response has not persisted; makes defensive movements or selective withdrawal
Reflex:
reactions
Social: Sustained social contact; listens to music; says “aah, ngah”
AT 4 MO
Prone: Lifts head and chest, with head in approximately vertical axis; legs extended
Symmetric posture predominates, hands in midline; reaches and grasps objects and brings them to
Supine:
mouth
No head lag when pulled to sitting position; head steady, tipped forward; enjoys sitting with full
Sitting:
truncal support
Standing: When held erect, pushes with feet
Adaptive: Sees pellet, but makes no move to reach for it
Social: Laughs out loud; may show displeasure if social contact is broken; excited at sight of food
AT 7 MO
Prone: Rolls over; pivots; crawls or creep-crawls (Knobloch)
Supine: Lifts head; rolls over; squirms
Sitting: Sits briefly, with support of pelvis; leans forward on hands; back rounded
Standing: May support most of weight; bounces actively
Reaches out for and grasps large object; transfers objects from hand to hand; grasp uses radial
Adaptive:
palm; rakes at pellet
Language: Forms polysyllabic vowel sounds
Social: Prefers mother; babbles; enjoys mirror; responds to changes in emotional content of social contact
AT 10 MO
Sitting: Sits up alone and indefinitely without support, with back straight
Standing: Pulls to standing position; “cruises” or walks holding on to furniture
Motor: Creeps or crawls
Grasps objects with thumb and forefinger; pokes at things with forefinger; picks up pellet with
Adaptive: assisted pincer movement; uncovers hidden toy; attempts to retrieve dropped object; releases
object grasped by other person

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Language: Repetitive consonant sounds (“mama,” “dada”)
Social: Responds to sound of name; plays peek-a-boo or pat-a-cake; waves bye-bye
AT 1 YR
Motor: Walks with one hand held (48 wk); rises independently, takes several steps (Knobloch)
Picks up pellet with unassisted pincer movement of forefinger and thumb; releases object to other
Adaptive:
person on request or gesture
Language: Says a few words besides “mama,” “dada”
Social: Plays simple ball game; makes postural adjustment to dressing

EMERGING PATTERNS OF BEHAVIOR FROM 1 TO 5 YR OF AGE*

15 MO
Motor: Walks alone; crawls up stairs
Adaptive: Makes tower of 3 cubes; makes a line with crayon; inserts raisin in bottle
Jargon; follows simple commands; may name a familiar object (e.g., ball); responds to his/her
Language:
name
Social: Indicates some desires or needs by pointing; hugs parents
18 MO
Runs stiffly; sits on small chair; walks up stairs with one hand held; explores drawers and
Motor:
wastebaskets
Adaptive: Makes tower of 4 cubes; imitates scribbling; imitates vertical stroke; dumps raisin from bottle
Language: 10 words (average); names pictures; identifies one or more parts of body
Feeds self; seeks help when in trouble; may complain when wet or soiled; kisses parent with
Social:
pucker
24 MO
Motor: Runs well, walks up and down stairs, one step at a time; opens doors; climbs on furniture; jumps
Makes tower of 7 cubes (6 at 21 mo); scribbles in circular pattern; imitates horizontal stroke; folds
Adaptive:
paper once imitatively
Language: Puts 3 words together (subject, verb, object)
Handles spoon well; often tells about immediate experiences; helps to undress; listens to stories
Social:
when shown pictures
30 MO
Motor: Goes up stairs alternating feet
Makes tower of 9 cubes; makes vertical and horizontal strokes, but generally will not join them to
Adaptive:
make cross; imitates circular stroke, forming closed figure
Language: Refers to self by pronoun “I”; knows full name
Social: Helps put things away; pretends in play
36 MO
Motor: Rides tricycle; stands momentarily on one foot
Makes tower of 10 cubes; imitates construction of “bridge” of 3 cubes; copies circle; imitates
Adaptive:
cross
Knows age and sex; counts 3 objects correctly; repeats 3 numbers or a sentence of 6 syllables;
Language:
most of speech intelligible to strangers

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 Plays simple games (in “parallel” with other children); helps in dressing (unbuttons clothing and
Social:
puts on shoes); washes hands
48 MO
Motor: Hops on one foot; throws ball overhand; uses scissors to cut out pictures; climbs well
Copies bridge from model; imitates construction of “gate” of 5 cubes; copies cross and square;
Adaptive:
draws man with 2 to 4 parts besides head; identifies longer of 2 lines
Language: Counts 4 pennies accurately; tells story
Plays with several children, with beginning of social interaction and role-playing; goes to toilet
Social:
alone
60 MO
Motor: Skips
Adaptive: Draws triangle from copy; names heavier of 2 weights
Language: Names 4 colors; repeats sentence of 10 syllables; counts 10 pennies correctly
Social: Dresses and undresses; asks questions about meaning of words; engages in domestic role-playing

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 HEMATOLOGY
1. Functions of spleen
2. Immune thrombocytopenic purpura
3. Polycythemia
4. Pancytopenia
5. Aplastic anemia
6. Clotting cascade/ hemostasis
7. Haemophilia
8. DIC
9. Clinical and laboratory evaluation of haemostasis
10. Hemolytic anemias
11. Hereditary spherocytosis
12. PNH
13. G6PD deficiency
14. Autoimmune hemolytic anemia
15. Fundus findings in blood disorders
16. Sickle cell anemia
17. IVIG
18. Stem cell transplantation
19. Tumour lysis syndrome printed/ written notes
20. Hematopoiesis
21. Approach to bleeding child
22.

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1. Functions of spleen

The unique anatomy and blood flow of the spleen enable it to perform reservoir, filtering,
and immunologic functions.

The spleen receives 5-6% of the cardiac output, but normally contains only 25 mL of
blood.

Reservoir: Hematopoiesis is a major splenic function at 3-6

mo of fetal life but then disappears. Splenic hematopoiesis can be resumed in patients with
myelofibrosis or severe hemolytic anemia. Factor VIII and one third of the circulating
platelet mass are sequestered in the spleen and can be released by stress or epinephrine
injection. Thrombocytosis and leukocytosis occur with loss of the splenic reservoir
function.

Filtering: Slow blood flow past macrophages and through

small openings in the sinus walls facilitates the filtering functions of the spleen. Excess
membrane is removed from young red blood cells (RBCs); loss of this function is
characterized by target cells, poikilocytosis, and decreased osmotic fragility. The spleen is
the primary site for destruction of old RBCs. The spleen also removes damaged and
abnormal cells, such as spherocytes and antibody-coated RBCs.

Immunological: The spleen plays a large role in host defense against

infection. The spleen is the largest lymphoid organ in the body and contains nearly half of
the body's total immunoglobulin-producing B lymphocytes. The spleen processes foreign
material to stimulate production of opsonizing antibody. Thus, young (nonimmune) or
hyposplenic individuals are at increased risk for sepsis caused by pneumococci and other
encapsulated bacteria.

Phagocytosis: The spleen can use phagocytosis to trap and destroy intracellular
parasites.

Post spleenectomy-

1. Increased risk of infection with capsulated organisms like streptococcus pneumoniae,

hemophilus influenzae, and neisseria meningitides.

2. Hence in a febrile splenectomised patient should be treated with broad spectrum

cephalosporin (cefotaxime and ceftriaxone) together with vancomycin.

3. Splenectomised patients are also at increased risk for contracting protozoal infections,
such as malaria and babesiosis.

4. Pneumococcal, meningococcal, and H. influenzae conjugate vaccines given before

spleenectomy may reduce post spleenectomy sepsis.

5. The 23-valent pneumococcal polysaccharide vaccine should be given every 5 yr after the
initial vaccine series.

6. Prophylaxis with oral penicillin V (125 mg twice daily for children younger than 5 yr;
250 mg twice daily for children 5 yr or older) should be given for at least 2 yr after
splenectomy (to at least 6 yr of age).
246
7. In addition to postsplenectomy sepsis, splenectomized patients may be at risk for
thromboembolic complications, including arterial and venous thrombosis and pulmonary
hypertension.

8. Folic acid, 1 mg daily, should be administered to prevent deficiency and the resultant
decrease in erythropoiesis.

Hyposplenism

Congenital absence of the spleen is associated with complex cyanotic heart defects,
dextrocardia, bilateral trilobed lungs, and heterotopic abdominal organs (Ivemark
syndrome).

Splenic function is usually normal in children with congenital polysplenia.

Splenic hypofunction is characterized by

 RBC inclusions in peripheral blood smears (Howell-Jolly bodies or Heinz bodies).

 Thrombocytosis and leukocytosis occur with loss of Splenic function.
 “Pits” on interference microscopy.
 Poor uptake of technetium on spleen scan.

Patients with functional hyposplenism or asplenia are at increased risk for sepsis from
encapsulated bacteria.

2. ITP: The most common cause of acute onset of thrombocytopenia

in an otherwise well child is (autoimmune) idiopathic thrombocytopenic purpura (ITP).
Epidemiology

In a small number of children, 1-4 wk after exposure to a common viral infection, an

autoantibody directed against the platelet surface develops with resultant sudden onset of
thrombocytopenia.

The peak age is 1-4 yr, although the age ranges from early in infancy to the elderly.

ITP seems to occur more often in late winter and spring after the peak season of viral
respiratory illness.

Most common viruses have been described in association with ITP, including Epstein-Barr
virus and HIV.

In some patients ITP appears to arise in children infected with Helicobacter pylori or rarely
following the measles, mumps, rubella vaccine.

Pathogenesis:

The exact antigenic target for most such antibodies in most cases of childhood acute ITP
remains undetermined, although in chronic ITP most patients demonstrate antibodies
against the platelet glycoprotein complexes, α11b-B3 and GPIb. After binding of the
247
antibody to the platelet surface, circulating antibody-coated platelets are recognized by the
Fc receptor on splenic macrophages, ingested, and destroyed.

Clinical Manifestations

1. The classic presentation of ITP is a previously healthy 1-4 yr old child who has sudden
onset of generalized petechiae and purpura.
2. Findings on physical examination are normal, other than the finding of petechiae and
purpura.
3. Splenomegaly, lymphadenopathy, bone pain, and pallor are rare.

An easy to use classification system has been proposed to characterize the severity of
bleeding in ITP on the basis of symptoms and signs, but not platelet count:

1 No symptoms.
2 Mild symptoms: bruising and petechiae, occasional minor epistaxis, very little
interference with daily living.
3 Moderate: more severe skin and mucosal lesions, more troublesome epistaxis
and menorrhagia.
4 Severe: bleeding episodes—menorrhagia, epistaxis, melena—requiring
transfusion or hospitalization, symptoms interfering seriously with the quality of
life.

Outcome:

Severe bleeding is rare.

In 70-80% of children who present with acute ITP, spontaneous resolution occurs within 6
months.

The outcome/prognosis may be related more to age, as ITP in younger children is more
likely to resolve whereas the development of chronic ITP in adolescents approaches 50%.

Laboratory Findings:

1. Severe thrombocytopenia is common, and platelet size is normal or increased,

reflective of increased platelet turnover.
2. In acute ITP, the hemoglobin value, white blood cell (WBC) count, and differential
count should be normal.
3. Bone marrow examination shows normal granulocytic and erythrocytic series, with
characteristically normal or increased numbers of megakaryocytes. Indications for bone
marrow aspiration/biopsy include an abnormal WBC count or differential or unexplained
anemia as well as findings on history and physical examination suggestive of a bone marrow
failure syndrome or malignancy.
4. In adolescents with new-onset ITP, an antinuclear antibody test should be done to

248
evaluate for SLE.
5. HIV studies should be done in at-risk populations, especially sexually active teens.
6. A direct antiglobulin test (Coombs) should be done if there is unexplained anemia to
rule out Evans syndrome (autoimmune hemolytic anemia and thrombocytopenia) or before
instituting therapy with IV anti-D.

Treatment: Initial approaches to the management of ITP include the following:

1 No therapy other than education and counselling of the family and patient for
patients with no, mild, and moderate symptoms, as defined earlier.
2 IVIG at a dose of 0.8-1.0 g/kg/day for 1-2 days induces a rapid rise in platelet
count. IVIG therapy is both expensive and time-consuming to administer.
3 For Rh positive patients, IV anti-D at a dose of 50-75 mcg/kg causes a rise in
platelet count.
4 Doses of prednisone of 1-4 mg/kg/24 hr appear to induce a more rapid rise in
platelet count.
5. In the special case of intracranial hemorrhage, multiple modalities
should be
used, including platelet transfusion, IVIG, high-dose corticosteroids
and prompt
consultation by neurosurgery and surgery.

6. The role of splenectomy in ITP should be reserved for 1 of 2

circumstances.

 The older child (≥4 yr) with severe ITP that has lasted >1 yr (chronic ITP) and whose
symptoms are not easily controlled with therapy is a candidate for splenectomy.
 Splenectomy must also be considered when life-threatening hemorrhage (intracranial
hemorrhage) complicates acute ITP, if the platelet count cannot be corrected rapidly with
transfusion of platelets and administration of IVIG and corticosteroids.

Chronic Idiopathic Thrombocytopenic Purpura:

1. Approximately 20% of patients who present with acute ITP have persistent
thrombocytopenia for >12 mo and are said to have chronic ITP.
2. At that time, a careful re-evaluation for associated disorders should be performed,
especially for
 autoimmune disease, such as SLE;
 chronic infectious disorders, such as HIV; and
 nonimmune causes of chronic thrombocytopenia, such as type 2B and platelet-type von
Willebrand disease,
 X-linked thrombocytopenia,
 autoimmune lymphoproliferative syndrome,
 common variable immunodeficiency syndrome, autosomal macrothrombocytopenia, and
249
WAS (also X-linked).
 The presence of co-existing H. pylori infection should be treated.
3. Splenectomy is successful in inducing complete remission in 64-88% of children with
chronic ITP. This effect must be balanced against the lifelong risk of overwhelming post
splenectomy infection.
4. Rituximab, a chimeric monoclonal anti–B cell antibody, effectively induces a remission
in 30-50% of children with chronic ITP.
5. Two new effective agents that act to stimulate thrombopoiesis, romiplastin and
eltrombopag, have been approved.

3. Polycythemia:
Polycythemia exists when the red blood cell (RBC) count, hemoglobin level, and total RBC
volume all exceed the upper limits of normal.
In post pubertal individuals, an RBC mass > 25% above the mean normal value (based on
body surface area), or a hematocrit level > 60 (in males) or > 56 (in females) indicate
absolute erythrocytosis.

WHO DIAGNOSTIC CRITERIA FOR POLYCYTHEMIA VERA

MAJOR CRITERIA
1 Hgb > 18.5 g/dL (men) or Hgb > 16.5 g/dL (women)
OR
Hgb or Hct > 99th percentile of reference range for age, sex, or
altitude of residence
OR
Hgb > 17 g/dL (men) or Hgb > 15 g/dL (women) if associated with a
sustained increase of ≥ 2 g/dL from baseline that cannot be attributed
to correction of iron deficiency
OR
elevated red cell mass > 25% above mean normal predicted value.
2 Presence of JAK2 or similar mutation.
MINOR CRITERIA
1 Bone marrow trilineage myeloproliferation.
2 Subnormal serum erythropoietin level.
3 Endogenous erythroid colony growth.
DIAGNOSIS
Both major criteria and one minor criteria OR First major criteria and 2 minor
criteria.

Treatment

 Phlebotomy is the initial treatment of choice.

 Iron supplementation should be given.

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  Antiplatelet agents (aspirin) may reduce the risks of thrombosis and bleeding.
 If these treatments are unsuccessful, antiproliferative treatments (hydroxyurea,
anagrelide, interferon-α) may be helpful. (HAI)

Follow ROCCHEN for the flow chart.

Red cell mass, oxygen, CoHb, CT scan, hemoglobin levels, erythropoietin and normal

4. Pancytopenia:
Pancytopenia refers to a reduction below normal values of all 3 peripheral blood lineages:
leukocytes, platelets, and erythrocytes.

Pancytopenia requires microscopic examination of a bone marrow biopsy specimen and a

marrow aspirate to assess overall cellularity and morphology.

There are 3 general categories of pancytopenia depending on the marrow findings.

Hypocellular marrow on biopsy is seen with

Inherited (“constitutional”) marrow failure syndromes (Fanconis anemia,

Shwachman-Diamond syndrome, Dyskeratosis congenital, amegakaryocytic
thrombocytopenia)

Acquired aplastic anemia (see the table below)

The hypoplastic variant of myelodysplastic syndrome

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 Some cases of paroxysmal nocturnal hemoglobinuria with pancytopenia.

Cellular marrow is seen

(1) With primary bone marrow disease, such as acute leukemia, and MDS.

(2) Secondary to systemic disease, such as autoimmune disorders (SLE), vitamin B12 or
folate deficiency, storage disease (Gaucher and Niemann-Pick diseases), overwhelming
infection, sarcoidosis, and hypersplenism.

Bone marrow infiltration can cause pancytopenia in myelofibrosis, osteopetrosis,

hemophagocytic lymphohistiocytosis, and metastatic solid tumors.

Aplastic anemia:
Radiation Viruses- CMV, Immune diseases- autoimmune
drugs and EBV, HEP B, C, hypoimmunoglobulinemia
chemicals HIV, herpes thymoma
Pregnancy PNH Marrow replacement- leukemia, others
lymphoma, MDS

Pathology of aplastic anemia:

Bone marrow failure may be a consequence of a
1. direct cytotoxic effect on hematopoietic stem cells from a drug or chemical
2. cell-mediated
3. immune-mediated process or
4. antibody-dependent cytotoxicity.

Severe aplastic anemia is defined as a condition in which 2 or more cell components have
become seriously compromised (absolute neutrophil count [ANC] <500/mm3, platelet count
<20,000/mm3, reticulocyte count <1% after correction for hematocrit) in a patient whose
bone marrow biopsy material is moderately or severely hypocellular.
Approximately 65% of patients who first present with moderate aplastic anemia (ANC
500-1,500/mm3, platelet count 20,000-100,000/mm3, reticulocyte count <1%) eventually
progress to meet the criteria for severe disease if they are simply observed.

Clinical Manifestations, and Laboratory Findings:

Pancytopenia results in increased risks of cardiac failure, infection, bleeding, and fatigue.

1. Careful examination of the peripheral blood smear for RBC, leukocyte, and platelet
morphologic features is important.
2. Bone marrow examination should include both aspiration and a biopsy, and the
marrow should be carefully evaluated for morphologic features, cellularity, and cytogenetic
findings.
3. A reticulocyte count should be performed to assess erythropoietic activity.
4. Chromosomal breakage analysis should be performed to evaluate for Fanconi anemia.
5. The presence of fetal hemoglobin suggests congenital pancytopenia but is not

252
diagnostic.
6. For PNH, flow cytometric analysis of erythrocytes for CD55 and CD59 is the most
sensitive test.

Treatment:

1. The treatment of children with acquired pancytopenia requires comprehensive

supportive care coupled with an attempt to treat the underlying marrow failure.
2. For patients with an HLA-identical sibling marrow donor, allogeneic bone marrow
transplantation (BMT) offers a 90% chance of long-term survival.
3. For patients without a sibling donor, the major form of therapy is immunosuppression
with antithymocyte globulin (ATG) and cyclosporine, with a response rate of 60-80%.
4. For patients who show no response to immunosuppression or who experience relapse
after immunosuppression, matched unrelated donor marrow/stem cell transplant is a
treatment option.
5. High-dose cyclophosphamide has been used successfully in the treatment of patients
with newly diagnosed aplastic anemia and in patients without adequate response to
immunosuppression.
6. Broad spectrum antibiotic
7. Hematopoietic growth factors
8. Blood product replacement
9. Spleenectomy for pancytopenia
10. Other therapies that have been used in the past with inconsistent results include
androgens, corticosteroids, and plasmapheresis.

Complications:

1. Life-threatening bleeding from prolonged thrombocytopenia

2. Infection secondary to protracted neutropenia and at risk not only for serious bacterial
infections but also for invasive mycoses.
3. Immediate and late complications of BMT.

Prognosis:

1. Spontaneous recovery from pancytopenia rarely occurs.

2. If left untreated, severe pancytopenia has an overall mortality rate of approximately
50% within 6 mo of diagnosis and of >75% overall, with infection and hemorrhage being
the major causes of morbidity and mortality.
3. The majority of children with acquired severe aplastic anemia show response to
allogeneic marrow transplantation or immunosuppression, leaving them with normal or
near-normal blood cell counts.

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6. Clotting cascade/ Haemostasis

7. Haemophilia:
254
Deficiencies of factors VIII and IX are the most common severe inherited bleeding
disorders.

Pathophysiology:

Factors VIII and IX participate in a complex required for the activation of factor X. Together
with phospholipid and calcium, they form the “tenase,” or factor X–activating, complex.

After injury, the initial hemostatic event is formation of the platelet plug, together with the
generation of the fibrin clot that prevents further hemorrhage.

In hemophilia A or B, clot formation is delayed and is not robust.

Inadequate thrombin generation leads to failure to form a tightly cross-linked fibrin clot to
support the platelet plug.

Patients with hemophilia slowly form a soft, friable clot.

When untreated bleeding occurs in a closed space, such as a joint, cessation of bleeding may
be the result of tamponade.

The clot that is formed may be friable, and rebleeding occurs with minimal new trauma.

Clinical Manifestations:

Severe hemophilia is characterized as having <1% activity of the specific clotting factor
and bleeding is often spontaneous.

Patients with moderate hemophilia have factor levels of 1-5% and usually require mild
trauma to induce bleeding.

Individuals with mild hemophilia have levels >5%, may go many years before the
condition is diagnosed, and frequently require significant trauma to cause bleeding.

Treatment:

Early, appropriate therapy is the hallmark of excellent hemophilia care.

When mild to moderate bleeding occurs, values of factor VIII or factor IX must be raised to
hemostatic levels, in the 35-50% range.

For life-threatening or major hemorrhages, the dose should aim to achieve levels of 100%
activity.

Dose of FVIII = body weight (kg) x desired increase of factor x 0.5

Dose of F IX = body weight (kg) x desired increase of factor x 1.4

255
 TREATMENT OF HEMOPHILIA

TYPE OF
HEMORRHA HEMOPHILIA A
GE
50 IU/kg factor VIII concentrate on day 1; then
20IU/kg on days 2, 3, 5 until joint function is
Hemarthrosis normal or back to baseline. Consider additional
treatment every other day for 7-10 days. Consider
prophylaxis.
Muscle or
50 IU/kg factor VIII concentrates; 20 IU/kg
significant
every-other-day treatment may be needed until
subcutaneous
resolved.
hematoma
Mouth,
deciduous 20 IU/kg factor VIII concentrate; antifibrinolytic
tooth, or tooth therapy; remove loose deciduous tooth.
extraction
Apply pressure for 15-20 min; pack with petrolatum
Epistaxis gauze; give antifibrinolytic therapy; 20 IU/kg
factor VIII concentrate if this treatment fails.
50-75 IU/kg factor VIII concentrate, then initiate
continuous infusion of 2-4 IU/kg/hr to maintain
Major surgery,
factor VIII >100 IU/dL for 24 hr‘ then give 2-3
life-threatening
IU/kg/hr continuously for 5-7 days to maintain the
hemorrhage
level at >50 IU/dL and an additional 5-7 days to
maintain the level at >30 IU/dL.
50 IU/kg factor VIII concentrate, then 25 IU/kg
Iliopsoas
every 12 hr until asymptomatic, then 20 IU/kg every
hemorrhage
other day for a total of 10-14 days.
Bed rest; 1 ½ maintenance fluids; if not controlled
in 1-2 days, 20 IU/kg factor VIII concentrate; if not
Hematuria
controlled, give prednisone (unless patient is
HIV-infected). No antifibrinolytic therapy.
Secondary 20-40 IU/kg factor VIII concentrates every other
prophylaxis day to achieve a trough level ≥1%.

Primary prophylaxis:

With mild factor VIII hemophilia, the patient's endogenously produced factor VIII can be
released by the administration of desmopressin acetate (DDAVP). The risk of exposing the
patient with mild hemophilia to transfusion-transmitted diseases and the cost of recombinant
products warrant the use of desmopressin, if it is effective.

A concentrated intranasal form of desmopressin acetate, can also be used to treat patients
256
 with mild hemophilia A. The dose is 150 mcg (1 puff) for children weighing <50 kg and 300
mcg (2 puffs) for children and young adults weighing >50 kg.

Fundamentals of treatment:

Do’s Dont’s

Local treatment- ice application, local pressure IM injections

Early factor correction Contact sports

Hep A and B immunization and educate parents. aspirin

Adjunctive management:

1. RICE- rest, ice application, compression, elevation.

2. Pain and anti-inflammatory action- paracetamol and codeine
3. Antifibrinolytic action- EACA and tranexamic acid

Genetics:

If mother is a carrier - 50% of sons will be affected and 50% of daughters will be
carriers.

If father is affected then all daughters will be carriers and all sons will be normal.

Prenatal diagnosis:

1. Molecular diagnosis of haemophiliacs

2. Non invasive prenatal diagnosis from maternal blood

a) Isolation of fetal nucleated RBC’s

b) Isolation of circulatory cell free DNA from maternal plasma

c) Detection of fetal RNA from maternal blood and obtain fetal gene expression analysis

3. Pre implantation genetic diagnosis

4. CVS and Amniocentesis – DNA analysis if affected fetus then MTP.

8. DIC:

Thrombotic microangiopathy refers to a heterogeneous group of conditions, including

disseminated intravascular coagulation (DIC) that is characterised by accelerated
intravascular coagulation associated with increased consumption of platelets, plasma
clotting factors and anticoagulants resulting in prolonged bleeding, tissue ischemia and
necrosis.

MALIGNANCY TISSUE INJURY INFECTIOUS

Acute promyelocytic leukemia Central nervous system Meningococcemia(purpura
trauma
257 fulminans)
Acute monoblastic or Multiple fractures with Bacterial sepsis (staphylococcal,
promyelocytic leukemia fat emboli streptococcal, Escherichia coli,
Widespread malignancies Crush injury Salmonella)
(neuroblastoma) Profound shock or Rickettsia (Rocky Mountain
asphyxia spotted fever)
Hypothermia or Virus (cytomegalovirus, herpes
hyperthermia simplex, hemorrhagic fevers)
VENOM OR Malaria
Massive burns
TOXIN
Fungus
Snake bites
Insect bites Miscellaneous- GVHD, blood
transfusion

MICROANGIOPATHIC NEWBORN GASTROINTESTINAL

DISORDERS Maternal DISORDERS
“Severe” thrombotic toxemia Fulminant hepatitis
thrombocytopenic purpura Bacterial or Severe inflammatory
or hemolytic-uremic viral sepsis bowel disease
syndrome (group B Pancreatitis
Giant hemangioma streptococcus,
(Kasabach-Merritt herpes simplex)
syndrome) Abruptio
placentae
Severe
respiratory
distress
syndrome
Necrotizing
enterocolitis
Erythroblastosis
fetalis
Fetal demise of
a twin

Clinical features:

1. DIC accompanies a severe systemic disease process, usually with shock.

2. Bleeding frequently first occurs from sites of venipuncture or surgical incision.
3. The skin may show petechiae and ecchymoses.
4. Tissue necrosis may involve many organs and can be most spectacularly seen as
infarction of large areas of skin, subcutaneous tissue, or kidneys.

258
5. Anemia caused by hemolysis may develop rapidly, owing to microangiopathic
hemolytic anemia.
6. CNS: delirium, IC bleed and coma
7. Renal: Oliguria, cortical necrosis, hematuria and azotemia
8. RS: ARDS

Laboratory Findings:

1. Certain coagulation factors (factors II, V, and VIII, and fibrinogen) and platelets may be
consumed.
2. Prolongation of the prothrombin, partial thromboplastin, and thrombin times.
3. The blood smear may contain fragmented and burr- and helmet-shaped red blood cells
(schistocytes).
4. In addition, because the fibrinolytic mechanism is activated, fibrinogen degradation
products (FDPs, D-dimers) appear in the blood.
5. Decreased fibrinogen.

Treatment

The 1st 2 steps in the treatment of DIC are the most critical:

(1) Treat the trigger that caused DIC and

(2) Restore normal homeostasis by correcting the shock, acidosis, and hypoxia that usually
complicate DIC.

Blood components are used for replacement therapy in patients with hemorrhage and may
consist of platelet infusions (for thrombocytopenia), cryoprecipitate (for
hypofibrinogenemia), and/or fresh frozen plasma (for replacement of other coagulation
factors and natural inhibitors).

Activated protein C concentrate (APC) in DIC associated with sepsis.

The role of heparin in DIC is limited to patients who have vascular thrombosis in association
with DIC.

9. Clinical and Laboratory Evaluation of Hemostasis

(History physical examination and laboratory investigations)

History:

For most hemostatic disorders, the clinical history provides the most useful information.
259
 To evaluate for a bleeding disorder, the history should determine the site or sites of
bleeding, the severity and duration of hemorrhage, and the age at onset.
 Was the bleeding spontaneous, or did it occur after trauma?
 Was there a previous personal or family history of similar problems?
 Did the symptoms correlate with the degree of injury or trauma?
 Does bruising occur spontaneously?
 If the patient had previous surgery or significant dental procedures, was there any
increased bleeding?
 In postpubertal females, it is important to take a careful menstrual history.
 History of any drug intake?

Physical Examination:

 The physical examination should focus on whether bleeding symptoms are associated
primarily with the mucous membranes or skin (mucocutaneous bleeding) or with the
muscles and joints (deep bleeding).
 The examination should determine the presence of petechiae, ecchymoses, hematomas,
hemarthroses, or mucous membrane bleeding.
 Patients with defects in platelet-blood vessel wall interaction (VWD or platelet
function defects) usually have mucocutaneous bleeding.
 Individuals with a clotting factor deficiency of factor VIII or IX (hemophilia A or B)
have symptoms of deep bleeding into muscles and joints, with much more extensive
ecchymoses and hematoma formation.
 Individuals with disorders of the collagen matrix and vessel wall may have loose joints
and lax skin associated with easy bruising (Ehlers-Danlos syndrome).
 Should be asked about swollen, warm, tender extremities or internal organs (venous
thrombosis),
 Unexplained dyspnea or persistent “pneumonia,” especially in the absence of fever
(pulmonary emboli).

Laboratory Tests:

1. Platelet Count:

Platelet count is essential in the evaluation of the child with a positive bleeding history
because thrombocytopenia is the most common acquired cause of a bleeding diathesis in
children. Patients with a platelet count of > 50,000/mm3 rarely have significant clinical
bleeding.

2. Prothrombin Time and partial thromboplastin time:

The dual mechanisms of activating clotting have been termed the intrinsic (surface
activation) and extrinsic (tissue factor–mediated) pathways. In most laboratories, the normal
PT value is 10-13 sec. PT has been standardized using the International Normalized Ratio
(INR) so that values can be compared from 1 laboratory or instrument to another.

(PT extrinsic pathway factor VII) (PTT Intrinsic pathway factor VIII)

260
3. Thrombin Time and Reptilase Time :

Thrombin time measures the final step in the clotting cascade, in which fibrinogen is
converted to fibrin. The normal thrombin time varies between laboratories but is usually
11-15 sec. Prolongation of thrombin time occurs with reduced fibrinogen levels
(hypofibrinogenemia or afibrinogenemia), with dysfunctional fibrinogen
(dysfibrinogenemia), or in the presence of substances that interfere with fibrin
polymerization, such as heparin and fibrin split products. If heparin contamination is a
potential cause of prolonged thrombin time, a reptilase time is usually ordered.

Reptilase time uses snake venom to clot fibrinogen. Unlike thrombin time, reptilase time is
not sensitive to heparin and is prolonged only by reduced or dysfunctional fibrinogen and
fibrin split products. Therefore, if thrombin time is prolonged but reptilase time is normal,
the prolonged thrombin time is due to heparin and does not indicate the presence of fibrin
split products or reduced concentration or function of fibrinogen.

4. Mixing Studies:

If there is unexplained prolongation of PT, PTT, or thrombin time, a mixing study is usually
performed. Normal plasma is added to the patient's plasma, and the PT or PTT is repeated.

 Correction of PT or PTT by 1 : 1 mixing with normal plasma suggests deficiency of a

clotting factor.
 If the mixing study is not corrected or if its result becomes more prolonged and the
patient has clinical bleeding, an inhibitor of a specific clotting factor may be present.
 If the patient has no bleeding symptoms and both PTT and the mixing study are
prolonged, a lupus-like anticoagulant is often present.

5. Bleeding Time:

Bleeding time assesses the function of platelets and their interaction with the vascular wall.
After an incision is made with the bleeding time device, blood is blotted from the margin of
the incision at 30-sec intervals until bleeding ceases. Bleeding usually stops within 4-8 min.
Use of the bleeding time is declining in many centers.

6. Platelet Function Analyzer:

The greatest experience has been with the platelet function analyzer (PFA-100). The
PFA-100 measures platelet adhesion-aggregation in whole blood at high shear when
exposed to either collagen-epinephrine or collagen-ADP.

7. D-Dimer D-dimer is more specific for fibrinolysis than FDPs.

8. Clotting Factor Assays

By definition, 1 international unit (IU) of each factor is defined as that amount in 1 mL of

normal plasma.

For most clotting factors, the normal range is 50-150 IU/dL (50-150%).

One Bethesda unit is defined as the amount that will inhibit 50% of the clotting factor in
normal plasma.

261
9. Platelet Aggregation

When a qualitative platelet function defect is suspected, platelet aggregation testing is

usually ordered. Platelet-rich plasma from the patient is activated with 1 of a series of
agonists (ADP, epinephrine, collagen, thrombin or thrombin-receptor peptide, and
ristocetin).

10. Testing for Thrombotic Predisposition:

 Hereditary predisposition to thrombosis is associated with a reduction of anticoagulant

function (protein C, protein S, AT-III).
 the presence of a factor V molecule that is resistant to inactivation by protein C (factor
V Leiden).
 elevated levels of procoagulants (a mutation of the prothrombin gene); or
 a deficiency of fibrinolysis (plasminogen deficiency).

11. Elevated Homocysteine

Patients with homocysteine elevation are predisposed to arterial and venous thrombosis as
well as to an increase in arteriosclerosis.

12. Tests of the Fibrinolytic System

Euglobulin clot lysis time is a screening test used in some laboratories to assess fibrinolysis.

13. Electrophoresis studies for collagen types especially in Ehlars Danlos syndrome.

10. Hemolytic anemias:

where µ is a maturation factor of 1-3. The normal reticulocyte index is 1.0; therefore, the
index measures the fold increase in erythropoiesis (e.g., 2-fold, 3-fold).

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Causes of hemolytic anemia:

Cellular Extracellular
1. Membrane defects 1.Autoimmune
 Hereditary spherocytosis  Warm antibody
 Hereditary elliptocytosis  Cold antibody
 Hereditary pyropoikilocytosis 2. Fragmentation hemolysis
 Hereditary stomatocytosis  DIC, TTP, HUS ECMO
 Paroxysmal nocturnal hemoglobinuria  Prosthetic valve
2. Enzyme deficiencies  Burns, thermal injury
 Pyruvate kinase deficiency
 G6PD deficiency 3. Hypersplenism
3. Hemoglobinopathies 4. Plasma factors
 Liver diasease
 Infections
 Abetalipoproteinemia
 Wilson disease

11. Hereditary spherocytosis:

Hereditary spherocytosis is a common cause of hemolysis and hemolytic anemia, with a

wide spectrum.

It is the most common inherited abnormality of the red blood cell (RBC) membrane.

Etiopathogenesis:
263
Hereditary spherocytosis usually is transmitted as an autosomal dominant or, less
commonly, as an autosomal recessive disorder.

A deficiency in spectrin, protein 3, or ankyrin results in uncoupling in the “vertical”

interactions of the lipid bilayer skeleton and the loss of membrane microvesicles.

The loss of membrane surface area without a proportional loss of cell volume causes
sphering of the RBCs.

The decreased deformability of the spherocytic RBCs impairs cell passage from the splenic
cords to the splenic sinuses, and the spherocytic RBCs are destroyed prematurely in the
spleen.

Clinical features:

1. Hereditary spherocytosis may be a cause of hemolytic disease in the newborn and can
manifest as anemia and hyperbilirubinemia sufficiently severe to require phototherapy or
exchange transfusions.
2. The severity of symptoms in infants and children is variable.
3. Some patients remain asymptomatic into adulthood, but others have severe anemia
with pallor, jaundice, fatigue, and exercise intolerance.
4. Severe cases may be marked by expansion of the diplo of the skull and the medullary
region of other bones, but to a lesser extent than in thalassemia major.
5. After infancy, the spleen is usually enlarged, and pigmentary (bilirubin) gallstones can
form as early as age 4-5 years.
6. Because of the high RBC turnover and heightened erythroid marrow activity, children
with hereditary spherocytosis are susceptible to aplastic crisis, primarily as a result of
parvovirus B19 infection, and to hypoplastic crises associated with various other
infections.
7. The erythroid marrow failure can rapidly result in profound anemia (hematocrit <10%),
high-output heart failure, hypoxia, cardiovascular collapse, and death.

Laboratory Findings:

Blood- reticulocytosis, indirect Hyperbilirubinemia, anemia and decreased haptoglobin.

Roentgenographic- shows marrow expansion.

Ultrasonography- gallstones, splenomegaly.

The diagnosis of hereditary spherocytosis usually is established clinically from the blood
film, which shows many spherocytes and reticulocytes, from the family history, and from
264
splenomegaly.

The presence of spherocytes in the blood can be confirmed with an osmotic fragility test.
The RBCs are incubated in progressive dilutions of an iso-osmotic buffered salt solution.
Exposure to hypotonic saline causes the RBCs to swell, and the spherocytes lyse more
readily than biconcave cells in hypotonic solutions. This feature is accentuated by depriving
the cells of glucose overnight at 370C, known as the incubated osmotic fragility test.
Unfortunately, this test is not specific for hereditary spherocytosis, and results may be
abnormal in immune and other hemolytic anemias. A normal test result also may be found in
10-20% of patients.

Other tests, (ECHO) such as the cryohemolysis test, osmotic gradient ektacytometry, and the
eocin-5-maleimide test, may be more sensitive but are not readily available. Detection of a
population of hyperdense RBCs using a laser-based instrument or a Coulter counter may
prove more convenient as an approach to diagnosis.

As a research tool, the specific protein abnormality can be established in 80% of these
patients by RBC membrane protein analysis using gel electrophoresis and densitometric
quantitation.

Treatment:

 Spleenectomy eliminates most of the hemolysis associated with this disorder.

 After spleenectomy, osmotic fragility often improves. Anemia, reticulocytosis, and
hyperbilirubinemia then resolve.
 Folic acid, 1 mg daily, should be administered to prevent deficiency and the resultant
decrease in erythropoiesis.
 Vaccines (conjugated and/or capsular) for encapsulated organisms, such as
pneumococcus, meningococcus, and Haemophilus influenzae type b, should be administered
before splenectomy, and prophylactic oral penicillin V (age <5 yr, 125 mg twice daily; age 5
yr through adulthood, 250 mg twice daily) should be administered thereafter.

12. PNH

Paroxysmal nocturnal hemoglobinuria (PNH) reflects an abnormality of marrow stem cells

that affects each blood cell lineage.

It is an acquired disorder of hematopoiesis characterized by a defect in proteins of the cell

265
membrane (decay-accelerating factor, the C8 binding protein,) that renders the red blood
cells (RBCs) and other cells susceptible to damage by normal plasma complement proteins.

Mutations in the PIGA gene have been identified in children with PNH.

Clinical Manifestations:

 PNH is a rare disorder in children.

 Approximately 60% of pediatric patients have marrow failure.
 Nocturnal and morning hemoglobinuria is a classic finding in adults.
 In addition to chronic hemolysis, thrombocytopenia and leukopenia are often
characteristic.
 Thrombosis and thromboembolic phenomena are serious complications.
 Hypoplastic or aplastic pancytopenia can precede or follow the onset of PNH.
 PNH rarely progresses to acute myelogenous leukemia.
 The mortality in PNH is related primarily to the development of aplastic anemia or
thrombotic complications.

Laboratory Findings:

 The diagnosis of PNH was established classically by a positive result on either the
acidified serum hemolysis (Ham) test or the sucrose lysis test. These tests activate the
alternative and classic pathways of complement lysis, respectively. (a-a, c-c)
 Hemosiderinuria is common and reflects chronic intravascular hemolysis.
 Markedly reduced levels of RBC acetylcholinesterase activity and
decay-accelerating factor also are found.
 Flow cytometry currently is the diagnostic test of choice for PNH. With the use of
anti-CD59 for RBCs and anti-CD55 and anti-CD59 for granulocytes, flow cytometry is
more sensitive.
 Fluorescent aerolysin testing can heighten the sensitivity of detection.

Treatment:

 Prednisone (2 mg/kg/24 hr) to treat acute hemolytic episodes, and tapered as soon as
the hemolysis abates.
 Prolonged anticoagulation therapy may be of benefit when thromboses occur.
 Because of chronic urinary loss of iron as hemosiderin, iron therapy may be necessary.
 Androgens, antithymocyte globulin, cyclosporine, and growth factors (e.g.,
erythropoietin and granulocyte colony-stimulating factor) have been used to treat marrow
failure.
266
 Bone marrow transplantation is successful in treating some cases.
 Eculizumab, a humanized monoclonal antibody against complement protein C5,
stabilizes hemoglobin levels, reduces the number of transfusions, decreases the rate of
hemolysis, and decreases the risk of thrombosis in treated adults with PNH.
 No role for spleenectomy.

13. Enzyme deficiencies:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent disease

involving enzymes of the hexose monophosphate pathway.

An example of “balanced polymorphism,”

X-linked inheritance

Pathophysiology:

G6PDdeficiency decreased NADPH decreased Glutathione so decreased

protection from oxidative stress

Clinical features:

The degree of hemolysis varies with the inciting agent, amount ingested, and severity of the
enzyme deficiency

2 clinical syndromes, episodic hemolytic anemia, and chronic nonspherocytic hemolytic

anemia.

Most individuals with G6PD deficiency are asymptomatic, with no clinical manifestations of
illness unless triggered by infection, drugs, or ingestion of fava beans.

Typically, hemolysis ensues in about 24-48 hr after a patient has ingested a substance with
oxidant properties.

In severe cases, hemoglobinuria and jaundice result, and the hemoglobin concentration
may fall precipitously.

Drugs:

 Antibacterial: sulphonamides, dapsone, Trimethoprim-sulfamethoxazole, nalidixic acid,

nitrofurantoin
 Antimalarial: primaquine, chloroquine
 Others: vit k analogs, methylene blue, acetyisalicylic acid
 Chemicals: benzene, naphthalene
 Illness: diabetic acidosis, hepatitis, sepsis

267
 Laboratory diagnosis:

 The onset of acute hemolysis results in a precipitous fall in hemoglobin and hematocrit.
 Decreased haptoglobin.
 Free hemoglobin may appear in the plasma and subsequently in the urine.
 Supravital preparations of RBCs reveal precipitated hemoglobin, known as Heinz
bodies.
 Peripheral smear- fragmented polychromatophilic cells representing reticulocytosis

Diagnosis:

 The diagnosis depends on direct or indirect demonstration of reduced G6PD activity in

RBCs.
 Satisfactory screening tests are based on decoloration of methylene blue, reduction of
methemoglobin, or fluorescence of NADPH.
 G6PD variants also can be detected by electrophoretic and molecular analysis.

Prevention and Treatment:

 Identifying at risk ethnic groups and testing G6PD status before starting oxidant drugs
 Blood transfusion at the time of hemolysis
 Adequate fluids at the time of shock due to severe hemolysis.
 Spleenectomy is of little value
 Counselling parents regarding avoiding few drugs.

Pyruvate kinase deficiency:

2- phosphoenolpyruvate Pyruvate

This reaction is mediated by Pyruvate kinase and 1 molecule of ATP is produced in this
reaction.

 Generation of adenosine triphosphate (ATP) within RBCs is impaired, and low levels of ATP,
pyruvate, and the oxidized form of nicotinamide adenine dinucleotide (NAD+) are found.
 The concentration of 2,3-diphosphoglycerate is increased.
 In addition, an unexplained decrease occurs in the sum of the adenine (ATP, adenosine
diphosphate, and adenosine monophosphate) and pyridine (NAD+ and the reduced form of
NAD) nucleotides, further impairing glycolysis.

268
 As a consequence of decreased ATP, RBCs cannot maintain their potassium and water
content.
 The cells become rigid, and their life span is considerably reduced.
 Treatment: Phototherapy and exchange transfusions may be indicated for
hyperbilirubinemia in newborns. Transfusions of packed RBCs are necessary for severe
anemia or for aplastic crises. If the anemia is consistently severe or if frequent transfusions
are required, splenectomy should be performed after the child is 5-6 yr of age.

14. Autoimmune hemolytic anemia:

A number of extrinsic agents and disorders may lead to premature destruction of red blood
cells (RBCs) and there by increased erythropoiesis.

Classification:

AHA DUE TO WARM REACTIVE AUTOANTIBODIES

Primary (idiopathic)
Secondary
Lymphoproliferative disorders
Connective tissue disorders (especially systemic lupus erythematosus)
Nonlymphoid neoplasms (e.g., ovarian tumors)
Chronic inflammatory diseases (e.g., ulcerative colitis)
Immunodeficiency disorders
AHA DUE TO COLD REACTIVE AUTOANTIBODIES
Primary (idiopathic) cold agglutinin disease
Secondary cold agglutinin disease
Lymphoproliferative disorders
Infections (Mycoplasma pneumoniae, Epstein-Barr virus)
Paroxysmal cold hemoglobinuria
Viral syndromes (most common)
Congenital or tertiary syphilis
DRUG-INDUCED IMMUNE HEMOLYTIC ANEMIA
Hapten/drug adsorption (e.g., penicillin)
Ternary (immune) complex (e.g., quinine or quinidine)
True autoantibody induction (e.g., methyldopa)

Warm antibody: Clinical Manifestations occur in either of 2 general clinical

patterns.

Acute form Chronic form

269
 more common less common
2- 12 years Infants and children > 12 years,
Lasts 6- 12 months Months to years
Pallor, jaundice, fever and Pallor, jaundice, fever and hemoglobinuria
hemoglobinuria
Consistent response to Inconsistent response to glucocorticoids
glucocorticoids
Low mortality, full recovery 10 % mortality

Laboratory investigations:

 Profound anemia, leukocytosis

 Positive coombs test
 Smear- spherocytosis and polychromasia (reflecting the reticulocyte response) are
present and look for malignant cells.
 ANA and dsDNA for SLE.
 Mycoplasma IgM for Mycoplasma and EBV VCA Ig M.
 Lymphnode biopsy or FNAC to r/o malignancy.
 USG abdomen for ovarian tumours
 Colonoscopy for ulcerative colitis

Treatment:
 Stop all the offending drugs
 Blood transfusion
 Glucocorticoids
 IVIG
 Monoclonal antibody- rituximab
 Plasmapheresis
 Spleenectomy (with age appropriate prophylactic vaccines to be given).

Fundus changes in blood disorders:

 In primary and secondary anemias, retinopathy in the form of hemorrhages and cotton-wool
patches can occur. Vision can be affected if hemorrhage occurs in the macular area. The
hemorrhages may be light and feathery or dense and preretinal.
 In polycythemia vera, the retinal veins are dark, dilated, and tortuous. Retinal
hemorrhages, retinal edema, and papilledema may be observed.
 In leukemia, the veins are characteristically dilated, with sausage-shaped constrictions;
hemorrhages, particularly white-centered hemorrhages and exudates, are common during the
acute stage.
 In the sickling disorders, fundus changes include vascular tortuosity, arterial and venous
occlusions, salmon patches, refractile deposits, pigmented lesions, arteriolar-venous

270
 anastomoses, and neovascularization (with sea-fan formations), sometimes leading to
vitreous hemorrhage and retinal detachment.
 Patients with HbSC and HbS-β-thalassemia hemoglobinopathies are at a higher risk for
developing retinopathy than are those with HbSS disease.

271
 INFECTIOUS DISEASE

1. Pertussis:
2. Meningococci
3. E.coli
4. Fever without focus
5. Fever of unknown origin
6. Measles
7. Antimicrobial resistance and susceptible testing
8. Febrile neutropenia
9. Enteric fever
10. Hlh
11. Microscopy and stains
12. Molecular diagnostic testing
13. Vaccine development and testing
14. Chemoprophylaxis in malaria
15. Fever
16. Staphylococcus/ TSS/
17. streptococci
18. diphtheria
19. Mycoplasma pneumoniae
20. Ricketssial infections
21. cysticercosis
22. Polio/ AFP and surveillance
23. Fever with rash article ijpp 2003 jan-mar
24. HIV

Pertussis:
B. Pertussis and B. Parapertussis

Epidemiology:
Attack rates are 100% Subclinical rates are 80%.
Neither natural disease nor vaccination provides complete or lifelong immunity against pertussis
re-infection or disease.

Pathogenesis:
Pertussis toxin filamentous hemagglutinin tracheal cytotoxin

Clinical manifestations:

The catarrhal stage (1-2 wk) begins insidiously after an incubation period ranging from 3-12 days
with nondistinctive symptoms of congestion and rhinorrhea variably accompanied by low-grade fever,
sneezing, lacrimation, and conjunctival suffusion.

As initial symptoms wane, coughing marks the onset of the paroxysmal stage (2-6 wk). The cough
begins as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms that are the
hallmark of pertussis. A well-appearing, playful toddler with insignificant provocation suddenly
expresses an anxious aura and may clutch a parent or comforting adult before beginning a
machine-gun burst of uninterrupted cough on a single exhalation, chin and chest held forward,
tongue protruding maximally, eyes bulging and watering, face purple, until coughing ceases
and a loud whoop follows as inspired air traverses the still partially closed airway. Post-tussive
272
emesis is common, and exhaustion is universal.

As the paroxysmal stage fades into the convalescent stage (≥2 wk), the number, severity, and
duration of episodes diminish.

Diagnosis:

1. Clinical features: Pertussis should be suspected in older children whose cough illness is
escalating at 7-10 days and whose coughing episodes are not continuous.

2. CBC: Leukocytosis (15,000-100,000 cells/mm3) due to absolute lymphocytosis is characteristic in

the catarrhal stage. Absolute increase in neutrophils suggests a different diagnosis or secondary
bacterial infection. Eosinophilia is not a manifestation of pertussis.

3. Chest radiographic findings are only mildly abnormal in the majority of hospitalized infants,
showing perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis.
Pneumothorax, pneumomediastinum, and subcutaneous emphysema can be seen occasionally.

4. Blood cultures: All current methods for confirmation of infection due to B. pertussis have
limitations in sensitivity, specificity, or practicality. Isolation of B. pertussis in culture remains the
gold standard for diagnosis.

5. Direct fluorescent antibody (DFA) testing of potential isolates using specific antibody for B.
pertussis and B. parapertussis maximizes recovery rates. Direct testing of nasopharyngeal secretions
by DFA is a rapid test but is reliable only in laboratories with continuous experience.

6. Polymerase chain reaction (PCR) analysis to test nasopharyngeal wash specimens has a sensitivity
similar to that of culture and averts difficulties of isolation, but a standardized validated test is not
yet available universally.

7. A single serum sample showing immunoglobulin G (IgG) antibody to Pertussis toxin elevated >2
standard deviations above the mean of the immunized population indicates recent infection.

TREATMENT: Goals of therapy are to limit the number of paroxysms, to

observe the severity of the cough, to provide assistance when necessary, and to maximize nutrition,
rest, and recovery without sequelae.

Patients with suspected Pertussis are placed in respiratory isolation with the use of masks.

RECOMMENDED ANTIMICROBIAL TREATMENT AND POSTEXPOSURE

PROPHYLAXIS FOR PERTUSSIS, BY AGE GROUP
PRIMARY AGENTS
AGE GROUP
Azithromycin Erythromycin
Not preferred
Erythromycin is substantially associated
Recommended agent. 10 mg/kg/day in a single with infantile hypertrophic pyloric
<1 mo dose for 5 days (only limited safety data stenosis
available) Use if azithromycin is unavailable;
40-50 mg/kg/day in 4 divided doses for
14 days
273
 PRIMARY AGENTS
AGE GROUP
Azithromycin Erythromycin
40-50 mg/kg/day in 4 divided doses for
1-5 mo 10 mg/kg/day in a single dose for 5 days
14 days
10 mg/kg in a single dose on day 1 (maximum
Infants aged ≥6 40-50 mg/kg/day (maximum 2 g/day) in
500 mg), then 5 mg/kg/day (maximum 250 mg)
mo and children 4 divided doses for 14 days
on days 2-5
500 mg in a single dose on day 1 then 250
Adults 2 g/day in 4 divided doses for 14 days
mg/day on days 2-5

Exchange transfusion or leukopheresis, however, has been associated with drop in lymphocyte and
platelet counts, with recovery in several reported cases.

Complications: intubation and mechanical ventilation, pneumonia, seizures, encephalopathy,

pulmonary hypertension, cardiogenic shock and death.

Prevention: Universal immunization of children with pertussis vaccine, beginning in infancy with
periodic reinforcing doses through adolescence and adulthood, is central to the control of Pertussis.

2. Meningococcus:

Neisseria meningitidis (also referred to as meningococcus) lives as a commensal in the nasopharynx.

Meningococci are transmitted by aerosol droplets or through contact with respiratory secretions,
such as through kissing or sharing a drinking glass.

Clinical features: The spectrum of meningococcal disease varies widely, and recognized patterns
include
1. bacteremia without sepsis, 2. meningococcemia without meningitis, 3. meningitis with or without
meningococcemia, and 4. chronic infection.

Acute meningococcemia may initially mimic illnesses caused by viruses or other bacteria. In
fulminant meningococcemia, the disease progresses rapidly over several hours from fever without
other signs to septic shock characterized by prominent petechiae and purpura (purpura fulminans),
hypotension, DIC, acidosis, adrenal hemorrhage (Waterhouse-Friderichsen syndrome), renal
failure, myocardial failure, and coma.

Diagnosis:
1. leukocytopenia or leukocytosis, thrombocytopenia, proteinuria, and hematuria. Elevations of
erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), hypoalbuminemia,
hypocalcemia, and metabolic acidosis, often with increased lactate levels, are common. Patients with
DIC have decreased serum concentrations of prothrombin and fibrinogen and prolonged
coagulation times.
2. Gram staining- from skin lesions
3. Isolation of N. meningitides from blood, csf or synovial fluid.
4. Latex agglutination tests
5. PCR based assays.

Treatment: therapy is generally continued for 5-7 days.

274
TREATMENT OF NEISSERIA MENINGITIDIS INVASIVE INFECTIONS
ROUTE OF
DRUG DOSE
ADMINISTRATION
Penicillin G IM or IV 250,000-300,000 U/kg/day
Ampicillin IM or IV 200-400 mg/kg/day
Cefotaxime IM or IV 200-300 mg/kg/day
Ceftriaxone IM or IV 100 mg/kg/day
Alternative therapy: in the face of life-threatening β -lactam allergy
Chloramphenicol* IV 50-100 mg/kg/day
Ciprofloxacin[†] IV 18-30 mg/kg/day
Meropenem IV 60-120 mg/kg/day

Antibiotic prophylaxis is indicated for household, daycare, and nursery school contacts and for
anyone who has had contact with the patient's oral secretions during the 7 days before onset of illness.
Prophylaxis of contacts should be offered as soon as possible, ideally within 24 hr of diagnosis of
the patient.

ANTIBIOTIC PROPHYLAXIS TO PREVENT NEISSERIA MENINGITIDIS INFECTION

DRUG DOSE DURATION
1. Rifampin: 2 days (4 doses)
Infants <1 mo 5 mg/kg PO every 12 hr
Children >1 mo 10mg/kg PO every 12hr
2. Ceftriaxone:
Children <15 yr 125 mg IM 1 dose
Children >15 yr 250 mg IM 1 dose
3. Ciprofloxacin, persons >18 yr 500 mg PO 1 dose

RECOMMENDATIONS FOR MENINGOCOCCAL VACCINATION

POPULATION
<2 YR 2-10 YR 11-19 YR
GROUP
A single dose of MCV4 or
MenACYW-CRM at age 11-12 yr (at
Not
General population Not recommended preadolescent assessment visit) or at high
recommended
school entry (at approximately age 15 yr). A
booster dose 5 yr later.

Groups at Increased Risk

Two doses of
Anatomic or Two doses of MCV4-DT or
Not usually MCV4-DT, separated by
immune MenACYW-CRM, separated by 8 wk with
recommended 8 wk with a booster dose
compromised a booster dose at 5 yr
3-5 yr later

275
 POPULATION
<2 YR 2-10 YR 11-19 YR
GROUP
A single dose of A single dose of MCV4-DT or
Not usually
Increased exposure MCV4-DT with a MenACYW-CRM with a booster dose 5 yr
recommended
booster dose 3-5 yr later later

3. E. coli:

CLINICAL CHARACTERISTICS, PATHOGENESIS, AND DIAGNOSIS OF

DIARRHEAGENIC ESCHERICHIA COLI
CHARACTERISTICS OF
POPULATIONS AT DIARRHEA
PATHOGEN
RISK
Watery Bloody Toxins
>1 yr old and travellers Heat-labile enterotoxin (LT)
ETEC +++ —
Heat-stable enterotoxin (ST)
EIEC >1 yr old + ++
<2 yr old, especially
EPEC +++ — EspF, Map, EAST1
infants <6 mo
Shiga toxins (Stx1, Stx2, and
STEC 6 mo–10 yr and the elderly + +++
variants of Stx2)
EAEC <2 yr old and travellers +++ — ShET1, EAST1, Pet
DAEC >1 yr old and travellers ++ — Not fully defined
TAP – diarrhea IS—bloody diarrhea
Pathogenesis:

ETEC cause few or no structural alterations in the gut mucosa. Diarrhea is caused by colonization of
the small intestine and subsequent elaboration of enterotoxins. ETEC strains secrete a heat-labile
enterotoxin (LT) and/or a heat-stable enterotoxin (ST). LT, a large molecule consisting of five
receptor-binding subunits and one enzymatically active subunit, is structurally, functionally, and
immunologically related to cholera toxin produced by Vibrio cholerae. LT stimulates adenylate
cyclase, resulting in increased cyclic adenosine monophosphate (cAMP). ST is a small molecule not
related to LT or cholera toxin. ST stimulates guanylate cyclase, resulting in increased cyclic
guanosine monophosphate (cGMP).

EIEC cause colonic lesions with ulcerations, hemorrhage, mucosal and submucosal edema, and
infiltration by polymorphonuclear leukocytes. EIEC strains behave like Shigella in their capacity to
invade gut epithelium and produce a dysentery-like illness. The invasive process involves initial
entry into cells, intracellular multiplication, intracellular and intercellular spread, and host-cell
death.

EPEC are a major cause of acute and persistent diarrhea in children <2 yr. In developed countries,
EPEC are responsible for occasional outbreaks in daycare centers and pediatric wards. Profuse
watery, nonbloody diarrhea with mucus, vomiting, and low-grade fever are common symptoms.
Studies have shown that breast-feeding is protective against diarrhea due to EPEC. EPEC
colonization causes blunting of villi, inflammatory changes, and sloughing of superficial mucosal
cells; these lesions can be found from the duodenum through the colon. EPEC induce a
characteristic attaching and effacing (A/E) histopathologic lesion, which is defined by the
276
intimate attachment of bacteria to the epithelial surface and effacement of host cell microvilli.

EAEC are associated with acute and persistent pediatric diarrhea in developing countries, most
prominently in children <2 yr of age. EAEC are also etiologic agents in AIDS-associated chronic
diarrhea and acute traveler's diarrhea.

The proposed model of pathogenesis of EAEC involves three phases: adherence to the intestinal
mucosa by way of the aggregative adherence fimbriae or related adhesins; enhanced production of
mucus; and production of toxins and inflammation that results in damage of the mucosa and
intestinal secretion. EAEC form a characteristic biofilm on the intestinal mucosa and induce
shortening of the villi, hemorrhagic necrosis, and inflammatory responses.

4. Fever without localising signs:

Fever without a focus refers to a rectal temperature of 38oC or higher as the sole presenting feature.
The terms “fever without localizing signs” and “fever of unknown origin” (FUO) are subcategories
of fever without a focus.

The etiology and evaluation of fever without localizing signs depends on the age of the child.
Traditionally, 3 age groups are considered: neonates or infants to 1 mo of age, infants >1 mo to 3 mo
of age, and children >3 mo to 3 yr of age.

LOW RISK CRITERIA IN 1-3 MONTHS OLD WITH FEVER:

ROCHESTER CRITERIA
Infants are at low risk if they appear well, have a normal physical examination, and laboratory findings are as
follows:
• CBC: 5,000-15,000 WBC/mm3; absolute band count ≤1500/mm3
• Urine: <10 WBC/HPF
• Stool: <5 WBC/HPF if diarrhea

Other criteria/ protocol used are – BOSTON criteria, PHILADELPHIA protocol and PITTSBURGH
guidelines

MANAGEMENT OF FEVER WITHOUT LOCALIZING SIGNS

GROUP MANAGEMENT
Any toxic-appearing
child 0-36 mo and Hospitalize, broad cultures plus other tests,* parenteral antibiotics
temperature ≥38?C
Child <1 mo and
Hospitalize, broad cultures plus other tests,* parenteral antibiotics
temperature ≥38?C
Two-step process
1 Determine risk based on history, physical examination, and laboratory
Child 1-3 mo and studies.
temperature ≥38?C Low risk:
• Uncomplicated medical history
• Normal physical examinat
277
 GROUP MANAGEMENT

on
• Normal laboratory studies
• Urine: negative leukocyte esterase, nitrite and <10 WBC/HPF
• Peripheral blood: 5,000-15,000 WBC/mm3; <1,500 bands or
band : total neutrophil ratio <0.2
• Stool studies if diarrhea (no RBC and <5 WBC/HPF)
• CSF cell count (<8 WBC/mm3) and negative Gram stain
• Chest radiograph without infiltrate
2 If child fulfills all low-risk criteria, administer no antibiotics, ensure
follow-up in 24 hr and access to emergency care if child deteriorates. Daily
follow-up should occur until blood, urine, and CSF cultures are final. If any
cultures are positive, child returns for further evaluation and treatment. If
child does not fulfill all low-risk criteria, hospitalize and administer
parenteral antibiotics until all cultures are final and definitive diagnosis
determined and treated.
Child 3-36 mo and Reassurance that diagnosis is likely self-limiting viral infection, but advise return with
temperature 38-39?C persistence of fever, temperatures >39?C, and new signs and symptoms

*
Other tests may include chest radiograph, stool studies, herpes simplex polymerase chain reaction.

5. Fever of unknown origin:

Fever without a focus refers to a rectal temperature of 38?C or higher as the sole presenting feature.
The terms “fever without localizing signs” and “fever of unknown origin” (FUO) are subcategories
of fever without a focus.

The classification of FUO is best reserved for children with fever documented by a health care
provider and for which the cause could not be identified after 3 wk of evaluation as an outpatient or
after 1 wk of evaluation in the hospital.

FOUR SUBTYPES OF FEVER OF UNKNOWN ORIGIN

HEALTH
IMMUNE-DEFICIEN
FEATURE CLASSIC FUO CARE–ASSOC HIV-RELATED FUO
T FUO
IATED FUO
≥38.0?C, >1 wk, ≥38.0?C, >3 wk for
≥38.0?C, >1 wk,
>38.0?C, >3 wk, >2 visits not present or outpatients, >1 wk for
Definition negative cultures after
or 1 wk in hospital incubating on inpatients, HIV infection
48 hr
admission confirmed
Patient Community, clinic, or Acute care Hospital or clinic Community, clinic, or
278
 HEALTH
IMMUNE-DEFICIEN
FEATURE CLASSIC FUO CARE–ASSOC HIV-RELATED FUO
T FUO
IATED FUO
location hospital hospital hospital
HIV (primary infection),
typical and atypical
Health
mycobacteria, CMV,
Cancer, infections, care–associated Majority due to
lymphomas,
Leading inflammatory conditions, infections, infections, but cause
toxoplasmosis,
causes undiagnosed, habitual postoperative documented in only
cryptococcosis, immune
hyperthermia complications, 40-60%
reconstitution
drug fever
inflammatory syndrome
(IRIS)
Travel, contacts, animal Operations and
Stage of chemotherapy,
and insect exposure, procedures,
drugs administered, Drugs, exposures, risk
History medications, devices,
underlying factors, travel, contacts,
emphasis immunizations, family anatomic
immunosuppressive stage of HIV infection
history, cardiac valve considerations,
disorder
disorder drug treatment
Fundi, oropharynx,
temporal artery, abdomen,
lymph nodes, spleen, Wounds, drains, Mouth, sinuses, skin,
Examination Skin folds, IV sites,
joints, skin, nails, devices, sinuses, lymph nodes, eyes,
emphasis lungs, perianal area
genitalia, rectum or urine lungs, perianal area
prostate, lower limb deep
veins
Blood and lymphocyte
count; serologic tests;
CXR; stool
Imaging, biopsies,
Investigatio Imaging, examination; biopsies of
sedimentation rate, skin CXR, bacterial cultures
n emphasis bacterial cultures lung, bone marrow, and
tests
liver for cultures and
cytologic tests; brain
imaging
Observation, outpatient Antiviral and
temperature chart, antimicrobial protocols,
Managemen Depends on Antimicrobial treatment
investigations, avoidance vaccines, revision of
t situation protocols
of empirical drug treatment regimens,
treatments good nutrition
Time course Months Weeks Days Weeks to months

Etiology:
Abscess Bacteria Fungal Viral
Abdominal, dental, Actinomyces, bartonella Blastomycosis, ricketssial Cmv, hiv, ebv, hepatitis
perinephric , subphrenic Brucellosis, tuberculosis psittacosis Q fever

279
Localised infection Parasitic Rheumatological Hypersensitivity
Cholangitis, osteomyelitis Amoebiasis, giardiasis Jra, sle, rheumatic fever Serum sickness
Sinusitis, mastoiditis Malaria, toxoplasmosis behcets Drug fever

Neoplasm Granulomatous Family and hereditary Miscellaneous

Hodgkin, leukemia, Sarcoidosis, crohn disease Factitious, cyclical
neuroblastoma disease Familial dysautonomia, neutropenia, periodic
Familial Mediterranean fevers, Kawasaki fever
fever

Diagnosis:
History physical examination lab investigations
Cbc esr crp thyroid profile
Travel history Sinus tenderness Tooth ache Cultures – urine, blood
Contact with animals, Temporal artery pulsations Serological tests
birds, fundus- Roth spots, petechial X ray chest, mastoids, sinuses
Drug ingestion Tuberculin skin testing
h/o pica Skin- splinter hemorhages, Fundus examination
genetic back ground subcutaneous nodules, clubbing ECHO
immunisation Abdomen- Lymphadenopathy, Rectal examination
contact history with Tb splenomegaly Bone marrow examination
patient Radionuclide scans
Cvs- murmur Ct/ mri
Thyroid – enlargement, tendernes Scopies- broncho. Lapro, mediastino, GI
Perirectal and prostatic tenderness endo

6. Measles:
Measles virus is a single-stranded, lipid-enveloped RNA virus in the family Paramyxoviridae and
genus Morbillivirus.

Transimission: The portal of entry of measles virus is through the respiratory tract or
conjunctivae following contact with large droplets or small-droplet aerosols in which the virus is
suspended. Patients are infectious from 3 days before to up to 4-6 days after the onset of rash.

Pathology: Measles infection causes necrosis of the respiratory tract epithelium and an
accompanying lymphocytic infiltrate. Measles produces a small vessel vasculitis on the skin and on
the oral mucous membranes. Fusion of infected cells results in multinucleated giant cells, the
Warthin-Finkeldey giant cells that are pathognomonic for measles.

Clinical manifestations: After an incubation period of 8-12 days, the prodromal phase begins
with a mild fever followed by the onset of conjunctivitis with photophobia, coryza, a prominent
cough, and increasing fever. Koplik spots represent the enanthem and are the pathognomonic sign
of measles, appearing 1 to 4 days prior to the onset of the rash. The rash begins on the forehead
(around the hairline), behind the ears, and on the upper neck as a red maculopapular eruption. It
then spreads downward.

Atypical measles: Patients had onset of high fever and

headache followed by the appearance of a maculopapular rash on the extremities that become
petechial and purpuric and progressed in a centripetal direction. The illness was frequently
280
complicated by pneumonia and pleural effusions.

Diagnosis: IgM antibody appears 1-2 days

after the onset of the rash and remains detectable for about 1 month. Viral isolation from blood, urine,
or respiratory secretions can be accomplished by culture.

Treatment: Management of measles is

supportive. Antiviral therapy is not effective in the treatment of measles in otherwise normal patients.
Maintenance of hydration, oxygenation, and comfort are goals of therapy. Antipyretics for comfort
and fever control are useful. Respiratory failure due to croup or pneumonia may require ventilatory
support. Prophylactic antimicrobial therapy to prevent bacterial infection is not indicated.

Complications:

Respiratory:

1. Pneumonia is the most common cause of death in measles. Giant cell pneumonia ultimately
leading to bronchiolitis obliterans.

2. Croup, tracheitis, and bronchiolitis are common complications in infants and toddlers with
measles.

3. Activation of pulmonary tuberculosis.

Ent:

1. Acute otitis media is the most common complication of measles.

2. retropharyngeal abscess

3. sinusitis and mastoiditis

Cns:

1. febrile seizure

2. Encephalitis

3. sspe

Cvs- myocarditis

Black or hemorrhagic measles – severe form rarely seen now

7. antimicrobial resistance:

Antimicrobial resistance occurs through many modifications of the bacterial genome.

Mechanisms include

281
a. enzyme inactivation of the antibiotic,

b. decreased cell membrane permeability to intracellularly active antibiotics,

c. efflux of antibiotics out of the bacteria,

d. protection or alteration of the antibiotic target site,

e. excessive production of the target site, or

f. bypassing the antimicrobial site of action.

ESBL producing organisms:

Β lactamase are enzymes produced by some bacteria and responsible for their resistance to β lactam
abx like penicillin, cephalosporin and carbapenam. The lactamase enzyme break opens the β lactam
ring there by deactivating the antibacterial property of abx.

MECHANISMS OF RESISTANCE TO β-LACTAM ANTIBIOTICS

Alter the target site Destroy the β lactam antibiotic Decrease the conc of β
(PBP, penicillin binding lactam abx inside the cell
protein)
Decrease the affinity of 1. increase production of β lactamase Restrict the entry(loss of
PBP for β lactam abx porins)
Acquire more efficient promoter
Modify existing Pump it out(efflux
PBP Deregulate control of β lactamase production mechanisms)

Import new PBP 2. modify the structure of resident β lactamase

(MRSA)
3. import new β lactamase

Mechanism of transmission of resistance in MRSA:

1. Transformation: transfer of free DNA from dead bacteria.

2. Transduction: Transfer of resistant gene by viral infection of the bacterium.

3. Conjugation: resistant gene in the donor plasmid.

Treatment: see below in staph que no 17.

Phage therapy and maggot therapy are newer techniques.

282
Treatment of carriers: mupirocin l/a x 5 days. Chlorhexidine body wash x 5 days.

ACQUIRED RESISTANCE MECHANISMS AMONG ENTEROCOCCUS

ANTIMICROBIAL MECHANISM
Ampicillin, penicillin (high level) Mutation of PBP-5
Aminoglycoside (high level) Enzyme modification
Quinolones DNA gyrase mutation
Chloramphenicol Efflux pump
Glycopeptide Altered cell wall binding
Quinupristin/dalfopristin Ribosomal modification, efflux pump
Linezolid Point mutation
Daptomycin Unknown

Antimicrobial Susceptibility Testing:

Antimicrobial susceptibility tests are generally performed on all organisms of clinical significance
except for a few that have predictable antimicrobial susceptibility patterns (group A streptococci
remain universally susceptible to penicillin).

1. The most common technique is the agar disk diffusion method (Bauer-Kirby method), in which
a standardized inoculum of the organism is seeded onto an agar plate. Antibiotic-impregnated filter
paper disks are then placed on the agar surface. After 18-24 hr of incubation, the zone of inhibition
of bacterial growth around each disk is measured and compared with nationally determined standards
for susceptibility or resistance.

2. The other widely used technique for susceptibility testing is dilution testing. A standard
concentration of a microorganism is inoculated into serially diluted concentrations of antibiotic, and
the minimum inhibitory concentration (MIC) in ?g/mL, the lowest concentration of antibiotic
required to inhibit growth of the microorganism, is determined. Dilution testing also permits
determination of the minimum bactericidal concentration (MBC), the lowest concentration of
antibiotic required to kill the organism.

3. The E-test is used to measure the MIC of individual antibiotics on an agar plate. Major
advantages of the E-test are reliable interpretation, reproducibility, and applicability to organisms
that require special media or growth conditions, including anaerobic bacteria.

Antimicrobial susceptibility patterns are rapidly changing as microbes evolve new resistance
mechanisms. Recommendations for performance standards for antimicrobial susceptibility tests and
their interpretation are regularly updated by the Clinical and Laboratory Standards Institute
(CLSI).

8. Febrile neutropenia:

Patients are at particular risk for bacterial infections if the absolute neutrophil count decreases to
<500 cells/mm3. The lack of neutrophils can lead to a loss of inflammatory response, and fever may
be the only manifestation of infection.

283
Etiology:

APPROXIMATE
CAUSES
FREQUENCY (%)

Fungal infections susceptible to empirical therapy 40

Fungal infections resistant to empirical antifungal therapy 5
Bacterial infections (with cryptic foci, biofilms, and resistant organisms) 10
Toxoplasma gondii, mycobacteria, or fastidious pathogens (Legionella,
5
Mycoplasma, Chlamydophila pneumoniae, Bartonella)
Viral infections (herpesviruses, cytomegalovirus, Epstein-Barr virus, human
herpesvirus 6, varicella-zoster virus, herpes simplex virus, parainfluenza virus, 5
respiratory syncytial virus, influenza viruses)
Graft vs host disease after hematopoietic stem cell transplantation 10
Undefined (e.g., drug fever, toxic effects of chemotherapy, antitumor responses,
25
undefined pathogens)

Investigations:

Because patients with fever and neutropenia might only have subtle signs and symptoms of infection,
the presence of fever warrants a

1. Thorough physical examination with careful attention to the oropharynx, lungs, perineum and anus,
skin, nail beds, and intravascular catheter insertion sites.

2. Complete blood cell count, serum creatinine, blood urea nitrogen, and serum transaminases

3. Blood cultures should be taken from each port of any central venous catheter.

4. Nasal aspirate for viruses in patients with upper respiratory findings;

5. Stool for rotavirus in the winter months and for Clostridium difficile toxin in patients with
diarrhea.

6. Urinalysis and culture

7. Biopsy and culture of Cutaneous lesions.

8. Chest radiographs , Sinus films should be obtained if rhinorrhea is prolonged.

9. Abdominal CT scans

10. Biopsies for cytology, Gram stain, and culture should be considered if abnormalities are found
during endoscopic procedures or if lung nodules are identified radiographically.

284
TREATMENT:

Reassessed after 3 days

afebrile, well febrile, reassessed

anc > 100 clinically well

abx changed to cont abx iv for
oral regimen 7 days

anc< 100 1. still febrile add

antifungal
cont iv abx for 2. no complications
5-7 days anc> 500 stop abx

285
9. EXTRAINTESTINAL INFECTIOUS COMPLICATIONS OF TYPHOID FEVER

ORGAN SYSTEM
COMPLICATIONS
INVOLVED
Encephalopathy, cerebral edema, subdural empyema, cerebral abscess, meningitis,
Central nervous
ventriculitis, transient parkinsonism, motor neuron disorders, ataxia, seizures,
system
Guillain-Barre syndrome, psychosis
Cardiovascular
Endocarditis, myocarditis, pericarditis, arteritis, congestive heart failure
system
Pulmonary system Pneumonia, empyema, bronchopleural fistula
Bone and joint Osteomyelitis, septic arthritis
Hepatobiliary system Cholecystitis, hepatitis, hepatic abscesses, splenic abscess, peritonitis, paralytic ileus
Urinary tract infection, renal abscess, pelvic infections, testicular abscess, prostatitis,
Genitourinary system
epididymitis
Soft tissue infections Psoas abscess, gluteal abscess, cutaneous vasculitis
Hematologic Hemophagocytosis syndrome

`TREATMENT OF TYPHOID FEVER IN CHILDREN

OPTIMAL THERAPY ALTERNATIVE EFFECTIVE DRUGS
SUSCEPTIBILITY Daily Dose Daily Dose
Antibiotic Days Antibiotic Days
(mg/kg/day) (mg/kg/day)
UNCOMPLICATED TYPHOID FEVER
Fluoroquinolone, e.g.,
14-2
Chloramphenicol 50-75 ofloxacin or 15 5-7*
Fully sensitive 1
ciprofloxacin
Amoxicillin 75-100 14
Fluoroquinolone 15 5-7 Azithromycin 20 7
Multidrug-resistant or
Cefixime 15-20 7-14 Cefixime 15-20 7-14
Azithromycin 8-10 7 Cefixime 20 7-14
Quinolone-resistant[† or
]
10-1
Ceftriaxone 75
4
SEVERE TYPHOID FEVER
Fluoroquinolone, e.g.,
10-1
Ampicillin 100 14 ofloxacin or 15
4
ciprofloxacin
Fully sensitive
or
10-1
Ceftriaxone 60-75
4
Multidrug-resistant Fluoroquinolone 15 10-1 Ceftriaxone 60 10-1
286
 OPTIMAL THERAPY ALTERNATIVE EFFECTIVE DRUGS
SUSCEPTIBILITY Daily Dose Daily Dose
Antibiotic Days Antibiotic Days
(mg/kg/day) (mg/kg/day)
4 4
or
10-1
Cefotaxime 80
4
10-1
Ceftriaxone 60-75 Azithromycin 20 7
Quinolone-resistant 4
Gatifloxacin 10 7

10.
CLASSIFICATION OF THE CHILDHOOD HISTIOCYTOSES
CELLULAR CHARACTERISTICS OF
CLASS DISEASE TREATMENT
LESIONS
Local therapy for isolated
Langerhans cell Langerhans cells (CD1a-positive,
I lesions; chemotherapy for
histiocytosis CD207-positive) with Birbeck granules
disseminated disease
Familial
erythrophagocytic Morphologically normal reactive
lymphohistiocytosis macrophages with prominent Chemotherapy; allogeneic
II
Infection-associated erythrophagocytosis, and CD8-positive T bone marrow transplantation
hemophagocytic cells
syndrome
Neoplastic proliferation of cells with Antineoplastic
Malignant histiocytosis characteristics of monocytes/macrophages chemotherapy, including
III or their precursors anthracyclines
Acute monocytic Antineoplastic
M5 by FAB classification
leukemia chemotherapy

INFECTIONS ASSOCIATED WITH HEMOPHAGOCYTIC SYNDROME

VIRAL
Adenovirus
Cytomegalovirus
Dengue virus
Epstein-Barr virus
Herpes simplex virus (HSV1, HSV2, HHV6, HHV8)
Human immunodeficiency virus
Parvovirus B19
287
 Varicella-zoster virus
Hepatitis viruses
BACTERIAL
Babesia microti
Brucella abortus
Enteric gram-negative rods
Haemophilus influenzae
Mycoplasma pneumoniae
Staphylococcus aureus
Streptococcus pneumoniae
FUNGAL
Candida albicans
Cryptococcus neoformans
Histoplasma capsulatum
MYCOBACTERIAL
Mycobacterium tuberculosis
RICKETTSIAL
Coxiella brunetii
PARASITIC
Leishmania donovani

DIAGNOSTIC GUIDELINES FOR HLH

The diagnosis of HLH is established by fulfilling 1 or 2 of the following criteria:
1 A molecular diagnosis consistent with HLH (e.g., PRF mutations, SAP mutations)
OR
2 Having 5 out of 8 of the following:
a Fever
b Splenomegaly
c Cytopenia (affecting ≥2 cell lin
ages; hemoglobin ≤9 g/dL (or ≤10 g/dL for infants <4 wk of age, platelets <100,000/?L,
neutrophils <1,000/?L)
d Hypertriglyceridemia (≥265 mg/dL) and/or hypofibrinogenemia (≤150 mg/dL)
e Hemophagocytosis in the bone marrow, spleen, or lymph nodes without evidence of malignancy
f Low or absent NK cell cytotoxicity
g Hyperferritinemia (≥500 ng/mL)
h Elevated soluble CD25 (IL-2Rα chain; ≥2,400 U/mL)

When FHLH (gene mutations in perforin or Munc 13-4 proteins) is diagnosed or suspected and when
an infection cannot be documented, therapy currently includes etoposide, corticosteroids, and
intrathecal methotrexate. It should be stressed that pancytopenia is not a contraindication to cytotoxic
therapy in FHLH. Some recommend antithymocyte globulin and cyclosporine for maintenance
288
therapy. Nevertheless, even with chemotherapy, FHLH remains ultimately fatal, often after a relapse
of the disease. Allogeneic stem cell transplantation is effective in curing approximately 60% of
patients with FHLH.

11. Microscopy and stains:

The Gram stain remains an extremely useful diagnostic technique because it is a rapid, inexpensive
method for demonstrating the presence of bacteria and fungi, as well as inflammatory cells. A
preliminary assessment of the etiologic agent can be made by noting the morphology (cocci vs rods)
and the color (gram-positive is blue, gram-negative is red) of the microorganisms.

STAINS USED FOR MICROSCOPIC EXAMINATION

TYPE OF STAIN CLINICAL USE
Gram stain Stains bacteria, fungi, leukocytes, and epithelial cells
A 10% solution dissolves cellular and organic debris and facilitates detection
Potassium hydroxide (KOH)
of fungal elements
Nonspecific fluorochrome that binds to cellulose and chitin in fungal cell
Calcofluor white stain
walls
Acid-fast stains, using basic carbolfuchsin, followed by acid-alcohol
Ziehl-Neelsen and Kinyoun decolorization and methylene blue counterstaining
stains Acid-fast organisms (e.g., Mycobacterium, Cryptosporidium, and
Cyclospora) resist decolorization and stain pink
At acid pH, bacteria and fungi stain orange, and background cellular
Acridine orange stain material stains green

Acid-fast stain using fluorochromes that bind to mycolic acid in

Auramine-rhodamine stain
mycobacterial cell walls and resist acid-alcohol decolorization
Detects Cryptococcus neoformans, an encapsulated yeast, by excluding ink
India ink stain
particles from the polysaccharide capsule
Methenamine silver stain
Grocott-Gomori silver stain Stains fungal elements and Pneumocystis cysts in tissues
toluidine blue stain
Added to wet preparations of fecal specimens for ova and parasites to
Lugol iodine stain
enhance contrast of the internal structures (nuclei, glycogen vacuoles)
Primarily for detecting blood parasites (Plasmodium, Babesia, and
Wright and Giemsa stains
Leishmania) and fungi in tissues (yeasts, Histoplasma)
Trichrome stain Stains stool specimens for identification of protozoa
289
 TYPE OF STAIN CLINICAL USE
Used for direct detection of a variety of organisms in clinical specimens by
Direct fluorescent-antibody
using specific fluorescein-labeled antibodies (e.g., Bordetella pertussis,
stain
Legionella, Chlamydia trachomatis, Pneumocystis jiroveci, many viruses)

12. Molecular Diagnostic Techniques:

Molecular diagnostic techniques are most useful for detecting and identifying pathogens for which
culture and serologic tests are difficult, slow, or not available.

Two of the widely used techniques in clinical microbiology are DNA probes for direct detection and
nucleic acid amplification using polymerase chain reaction (PCR). Microbiologic applications of
techniques such as miniaturized DNA chip technology and microarrays are also being developed.

1. DNA probes detect or identify organisms by hybridization of the probe to complementary

sequences in DNA or ribosomal RNA. Probes for mycobacterial species can rapidly distinguish M.
tuberculosis from M. avium complex growing in broth cultures. Commercially available probes for
direct detection of pathogen from specimens include combination probes for detection of C.
trachomatis and gonococci from genitourinary specimens.

2. The high sensitivity and specificity of PCR amplification make this the method of choice for
direct detection of microbial nucleic acid from clinical specimens. The PCR method is based on the
ability of thermostable DNA or RNA polymerase to copy targeted gene sequences using
complementary nucleotides as primers to amplify a conserved region of the genome. PCR tests are
available using commercial reagents for many respiratory viruses, HIV, hepatitis B and C viruses,
CMV, and C. trachomatis. Traditional PCR methods are technically complex and labor intensive.
False-positive reactions are a major problem.

3. Technical improvements in thermocycler equipment (quantitative real-time PCR) using sealed

tubes incorporating fluorescent probes have significantly reduced processing times and
postamplification contamination. Real-time PCR has been used for rapid detection of many
pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant
enterococcal colonization, and respiratory viruses.

13. Vaccine development and testing:

290
Instead of FDA write NAB (national advisory board).
Instead of CDC write NAB/ DCGI (drugs controller general of INDIA)
Instead of AAP board write IAP board members
MMWR morbidity and mortality weekly report

Phases in vaccine development:

Phase 1 trials: are conducted on small number of healthy human volunteers for assessing vaccine
immunogenicity and safety.

Phase 2: are conducted with a similar objective in larger number of subjects.

Phase 3: are randomised controlled trials in large number of subjects for assessing vaccine efficacy
and safety

14. CHEMOPROPHYLAXIS OF MALARIA FOR CHILDREN

DRUG DOSAGE (ORAL)
CHLOROQUINE-RESISTANT AREA
<10 kg: 4.6 mg base (5 mg salt)/kg/wk
10-19 kg: ¼ tab/wk
Mefloquine*,[†]
20-30 kg: ½ tab/wk
31-45 kg: ¾ tab/wk
291
 DRUG DOSAGE (ORAL)
>45 kg: 1 tab/wk (228 mg base)
Doxycyline[‡] 2 mg/kg daily (max 100 mg)
Pediatric tabs: 62.5 mg atovaquone/25 mg proguanil
Adult tabs: 250 mg proguanil/100 mg proguanil
5-8 kg: ½ pediatric tab once daily (off-label)
9-10 kg: ¾ pediatric tab once daily (off-label)
Atovaquone-proguanil[?] (Malarone)
11-20 kg: 1 pediatric tab once daily
21-30 kg: 2 pediatric tabs once daily
31-40 kg: 3 pediatric tabs once daily
>40 kg: 1 adult tab once daily
CHLOROQUINE-SENSITIVE AREA
Chloroquine phosphate 5 mg base/kg/wk (max 300 mg base)

On leaving an area endemic for P. vivax or P. ovale after a prolonged visit (usually >3 mo), travelers
might require terminal prophylaxis with primaquine (0.5 mg/kg base) daily, for 14 days) to
eliminate extraerythrocytic forms of P. vivax and P. ovale and prevent relapses. Screening for
glucose-6-phosphate dehydrogenase (G6PD) deficiency is mandatory before primaquine treatment,
because primaquine can cause severe hemolysis in G6PD-deficient persons and is therefore
contraindicated in them.
*
Chloroquine and mefloquine should be started 1-2 wk before departure and continued for 4 wk after last
exposure.
‡
Doxycycline should be started 1-2 days before departure and continued for 4 wk after last exposure. Do not
use in children <8 yr of age or in pregnant women.
?
Atovaquone-proguanil should be started 1-2 days before departure and continued for 7 days after last
exposure. Not recommended in pregnant women, children <5 kg, and women breastfeeding infants <5 kg.

15. Fever:

Definition: Fever is defined as a rectal temperature ≥38oC, and a value >40oC is called
hyperpyrexia. Body temperature fluctuates in a defined normal range (36.6oC-37.9oC rectally), so that
the highest point is reached in early evening and the lowest point is reached in the morning.

Thermoregulatory mechanisms: Body temperature is regulated by thermosensitive neurons

located in the preoptic or anterior hypothalamus that respond to changes in blood temperature as
well as cold and warm receptors located in skin and muscles. Thermoregulatory responses include (a)
redirecting blood to or from cutaneous vascular beds, (b) increased or decreased sweating, (c)
regulation of extracellular fluid volume via arginine vasopressin, and (d) behavioral responses, such
as seeking a warmer or cooler environmental temperature.

Pathogenesis:

Three different mechanisms can produce fever: pyrogens, heat production exceeding loss, and
defective heat loss.

1. The first mechanism involves endogeneous and exogenous pyrogens that raise the
292
 hypothalamic temperature set point. Endogenous pyrogens include the cytokines interleukin 1
(IL)-1 and IL-6, tumor necrosis factor-α (TNF-α), and interferon (IFN)-β and IFN-γ.
Microbes, microbial toxins, or drugs (vancomycin, amphotericin B, and allopurinol) are the
most common exogenous pyrogens and stimulate macrophages and other cells to produce
endogenous pyrogens.
2. Heat production exceeding heat loss is the second mechanism that leads to fever, with
examples including salicylate poisoning and malignant hyperthermia.
3. Defective heat loss is the third mechanism of fever genesis, for example, in children with
ectodermal dysplasia or victims of severe heat exposure.

Etiology: The causes of fever can be organized into 4 main categories: infectious,
inflammatory, neoplastic, and miscellaneous.

Types:

1. Biphasic fever indicates a single illness with 2 distinct periods (camelback fever pattern);
poliomyelitis is the classic example. A biphasic course is also characteristic of other enteroviral
infections, leptospirosis, dengue fever, yellow fever, Colorado tick fever, spirillary rat-bite fever
(Spirillum minus), and the African hemorrhagic fevers (Marburg, Ebola, and Lassa fevers).

2. Relapsing fever: Relapsing fever is characterized by febrile periods that are separated by
intervals of normal temperature; tertian fever occurs on the first and third days (malaria caused by
Plasmodium vivax), and quartan fever occurs on the first and fourth days (malaria caused by
Plasmodium malariae). The double quotidian fever (or fever that peaks twice in 24 hours) is
classically associated with inflammatory arthritis.

Fever prone to relapse:

Infectious Non infectious Periodic fever

syndromes
1. Relapsing fever 1. Behcet disease
2. Trench fever 2. Crohn disease 1. Familial Mediterranean
3. Q fever 3. Systemic lupus erythematosus fever
4. Typhoid fever 4. Weber Christian disease 2. Cyclic neutropenia
5. Dengue fever (panniculitis) 3. Periodic fever, apthous
6. Leptospirosis 5. sweet syndrome stomatitis, pharyngitis,
7. Malaria adenopathy (PFAPA)
8. Acute rheumatic fever 4. Hyper Ig D syndrome
9. EBV infection 5. Hibernian fever (tumor
necrosis factor super family
Ig A- associated periodic
syndrome [TRAPS])
6. Muckle- wells syndrome

3. Factitious fever, or self-induced fever, may be caused by intentional manipulation of the

thermometer or injection of pyrogenic material.

293
 EVALUATION OF ACUTE FEVER
Thorough history: onset, other symptoms, exposures (daycare, school, family, pets, playmates), travel,
medications, other underlying disorders, immunizations
Physical examination: complete, with focus on localizing symptoms
Laboratory studies on a case-by-case basis:
• Rapid antigen testing
• Nasopharyngeal: respiratory viruses
• Throat: group A streptococcus
• Stool: rotavirus
• Throat culture
• Blood: complete blood count, blood culture, C-reactive protein, sedimentation rate
• Urine: urinalysis, culture
• Stool: hemocult, culture
• Cerebrospinal fluid: cell count, glucose, protein, Gram stain, culture
Chest radiograph or other imaging studies on a case-by-case basis

Treatment:

1. Encouraging good hydration is the first step to replace fluids that are lost related to the
increased metabolic demands of fever.
2. Physical measures such as tepid baths and cooling blankets are not considered effective to
reduce fever.
3. Acetaminophen at a dose of 10-15 mg/kg/dose every 4 hr and ibuprofen in children older than
6 months at a dose of 5-10 mg/kg/dose every 8 hours are the most commonly employed
antipyretics.
4. Fever due to specific underlying etiologies resolves when the condition is properly treated.
Examples include administration of intravenous immunoglobulin to treat Kawasaki disease or
the administration of antibiotics to treat bacterial infections.

16. Staphylococcus aureus:

Enzymes/ toxins: Coagulase, protein A, penicillinase or β lactamase, exfoliotoxins A and

B, enterotoxins A, B, C, D and E and toxic short syndrome toxin- 1.

Clinical manifestations:

1. New born
2. Skin- impetigo contagiosa, ecthyma, bullous impetigo, folliculitis, hydradenitis, furuncles,
carbuncles, staphylococcal scalded skin syndrome, and staphylococcal scarlet fever.
3. Respiratory tract: otitis media, sinusitis, tracheitis, pneumonia and necrotising pneumonia
(that may be associated with development of empyema, pneumatoceles, pyopneumothorax,
and bronchopleural fistulas.).
294
 4. Sepsis
5. Muscle- pyomyositis
6. Bones and joints- osteomyelitis, suppurative arthritis
7. CNS- meningitis
8. Heart- endocarditis, myocardial abscess, pericarditis
9. Renal- perinephric abscess
10. GIT- food poisoning
11. TSS

PARENTERAL ANTIMICROBIAL AGENT(S) FOR TREATMENT OF BACTEREMIA AND

OTHER SERIOUS STAPHYLOCOCCUS AUREUS INFECTIONS

ANTIMICROBIAL
SUSCEPTIBILITY COMMENTS
AGENTS
I. INITIAL EMPIRIC THERAPY (ORGANISM OF UNKNOWN SUSCEPTIBILITY)
For life-threatening infections (i.e., septicemia,
Vancomycin ? gentamicin endocarditis, CNS infection); linezolid could be
or rifampin substituted if the patient has received several
recent courses of vancomycin
For non–life-threatening infection without
signs of sepsis (e.g., skin infection, cellulitis,
Nafcillin or oxacillin* osteomyelitis, pyarthrosis) when rates of MRSA
colonization and infection in the community are
Drugs of choice: low
For non–life-threatening infection without
signs of sepsis when rates of MRSA
Clindamycin colonization and infection in the community are
substantial and prevalence of clindamycin
resistance is low
For non–life-threatening, hospital-acquired
Vancomycin
infections
II. METHICILLIN-SUSCEPTIBLE, PENICILLIN-RESISTANT S. AUREUS (MSSA)
Drugs of choice: Nafcillin or oxacillin[,†]
Cefazolin*
Clindamycin
Alternatives (depending on
susceptibility results): Only for penicillin- and cephalosporin-allergic
Vancomycin
patients
Ampicillin + sulbactam
III. MRSA
A. Health Care–Associated (Multidrug-Resistant)
Vancomycin ? gentamicin
Drugs of choice:
or ? rifampin[†]
Alternatives: susceptibility
testing results available before Trimethoprim-sulfametho
alternative drugs are used xazole
295
 ANTIMICROBIAL
SUSCEPTIBILITY COMMENTS
AGENTS
Linezolid[‡]
Quinupristin-dalfopristin[
‡]

Not recommended for people younger than 18 yr

Fluoroquinolones
of age or as monotherapy
B. Community (Not Multidrug-Resistant)
Vancomycin[†] For life-threatening infections
For pneumonia, septic arthritis, osteomyelitis,
Drugs of choice: Vancomycin ? gentamicin skin or soft tissue infections
(or ? rifampin[†])
For skin or soft tissue infections
Clindamycin (if strain
susceptible by “D test)
Alternatives:
Trimethoprim-sulfametho
xazole
IV. VANCOMYCIN INTERMEDIATELY SUSCEPTIBLE OR VANCOMYCIN-RESISTANT S. AUREUS[†]
Optimal therapy is not
Dependent on in vitro susceptibility test results
known
Drugs of choice: Linezolid
Daptomycin
Quinupristin-dalfopristin
Vancomycin + linezolid
gentamicin
Alternatives: Vancomycin +
trimethoprim-sulfametho
xazole

Toxic Shock Syndrome:

TSS is an acute multisystem disease characterized by fever, hypotension, an erythematous rash

with subsequent desquamation on the hands and feet, and multisystem involvement including
vomiting, diarrhea, myalgias, nonfocal neurologic abnormalities, conjunctival hyperemia, and
strawberry tongue.

Etiology: TSS is caused by TSST-1–producing and some enterotoxin-producing strains

of S. aureus, which may colonize the vagina or cause focal sites of staphylococcal infection.

Clinical Manifestations:

DIAGNOSTIC CRITERIA OF STAPHYLOCOCCAL TOXIC SHOCK SYNDROME

MAJOR CRITERIA (ALL REQUIRED)

296
 Acute fever; temperature >38.8?C
Hypotension (orthostatic, shock; below age-appropriate norms)
Rash (erythroderma with convalescent desquamation)
MINOR CRITERIA (ANY 3 OR MORE)
Mucous membrane inflammation (vaginal, oropharyngeal or conjuctival hyperemia, strawberry tongue)
Vomiting, diarrhea
Liver abnormalities (bilirubin or transaminase greater than twice upper limit of normal)
Renal abnormalities (urea nitrogen or creatinine greater than twice upper limit of normal, or greater than
5 white blood cells per high power field)
Muscle abnormalities (myalgia or creatinine phosphokinase greater than twice upper limit of normal)
Central nervous system abnormalities (alteration in consciousness without focal neurological signs)
Thrombocytopenia (100,000/mm3 or less)
EXCLUSIONARY CRITERIA
Absence of another explanation
Negative blood cultures (except occasionally for Staphylococcus aureus)

Complications, including acute respiratory distress syndrome, myocardial dysfunction, and renal
failure, are commensurate with the degree of shock.

Diagnosis: There is no specific laboratory test; appropriate selective tests reveal

involvement of multiple organ systems.

Differential Diagnosis: Scarlet fever, Kawasaki disease Rocky Mountain spotted fever,
leptospirosis, toxic epidermal necrolysis, sepsis, group A streptococcus (GAS) and measles must also
be considered in the differential diagnosis.
Treatment

Treatment:

1. Parenteral administration of a β-lactamase–resistant antistaphylococcal antibiotic (nafcillin,

oxacillin, or a 1st generation cephalosporin) or vancomycin in areas where MRSA is common is
recommended after appropriate cultures have been obtained. The addition of clindamycin is
recommended to reduce toxin production.

2. Fluid replacement should be aggressive to prevent or treat hypotension, renal failure, and
cardiovascular collapse.

3. Inotropic agents may be needed to treat shock;

4. Corticosteroids and intravenous immunoglobulin may be helpful in severe cases.

5. Drainage of the vagina by removal of any retained tampons in menstrual TSS and of focally
infected sites in nonmenstrual TSS is important for successful treatment.

Prevention: Changing tampons at least every 8 hr is recommended. If a fever, rash, or

dizziness develops during menstruation, any tampon should be removed immediately and medical
attention should be sought.
297
17. Streptococci

Group A streptococcus (GAS), also known as Streptococcus pyogenes, is a common cause of

infections of the

Resp: Upper respiratory tract pharyngitis, pneumonia, scarlet fever

Skin: Impetigo, pyoderma, necrotizing fasciitis and erysipelas

Sepsis: Perianal cellulitis, vaginitis, septicaemia, toxic shock syndrome and omphalitis.

Heart: Endocarditis, pericarditis, rheumatic fever

Bone, muscle and skin: osteomyelitis, suppurative arthritis, myositis, cellulitis,

Kidney: Acute Glomerulonephritis

CNS: PANDAS

Pathogenesis: GAS produces a large variety of enzymes and toxins, including erythrogenic toxins
(known as streptococcal pyrogenic exotoxins A, B, and C)

DEFINITION OF STREPTOCOCCAL TOXIC SHOCK SYNDROME

Clinical criteria
Hypotension plus 2 or more of the following:
Renal impairment
Coagulopathy
Hepatic involvement
Adult respiratory distress syndrome
Generalized erythematous macular rash
Soft tissue necrosis
Definite case
Clinical criteria plus group A streptococcus from a normally sterile site
Probable case
Clinical criteria plus group A streptococcus from a non sterile site

18. Diphtheria:

Diphtheria is an acute toxic infection caused by Corynebacterium species, typically Corynebacterium

diphtheriae and rarely toxigenic strains of Corynebacterium ulcerans.

Epidemiology: Spread is primarily by airborne respiratory droplets, direct contact with

respiratory secretions of symptomatic individuals, or exudate from infected skin lesions.
Asymptomatic respiratory tract carriage is important in transmission.

Clinical manifestations:
298
1. Respiratory Tract Diphtheria: After an average incubation period of 2-4 days, local
signs and symptoms of inflammation develop. Shallow ulceration of the external nares and upper
lip is characteristic. In tonsillar and pharyngeal diphtheria, sore throat is the universal early
symptom. The degree of local extension correlates directly with profound prostration, bull-neck
appearance, and fatality due to airway compromise or toxin-mediated complications.

2. Cutaneous Diphtheria: Classic cutaneous diphtheria is an indolent, nonprogressive

infection characterized by a superficial, ecthymic, nonhealing ulcer with a gray-brown membrane.
Extremities are more often affected than the trunk or head. Pain, tenderness, erythema, and exudate
are typical.

3. Infection at Other Sites: C. diphtheriae occasionally causes mucocutaneous

infections at other sites, such as the ear (otitis externa), the eye (purulent and ulcerative
conjunctivitis), and the genital tract (purulent and ulcerative vulvovaginitis).

Diagnosis: Specimens for culture should be obtained from the nose and throat and any
other mucocutaneous lesion. A portion of membrane should be removed and submitted for culture
along with underlying exudate. The laboratory must be notified to use selective medium.

Complications:

1. Respiratory tract obstruction by pseudomembranes may require bronchoscopy or intubation and

mechanical ventilation.

2. Toxic Cardiomyopathy: The 1st evidence of cardiac toxicity characteristically occurs during
the 2nd and 3rd weeks of illness as the pharyngeal disease. Tachycardia out of proportion to fever
is common and may be evidence of cardiac toxicity or autonomic nervous system dysfunction. Single
or progressive cardiac dysrhythmias can occur, including 1st-, 2nd-, and 3rd-degree heart block. A
prolonged PR interval and changes in the ST-T wave on an electrocardiographic tracing are
relatively frequent findings; dilated and hypertrophic cardiomyopathy detected by echocardiogram
has been described. Recovery from toxic myocardiopathy is usually complete, although survivors of
more severe dysrhythmias can have permanent conduction defects.

3. Toxic Neuropathy: Acutely or 2-3 wk after onset of oropharyngeal inflammation, it is

common for hypesthesia and local paralysis of the soft palate to occur. Weakness of the posterior
pharyngeal, laryngeal, and facial nerves may follow, causing a nasal quality in the voice, difficulty
in swallowing, and risk for aspiration. Cranial neuropathies characteristically occur in the 5th wk,
leading to oculomotor and ciliary paralysis, which can cause strabismus, blurred vision, or difficulty
with accommodation. Symmetric polyneuropathy has its onset 10 days to 3 mo after oropharyngeal
infection and causes principally motor deficits with diminished deep tendon reflexes. Distal muscle
weakness in the extremities with proximal progression is more commonly described than
proximal muscle weakness with distal progression. Complete neurologic recovery is likely.

Treatment:

Specific antitoxin is the mainstay of therapy and should be administered on the basis of clinical
diagnosis. Antitoxin is administered as a single empirical dose of 20,000-120,000 U based on the
degree of toxicity, site and size of the membrane, and duration of illness.

299
The role of antimicrobial therapy is to halt toxin production, treat localized infection, and prevent
transmission of the organism to contacts.

Appropriate therapy is erythromycin (40-50 mg/kg/day divided every 6 hr by mouth [PO] or

intravenously [IV]; maximum 2 g/day), aqueous crystalline penicillin G (100,000-150,000
U/kg/day divided every 6 hr IV or intramuscularly [IM]), or procaine penicillin (25,000-50,000
U/kg/day divided every 12 hr IM) for 14 days.

Elimination of the organism should be documented by negative results of at least 2 successive

cultures of specimens from the nose and throat (or skin) obtained 24 hr apart after completion of
therapy. Treatment with erythromycin is repeated if either culture yields C. diphtheriae.

Prevention:

All suspected diphtheria cases should be reported to local and state health departments.

1. Asymptomatic Case Contacts: All household contacts and people who have had intimate
respiratory or habitual physical contact with a patient are closely monitored for illness through the
7-day incubation period. Cultures of the nose, throat, and any cutaneous lesions are performed.
Antimicrobial prophylaxis is presumed effective and is administered regardless of immunization
status, using erythromycin (40-50 mg/kg/day divided qid PO for 10 days; maximum 2 g/day) or a
single injection of benzathine penicillin G (600,000U IM for patients <30 kg, 1,200,000U IM for
patients ≥30 kg). Diphtheria toxoid vaccine, in age-appropriate form, is given to immunized
individuals who have not received a booster dose within 5 yr.

2. Asymptomatic Carriers: When an asymptomatic carrier is identified, antimicrobial

prophylaxis is given for 10-14 days and an age-appropriate preparation of diphtheria toxoid is
administered immediately if a booster has not been given within 1 yr. Antitoxin is not
recommended for asymptomatic close contacts or carriers, even if they are inadequately immunized.

3. Vaccine: Universal immunization with diphtheria toxoid throughout life, to

provide constant protective antitoxin levels and to reduce severity of C. diphtheriae disease, is the
only effective control measure.

19. Mycoplasma pneumoniae:

Among the 5 Mycoplasma species isolated from the human respiratory tract, Mycoplasma
pneumoniae is the only recognized human pathogen and is a major cause of respiratory infections
in school-aged children and young adults. They are distinguished by the complete absence of a cell
wall, double-stranded DNA, and small genomes. M. pneumoniae is fastidious.

Clinical features: Tracheobronchitis and bronchopneumonia are the most commonly

recognized clinical syndromes associated with M. pneumoniae infection. Otitis media and bullous
myringitis have been described but are rarely seen without associated lower respiratory tract
infection. Encephalitis and postinfectious demyelination occur but are less common than
respiratory tract infections.

Diagnosis: No specific clinical, epidemiologic, or laboratory observations permit a definite

diagnosis of mycoplasmal infection early in the clinical course. Positive M. pneumoniae
immunoglobulin M (IgM) antibody identified by indirect fluorescence or enzyme-linked immune
assay (EIA) more specifically supports the diagnosis. PCR of a nasopharyngeal or throat swab (doing
300
both can increase sensitivity) for M. pneumoniae DNA is very specific (>97%).

Treatment: The recommended treatment is clarithromycin (15 mg/kg/day divided bid PO

for 10 days) or azithromycin (10 mg/kg once PO on day 1 and 5 mg/kg once daily PO on days 2-5).
Prophylaxis with azithromycin has been shown to substantially reduce the secondary attack rate in
institutional outbreaks.

Complications: Complications are unusual.

1. Skin: Skin lesions include a variety of exanthemas, most notably maculopapular

rashes, erythema multiforme, and Stevens-Johnson syndrome (SJS). M. pneumoniae is the most
common infectious agent identified as a cause of SJS.

2. Neurological: Neurologic complications include meningoencephalitis, transverse myelitis,

aseptic meningitis, cerebellar ataxia, Bells palsy, deafness, brainstem syndrome, acute demyelinating
encephalitis, and Guillain-Barre syndrome.

3. Haematological: Common hematologic complications include mild degrees of

hemolysis with a positive Coombs test and minor reticulocytosis 2-3 wk after the onset of illness.
Severe hemolysis is associated with high titers of cold hemagglutinins (≥1 : 512) and occurs rarely.
Thrombocytopenia and coagulation defects occur occasionally.

4. Cardiac: Myocarditis, pericarditis, and a rheumatic fever–like syndrome are

uncommon manifestations, but arrhythmias, ST- and T-wave changes, and cardiac dilation with
heart failure can accompany M. pneumoniae infection, particularly in adults.

5. GIT: Mild hepatitis, pancreatitis, and protein-losing hypertrophic gastropathy

are rarely reported gastrointestinal complications.

6. Musculoskeletal: Transient monoarticular arthritis has been reported.

20. Rickettsial infections:

Ricketssial diseases are a group of specific communicable diseases caused by obligate intracellular
gram negative bacilli and transmitted to man by arthropod vectors (except Q fever).

Classic triad is fever, rash and headache.

1. SPOTTED FEVER GROUP

Doxycycline
Rocky Mountain Rickettsia Tick Fever, headache, rash, emesis, diarrhea,
Tetracycline
spotted fever rickettsii bite tender calf muscles
Chloramphenicol
Mediterranean spotted Rickettsia Tick
Doxycycline
fever conorii bite
Tick
African tick-bite fever Doxycycline
bite

301
Tick-borne
Tick
lymphadenopathy
bite
(TIBOLA)

2. TRANSITIONAL GROUP
Rickettsial Rickettsia Mite Painless eschar, ulcer or papule; tender regional Doxycycline
pox akari bite lymphadenopathy, fever, headache, rash Chloramphenicol

3. TYPHUS GROUP
Rickettsia Flea Fever, headache, rash, myalgias, emesis, Doxycycline
Murine typhus
typhi feces lymphadenopathy, hepatosplenomegaly Chloramphenicol
Epidemic Doxycycline
Rickettsia Louse Fever, headache, abdominal pain, rash, CNS
(louse-borne) Tetracycline
prowazekii feces involvement
typhus Chloramphenicol

4. SCRUB TYPHUS
Doxycycline
Fever, rash, headache, painless eschar, Tetracycline
Scrub Orientia Chigger
hepatosplenomegaly, gastrointestinal If Doxycycline
typhus tsutsugamushi bite:
symptoms resistant: Rifampicin
Azithromycin

5. Q FEVER
Inhale infected Doxycycline
Q Fever: Fever, headache, arthralgias, myalgias,
aerosols: contact Tetracycline
acute (for Coxiella gastrointestinal symptoms, cough,
with parturient Fluoroquinolones
chronic, see burnetti pneumonia. rash which is typical in
animals, Trimethoprim-sulfa
text) ricketssial fever is not seen here
? ticks methoxazole

6. EHRLICHIOSIS

Blood- anemia, thrombocytopenia, hyponatremia and elevated aminotransferases are common.

Leukocytosis develops as the disease progresses.

Common investigations for all are PCR in first week and immunofluorescence in second week.

Immunofluorescence is the gold standard test for serodiagnosis of ricketssial disease. IgM > 1:64
suggest acute infection.

Weil felix can be used as screening test in developing countries.

302
Prevention:

1. No vaccines are available. Known tick infested areas should be avoided.

2. Daily inspection of body for ticks is particularly important.
3. Disinfection of dogs will minimize the tick population.
4. Health education of people about mode of transmission by ticks and means of personal
protection is equally important.

21. Neurocysticercosis:

Etiology: Infection with the invasive intermediate stage (cysticercus) is called

cysticercosis. Unlike Taenia saginata, the intermediate stage of T. solium is invasive with a tropism
for the central nervous system (CNS) in humans, causing neurocysticercosis.

The risk of cysticercosis may be the same for individuals who eat or do not eat pork, since humans
acquire the intermediate form by ingestion of food or water contaminated with the eggs of T. solium.

Pathogenesis: Living, intact cystic stages usually do not provoke a strong immunologic
response. Most cysts remain viable for 5-10 yr and then begin to degenerate, followed by a vigorous
host response.

Clinical Manifestations:

Parenchymal neurocysticercosis produces seizures as well as focal neurologic deficits. A fulminant

encephalitis-like presentation also occurs, most frequently in children who have had a massive
initial infection.

Intraventricular neurocysticercosis is associated with hydrocephalus and acute, subacute, or

intermittent signs of increased intracranial pressure without localizing signs. The 4th ventricle is the
most common site for obstruction and symptoms.

Meningeal neurocysticercosis is associated with signs of meningeal irritation and also increased
intracranial pressure that results from edema, inflammation, or the presence of a cyst obstructing flow
of CSF.

Spinal neurocysticercosis presents with evidence of spinal cord compression, nerve root pain,
transverse myelitis, or meningitis.

Ocular neurocysticercosis causes decreased visual acuity due to cysticerci floating in the vitreous,
retinal detachment, iridocyclitis, or orbital mass effect.

Diagnosis:

Neurocysticercosis should be suspected in a child with onset of any neurologic, cognitive, or

personality disorder and who also has a history of residence in an endemic area or a care provider
from an endemic area.

1. stool examination: Proglottids (segments) or eggs are observed in feces from only 25% of
303
cases of neurocysticercosis;

2. MRI: The most useful diagnostic study for parenchymal disease is MRI of the head. MRI
provides the most information about cyst viability and associated inflammation. The protoscolex is
sometimes visible within the cyst, which provides a pathognomonic sign for cysticercosis. The MRI
also better detects basilar arachnoiditis, intraventricular cysts, as well as those in the spinal cord.

3. CT: CT is best for identifying calcifications. A solitary parenchymal cyst, with or

without contrast enhancement, and numerous calcifications are the most common findings in
children.

Treatment

1. Most associated seizures can be readily controlled using standard anticonvulsant regimens. If
seizures are recurrent or associated with calcified lesions, treatment should be continued for 2-3 yr
before attempting weaning from anticonvulsants.

2. Ocular cysticercosis is essentially a surgical disease and enucleation is frequently required.

3. Albendazole is the antiparasitic drug of choice (15 mg/kg/day PO divided bid for 7 days;
maximum 800 mg/day).

4. Praziquantel is an alternative (50-100 mg/kg/day PO divided tid for 28 days), but requires more
complicated management due to an interaction with corticosteroids.

Caution: A worsening of symptoms can follow the use of either drug due to the host's
inflammatory response to the dying parasite. Patients should be medicated with prednisolone 2
mg/kg/day or 0.15 mg/kg/day oral dexamethasone, either concurrent with albendazole, or starting
albendazole on the third day of corticosteroids.

22. Polio:

The polioviruses are nonenveloped, positive-stranded RNA viruses belonging to the Picornaviridae
family, in the genus Enterovirus, and consist of 3 antigenically distinct serotypes (types 1, 2, and 3).

Clinical Manifestations:

The incubation period of poliovirus from contact to initial clinical symptoms is usually considered to
be 8-12 days, with a range of 5-35 days.

Poliovirus infections with wild-type virus may follow 1 of several courses:

1. inapparent infection, which occurs in 90-95% of cases and causes no disease and no
sequelae;
2. Abortive poliomyelitis: Fever, malaise, anorexia, and headache are prominent features, and
there may be sore throat and abdominal or muscular pain. Recovery is complete, and no
304
 neurologic signs or sequelae develop.
3. Nonparalytic poliomyelitis: More intense headache, nausea, and vomiting, as well as
soreness and stiffness of the posterior muscles of the neck, trunk, and limbs. Approximately
two thirds of these children have a short symptom-free interlude between the 1st phase
(minor illness) and the 2nd phase (CNS disease or major illness). Nuchal rigidity and
spinal rigidity are the basis for the diagnosis of nonparalytic poliomyelitis during the 2nd
phase.
4. Paralytic poliomyelitis: Paralytic poliomyelitis develops in about 0.1% of persons infected
with poliovirus, causing 3 clinically recognizable syndromes that represent a continuum of
infection differentiated only by the portions of the CNS most severely affected. These are (1)
spinal paralytic poliomyelitis, (2) bulbar poliomyelitis, and (3) polioencephalitis.

Diagnosis:

1. In suspected cases of acute flaccid paralysis, 2 stool specimens (ideally a minimum of 8-10 g of
stool should be collected.) should be collected 24-48 hr apart as soon as possible after the diagnosis
of poliomyelitis is suspected. In laboratories that can isolate poliovirus, isolates should be sent to
one of the WHO-certified poliomyelitis laboratories where DNA sequence analysis can be
performed to distinguish between wild poliovirus and neurovirulent, revertant OPV strains.

2. The CSF is often normal during the minor illness and typically contains a pleocytosis with 20-300
cells/mm3 with CNS involvement.

DIFFERENTIAL DIAGNOSIS OF ACUTE FLACCID PARALYSIS

REDUC
TION
SENSO OR
SITE, RY ABSEN RESIDU
PROGRESSI
CONDITION, CLINICAL ONSET OF SIGNS CE of AL PLEOCY
ON OF
FACTOR, OR FINDINGS PARALYSIS AND DEEP PARAL TOSIS
PARALYSIS
AGENT SYMPT TENDO YSIS
OMS N
REFLE
XES
1. ANTERIOR HORN CELLS OF SPINAL CORD
24-48 hr to Aseptic
Poliomyelitis
onset of full meningiti
(wild and Incubation period
paralysis; s
vaccine-associate Paralysis 7-14 days (4-35 No Yes Yes
proximal → (moderat
d paralytic days)
distal, e
poliomyelitis)
asymmetric polymorp

305
 REDUC
TION
SENSO OR
SITE, RY ABSEN RESIDU
PROGRESSI
CONDITION, CLINICAL ONSET OF SIGNS CE of AL PLEOCY
ON OF
FACTOR, OR FINDINGS PARALYSIS AND DEEP PARAL TOSIS
PARALYSIS
AGENT SYMPT TENDO YSIS
OMS N
REFLE
XES
honuclear
leukocyte
s at 2-3
days)
Hand-foot-and-
mouth disease,
aseptic As in
Nonpolio As in As in
meningitis, No Yes Yes poliomye
enterovirus poliomyelitis poliomyelitis
acute litis
hemorrhagic
conjunctivitis
Meningitis As in As in
West Nile virus No Yes Yes Yes
encephalitis poliomyelitis poliomyelitis
2. OTHER NEUROTROPIC VIRUSES
Acute,
Rabies virus Mo- yr symmetric, Yes Yes No ?
ascending
Exanthematous Acute,
Varicella-zoster Incubation period
vesicular symmetric, Yes ? ? Yes
virus 10-21 days
eruptions ascending
Acute,
Japanese Incubation period
proximal, ? ? ? Yes
encephalitis virus 5-15 days
asymmetric
3. GUILLAIN-Barre SYNDROME
Acute,
Acute Preceding
symmetric,
inflammatory infection,
Hours to 10 days ascending Yes Yes ? No
polyradiculoneuro bilateral facial
(days to 4
pathy weakness
wk)
Fulminant,
widespread
Acute motor paralysis,
axonal bilateral facial Hours to 10 days 1-6 days No Yes ? No
neuropathy weakness,
tongue
involvement
4. ACUTE TRAUMATIC SCIATIC NEURITIS
Intramuscular Acute, Complete,
Hours to 4 days Yes Yes ? No
gluteal injection asymmetric affected limb

306
 REDUC
TION
SENSO OR
SITE, RY ABSEN RESIDU
PROGRESSI
CONDITION, CLINICAL ONSET OF SIGNS CE of AL PLEOCY
ON OF
FACTOR, OR FINDINGS PARALYSIS AND DEEP PARAL TOSIS
PARALYSIS
AGENT SYMPT TENDO YSIS
OMS N
REFLE
XES
Preceding
Mycoplasma
pneumoniae Acute, symmetric
Acute transverse Hours to Yes,
Schistosoma, hypotonia of Yes Yes Yes
myelitis days early
other parasitic lower limbs
or viral
infection
Headache,
back pain,
Epidural abscess local spinal Complete Yes Yes ? Yes
tenderness,
meningismus
Spinal cord
Hours to
compression; Complete Yes Yes ? ?
days
trauma
5. NEUROPATHIES
In severe cases, Incubation period
Exotoxin of
palatal 1-8 wk (paralysis
Corynebacterium Yes Yes ?
paralysis, 8-12 wk after
diphtheriae
blurred vision onset of illness)
Abdominal
Toxin of pain, diplopia, Rapid,
Incubation period
Clostridium loss of descending, ? No No
18-36 hr
botulinum accommodatio symmetric
n, mydriasis
Acute,
Tick bite Ocular Latency period
symmetric, No Yes No
paralysis symptoms 5-10 days
ascending
6. DISEASES OF THE NEUROMUSCULAR JUNCTION
Weakness,
fatigability,
Myasthenia
diplopia, Multifocal No No No No
gravis
ptosis,
dysarthria
7. DISORDERS OF MUSCLE
Neoplasm,
Subacute, Weeks to
Polymyositis autoimmune No Yes No
proximal → distal months
disease
Hours to
Viral myositis Pseudoparalysis No No No
days
307
 REDUC
TION
SENSO OR
SITE, RY ABSEN RESIDU
PROGRESSI
CONDITION, CLINICAL ONSET OF SIGNS CE of AL PLEOCY
ON OF
FACTOR, OR FINDINGS PARALYSIS AND DEEP PARAL TOSIS
PARALYSIS
AGENT SYMPT TENDO YSIS
OMS N
REFLE
XES
8. METABOLIC DISORDERS
Hypokalemic Proximal limb,
Sudden
periodic respiratory No Yes ? No
postprandial
paralysis muscles
9. INTENSIVE CARE UNIT WEAKNESS
Acute, following
Flaccid limbs systemic
Critical illness Hours to
and respiratory inflammatory ? Yes ? No
polyneuropathy days
weakness response
syndrome/sepsis

Treatment

There is no specific antiviral treatment for poliomyelitis. All intramuscular injections and surgical
procedures are contraindicated during the acute phase of the illness, especially in the 1st week of
illness, because they might result in progression of disease.

Abortive Poliomyelitis: Supportive treatment with analgesics, sedatives, an attractive diet, and
bed rest until the child's temperature is normal for several days is usually sufficient.

Nonparalytic Poliomyelitis: Treatment for the nonparalytic form is similar to that for the
abortive form; Analgesics are more effective when they are combined with the application of hot
packs for 15-30 min every 2-4 hr.

Paralytic Poliomyelitis: Most patients with the paralytic form of poliomyelitis require
hospitalization with complete physical rest in a calm atmosphere for the 1st 2-3 weeks. Moist hot
packs may relieve muscle pain and spasm. When bladder paralysis occurs, a parasympathetic
stimulant such as bethanechol may induce voiding in 15-30 min; Adequate dietary and fluid intake
can be maintained by placement of a central venous catheter. An orthopedist and a physiatrist
should see patients as early in the course of the illness.

The management of pure bulbar poliomyelitis consists of maintaining the airway and avoiding all
risk of inhalation of saliva, food, and vomitus. Mounting anxiety, restlessness, and fatigue are early
308
indications for preemptive intervention. Tracheostomy is indicated for some patients with pure
bulbar poliomyelitis, spinal respiratory muscle paralysis, or bulbospinal paralysis because such
patients are generally unable to cough, sometimes for many months.

Prevention: To achieve it, the WHO used 4 basic strategies: routine immunization, National
Immunization Days (NIDs), acute flaccid paralysis surveillance, and “mop-up” immunization.

309
 HIV
Hiv Structure:

Transmission:

Transmission of HIV-1 occurs via

1) sexual contact, 2) parenteral exposure to blood and 3) vertical transmission from mother to child.

The primary route of infection in the pediatric population is vertical transmission, accounting for
almost all new cases. Perinatal treatment of HIV-infected mothers with antiretroviral drugs has
dramatically decreased these rates to <2% in pregnant women on effective therapy.

1) In the pediatric population, sexual transmission is infrequent, but a small number of cases
resulting from sexual abuse have been reported. Sexual contact is a major route of transmission in the
adolescent population, accounting for most of the cases.

2) Transfusions of infected blood or blood products has accounted for 3-6% of all pediatric AIDS
cases. Although HIV can be isolated rarely from saliva, it is in very low titres (<1 infectious
particle/mL) and has not been implicated as a transmission vehicle.

3) Vertical transmission of HIV can occur

a) before (intrauterine), b) during (intrapartum), or c) after delivery (through breast-feeding).

a) It is generally accepted that 30-40% of infected newborns are infected in utero.

b) The highest percentage of HIV-infected children acquires the virus intrapartum, evidenced by
the fact that 60-70% of infected infants do not demonstrate detectable virus until after 1 wk of age.
The mechanism of transmission appears to be exposure to infected blood and cervicovaginal
secretions in the birth canal.

c) Breast-feeding is the least common route of vertical transmission in industrialized. WHO

recommends that in developing countries where other diseases (diarrhea, pneumonia, malnutrition)
substantially contribute to a high infant mortality rate, the benefit of breast-feeding outweighs the
risk for HIV transmission, and HIV-infected women in developing countries should breast-feed
310
their infants for at least the 1st 6 mo of life.

Factors which influence the rate of vertical transmission:

A) Viral factors- high viral load

B) Maternal factors

1. Advanced disease.

2. A low maternal antenatal CD4 count.

3. Use of recreational drugs during pregnancy.

4. The most important variables appear to be >4 hr duration of ruptured membranes and

5. Mother not on ART.

C) Feto placental factors- Chorioamnionitis, placenta previa, prematurity.

D) Post natal factors- breast feeding, higher breast milk viral load, mastitis or nipple lesions

E) Infant factors - HLA concordance with mother, Preterm delivery (<34 wk gestation), Birth weight
<2,500 g, each of which doubles the transmission rate.

Clinical manifestations: The HIV classification system is used to categorize the stage of pediatric
disease by using 2 parameters: clinical status and degree of immunologic impairment.

Category N: not symptomatic

Category A (mild symptoms) includes children with at least 2 mild symptoms such as
lymphadenopathy, parotitis, recurrent or persistent sinusitis or otitis media, hepatomegaly,
splenomegaly and dermatitis.

Category B (moderate symptoms) includes children with LIP (lymphocytic interstitial pneumonitis),
oropharyngeal thrush persisting for >2 mo, recurrent or chronic diarrhea, persistent fever for >1 mo,
recurrent (HSV) stomatitis, HSV esophagitis, HSV pneumonitis, disseminated varicella (i.e., with
visceral involvement), hepatitis, cardiomegaly, or nephropathy.

Category C (severe symptoms) includes children with opportunistic infections (e.g. esophageal or
lower respiratory tract candidiasis, cryptosporidiosis (>1 mo), disseminated mycobacterial or
cytomegalovirus infection, Pneumocystis pneumonia, or cerebral toxoplasmosis [onset >1 mo of
age]), recurrent bacterial infections (sepsis, meningitis, pneumonia), encephalopathy, malignancies,
and severe weight loss.

311
PEDIATRIC HIV CLASSIFICATION FOR CHILDREN YOUNGER THAN 13 YEARS

IMMUNOLOGIC CATEGORIES
AGE-SPECIFIC CD4+
T-LYMPHOCYTE
COUNT AND PERCENTAGE OF TOTAL CLINICAL CLASSIFICATIONS
LYMPHOCYTES
IMMUNOLOGI <12 mo 1-5 yr 6-12 yr N:
C DEFINITIONS No
Signs A: Mild B: Moderate C: Severe
or Signs and Signs and Signs and
µL % µL % µL % Sym Symptoms Symptoms Symptoms
ptom
s
1: No evidence of ≥2
≥1500 ≥1000 ≥25 ≥500 ≥25 N1 A1 B1 C1
suppression 5
2: Evidence of 15
750-14 500-99 15-2 200-4 15-2
moderate -2 N2 A2 B1 C2
99 9 4 99 4
suppression 4
3: Severe <1
<750 <500 <15 <200 <15 N3 A3 B3 C3
suppression 5

Diagnosis:

1. All infants born to HIV-infected mothers test antibody-positive at birth because of passive
transfer of maternal HIV antibody across the placenta during gestation. Infants continue to test HIV
antibody positive for up to 18 mo of age, positive IgG antibody tests, including the rapid tests,
cannot be used to make a definitive diagnosis of HIV infection in infants younger than this age.

2. The presence of IgA or IgM anti-HIV in the infant's circulation can indicate HIV infection;
however, these assays have been both insensitive and nonspecific and therefore are not valuable for
clinical use.

3. Breast-fed infants should have antibody testing performed 12 wk following cessation of

breast-feeding to identify those who became infected at the end of lactation by the HIV-infected
mother.

Incorporating rapid HIV testing during delivery or immediately after birth is crucial for the care of
HIV-exposed newborns whose HIV status was unknown during pregnancy. A positive rapid test has
to be confirmed by Western blot testing.

4. LABORATORY DIAGNOSIS OF HIV

INFECTION
312
TEST COMMENT
Preferred test to diagnose HIV-1 subtype B infection in infants and children younger than 18
HIV
mo of age; highly sensitive and specific by 2 wk of age and available; performed on
DNA
peripheral blood mononuclear cells. False negatives can occur in non-B subtype HIV-1
PCR
infections
HIV
Expensive, not easily available, requires up to 4 wk to do test; not recommended
culture
HIV Less sensitive than DNA PCR for routine testing of infants, because a negative result cannot
RNA be used to exclude HIV infection definitively. Some assays preferred test to identify non-B
PCR subtype HIV-1 infections.

5. Viral diagnostic testing should be performed within the 1st 12-24 hr of life.

In exposed children with negative virologic testing at 1-2 days of life, additional testing should be
done at 1-2 mo of age and at 4-6 mo of age.

6. A positive virologic assay (i.e., detection of HIV by PCR, culture, or p24 antigen) suggests HIV
infection and should be confirmed by a repeat test on a 2nd specimen as soon as possible. A
diagnosis of HIV infection can be made with 2 positive virologic test results obtained from
different blood samples.

Opportunistic infections (OIs) are generally seen in children with severe depression of the CD4
count.

1. Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia, the most common

opportunistic infection in the pediatric population. The peak incidence of Pneumocystis pneumonia
occurs at age 3-6 mo in the setting of undiagnosed perinatally acquired disease, with the highest
mortality rate in children <1 yr of age.

The classic clinical presentation of Pneumocystis pneumonia includes acute onset of fever,
tachypnea, dyspnea, and marked hypoxemia.

Chest x-ray findings most commonly consist of interstitial infiltrates or diffuse alveolar disease,
which rapidly progresses. Nodular lesions, streaky or lobar infiltrates, or pleural effusions may
occasionally be seen.

Diagnosis is established by demonstration of P. jirovecii with appropriate staining of

bronchoalveolar fluid lavage; rarely, an open lung biopsy is necessary.

The 1st line therapy for Pneumocystis pneumonia is intravenous trimethoprim-sulfamethoxazole

(TMP-SMZ) (15-20 mg/kg/day of the TMP component every 6 hr IV) with adjunctive
corticosteroids if the Pao2 is <70 mm Hg while breathing room air.

Alternative therapy for Pneumocystis pneumonia includes intravenous administration of

pentamidine.

Other regimens such as TMP plus dapsone, clindamycin plus primaquine, or atovaquone are used
as alternatives in adults but have not been widely used in children to date.

2. Oral candidiasis is the most common fungal infection seen in HIV-infected children.

313
Oral thrush progresses to involve the esophagus in as many as 20% of children with severe CD4
depletion, presenting with symptoms such as anorexia, dysphagia, vomiting, and fever.

Oral nystatin suspension is often effective. Clotrimazole troches or fluconazole are an effective
alternative. Fungemia rarely occurs, usually in the setting of indwelling venous catheters, and up to
50% of cases may be caused by non-albicans species.

3. Viral infections, especially with the herpesvirus group, pose significant problems for
HIV-infected children. HSV causes recurrent gingivostomatitis, which may be complicated by local
and distant cutaneous dissemination. Primary varicella-zoster virus (VZV) infection (chickenpox)
may be prolonged and complicated by bacterial infections or visceral dissemination, including
pneumonitis. Prolonged treatment with acyclovir is required.

Disseminated cytomegalovirus (CMV) infection occurs in the setting of severe CD4 depletion (<50
CD4 cells/mm3) and may involve single or multiple organs. Retinitis, pneumonitis, esophagitis,
gastritis with pyloric obstruction, hepatitis, colitis, and encephalitis have been reported, but these
complications are rarely seen if HAART is given.

Ganciclovir and foscarnet are the drugs of choice and are often given together in children with
sight-threatening CMV retinitis. An intraocular ganciclovir implant plus oral valganciclovir has also
been efficacious in adults and older children with CMV retinitis.

Measles may occur despite immunization and may present without the typical rash. It often
disseminates to the lung or brain with a high mortality rate.

Initiation of Therapy:

1. HIV-infected children with symptoms (clinical category A, B, or C) or with evidence of

immune dysfunction (immune category 2 or 3) should be treated with antiretroviral therapy,
regardless of age or viral load.
2. Children <1 yr of age are at high risk for disease progression, and immunologic and virologic
tests to identify those likely to develop rapidly progressive disease are less predictive than in
older children. Therefore, such infants should be treated with antiretroviral agents as soon as
the diagnosis of HIV infection has been confirmed, regardless of clinical or immunologic
status or viral load.
3. Data suggest that HIV-infected infants who are treated before the age of 3 months control
their HIV infection better than infants whose antiretroviral therapy started later than 3 mo of
age.
4. There is still a debate on when to start therapy in children older than 1 yr of age.
5. Most guidelines recommend deferring treatment if the CD4 is ≥25% in children 1-5 yr of age
or the CD4 count is above 350-500 cells/mm3 in children >5 yr of age, with a viral load of
<100,000 copies/mm3 because there are concerns regarding drug adherence, safety, and
durability of antiretroviral response. These children should be monitored regularly for
evidence of virologic, immunologic, or clinical progression, at which point therapy should be
initiated as long as potential adherence issues are addressed.

Monitoring Antiretroviral Therapy:

1. Children need to be seen within 1 to 2 wk after initiation of new antiretroviral therapy to

assure compliance and to screen for potential side effects.
2. Virologic and immunologic surveillance (using HIV RNA copy number and CD4
lymphocyte count or percentage) as well as clinical assessment should be performed
regularly during antiretroviral therapy.
3. Initial virologic response (i.e., at least a 5-fold reduction in viral load) should be achieved
314
 within 4-8 wk of initiating antiretroviral therapy.
4. HIV RNA levels should be measured at 4 wk and 3-4 months after therapy initiation.
5. Once an optimal response has occurred, viral load should then be measured at least every 3-6
months.
6. If the response is unsatisfactory, another viral load should be performed as soon as possible
to verify the results before a change in therapy is considered.
7. The CD4 cells respond more slowly to successful treatment and, therefore, can be monitored
less frequently.
8. Potential toxicity should be monitored closely for the 1st 8-12 wk, and if no clinical or
laboratory toxicity is documented, a follow-up visit every 3-4 mo is adequate.
9. Monitoring for potential toxicity should be tailored to the drugs taken. These toxicities
include hematologic complications (e.g., ZDV); hypersensitivity rash (e.g., EFV);
lipodystrophy (e.g., redistribution of body fat seen with NRTIs, protease inhibitors);
hyperlipidemia (elevation of cholesterol and triglyceride concentrations), hyperglycemia
and insulin resistance, and mitochondrial toxicity leading to severe lactic acidosis (e.g., D4T,
ddI), ECG abnormalities (e.g., atazanavir, lopinavir), abnormal bone mineral metabolism
(e.g., tenofavir), and hepatic toxicity including severe hepatomegaly with steatosis.

Class Drugs Common side effects Individual drug side effects

315
NRTI Zidovudine, Nausea, vomiting, Tenofovir- renal toxicity
lamivudine, anorexia, fever,
stavudine and emtricitabine- peripheral neuropathy
Stavudine, headache, diarrhea
abacavir Lactic acidosis with zidovudine- bone marrow supression
tenofovir hepatic steatosis,
Didanosine, pancreatitis
emtricitabine
NNRTI Nevirapine, Rash-mild to severe, Nevirapine- induces hepatic CYP 450A enzymes.
efavirenz, usually within 1st 6 wk.
Nevirapine dec concentration of protease inhibitors
etravirine Discontinue the drug if
severe rash (with and ketoconazole
blistering, desquamation,
Rifampin decreases nevirapine concentration
muscle involvement, or
fever).
Protease Indinavir, Hyperglycemia, renal stones – indinavir, Atazanir, fosamprenavir
inhibitors saquinavir, hyperlipidemia (except
All undergo hepatic metabolism, mostly by CYP 3A4,
ritonavir, atazanavir),
nelfinavir, lipodystrophy, increased with many drug interactions!
atazanavir, transaminases, increased
darunavir, bleeding disorders in
lopinavir hemophiliacs.fat
redistribution.
Fusion enfuviritide Local injection site Must be given subcutaneously. Severity of reactions
inhibitors reactions
increased if given intramuscularly.
Less common: Increased
incidence of bacterial Apply ice after injection and massage the area
pneumonia,
to reduce local reactions.
hypersensitivity
immune-mediated Injection sites should be rotated.
reactions
Entry maraviroc Fever, URI symptoms, Not approved for children or adolescents <16 yr
inhibitors skin rashes, abdominal
pain, musculoskeletal
symptoms, dizziness
Integrase raltegravir Nausea, headache, <16 yr: Not established
inhibitors dizziness, diarrhea,
fatigue

Risk factors for human milk transmission of HIV

Risk factor
Category
Duration of breast feeding Longer duration
Maternal characteristics Younger age, higher parity, lower CD4 count, higher viral load, breast
abscess/mastitis/nipple lesions
Infant characteristics Oral candidiasis
Human milk characteristics Higher viral load, lower concentration of anti-viral substances like
lactoferrin, lysozyme, epidermal growth factor, lower concentration of
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 viral specific cytotoxic T lymphocytes, lower IgA & IgM
Exclusivity of breastfeeding Mixed breast and replacement feeding

Mothers known to be HIV-infected should consider giving RF (replacement feeding) to their infants
only when ALL of the following conditions are met:

1. Safe water and sanitation are assured at the household level and in the community, and

2. The mother, or other caregiver can reliably afford to provide sufficient RF (milk), to support
normal growth and development of the infant, and

3. The mother or caregiver can prepare it frequently enough in a clean manner so that it is safe and
carries a low risk of diarrhoea and malnutrition, and

4. The mother or caregiver can, in the first six months exclusively give RF, and

5. The family is supportive of this practice, and

6. The mother or caregiver can access health care that offers comprehensive child health services.

For PMTCT, the World Health Organization (WHO) promotes a comprehensive approach :

 Primary prevention of HIV infection among women of childbearing age.

 Preventing unintended pregnancies among women living with HIV.
 Preventing HIV transmission from a woman living with HIV to her infant; and
 Providing appropriate treatment, care and support to mothers living with HIV and their
children and families.

Common Clinical Problems in Children Living with HIV/AIDS: Systemic Approach: ijp nov 2012

Clinical Manifestations

The presentation varies widely among infants, children and adolescents; most are asymptomatic at
birth and do not have any abnormal findings, but adolescents have clinical features similar to adults.
One of the earliest Indian studies reported protein energy malnutrition, hepatosplenomegaly,
recurrent or persistent diarrhea and persistent generalized lymphadenopathy as the most common
early symptoms.

1. Growth / Nutrition / Endocrine System:

 Pediatric HIV infection is associated with linear and ponderal growth retardation and delayed
sexual maturation.
 In early infancy, an apparent growth delay with symmetrical decrease in height and weight
occurs, while in late childhood there is a relative loss of weight for height with a tendency to
remain below the standards for age and gender in subsequent follow ups.
 The use of antiviral medications that reduce viral burden is associated with improvements in
317
 anthropometric indices of growth.
 The earlier the onset and severity of disease, the greater the negative effect on pubertal
growth.
 Protein energy malnutrition is known to have adverse effects on the immune system, and
coupled with HIV, the immunosuppression is exacerbated.

2. Skin:

Lesions observed exclusively in HIV infection Oral hairy leukoplakia

Bacillary angiomatosis
Kaposi’s sarcoma
Commonly encountered AIDS - defining skin Kaposi’s sarcoma
conditions
Herpes simplex ulcers for >1 mo
Cryptococcosis
Histoplamosis
Atypical mycobacterial infection

3. Respiratory System:

Pulmonary disease continues to be the major cause of morbidity and mortality. Recurrent upper
respiratory tract infections such as otitis media and sinusitis are common. Where tuberculosis is
endemic, pulmonary TB far exceeds Pneumocystis jiroveci pneumonia (PCP) or lymphoid interstitial
pneumonitis (LIP).

Pneumocystis jiroveci Pneumonia (PCP), a life threatening complication caused by Pneumocystis

jiroveci, is considered to be the most common AIDS-defining condition in children. Primary
asymptomatic infection occurs in a large number of immunocompetent children by 2–4 y of age,
suggested by the presence of serum antibodies to the organism. However, patients at risk are those
with advanced infection and impaired cell mediated immunity. Clinical features include tachypnea,
cough and respiratory distress, and hypoxia less responsive to oxygen administration. Common
radiographic abnormalities are diffuse bilateral interstitial infiltration and hyperinflation. Response
to a trial of highdose cotrimoxazole (20 mg/ kg/ d of Trimethoprim component) which should be
instituted without delay, combined with corticosteroids if there is severe dyspnoea. Primary
prophylaxis with cotrimoxazole (dose of 5 mg/kg/d of Trimethoprim component as a single daily
dose) is a standard component of HIV care in children.

4. CNS:

1. Contrasting features of AIDS Dementia Complex (ADC) in adults and HIV-1-associated

Progressive Encephalopathy of Childhood (PE) in children

Adults Children
Mature CNS at primary infection Immature CNS at primary infection

Brain atrophy Acquired microcepahy, impaired brain growth

318
Psychiatric changes are common Neurobehavioural changes are common

Motor deterioration/cognitive decline/dementia Progressive motor dysfunction/

neurodevelopmental delay/ regression

No intracranial calcifications Basal ganglionic calcifications

CSF non-specific for ADC CSF non-specific for PE

Seizures frequent Seizures infrequent

Opportunistic infections in CNS frequent Opportunistic infections in CNS infrequent

2. The most frequent opportunistic infections involving the CNS are tuberculosis, toxoplasmosis,
cryptococcosis and cytomegalovirus.

3. Progressive Multifocal Leukoencephalopathy (PML) is a severe demyelinating disease of the CNS

seen in immunocompromised patients.

5. Gastrointestinal and Hepatobiliary Tract:

The gastrointestinal tract problems include oral and esophageal lesions, malabsorption, abdominal
pain, dysphagia and acute or chronic diarrhea. Druginduced hepatotoxicity should be strongly
considered.

6. Cardiovascular System:

Cardiac complications generally occur late and may be due to prolonged immunosuppression,
opportunistic infections, viral infections, autoimmune response, pulmonary hypertension, infective
endocarditis drug-related cardiotoxicity and nutritional deficiencies.

7. Renal System:

Renal disease in HIV can be divided into four major groups, based on manifestations in adults:

(1) HIV-associated nephropathy (HIVAN)

(2) HIV-associated Immune Complex Kidney disease (HIVICK)

(3) Acute tubular dysfunction

(4) HIV-associated thrombotic microangiopathies.

8. Hematological System:

 Impaired hematopoiesis, immune-mediated cytopenias and altered coagulation mechanisms

can occur.
 Anemia occurs in 50–90 % of HIV-infected children, common causes being iron, folic acid
and vitamin B12 deficiencies, immune hemolysis, drug toxicities, malignancy, bone marrow
suppression due to HIV and Parvovirus B-19 infection.
 Thrombocytopenia may be due to immune-mediated platelet destruction, thrombotic
319
 thrombocytopenic purpura, impaired hematopoiesis and toxic effects of medications.

Read also

1. National aids prevention and control- spm

2. Counselling - spm
3. Treatment – flow chart – WHO
4.

320
 IMMUNOLOGY
1. evaluation of immunodeficiency
2. INITIAL IMMUNOLOGIC TESTING OF THE CHILD WITH RECURRENT INFECTIONS

3. A diagnostic testing algorithm for primary immunodeficiency diseases.

4. Classification of primary immunodeficiency’s

5. approach to immunodeficiency

6. CGD

7. macrophages

1. Evaluation of immunodeficiency:
Evaluation of immune function should be initiated in those rare infants or children who do have
clinical manifestations of a specific immune disorder and in all who have unusual, chronic, or
recurrent infections such as
(1) 1 or more systemic bacterial infections (sepsis, meningitis).
(2) 2 or more serious respiratory or documented bacterial infections (cellulitis, abscesses, draining
otitis media, pneumonia, lymphadenitis) within 1 yr.
(3) Serious infections occurring at unusual sites (liver, brain abscess).
(4) Infections with unusual pathogens (Pneumocystis jiroveci, Aspergillus, Serratia, Nocardia,
Burkholderia); and
(5) Infections with common childhood pathogens but of unusual severity .
Additional clues to immunodeficiency include:
 Failure to thrive with or without chronic diarrhea,
 Persistent infections after receiving live vaccines, and
 Chronic oral or cutaneous moniliasis.

CHARACTERISTIC FEATURES OF PRIMARY

IMMUNODEFICIENCY

PREDOMINANT PREDOMINANT GRANULOCYTE COMPLEMENT

CHARACTERISTIC
T-CELL DEFECT B-CELL DEFECT DEFECT DEFECT

321
 PREDOMINANT PREDOMINANT GRANULOCYTE COMPLEMENT
CHARACTERISTIC
T-CELL DEFECT B-CELL DEFECT DEFECT DEFECT

Onset after maternal

antibodies diminish,
Age at the onset of Early onset, usually Onset at any
usually after 5-7 mo of Early onset
infection 2-6 mo of age age
age, later childhood to
adulthood

Bacteria:
Bacteria: common pneumococci, Bacteria:
gram-positive and streptococci, staphylococci, Bacteria:
gram-negative staphylococci, Pseudomonas, pneumococci,
bacteria and Haemophilus, Klebsiella, Neisseria
mycobacteria Campylobacter, Salmonella
Specific pathogens Mycoplasma
involved
Viruses: CMV, EBV,
Viruses: enterovirus*
varicella, enterovirus
Fungi and parasites:
Fungi: Candida and Fungi and parasites:
Candida,
Pneumocystis giardia,
Aspergillus
jiroveci cryptosporidia
Nocardia
Skin: abscesses,
impetigo,
cellulitis Infections:
Recurrent Lymph nodes:
Extensive Meningitis,
sinopulmonary suppurative
mucocutaneous
infections, adenitis
candidiasis, Arthritis,
Affected organs Oral cavity:
malabsorption,
failure to thrive, gingivitis, septicemia,
enteroviral mouth ulcers
protracted diarrhea recurrent
meningoencephalitis Internal sinopulmonary
organs: infections
abscesses,
osteomyelitis

Graft-versus-hos
t disease Lymphoreticular
malignancy: Autoimmune
Postvaccination lymphoma, Prolonged
disseminated disorders:
thymoma attachment of
Special features BCG or umbilical cord,
varicella Postvaccination SLE,
paralytic polio poor wound healing
angioedema
Hypocalcemic
tetany in infancy

322
 PREDOMINANT PREDOMINANT GRANULOCYTE COMPLEMENT
CHARACTERISTIC
T-CELL DEFECT B-CELL DEFECT DEFECT DEFECT

INITIAL IMMUNOLOGIC TESTING OF THE CHILD WITH RECURRENT

INFECTIONS

COMPLETE BLOOD COUNT, MANUAL DIFFERENTIAL, AND ERYTHROCYTE

SEDIMENTATION RATE
Absolute lymphocyte count (normal result rules against T-cell defect)
Absolute neutrophil count (normal result rules against congenital or acquired neutropenia and
[usually] both forms of leukocyte adhesion deficiency, in which elevated counts are present even
between infections)
Platelet count (normal result excludes Wiskott-Aldrich syndrome)
Howell-Jolly bodies (absence rules against asplenia)
Erythrocyte sedimentation rate (normal result indicates chronic bacterial or fungal infection
unlikely)
SCREENING TESTS FOR B-CELL DEFECTS
IgA measurement; if abnormal, IgG and IgM measurement
Isohemagglutinins
Antibody titers to blood group substances, tetanus, diphtheria, Haemophilus influenzae, and
pneumococcus
SCREENING TESTS FOR T-CELL DEFECTS
Absolute lymphocyte count (normal result indicates T-cell defect unlikely)
Candida albicans intradermal skin test: 0.1 mL of a 1 : 1,000 dilution for patients ≥6 yr, 0.1
mL of a 1 : 100 dilution for patients <6 yr
SCREENING TESTS FOR PHAGOCYTIC CELL DEFECTS
Absolute neutrophil count
Respiratory burst assay using rhodamine dye
SCREENING TEST FOR COMPLEMENT DEFICIENCY
CH 50
Measurement of C4 can be helpful

Prenatal diagnosis and carrier detection:

323
Carriers of ADA (adenosine deaminase ) and PNP (purine nucleoside phosphorylase) deficiency can
be detected by quantitative enzyme analyses of blood samples.

Carriers of X-linked agammaglobulinemia, X-linked SCID, or the Wiskott-Aldrich syndrome can be

identified by direct mutation analysis if the family's mutation is known.

Properdin deficiency is X linked, but all of the other complement deficiencies are autosomal.

A diagnostic testing algorithm for primary immunodeficiency diseases.

Classification of primary immunodeficiency’s:

1. Humoral immunodeficiency
a. X- linked agammaglobulinemia
b. Common variable immunodeficiency
c. Transient hypogammaglobulinemia of infancy
d. Ig A deficiency
e. Ig G subclass deficiency
2. Combined immunodeficiency
324
 a. Severe combined immunodeficiency
b. Adenosine deaminase deficiency
3. Defects of phagocytic function
a. Chronic Granulomatous Disease
b. Myeloperoxidase deficiency
c. Chediak higashi disease
4. Complement deficiencies
5. miscellaneous - ataxia telangiectasia, wiskott Aldrich syndrome

APPROACH TO A CHILD SUSPECTED IMMUNODEFICIENCY

Immunodeficiency should be suspected in:
1. one or more systemic bacterial infections (sepsis, meningitis)
2. two or more serious respiratory or documented bacterial infections (cellulitis, draining otitis
media, pneumonia, lymphadenitis) within 1 yr
3. serious infections occurring at unusual sites (liver, brain abscess)
4. infections with unusual pathogens (Aspergillus, Serratia marcescens, Nocardia,
Burkholderia cepacia)
5. infections with common childhood pathogens but of unusual severity

ADDITIONAL CLUES:
1. >8 ear infections per yr
2. >2 serious sinus infections per yr
3. >2 mo treatment with antibiotics with poor results
4. failure to thrive with or without chronic diarrhea
5. the need for intravenous antibiotics to successfully treat an infection usually treated with oral
antibiotics

The initial evaluation of immunocompetence includes a:

thorough history, physical examination, and family history
DERMATOLOGIC
Eczema T- or B-cell immune deficiency, Wiskott-Aldrich syndrome,
Sparse and/or hypopigmented hair Cartilage hair hypoplasia, Chediak-Higashi syndrome,
Ocular telangiectasia Ataxia-telangiectasia
Oculocutaneous albinism Chediak-Higashi syndrome
Recurrent abscesses, of lung especially Hyper-IgE syndrome
Recurrent organ abscesses, Chronic granulomatous disease
liver and rectum especially

Recurrent skin infections, abscesses Leukocyte adhesion defect, hyper-IgE syndrome

Oral or nail candidiasis T-cell defects; mucocutaneous candidiasis, hyper-IgE syndrome

Vitiligo, conjunctivitis, alopecia B-cell defects, mucocutaneous candidiasis

EXTREMITIES
Clubbing of the nails Chronic lung disease due to antibody defects
325
Arthritis Antibody defects, Wiskott-Aldrich syndrome, hyper-IgM

ENDOCRINOLOGIC
Hypoparathyroidism DiGeorge's syndrome, mucocutaneous candidiasis
Endocrinopathies (autoimmune) Mucocutaneous candidiasis
Growth hormone deficiency X-linked agammaglobulinemia
Gonadal dysgenesis Mucocutaneous candidiasis

HEMATOLOGIC
Hemolytic anemia B- and T-cell immune defects, ALPS
Thrombocytopenia, small platelets Wiskott-Aldrich syndrome
Neutropenia Hyper-IgM syndrome, Wiskott-Aldrich variant
Immune thrombocytopenia B-cell immune defects, ALPS

SKELETAL
Short-limb dwarfism Short-limb dwarfism with T- and/or B-cell immune defects
Bony dysplasia ADA deficiency, SCID

6. CGD
Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is characterized by neutrophils and monocytes capable of

normal chemotaxis, ingestion, and degranulation, but unable to kill catalase-positive
microorganisms because of a defect in the generation of microbicidal oxygen metabolites.

CGD is a rare disease caused by 4 genes, 1 X-linked and 3 autosomal recessive in inheritance.

Pathogenesis

The metabolic deficiency of the CGD neutrophil predisposes the host to infection. The CGD
phagocytic vacuoles lack microbicidal reactive oxygen species and remain acidic, so bacteria are not
killed or digested properly.

326
  The pathogenesis of chronic granulomatous disease (CGD). Normal neutrophils stimulate
hydrogen peroxide in the phagosome containing ingested Escherichia coli. The quantity of
hydrogen peroxide produced by the normal neutrophil is sufficient to exceed the capacity of
catalase, a hydrogen peroxide-catabolizing enzyme of many aerobic microorganisms

 When organisms such as E. coli gain entry into CGD neutrophils, they are not exposed to
hydrogen peroxide because the neutrophils do not produce it, and the hydrogen peroxide
generated by microorganisms themselves is destroyed by their own catalase.

 When CGD neutrophils ingest streptococci, which lack catalase, the organisms generate
enough hydrogen peroxide to result in a microbicidal effect.

 As indicated (middle), catalase-positive microbes such as E. coli can survive within the
phagosome of the CGD neutrophil

Clinical Manifestations

 Although the clinical presentation is variable, several features suggest the diagnosis of CGD.
 Any patient with recurrent pneumonia, lymphadenitis, hepatic or other abscesses,
osteomyelitis at multiple sites, a family history of recurrent infections, or any infection with
an unusual catalase-positive organism requires evaluation.
 The onset of clinical signs and symptoms may occur from early infancy to young adulthood.
 The most common pathogen is S. aureus, although any catalase-positive microorganism may
be involved. Other organisms frequently causing infections include Serratia marcescens,
Burkholderia cepacia, Aspergillus, Candida albicans, Nocardia, and Salmonella.
 Granuloma formation and inflammatory processes are a hallmark of CGD and may be the
presenting symptoms.

Laboratory Findings

 The diagnosis is most often made by performing flow cytometry using dihydrorhodamine
123 (DHR) to measure oxidant production through its increased fluorescence when oxidized
by H2O2.

 The nitroblue tetrazolium (NBT) dye test is frequently cited in the literature but is now only
rarely used clinically.

Treatment

 HSCT is the only known cure for CGD.

 For supportive care, patients with CGD should be given daily oral
trimethoprim-sulfamethoxazole and an antifungal drug, such as itraconazole, for
prophylaxis of infections.
 Granulocyte transfusions may be necessary if antibiotics are ineffective.
 Granulomas may be sensitive to low doses of prednisone (0.5 mg/kg/day).
 Interferon-γ (IFN-γ) 3 times /wk reduces the number of hospitalizations and serious
infections.

Genetic Counseling
327
  Identifying a patient's specific genetic subgroup is useful primarily for genetic counseling and
prenatal diagnosis.
 In cases of suspected X-linked CGD, further analysis is not necessary if the fetus is initially
demonstrated to be a 46, XX female.
 Fetal blood sampling and oxidase function analysis of fetal neutrophils can be used for
prenatal diagnosis of CGD.
 DNA analysis of amniotic fluid cells or chorionic villus biopsy is an option for early prenatal
diagnosis in families in which the specific mutation is known.

Prognosis

The development of effective infection prophylactic regimens, close surveillance for signs of
infections, and aggressive surgical and medical interventions has improved the prognosis.

7. Macrophages
The phagocyte system includes both granulocytes (neutrophils, eosinophils, and basophils) and
mononuclear phagocytes (monocytes and tissue macrophages).
PRINCIPAL SITES OF MACROPHAGES IN TISSUES
Liver (Kupffer cells)
Lung (interstitial and alveolar macrophages)
Connective tissue and interstitium of major organs and skin
Serosal cavities (pleural and peritoneal macrophages)
Synovial membrane (type A synoviocytes)
Bone (osteoclasts)
Brain and retina (microglial cells)
Spleen, lymph nodes, bone marrow
Intestinal wall
Breast milk
Placenta
Granulomas (multinucleated giant cells)
Skin Dendritic cells

All macrophages have at least 3 major functions in common:

 Phagocytosis
 Presentation of antigens to lymphocytes, and
 Enhancement or suppression of the immune response.
At sites of inflammation, monocytes and macrophages can fuse to form multinucleated giant cells;
these cells maintain the antimicrobial functions of macrophages.
Neutrophil defects:
 Chediak-Higashi syndrome
 Leukocyte adhesion deficiency
 Chronic granulomatous disease
 G6PD deficiency
 Myeloperoxidase deficiency

328
Osteoclast defect:
 Osteopetrosis
The monocyte-macrophage defects:
 lipid storage diseases like sphinolipidosis
 HLH.

329
 NEPHROLOGY
1. Renal failure
2. Chronic kidney disease
3. Indications for renal biopsy
4. PSGN
5. RPGN
6. PROTEINURIA
7. Dialysis/ renal replacement therapy
8. Imaging in nephrology
9. Renal calculi
10. eneuresis
11. antenatal hydronephrosis

12. Anemia in crf – sagar sirs notes

13. Hematuria
14. Gfr
15. Urine examination
16. Hus
17. Polyuria articles and notes
18. Rta
19. Ns/ srns
20. Sle
21. Htn
22. Read UROLOGY also.

Renal failure:
Def: Acute renal failure (ARF), also termed acute renal insufficiency, is a clinical syndrome in
which a sudden deterioration in renal function results in the inability of the kidneys to maintain fluid
and electrolyte homeostasis.
Pathogenesis: ARF has been conventionally classified into 3 categories: prerenal, intrinsic renal, and
postrenal.

330
PRERENAL INTRINSIC RENAL POSTRENAL

Posterior urethral valves

Dehydration
Glomerulonephritis
Ureterocele
Hemorrhage  Post infectious/
poststreptococcal
 SLE Urolithiasis
Sepsis
 HSP
Hemorrhagic cystitis
burns  Membranoproliferative
 Anti GBM Ureteropelvic junction
obstruction
Hypoalbuminemia Ureterovesicular
Hemolytic-uremic syndrome junction obstruction
Tumor
Acute tubular necrosis
Cortical necrosis
Cardiac failure
Renal vein thrombosis
Rhabdomyolysis
Acute interstitial nephritis
Tumor infiltration
Tumor lysis syndrome
Clinical features:
A carefully taken history is critical in defining the cause of ARF.
1. History of vomiting and diarrhea most likely has prerenal ARF caused by volume depletion.
2. Child with a recent pharyngitis with periorbital edema, hypertension, and gross hematuria most
likely has intrinsic ARF related to acute postinfectious Glomerulonephritis.
3. A critically ill child with a history of exposure to nephrotoxic medications most likely has ATN.
4. A neonate with a history of hydronephrosis on prenatal ultrasound and a palpable bladder and
prostate most likely has congenital urinary tract obstruction, probably related to posterior urethral
valves.
The physical examination must be thorough, with careful attention to volume status.
1. Tachycardia, dry mucous membranes, and poor peripheral perfusion suggest inadequate circulating
volume and the possibility of Prerenal ARF.
2. Peripheral edema, rales, and a cardiac gallop suggest volume overload and the possibility of
intrinsic ARF.
3. The presence of a rash and arthritis might suggest systemic lupus erythematosus (SLE) or Henoch
- Schonlein purpura nephritis.
4. Palpable flank masses might suggest renal vein thrombosis, tumors, cystic disease, or urinary tract
obstruction.
Investigations:
1. CBC - anemia, leukopenia, thrombocytopenia
2. RFT - hyponatremia, metabolic aciodsis, elevated Ur and Cr, Hyperkalemia, hypocalcemia
3. Urine - hematuria, proteinuria, casts and urinary eosinophils.
4. Chest X ray -cardiomegaly, pleural effusions
5. Renal ultra sound- hydronephrosis, nephromegaly
6. Rest: C3 levels, ANA, cytoplasmic and basement membrane antibodies
7. Renal doppler
8. Biomarkers for kidney functioning - plasma neutrophil gelatinase-associated lipocalin
(NGAL) and cystatin C levels and urinary changes in NGAL, interleukin-18 (IL-18), and
kidney injury molecule-1 (KIM-1).
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 9. Renal biopsy
URINALYSIS, URINE CHEMISTRIES, AND OSMOLALITY IN ACUTE RENAL FAILURE
HYPOVOLEMIA ATN OBSTRUCTION
Broad, brownish
Sediment Bland Bland or bloody
granular casts
<20 (acute)
Urine sodium, mEq/L <20 >30
>40 (few days)
Urine osmolality, mOsm/kg >400 <350 <350
<1 (acute)
Fractional excretion of sodium % <1 >1
>1 (few days)

Management: follow FRICHMAN

1. PUV Bladder catheterization Monitor urine out put
2. Volume status Fluid boluses -if no evidence of cardiac failure
no improvement in urine output
Single dose diuretic/ mannitol/ bumetanide
still no improvement
Cont diuretic infusion with or without dopamine
3. Hyperkalemia 1. Stop all potassium in IV fluids.
2. If ECG changes calcium gluconate 1-2 ml/kg over 5-10 min under
cardiac monitoring.
3. If k 6-6.5meq/l
a. soda bicarb 1 mEq/kg over 15-30 mins
intravenous
b. kayexalate 1gm/kg q6h per rectally
4. If k 6.5- 7.5 mEq/l
a. Glucose- insulin infusion 0.05u/kg of
regular insulin with 2ml/kg of 10% D
b. salbutamol nebulisation
5. If k > 7.5 mEq/l
a. Exchange transfusion with washed RBC
reconstituted with 5 % albumin
b. Dialysis.
4. Hypocalcaemia Low phosphate diet, Phosphate binders, IV calcium if tetany
5. Hyponatremia 3% nacl if symptomatic- and not to correct sodium rapidly
6. GI bleeding- risk H2 blockers
7. Metabolic acidosis Sodium bicarbonate oral/ I.V
8. Hypertension Salt and water restriction.
Ccb or β blockers to control
If symptomatic hypertension
Sodium Nitroprusside and Labetalol or esmolal
9. Neurological symptoms Diazepam
10. Anemia PRBC if Hb <7
11. Nutrition Restricted protein, High calorie intake
Essential amino acids if critically ill

AKIN Serum creatinine Urine output Equivalent P rifle

stage criteria
1 End creatine clearance decreases by 25 % <0.5ml/kg/hr for RISK
more than 8
hours
332
2 End creatine clearance decreases by 50 % <0.5ml/kg/hr for INJURY
more than 16
hours
3 End creatine clearance decreases by 75 % <0.3ml/kg/hr for FAILURE
24 hours or
anuria for 12
hours
Persistent loss of kidney function for more LOSS
than 4 weeks
End stage renal disease for more than 3 END STAGE
months

2. Chronic kidney disease:

Chronic kidney disease (CKD) is defined as renal injury (proteinuria) and/or a glomerular filtration
rate <60 mL/min/1.73 m2 for >3 months.
Etiology:
CKD in children
A) <5 yr old is most commonly a result of congenital abnormalities such as renal hypoplasia,
dysplasia, or obstructive uropathy. Additional causes include congenital nephrotic syndrome, prune
belly syndrome and cortical necrosis.
B) >5 yr of age
Acquired diseases (glomerulonephritis including lupus nephritis)
Inherited disorders (familial juvenile nephronophthisis, Alport syndrome) predominate.
C) Throughout the childhood years - CKD related to metabolic disorders (cystinosis,
hyperoxaluria) and certain inherited disorders (polycystic kidney disease) can occur throughout the
childhood years.
PATHOPHYSIOLOGY OF CHRONIC KIDNEY DISEASE:
MANIFESTATION MECHANISMS
1.Accumulation of nitrogenous waste
Decrease in glomerular filtration rate
products
Decreased ammonia synthesis
2.Acidosis Impaired bicarbonate reabsorption
Decreased net acid excretion
Excessive renin production
3.Sodium retention
Oliguria

4.Sodium wasting and Urinary Solute diuresis

concentrating defect Tubular damage
Decrease in glomerular filtration rate
Metabolic acidosis
5.Hyperkalemia
Excessive potassium intake
Hyporeninemic hypoaldosteronism
Impaired renal production of
1,25-dihydroxycholecalciferol
6.Renal osteodystrophy Hyperphosphatemia Hypocalcemia

Secondary hyperparathyroidism
7.Growth retardation Inadequate caloric intake
333
MANIFESTATION MECHANISMS
Renal osteodystrophy
Metabolic acidosis Anemia

Growth hormone resistance

Decreased erythropoietin production
Iron deficiency Folate deficiency
8.Anemia
Vitamin B12 deficiency
Decreased erythrocyte survival
9.Bleeding tendency Defective platelet function
Defective granulocyte function
10.Infection Impaired cellular immune functions
Indwelling dialysis catheters
11.Neurologic symptoms (fatigue, poor Uremic factor(s)
concentration, headache, drowsiness, Aluminium toxicity
memory loss, seizures, peripheral
neuropathy) Hypertension

12.Gastrointestinal symptoms (feeding Gastroesophageal reflux

intolerance, abdominal pain) Decreased gastrointestinal motility
Volume overload
13.Hypertension
Excessive renin production
Decreased plasma lipoprotein lipase
14.Hyperlipidemia
activity
Uremic factor(s)
15.Pericarditis, cardiomyopathy Hypertension
Fluid overload
16.Glucose intolerance Tissue insulin resistance

TERMINOLOGY FOR STAGES OF CHRONIC KIDNEY DISEASE

STAGE DESCRIPTION GFR (mL/min/1.73 m2)

1 Kidney damage with normal or increased GFR >90
2 Kidney damage with mild decrease in GFR 60-89
3 Moderate decrease in GFR 30-59
4 Severe decrease in GFR 15-29
5 Kidney failure <15 or on dialysis

Laboratory Findings:
 Increased: urea, creatinine, potassium, phosphate, cholesterol and triglycerides.
 Decreased: sodium, calcium, albumin.

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  Urinalysis shows hematuria and proteinuria.
 Inulin clearance is the gold standard to determine GFR, but it is not easy to measure.
other markers - cystatin C and iohexol.
 Schwartz formula to calculate GFR

where k is 0.55 for children and adolescent girls, and 0.7 for adolescent boys.
Treatment:
1. Water and electrolyte management Most children with CKD maintain normal
sodium and water balance.
Restriction of dietary potassium intake.
2. Acidosis Use sodium bicarbonate
3. Nutrition Dietary phosphorus, potassium, and sodium
should be restricted.
Protein intake should be 2.5 g/kg/24 hr and
should consist of proteins of high biologic
value.
Water soluble vitamins supplementation
4. Growth Recombinant human GH (rHuGH).
5. Renal osteodystrophy Ergocalciferol/ calcitriol based on vit D
levels
Newer vit D analogs Paricalcitol and
doxercalciferol are increasingly used.

6. Anemia Erythropoietin is usually initiated when the

patient's hemoglobin concentration falls
below 10 g/dL, at a dose of 50-150
mg/kg/dose subcutaneously 1-3 times
weekly.
An alternative option is darbepoetin alfa a
longer-acting agent
7. Hypertension Salt restricted diet
CKD stages 1-3 thiazide diuretics
CKD stages > 3 loop diuretics
If proteinuria ACE inhibitors
Adjunctive drugs CCB and β Blockers
8. Immunizations Children with CKD should receive all
standard immunizations according to the
schedule used for healthy children.
An exception must be made in withholding
live vaccines during treatment with
immunosuppressive medications.
Yearly influenza vaccine
9. Adjustment in drug dose Because many drugs are excreted by the
kidneys, their dosing might need to be
adjusted in patients with CKD to maximize
effectiveness and minimize the risk of

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 toxicity.
10. Infections Prompt treatment of infectious
complications.
11. other Control of hyperlipidemia
Avoidance of smoking
Prevention of obesity
Minimise use of NSAIDS
3. Indications for renal biopsy: (total 8)
1. Acute nephritic syndrome 2..Nephrotic syndrome
Macroscopic hematuria beyond 4-6 weeks
Persistent hypertension beyond 6 weeks At the onset of nephrotic syndrome (NS) if
Presenting with or progressing to severe renal • Age < 1 year and > 12 years
failure • Persistent microscopic/gross hematuria, low C3
• Sustained hypertension
Persistent mild-to-moderate renal failure • Renal failure not attributable to hypovolemia
Persistent hypocomplementemia beyond • Suspected secondary causes of NS
8 weeks or absence of it at the onset
After initial treatment of the disease
Associated systemic features like arthralgia, • Steroid resistant NS
arthritis, skin rashes and recurrent • Steroid dependent NS / frequently relapsing
abdominal pain • Before cytotoxic therapy
B 3. Transplantation 4. Isolated persistent hematuria
Suspected acute rejection When glomerular hematuria is suspected
Drug toxicity • After ruling out hypercalciurea
Detecting the development of de novo or • After ruling out familial or urological
recurrent disease disease
Chronic rejection
5. Acute renal failure 6. Chronic renal failure
Associated with acute nephritic syndrome (as To determine the risk of recurrence on eventual
mentioned above) renal transplant if etiology of CRF is uncertain
Nephrotic children with acute renal failure 7. Systemic diseases
(as mentioned above) To assess activity and chronicity of the renal
Presenting with evidence of vasculitis involvement in diseases like HUS, HSP and SLE
RPGN 8. Follow-up diseases
Occurring with evidence of systemic diseases To document renal toxicity of cytotoxic
When the cause is not clear and with therapy
persistence of renal failure • In Glomerulonephritis
• In transplantation follow-up
Complications -- hematuria, perinephric hematoma and arterio-venous fistula

4. PSGN:
Acute poststreptococcal glomerulonephritis (APSGN) is a classic example of the acute nephritic
syndrome characterized by the sudden onset of gross hematuria, edema, hypertension, and renal
insufficiency.
Most common in children aged 5-12 yr.
ETIOLOGY:
Poststreptococcal GN commonly follows streptococcal pharyngitis (serotype 12) during cold-weather
months and streptococcal skin infections (serotype 49) or pyoderma during warm-weather months.
PATHOGENESIS:
Circulating immune Molecular mimicry whereby
complex formation with circulating antibodies elicited The nephritogenic antigens
streptococcal antigens and by streptococcal antigens are streptococcal pyogenic
subsequent glomerular react with normal glomerular exotoxin (SPE B) and
336
deposition antigens, in situ immune nephritis-associated
complex formation of streptococcal plasmin
antistreptococcal antibodies receptor (NAPlr).
with glomerular deposited
antigen, and complement
activation

CLINICAL FEATURES:
The severity of kidney involvement varies from asymptomatic microscopic hematuria with normal
renal function to gross hematuria with acute renal failure.
Renal- Edema, hypertension, and Oliguria based on severity.
CVS- Hypertensive encephalopathy must be considered in patients with blurred vision, severe
headaches, altered mental status, or new seizures.
Resp- Respiratory distress, orthopnea, and cough may be symptoms of pulmonary edema and heart
failure.
DIAGNOSIS:
1. Urinalysis - red blood cells (RBCs), often in association with RBC casts, proteinuria, and
polymorphonuclear leukocytes.
2. A mild normochromic anemia.
3. The serum C3 level is reduced in >90% of patients in the acute phase with normal C4.
4. The antistreptolysin O titer is commonly elevated after a pharyngeal infection.
5. Anti-deoxyribonuclease (DNase) B is usually elevated after a Cutaneous infection.
6. Positive streptozyme test.
7. Magnetic resonance imaging of the brain can demonstrate reversible posterior
leukoencephalopathy.
8. Chest x-ray for pulmonary edema.
9. ECHO for cardiac failure.
Treatment:
Although a 10-day course of systemic antibiotic therapy with penicillin is recommended to limit the
spread of the nephritogenic organisms, antibiotic therapy does not affect the natural history of GN.
Sodium restriction, diuresis usually with intravenous Furosemide and pharmacotherapy with
calcium channel antagonists, vasodilators, or angiotensin-converting enzyme inhibitors are
standard therapies used to treat hypertension.
Complications:
Hypertension Renal failure dyselectrolytemia seizures
cardiac failure
Prognosis:
Complete recovery occurs in >95% of children with APSGN.
Recurrences are extremely rare.
5. RPGN:
“Rapidly progressive” describes the clinical course of several forms of glomerulonephritis (RPGN)
whose unifying feature is the histopathologic finding of crescents in the majority of glomeruli.
CLASSIFICATION:
ANTI-GBM ANTIBODY-MEDIATED RPGN ASSOCIATED WITH GRANULAR
RPGN IMMUNE DEPOSITS
Postinfectious
• Poststreptococcal
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 Goodpasture syndrome glomerulonephritis
• Bacterial endocarditis
Idiopathic anti-GBM nephritis • Shunt nephritis
Membranous nephropathy with Noninfectious
crescents • Systemic lupus
erythematosus
RPGN WITHOUT GLOMERULAR • Henoch-Schonlein purpura
IMMUNE DEPOSITS • Mixed cryoglobulinemia
Primary renal disease
Vasculitis
• Membranoproliferative
• Polyarteritis
glomerulonephritis
• Hypersensitivity vasculitis • IgA nephropathy
• Wegener granulomatosis • Idiopathic immune-complex
nephritis

Pathology and Pathogenesis:

The hallmark of Cresentic GlomeruloNephritis is the histopathologic finding of crescents in

glomeruli. Fibrin deposition and macrophage infiltration. Crescents are replaced by collagen, is a
late finding.

Prognosis and Treatment:

Although the outcome is not uniformly positive, children with rapidly progressive poststreptococcal
GN and CGN can spontaneously recover.

Having a majority of fibrous crescents on the renal biopsy portends a poor prognosis, because the
disease usually has progressed to irreversible injury.

The consensus of most nephrologists is that the combination of high-dose corticosteroids and
cyclophosphamide may be effective in preventing progressive renal failure.

Evaluation of asymptomatic proteinuria in children:

Random urine examination positive for protein

Repeat urine dipstick examination and U Pr/Cr ratio

Negative Both positive

Dipstick negative
Transient proteinuria Persistent proteinuria And U Pr/Cr < 0.2

No follow up Inv- Ur, Cr, lytes, proteins, albumin Orthostatic proteinuria

Compliment levels, CBC
USG abd Annual follow up for
proteinuria, hematuria,
Renal biopsy hypertension, edema
and diminished renal
SRNS function.
NS plus persistent renal failure
338
 Renal vasculitis

6. PROTEINURIA: The demonstration of proteinuria on a routine screening urinalysis is common.

CAUSES: Transient or persistent. Persistent – orthostatic or fixed. Fixed- glomerular or
tubular
Persons found to have significant proteinuria on a first morning urine sample on 3 consecutive days
(>1+ on dipstick with urine specific gravity >1.015 or protein : creatinine ratio >0.2) have fixed
proteinuria.
Glomerular proteinuria should be suspected in any patient with a first morning urine
protein : creatinine ratio >1.0, or proteinuria of any degree, accompanied by hypertension, hematuria,
edema, or renal dysfunction.
TRANSIENT GLOMERULAR TUBULAR DISEASES
PROTEINURIA DISEASES
Cystinosis
CHARACTERIZED BY
ISOLATED Wilson disease
PROTEINURIA Lowe syndrome
Idiopatic (minimal Dent disease
Cold exposure change) nephrotic Galactosemia
Congestive heart failure syndrome Heavy metal
Dehydration Focal segmental poisoning
Exercise glomerulosclerosis Acute tubular necrosis
Fever Mesangial proliferative Polycystic kidney
Seizure glomerulonephritis disease
Stress Membranous Reflux nephropathy
nephropathy
The proteinuria usually does Membranoproliferative
not exceed 1-2+ on the glomerulonephritis
dipstick. No evaluation or 5. Indications for renal
Amyloidosis
therapy is needed for biopsy include increasing
children with this benign Diabetic nephropathy proteinuria
condition. Persistence of Sickle cell nephropathy (protein:creatinine >1.0)
proteinuria, even if low and/or the development of
grade, suggests the need for hematuria, hypertension, or
additional evaluation. diminished renal function.
GLOMERULAR ORTHOSTATIC 3. The dipstick is reported as
DISEASES WITH (POSTURAL) negative,
PROTEINURIA AS A PROTEINURIA. Most trace (10-20 mg/dL),
PROMINENT FEATURE common cause of persistent 1+ (30 mg/dL),
proteinuria in school aged 2+ (100 mg/dL),
Acute postinfectious children and adolescents. 3+ (300 mg/dL),
glomerulonephritis 4+ (1000-2000 mg/dL).
339
 The cause of orthostatic
proteinuria is unknown, 4. spot urine7.
Henoch-Schonlein
although altered renal protein:creatinine Dial
ratio
purpura nephritis
hemodynamics and partial (UPr:UCr). ysis/
Lupus nephritis renal vein obstruction in the ren
Ratios <0.5 in children <2 yr
Alport syndrome upright position are possible of age al
1. Microalbuminuria is causes. Hematuria, repl
and <0.2 in children ≥2 yr of
defined as the presence of hypertension, edema and age suggest normal protein ace
albumin in the urine above renal dysfunction are absent. excretion. men
the normal level but below 2. Normal protein excretion A ratio >2 suggests t
the detectable range of in children is defined as ≤4 ther
nephrotic-range proteinuria
conventional urine dipstick mg/m2/hr; apy
methods abnormal is defined as 4-406. 24 hr urine protein :
mg/m2/hr; excretion >150 mg/dl is Prin
and nephrotic range is significant. cipl
defined as >40 mg/m2/hr e of
exce
ss water and solute removal by running it through a semipermeable membrane and discarding the
waste products.
Clinical indications Biochemical indications

Refractory fluid overload GFR falls to <15ml/min/1.73m2

Pulmonary oedema Serum creatinine of more than 4.0 mg/dL,

Uncontrollable hypertension Intractable metabolic acidosis,

Persistent vomiting, drowsiness and Refractory hyperkalemia

Convulsions with no definable cause
Hyponatremia with serum sodium of less
Growth failure than 120 mEq/L.

Drug intoxication Hyperphosphatemia

TYPES
EXTRA CORPOREAL DIALYSIS INTRA CORPOREAL DIALYSIS
a) manually- continuous ambulatory
a) Continuous RRT (CVVH, CVVHD) peritoneal dialysis (CAPD)

b) Intermittent Hemodialysis (IHD) b)automated devices- continuous cycling

peritoneal dialysis (CCPD)

Hemodialysis Peritoneal dialysis

Principle See pic in hematuria article See pic in hematuria article
Advantages Ability to accurately Safe and simple
regulate volume control Uremic toxins are better removed
No need for technician or vascular access or
Ultra filtration and solute water.
removal can be isolated Fluid and dietary intake is quite liberal
Child can continue his daytime routine
Exact amount of Less mortality
ultrafiltration can be
programmed and achieved
Complications Steal syndrome Pain shock
Dev of aneurysm Leakage from the catheter enter site
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 Infections Perforation of the viscera
Dialysis disequilibrium Respiratory distress
Peritonitis Hypothermia
Recurrent thrombosis, Dyselectrolytemia
stenosis and recirculation. Protein loss- malnutrition
Dialysis disequilibrium syndrome (DDS)
Over anticoagulation Seizures Catheter malfunctioning
limitations Hemodynamic instability Clearance of small molecules is inadequate
Need for anticoagulation Risk of peritonitis
Risk of bleeding
Technical challenges
Need for NG feeding
Available only at specialised
centers
8. IMAGING OF URINARY TRACT: (TOTAL 9)
1. Plain X ray film of the abdomen: The utility of plain x ray abdomen has decreased with
the introduction of ultrasonography. X ray still has a role in detecting a) small renal calculi, ureteric
calculi, b) spinal evaluation in neurogenic states, c) evaluation of metastatic bone disease from
neuroblastoma and d) screening for renal osteodystrophy.
2. Excretory urography/ intravenous pyelography: non ionic compounds are preferred because
of isoosomlar composition, better safety and decreased adverse reactions. But newer techniques have
largely replaced these.
3. Ultrasonography: Provides excellent anatomy of the urinary tract. The procedure is ideally
suited as it is painless and requires no sedation or administration of any contrast agent. It is carried
out even at bedside and repeated as often as required. Ultra sound guidance can be used in invasive
procedures eg FNAC and biopsy. The major drawback is that it is operator dependent.
Considerable experience is required for interpretation.
4. Antenatal ultrasonography: During pregnancy can detect many fetal anomalies.PUV should
be suspected if b/l hydronephrosis, distended bladder and dilated posterior urethra are seen.
5. Computed tomography: Besides providing anatomical information also gives functional
status of the kidney if an IV contrast is used. Main role of CT is in examining mass lesions of kidney,
bladder or retroperitonium. Multidetector row CT (MDCT) is crucial for extent assessment of renal
or retroperitoneal masses. Radiation dose should be kept in mind.
6. Micturating cystourethrogram (MCU): An important procedure for the diagnosis and evaluation
of severity of VUR and other abnormalities of bladder and urethra.
7. MRI: It has several advantages like a) non ionizing nature, b) multiplanar imaging capability
and c) superior soft tissue contrast resolution. The added advantage in evaluation of renal masses
is that d) IVC thrombus can be detected without any contrast.
8. DTPA radionuclide scan: To determine the function of kidney.
9. DMSA radionuclide scan: More sensitive in determining the sequel of reflux nephropathy.

10. Renal stones

The wide geographic variation in the incidence of lithiasis in childhood is related to climatic, dietary,
and socioeconomic factors.
Classification of urolithiasis:
1. Calcium oxalate (calcium oxalate and calcium phosphate)
 Hypercalciuria- absorptive, resorptive, renal leak and iatrogenic (diuretics, ketogenic diet)
 Distal RTA
 Vit D excess
 Immobilisation
 Hyperuricosuria
 Hyperoxaluria
2. Cystine stones- cystinuria
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3. Struvite stones (magnesium ammonium phospate)- UTI, foreign body and urinary stasis
4. Uric acid stones- hyperuricosuria, lesch nyhan syndrome and after chemotherapy.
5. Nephrocalcinosis

Stone formation depends on four factors:

 Matrix is a mixture of protein, non-amino sugars, glucosamine, water, and organic ash that
makes up 2-9% of the dry weight of urinary stones and is arranged within the stones in
organized concentric laminations.
 Precipitation-crystallization refers to supersaturation of the urine with specific ions
composing the crystal. Crystals aggregate by chemical and electrical forces. Increasing the
saturation of urine with respect to the ions increases the rate of nucleation, crystal growth, and
aggregation and increases the likelihood of stone formation and growth.
 Epitaxy refers to the aggregation of crystals of different composition but similar lattice
structure, thus forming stones of a heterogeneous nature.
 Urine also contains inhibitors of stone formation, including citrate, diphosphonate, and
magnesium ion.

Clinical manifestations:

 Children with urolithiasis usually have gross or microscopic hematuria.

 If the calculus is in the renal pelvis, calyx, or ureter and causes obstruction, then severe
abdominal or flank pain (renal colic) occurs. Typically the pain radiates anteriorly to the
scrotum or labia.
 If the calculus is in the distal ureter, the child can have irritative symptoms of dysuria,
urgency, and frequency.
 If the stone passes into the bladder, the child usually is asymptomatic.
 If the stone is in the urethra, dysuria and difficulty voiding can result, particularly in boys.
 Stones can also be asymptomatic.

Investigations:
X ray KUB- calcium and struvite stones are radio opaque . cystine, xanthine and uric acid stones may
be radiolucent
The most accurate study is an unenhanced spiral CT scan of the abdomen and pelvis
Ultrasonography
SERUM Urine

Calcium Urine analysis

Phosphorus Urine culture
Uric acid Calcium:creatinine ratio
Electrolytes and anion gap Spot test for cystinuria
Creatinine
Alkaline phosphatase 24 hr urine for calcium, phosphate, oxalate, uric acid and
creatinine clearance.

Treatment:
 In a child with a renal or ureteral calculus, the decision whether to remove the stone depends
on its location, size, and composition (if known) and whether obstruction and/or infection are
present.
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  Small ureteral calculi often pass spontaneously, although the child might experience severe
renal colic.
 The narrow parts of the ureter include the ureteropelvic junction and the midureter, where it
crosses the common iliac artery; the narrowest segment is the ureterovesical junction.
 In children with hypercalciuria, some reduction in calcium and sodium intake is necessary,
but caution is urged in the growing child. Thiazide diuretics also reduce renal calcium
excretion. Addition of potassium citrate, an inhibitor of calcium stones is beneficial.
 In patients with uric acid stones, allopurinol is effective. In addition, urinary alkalinization
with sodium bicarbonate or sodium citrate is beneficial.
 Maintaining a high urine pH can also prevent recurrence of cystine calculi.
 Treatment of type 1 RTA involves correcting the metabolic acidosis and replacing lost
potassium and sodium.
 Treatment of primary hyperoxaluria involves liver transplantation.
 Lithotripsy and percutaneous nephroscopy are surgical alternatives if not responding to
medical therapy.

11. Enuresis:

Def: Nocturnal enuresis refers to the occurrence of involuntary voiding at night after 5 yr, the age
when volitional control of micturition is expected.

Classification:

Diurnal enuresis defines wetting while awake.

Nocturnal enuresis refers to voiding during sleep.

Primary enuresis occurs in children who have never been consistently dry through the night.

Secondary enuresis refers to the resumption of wetting after at least 6 months of dryness.

Monosymptomatic enuresis has no associated daytime symptoms (urgency, frequency, daytime

enuresis)

Nonmonosymptomatic enuresis, which is more common, often has at least one subtle daytime
symptom.

Epidemiology:

 Approximately 60% of children with nocturnal enuresis are boys.

 Family history is positive in 50% of cases.
 Although primary nocturnal enuresis may be polygenetic, candidate genes have been
localized to chromosomes 12 and 13.
 By 5 yr of age, 90-95% of children are nearly completely continent during the day, and
80-85% are continent at night.


CAUSES of nocturnal enuresis

Delayed maturation of the cortical mechanisms that allow voluntary control of the micturition

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 reflex
Sleep disorders- Sleep apnea (snoring) secondary to enlarged adenoids
“Deep sleeping” (no specific sleep pattern identified)
Reduced antidiuretic hormone production at night, resulting in an increased urine output
Genetic factors, with chromosomes 12 and 13q the likely sites of the gene for enuresis
Overactive bladder
Constipation
Organic factors, such as urinary tract infection or obstructive uropathy
Psychologic factors more often implicated in secondary enuresis

OTHER FEATURES
Enuresis can occur in any stage of sleep
All children are most difficult to arouse in the 1st third of the night and easiest to awaken in the
last third, but enuretic children are more difficult to arouse than those with normal bladder
control.

Family history in enuretic children often positive for enuresis.

Clinical features:
 A careful history should be obtained, especially with respect to fluid intake at night and
pattern of nocturnal enuresis.
 Children with diabetes insipidus, diabetes mellitus, and chronic renal disease can have a
high obligatory urinary output and a compensatory polydipsia.
 The family should be asked whether the child snores loudly at night.
 A complete physical examination should include palpation of the abdomen and rectal
examination after voiding to assess the possibility of a chronically distended bladder.
 The child with nocturnal enuresis should be examined carefully for neurologic and spinal
abnormalities.
Investigations:
 There is an increased incidence of bacteriuria in enuretic girls, and, if found, it should be
investigated and treated, although this does not always lead to resolution of bed-wetting.
 A urine sample should be obtained after an overnight fast and evaluated for specific gravity
or osmolality to exclude polyuria as a cause of frequency and incontinence and to ascertain
that the concentrating ability is normal.
 The absence of glycosuria should be confirmed.
 A renal ultrasonogram is reasonable in an older child with enuresis or in children who do
not respond appropriately to therapy.
 If there are no daytime symptoms, the physical examination and urinalysis are normal, and
the urine culture is negative, further evaluation for urinary tract pathology generally is not

344
 warranted.
Treatment: NON PHARMACOLOGICAL:
1.General advice:

 The best approach to treatment is to reassure the child and parents that the condition is
self-limited and to avoid punitive measures that can affect the child's psychologic
development adversely.
 Fluid intake should be restricted to 2 oz after 6 or 7 pm.
 The parents should be certain that the child voids at bedtime.
 Avoiding extraneous sugar and caffeine after 4 pm also is beneficial.
 If the child snores and the adenoids are enlarged, referral to an otolaryngologist should be
considered, because adenoidectomy can cure the enuresis.
 Active treatment should be avoided in children <6 yr of age, because enuresis is extremely
common in younger children.
 Treatment is more likely to be successful in children approaching puberty compared with
younger children.

2. The simplest initial measure is motivational therapy and includes a star chart for dry nights.
Waking children a few hours after they go to sleep to have them void often allows them to awaken
dry, although this measure is not curative.

3. Conditioning therapy involves use of a loud auditory or vibratory alarm attached to a moisture
sensor in the underwear. The alarm sounds when voiding occurs and is intended to awaken children
and alert them to void.

4. Hypnotherapy: Another form of therapy to which some children respond is self-hypnosis.

5. Psychotherapy: The primary role of psychologic therapy is to help the child deal with enuresis
psychologically and help motivate the child to void at night if he or she awakens with a full bladder.

Pharmacological therapy:
1. Desmopressin acetate: a synthetic analog of antidiuretic hormone that reduces urine production
overnight. It is available as a tablet, with a dosage of 0.2-0.6 mg at bedtime. Nasal spray no longer
used because of side effects.
2. For therapy-resistant enuresis or children with symptoms of an overactive bladder, anticholinergic
therapy is indicated. Oxybutynin 5 mg at bedtime. The clinician should monitor for constipation as a
potential side effect.
3. A third-line treatment is imipramine, which is a tricyclic antidepressant. This medication has mild
anticholinergic and α-adrenergic effects, reduces urine output slightly, and also might alter the sleep
pattern.
4. Combination therapy:

TREATMENT REGIMEN FOR MONOSYMPTOMATIC NOCTURNAL ENURESIS

345
 • Limit fluids to 8 oz at supper 3 to 3.5 hours before bedtime; no fluids thereafter.
• Empty the bladder before sleeping.
• Make a bedtime “resolution” to stay dry.
• Discuss mode of action of drugs or moisture alarm and drug side effects; dispense drug or
alarm.
• Advice that medication or alarm is the “coach” and the child is the “player.”
• Advice that positive internal and external biofeedback signals help hasten central nervous
system control of the bladder.
• Keep a calendar of dry and wet nights.
• Encourage the child's participation in cleaning up personal clothing and bedclothes.
• Schedule follow-up visits or phone calls at least every 2 wk, with positive reinforcement for
dry nights and efforts.
• Continue use of alarm until 28 consecutive dry nights are achieved, then stop; use
medications as directed.
• If bedwetting returns on tapering or discontinuation of medication or alarm, restart nightly
medication or alarm.
• If the child is not dry every night, despite motivation and efforts, substitute or add another
drug or alarm and rule out undisclosed diurnal voiding problems.

Autosomal Recessive Polycystic Kidney Disease

Also known as infantile polycystic disease, autosomal recessive polycystic kidney disease (ARPKD)
is an autosomal recessive disorder occurring with an incidence of 1 : 10,000 to 1 : 40,000. The gene
for ARPKD (PKHD1) encodes fibrocystin, a large protein (>4,000 amino acids) with multiple
isoforms.
Pathology
Both kidneys are markedly enlarged and grossly show innumerable cysts throughout the cortex and
medulla. Microscopic studies demonstrate dilated, ectatic collecting ducts radiating from the medulla
to the cortex. Development of progressive interstitial fibrosis and tubular atrophy during advanced
stages of disease eventually leads to renal failure. Liver involvement is characterized by a basic
ductal plate abnormality that leads to bile duct proliferation and ectasia, as well as hepatic fibrosis.
Clinical Manifestations:
The typical child presents with bilateral flank masses during the neonatal period or early infancy.
ARPKD may be associated with oligohydramnios, pulmonary hypoplasia, respiratory distress, and
spontaneous pneumothorax in the neonatal period. Components of the oligohydramnios complex
including low-set ears, micrognathia, flattened nose, limb-positioning defects, and growth deficiency
may be present. Hypertension is usually noted within the first few weeks of life and is often severe
and difficult to control. Oliguria and acute renal failure are uncommonly seen. Infrequently,
ARPKD manifests beyond infancy, in young infants with a mixed clinical picture of renal and hepatic
findings: variable degrees of portal hypertension (hepatosplenomegaly, gastroesophageal varices,
prominent cutaneous periumbilical veins, reversal of portal vein flow, thrombocytopenia) and
variable renal findings that range from asymptomatic abnormal renal ultrasonography to systemic
hypertension and renal insufficiency.
Patients with ARPKD are at risk for developing ascending cholangitis, varices, and hypersplenism
related to portal hypertension; they are also at risk for progressive liver fibrosis.
Diagnosis
The diagnosis of ARPKD is strongly suggested by bilateral palpable flank masses in an infant with
pulmonary hypoplasia, oligohydramnios, and hypertension and the absence of renal cysts by
sonography of the parents. Markedly enlarged and uniformly hyperechogenic kidneys with poor
corticomedullary differentiation are commonly seen on ultrasonography.
The diagnosis is supported by clinical and laboratory signs of hepatic fibrosis, pathologic findings of
ductal plate abnormalities seen on liver biopsy, anatomic and pathologic proof of ARPKD in a sibling,
346
or parental consanguinity.
The differential diagnosis includes other causes of bilateral renal enlargement and/or cysts, such as
multicystic dysplasia, hydronephrosis, Wilms tumor, and bilateral renal vein thrombosis.
Prenatal diagnostic testing using genetic linkage analysis or direct mutation analysis is available in
families with ≥1 affected child.
Treatment:
The treatment of ARPKD is supportive. Aggressive ventilatory support is often necessary in the
neonatal period secondary to pulmonary hypoplasia, hypoventilation, and the many respiratory
illnesses of prematurity (which are common).
Careful management of hypertension, fluid and electrolyte abnormalities, and clinical
manifestations of renal insufficiency is essential.
Children with severe respiratory failure or feeding intolerance from enlarged kidneys can require
unilateral or bilateral nephrectomies, prompting the need for renal replacement therapy.
In families with a previous affected child, preimplantation genetic diagnosis coupled with in vitro
fertilization is available in specialized centers and can lead to the birth of unaffected children in
at-risk families.
Prognosis:
Mortality has improved dramatically, although approximately 30% of patients die in the neonatal
period of complications from pulmonary hypoplasia.
Neonatal respiratory support and renal replacement therapies have increased the 10-yr survival of
children surviving beyond the 1st year of life to >80%.

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 ONCOLOGY
1. Signs and symptoms of cancer
2. Oncological emergencies
3. Late effects of cancer treatment
4. Brain tumors
5. retinoblastoma
6. ALL
7. AML
8. Wilms
9. Neuroblastoma notes
10. Hodgkins lymphoma
11. NHL

1. Signs and symptoms of cancer in children:

Common manifestations of childhood malignancies:
Haematological: pallor, anemia, thrombocytopenia, petechiae, neutropenia
Musculoskeletal: bone pain, tenderness, limp, arthralgia, soft tissue mass,
blue berry muffin spots
Neurological: emesis, headache, papilledema, ataxia, cranial nerve palsies.
Systemic: fever of unknown origin, persistent or recurrent infections,
diarrhea, weight loss, night sweats, painless lymphadenopathy,
hepatosplenomegaly, abdominal mass, diabetes insipidus, galactorrhea.
Ophthalmological: leukokoria, periorbital ecchymoses, opsoclonus,
proptosis, exopthalmos, miosis, ptosis.
Mass effect:
Anterior mediastinal mass- Cough, stridor, pneumonia, tracheal-bronchial
compression; superior vena cava syndrome.
Posterior mediastinal mass- Vertebral or nerve root compression; dysphagia
Uncommon manifestations.
RELATED DIRECTLY TO TUMOR NOT RELATED DIRECTLY TO
TUMOR GROWTH
Superior vena cava syndrome Chronic diarrhea

Subcutaneous nodules Polymyoclonus-opsoclonus

Leukemoid reaction Failure to thrive
Myasthenia gravis Cushing syndrome
Heterochromia Pseudomuscular dystrophy

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2. ONCOLOGIC EMERGENCIES

CONDITION MANIFESTATIONS ETIOLOGY MALIGNANCY TREATMENT

METABOLIC
Allopurinol, alkalinize
Tumor lysis Lymphoma,
Hyperuricemia Uric acid nephropathy urine; hydration and
syndrome leukemia
diuresis, rasburicase.
Kayexalate, sodium
bicarbonate, glucose,
Arrhythmias, cardiac Tumor lysis Lymphoma, and insulin; check for
Hyperkalemia
arrest syndrome leukemia pseudohyperkalemia
from leukemic cell
lysis in test tube
Hydration, forced
Hypocalcemic tetany; diuresis; stop
Tumor lysis Lymphoma,
Hyperphosphatemia metastatic calcification, alkalinization; oral
syndrome leukemia
photophobia, pruritus aluminum hydroxide
to bind phosphate
SIADH; fluid, Restrict free water for
Seizure, lethargy, Leukemia, CNS
Hyponatremia sodium losses in SIADH; replace
asymptomatic tumor
vomiting sodium if depleted
Hydration and
Anorexia, nausea, Bone resorption; furosemide
polyuria, pancreatitis, ectopic Metastasis to bone, diuresis;
Hypercalcemia gastric ulcers; parathormone, rhabdomyosarcoma, corticosteroids;
prolonged PR, vitamin D, or leukemia mithramycin;
shortened QT interval prostaglandins calcitonin,
diphosphonates
HEMATOLOGIC
Bone marrow
Pallor, weakness, heart suppression or Any with Packed red blood cell
Anemia
failure infiltration; blood chemotherapy transfusion
loss
Bone marrow Any with
Thrombocytopenia Petechiae, hemorrhage Platelet transfusion
suppression chemotherapy
Disseminated Fresh frozen plasma;
Sepsis, hypotension, Promyelocytic
intravascular Shock, hemorrhage platelets, treat
tumor factors leukemia, others
coagulation infection
If febrile, administer
Bone marrow broad-spectrum
Any with
Neutropenia Infection suppression or antibiotics, and
chemotherapy
infiltration filgrastim (G-CSF) if
appropriate
Hemorrhage,
Hyperleukocytosis thrombosis; pulmonary Leukostasis; Leukapheresis;
Leukemia
(>50,000/mm3) infiltrates, hypoxia; vascular occlusion chemotherapy
tumor lysis syndrome
Graft versus host Dermatitis, diarrhea, Immunosuppression Any with Corticosteroids;
disease hepatitis and nonirradiated immunosuppression cyclosporine;
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 CONDITION MANIFESTATIONS ETIOLOGY MALIGNANCY TREATMENT
blood products; tacrolimus;
bone marrow antithymocyte
transplantation globulin
SPACE-OCCUPYING LESIONS
Back pain ? radicular
Cord above T10:
symmetric weakness,
increased deep tendon
reflex; sensory level
present; toes up
Conus medullaris
(T10-L2): symmetric MRI or myelography
weakness, increased Metastasis to for diagnosis;
Spinal cord knee reflexes; vertebra and Neuroblastoma; corticosteroids;
compression decreased ankle extramedullary medulloblastoma radiotherapy;
reflexes; saddle space laminectomy;
sensory loss; toes up or chemotherapy
down
Cauda equina (below
L2): asymmetric
weakness; loss of deep
tendon reflex and
sensory deficit; toes
down
Confusion, coma, CT or MRI for
emesis, headache, diagnosis;
Increased hypertension, Primary or corticosteroids;
Neuroblastoma,
intracranial bradycardia, seizures, metastatic brain phenytoin;
astrocytoma; glioma
pressure papilledema, tumor ventriculostomy tube;
hydrocephalus; cranial radiotherapy;
nerve III and VI palsies chemotherapy
Distended neck veins
plethora, edema of
Superior vena cava Superior mediastinal Chemotherapy;
head and neck, Lymphoma
syndrome mass radiotherapy
cyanosis, proptosis,
Horner syndrome
Tracheal Mediastinal mass Radiation,
Respiratory distress Lymphoma
compression compressing trachea corticosteroids

For tumour lysis syndrome refer also the article in IJP. july 2012

3. Late adverse effects of cancer treatment:

1. Neurocognitive defects- functional defects in executive function,

sustained attention, memory, learning deficits, diminished IQ and behavioral
change.

2. Neurosensory defects: hearing loss, visual impairment, glaucoma, retinopathy, peripheral

350
neuropathy

3. Endocrine: GH deficiency, precocious puberty, obesity, hypothyroidism, adrenal

insufficiency

4. Reproductive: gonadal defects, delayed or arrested puberty, premature menopause,

infertility.

5. Cardiac: cardiomyopathy, arrhythmias, myocardial infarction, pericardial fibrosis.

6. Respiratory: pulmonary fibrosis, interstitial pneumonitis, restrictive or obstructive lung

disease

7. Gastrointestinal: chronic enterocolitis, strictures and bowel obstruction

8. Hepatic: hepatic fibrosis and cirrhosis

9. Renal: renal insufficiency, hypertension, glomerular injury and tubular injury.

10. Secondary cancers.

5. BRAIN tumors:
Etiology: not well defined, familial syndromes, cranial irradiation.
Epidemiology: The incidence of CNS tumors is highest in infants and
children ≤5 yr of age
GENES involved:
Neurofibromatosis NF1
Von hippel lindau syndrome VHL
Tuberous sclerosis TSC

Various tumours and incidence:

The Childhood Brain Tumor Consortium reported a slight predominance of infratentorial tumor
location (43.2%), followed by the supratentorial location (40.9%), spinal cord (4.9%), and multiple
sites (11%).

There are age-related differences in primary location of tumor.

 During the first year of life, supratentorial tumors predominate and include, most commonly,
choroid plexus complex tumors and teratomas.
 In children 1-10 yr of age, infratentorial tumors predominate, owing to the high incidence of
juvenile pilocytic astrocytoma and medulloblastoma.

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  After 10 yr of age, supratentorial tumors again predominate, with diffuse astrocytomas most
common.

Clinical features:

The clinical presentation of the patient with a brain tumor depends on the tumor location, the tumor
type, and the age of the child.

1. Signs and symptoms are related to obstruction of cerebrospinal fluid (CSF) drainage paths by
the tumor, leading to increased intracranial pressure (ICP) or causing focal brain dysfunction.
Subtle changes in personality, mentation, and speech may precede these classic signs and
symptoms.
2. Infants with open cranial sutures may present with signs of increased ICP, such as vomiting,
lethargy, and irritability, as well as the later finding of macrocephaly.
3. The classic triad headache, nausea, and vomiting as well as papilledema are associated with
midline or infratentorial tumors. Disorders of equilibrium, gait, and coordination occur with
infratentorial tumors.
4. Torticollis may result in cerebellar tonsil herniation.
5. Tumors of the brainstem region may be associated with gaze palsy, multiple cranial nerve
palsies, and upper motor neuron deficits (e.g., hemiparesis, hyperreflexia, clonus).
6. Supratentorial tumors are more commonly associated with focal disorders such as motor
weaknesses, sensory changes, speech disorders, seizures, and reflex abnormalities.
7. Optic pathway tumors manifest as visual disturbances, such as decreased visual acuity,
Marcus Gunn pupil (afferent pupillary defect), nystagmus, and/or visual field defects.
8. Suprasellar region tumors and third ventricular region tumors may manifest initially as
neuroendocrine deficits, such as diabetes insipidus, galactorrhea, precocious puberty,
delayed puberty, and hypothyroidism.
9. The diencephalic syndrome, which manifests as failure to thrive, emaciation, increased
appetite, and euphoric affect, occurs in infants and young children with tumors in these
regions.
10. Parinaud syndrome is seen with pineal region tumors and is manifested by paresis of
upward gaze, pupillary dilation reactive to accommodation but not to light, nystagmus to
convergence or retraction, and eyelid retraction.
11. Spinal cord tumors and spinal cord dissemination of brain tumors may manifest as long
nerve tract motor and/or sensory deficits, bowel and bladder deficits, and back or radicular

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 pain.

Astrocytoma:

On the basis of their clinicopathologic characteristics, they are grouped as

1. Low-grade astrocytomas (LGA; WHO grade II), (includes Pilocytic Astrocytoma and

fibrillary infiltrating Astrocytoma)

2. Malignant astrocytomas (anaplastic astrocytoma; WHO grade III), and

3. Glioblastoma multiforme (GBM; WHO grade IV).

Pilocytic Astrocytoma (WHO grade I) is the most common Astrocytoma in children.

Microscopically presence of Rosenthal fibers, which are condensed masses of glial filaments helps
establish the diagnosis.

The classic but not exclusive neuroradiologic finding in PA is the presence of a contrast
medium–enhancing nodule within the wall of a cystic mass.

The clinical management of LGAs focuses on a multimodal approach incorporating surgery as the
primary treatment as well as radiation therapy and chemotherapy. The outcome of PA is better than
with fibrillary LGAs.

POSTERIOR FOSSA TUMORS OF

CHILDHOOD

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 RELATIVE
TUMOR INCIDENCE PRESENTATION DIAGNOSIS PROGNOSIS
(%)

Heterogeneous or 65-85% survival;

homogeneously dependent on
2-3 mo of headaches, vomiting,
Medulloblastoma 35-40 enhancing fourth stage/type;
truncal ataxia
ventricular mass; may poorer (20-70%)
be disseminated in infants

Cerebellar hemisphere
90-100%
mass, usually with
Cerebellar 3-6 mo of limb ataxia; secondary survival in
35-40 cystic and solid
astrocytoma headaches, vomiting totally resected
(mural nodule)
pilocytic type
components

Diffusely expanded,
1-4 mo of double vision, minimally or partially
>90% mortality
unsteadiness, weakness, and enhancing mass in
Brain stem in diffuse
10-15 other cranial nerve deficits, 80%; 20% more focal
glioma tumors; better in
facial weakness, swallowing tectal or
localized
deficits, and other deficits cervicomedullary
lesion

Usually enhancing,
2-5 mo of unsteadiness, headaches, fourth ventricular >75% survival in
Ependymoma 10-15 double vision, and facial mass with totally resected
asymmetry cerebellopontine lesions
predilection

As in medulloblastoma, but As in
10-20% (or less)
Atypical primarily in infants; often medulloblastoma, but
>5 survival in
teratoid/rhabdoid associated facial weakness and often more laterally
infants
strabismus extended

5. Retinoblastoma:
Retinoblastoma is an embryonal malignancy of the retina and is the most
common intraocular tumor in children.

Epidemiology:

The median age at diagnosis is approximately 2 yr, and over 90% of cases are diagnosed in children
under 5 yr of age. Overall, about 65- 75% of children with retinoblastoma have unilateral tumors,
with the remainder having bilateral retinoblastoma. Bilateral involvement is more common in
younger children, particularly in those diagnosed under the age of 1 yr.

Retinoblastoma can be either hereditary or sporadic.

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Hereditary cases usually are diagnosed at a younger age and are multifocal and bilateral. The
hereditary form is associated with loss of function of the retinoblastoma gene (RB1) via gene
mutation or deletion.

While sporadic cases are usually diagnosed in older children who tend to have unilateral, unifocal
involvement.

According to Knudson's “two-hit” model of oncogenesis, two mutational events are required for
retinoblastoma tumor development.

Pathogenesis:

Histologically, retinoblastoma appears as a small round blue cell tumor with rosette formation
(Flexner-Wintersteiner rosettes). Retinoblastoma tumors tend to outgrow their blood supply, resulting
in necrosis and calcification.

Endophytic tumors arise from the inner surface of the retina and grow into the vitreous, and can
also grow as tumors suspended within the vitreous itself, known as vitreous seeding. Exophytic
tumors grow from the outer retinal layer and can cause retinal detachment. Tumors can also be both
endophytic and exophytic.

Clinical Manifestations:

1. Retinoblastoma classically presents with leukocoria, a white pupillary reflex, which often is
first noticed when a red reflex is not present at a routine newborn or well child examination or
in a flash photograph of the child.
2. Strabismus often is an initial presenting complaint.
3. Orbital inflammation, hyphema, and pupil irregularity can occur with advancing disease.
4. Pain can occur if secondary glaucoma is present.
5. Only about 10% of retinoblastoma cases are detected by routine ophthalmologic screening in
the context of a positive family history.
6. Children with germ line RB1 mutations are at significant risk for development of second
malignancies, especially osteosarcoma and also soft tissue sarcomas and malignant
melanoma.

Diagnosis:

1. The diagnosis is established by the characteristic ophthalmologic findings.

2. Imaging studies are not diagnostic, and biopsies are contraindicated.
3. Indirect ophthalmoscopy with slit-lamp evaluation can detect retinoblastoma tumors, but a
complete evaluation requires an examination under general anesthesia by an experienced
ophthalmologist.
4. Orbital ultrasonography, CT, or MRI are used to evaluate the extent of intraocular disease
and extraocular spread. Occasionally, a pineal area tumor is detected in a child with hereditary
retinoblastoma, a phenomenon known as trilateral retinoblastoma. MRI allows for better
355
 evaluation of optic nerve involvement.
5. Evaluation of the cerebrospinal fluid and bone marrow for tumor metastasis is required
only if indicated by other clinical, laboratory, or imaging findings.

The differential diagnosis of retinoblastoma includes other causes of leukocoria, including persistent
hyperplastic primary vitreous, Coats disease, cataract, endophthalmitis from Toxocara canis,
choroidal coloboma, and retinopathy of prematurity. (C3 HER)

Treatment:

Treatment is determined by

1. the size and location of the tumors and

2. Whether the child has hereditary or sporadic disease.

As newer modalities for local control of intraocular tumors and more effective systemic
chemotherapy have emerged, primary enucleation is being performed less often.

Most unilateral disease presents with a solitary, large tumor. Enucleation is performed if there is no
potential for the salvage of useful vision.

With bilateral disease, chemoreduction in combination with focal therapy (laser photocoagulation
or cryotherapy) has replaced the traditional approach of enucleation of the more severely affected eye
and irradiation of the remaining eye.

Alternative treatment options currently under investigation include other systemic chemotherapy
agents such as topotecan and other sites of chemotherapy administration, including periocular and
ophthalmic artery infusions.

All first-degree relatives of children with known or suspected hereditary retinoblastoma should
have retinal examinations.

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 PULMONOLOGY

1. Pediatric interstitial lung diseases (ILDs)

2. Pneumothorax:
3. EMPYEMA:
4. Diaphragmatic hernia:
5. Bronchiectasis:
6. Tonsils and adenoids:
7. Cystic fibrosis:
8. Chronic recurrent aspirations: see also jun- sep 2012 ijpp
9. Asthma: see also jun- sep 2012 ijpp
10. Community acquired pneumonia see also jun- sep 2012 ijpp
11. OSAS:
12. Pulmonary function tests:
13. STRIDOR:
14. Croup (ALTB)
15. SIDS
16. Primary ciliary diskinesia
17. Recurrent pneumonia see also jun- sep 2012 ijpp
18. Non invasive ventilation: see also jun- sep 2012 ijpp
19. Epistaxis
20. Ards
21. Congenital malformations of lung
22. Bronchiolitis
23. Respiratory failure
24. Hemoptysis - article ip 2010 march
25. Discuss the approach to diagnosis, treatment and also outline the prognosis of Wheezing in
infancy.

1. Pediatric interstitial lung diseases (ILDs) are a group of uncommon, heterogeneous, familial, or
sporadic diseases that cause disruption of alveolar interstitium and sometimes involve airway
pathology.
PEDIATRIC INTERSTITIAL LUNG DISEASES
1. DISORDERS MORE COMMON IN INFANCY AND YOUNG CHILDREN

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 Diffuse developmental disorders: acinar dysplasia, congenital alveolar dysplasia, alveolar
capillary dysplasia with misalignment of pulmonary veins
Growth abnormalities reflecting deficient alveolarization: pulmonary hypoplasia, chronic
neonatal lung disease, chromosomal disorders, congenital heart disease
Neuroendocrine cell hyperplasia of infancy
Pulmonary interstitial glycogenosis
Surfactant dysfunction disorders: surfactant protein–B mutation, surfactant protein–C
mutation, ABCA3 mutation
2. DISORDERS OF KNOWN ASSOCIATION
Infectious/post-infectious processes
Environmental agents: hypersensitivity pneumonitis, toxic inhalation
Aspiration syndromes
3. DISORDERS OF IMMUNOCOMPROMISED HOSTS
Opportunistic infections
Human herpes virus 8 associated with common variable immunodeficiency syndrome
Lymphoid intestinal pneumonia (HIV infection)
Therapeutic interventions: chemotherapy, radiation, transplantation, and rejection
4. INTERSTITIAL LUNG DISEASES OF UNKNOWN ETIOLOGY
Usual interstitial pneumonitis
Desquamative pneumonitis
Lymphocytic interstitial pneumonitis

Eosinophilic pneumonia
Pulmonary hemosiderosis
Pulmonary alveolar proteinosis
Pulmonary vascular disorders
Pulmonary lymphatic disorders

5. SYSTEMIC DISORDERS WITH PULMONARY INVOLVEMENT

Immune-mediated/collagen vascular disorders
Malignant infiltrates
Langerhans cell histiocytosis
Sarcoidosis
Neurocutaneous syndromes
Storage diseases

Clinical Manifestations:

1. Tachypnea, dyspnea, cough, and failure to thrive are commonly present.

2. A positive family history, is suggestive of a genetic or familial disease, such as a surfactant
dysfunction. Symptoms are usually insidious and occur in a continuous, not episodic,
pattern.

358
 3. Tachypnea, crackles, and retractions are noted on physical examination in the majority of
children with ILD, but chest auscultation findings can be normal.
4. Wheezing and fever are not common complaints.
5. Pulmonary hypertension, failure to thrive, and severe fibrosis are considered poor prognostic
indicators
6. Cyanosis and a prominent 2nd heart sound are suggestive of severe disease.
7. Anemia or hemoptysis suggests a pulmonary vascular disease or pulmonary hemosiderosis.
8. Rashes or joint complaints are consistent with an underlying connective tissue disease.

Diagnosis:

Chest radiographic abnormalities can be classified as interstitial, reticular, nodular, reticulonodular,

or honeycombed. The chest radiographic appearance may also be normal despite significant clinical
impairment and may correlate poorly with the extent of disease.

High-resolution CT (HRCT) of the chest better defines the extent and distribution of disease and can
provide specific information for selection of a biopsy site. Serial HRCT scans may be of benefit in
monitoring disease progression and severity.

Pulmonary function tests (PFTs) including infant PFTs, are important in defining the degree of
pulmonary dysfunction and in following the response to treatment.

Bronchoalveolar lavage (BAL) may provide helpful information regarding secondary infection,
bleeding, and aspiration, and allows cytologic and molecular analyses. Although BAL does not
usually determine the exact diagnosis, it can be diagnostic for disorders such as pulmonary alveolar
proteinosis.

Lung biopsy for histopathology is usually the final step and is often necessary for a diagnosis.

Genetic testing for surfactant dysfunction mutational analysis is now available.

Evaluation for possible systemic disease may also be necessary.

Treatment:

Supportive care - supplemental oxygen for hypoxia and adequate nutrition for growth failure.

Antimicrobial treatment may be necessary for intercurrent infections.

Anti-inflammatory treatment with corticosteroids remains the initial treatment of choice. The usual
dose of prednisone is 1-2 mg/kg/24 hr for 6-8 wk with tapering of dosage dictated by clinical
response.

Alternative, but not adequately evaluated, agents include hydroxychloroquine, azathioprine,

cyclophosphamide,

Lung transplantation for progressive or end-stage ILD is successful in some infants and children.
359
Appropriate treatment for underlying systemic disease is indicated.

Supervised pulmonary rehabilitation programs may be helpful.

Genetic counseeling

Prognosis: The overall mortality of ILD is very variable and depends on specific
diagnosis. Some children recover spontaneously without treatment, but other children steadily
progress to death.

2. Pneumothorax:

Pneumothorax is the accumulation of extrapulmonary air within the chest, most commonly from
leakage of air from within the lung.

CAUSES OF PNEUMOTHORAX
IN CHILDREN
SPONTANEOUS
Primary idiopathic—usually resulting from ruptured subpleural
blebs
Secondary blebs
Congenital lung disease:
Congenital cystic adenomatoid malformation
Bronchogenic cysts
Pulmonary hypoplasia
Conditions associated with increased intrathoracic pressure:
Asthma
Bronchiolitis
Air-block syndrome in neonates
Cystic fibrosis
Airway foreign body
Infection:
Pneumatocele
Lung abscess
Bronchopleural fistula
Diffuse lung disease:
Langerhans cell
histiocytosis
Tuberous sclerosis
Marfan syndrome
Ehlers-Danlos syndrome
Metastatic neoplasm—usually osteosarcoma (rare)
TRAUMATIC
Non iatrogenic

360
 Penetrating trauma
Blunt trauma
Loud music (air
pressure)
Iatrogenic
Thoracotomy
Thoracoscopy, thoracentesis
Tracheostomy
Tube or needle puncture
Mechanical ventilation
Catamenial

Diagnosis:

Clinical examination: Usually, there is respiratory distress, with retractions,

markedly decreased breath sounds, and a tympanitic percussion note over the involved hemithorax.
The larynx, trachea, and heart may be shifted toward the unaffected side. When fluid is present, there
is usually a sharply limited area of tympany above a level of flatness to percussion. The presence of
amphoric breathing or, when fluid is present in the pleural cavity, of gurgling sounds synchronous
with respirations suggests an open fistula connecting with air-containing tissues.

Radiological examination: The diagnosis of pneumothorax is usually established by

radiographic examination. The amount of air outside the lung varies with time. A radiograph that is
taken early shows less lung collapse than one taken later if the leak continues.

Treatment:

Therapy varies with the extent of the collapse and the nature and severity of the underlying disease.

Medical:

A small (<5%) or even moderate-sized pneumothorax in an otherwise normal child may resolve
without specific treatment, usually within about 1 wk. A small pneumothorax complicating asthma
may also resolve spontaneously.

Administering 100% oxygen may hasten resolution. Pleural pain

deserves analgesic treatment.

Surgical:

Treatment of the underlying pulmonary disease should begin on admission and should be continued
throughout the course of treatment directed at the air leak.

Needle aspiration may be required on an emergency basis for tension pneumothorax.

If the pneumothorax is recurrent, secondary, or under tension, or there is >5% collapse, chest tube
drainage is necessary.

Thoracotomy either closed or open

VATS is a preferred therapy for blebectomy, pleural stripping, pleural brushing, and instillation of
361
sclerosing agents.

Chemical pleurodesis. This is carried out by the introduction of talc, doxycycline, or

iodopovidone into pleural space.

Complications: hydropneumothorax, pyopneumothorax, empyema, thickened pleura

3. EMPYEMA:

Etiology: Empyema is an accumulation of pus in the pleural

space.
Streptococcus pneumoniae, Staphylococcus aureus Haemophilus influenzae, Group A streptococcus,
gram-negative organisms, tuberculosis, fungi, and malignancy are less common causes.
The disease can also be produced by rupture of a lung abscess into the pleural space, by
contamination introduced from trauma or thoracic surgery, or, rarely, by mediastinitis or the extension
of intra-abdominal abscesses.

Epidemiology: Empyema is most frequently encountered in infants and preschool

children. It occurs in 5-10% of children with bacterial pneumonia and in up to 86% of children with
necrotizing pneumonia.

Pathology: Empyema has 3 stages: During the exudative stage,

fibrinous exudate forms on the pleural surfaces. In the fibrinopurulent stage, fibrinous septa form,
causing loculation of the fluid and thickening of the parietal pleura. During the organizational stage,
there is fibroblast proliferation; pockets of loculated pus may develop into thick-walled abscess
cavities or the lung may collapse and become surrounded by a thick, inelastic envelope (peel).

Clinical Manifestations: The initial signs and symptoms are primarily those of bacterial
pneumonia.

Laboratory Findings:

1. Leukocytosis and an elevated sedimentation rate may be found.

2. Radiographically, all pleural effusions appear similar, but the absence of a shift of the fluid
with a change of position indicates a loculated empyema.
3. Septa may be confirmed by ultrasonography or CT.
4. The maximal amount of fluid obtainable should be withdrawn by thoracentesis. The effusion
is empyema if bacteria are present on Gram staining, the pH is <7.20, and there are
>100,000 neutrophils/µL.
5. In patients with negative blood culture results for pneumococcus, the pneumococcal
polymerase chain reaction (PCR) analysis is most helpful to making a diagnosis.
6. Blood cultures have a high yield, possibly higher than cultures of the pleural fluid.

Complications: Bronchopleural fistulas and pyopneumothorax commonly

develop. Other local complications include purulent pericarditis, pulmonary abscesses, peritonitis
from extension through the diaphragm, and osteomyelitis of the ribs. Septicemia.
Temporary scoliosis.

Treatment: Treatment includes systemic antibiotics and thoracentesis

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and possibly chest tube drainage with or without a fibrinolytic agent, video-assisted thorascopic
surgery (VATS), or open decortications. Clinical response in empyema is slow; even with optimal
treatment, there may be little improvement for as long as 2 wk.

Instillation of fibrinolytic agents into the pleural cavity via the chest tube may promote drainage,
decrease fever, lessen need for surgical intervention, and shorten hospitalization. Streptokinase
15,000 U/kg in 50 mL of 0.9% saline daily for 3-5 days and urokinase 40,000 U in 40 mL saline
every 12 hr for 6 doses have been evaluated in randomized trials in children.

If pneumatoceles form, no attempt should be made to treat them surgically or by aspiration, unless
they reach sufficient size to cause respiratory embarrassment or become secondarily infected.
Pneumatoceles usually resolve spontaneously with time. The long-term clinical prognosis for
adequately treated empyema is excellent.

Supportive treatment- antipyretics, nutrition and chest physiotherapy.

4. Diaphragmatic hernia:

A diaphragmatic hernia is defined as a communication between the abdominal and thoracic cavities
with or without abdominal contents in the thorax.

Embryology:

 Septum transversum – gives rise to central tendon

 Pleuroperitoneal membrane – gives rise to dorsolateral portion of diaphragm
 Esophageal mesentry – gives rise to dorsal crura
 Interstitial muscle groups – gives rise to muscular portion of the body wall

Fetal lung development:

 Pseudoglandular phase: lung bud formation begins at 5th week and ends at 16- 17th week.
 Canalicular stage: 16 wk- 25wk
 Saccular stage: 26- 36 wks alveolar sac development
 Alveolar stage: till 8 years of life alveoli continue to develop

The etiology may be congenital or traumatic.

The defect may be at the

1. Esophageal hiatus (hiatal),

2. Paraesophageal (adjacent to the hiatus),
3. Retrosternal (Morgagni), or at the
4. Posterolateral (Bochdalek) portion of the diaphragm.

The term congenital diaphragmatic hernia typically refers to the Bochdalek form.

The Bochdalek hernia accounts for up to 90% of the hernias seen in the newborn period, with
80-90% occurring on the left side. The Morgagni hernia accounts for 2-6% of congenital
diaphragmatic defects.

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Epidemiology: females left most are sporadic syndromes
turner, trisomy 21,13,18.

Pathology: Although CDH is characterized by a structural diaphragmatic defect, a major limiting

factor for survival is the associated pulmonary hypoplasia.

Diagnosis and Clinical Presentation:

CDH can be diagnosed on prenatal ultrasonography (between 16 and 24 wk of gestation) in > 50%
of cases. High-speed fetal MRI can further define the lesion.

Findings on ultrasonography may include polyhydramnios, chest mass, mediastinal shift, gastric
bubble or a liver in the thoracic cavity, and fetal hydrops.

Respiratory distress is a cardinal sign in babies with CDH. It may occur immediately after birth, or
there may be a “honeymoon” period of up to 48 hr during which the baby is relatively stable.
Respiratory distress is characterized clinically by tachypnea, grunting, use of accessory muscles, and
cyanosis. Children with CDH also have a scaphoid abdomen and increased chest wall diameter.
Bowel sounds may also be heard in the chest with decreased breath sounds bilaterally. The point of
maximal cardiac impulse may be displaced away from the side of the hernia if mediastinal shift has
occurred.

A chest radiograph and passage of a nasal gastric tube are all that is usually required to confirm the
diagnosis.

Differential diagnosis - pulmonary sequestration, cystic adenomatoid malformation.

Treatment

1. Initial Management: Aggressive respiratory support is often needed in

children with CDH. This includes rapid endotracheal intubation, sedation, and possibly paralysis.
Prolonged mask ventilation in the delivery room, which enlarges the stomach and small bowel and
thus makes oxygenation more difficult, must be avoided. Gentle ventilation with permissive
hypercapnia reduces lung injury and mortality. Although surfactant is commonly used, no study has
proven that it is beneficial in treatment of CDH.

2. Ventilation Strategies: Conventional mechanical ventilation, HFOV, and ECMO are

the 3 main strategies to support respiratory failure in the newborn with CDH. The goal is to maintain
oxygenation without inducing barotrauma. NO is a selective pulmonary vasodilator. Its use reduces
ductal shunting and pulmonary pressures and results in improved oxygenation. If the patient cannot
be weaned from ECMO after repair of CDH, options include discontinuing support and, in rare cases,
lung transplantation.

3. Novel Strategies: There are no reliable prenatal prognosticators of

outcomes in children with CDH. The most widely studied is fetal ultrasonography. (A)There were no
survivors when the LHR (lung to head size ratio) was <1, and all babies with LHR >1.4 survived.
(B) A second important consideration was the presence of liver in the thoracic cavity, which is a
poor prognostic feature. A study is under way to evaluate the role of Partial Liquid Ventilation in
neonates with CDH. EXIT procedure. Tracheal occlusion inutero.

4. Surgical Repair: The ideal time to repair the diaphragmatic defect is

under debate. Most centers wait at least 48 hr after stabilization and resolution of the pulmonary
hypertension. Good relative indicators of stability are the requirement for conventional
ventilation only, a low PIP, and a Fio2 <50.
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Complications: Pulmonary problems continue to be a source of morbidity for long-term
survivors of CDH.

Gastroesophageal reflux disease (GERD), delayed growth,

pulmonary hypertension,

Neurocognitive defects, scoliosis.

Relative predictors of a poor prognosis include an

 associated major anomaly,

 symptoms before 24 hr of age,
 severe pulmonary hypoplasia,
 herniation to the contralateral lung, and the
 need for ECMO

5. Bronchiectasis:

Bronchiectasis, a disease characterized by irreversible abnormal dilatation and anatomic

distortion of the bronchial tree, likely represents a common end stage of a number of nonspecific and
unrelated antecedent events.

Etiology: cystic fibrosis is the most common cause of clinically significant bronchiectasis.

Other conditions - primary ciliary dyskinesia, foreign body aspiration, aspiration of gastric
contents, immune deficiency syndromes (especially humoral immunity), and infection, especially
pertussis, measles, and tuberculosis.

Bronchiectasis can also be congenital, as in Williams-Campbell syndrome, Marnier-Kuhn

syndrome, right middle lobe syndrome, yellow nail syndrome.

Pathogenesis: Three basic mechanisms are involved in the

pathogenesis of bronchiectasis. Obstruction, Infections, Chronic inflammation. The common
thread in the pathogenesis of bronchiectasis consists of difficulty clearing secretions and recurrent
infections with a “vicious circle” of infection and inflammation resulting in airway injury and
remodeling.

Three pathologic forms, best defined by high-resolution CT (HRCT) scan. Cylindrical

Bronchiectasis, Varicose bronchiectasis, Saccular (cystic) Bronchiectasis this is the most severe
form of bronchiectasis.

The following definitions have been proposed:

prebronchiectasis (chronic or recurrent endobronchial infection with nonspecific HRCT

changes—may be reversible); HRCT bronchiectasis (clinical symptoms with HRCT
evidence of bronchial dilation—may persist, progress, or improve and resolve);
established bronchiectasis (like the previous but with no resolution within 2 yr).

Clinical Manifestations: Production of copious purulent sputum. Hemoptysis , Fever ,

anorexia and poor weight gain. Physical examination - crackles , wheezing, digital clubbing.
Pulmonary function studies may demonstrate an obstructive, restrictive, or mixed pattern.
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Diagnosis : Conditions that can be associated with bronchiectasis should be ruled out by
appropriate investigations (e.g., sweat test, immunologic work-up).

Chest radiographs of patients with bronchiectasis tend to be nonspecific. Typical findings can
include increase in size and loss of definition of bronchovascular markings, crowding of bronchi, and
loss of lung volume. In more severe forms, cystic spaces, occasionally with air-fluid levels and
honeycombing, may occur.

Thin-section HRCT scanning is the gold standard, because it has excellent sensitivity and
specificity. The addition of radiolabeled aerosol inhalation to CT scanning can provide even more
information.

The CT findings in patients with bronchiectasis typically include

cylindrical (“tram lines,” “signet ring appearance”), varicose (bronchi
with “beaded contour”), cystic (cysts in “strings and clusters”).
The lower lobes are most commonly affected.

Treatment:
 Chest physiotherapy (postural drainage), antibiotics, and bronchodilators are essential.
 Any underlying disorder (immunodeficiency, aspiration) that may be contributing must be
addressed.
 When localized bronchiectasis becomes more severe or resistant to medical management,
segmental or lobar resection may be warranted.
 Lung transplantation can also be performed in patients with bronchiectasis.
 Overall, however, the prognosis for patients with bronchiectasis has improved considerably in
the past few decades.

6. Tonsils and adenoids:

Waldeyer ring refers to the lymphoid tissue that surrounds the opening of the oral and nasal cavities
into the pharynx. It is composed of the palatine tonsils, the pharyngeal tonsil or adenoid, lymphoid
tissue surrounding the eustachian tube orifice in the lateral walls of the nasopharynx, the lingual
tonsil at the base of the tongue, and scattered lymphoid tissue throughout the remainder of the
pharynx.

Pathology 4 headings
Acute Infection: Most episodes of acute pharyngotonsillitis are caused by
viruses. Group A β-hemolytic streptococcus (GABHS) is the most common cause of bacterial
infection in the pharynx. Other viruses being adeno, corona, ebv and rsv.

Chronic Infection: The tonsillar crypts can accumulate desquamated epithelial

cells, lymphocytes, bacteria, and other debris, causing cryptic tonsillitis. With time, these cryptic
plugs can calcify into tonsillar concretions or tonsillolith.

Airway Obstruction: Both the tonsils and adenoids are a major cause of upper
airway obstruction in children. Airway obstruction in children is typically manifested in
sleep-disordered breathing, including obstructive sleep apnea, obstructive sleep hypopnea, and upper
airway resistance syndrome. Sleep-disordered breathing secondary to adenotonsillar breathing is a
cause of growth failure.

Tonsillar Neoplasm: Rapid enlargement of one tonsil is highly suggestive of a

tonsillar malignancy, typically lymphoma in children.

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Clinical features: 4 features

Acute Infection: Symptoms of GABHS infection include odynophagia,

dry throat, malaise, fever and chills, dysphagia, referred otalgia, headache, muscular aches, and
enlarged cervical nodes. Signs include dry tongue, erythematous enlarged tonsils, tonsillar or
pharyngeal exudate, palatine petechiae, and enlargement and tenderness of the jugulodigastric lymph
nodes .

Chronic Infection: Children with chronic or cryptic tonsillitis often present

with halitosis, chronic sore throats, foreign body sensation, or a history of expelling foul-tasting and
foul-smelling cheesy lumps. Examination can reveal tonsils of almost any size and often they
contain copious debris within the crypts.

Airway Obstruction: In many children, the diagnosis of airway obstruction can

be made by history and physical examination. Daytime symptoms of airway obstruction, secondary
to adenotonsillar hypertrophy, include chronic mouth breathing, nasal obstruction, hyponasal speech,
hyposmia, decreased appetite, poor school performance, and, rarely, symptoms of right-sided heart
failure. Night time symptoms consist of loud snoring, choking, gasping, frank apneas, restless sleep,
abnormal sleep positions, somnambulism, night terrors, diaphoresis, enuresis, and sleep talking.
Large tonsils are typically seen on examination, although the absolute size might not indicate the
degree of obstruction.

Tonsillar Neoplasm: The rapid unilateral enlargement of a tonsil, especially if

accompanied by systemic signs of night sweats, fever, weight loss, and lymphadenopathy, is highly
suggestive of a tonsillar malignancy.

Treatment
Medical Management:

Penicillin V is inexpensive and is given bid or tid for 10 days: 250 mg/dose for children <27 kg (60
lb) and 500 mg/dose for larger children and adults.

Oral amoxicillin is often preferred for children because of taste, availability as chewable tablets, and
convenience of once-daily dosing (750 mg fixed dose or 50 mg/kg, maximum 1 g) given orally for 10
days.

For patients allergic to penicillin--Erythromycin or azithomycin or clarithromycin or clindamycin can

be used.

Surgical management:

Tonsillolith or debris may be expressed manually with either a cotton-tipped applicator or a water jet.
Chronically infected tonsillar crypts can be cauterized using silver nitrate.

Tonsillectomy Tonsillectomy alone is usually performed for recurrent or chronic

pharyngotonsillitis. Indications for surgery remain uncertain --Potential but nonevidenced based
indications include 7 or more throat infections treated with antibiotics in the preceding yr, 5 or more
throat infections treated in each of the preceding 2 yr, or 3 or more throat infections treated with
antibiotics in each of the preceding 3 yr. Rarely in children, tonsillectomy is indicated for biopsy of a
unilaterally enlarged tonsil to exclude a neoplasm or to treat recurrent hemorrhage from superficial
tonsillar blood vessels.
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Adenoidectomy Adenoidectomy alone may be indicated for the treatment of chronic
nasal infection (chronic adenoiditis), chronic sinus infections that have failed medical management,
and recurrent bouts of acute otitis media. Adenoidectomy alone may be curative in the management
of patients with nasal obstruction, chronic mouth breathing, and loud snoring suggesting
sleep-disordered breathing.

Complications:

Acute Pharyngotonsillitis Peritonsillar Infection

Retropharyngeal Space Infection
Parapharyngeal Space Infection
Recurrent or Chronic Pharyngotonsillitis

7. Cystic fibrosis:
Characterized by obstruction and infection of airways and maldigestion and its consequences, cystic
fibrosis (CF) is an inherited multisystem disorder of children and adults.
Genetics: Dysfunction of the cystic fibrosis transmembrane conductance regulator protein (CFTR),
the primary defect, leads to a wide and variable array of presenting manifestations and complications.
The most prevalent mutation of CFTR is the deletion of a single phenylalanine residue at amino acid
508 (ΔF508).

Pathogenesis:

Clinical
features:

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Dios- distal intestinal obstruction syndrome HPOA- hypertrophic pulmonary osteoarthritis
DIAGNOSTIC CRITERIA FOR CYSTIC FIBROSIS (CF)
Presence of typical clinical features (respiratory, gastrointestinal, or genitourinary)
OR A history of CF in a sibling OR A positive newborn
screening test

PLUS
Laboratory evidence for CFTR (CF transmembrane regulator) dysfunction:
Two elevated sweat chloride concentrations obtained on separate days
OR Identification of two CF mutations

OR An abnormal nasal potential difference measurement

Treatment

The treatment plan should be comprehensive and linked to close monitoring and early, aggressive
intervention.

1. General Approach to Care: Initial efforts after diagnosis should be intensive and
should include baseline assessment, initiation of treatment, clearing of pulmonary involvement, and
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education of the patient and parents. Because secretions of CF patients are not adequately
hydrated, attention in early childhood to oral hydration, especially during warm weather or with
acute gastroenteritis, may minimize complications associated with impaired mucus clearance.
Intravenous therapy for dehydration should be initiated early. Special emphasis on nutrition should
be advised.

2. Pulmonary Therapy: The object of pulmonary therapy is to

clear secretions from airways and to control infection.

3. Inhalation Therapy: Metered-dose inhalers can deliver some

agents, such as bronchodilators and corticosteroids, with a spacer for younger children. Human
recombinant DNase (2.5 mg), given as a single daily aerosol dose. Nebulized hypertonic saline is
also useful.

4. Airway Clearance Therapy: Airway clearance treatment usually consists of chest

percussion combined with postural drainage. Chest physical therapy (PT) can be particularly useful.
Chest PT is recommended 1-4 times a day, depending on the severity of lung dysfunction.

5. Antibiotic Therapy: Antibiotics are the mainstay of therapy designed

to control progression of lung infection. The goal is to reduce the intensity of endobronchial
infection and to delay progressive lung damage. Aerosol delivery of antibiotics has been used as an
option for home delivery of additional agents, such as tobramycin, colistin, and gentamicin.

6. Anti-Inflammatory Agents: Corticosteroids are useful for the treatment of allergic

bronchopulmonary aspergillosis and severe reactive airway disease occasionally encountered in
children with CF.

7. Endoscopy and Lavage: Treatment of obstructed airways sometimes includes

tracheobronchial suctioning or lavage, especially if atelectasis or mucoid impaction is present.

8. pancreatic enzyme replacement

9. Emerging Therapies: mannitol inhalation, role of Aminoglycosides, PTC

124, heart lung transplantation and gene therapy.

8. Chronic recurrent aspirations:

CONDITIONS PREDISPOSING TO ASPIRATION LUNG INJURY IN CHILDREN

ANATOMICAL AND MECHANICAL
Tracheoesophageal fistula Tracheostomy
Endotracheal tube
Laryngeal cleft Cleft palate
Vascular ring Gastroesophageal reflux
disease Obesity

Micrognathia Macroglossia
Achalasia

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ANATOMICAL AND MECHANICAL

NEUROMUSCULAR
Altered consciousness Increased intracranial pressure
Immaturity of swallowing/Prematurity

Hydrocephalus Vocal cord paralysis

Cerebral palsy Muscular dystrophy

Myasthenia gravis Guillain-Barre syndrome

MISCELLANEOUS
Poor oral hygiene
Prolonged hospitalization
Poor feeding techniques (bottle propping, overfeeding, inappropriate foods for toddlers)

SUMMARY OF DIAGNOSTIC TESTS OF

ASPIRATION
EVALUATION BENEFITS LIMITATIONS
Inexpensive and widely available
Insensitive to early subtle changes of
1.Chest radiograph Assesses accumulation of injury over
lung injury
time
Sensitive in detecting lung injury, such as More radiation exposure than plain
2. HRCT bronchiectasis, Less radiation than radiograph
conventional CT Expensive
Information limited if child consumes
3.VSS Evaluates all phases of swallowing
only small quantities
(videoflouroscopic Evaluates multiple consistencies
Difficult to perform in child who has
swallow study)
not been feeding by mouth

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EVALUATION BENEFITS LIMITATIONS
Radiation exposure proportional to
study duration Cannot be
performed at bedside
Ability to thoroughly evaluate functional
Blind to oesophageal phase and actual
anatomy
4. FEES/with swallow
Can assess risk of aspiration in non orally
sensory testing Invasive Expensive
feeding child. No radiation exposure
Not widely available
Can be performed at bedside.
Evaluates anatomy of airways Uncertainty regarding interpretation of
sample available for multiple cytological lipid-laden macrophage index
5. BAL
and microbiological tests Requires sedation
Becoming more widely available Invasive Expensive
Difficult to establish causal
6. Esophageal pH Current gold standard for diagnosis of
relationship between GOR and
monitoring GOR
aspiration
Likely future gold standard for diagnosis
7. Esophageal Lack of normative data for children
of GERD
impedance Somewhat invasive
Able to evaluate for GERD without
monitoring Expensive and Not widely available
stopping medications
8. Performed under physiological Poor sensitivity
Gastrooesophageal conditions May not differentiate between
scintigraphy Low radiation exposure aspiration from dysphagia or GERD
Child does not have to be challenged
9. Radionuclide Unknown relationship to disease
with food bolus
salivagram outcomes
Low radiation exposure
screening test or confirmatory test
Can only be performed in children with
10. Dye studies Repeating over time allows for broader
tracheostomies
evaluation
HRCT: high-resolution computed tomography; VSS: videofluoroscopic
swallow study; FEES: fibreoptic-endoscopic evaluation of
swallowing;

Treatment:

1. Medical treatment with anticholinergics, such as glycopyrrolate or scopolamine, may

significantly reduce morbidity from salivary aspiration but often has side effects.

2. Nasogastric tube feedings.

3. Fundoplication with gastrostomy or jejunostomy feeding tube.

4. Aggressive surgical intervention with salivary gland excision, ductal ligation, laryngotracheal

separation, or esophagogastric disconnection can be considered in severe, unresponsive cases.

Asthma: Etiology Simplea, rail bag, l- rape, a- para

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 Although the genetic linkages to asthma have sometimes differed between cohorts, asthma has been
consistently linked with loci containing proallergic, proinflammatory genes (the interleukin [IL]-4
gene cluster on chromosome 5).

EARLY CHILDHOOD RISK FACTORS FOR PERSISTENT ASTHMA:

1. Parental asthma
3. Severe lower respiratory tract infection:
2. Allergy: Pneumonia
Atopic dermatitis (eczema) Bronchiolitis requiring
hospitalization
Allergic rhinitis
4. Wheezing apart from colds 5. Male
Food allergy gender
Inhalant allergen sensitization 6. Low birth weight
7. Reduced lung function at birth
Food allergen sensitization
8. Environmental tobacco smoke exposure
9. Possible use of acetaminophen
(paracetamol)
10. Exposure to chlorinated swimming
pools

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Types of childhood asthma:

3 types

(1) Recurrent wheezing in early childhood, primarily triggered by common viral infections of the
respiratory tract.

(2) Chronic asthma associated with allergy that persists into later childhood and often adulthood.

(3) A 3rd type of childhood asthma typically emerges in females who experience obesity and
early-onset puberty (by 11 yr of age).

RECURRENT COUGHING/ WHEEZING PATTERNS IN CHILDHOOD, BASED ON

NATURAL HISTORY

1. TRANSIENT EARLY WHEEZING

Common in early preschool years

Recurrent cough/wheeze, primarily triggered by common respiratory viral infections
Tends to resolve during the preschool years, without increased risk for asthma in later life.

2. PERSISTENT ATOPY-ASSOCIATED ASTHMA

Begins in early preschool years
Associated with atopy in early preschool years:
Clinical (e.g., atopic dermatitis in infancy, allergic rhinitis, food allergy)
Biologic (e.g., early inhalant allergen sensitization, increased serum immunoglobulin E,
increased blood eosinophils)

Highest risk for persistence into later childhood and adulthood

Lung function abnormalities

3. NONATOPIC WHEEZING

Wheezing/coughing beginning in early life, often with respiratory syncytial virus infection;
resolves in later childhood without increased risk of persistent asthma
Associated with bronchial hyperresponsiveness near birth
4. ASTHMA WITH DECLINING LUNG FUNCTION

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 Children with asthma with progressive increase in airflow limitation
Associated with hyperinflation in childhood, male gender

5. LATE-ONSET ASTHMA IN FEMALES, ASSOCIATED WITH OBESITY AND EARLY-ONSET PUBERTY

Onset between 8 and 13 yr of age

Associated with obesity and early-onset puberty; specific for females

6. OCCUPATIONAL-TYPE ASTHMA IN CHILDREN

Children with asthma associated with occupational-type exposures known to trigger asthma
in adults in occupational settings (e.g., endotoxin exposure in children raised on farms)

Pathogenesis:

Hypersensitivity or susceptibility to a variety of provocative exposures or triggers can lead to airway

SAME SBI

1. inflammation, 2. AHR, 3. edema,

4. basement membrane thickening,

5. subepithelial collagen deposition, 6. smooth

muscle and mucous gland hypertrophy,

and 7. mucus hypersecretion— all processes that contribute to airflow obstruction.

Asthma triggers:

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 1.Common viral infections of the respiratory tract
2. Aeroallergens in sensitized asthmatic patients: 4. Environmental tobacco smoke
Animal dander 5. Air pollutants
Indoor allergens Ozone
Dust mites Sulfur dioxide
Cockroaches Particulate matter
Molds Wood- or coal-burning smoke
3. Seasonal aeroallergens: Endotoxin, mycotoxins
Pollens (trees, grasses, weeds) Dust
Seasonal molds 6. Strong or noxious odors or fumes:
Perfumes, hairsprays
8. Cold air, dry air
Cleaning agents
9. Exercise
10. Crying, laughter, hyperventilation 7. Occupational exposures:
11. Co-morbid conditions: Farm and barn exposures
Rhinitis Sinusitis Gastroesophageal Formaldehydes, paint fumes
reflux

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Symptoms While at rest (infant—shorter While at rest (infant—sto
While walking
Breathlessness cry, difficulty feeding) feeding)

Position Can lie down Prefers sitting Sits upright

Talks in Sentences Phrases Words

Alertness May be agitated Usually agitated Usually agitated

Signs Respiratory rate Increased Increased Often >30 breaths/min

Use of accessory muscles;

Usually not Commonly Usually
suprasternal retractions

Moderate; often only Usually loud; througho

Wheeze Loud, throughout exhalation
end-expiratory inhalation and exhalation

Pulse rate (beats/min)[‡] <100 100-120 >120

Often present
Absent May be present
Pulsus paradoxus <10 mm >25 mm Hg (adult)
10-25 mm Hg
Hg
20-40 mm Hg
(child)

Peak expiratory flow (value Approx. 40-69% or

≥70% <40%
predicted or personal best) response lasts <2 hr

Pao2 <60 mm Hg; possib

Normal ≥60 mm Hg
cyanosis

≥42 mm Hg; possib

Pco2 <42 mm Hg <42 mm Hg
respiratory failure

Sao2 >95% 90-95% <90%

377
Laboratory findings:

Lung function tests can help to confirm the diagnosis of asthma and to determine disease severity.

Spirometry

A, Spirometric flow-volume loops. A is an expiratory flow-volume loop of a nonasthmatic person

without airflow limitation. B through E are expiratory flow-volume loops in asthmatic patients with
increasing degrees of airflow limitation (B is mild; E is severe). Note the “scooped” or concave
appearance of the asthmatic expiratory flow-volume loops; with increasing obstruction, there is
greater “scooping.”

B, Spirometric volume-time curves. Subject 1 is a nonasthmatic person; subject 2 is an asthmatic

patient. Note how the FEV 1 and FVC lung volumes are obtained. The FEV 1 is the volume of air
exhaled in the 1st sec of a forced expiratory effort. The FVC is the total volume of air exhaled during
a forced expiratory effort. Note that subject 2's FEV 1 and FEV 1 /FVC ratio are smaller than subject
1's, demonstrating airflow limitation. Also, subject 2's FVC is very close to what is expected. FEV 1 ,
forced expiratory volume in 1 sec; FVC, forced vital capacity.

LUNG FUNCTION ABNORMALITIES IN ASTHMA

Spirometry (in clinic):
Airflow limitation:
Low FEV1 (relative to percentage of predicted
norms)
FEV1/FVC ratio <0.80
Bronchodilator response (to inhaled β-agonist):
Improvement in FEV1 ≥12% and ≥200

378
 mL*
Exercise challenge:
Worsening in FEV1
≥15%*
Daily peak flow or FEV1 monitoring: day to day and/or am-to-pm variation
≥20%*

Treatment

The key components to optimal asthma management are specified.

Management of asthma should have the following components:

(1) Assessment and monitoring of disease activity.

(2) Provision of education to enhance the patient's and family's knowledge and skills for
self-management.

(3) Identification and management of precipitating factors and co-morbid conditions that may worsen
asthma.

(4) Appropriate selection of medications to address the patient's needs. The long-term goal of asthma
management is attainment of optimal asthma control.

The key elements to optimal asthma management. SABA, short-acting β-agonist.

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Patient Education:

KEY ELEMENTS OF PRODUCTIVE CLINIC VISITS FOR ASTHMA

1. Specify goals of asthma management
2. Explain basic facts about asthma:
Contrast normal vs asthmatic airways
Link airways inflammation, “twitchiness,” and bronchoconstriction
Long-term-control and quick-relief medications
3. Address concerns about potential adverse effects of asthma pharmacotherapy
4. Teach, demonstrate, and have patient show proper technique for:
Inhaled medication use (spacer use with metered-dose inhaler)
Peak flow measures
5. Investigate and manage factors that contribute to asthma severity:
Environmental exposures
Co-morbid conditions
6. Written two-part asthma management plan:
Daily management
Action plan for asthma exacerbations
7. Regular follow-up visits:
Twice yearly (more often if asthma not well-controlled)
Monitor lung function annually

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN CHILDREN*

CLASSIFICATION OF ASTHMA CONTROL
Well-Controlled Not Well-Controlled Very Poorly Controlled
COMPONENTS OF CONTROL
Impairment
≤2 days/wk but not
>2 days/wk or multiple
Symptoms more than once on Throughout the day
times on ≤2 days/wk
each day
Nighttime awakenings:
Age 0-4 yr ≤1?/mo >1?/mo >1?/wk
Age 5-11 yr ≤1?/mo ≥2?/mo ≥2?/wk
Age ≥12 yr ≤2?/mo 1-3?/wk ≥4?/wk
Short-acting β2-agonist use
for symptoms (not for
exercise-induced ≤2 days/wk >2 days/wk Several times per day
bronchos8pasm
pretreatment)
Interference with normal
None Some limitation Extremely limited
activity
Lung function:
Age 5-11 yr:

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 CLASSIFICATION OF ASTHMA CONTROL
Well-Controlled Not Well-Controlled Very Poorly Controlled
FEV1 (% predicted or peak >80% predicted or 60-80% predicted or <60% predicted or personal
flow) personal best personal best best
FEV1/FVC: >80% 75-80% <75%
Age ≥ 12 yr:
FEV1 (% predicted or peak >80% predicted or 60-80% predicted or <60% predicted or personal
flow) personal best personal best best
Validated questionnaires[†]:
Age ≥ 12 yr:
ATAQ 0 1-2 3-4
ACQ ≤0.75 ≤1.5 N/A
ACT ≥220 16-19 ≤15
Risk
Exacerbations requiring
systemic corticosteroids:
Age 0-4 yr 0-1/yr 2-3/yr >3/yr
Age ≥5 yr 0-1/yr ≥2/yr (see notes)
Consider severity and interval since last exacerbation.
Medication side effects can vary in intensity from none to very
Treatment-related adverse troublesome and worrisome. The level of intensity does not correlate to
effects specific levels of control but should be considered in the overall
assessment of risk.
Reduction in lung growth
or progressive loss of lung Evaluation requires long-term follow-up care.
function
RECOMMENDED ACTION FOR TREATMENT
Maintain current Step up (1 step) Consider short course
step. and reevaluate in of oral corticosteroids.
Regular 2-6 wk. Step up[?] (1-2 steps)
follow-up every If no clear benefit in and reevaluate in 2
1-6 mo to 4-6 wk, consider weeks.
maintain control. alternative If no clear benefit in 4-6
Consider step diagnoses or wk, consider alternative
down if adjusting therapy. diagnoses or adjusting
well-controlled For side effects, therapy.
for at least 3 consider alternative For side effects,
mo. options. consider alternative
options.

Drugs used for long term control.

1. inhaled corticosteroids: budesonide, beclomethasone, fluticasone, mometasone

381
2. leukotrienes receptor antagonists: monteleukast, zafirleukast.

3. 5- lipoxygenase inhibitor zileuton

4. Theophylline

5. immunomodulator- omalizumab.

AEROSOL THERAPY:

< 5mcg size particle so that can directly enter lungs and act quickly.

Aerosol therapy is the cornerstone in asthma management. There are number of delivery systems
available that are suitable for different ages.

The advantages of aerosol therapy are smaller dose, target delivery, quick action, safety and fewer
side-effects.

The delivery systems that are commonly utilized are: metered dose inhalers (MDI), dry powder
inhalers (DPI) and nebulisers.

Successful pharmacologic management of asthma should incorporate two major strategies:

1. Reversal of acute and chronic airway obstruction

2. Long-term attenuation and prophylaxis of the intrabronchial sequelae due to inflammatory cells
and their mediators.

The current treatment of asthma involves two major classes of drugs:

a) Relievers, i.e. bronchodilators used for immediate relief of symptoms. e.g. salbutamol, terbutaline.

b) Controllers, i.e. anti-inflammatory drugs that help in stopping bronchial wall remodelling and in
prevention of exacerbations.

Age appropriate devices:

Device Suitable age

% of drug delivery

MDI + <4 years

10-15%
Spacer + (preschool)
Face mask

MDI + >4 –6 years

10-15%
Spacer (early school age)

382
DPI >7-8 years
5-10%
(late childhood)

MDI adolescence
5-10%

Home all ages

1-5%
nebuliser*

* Not recommended routinely

Add a note on advantages and disadvantages for each.

Community acquired pneumonia:

Definition: Community acquired pneumonia is an acute infection of the pulmonary parenchyma in a

previously healthy child, acquired outside of a hospital setting. The patient should not have been
hospitalized within 14 days prior to the onset of symptoms or has been hospitalised less than 4 days
prior to onset of symptoms.

Epidemiology: In developing countries, the introduction of measles vaccine has greatly

reduced the incidence of measles-related pneumonia deaths.

ETIOLOGIC AGENTS GROUPED BY AGE

OF THE PATIENT

AGE
FREQUENT PATHOGENS (IN ORDER OF FREQUENCY)
GROUP
Neonates Group B streptococcus, Escherichia coli, Streptococcus pneumoniae, Haemophilus
(<3 wk) influenzae (type b,* nontypable)
Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza
3 wk-3 mo viruses, adenovirus), S. pneumoniae, H. influenzae (type b,* nontypable); if patient is
afebrile, consider Chlamydia trachomatis
Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza
4 mo-4 yr viruses, adenovirus), S. pneumoniae, H. influenzae (type b,* nontypable), Mycoplasma
pneumoniae, group A streptococcus
M. pneumoniae, S. pneumoniae, Chlamydophila pneumoniae, H. influenzae (type b,*
≥5 yr nontypable), influenza viruses, adenovirus, other respiratory viruses, Legionella
pneumophila

Pathogenesis:

Host protective factors: The lower respiratory tract is normally kept sterile by physiologic
383
defense mechanisms, including mucociliary clearance, the properties of normal secretions such as
secretory immunoglobulin A (IgA), and clearing of the airway by coughing.

Respiratory tract organisms (viral or bacterial or both) colonize the trachea

Subsequently gain access to the lungs. Direct injury of the respiratory epithelium

Resulting in airway obstruction from swelling, abnormal secretions, and cellular debris.

Atelectasis, interstitial edema, and ventilation-perfusion mismatch causing significant hypoxemia.

CLINICAL FEATURES:

These infants appear ill, with respiratory distress manifested as grunting; nasal flaring; retractions of
the supraclavicular, intercostal, and subcostal areas; tachypnea; tachycardia; air hunger; and often
cyanosis.

Fever is usually present.

Results of physical examination may be misleading, particularly in young infants, with meager
findings disproportionate to the degree of tachypnea.

If severe- respiratory distress, cyanosis and grunting.

Stages:

 Stage of consolidation for 1-2 days

 Stage of red hepatisation for 2- 4 days
 Stage of grey hepatisation 4- 8 days
 Stage of resolution 8th to 10th day

Diagnosis:

CBC, ESR, CRP, ASO,

Blood culture PCR for M. Pneumoniae, RSV and adeno.

CHEST X ray:

 Acute lobar pneumonia- pneumococcal

 Right UL- aspiration
 UL pneumonia with cavitation- Tb
 Lower lobe pneumonia- chemical pneumonitis
 Pneumatoceles- staphylococcus

Treatment:

A) General – monitoring, oxygen, feeding, IV fluids

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B) Supportive management – antipyretics, antitussives, bronchodilators, antiemetic and
physiotherapy.

C) Specific- antibiotics

For mildly ill children who do not require hospitalization high doses of amoxicillin (80-90 mg/kg/24
hr) should be prescribed for atleast 10-14 days. Therapeutic alternatives include cefuroxime axetil
and amoxicillin/clavulanate.

For school-aged children and in children in whom infection with M. pneumoniae or C. pneumoniae
is suggested, a macrolide antibiotic such as azithromycin is an appropriate choice for atleast 5 days.

In adolescents, a respiratory fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin) may be

considered as an alternative.

Parenteral cefotaxime or ceftriaxone is the mainstay of therapy when bacterial pneumonia is

suggested.

If viral pneumonia is suspected, it is reasonable to withhold antibiotic therapy, especially for those
patients who are mildly ill, have clinical evidence suggesting viral infection, and are in no respiratory
distress.

If clinical features suggest staphylococcal pneumonia-- vancomycin or clindamycin.

Zinc 20mg/ kg should also be given as an adjuvant therapy.

For empyema: thoracostomy, intra pleural fibrinolytic therapy, VATS.

Complications: Pleural effusion, empyema, pericarditis. Bacteremia and hematologic spread.

Meningitis, suppurative arthritis, and osteomyelitis.

Prevention:

A) General – reduce the risk of exposure to respiratory pathogens by droplet.

B) Immunizations- BCG, Influenza and Pneumococcal

C) Preventive therapy-

1. isoniazid prophylaxis for < 6 years of age with h/o of contact

2. Hemophilus influenza type B infection- rifampicin 20 mg/kg daily for 4 days

DIFFERENTIATION OF PLEURAL FLUID

TRANSUDATE EMPYEMA
Appearance Clear Cloudy or purulent

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 TRANSUDATE EMPYEMA
Often >50,000 (cell count has limited predictive
Cell count (per mm3) <1000
value)
Lymphocytes,
Cell type Polymorphonuclear leukocytes (neutrophils)
monocytes
Lactate dehydrogenase <200 U/L >1000 U/L
Pleural fluid/serum LDH ratio <0.6 >0.6
Protein >3g Unusual Common
Pleural fluid/serum protein
<0.5 >0.5
ratio
Glucose* Normal Low (<40 mg/dL)
pH* Normal (7.40-7.60) <7.10
Gram stain Negative Occasionally positive (less than one-third of cases)

RECURRENT PNEUMONIA:

Recurrent pneumonia is defined as 2 or more episodes in a single year or 3 or more episodes ever,
but with complete clinical and radiographic clearing between episodes.

Persistent or non resolving pneumonia: when there is clinical and radiological evidence of
pneumonia for more than a month despite a course of adequate and appropriate antibiotic therapy
for 10 days.

Etiological factors for recurrent pneumonia:

Congenital Aspirations Defects in clearance Disorders of local/

malformations of airway secretions systemic immunity
GER
Airways -- cleft palate, CF Primary
Pierre robin syndrome, Foreign body immunodeficiency
tracheomalacia TEF Abnormalities of
Anomalies of upper ciliary structures Secondary- HIV,
Lungs – pulmonary airways malnutrition
hypoplasia, pulmonary Mediastinal tubercular
sequestration, CCAM Swallowing lymphadenopathy
abnormalities
Cardiovascular – CHD,
vascular ring

Conditions causing recurrent pneumonia in single lobe-

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A) Intraluminal causes- foreign body, bronchial tumor, adenoma, lipoma

B) Extraluminal- infectious lymphadenopathy, non infectious lymphadenopathy, tuberculosis,

vascular ring

C) Structural abnormalities- tracheal bronchus, bronchial stenosis or atresia, right middle lobe
syndrome, CCAM

Conditions causing recurrent pneumonia in multiple lobes:

A) Recurrent microaspiration: impaired swallowing, esophageal obstruction, esophageal dysmotility

and GER

B) Asthma

C) Immunodeficiency syndromes- phagocytic, antibody, complement and T cell defects

D) Mucociliary dysfunction: CF, ciliary dyskinesia

E) Structural abnormalities: tracheobronchomegaly, cartilage deficiency

F) CHD

G) BPD

F) misc- hypersensitivity pneumonitis, alveolar proteinosis

Investigational approach to recurrent pneumonia:

Recurrent pneumonia Same lobe Different lobes

Barium swallow/ milk scan
Perform HRCT 2 D ECHO NBT test
Bronchoscopy Immunoglobulin profile
TB studies Sweat test/mutation tests

Sleep disordered breathing in children encompasses a broad spectrum of respiratory disorders that
occur exclusively in or are exacerbated by sleep, and includes primary snoring and upper airway
resistance syndrome, as well as apnea of prematurity and central apnea.

11. OSAS:

Obstructive sleep apnea (OSA), the most important clinical entity within the Sleep Disordered
Breathing (SDB) spectrum, is a respiratory disorder that is characterized by repeated episodes of
prolonged upper airway obstruction during sleep despite continued or increased respiratory effort,
resulting in complete (apnea) or partial (hypopnea; ≥50% reduction in airflow) cessation of airflow at
the nose and/or mouth, as well as in disrupted sleep.

ANATOMIC FACTORS THAT PREDISPOSE TO OBSTRUCTIVE

SLEEP APNEA
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NOSE CRANIOFACIAL

Anterior nasal stenosis Micrognathia/retrognathia

Midface hypoplasia
Mandibular hypoplasia
Deviated nasal septum (Pierre Robin sequence,
Choanal stenosis/atresia Treacher Collins, Cornelia
Seasonal or perennial de Lange)
rhinitis Craniofacial trauma
Nasal polyps, foreign
body, hematoma, mass Storage diseases (e.g.,
lesion glycogen, Hunter, Hurler
syndrome)
NASOPHARYNGEAL
AND OROPHARYNGEAL

Adenotonsillar NEURO MUSCULAR

hypertrophy Hypotonic cerebral palsy
Macroglossia Muscular dystrophies
Hypothyroidism.
Cystic hygroma
Reduced central ventilatory drive may be present in some
children with Arnold-Chiari malformation and
Cleft palate repair
meningomyelocele
Pharyngeal mass
lesion
GER
Functional: obesity drugs

Pathogenesis:

1. The up regulation of inflammatory pathways Peripheral markers of inflammation such as

C-reactive protein

Appear to be linked to metabolic dysfunction (e.g., insulin

resistance, dyslipidemia)

2. Systemic inflammation Increases in sympathetic autonomic nervous system activity. Altered

vasomotor tone

Contributors to increased cardiovascular risk

Leukotrienes.
Altered endothelial function.

3. Repeated episodic arousals and resulting sleepiness.

Intermittent hypoxia.

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 Associated with cognitive dysfunction

CRP and cytokine IL-6

Clinical features:

Age: 2- 5 years

Sleep-related: loud, frequent, and disruptive snoring, breathing pauses, choking or gasping
arousals, restless sleep, and nocturnal diaphoresis.

Daytime symptoms: mouth breathing and dry mouth, chronic nasal congestion/rhinorrhea,
hyponasal speech, morning headaches, difficulty swallowing, and poor appetite

Neurobehavioral: daytime sleepiness with drowsiness, difficulty in morning waking, and

unplanned napping or dozing off during activities associated with disturbances in mood, behavior,
learning, and academic functioning. Sometimes secondary eneuresis, sleep walking and sleep
terrors are also noted.

In very severe cases, there may be evidence of pulmonary hypertension, right-sided heart failure, and
cor pulmonale.

Diagnosis: Because no combination

of clinical history and physical findings can accurately predict which children with snoring have
OSA, the gold standard for diagnosing OSA remains an overnight polysomnogram (PSG). The
polysomnographic parameter most commonly used in evaluating for sleep disordered breathing is the
apnea/hypopnea index (AHI), which indicates the number of apneic and hypopneic events per hr of
sleep.

Treatment:

Any child with an apnea index >5 should be treated.

Medical:

 Some evidence that intranasal corticosteroids and leukotriene inhibitors may be helpful in
mild OSA
 Oral appliances, such as mandibular advancing devices and tongue retainers in adolescents.
 Continuous or bilevel positive airway pressure (nasal CPAP or BiPAP) is the most common
treatment for OSA in adults and can be used successfully in children and adolescents.

Surgical:

 In the majority of cases of pediatric OSA, adenotonsillectomy is the first-line treatment in

any child with significant adenotonsillar hypertrophy.
 Other surgical procedures, such as uvulopharyngopalatoplasty, and maxillofacial surgery are
seldom performed.
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Additional treatment measures –

 weight loss,
 positional therapy and
 aggressive treatment of additional risk factors when present, such as asthma, seasonal
allergies, gastroesophageal reflux and hypothyroidism.

12. Pulmonary function tests:

The measurement of respiratory function in infants and young children can be difficult because of the
lack of cooperation.

1. Peak flow meters: Airway obstruction is most commonly

evaluated from determinations of gas flow in the course of a forced expiratory manoeuvre. The peak
expiratory flow is reduced in advanced obstructive disease. The wide availability of simple devices
that perform this measurement at the bedside makes it useful for assessing children who have airway
obstruction. Evaluation of peak flows requires a voluntary effort, and peak flows may not be altered
when the obstruction is moderate or mild. Cooperation and good muscle strength are therefore
necessary for the measurements to be reproducible.

2. Spirometer: A spirometer is used to measure VC and its subdivisions and

expiratory (or inspiratory) flow rates. Expected normal values for VC, FRC, TLC, and residual
volume are obtained from prediction equations based on body height. Flow rates measured by
spirometry usually include the FEV1sec and the maximal mid expiratory flow rate but not residual
capacity

3. Plethysmography: Airway resistance (RAW) is measured in a

plethysmograph, or, alternatively, the reciprocal of RAW, airway conductance (GAW), may be used.
Because airway resistance measurements vary with the lung volume at which they are taken, it is
convenient to use specific airway resistance, SRAW (SRAW = RAW/lung volume), which is nearly
constant in subjects >6 yr old (normally <7 sec/cm H2O). Also useful to measure residual capacity.

4. DLCO: The diffusing capacity for carbon monoxide (DLCO) is related to oxygen
diffusion and is measured by rebreathing from a container having a known initial concentration of
carbon monoxide or by using a single-breath technique.

USES OF Lung Function Tests:

Pulmonary function testing, although rarely resulting in a diagnosis, is helpful in defining the

a. Type of process (obstruction, restriction).

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b. The degree of functional impairment.

c. In following the course and treatment of disease.

d. In estimating the prognosis.

e. It is also useful in preoperative evaluation.

f. In confirmation of functional impairment in patients having subjective complaints but a normal

physical examination.

STRIDOR:

Def: Stridor is a harsh vibratory sound of variable pitch caused by partial obstruction of the upper
airway.

Classification: Stridor can be categorized in relation to the phase of the respiratory cycle during
which it occurs.

a) Inspiratory stridor: During inspiration, the relatively mobile, poorly supported structures of
infantile supraglottis tend to be drawn into the glottic aperture, and a low pitched, harsh inspiratory
stridor is produced.

b) Biphasic stridor: The relatively rigid walls of rima glottis, subglottis and trachea prevent collapse
of airway, but in severe obstruction biphasic and to and fro stridor may result.

Etiology:

Infections Trauma Others

a) Acute laryngotracheobronchitis – a) Angioedema
ALTB (Classical croup) a) Foreign body (FB)
b) Acute epiglottitis in glottis, subglottis or esophagus b) Spasmodic
c) Diphtheria croup
b) External trauma to neck c) Tumors (eg.
d) Bacterial tracheitis c) Burns causing edema in upper airway lymphoma in
e) Retropharyngeal abscess anterior
f) Peritonsillar abscess d) Post extubation mediastinum)
e) Post instrumentation
g) Ludwig’s angina d) Hypocalcemic
h) Any respiratory infection in a child tetany
with laryngomalacia or congenital
anomalies of laryngeal structures

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 Conditions causing acute stridor and their characteristics

Features ALTB Bacterial Acute

Diphtheria FB Spasmodic
Tracheitis epiglottitis
airway croup

Age 6 mo - 6 yrs 1 mo - 6 yrs 2-6 yrs 1-10 years

1-4 yrs 6 mo - 3 yrs

Etiology Parainfl, infl, S.aureus, H.influenzae C.diphtheriae

FB Viral,
adeno, RSV H.influenzae,
aspiration allergy

Onset Insiduous, Insiduous, Abrupt Gradual

Abrupt, Abrupt
preceding preceding
history of
URI URI / ALTB
FB

Fever May or may Present Present, Present,

Absent Usually
not be present toxic toxic toxic
absent

Cough Barking cough, Brassy cough, Weak cough, Barking cough, Cough
Metallic

Voice hoarseness, hoarseness muffled voice, nasal twang, may

or cough
posture worsening at drooling, pseudomembrane
may not mostly at other night dysphagia,
over throat be night,
features leaning over
present hoarseness

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Stridor High pitched Moderate, Low pitched Can be severe Variable
Moderate
Severe
Radiology Subglottic Subglottic Enlarged Soft tissue
Radio Subglottic
narrowing narrowing epiglottis swelling of
opaque narrowing
(steeple sign) (subglottic air (thumb sign) neck
FB
Column diffusely hazy
with multiple soft tissue irregularities)
antibiotics no need ampi+clox ampi+sulbactum penicillin+ anti dipt serum

Management
Management of acute stridor depends upon the cause. It is a sign of narrowing of the air passage and
is an emergency. A child with stridor should be immediately evaluated by someone who is skilled in
intubation.

General principles of management

1) Ensure adequacy of the airway. Allow the child to maintain position of comfort –Maintain calm
atmosphere. Administer O2 by a non rebreathing mask with the child on mother’s lap.

2) If the airway is maintainable, and one is suspecting laryngotracheobronchitis, nebulized

epinephrine and budesonide should be considered. However, an intubation may be considered any
time.

3) A team approach with a pediatrician, an otolaryngologist and if required, an anesthesiologist is

considered the optimal approach in severe stridor.

4) An ENT specialist has to be involved in all cases of suspected foreign body, trauma, vocal cord
palsy, tumors, congenital structural malformations and in all cases where tracheostomy is indicated.

5) If there is an impending respiratory failure, oxygenation followed by immediate nasotracheal

intubation should be considered.

6) If somehow intubation fails, an emergency tracheostomy is advised.

7) Antibiotics are required only when one suspects bacterial tracheitis, epiglottitis, diphtheria or
when the cause is not determined.

Role of antibiotics in acute stridor

· For laryngotracheobronchitis and viral croup, no antibiotics are indicated.

· For acute epiglottitis, a third generation cephalosporin or a combination of ampicillin and sulbactum
may be used.

· For bacterial tracheitis, a combination of ampicillin and cloxacillin, and a third generation
cephalosporin may be started and stepped down when culture reports are available

· For diphtheria, crystalline penicillin is indicated, along with antidiphtheretic serum.

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Croup (ALTB) Management of croup

(Clinically diagnosed after excluding foreign body aspiration, epiglottitis, etc)

Allow the child to assume position of comfort

Minimise upsetting examination or procedures
Oxygen as necessary (in a non-threatening manner) to keep SaO2 > 93%

If stridor at rest and respiratory distress

Nebulized epinephrine (adrenaline) 1:1,000 0.5 ml/kg

Corticosteroid along with nebulised epinephrine in all but the mildest of cases
(Dexamethasone 0.6 mg/kg PO or IM
(or)
Prednisolone 1 mg/kg PO
(or)
Nebulised budesonide 2 mg)

Improvement

Discharge home if: Admit to Hospital if:

No improvement

Consider need for intubation and

arrange admission to ICU

· No stridor at rest Infant <1 year
· Vitals are normal severe croup on presentation
· Child has been observed Persistent stridor at rest
for 4 hours after adrenaline Child looks toxic
(for ‘rebound’ phenomenon) Uncertain about diagnosis
Unable to satisfy
discharge criteria

Sudden infant death syndrome:

Def: The sudden, unexpected death of an infant that is unexplained by a thorough postmortem
examination, which includes a complete autopsy, investigation of the scene of death, and review of
the medical history, constitutes sudden infant death syndrome (SIDS).

Mechanism of sudden death:

There are 3 mechanisms of sudden death: arrhythmic, nonarrhythmic cardiac (circulatory and
vascular causes), and noncardiac.

Ventricular fibrillation (VF), is the most common final cause of sudden death in 10-20% of
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children.

More commonly, bradycardia leads either to VF or asystole.

Etiopathogenesis:

Risk factors:

Modifiable risk factors Non modifiable risk factors

Pregnancy related factors Lower socio economic strata

Cigarette smoking Winter season

Drug and alcohol use Male infants

Infant sleep environment Prematurity

Infant sleep position

Infant feeding care practices

Reducing the Risk of SIDS

Reducing risk behaviors and increasing protective behaviors among infant caregivers to achieve
further reductions and eventual elimination of SIDS is a critical goal. The major components are as
follows:

• Full-term and premature infants should be placed for sleep in the supine position. Side sleeping is
not recommended.

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• It is recommended that infants sleep in the same room as their parents but in their own crib.
• Infants should be put to sleep on a firm mattress. Waterbeds, sofas, soft mattresses, or other soft
surfaces should not be used.
• Soft materials in the infant's sleep environment—over, under, or near the infant—should be
avoided.
• Avoid overheating and over bundling.
• Infants should have some time in the prone position (tummy time) while awake and observed.

• Home respiratory, cardiac, and O2 saturation monitoring is not recommended for this purpose.
• Consider offering a pacifier at bedtime and naptime.
• Mothers should not smoke during pregnancy and infants should not be exposed to second hand
smoke.
• Health care professionals in intensive care and normal newborn nurseries should implement these
recommendations well before anticipated discharge.

Immotile cilia syndrome:

Normal structure of motile cilia: It contains a cylinder of microtubule doublets, arranged around a
central pair of microtubules, the characteristic “9+2” arrangement as viewed by cross-sectional views
on electron microscopy. Each cell contains about 200 cilia. Frequency is around 1- 20 hz

Normal structure of immotile cilia: sensory or primary cilia lack a central microtubule doublet and
outer dynein arms, thus creating a “9+0” arrangement and leaving these structures immotile.

Clinical features:

Respiratory system Infertility

Lung neonatal respiratory distress, chronic Situs inversus

cough,
Heterotaxy
Recurrent pneumonia,
Bronchiectasis Retinitis pigmentosa

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Ear- chronic otitis media, conductive hearing loss Hydrocephalus

Paranasal sinusitis- neonatal rhinitis, chronic Kartagener triad, defined as situs inversus
totalis, chronic sinusitis, and bronchiectasis.
mucopurulent
rhinitis, nasal polyposis

Diagnosis:

Imaging studies show extensive involvement of the paranasal sinuses.

Chest radiographs frequently demonstrate bilateral lung overinflation, peribronchial infiltrates, and
lobar atelectasis and dextrocardia in situs inversus.

CT of the chest often reveals Bronchiectasis.

Pulmonary function testing of older children typically shows a progressive intrathoracic airway
obstruction.

Transmission electron microscopy is the current gold standard to assess ultrastructural defects
within the cilium. Shortening or absence of dynein arms is the most common abnormality seen in
PCD.

Genetic testing for PCD is available, and commercial laboratories offer testing for specific DNAI1
and DNAH5 mutations.

Screening tests:

1. The saccharin test has been applied to qualitatively assess mucociliary function. It is not
standardized.

2. Another approach exploits the observation that nasal nitric oxide (NO) concentrations are
reduced in subjects with PCD. Because nasal NO measurements are relatively easy to perform and
noninvasive, this method is a promising screen for PCD in patients >5 yr of age, provided that cystic
fibrosis has been excluded.

Treatment:

Chest physiotherapy nebulisations with bronchodilators surgical resection of

bronchiectatic lung

Heart lung transplantation. Avoid smoking and prevent infections

Epistaxis:

Anatomy

The most common site of bleeding is the Kiesselbach plexus, an area in the anterior septum where
vessels from both the internal carotid (anterior and posterior ethmoid arteries) and external carotid
(sphenopalatine and terminal branches of the internal maxillary arteries) converge.

397
The thin mucosa in this area, as well as the anterior location, makes it prone to exposure to dry air
and trauma.

COMMON CAUSES OF EPISTAXIS

Epistaxis digitorum (nose picking)

Rhinitis, Chronic sinusitis, Foreign bodies

Intranasal neoplasm or polyps

Irritants (e.g., cigarette smoke)
Septal deviation, perforation
Trauma including child abuse
Vascular malformation or telangiectasia
Hemophilia, Platelet dysfunction, Thrombocytopenia

Hypertension, Leukemia, Liver disease (e.g., cirrhosis)

Medications (e.g., aspirin, anticoagulants, NSAID, topical corticosteroids)

Cocaine abuse

Clinical Manifestations:

Epistaxis usually occurs without warning, with blood flowing slowly but freely from one nostril or
occasionally from both. When bleeding occurs at night, the blood may be swallowed and become
apparent only when the child vomits or passes blood in the stools. Posterior epistaxis can manifest as
anterior nasal bleeding or, if bleeding is copious, the patient might vomit blood as the initial
symptom.

Treatment:

1. Most nosebleeds stop spontaneously in a few minutes.

2. The nares should be compressed and the child kept as quiet as possible, in an upright position
with the head tilted forward to avoid blood trickling back into the throat.
3. Cold compresses applied to the nose can also help.
4. If these measures do not stop the bleeding, local application of a solution of oxymetazoline
may be useful.
5. If bleeding persists, an anterior nasal pack might need to be inserted; if bleeding originates
in the posterior nasal cavity, combined anterior and posterior packing is necessary.
6. After bleeding has been controlled, and if a bleeding site is identified, its obliteration by
cautery with silver nitrate may prevent further difficulties.
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 7. In patients with severe or repeated epistaxis, blood transfusions may be necessary.
8. Otolaryngologic evaluation is indicated for these children and for those with bilateral
bleeding or with hemorrhage that does not arise from the Kiesselbach plexus.
9. Hematologic evaluation (for coagulopathy and anemia), along with nasal endoscopy and
diagnostic imaging, may be needed to make a definitive diagnosis in cases of severe recurrent
epistaxis.
10. Replacement of deficient clotting factors may be required for patients who have an
underlying hematologic disorder.
11. Control hypertension appropriately
12. Profuse unilateral epistaxis associated with a nasal mass in an adolescent boy near puberty
might signal a juvenile nasopharyngeal angiofibroma.
13. Surgical intervention may also be needed for bleeding from the internal maxillary artery.

Prevention:

The discouragement of nose picking, and attention to proper humidification of the bedroom during
dry winter months helps to prevent many nosebleeds.

Prompt attention to nasal infections and allergies is beneficial to nasal hygiene.

Prompt cessation of nasal steroid sprays prevents ongoing bleeding.

20. ARDS:

Definition: as in flow chart 4 points.

Etiology:

Direct Indirect
Usual : Usual:

 Pneumonia  Sepsis
 Aspiration pneumonia  Severe trauma
 Multiple transfusions of blood
products

Rare: Rare:

 Inhalational injury  Acute pancreatitis

 Pulmonary contusion  Drug overdose
 Near drowning  DIC
 Reperfusion injury  Burns
 Head injury

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 Stages :

a.Exudative phase
b. Proliferative phase
c.Fibrotic phase

Pathophysiology:
Inciting agent

Inflammation

Endothelial damage

Fluid leak

v/q mismatch and decreased surfactant  rt –lt shunt & decreased FRC

Protocol approach to suspected ARDS child:

400
Respiratory management in ARDS:

401
402
21. Developmental anomalies of lung:

Write a note on development of lung-

Causes:

Cong anomalies of Cong anomalies of larynx, Cong anomalies of lung

nose trachea and bronchi
Arhinia- absence of Laryngomalacia 1. Pulmonary agenesis and
nose aplasia
Tracheomalacia 2. Pulmonary hypoplasia
Nasal hypoplasia 3. CCAM
bronchomalacia
Choanal aplasia 4. Pulmonary sequestration
Cong subglottic stenosis 5. Bronchogenic cysts
Congenital defects of 6. Congenital pulmonary
nasal septum Vocal cord paralysis Lymphangiectasia
7. Lung hernia
Cong laryngeal webs 8. Congenital lobar emphysema
and pulmonary cysts
Cong subglottic haemangioma
9. Pulmonary arteriovenous
Laryngocele malformation
10. Bronchobiliary fistula
Vascular ring

Cystic adenomatoid malformation:

Pathology:

Congenital cystic adenomatoid malformation (CCAM) consists of hamartomatous or dysplastic lung

tissue mixed with more normal lung, generally confined to one lobe.

Type 1 (50%) is macrocystic and consists of a single or several large (>2 cm in diameter) cysts lined
with ciliated pseudostratified epithelium. This type has a good prognosis for survival.

Type 2 (40%) is microcystic and consists of multiple small cysts with histology similar to that of the
type 1 lesion. Type 2 is associated with poor prognosis.

In type 3 (<10%), the lesion is solid with bronchiole-like structures. This lesion carries the poorest
prognosis.

Etiology:

The lesion probably results from an embryologic insult before the 35th day of gestation, with
maldevelopment of terminal bronchiolar structures. Histologic examination reveals little normal lung
403
and many glandular elements. Cysts are very common; cartilage is rare.

Diagnosis:

1. Prenatal ultrasonographic findings are classified as macrocystic (single or multiple cysts >5 mm)
or microcystic (echogenic cysts <5 mm).

2. CT allows accurate diagnosis and sizing of the lesion.

Clinical features:

Patients can present in the newborn period or early infancy with respiratory distress, recurrent
respiratory infection, and pneumothorax. The lesion may be confused with a diaphragmatic hernia,
lung abscess.

Patients with smaller lesions are usually asymptomatic until mid-childhood, when episodes of
recurrent or persistent pulmonary infection or chest pain occur.

Breath sounds may be diminished, with mediastinal shift away from the lesion on physical
examination.

Chest radiographs reveal a cystic mass, sometimes with mediastinal shift.

Treatment:

Antenatal interventions include excision of the affected lobe for microcystic lesions, aspiration of
macrocystic lesions, and, rarely, open fetal surgery.

In the postnatal period, surgery is indicated for symptomatic patients.

Although surgery may be delayed for asymptomatic infants because postnatal resolution has been
reported.

Surgical resection by 1 yr of age is recommended to limit malignant potential.

22. Bronchiolitis:

Acute bronchiolitis is predominantly a viral disease.

RSV is responsible for >50% of cases. There is no evidence of a bacterial cause for bronchiolitis

Other agents include parainfluenza, adenovirus, human bocavirus, human metapneumovirus and
Mycoplasma.

Common in boys, in those who have not been breast fed, and in those who live in crowded
conditions.

Pathogenesis:

Host anatomic and immunologic factors play a significant role in the severity of the clinical
syndrome, as does the nature of the viral pathogen.

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In addition, RSV infection incites a complex immune response.

Acute bronchiolitis is characterized by bronchiolar obstruction with edema, mucus, and cellular
debris. Even minor bronchiolar wall thickening significantly affects airflow.

If obstruction becomes complete, trapped distal air will be resorbed and the child will develop
atelectasis.

Hypoxemia is a consequence of ventilation-perfusion mismatch early in the course.

With severe obstructive disease and tiring of respiratory effort, hypercapnia can develop.

Clinical features:

Acute bronchiolitis is usually preceded by exposure to an older contact with a minor respiratory
syndrome within the previous week.

The infant 1st develops a mild upper respiratory tract infection with sneezing and clear rhinorrhea.
This may be accompanied by diminished appetite and fever.

Gradually, respiratory distress ensues, with paroxysmal wheezy cough, dyspnea, and irritability.

The physical examination is often dominated by wheezing.

Work of breathing may be markedly increased, with nasal flaring and retractions. Auscultation might
reveal fine crackles or overt wheezes, with prolongation of the expiratory phase of breathing.

Barely audible breath sounds suggest very severe disease with nearly complete bronchiolar
obstruction.

The diagnosis of acute bronchiolitis is clinical.

 Chest radiography can reveal hyperinflated lungs with patchy atelectasis.

 The white blood cell and differential counts are usually normal.
 Viral testing (polymerase chain reaction, rapid immunofluorescence, or viral culture) is
helpful if the diagnosis is uncertain or for epidemiologic purposes.

Risk factors for severe disease include age <12 wk, preterm birth, or underlying comorbidity such as
cardiovascular, pulmonary, or immunologic disease.

The mainstay of treatment is supportive.

 Hypoxemic children should receive cool humidified oxygen.

 Suctioning of secretions.
 The infant may be fed through a nasogastric tube.
 Bronchodilators can produce modest short-term improvement in clinical features.
 Ribavirin, an antiviral agent administered by aerosol, has been used for infants with
congenital heart disease or chronic lung disease.
 Nebulized hypertonic saline has also been reported to have some benefit.

405
  Mechanical ventilation if impending respiratory failure.

Prognosis:

 Self limiting with median duration of symptoms of 12 days

 Case fatality rate of < 1%
 Infants with CHD, immunodeficiency have poor prognosis
 Higher incidence of asthma and wheezing episodes in future.

Prevention:

Palivizumab should be considered for infants <2 yr of age with chronic lung disease, a history of
prematurity, and some forms of congenital heart disease.

Meticulous hand hygiene is the best measure to prevent nosocomial transmission.

RSV immunoglobulin.

23. RESPIRATORY FAILURE:

Respiratory failure occurs when oxygenation and ventilation are insufficient to meet the metabolic
demands of the body.

Respiratory failure may result from an abnormality in lung disease or respiratory pump failure

Lung disease Respiratory pump failure

1. Central airway obstruction 1. Chest wall deformity

Croup, epiglottitis, FB Flial chest, kyphoscoliosis

2. Peripheral airway obstruction 2. Brainstem

Bronchiolitis, Bronchial asthma Trauma, sleep apnea, poisoning

3. Diffuse alveolar damage 3. Spinal cord - SMA, trauma

Pneumonia, ILD, aspiration 4. Neuromuscular- GBS, myasthenia,

SIMPLIFIED CONSENSUS DEFINITION OF ACUTE LUNG INJURY

• Acute onset (<7 days)
• Severe hypoxemia (Pao2/Fio2 < 300 for acute lung injury, or <200 for acute respiratory distress
syndrome)
• Diffuse bilateral pulmonary infiltrates on frontal radiograph consistent with pulmonary edema
(these can be patchy and asymmetric, and pleural effusions can be present)
• Absence of left atrial hypertension (pulmonary artery wedge pressure <18 mm Hg if measured)

Pathophysiology of Respiratory Failure

406
Respiratory failure can be classified into 2 categories:

Type 1 hypoxic respiratory failure (failure of oxygenation) and

Type 2 hypercarbic respiratory failure (failure of ventilation).

The two entities may coexist as a combined failure of oxygenation and ventilation.

The main function of the respiratory system is to move atmospheric gases into the alveolar capillary
units of the lung and to move alveolar gas back out into the atmosphere.

The arterial gas composition depends on the (doc put one diagram here indicating all four things)

1. Gas composition of the atmosphere (inhalational injury)

2. Effectiveness of alveolar ventilation (pneumonia, aspiration pneumonia, severe trauma)

3. Pulmonary capillary perfusion (reperfusion injury, DIC, burns, sepsis, pancreatitis, drug overdose,)

4. Diffusion across the alveolar capillary membrane (drowning)

Abnormality at any of these steps can result in respiratory failure.

Monitoring:

Clinical examination Pulse oximetry Chest x ray Capnography

Blood gases DLCO

MANAGEMENT:

1. Control of causative factors.

2. Careful fluid administration.

3. Oxygen administration: nasal cannula, SFM, bubble humidifier, venturi and NRM.

4. Air way adjuncts: oropharyngeal and nasopharyngeal air way

5. Inhaled gases: heliox, nitric oxide

6. Surfactant, corticosteroids and other nsiads.

7. Positive pressure respiratory support: CPAP and BiPAP

8. Endotracheal intubation and ventilation.

9. Positioning (prone ventilation)

10. HFOV, liquid ventilation

11. Supportive therapy: analgesia, sedation, nutrition and psychological support

25. Discuss the approach to diagnosis, treatment and also outline the prognosis of Wheezing in
407
infancy.

Definition: A wheeze is a musical and continuous sound that originates from oscillations in narrowed
airways. Wheezing is heard mostly on expiration as a result of critical airway obstruction.

Why infants are more prone:

 Infants are prone to wheeze, owing to a differing set of lung mechanics in comparison to older
children and adults.
 The obstruction to flow is affected by the airway caliber and compliance of the infant lung.
 Resistance to airflow through a tube is inversely related to the radius of the tube to the 4th
power.
 In children <5 yr old, small-caliber peripheral airways can contribute up to 50% of the total
airway resistance.
 Marginal additional narrowing can cause further flow limitation and a subsequent wheeze.
 In comparison to older children and adults, infants tend to have higher levels of lymphocytes
and neutrophils, rather than mast cells and eosinophils, in bronchoalveolar lavage fluid.

Etiology:

DIFFERENTIAL DIAGNOSIS OF WHEEZING IN INFANCY

INFECTION
Viral
Respiratory syncytial virus (RSV)
Human metapneumovirus
Parainfluenza
Adenovirus
Influenza
Rhinovirus
Bocavirus
Other
Chlamydia trachomatis
Tuberculosis
Histoplasmosis
Papillomatosis
ASTHMA
Transient wheezer

• Initial risk factor is primarily diminished lung size

Persistent wheezers

• Initial risk factors include passive smoke exposure, maternal asthma history, and an elevated
immunoglobulin E (IgE) level in the 1st year of life
• At increased risk of developing clinical asthma

408
 Late-onset wheezer
ANATOMIC ABNORMALITIES
Central Airway Abnormalities
Malacia of the larynx, trachea, and/or bronchi
Tracheoesophageal fistula (specifically H-type fistula)
Laryngeal cleft (resulting in aspiration)
Extrinsic Airway Anomalies Resulting in Airway Compression
Vascular ring or sling
Mediastinal lymphadenopathy from infection or tumor
Mediastinal mass or tumor
Esophageal foreign body
Intrinsic Airway Anomalies
Airway hemangioma, other tumor
Cystic adenomatoid malformation
Bronchial or lung cyst
Congenital lobar emphysema
Aberrant tracheal bronchus
Sequestration
Congenital heart disease with left-to-right shunt (increased pulmonary edema)
Foreign body
Immunodeficiency States
Immunoglobulin A deficiency
B-cell deficiencies
Primary ciliary dyskinesia
AIDS
Bronchiectasis
MUCOCILIARY CLEARANCE DISORDERS
Cystic fibrosis
Primary ciliary dyskinesias
Bronchiectasis
ASPIRATION SYNDROMES
Gastroesophageal reflux disease
Pharyngeal/swallow dysfunction
OTHER
Bronchopulmonary dysplasia
Interstitial lung disease, including bronchiolitis obliterans
Heart failure
Anaphylaxis
Inhalation injury—burns
409
Acute bronchiolitis is predominantly a viral disease. RSV is responsible for >50% of cases. Other
agents include parainfluenza, human metapneumovirus, human bocavirus, adenovirus, and
Mycoplasma. Concurrent infection with viral bronchiolitis and pertussis has been described.

Chronic infectious causes of wheezing should be considered in infants who seem to fall out of the
range of a normal clinical course. Cystic fibrosis is one such entity.

Allergy and asthma are important causes of wheezing. Three identified patterns of infant wheezing
are the transient early wheezer, the persistent wheezer, and the late-onset wheezer.

Congenital malformations of the respiratory tract cause wheezing in early infancy. These findings
can be diffuse or focal and can be from an external compression or an intrinsic abnormality. External
vascular compression includes a vascular ring.

Foreign body aspiration can cause acute or chronic wheezing.

Gastroesophageal reflux can cause wheezing with or without direct aspiration into the
tracheobronchial tree.

Trauma and tumors are much rarer causes of wheezing in infants.

History and Physical Examination:

 Initial history of a wheezing infant should include accounts of the recent event including
onset, duration, and associated factors.
 Birth history includes weeks of gestation, neonatal intensive care unit admission, history of
intubation or oxygen requirement, maternal complications including infection with herpes
simplex virus (HSV) or HIV, and prenatal smoke exposure.
 Past medical history includes any comorbid conditions including syndromes or associations.
 Family history of cystic fibrosis, immunodeficiencies, asthma in a 1st-degree relative, or any
other recurrent respiratory conditions in children should be obtained.
 Social history should include an environmental history including any smokers at home, inside
or out, daycare exposure, number of siblings, occupation of inhabitants of the home, pets,
tuberculosis exposure, and concerns regarding home environment (e.g., dust mites,
construction dust, heating and cooling techniques, mold, cockroaches).

On physical examination,

 Evaluation of the patient's vital signs with special attention to the respiratory rate and the
pulse oximetry reading for oxygen saturation is an important initial step.
 There should also be a thorough review of the patient's growth chart for signs of failure to
thrive.
 Signs of respiratory distress include tachypnea, increased respiratory effort, nasal flaring,
tracheal tugging, subcostal and intercostal retractions, and excessive use of accessory
410
 muscles.
 In the upper airway, signs of atopy, including boggy turbinates.
 It is also useful to evaluate the skin of the patient for eczema and any significant
hemangiomas.
 Digital clubbing should be noted.

Diagnostic Evaluation:

 The chest radiograph may also be useful for evaluating hyperinflation (common in
bronchiolitis and viral pneumonia), signs of chronic disease such as bronchiectasis, or a
space-occupying lesion causing airway compression.
 A trial of bronchodilator may be diagnostic as well as therapeutic because these medications
can reverse conditions such as bronchiolitis (occasionally) and asthma but will not affect a
fixed obstruction. Bronchodilators potentially can worsen a case of wheezing caused by
tracheal or bronchial malacia.
 A sweat test to evaluate for cystic fibrosis and evaluation of baseline immune status are
reasonable in infants with recurrent wheezing or complicated courses.
 Further evaluation such as upper gastrointestinal (GI) contrast x-rays, chest CT, bronchoscopy,
infant pulmonary function testing, video swallow study, and pH probe can be considered
second-tier diagnostic procedures in complicated patients.
 Viral testing (polymerase chain reaction, rapid immunofluorescence, or viral culture) is
helpful if the diagnosis is uncertain or for epidemiologic purposes.

Treatment:

 Treatment of an infant with wheezing depends on the underlying etiology.

 Response to bronchodilators is unpredictable, regardless of cause, but suggests a component
of bronchial hyperreactivity. Ipratropium bromide is also useful in infants with significant
tracheal and bronchial malacia who may be made worse by β2 agonists such as albuterol
because of the subsequent decrease in smooth muscle tone.
 A trial of inhaled steroids may be warranted in a patient who has responded to multiple
courses of oral steroids and who has moderate to severe wheezing or a significant history of
atopy including food allergy or eczema.
 Infants with acute bronchiolitis who are experiencing respiratory distress (hypoxia, inability
to take oral feedings, extreme tachypnea) should be hospitalized.
 Hypoxemic children should receive cool humidified oxygen. Sedatives are to be avoided
because they can depress respiratory drive.
 The infant is sometimes more comfortable if sitting with head and chest elevated at a
30-degree angle with neck extended.
 The risk of aspiration of oral feedings may be high in infants with bronchiolitis, owing to
tachypnea and the increased work of breathing. The infant may be fed through a nasogastric
tube.
 If there is any risk for further respiratory decompensation potentially necessitating tracheal
intubation, the infant should not be fed orally but be maintained with parenteral fluids.
 Frequent suctioning of nasal and oral secretions often provides relief of distress or cyanosis.
 A trial dose of inhaled bronchodilator may be reasonable, with further therapy predicated on
response in the individual patient.Nebulized hypertonic saline has also been reported to have
some benefit.

Prognosis:

 Infants with acute bronchiolitis are at highest risk for further respiratory compromise in the
1st 48-72 hr after onset of cough and dyspnea.
411
 The case fatality rate is <1%, with death attributable to apnea, respiratory arrest, or severe
dehydration.
 The median duration of symptoms in ambulatory patients is ∼12 days.
 There is a higher incidence of wheezing and asthma in children with a history of bronchiolitis
unexplained by family history or other atopic syndromes.
 Approximately 60% of infants who wheeze will stop wheezing.

412
 UROLOGY
1. Neuropathic bladder:
2. VUR:
3. Antenatal hydrouretero nephrosis – sagar sir endo notes

1. Neuropathic bladder:
Causes
Congenital Acquired
Traumatic lesions of the spinal cord
Neural tube defects CNS tumours
Spinal Sacrococcygeal teratoma
abnormalities Spinal abnormalities with imperforate
anus

Clinical features and diagnosis:

Renal damage Urinary incontinence
Renal damage usually results from failure of Incontinence in the child with neuropathic
bladder can result from
the sphincter to relax during a spontaneous
bladder contraction. This dyssynergia results in  total or partial denervation of the
functional obstruction of the bladder outlet, sphincter

leading to high intravesical pressure, bladder  bladder hyperreflexia

muscle hypertrophy and trabeculation, and
 poor bladder compliance
transmission of the high pressure into the upper
urinary tracts, causing hydronephrosis.  chronic urinary retention, or

 Combination of these factors.

Vesicoureteral reflux and UTI compound the
The urinary tract should be re-evaluated with
problem. renal ultrasonography, a voiding
cystourethrogram, and urodynamic study,
Treatment includes reduction of bladder including bladder capacity.
pressure with anticholinergic drugs
Treatment:
(oxybutynin, 0.2 mg/kg/24 hr in 2 or 3 divided 1. Artificial sphincter
doses) and clean intermittent catheterization 2. Bladder neck reconstructive procedures.
every 3-4 hr. 3. Augmentation cystoplasty or
Enterocystoplasty
If there is vesicoureteral reflux or UTI,
antimicrobial prophylaxis also is prescribed. future management:

4. Tissue engineering
Antireflux surgery
Botulinum toxin into detrusor muscle 5. Nerve rerouting procedures
Cutaneous vesicostomy

413
Grouping of neurogenic bladder dysfunction according to the innervation, tonicity, and coordination
of the detrusor and sphincters described by Guzman. Patients in group B are at risk of developing
reflux and hydronephrosis. For guidance in the treatment of incontinence, group A benefits from
procedures that increase outlet resistance, group B from anticholinergics or bladder augmentation
surgery, and group C from intermittent catheterization. Group D requires both increased outlet
resistance and pharmacologic or surgical bladder enlargement. Most patients require intermittent
catheterization to empty.
COMPLICATIONS:
1. UTI 4. Bladder calculi
2. Spontaneous perforation 5. Malignant neoplasm
3. Metabolic acidosis

2. VUR:
Vesicoureteral reflux refers to the retrograde flow of urine from the bladder to the ureter and kidney.
Classification
Grading:

Grade I: reflux into a nondilated ureter.

Grade II: reflux into the upper collecting system without dilatation.
Grade III: reflux into dilated ureter and/or blunting of calyceal fornices.
Grade IV: reflux into a grossly dilated ureter.
414
Grade V: massive reflux, with significant ureteral dilatation and tortuosity and loss of the papillary
impression

Clinical Manifestations:

 Reflux usually is discovered during evaluation for a UTI.

 Among these children, 80% are female, and the average age at diagnosis is 2-3 yr.
 Primary reflux also may be discovered during evaluation for prenatal hydronephrosis.
 In this select population, 80% of affected children are male.
Diagnosis:
1. Contrast VCUG
2. Radionuclide cystogram (RNC)
Reflux occurring during bladder filling is termed low-pressure or passive reflux;
Reflux during voiding is termed high-pressure or active reflux.
3. Indirect cystography is a technique of detecting reflux without catheterization that involves
injecting an intravenous radiopharmaceutical that is excreted by the kidneys, waiting for it to
be excreted into the bladder, and imaging the lower urinary tract while the patient voids. This
technique detects only 75% of reflux cases.
Treatment:

The goals of treatment are to prevent pyelonephritis, reflux-related renal injury, and other
complications of reflux.

1. Children with an overactive bladder often undergo a regimen of behavioral modification

with timed voiding, and, on occasion, anticholinergic therapy.
2. After diagnosis, the child's height, weight, and blood pressure should be measured and
monitored.
3. If upper tract imaging shows renal scarring, a serum creatinine measurement should be
obtained.
4. The urine should be assessed for infection and proteinuria.

Medical therapy is based on the principle that reflux often resolves over time and that if UTI can be
prevented, the morbidity or complications of reflux may be avoided without surgery.

In addition, evaluation for bladder and bowel dysfunction (BBD) is considered a standard part of
initial and ongoing patient evaluation in children with reflux.

The basis for surgical therapy is that in selected children, ongoing reflux has caused or has
significant potential for causing renal injury or other reflux-related complications and that
elimination of reflux minimizes the likelihood of these problems.

Surgery is usually indicated in children who fail medical management (breakthrough UTI, persistent
reflux), or those with high reflux grades that are unlikely to resolve.

Correction of mega ureter.

If the refluxing kidney is poorly functioning, nephrectomy or nephroureterectomy is indicated.

Prophylaxis: Drugs commonly used for prophylaxis include

trimethoprim-sulfamethoxazole (TMP-SMX), trimethoprim, nitrofurantoin, or cephalexin, which are
administered once daily at a dose of 25-30% of the dosage necessary to treat an acute infection.
Prophylaxis is continued until reflux resolved or until the risk of reflux to the patient was considered
415
to be low.

Natural History –
1. Mean age at reflux resolution is 6 yr.

2. With bladder growth and maturation, the reflux grade can resolve or improve over time.

3. For grades I and II reflux, the likelihood of resolution is similar regardless of age at diagnosis and
whether it is unilateral or bilateral.

4. For grade III, a younger age at diagnosis and unilateral reflux usually are associated with a higher
rate of spontaneous resolution.

5. Bilateral grade IV reflux is much less likely to resolve than is unilateral grade IV reflux.

6. Grade V reflux rarely resolves.

416
 NUTRITION

1. Weaning principles

The systematic process of introduction of suitable food at the right time in addition to mothers milk
in order to provide needed nutrients to the baby.

IMPORTANT PRINCIPLES FOR WEANING

Begin at 4-6 mo of age
At the proper age, encourage a cup rather than a bottle
Introduce 1 food at a time
Energy density should exceed that of breast milk
Iron-containing foods (meat, iron-supplemented cereals) are required
Zinc intake should be encouraged with foods such as meat, dairy products, wheat, and rice
Phytate intake should be low to enhance mineral absorption
Breast milk should continue to 12 mo, formula or cow's milk is then substituted.
• Give no more than 24 oz/day of cow's milk
Fluids other than breast milk, formula, and water should be discouraged.
• Give no more than 4-6 oz/day of fruit juices. No soda.

AAP provides the following recommendations for initiating complementary foods

• Introduce 1 single nutrient ingredient food at a time, and do not introduce other new foods for 3-5
days to observe for tolerance. Although iron-fortified rice cereal is most commonly introduced,
ethnic and cultural variations should be respected and understood.
• Choose foods that provide key nutrients and help meet energy needs: iron-fortified cereals or
pureed meats that are rich in protein, iron, and zinc.
• Introduce a variety of foods by the end of the 1st yr, helping to establish healthy eating habits.
When offering a new food, 8-10 attempts to offer might need to be made before the infant accepts
the new food.
• Withhold cow's milk and other milks not formulated for infants during the 1st yr of life.
• Ensure adequate calcium intake while transitioning to complementary foods.
• Do not give fruit juices during the first 6 mo of life and limited amounts of 100% juices
thereafter (4-6 oz/day for ages 1-6 yr, and 8-12 oz per day for ages 7-18 yr).
• Ensure safe ingestion to decrease choking hazard and adequate nutrition when choosing and
preparing homemade foods: mash or puree solid foods; avoid hot dogs, nuts, grapes, and popcorn
in the first 3-4 yr of life; avoid adding salt or sugar; and ensure nutrient and energy sufficiency

417
 VITAMINS

1. VITAMIN A
2. WATER-SOLUBLE VITAMINS
3. PHYSICAL AND METABOLIC PROPERTIES AND FOOD SOURCES OF THE
VITAMINS (D, E, AND K)
4. RICKETS
 CAUSES OF RICKETS
 CLINICAL FEATURES OF RICKETS
 INVESTIGATIONS:
5. TRACE ELEMENTS
6. Extra skeletal manifestations of rickets- sagar endocrinology notes
7. Refractory rickets

418
 VITAMIN A
NAMES AND CHARACTERISTI BIOCHEMICA EFFECTS OF EFFECTS
SOURCES
SYNONYMS CS L ACTION DEFICIENCY OF EXCESS
Nyctalopia
In vision, as
retinal, for Photophobia,
synthesis of the xerophthalmia,
visual pigments Bitot spots,
conjunctivitis, Anorexia,
rhodopsin and Liver, fish
Retinol (vitamin keratomalacia slow growth,
iodopsin liver oils
A1); 1 ?g retinol leading to drying and
= 3.3 IU vitamin In growth, cracking of Dairy
blindness
A = 1 RAE reproduction, skin, products,
embryonic and Faulty
Provitamins A: Fat-soluble; epiphyseal enlargement except skim
fetal
the plant heat-stable; bone of liver and milk
pigments α-, β-, destroyed by development, spleen, Egg yolk,
bone growth, formation
and γ-carotenes oxidation, drying Defective
swelling and fortified
and Bile necessary for immune and pain of long margarine,
absorption epithelial tooth enamel bones, bone
cryptoxanthin fortified skim
functions, via Keratinization fragility,
have partial Stored in liver milk
retinoic acid as of mucous increased
retinol activity: Protected by vitamin Carotenoids
a ligand for membranes intracranial
12 ?g β-carotene, E from plants:
specific nuclear and skin pressure,
or 24 ?g other green
transcription Retarded alopecia,
provitamin A vegetables,
factors, growth carotenemia
carotenoids = yellow fruits
regulating
1 ?g retinol Impaired Fetal and vegetables
genes involved
resistance to abnormalities
in many
infection,
fundamental
anemia,
cellular
reproductive
processes
failure, fetal
abnormalities
RAE, retinol activity equivalent.

WHO classification
Primary signs Secondary signs
X 1 A conjunctival xerosis
X 1 B bitot spots X N night blindness
X2 corneal xerosis X F xeropthalmia fundus
X 3 A corneal ulceration(<1/3 rd) X s corneal scars
X 3 B keratomalacia

419
 WATER-SOLUBLE VITAMINS
TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY
0-6 mo:
0.2
mg/day
7-12 mo:
0.3
Neurologic mg/day
(dry beriberi): 1-3 yr:
Meat,
Irritability, Polished 0.5
especially
Coenzyme in peripheral rice–based pork; fish;
mg/day
carbohydrate neuritis, diets 4-8 yr:
liver
metabolism muscle Malabsorptve 0.6
tenderness, 3-5 mg/day Rice
Thiamine Nucleic acid ataxia states mg/day
PO thiamine (unmilled)
(vitamin B1) synthesis Severe , wheat 9-13 yr:
Cardiac (wet for 6 wk malnutrition 0.9
Neurotransmitter beriberi): germ;
synthesis Malignancies enriched mg/day
tachycardia,
Alcoholism cereals; 14-18 yr:
edema,
legumes Girls:
cardiomegaly,
cardiac failure 1.0
mg/da
y
Boys:
1.2
mg/da
y

420
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY
0-6 mo:
0.3
mg/day
7-12 mo:
0.4
mg/day
1-3 yr:
Severe 0.5
Constituent of mg/day
flavoprotein malnutrition
Glossitis, Milk, milk 4-8 yr:
enzymes important Malabsorptive
photophobia, products, 0.6
in states
lacrimation, 3-10 mg/day eggs, mg/day
Riboflavin oxidation-reduction Prolonged
corneal PO fortified 9-13 yr:
(vitamin B2) reactions: amino treatment with
vascularization, riboflavin cereals, 0.9
acid, fatty acid, and phenothiazine
poor growth, green mg/day
carbohydrate s, probenecid,
cheilosis vegetables
metabolism and or OCPs 14-18 yr:
cellular respiration Girls:
1.0
mg/da
y
Boys:
1.3
mg/da
y

421
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY

0-6 mo: 2
mg/day
7-12 mo:
4 mg/day
1-3 yr: 6
Pellagra mg/day
manifesting as Predominantl 4-8 yr: 8
Constituent of Meat, fish,
diarrhea, y maize-based mg/day
NAD and NADP, poultry
symmetric scaly diets
important in 9-13 yr:
dermatitis in 50-300 Cereals,
Niacin respiratory chain, Anorexia 12
sun-exposed mg/day PO legumes,
(vitamin B3) fatty acid nervosa mg/day
areas, and niacin green
synthesis, cell Carcinoid 14-18 yr:
neurologic vegetables
differentiation, and syndrome Girls:
symptoms of
DNA processing 14
disorientation
and delirium mg/da
y
Boys:
16
mg/day

422
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY
0-6 mo:
0.1
mg/day
7-12 mo:
0.3
mg/day
1-3 yr:
0.5
5-25 mg/day
Constituent of Irritability, Fortified mg/day
PO for
coenzymes for convulsions, deficiency ready-to-eat 4-8 yr:
amino acid and hypochromic states Prolonged cereals, 0.6
glycogen anemia treatment with meat, fish, mg/day
Pyridoxine 100 mg IMINH,
metabolism, heme poultry, 9-13 yr:
(vitamin B6) Failure to or IV for
synthesis, steroid penicillamine, liver, 1.0
thrive pyridoxine-OCPs
action, bananas, mg/day
neurotransmitter Oxaluria dependent rice.
synthesis seizures potatoes 14-18 yr:
Girls:
1.2
mg/da
y
Boys:
1.3
mg/da
y

423
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY
Consumption
of raw eggs
for prolonged
periods
Parenteral
0-6 mo:
nutrition with
5 ?g/day
infusates
Scaly lacking biotin 7-12 mo:
Cofactor for periorificial 6 ?g/day
Valproate
carboxylases, dermatitis, therapy 1-3 yr:
important in conjunctivitis, 8 ?g/day
1-10 mg/day Liver, organ
Biotin gluconeogenesis, alopecia, 4-8 yr:
PO biotin meats, fruits
fatty acid and lethargy, 12 ?g/day
amino acid hypotonia and 9-13 yr:
metabolism withdrawn 20 ?g/day
behavior
14-18 yr:
25 ?g/day

0-6 mo:
1.7
Experimentally Beef, mg/day
produced organ 7-12 mo:
deficiency in meats, 1.8
Component of humans: poultry, mg/day
Isolated seafood,
Pantothenic coenzyme A and irritability, 1-3 yr: 2
deficiency egg yolk
acid (vitamin acyl carrier protein fatigue, mg/day
extremely rare in
B5) involved in fatty numbness, Yeast, 4-8 yr: 3
humans
acid metabolism paresthesias soybeans, mg/day
(burning feet mushroom
syndrome), 9-13 yr: 4
s
muscle cramps mg/day
14-18 yr:
5 mg/day

424
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY
0-6 mo:
65 ?g/day
7-12 mo:
80 ?g/day
Megaloblastic Malnutrition
1-3 yr:
anemia Malabsorptive 150 ?g/da
Coenzymes in states Enriched
Growth y
amino acid and cereals,
retardation, 0.5-1 Malignancies
nucleotide beans, leafy 4-8 yr:
Folic acid glossitis mg/day PO Hemolytic 200 ?g/da
metabolism as an vegetables,
acceptor and donor Neural tube folic acid anemias citrus fruits, y
of one-carbon units defects in Anticonvulsa papaya 9-13 yr:
progeny nt therapy 300 ?g/da
y
14-18 yr:
400 ?g/da
y

As 0-6 mo:
deoxy-adenosylco 0.4 ?g/d
balamin, acts asMegaloblastic Vegan diets
7-12 mo:
cofactor for lipidanemia, Malabsorptiv Organ 0.5 ?g/d
and carbohydrateirritability, e states meats, sea
developmental 1-3 yr:
metabolism Crohn disease foods
delay, 0.9 ?g/d
Cobalamin As 1,000 ?g IM Intrinsic poultry, egg
developmental 4-8 yr:
(vitamin B12) methycobalamin, regression, vitamin B12 factor yolk, milk,
fortified 1.2 ?g/d
important forinvoluntary deficiency
conversion ofmovements, ready-to-eat 9-13 yr:
(pernicious
homocysteine tohyperpigmentati cereals 1.8 ?g/d
anemia)
methionine andon 14-18 yr:
folic acid 2.4 ?g/d
metabolism

425
 TREATME
NAMES AND BIOCHEMICAL EFFECTS OF NT OF CAUSES OF DIETARY
RDA*
SYNONYMS ACTION DEFICIENCY DEFICIEN DEFICIENCY SOURCES
CY

0-6 mo:
40
mg/day
7-12 mo:
50
mg/day
Important forScurvy 1-3 yr: 15
collagen manifesting as Citrus fruits mg/day
synthesis, irritability, Predominantl and fruit 4-8 yr: 25
metabolism oftenderness and 100-200 y milk-based juices, mg/day
cholesterol andswelling of legs, mg/day PO (non–human peppers, 9-13 yr:
Ascorbic acid neurotransmitters bleeding gums, ascorbic milk) diets berries,
45
(vitamin C) petechiae, melons,
Antioxidant acid for up Severe mg/day
ecchymoses, tomatoes,
functions andfollicular to 3 mo malnutrition 14-18 yr:
cauliflower,
nonheme ironhyperkeratosis, leafy green Girls:
absorption and poor wound vegetables 65
healing mg/da
y
Boys:
75
mg/da
y

INH, isoniazid; NAD, nicotinamide adenine dinucleotide ; NADP, nicotinamide adenine dinucleotide
phosphate; OCP, oral contraceptive pill; RDA, recommended dietary allowance

PHYSICAL AND METABOLIC PROPERTIES AND FOOD SOURCES OF THE VITAMINS

(D, E, AND K)
EFFECTS OF
NAMES AND CHARACTERISTIC BIOCHEMICA EFFECTS OF
DEFICIENC SOURCES
SYNONYMS S L ACTION EXCESS
Y
VITAMIN D

426
 EFFECTS OF
NAMES AND CHARACTERISTIC BIOCHEMICA EFFECTS OF
DEFICIENC SOURCES
SYNONYMS S L ACTION EXCESS
Y
Exposure
Vitamin D3
Hypercalcemia to sunlight
(3-cholecalcifer Necessary for GI
Fat-soluble, stable to , which can (UV light);
ol), which is absorption of Rickets in
heat, acid alkali, and cause emesis, fish oils,
synthesized in calcium; also growing
oxidation; bile anorexia, fatty fish,
the skin, and increases children;
necessary for pancreatitis, egg yolks,
vitamin D2 absorption of osteomalacia;
absorption; hypertension, and
(from plants or phosphate; direct hypocalcemia
hydroxylation in the arrhythmias, vitamin
yeast) are actions on bone, can cause
liver and kidney CNS effects, D–fortified
biologically including tetany and
necessary for biologic polyuria, formula,
equivalent; 1 ?g mediating seizures
activity nephrolithiasis, milk,
= 40 IU vitamin resorption
renal failure cereals,
D
bread

VITAMIN E
Red cell
Group of related hemolysis in
compounds with Antioxidant; premature Vegetable
Fat-soluble; readily
similar biologic protection of cell infants; oils, seeds,
oxidized by oxygen,
activities; membranes from posterior nuts, green
iron, rancid fats; bile Unknown
α-tocopherol is lipid peroxidation column and leafy
acids necessary for
the most potent and formation of cerebellar vegetables,
absorption
and the most free radicals dysfunction; margarine
common form pigmentary
retinopathy
VITAMIN K

Group of Vitamin Not

naphthoquinone Natural compounds are K–dependent established; Green leafy
s with similar fat-soluble; stable to proteins include analogs (no vegetables,
Hemorrhagic
biologic heat and reducing coagulation longer used) liver,
manifestations;
activities; K1 agents; labile to factors II, VII, caused certain
long-term bone
(phylloquinone) oxidizing agent, strong IX, and X; hemolytic legumes
and vascular
from diet; K2 acids, alkali, light; bile proteins C, S, Z; anemia, and plant
health
(menaquinones) salts necessary for matrix gla jaundice, oils; widely
from intestinal intestinal absorption protein, kernicterus, distributed
bacteria osteocalcin death

CNS, central nervous system; GI, gastrointestinal; UV, ultraviolet.

-- CAUSES OF RICKETS
VITAMIN D DISORDERS
427
 Nutritional vitamin D deficiency
Congenital vitamin D deficiency
Secondary vitamin D deficiency
Malabsorption
Increased degradation
Decreased liver 25-hydroxylase
Vitamin D–dependent rickets type 1
Vitamin D–dependent rickets type 2
Chronic renal failure
CALCIUM DEFICIENCY
Low intake
Diet
Premature infants (rickets of prematurity)
Malabsorption
Primary disease
Dietary inhibitors of calcium absorption
PHOSPHORUS DEFICIENCY
Inadequate intake
Premature infants (rickets of prematurity)
Aluminum-containing antacids
RENAL LOSSES
X-linked hypophosphatemic rickets*
Autosomal dominant hypophosphatemic rickets*
Autosomal recessive hypophosphatemic rickets*
Hereditary hypophosphatemic rickets with hypercalciuria
Overproduction of phosphatonin
Tumor-induced rickets*
McCune-Albright syndrome*
Epidermal nevus syndrome*
Neurofibromatosis*
Fanconi syndrome
Dent disease
Distal renal tubular acidosis
*
Disorders secondary to excess phosphatonin.

Clinical Manifestations

Most manifestations of rickets are due to skeletal changes (Table 48-3). Craniotabes is a softening of
the cranial bones and can be detected by applying pressure at the occiput or over the parietal bones.
The sensation is similar to the feel of pressing into a Ping-Pong ball and then releasing. Craniotabes
may also be secondary to osteogenesis imperfecta, hydrocephalus, and syphilis. It is a normal finding
in many newborns, especially near the suture lines, but it typically disappears within a few months of
birth. Widening of the costochondral junctions results in a rachitic rosary, which feels like the beads
of a rosary as the examiner's fingers move along the costochondral junctions from rib to rib (Fig.
428
48-1). Growth plate widening is also responsible for the enlargement at the wrists and ankles. The
horizontal depression along the lower anterior chest known as Harrison groove occurs from pulling
of the softened ribs by the diaphragm during inspiration (Fig. 48-2). Softening of the ribs also impairs
air movement and predisposes patients to atelectasis and pneumonia.

Table 48-3 -- CLINICAL FEATURES OF RICKETS

GENERAL
Failure to thrive
Listlessness
Protruding abdomen
Muscle weakness (especially proximal)
Fractures
HEAD
Craniotabes
Frontal bossing
Delayed fontanel closure
Delayed dentition; caries
Craniosynostosis
CHEST
Rachitic rosary
Harrison groove
Respiratory infections and atelectasis*
BACK
Scoliosis
Kyphosis
Lordosis
EXTREMITIES
Enlargement of wrists and ankles
Valgus or varus deformities
Windswept deformity (combination of valgus deformity of 1 leg with varus deformity of the other leg)
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
HYPOCALCEMIC SYMPTOMS[†]
Tetany
Seizures
Stridor due to laryngeal spasm

INVESTIGATIONS:
LABORATORY FINDINGS IN DISORDERS CAUSING RICKETS
429
 25-(OH 1,25-(OH)2 ALK URINE
Disorder Ca Pi PTH URINE Pi
)D D PHOS Ca
N,
Vitamin D deficiency ↓ ↑ ↓ ↓, N, ↑ ↑ ↓ ↑
↓
N,
VDDR, type 1 ↓ ↑ N ↓ ↑ ↓ ↑
↓
N,
VDDR, type 2 ↓ ↑ N ↑↑ ↑ ↓ ↑
↓
N,
Chronic renal failure ↑ ↑ N ↓ ↑ N, ↓ ↓
↓
Dietary Pi deficiency N ↓ N, ↓ N ↑ ↑ ↑ ↓
XLH N ↓ N N RD ↑ ↓ ↑
ADHR N ↓ N N RD ↑ ↓ ↑
HHRH N ↓ N, ↓ N RD ↑ ↑ ↑
ARHR N ↓ N N RD ↑ ↓ ↑
Tumor-induced rickets N ↓ N N RD ↑ ↓ ↑
Fanconi syndrome N ↓ N N RD or ↑ ↑ ↓ or ↑ ↑
N,
Dietary Ca deficiency ↓ ↑ N ↑ ↑ ↓ ↑
↓
ADHR, autosomal dominant hypophosphatemic rickets; Alk Phos, alkaline phosphatase; ARHR, autosomal
recessive hypophosphatemic rickets; Ca, calcium; HHRH, hereditary hypophosphatemic rickets with
hypercalciuria; N, normal; Pi, inorganic phosphorus; PTH, parathyroid hormone; RD, relatively decreased
(because it should be increased given the concurrent hypophosphatemia); VDDR, vitamin D–dependent
rickets; XLH, X-linked hypophosphatemic rickets; 1,25-(OH)2D, 1,25-dihydroxyvitamin D; 25-OHD,
25-hydroxyvitamin D; ↓, decreased; ↑, increased; ↑↑, extremely increased.

Radiology

Rachitic changes are most easily visualized on posteroanterior radiographs of the wrist, although
characteristic rachitic changes can be seen at other growth plates (Figs. 48-3 and 48-4). Decreased
calcification leads to thickening of the growth plate. The edge of the metaphysis loses its sharp
border, which is described as fraying. The edge of the metaphysis changes from a convex or flat
surface to a more concave surface. This change to a concave surface is termed cupping and is most
easily seen at the distal ends of the radius, ulna, and fibula. There is widening of the distal end of the
metaphysis, corresponding to the clinical observation of thickened wrists and ankles as well as the
rachitic rosary. Other radiologic features include coarse trabeculation of the diaphysis and
generalized rarefaction.

Diagnosis:

Most cases of rickets are diagnosed based on the presence of classic radiographic abnormalities. The
diagnosis is supported by physical examination findings and a history and laboratory test results that
are consistent with a specific etiology.

Clinical Evaluation:

Because the majority of children with rickets have a nutritional deficiency, the initial evaluation
should focus on a dietary history, emphasizing intake of vitamin D and calcium.

430
Cutaneous synthesis mediated by sunlight exposure is an important source of vitamin D. It is
important to ask about time spent outside, sunscreen use, and clothing, especially if there may be a
cultural reason for increased covering of the skin. Because winter sunlight is ineffective at
stimulating cutaneous synthesis of vitamin D, the season is an additional consideration. Children with
increased skin pigmentation are at increased risk for vitamin D deficiency because of decreased
cutaneous synthesis.

The presence of maternal risk factors for nutritional vitamin D deficiency, including diet and sun
exposure, is an important consideration when a neonate or young infant has rachitic findings,
especially if the infant is breast-fed. Determining a child's intake of dairy products, the main dietary
source of calcium, provides a general sense of calcium intake. High dietary fiber can interfere with
calcium absorption.

The child's medication use is relevant, because certain medications such as the anticonvulsants
phenobarbital and phenytoin increase degradation of vitamin D, and aluminum-containing antacids
interfere with the absorption of phosphate.

Malabsorption of vitamin D is suggested by a history of liver or intestinal disease. Undiagnosed

liver or intestinal disease should be suspected if the child has gastrointestinal (GI) symptoms,
although occasionally rickets is the presenting complaint. Fat malabsorption is often associated with
diarrhea or oily stools, and there may be signs or symptoms suggesting deficiencies of other
fat-soluble vitamins .

A history of renal disease (proteinuria, hematuria, urinary tract infections) is an additional significant
consideration, given the importance of chronic renal failure as a cause of rickets. Polyuria can occur
in children with chronic renal failure or Fanconi syndrome.

Children with rickets might have a history of dental caries, poor growth, delayed walking, waddling
gait, pneumonia, and hypocalcemic symptoms.

The family history is critical, given the large number of genetic causes of rickets, although most of
these causes are rare. Undiagnosed disease in the mother is not unusual in X-linked
hypophosphatemia.

The initial laboratory tests in a child with rickets should include serum calcium, phosphorus,
alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3,
creatinine, and electrolytes.

Urinalysis is useful for detecting the glycosuria and aminoaciduria (positive dipstick for protein) seen
with Fanconi syndrome. Evaluation of urinary excretion of calcium (24 hr collection for calcium or
calcium:creatinine ratio) is helpful if hereditary hypophosphatemic rickets with hypercalciuria or
Fanconi syndrome is suspected. Direct measurement of other fat-soluble vitamins (A, E, and K) or
indirect assessment of deficiency (prothrombin time for vitamin K deficiency) is appropriate if
malabsorption is a consideration.

TREATMENT:

Nutritional Vitamin D Deficiency

Children with nutritional vitamin D deficiency should receive vitamin D and adequate nutritional
intake of calcium and phosphorus. There are 2 strategies for administration of vitamin D. With stoss
therapy, 300,000-600,000 IU of vitamin D are administered orally or intramuscularly as 2-4 doses
over 1 day. Because the doses are observed, stoss therapy is ideal in situations where adherence to
therapy is questionable. The alternative is daily, high-dose vitamin D, with doses ranging from
431
2,000-5,000 IU/day over 4-6 wk. Either strategy should be followed by daily vitamin D intake of 400
IU/day if <1 yr old or 600 IU/day if >1 yr, typically given as a multivitamin. It is important to ensure
that children receive adequate dietary calcium and phosphorus; this dietary intake is usually provided
by milk, formula, and other dairy products.

Children who have symptomatic hypocalcemia might need intravenous calcium acutely, followed by
oral calcium supplements, which typically can be tapered over 2-6 wk in children who receive
adequate dietary calcium. Transient use of intravenous or oral 1,25-D (calcitriol) is often helpful in
reversing hypocalcemia in the acute phase by providing active vitamin D during the delay as
supplemental vitamin D is converted to active vitamin D. Calcitriol doses are typically
0.05 ?g/kg/day. Intravenous calcium is initially given as an acute bolus for symptomatic
hypocalcemia (20 mg/kg of calcium chloride or 100 mg/kg of calcium gluconate).

Secondary Vitamin D Deficiency:

Treatment of vitamin D deficiency due to malabsorption requires high doses of vitamin D. Because
of its better absorption, 25-D (25-50 ?g/day or 5-7 ?g/kg/day) is superior to vitamin D3. The dose is
adjusted based on monitoring of serum levels of 25-D. Alternatively, patients may be treated with
1,25-D, which also is better absorbed in the presence of fat malabsorption, or with parenteral vitamin
D. Children with rickets due to increased degradation of vitamin D by the CYP system require the
same acute therapy as indicated for nutritional deficiency (discussed earlier), followed by long-term
administration of high doses of vitamin D (e.g., 1,000 IU/day), with dosing titrated based on serum
levels of 25-D. Some patients require as much as 4,000 IU/day.

Vitamin D–Dependent Rickets, Type 1:

These patients respond to long-term treatment with 1,25-D (calcitriol). Initial doses are 0.25-2 ?g/day,
and lower doses are used once the rickets has healed. Especially during initial therapy, it is important
to ensure adequate intake of calcium. The dose of calcitriol is adjusted to maintain a low-normal
serum calcium level, a normal serum phosphorus level, and a high-normal serum PTH level.
Targeting a low-normal calcium concentration and a high-normal PTH level avoids excessive dosing
of calcitriol, which can cause hypercalciuria and nephrocalcinosis. Hence, patient monitoring
includes periodic assessment of urinary calcium excretion, with a target of <4 mg/kg/day.

Vitamin D–Dependent Rickets, Type 2:

Some patients respond to extremely high doses of vitamin D2, 25-D or 1,25-D, especially patients
without alopecia. This response is due to a partially functional vitamin D receptor. All patients with
this disorder should be given a 3-6 mo trial of high-dose vitamin D and oral calcium. The initial dose
of 1,25-D should be 2 ?g/day, but some patients require doses as high as 50-60 ?g/day. Calcium doses
are 1,000-3,000 mg/day. Patients who do not respond to high-dose vitamin D may be treated with
long-term intravenous calcium, with possible transition to very high dose oral calcium supplements.
Treatment of patients who do not respond to vitamin D is difficult.

Chronic Renal Failure

Therapy requires the use of a form of vitamin D that can act without 1-hydroxylation by the kidney
(calcitriol), which both permits adequate absorption of calcium and directly suppresses the
parathyroid gland. Because hyperphosphatemia is a stimulus for PTH secretion, normalization of the
serum phosphorus level via a combination of dietary phosphorus restriction and the use of oral
phosphate binders is as important as the use of activated vitamin D.

432
Hypervitaminosis D:

Etiology: Hypervitaminosis D is secondary to excessive intake

of vitamin D. Most cases are secondary to misuse of prescribed or over-the-counter vitamin D
supplements, but other cases have been secondary to accidental overfortification of milk,
contamination of table sugar, and inadvertent use of vitamin D supplements as cooking oil. The
recommended upper limits for long-term vitamin D intake are 1,000 IU for children <1 year old and
2,000 IU for older children and adults. Vitamin D intoxication is never secondary to excessive
exposure to sunlight, probably because ultraviolet irradiation can transform vitamin D3 and its
precursor into inactive metabolites.

Clinical Manifestations: The signs and symptoms of vitamin D

intoxication are secondary to hypercalcemia. GI manifestations include nausea, vomiting, poor
feeding, constipation, abdominal pain, and pancreatitis. Possible cardiac findings are hypertension,
decreased Q-T interval, and arrhythmias. The central nervous system effects of hypercalcemia
include lethargy, hypotonia, confusion, disorientation, depression, psychosis, hallucinations, and
coma. Hypercalcemia impairs renal concentrating mechanisms, which can lead to polyuria,
dehydration, and hypernatremia. Hypercalcemia can also lead to acute renal failure, nephrolithiasis,
and nephrocalcinosis, which can result in chronic renal insufficiency. Deaths are usually associated
with arrhythmias or dehydration.

Laboratory Findings and Diagnosis: The classic findings

in vitamin D intoxication are hypercalcemia and extremely elevated levels of 25-D (>150 ng/mL).
Hyperphosphatemia is also common. PTH levels are appropriately decreased owing to
hypercalcemia. Hypercalciuria is universally present and can lead to nephrocalcinosis.

Surprisingly, levels of 1,25-D are usually normal. Anemia is sometimes present.

The differential diagnosis

Hyperparathyroidism Williams syndrome Subcutaneous fat necrosis familial benign
hypocalciuric hypercalcemia Hypercalcemia of malignancy

Treatment: The treatment of vitamin D

intoxication focuses on control of hypercalcemia. Normal saline, with or without a loop diuretic, is
often adequate for treating mild or moderate hypercalcemia. Glucocorticoids decrease intestinal
absorption of calcium by blocking the action of 1,25-D. The usual dosage of prednisone is 1-2
mg/kg/24 hr.

Calcitonin, which lowers calcium by inhibiting bone resorption, is a useful adjunct, but its effect is
usually not dramatic.

There is an excellent response to intravenous or oral bisphosphonates in vitamin D intoxication.

Hemodialysis using a low or 0 dialysate calcium can rapidly lower serum calcium in patients with
severe hypercalcemia that is refractory to other measures.

Along with controlling hypercalcemia, it is imperative to eliminate the source of excess vitamin D.
Avoidance of sun exposure, including the use of sunscreen, is prudent. The patient should also
restrict calcium intake.

Prognosis: Most children make a full recovery, but hypervitaminosis D may be fatal or can lead
433
to chronic renal failure.

TRACE ELEMENTS
ELEMEN EFFECTS OF EFFECTS OF DIETARY
PHYSIOLOGY
T DEFICIENCY EXCESS SOURCES

Impaired glucose
Meat, grains,
Potentiates the action tolerance, peripheral
Chromium Unknown fruits, and
of insulin neuropathy, and
vegetables
encephalopathy

Acute: nausea,
Circulates bound to
emesis, abdominal
ceruloplasmin
pain, coma, and Vegetables,
Enzyme cofactor Microcytic anemia,
hepatic necrosis grains, nuts,
(superoxide osteoporosis, neutropenia,
Chronic toxicity liver,
Copper dismutase, neurologic symptoms,
(liver and brain margarine,
cytochrome oxidase, depigmentation of hair and
injury) occurs in legumes, corn
and enzymes involved skin
Wilson disease and oil
in iron metabolism
secondary to
and connective tissue
excess intake
formation)

Toothpaste,
Chronic: dental
Fluoride Incorporated into bone Dental caries fluoridated
fluorosis
water
Hypothyroidism
and goiter;
maternal excess
Component of thyroid Saltwater fish,
Iodine Hypothyroidism can cause
hormone iodized salt
congenital
hypothyroidism
and goiter

434
ELEMEN EFFECTS OF EFFECTS OF DIETARY
PHYSIOLOGY
T DEFICIENCY EXCESS SOURCES

Acute : nausea,
Meat, fortified
vomiting, diarrhea,
foods
Component of abdominal pain,
Deficiency can
hemoglobin, and hypotension
Anemia, decreased also result from
Iron myoglobin, Chronic excess
alertness, impaired learning blood loss
cytochromes, and usually secondary
(hookworm
other enzymes to hereditary
infestation,
disorders causes
menorrhagia)
organ dysfunction

Hypercholesterolemia, Neurologic
Nuts, meat,
Manganese Enzyme cofactor weight loss, decreased manifestations,
grains, tea
clotting proteins cholestatic jaundice

Enzyme cofactor Tachycardia, tachypnea, Hyperuricemia and

Molybdenu Legumes,
(xanthine oxidase and night blindness, irritability, increased risk of
m grains, liver
others) coma gout

Nausea, diarrhea,
Enzyme cofactor neurologic Meat, seafood,
Cardiomyopathy (Keshan
Selenium (prevents oxidative manifestations, nail whole grains,
disease), myopathy
damage) and hair changes, garlic
garlic odour

Decreased growth,
dermatitis of extremities
Enzyme cofactor and around orifices,
Abdominal pain,
Constituent of impaired immunity, poor Meat, shellfish,
diarrhea, vomiting
Zinc zinc-finger proteins, wound healing, whole grains,
Can worsen copper
which regulate gene hypogonadism, diarrhea legumes, cheese
deficiency
transcription Supplements beneficial in
diarrhea and improve neuro
developmental outcome

435
 FLUID AND ELECTROLYTES

1. Regulation of Osmolality and Volume

2. Hypernatremia:

3. Hyponatremia:

4. SIADH:

5. Hypokalemia:

6. Hyperkalemia:

7. Hypomagnesemia:

8. Hypermagnesemia:

9. Acid base balance:

10. Metabolic Acidosis:

11. Metabolic alkalosis:

1. Regulation of Osmolality and Volume (2+3)

Regulation of Osmolality
1. The plasma osmolality is tightly regulated and maintained at 285-295 mOsm/kg. Modification
of water intake and excretion maintains normal plasma osmolality. In the steady state, the
combination of water intake and water produced by the body from oxidation balances water
losses from the skin, lungs, urine, and gastrointestinal tract. Only water intake and urinary
losses can be regulated.
Osmoreceptors in the hypothalamus sense the plasma osmolality.

An elevated effective osmolality leads to secretion of antidiuretic hormone (ADH) by neurons in the
supraoptic and paraventricular nuclei in the hypothalamus. The axons of these neurons terminate in
the posterior pituitary.

Circulating ADH binds to its V2 receptors in the collecting duct cells of the kidney, and, via the
generation of cyclic adenosine monophosphate, causes insertion of water channels (aqua Porin-2)
into the renal collecting ducts.

This produces increased permeability to water, permitting resorption of water into the hypertonic
renal medulla.
The end result is that the urine concentration increases and water excretion decreases.
2. Water intake is regulated by hypothalamic osmoreceptors, although these are different from the
osmoreceptors that determine ADH secretion. These hypothalamic osmoreceptors, by linking to the
cerebral cortex, stimulate thirst when the serum osmolality increases.
The normal response to increased plasma osmolality is conservation of water by the kidney.
In central diabetes insipidus, this does not occur because of an absence of ADH secretion.
Patients with nephrogenic diabetes insipidus have an inability to respond to ADH and produce
436
dilute urine despite an increase in plasma osmolality.

Regulation of Volume (3):

An appropriate intravascular volume is critical for survival; both volume depletion and volume
overload may cause significant morbidity and mortality. Because sodium is the principal extracellular
cation and it is restricted to the ECF, adequate body sodium is necessary for maintenance of
intravascular volume.
1. Urinary sodium excretion is regulated by both intrarenal and extrarenal mechanisms. The most
important determinant of renal sodium excretion is the volume status of the child; it is the effective
intravascular volume that influences urinary sodium excretion.
Sodium resorption occurs throughout the nephron. Whereas the majority of filtered sodium is
resorbed in the proximal tubule and the loop of Henle, the distal tubule and the collecting duct are
the main sites for precise regulation of sodium balance. Approximately 65% of the filtered sodium
is reclaimed in the proximal tubule, which is the major site for resorption of bicarbonate, glucose,
phosphate, amino acids, and other substances that are filtered by the glomerulus.
The loop of Henle is, in terms of absolute amount, the 2nd most important site of sodium resorption
along the nephron. The Na+, K+, 2Cl− cotransporter on the luminal side of the membrane reclaims
filtered sodium and chloride, whereas most of the potassium is recycled back into the lumen. ADH
stimulates sodium retention in this segment.
Sodium retention in the distal tubule is mediated by the thiazide-sensitive Na+,Cl− cotransporter.
This segment of the nephron is relatively impermeable to water, and along with sodium and chloride
retention, the distal tubule is important for delivery of fluid with a low sodium concentration to the
collecting duct.
The collecting duct, the final segment of the nephron, is important for the regulation of excretion of
water, potassium, acid, and sodium. Even though the amount of sodium resorbed in this segment is
less than in any other segment, this is the critical site for the regulation of sodium balance. Sodium
resorption occurs via a sodium channel that is regulated by aldosterone. When these channels are
open under the influence of aldosterone, almost all of the sodium can be resorbed.
2. The renin-angiotensin system is an important regulator of renal sodium excretion. The
juxtaglomerular apparatus produces renin in response to decreased effective intravascular volume.
Specific stimuli for renin release are decreased perfusion pressure in the afferent arteriole of the
glomerulus, decreased delivery of sodium to the distal nephron, and β1-adrenergic agonists,
which increase in response to intravascular volume depletion. Renin, a proteolytic enzyme, cleaves
angiotensinogen, producing angiotensin I. Angiotensin-converting enzyme (ACE) converts
angiotensin I into angiotensin II. The actions of angiotensin II include direct stimulation of the
proximal tubule to increase sodium resorption and stimulation of the adrenal gland to increase
aldosterone secretion. Aldosterone also stimulates potassium excretion, increasing urinary losses.
3. Volume expansion stimulates the synthesis of atrial natriuretic peptide, which is produced by
the atria in response to atrial wall distention. Along with increasing the GFR, atrial natriuretic peptide
inhibits sodium resorption in the medullary portion of the collecting duct, facilitating an increase in
urinary sodium excretion.
My code
PT- angiotensin 2
L O H- Na K 2Cl, A D H (all 3 letters)
D T- thiazide sensitive, Na Cl Co Transporter (all 2 letters)
CD- Aldosterone, ADH, ANP (all starting with letter A)

2. Hypernatremia:

Hypernatremia is a sodium concentration >145 mEq/L, although it is sometimes defined as >150

mEq/L.

Causes of hypernatremia:

437
Excessive sodium Water and sodium deficits:
Improperly mixed formula Gastrointestinal losses
Excess sodium bicarbonate Diarrhea
Ingestion of seawater or sodium chloride Emesis/ nasogastric suction
Intentional salt poisoning Osmotic cathartics
Intravenous hypertonic saline Cutaneous losses
Hyperaldosteronism Burns
Excessive sweating
WATER DEFICIT: Renal losses
Nephrogenic diabetes insipidus Osmotic diuretics
Central diabetes insipidus Diabetes mellitus
Increased insensible losses Chronic kidney disease
Premature infants Polyuric phase of acute tubular necrosis
Radiant warmers Post obstructive diuresis
Phototherapy
Inadequate intake
Ineffective breast feeding
Child neglect or abuse
Adipsia

Clinical Manifestations

 Most children with hypernatremia are dehydrated and show the typical clinical signs and
symptoms. Children with hypernatremic dehydration tend to have better preservation of
intravascular volume because of the shift of water from the intracellular space to the
extracellular space.
 Probably because of intracellular water loss, the pinched abdominal skin of a dehydrated,
hypernatremic infant has a “doughy” feel.
 Patients are irritable, restless, weak, and lethargic.
 Some infants have a high-pitched cry and hyperpnea.
 Alert patients are very thirsty, even though nausea may be present.
 Hypernatremia may cause fever, although many patients have an underlying process that
contributes to the fever.
 Brain hemorrhage is the most devastating consequence of hypernatremia. As the
extracellular osmolality increases, water moves out of brain cells, leading to a decrease in
438
 brain volume. This decrease can result in tearing of intracerebral veins and bridging blood
vessels as the brain moves away from the skull and the meninges. Seizures and coma are
possible sequelae of the hemorrhage.

TREATMENT:
 As hypernatremia develops, the brain generates idiogenic osmoles to increase the
intracellular osmolality and prevent the loss of brain water. This mechanism is not
instantaneous and is most prominent when hypernatremia has developed gradually. If the
serum sodium concentration is lowered rapidly, there is movement of water from the serum
into the brain cells to equalize the osmolality in the 2 compartments. The resultant brain
swelling manifests as seizures or coma.
 Because of the associated dangers, hypernatremia should not be corrected rapidly. The goal is
to decrease the serum sodium by <12 mEq/L every 24 hr, a rate of 0.5 mEq/L/hr.
 It is important to address the underlying cause of the hypernatremia, if possible. The child
with central diabetes insipidus should receive desmopressin acetate.
 The daily water intake of a child who is receiving tube feeding may need to be increased to
compensate for high losses.
 The patient with significant ongoing losses, such as through diarrhea, may need supplemental
water and electrolytes.
Determine time for correction on basis of initial sodium concentration:
[Na] 145-157 mEq/L: 24 hr
[Na] 158-170 mEq/L: 48 hr
[Na] 171-183 mEq/L: 72 hr
[Na] 184-196 mEq/L: 84 hr

3. HYPONATREMIA:
Hyponatremia, a very common electrolyte abnormality in hospitalized patients, is a serum sodium
level <135 mEq/L. Both total body sodium and TBW determine the serum sodium concentration.
Hyponatremia exists when the ratio of water to sodium is increased.
Causes:

2. HYPOVOLEMIC HYPONATREMIA: 1. PSEUDOHYPONATREMIA:

A. EXTRARENAL LOSSES: Hyperosmolality

Gastrointestinal (emesis, diarrhea) Hyperglycemia

Skin (sweating, burns) Iatrogenic (mannitol, sucrose)

Third space losses 3. EUVOLEMIC HYPONATREMIA:

B. Renal losses SIADH

Thiazide or loop diuretics Desmopressin acetate

439
 Osmotic diuresis Glucocorticoid deficiency

Post obstructive diuresis Hypothyroidism

Polyuric phase of acute tubular necrosis Water intoxication (iatrogenic, tap water
enema, child abuse, psychogenic polydipsia)
Juvenile nephronophthisis
4. HYPERVOLEMIC HYPONATREMIA:
ARPKD
CCF
Tubulointerstitial nephritis
Nephrotic syndrome
CSW
Renal failure
Obstructive uropathy
Cirrhosis

Protein losing enteropathy

Capillary leak due to sepsis

CLINICAL FEATURES:
Hyponatremia causes a decrease in the osmolality of the extracellular space.

Because the intracellular space then has a higher osmolality, water moves from the extracellular
space to the intracellular space to maintain osmotic equilibrium.
The increase in intracellular water causes cells to swell. Although cell swelling is not problematic in
most tissues, it is dangerous for the brain, which is confined by the skull.
As brain cells swell, there is an increase in intracranial pressure, which impairs cerebral blood flow.
Acute, severe hyponatremia can cause brainstem herniation and apnea; respiratory support is often
necessary.
Neurologic symptoms of hyponatremia include anorexia, nausea, emesis, malaise, lethargy, confusion,
agitation, headache, seizures, coma, and decreased reflexes. Hyponatremia can cause muscle
cramps and weakness.
Diagnosis:
 The history usually points to a likely etiology of the hyponatremia.
 Brain injury raises the possibility of SIADH or cerebral salt wasting.
 The traditional 1st step in the diagnostic process is determination of the plasma osmolality.A
normal osmolality in combination with hyponatremia occurs in pseudohyponatremia.
 Hypovolemic hyponatremia can have renal or nonrenal causes. In non renal causes the
urinary sodium concentration is low, typically <10 mEq/L. When the kidney is the cause of
the sodium loss, the urine sodium concentration is >20 mEq/L, reflecting the defect in renal
sodium retention.
 In the patient with hypervolemic hyponatremia, the urine sodium concentration is a helpful
parameter. It is usually <10 mEq/L, except in the patient with renal failure.
TREATMENT:
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The management of hyponatremia is based on the pathophysiology of the specific etiology. The
management of all causes requires judicious monitoring and avoidance of an overly quick
normalization of the serum sodium concentration. A patient with severe symptoms (seizures), no
matter the etiology, should be given a bolus of 4-6 mL/kg of 3% hypertonic saline to produce a
small, rapid increase in serum sodium.
With all causes of hyponatremia, it is important to avoid “overly rapid” correction. The reason is that
rapid correction of hyponatremia may cause central pontine myelinolysis (CPM). This syndrome,
which occurs within several days of rapid correction of hyponatremia, produces neurologic
symptoms, including confusion, agitation, flaccid or spastic quadriparesis, and death. Even though
CPM is rare in pediatric patients, it is advisable to avoid correcting the serum sodium concentration
by >12 mEq/L/24 hr or > 18 mEq/L/48 hr.
The child with hypovolemic hyponatremia has a deficiency in sodium and may have a deficiency in
water. The 1st step in treating any dehydrated patient is to restore the intravascular volume with
isotonic saline.
The management of hypervolemic hyponatremia is difficult. Patients with this disorder have an
excess of both water and sodium. The cornerstone of therapy is water and sodium restriction,
because the patients have volume overload. Diuretics may help by causing excretion of both sodium
and water. Vasopressin antagonists are effective in correcting the hypervolemic hyponatremia due to
heart failure or cirrhosis.
Specific hormone replacement is the cornerstone of therapy for the hyponatremia of
hypothyroidism or cortisol deficiency.
SIADH is a condition of excess water, with limited ability of the kidney to excrete water. The
mainstay of its therapy is fluid restriction. Vasopressin antagonists (conivaptan, tolvaptan),
which block the action of ADH and cause a water diuresis, are effective at correcting euvolemic
hyponatremia.
4. SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION:
SIADH most commonly occurs with
1. CNS (infection, hemorrhage, trauma, tumor, thrombosis)
2. Lung disease (infection, asthma, positive pressure ventilation)
3. Malignant tumours (producing ADH)
4. Medications 3, 4-methylenedioxymethylamphetamine (MDMA, or “Ecstasy”), opiates,
antiepileptic drugs (carbamazepine, oxcarbamazepine, valproate), tricyclic antidepressants,
vincristine, cytoxan, and selective serotonin reuptake inhibitors.
The diagnosis of SIADH is one of exclusion, because other causes of hyponatremia must be
eliminated. Because SIADH is a state of intravascular volume expansion, low serum uric acid and
BUN levels are supportive of the diagnosis.
DIAGNOSTIC CRITERIA:
1. Absence of renal, adrenal, thyroid insufficiency, heart failure, Nephrotic syndrome or cirrhosis.
Diuretic ingestion. Dehydration.
2. Urine osmolality > 100 mOsm/kg (usually > plasma).
3. Serum osmolality < 280 mOsm/kg and serum sodium < 135 mEq/L.
4. Urine sodium > 30 mEq/L
5. Reversal of “sodium wasting” and correction of hyponatremia with water restriction.

5. Hypokalemia:
Hypokalemia is common in children, with most cases related to gastroenteritis.
Causes:
1. Spurious 5. Renal losses
High WBC count 1.With metabolic acidosis
RTA DKA ureterosigmoidostomy
2. Decreased intake
Anorexia 2.Without specific AB disturbance
441
 Interstitial nephritis, diuretic phase of ATN,
3.Transcellular shifts Post obstructive diuresis
Tubular toxins
Alkalosis Amphotericin , cisplatin,
Insulin Aminoglycosides
Alpha adrenergic agonists 3.With metabolic alkalosis (Urinary K excretion
Drugs Theophylline Toluene >15mEq/L)
Hydroxychloroquine A. Low urine cl
Hypokalemic periodic paralysis Emesis/ NG suc
Refeeding syndrome Cl losing diarrhea
Loop/ diuretics
4. Extra renal losses Cystic fibrosis
(Urinary K excretion <15mEq/L) B. High urine cl with N BP
(TTKG < 4) Gitelman, Bartter
Diarrhea, Sweating EAST syndrome
Laxative abuse
kayexalate C. High urine cl with high BP
Adrenaladenoma
Renin secreting tumour
Cushing Syndrome
17 α hydox def, 11 β hydox def
Licorice ingestion
Liddle syndrome

Clinical features:
The heart and skeletal muscle are especially vulnerable to hypokalemia. ECG changes include a
flattened T wave, a depressed ST segment, and the appearance of a U wave, which is located between
the T wave (if still visible) and the P wave. Hypokalemia impairs bladder and bowel functions,
potentially leading to urinary retention and constipation.
Approach to
Hypokalemia:

442
6. HYPERKALEMIA:
Hyperkalemia—because of the potential for lethal arrhythmias—is one of the most alarming
electrolyte abnormalities.
Causes:
1. Spurious DECREASED EXCRETION
443
 haemolysis, tissue Renal failure
ischemia during blood Drawing, Primary adrenal disease:
thrombocytosis, leukocytosis Acquired Addison disease
21-Hydroxylase deficiency
3β-Hydroxysteroid dehydrogenase deficiency
2. increased intake intravenous or
Adrenoleukodystrophy
oral,

Blood transfusion
Hyporeninemic hypoaldosteronism:
3. transcellular shift
Urinary tract obstruction
Sickle cell disease
acidosis, rhabdomyolysis, tumour lysis Kidney transplant
syndrome, Lupus nephritis
succinylcholine, digitalis intoxication, Renal tubular disease:
Pseudohypoaldosteronism
fluoride intoxication, β adrenergic blockers,
exercise, insulin def, malignant Bartter syndrome
hyperthermia, hyperkalemic periodic Urinary tract obstruction
paralysis Sickle cell disease
Kidney transplant
Medications:
Changes in the electrocardiogram (ECG)
Angiotensin-converting enzyme inhibitors
begin with peaking of the T waves. This is Angiotensin II blockers
followed, as the potassium level increases, Potassium-sparing diuretics
by ST-segment depression, an increased PR Calcineurin inhibitors
interval, flattening of the P wave, and Nonsteroidal anti-inflammatory drugs
Trimethoprim
widening of the QRS complex.
Heparin
Yasmin-28 (oral contraceptive)

Treatment: 1. stop all potassium in iv fluids.

2. if ecg changes calcium gluconate 1-2 ml/kg over 5-10 min under cardiac monitoring.
3. if k 6-6.5meq/l a. soda bicarb 1 meq/kg over 15-30 mins intravenous
b. kayexalate 1gm/kg q6h per rectally
4. if k 6.5- 7.5 meq/l a. glucose- insulin infusion 0.05u/kg of regular insulin with 2ml/kg of
10% D
b. salbutamol nebulisation
5. if k > 7.5 meq/l a. Exchange transfusion with washed RBC reconstituted with 5 %
albumin
b. Dialysis.
7. Magnesium / Hypomagnesemia:

The normal plasma magnesium concentration is 1.5-2.3 mg/dL. It is important for membrane
stabilization and nerve conduction. Adenosine triphosphate (ATP) and guanosine triphosphate (GTP)
need associated magnesium when they are used by ATPases, cyclases, and kinases.
444
Hypomagnesemia is relatively common in hospitalized patients, although most cases are
asymptomatic.

Causes of hypomagnesemia:
Gastro intestinal Renal disorders
disorders Medications:
Diarrhea Amphotericin, cisplatin
Nasogastric suction or Cyclosporin, loop and thiazide
emesis diuretics
Inflammatory bowel
disease
Mannitol
Celiac disease
Cystic fibrosis
Aminoglycosides

Small bowel resection

or bypass
Pancreatitis Diabetes
Protein-calorie Acute tubular necrosis (recovery phase)
malnutrition Post obstructive nephropathy
Chronic kidney diseases:
Interstitial nephritis
Miscellaneous
causes Glomerulonephritis
Poor intake Post–renal transplantation
Hungry bone Hypercalcemia
syndrome
Insulin
administration

Intrauterine
growth
retardation Genetic diseases:
Infants of diabetic Gitelman syndrome
mothers Bartter syndrome
Exchange Familial hypomagnesemia with hypercalciuria
transfusion and nephrocalcinosis
Familial hypomagnesemia with hypercalciuria,
nephrocalcinosis, and severe ocular involvement

EAST syndrome

Clinical Manifestations:

 Hypomagnesemia causes secondary hypocalcemia by impairing the release of PTH by the

parathyroid gland and through blunting of the tissue response to PTH. Thus, hypomagnesemia
is part of the differential diagnosis of hypocalcemia. It usually occurs only at magnesium
levels <0.7 mg/dL.
 The dominant manifestations of hypomagnesemia are due to hypocalcemia: tetany, presence
of Chvostek and Trousseau signs, and seizures.

445
ECG changes with hypomagnesemia include flattening of the T wave and lengthening of the ST
segment. Arrhythmias may occur, almost always in the setting of underlying heart disease.

Treatment:
 Severe hypomagnesemia is treated with parenteral magnesium. Magnesium sulfate is given at
a dose of 0.05-0.1 mL/kg of a 50% solution.
 Long-term therapy is usually given orally. Preparations include magnesium gluconate (5.4
mg elemental magnesium/100 mg), magnesium sulfate (10 mg elemental magnesium/100 mg)
and magnesium oxide (60 mg elemental magnesium/100 mg).

8. Hypermagnesemia:
Symptoms usually do not appear until the plasma magnesium level is >4.5 mg/dL.
Etiology:
Almost always secondary to excessive intake.
Mild hypermagnesemia may occur in chronic renal failure, diabetic ketoacidosis, lithium ingestion,
milk-alkali syndrome, and tumor lysis syndrome.
Clinical features:
Hypermagnesemia inhibits acetylcholine release at the neuromuscular junction, producing
hypotonia, hyporeflexia, and weakness; paralysis occurs at high concentrations.
Direct CNS depression causes lethargy and sleepiness.
Hypotension can be profound at higher concentrations from a direct effect on cardiac function.
ECG changes include prolonged PR, QRS, and QT intervals.
Severe hypermagnesemia (>15 mg/dL) causes complete heart block and cardiac arrest.
Treatment:
Supportive care includes
 Monitoring of cardio respiratory status
 Provision of fluids, monitoring of electrolyte levels, and
 Use of pressors for hypotension.
Hemodialysis works faster than peritoneal dialysis.
Exchange transfusion in newborn infants.

9. ACID BASE BALANCE:

Close regulation of pH is necessary for cellular enzymes and other metabolic processes, which
function optimally at normal pH. A normal pH is 7.35-7.45. Control of acid-base balance depends on
the kidneys, the lungs, and buffers (bicarbonate and non bicarbonate like phosphates, proteins and
bone).
Lungs:
Carbon dioxide generated during normal metabolism is a weak acid. The lungs prevent an increase in
the partial pressure of CO2 (Pco2) in the blood by excreting the CO2 that the body produces. CO2
production varies according to the body's metabolic needs, increasing with physical activity. The
rapid pulmonary response to changes in the CO2 concentration occurs via central sensing of the Pco2
and a subsequent increase or decrease in ventilation to maintain a normal Pco2 (35-45 mm Hg). An
increase in ventilation decreases the Pco2, and a decrease in ventilation increases the Pco2.
Renal:

446
APPROPRIATE COMPENSATION DURING SIMPLE ACID-BASE DISORDERS

DISORDER EXPECTED COMPENSATION

Metabolic acidosis Pco2 = 1.5 x [HCO3−] + 8 + 2
Metabolic alkalosis Pco2 increases by 7 mm Hg for each 10-mEq/L increase in serum [HCO3−]
Respiratory acidosis
Acute [HCO3−] increases by 1 for each 10–mm Hg increase in Pco2
Chronic [HCO3−] increases by 3.5 for each 10–mm Hg increase in Pco2
Respiratory alkalosis
Acute [HCO3−] falls by 2 for each 10–mm Hg decrease in Pco2
Chronic [HCO3−] falls by 4 for each 10–mm Hg decrease in Pco2

447
10. Metabolic Acidosis:

There are many causes of a metabolic acidosis which occur via 3 basic mechanisms:

• Loss of bicarbonate from the body

• Impaired ability to excrete acid by the kidney.
• Addition of acid to the body (exogenous or endogenous).

Causes of metabolic acidosis

Normal anion gap

Increased anion gap
Diarrhea
1. lactic acidosis
RTA
Tissue hypoxia
Urinary tract diversions
Shock, Severe anemia

Liver failure, Malignancy,

NRTI, Metformin, Propofol

2. Ketoacidosis
Diabetic, starvation, alcoholic
and Renal failure

3. Poisoning

Ethylene glycol, methanol, salicylate,

Toluene

4. IEM
TREATMENT:

1. The most effective therapeutic approach for patients with a metabolic acidosis is repair of the
underlying disorder, if possible.
2. Insulin – diabetic ketoacidosis.
3. Intravenous fluids – shock and PRBC in case of severe anemia.
4. Base therapy- RTA, poisonings and renal failure.
5. Hemodialysis- renal insufficiency, methanol and ethylene glycol poisoning.
6. Peritoneal dialysis - renal insufficiency and uncontrolled dyselectrolytemia.
7. Administration of a glucocorticoid and a mineralocorticoid with adrenal insufficiency.
8. Patients with methanol or ethylene glycol ingestion should receive ethanol that prevents the
breakdown of the toxic substance to its toxic metabolites.
9. Fomepizole has supplanted ethanol as the treatment of choice.
11. Metabolic alkalosis:
448
Metabolic alkalosis in children is most commonly secondary to emesis or diuretic use. A metabolic
alkalosis, by decreasing ventilation, causes appropriate respiratory compensation. Pco2 increases by 7
mm Hg for each 10-mEq/L increase in the serum bicarbonate concentration.

Causes of metabolic alkalosis:

Chloride responsive (urinary chloride < 15 Eq/l) Chloride unresponsive (urinary chloride > 20
mEq/l)
1. High blood pressure
Gastric losses, emesis, nasogastric suction Adrenal adenoma or hyperplasia
Diuretics (loop or thiazide) Renovascular disease
Renin-secreting tumor
Chloride loosing diarrhea
Chloride deficient formula 17α-Hydroxylase deficiency
11β-Hydroxylase deficiency
Cystic fibrosis Cushing syndrome
Post hypercapnia
Licorice ingestion
Liddle syndrome

2. Normal blood pressure

Gitleman syndrome
Bartter syndrome

EAST syndrome
Base administration

Treatment:
1. The most effective approach is to address the underlying etiology.
2. In some children, nasogastric suction may be decreased or discontinued.
3. The addition of a gastric proton pump inhibitor reduces gastric secretion and losses of HCl.
4. Diuretics are an important cause of metabolic alkalosis, and if a change is tolerated, they should be
eliminated or the dose reduced.
5. In chloride-responsive etiologies administration of sufficient sodium chloride and potassium
chloride.
6. Arginine HCl may also be used to treat chloride-responsive metabolic acidosis if sodium or
potassium salts are not appropriate.
7. In children with the chloride-resistant causes of a metabolic alkalosis that are associated with
hypertension, volume repletion is contraindicated.
8. Adrenal adenomas can be resected, licorice intake can be eliminated, and renovascular disease can
be repaired.
9.17α-hydroxylase deficiency and 11β-hydroxylase deficiency respond to the administration of
449
glucocorticoids.
10. In children with Bartter syndrome and Gitelman syndrome, therapy includes oral potassium
supplementation and potassium-sparing diuretics.

450
 MISCELLANEOUS TOPICS

1. DEVELOPMENTAL ANOMALIES OF LUNG

2. CYSTIC ADENOMATOID MALFORMATION
3. EPISTAXIS
4. PULMONARY FUNCTION TESTS
5. DIAPHRAGMATIC HERNIA
6. PEDIATRIC INTERSTITIAL LUNG DISEASES
7. GENETIC COUNSELLING
8. CYTOGENETICS
9. DIALYSIS/ RENAL REPLACEMENT THERAPY
10. ADHD
11. PALS
12. HIGH RISK PREGNANCY

451
ARDS:

Definition: as in flow chart 4 points.

Etiology:

Direct Indirect
Usual : Usual:

 Pneumonia  Sepsis
 Aspiration pneumonia  Severe trauma
 Multiple transfusions of blood
products

Rare: Rare:

 Inhalational injury  Acute pancreatitis

 Pulmonary contusion  Drug overdose
 Near drowning  DIC
 Reperfusion injury  Burns
 Head injury

Stages :

d. Exudative phase
e.Proliferative phase
f. Fibrotic phase

Pathophysiology:
Inciting agent

Inflammation

Endothelial damage

Fluid leak

v/q mismatch and decreased surfactant  rt –lt shunt & decreased FRC

452
Protocol approach to suspected ARDS child:

453
Respiratory management in ARDS:

454
455
21. Developmental anomalies of lung:

Write a note on development of lung-

Causes:

Cong anomalies of Cong anomalies of larynx, Cong anomalies of lung

nose trachea and bronchi
Arhinia- absence of Laryngomalacia 11. Pulmonary agenesis and
nose aplasia
Tracheomalacia 12. Pulmonary hypoplasia
Nasal hypoplasia
13. CCAM
bronchomalacia
Choanal aplasia 14. Pulmonary sequestration
Cong subglottic stenosis 15. Bronchogenic cysts
Congenital defects of 16. Congenital pulmonary
nasal septum Vocal cord paralysis Lymphangiectasia
17. Lung hernia
Cong laryngeal webs
18. Congenital lobar emphysema
Cong subglottic and pulmonary cysts
haemangioma 19. Pulmonary arteriovenous
malformation
Laryngocele 20. Bronchobiliary fistula

Vascular ring

Cystic adenomatoid malformation:

Pathology:

Congenital cystic adenomatoid malformation (CCAM) consists of hamartomatous or dysplastic lung

tissue mixed with more normal lung, generally confined to one lobe.

Type 1 (50%) is macrocystic and consists of a single or several large (>2 cm in diameter) cysts lined
with ciliated pseudostratified epithelium. This type has a good prognosis for survival.

Type 2 (40%) is microcystic and consists of multiple small cysts with histology similar to that of the
type 1 lesion. Type 2 is associated with poor prognosis.

In type 3 (<10%), the lesion is solid with bronchiole-like structures. This lesion carries the poorest
prognosis.

Etiology:

The lesion probably results from an embryologic insult before the 35th day of gestation, with
456
maldevelopment of terminal bronchiolar structures. Histologic examination reveals little normal lung
and many glandular elements. Cysts are very common; cartilage is rare.

Diagnosis:

1. Prenatal ultrasonographic findings are classified as macrocystic (single or multiple cysts >5 mm)
or microcystic (echogenic cysts <5 mm).

2. CT allows accurate diagnosis and sizing of the lesion.

Clinical features:

Patients can present in the newborn period or early infancy with respiratory distress, recurrent
respiratory infection, and pneumothorax. The lesion may be confused with a diaphragmatic hernia,
lung abscess.

Patients with smaller lesions are usually asymptomatic until mid-childhood, when episodes of
recurrent or persistent pulmonary infection or chest pain occur.

Breath sounds may be diminished, with mediastinal shift away from the lesion on physical
examination.

Chest radiographs reveal a cystic mass, sometimes with mediastinal shift.

Treatment:

Antenatal interventions include excision of the affected lobe for microcystic lesions, aspiration of
macrocystic lesions, and, rarely, open fetal surgery.

In the postnatal period, surgery is indicated for symptomatic patients.

Although surgery may be delayed for asymptomatic infants because postnatal resolution has been
reported.

Surgical resection by 1 yr of age is recommended to limit malignant potential.

Epistaxis:
Anatomy

The most common site of bleeding is the Kiesselbach plexus, an area in the anterior septum where
vessels from both the internal carotid (anterior and posterior ethmoid arteries) and external carotid
(sphenopalatine and terminal branches of the internal maxillary arteries) converge.

The thin mucosa in this area, as well as the anterior location, makes it prone to exposure to dry air
and trauma.

COMMON CAUSES OF EPISTAXIS

Epistaxis digitorum (nose picking)

457
 Rhinitis, Chronic sinusitis, Foreign bodies

Intranasal neoplasm or polyps

Irritants (e.g., cigarette smoke)
Septal deviation, perforation
Trauma including child abuse
Vascular malformation or telangiectasia
Hemophilia, Platelet dysfunction, Thrombocytopenia

Hypertension, Leukemia, Liver disease (e.g., cirrhosis)

Medications (e.g., aspirin, anticoagulants, NSAID, topical corticosteroids)

Cocaine abuse

Clinical Manifestations:

Epistaxis usually occurs without warning, with blood flowing slowly but freely from one nostril or
occasionally from both. When bleeding occurs at night, the blood may be swallowed and become
apparent only when the child vomits or passes blood in the stools. Posterior epistaxis can manifest as
anterior nasal bleeding or, if bleeding is copious, the patient might vomit blood as the initial
symptom.

Treatment:

14. Most nosebleeds stop spontaneously in a few minutes.

15. The nares should be compressed and the child kept as quiet as possible, in an upright position
with the head tilted forward to avoid blood trickling back into the throat.
16. Cold compresses applied to the nose can also help.
17. If these measures do not stop the bleeding, local application of a solution of oxymetazoline
may be useful.
18. If bleeding persists, an anterior nasal pack might need to be inserted; if bleeding originates
in the posterior nasal cavity, combined anterior and posterior packing is necessary.
19. After bleeding has been controlled, and if a bleeding site is identified, its obliteration by
cautery with silver nitrate may prevent further difficulties.
20. In patients with severe or repeated epistaxis, blood transfusions may be necessary.
21. Otolaryngologic evaluation is indicated for these children and for those with bilateral
bleeding or with hemorrhage that does not arise from the Kiesselbach plexus.
22. Hematologic evaluation (for coagulopathy and anemia), along with nasal endoscopy and
diagnostic imaging, may be needed to make a definitive diagnosis in cases of severe recurrent
458
 epistaxis.
23. Replacement of deficient clotting factors may be required for patients who have an
underlying hematologic disorder.
24. Control hypertension appropriately
25. Profuse unilateral epistaxis associated with a nasal mass in an adolescent boy near puberty
might signal a juvenile nasopharyngeal angiofibroma.
26. Surgical intervention may also be needed for bleeding from the internal maxillary artery.

Prevention:

The discouragement of nose picking, and attention to proper humidification of the bedroom during
dry winter months helps to prevent many nosebleeds.

Prompt attention to nasal infections and allergies is beneficial to nasal hygiene.

Prompt cessation of nasal steroid sprays prevents ongoing bleeding.

Pulmonary function tests:

The measurement of respiratory function in infants and young children can be difficult because of
the lack of cooperation.

1. Peak flow meters: Airway obstruction is most commonly

evaluated from determinations of gas flow in the course of a forced expiratory manoeuvre. The peak
expiratory flow is reduced in advanced obstructive disease. The wide availability of simple devices
that perform this measurement at the bedside makes it useful for assessing children who have
airway obstruction. Evaluation of peak flows requires a voluntary effort, and peak flows may not be
altered when the obstruction is moderate or mild. Cooperation and good muscle strength are
therefore necessary for the measurements to be reproducible.

2. Spirometer: A spirometer is used to measure VC and its subdivisions and

expiratory (or inspiratory) flow rates. Expected normal values for VC, FRC, TLC, and residual volume
are obtained from prediction equations based on body height. Flow rates measured by spirometry
usually include the FEV1sec and the maximal mid expiratory flow rate but not residual capacity

3. Plethysmography: Airway resistance (RAW) is measured in a plethysmograph,

or, alternatively, the reciprocal of RAW, airway conductance (GAW), may be used. Because airway
resistance measurements vary with the lung volume at which they are taken, it is convenient to use
specific airway resistance, SRAW (SRAW = RAW/lung volume), which is nearly constant in subjects >6 yr
old (normally <7 sec/cm H2O). Also useful to measure residual capacity.

4. DLCO: The diffusing capacity for carbon monoxide (DLCO) is related to oxygen diffusion and
is measured by rebreathing from a container having a known initial concentration of carbon
monoxide or by using a single-breath technique.

459
USES OF Lung Function Tests:

Pulmonary function testing, although rarely resulting in a diagnosis, is helpful in defining the

a. Type of process (obstruction, restriction).

b. The degree of functional impairment.

c. In following the course and treatment of disease.

d. In estimating the prognosis.

e. It is also useful in preoperative evaluation.

f. In confirmation of functional impairment in patients having subjective complaints but a normal

physical examination.

Conditions causing recurrent pneumonia in single lobe-

A) Intraluminal causes- foreign body, bronchial tumor, adenoma, lipoma

B) Extraluminal- infectious lymphadenopathy, non infectious lymphadenopathy, tuberculosis,

vascular ring

C) Structural abnormalities- tracheal bronchus, bronchial stenosis or atresia, right middle lobe
syndrome, CCAM

Diaphragmatic hernia:

A diaphragmatic hernia is defined as a communication between the abdominal and thoracic cavities
with or without abdominal contents in the thorax.

Embryology:

 Septum transversum – gives rise to central tendon

 Pleuroperitoneal membrane – gives rise to dorsolateral portion of diaphragm
 Esophageal mesentry – gives rise to dorsal crura
 Interstitial muscle groups – gives rise to muscular portion of the body wall

Fetal lung development:

 Pseudoglandular phase: lung bud formation begins at 5th week and ends at 16- 17th week.
 Canalicular stage: 16 wk- 25wk
 Saccular stage: 26- 36 wks alveolar sac development
 Alveolar stage: till 8 years of life alveoli continue to develop

The etiology may be congenital or traumatic.

460
 The defect may be at the

5. Esophageal hiatus (hiatal),

6. Paraesophageal (adjacent to the hiatus),
7. Retrosternal (Morgagni), or at the
8. Posterolateral (Bochdalek) portion of the diaphragm.

The term congenital diaphragmatic hernia typically refers to the Bochdalek form.

The Bochdalek hernia accounts for up to 90% of the hernias seen in the newborn period, with
80-90% occurring on the left side. The Morgagni hernia accounts for 2-6% of congenital
diaphragmatic defects.

Epidemiology: females left most are sporadic syndromes

turner, trisomy 21,13,18.

Pathology: Although CDH is characterized by a structural diaphragmatic defect, a major limiting

factor for survival is the associated pulmonary hypoplasia.

Diagnosis and Clinical Presentation:

CDH can be diagnosed on prenatal ultrasonography (between 16 and 24 wk of gestation) in > 50%
of cases. High-speed fetal MRI can further define the lesion.

Findings on ultrasonography may include polyhydramnios, chest mass, mediastinal shift, gastric
bubble or a liver in the thoracic cavity, and fetal hydrops.

Respiratory distress is a cardinal sign in babies with CDH. It may occur immediately after birth, or
there may be a “honeymoon” period of up to 48 hr during which the baby is relatively stable.
Respiratory distress is characterized clinically by tachypnea, grunting, use of accessory muscles, and
cyanosis. Children with CDH also have a scaphoid abdomen and increased chest wall diameter.
Bowel sounds may also be heard in the chest with decreased breath sounds bilaterally. The point of
maximal cardiac impulse may be displaced away from the side of the hernia if mediastinal shift has
occurred.

A chest radiograph and passage of a nasal gastric tube are all that is usually required to confirm the
diagnosis.

Differential diagnosis - pulmonary sequestration, cystic adenomatoid malformation.

Treatment

1. Initial Management: Aggressive respiratory support is often needed in

children with CDH. This includes rapid endotracheal intubation, sedation, and possibly paralysis.
Prolonged mask ventilation in the delivery room, which enlarges the stomach and small bowel and
thus makes oxygenation more difficult, must be avoided. Gentle ventilation with permissive
hypercapnia reduces lung injury and mortality. Although surfactant is commonly used, no study has
proven that it is beneficial in treatment of CDH.

2. Ventilation Strategies: Conventional mechanical ventilation, HFOV, and ECMO are

the 3 main strategies to support respiratory failure in the newborn with CDH. The goal is to maintain
oxygenation without inducing barotrauma. NO is a selective pulmonary vasodilator. Its use reduces
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ductal shunting and pulmonary pressures and results in improved oxygenation. If the patient cannot
be weaned from ECMO after repair of CDH, options include discontinuing support and, in rare cases,
lung transplantation.

3. Novel Strategies: There are no reliable prenatal prognosticators of

outcomes in children with CDH. The most widely studied is fetal ultrasonography. (A)There were no
survivors when the LHR (lung to head size ratio) was <1, and all babies with LHR >1.4 survived.
(B) A second important consideration was the presence of liver in the thoracic cavity, which is a
poor prognostic feature. A study is under way to evaluate the role of Partial Liquid Ventilation in
neonates with CDH. EXIT procedure. Tracheal occlusion inutero.

4. Surgical Repair: The ideal time to repair the diaphragmatic defect is

under debate. Most centers wait at least 48 hr after stabilization and resolution of the pulmonary
hypertension. Good relative indicators of stability are the requirement for conventional
ventilation only, a low PIP, and a Fio2 <50.

Complications: Pulmonary problems continue to be a source of morbidity for long-term

survivors of CDH.

Gastroesophageal reflux disease (GERD), delayed growth,

pulmonary hypertension,

Neurocognitive defects, scoliosis.

Relative predictors of a poor prognosis include an

 associated major anomaly,

 symptoms before 24 hr of age,
 severe pulmonary hypoplasia,
 herniation to the contralateral lung, and the
 need for ECMO

PEDIATRIC INTERSTITIAL LUNG DISEASES

Pediatric interstitial lung diseases (ILDs) are a group of uncommon, heterogeneous, familial, or
sporadic diseases that cause disruption of alveolar interstitium and sometimes involve airway
pathology.
PEDIATRIC INTERSTITIAL LUNG DISEASES
1. DISORDERS MORE COMMON IN INFANCY AND YOUNG CHILDREN
Diffuse developmental disorders: acinar dysplasia, congenital alveolar dysplasia, alveolar
capillary dysplasia with misalignment of pulmonary veins
Growth abnormalities reflecting deficient alveolarization: pulmonary hypoplasia, chronic
neonatal lung disease, chromosomal disorders, congenital heart disease
Neuroendocrine cell hyperplasia of infancy
Pulmonary interstitial glycogenosis
Surfactant dysfunction disorders: surfactant protein–B mutation, surfactant protein–C
mutation, ABCA3 mutation
2. DISORDERS OF KNOWN ASSOCIATION

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 Infectious/post-infectious processes
Environmental agents: hypersensitivity pneumonitis, toxic inhalation
Aspiration syndromes
3. DISORDERS OF IMMUNOCOMPROMISED HOSTS
Opportunistic infections
Human herpes virus 8 associated with common variable immunodeficiency syndrome
Lymphoid intestinal pneumonia (HIV infection)
Therapeutic interventions: chemotherapy, radiation, transplantation, and rejection
4. INTERSTITIAL LUNG DISEASES OF UNKNOWN ETIOLOGY
Usual interstitial pneumonitis
Desquamative pneumonitis
Lymphocytic interstitial pneumonitis

Eosinophilic pneumonia
Pulmonary hemosiderosis
Pulmonary alveolar proteinosis
Pulmonary vascular disorders
Pulmonary lymphatic disorders

5. SYSTEMIC DISORDERS WITH PULMONARY INVOLVEMENT

Immune-mediated/collagen vascular disorders
Malignant infiltrates
Langerhans cell histiocytosis
Sarcoidosis
Neurocutaneous syndromes
Storage diseases

Clinical Manifestations:

9. Tachypnea, dyspnea, cough, and failure to thrive are commonly present.

10. A positive family history, is suggestive of a genetic or familial disease, such as a surfactant
dysfunction. Symptoms are usually insidious and occur in a continuous, not episodic,
pattern.
11. Tachypnea, crackles, and retractions are noted on physical examination in the majority of
children with ILD, but chest auscultation findings can be normal.
12. Wheezing and fever are not common complaints.
13. Pulmonary hypertension, failure to thrive, and severe fibrosis are considered poor prognostic
indicators
14. Cyanosis and a prominent 2nd heart sound are suggestive of severe disease.
15. Anemia or hemoptysis suggests a pulmonary vascular disease or pulmonary hemosiderosis.
16. Rashes or joint complaints are consistent with an underlying connective tissue disease.
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Diagnosis:

Chest radiographic abnormalities can be classified as interstitial, reticular, nodular, reticulonodular,

or honeycombed. The chest radiographic appearance may also be normal despite significant clinical
impairment and may correlate poorly with the extent of disease.

High-resolution CT (HRCT) of the chest better defines the extent and distribution of disease and can
provide specific information for selection of a biopsy site. Serial HRCT scans may be of benefit in
monitoring disease progression and severity.

Pulmonary function tests (PFTs) including infant PFTs, are important in defining the degree of
pulmonary dysfunction and in following the response to treatment.

Bronchoalveolar lavage (BAL) may provide helpful information regarding secondary infection,
bleeding, and aspiration, and allows cytologic and molecular analyses. Although BAL does not
usually determine the exact diagnosis, it can be diagnostic for disorders such as pulmonary alveolar
proteinosis.

Lung biopsy for histopathology is usually the final step and is often necessary for a diagnosis.

Genetic testing for surfactant dysfunction mutational analysis is now available.

Evaluation for possible systemic disease may also be necessary.

Treatment:

Supportive care - supplemental oxygen for hypoxia and adequate nutrition for growth failure.

Antimicrobial treatment may be necessary for intercurrent infections.

Anti-inflammatory treatment with corticosteroids remains the initial treatment of choice. The usual
dose of prednisone is 1-2 mg/kg/24 hr for 6-8 wk with tapering of dosage dictated by clinical
response.

Alternative, but not adequately evaluated, agents include hydroxychloroquine, azathioprine,

cyclophosphamide,

Lung transplantation for progressive or end-stage ILD is successful in some infants and children.

Appropriate treatment for underlying systemic disease is indicated.

Supervised pulmonary rehabilitation programs may be helpful.

Genetic counseeling

Prognosis: The overall mortality of ILD is very variable and depends on specific
diagnosis. Some children recover spontaneously without treatment, but other children steadily
progress to death.

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Genetic counselling:
Genetic counselling is a communication process in which the genetic contribution to health is
explained, along with specific risks of transmission of a trait and options to manage the condition and
its inheritance.
INDICATIONS FOR GENETIC COUNSELING
1. Advanced parental age
• Maternal age ≥35 yr
• Paternal age ≥50 yr
2. Previous child with or family history of
• Congenital abnormality
• Dysmorphology
• Mental retardation
• Isolated birth defect
• Metabolic disorder
• Chromosome abnormality
• Single-gene disorder
3. Adult-onset genetic disease (pre symptomatic testing)
• Cancer
• Huntington disease
4. Consanguinity
5. Teratogen exposure (occupational, abuse)
6. Repeated pregnancy loss or infertility
7. Pregnancy screening abnormality
• Maternal serum α-fetoprotein
• Maternal triple or quad screen or variant of this test
• Fetal ultrasonography
• Fetal karyotype
8. Heterozygote screening based on ethnic risk
• Sickle cell anemia
• Tay-Sachs, Canavan, Gaucher
diseases
• Thalassemia
9. Follow-up to abnormal neonatal genetic testing

Genetic Counselling (remember total 9 points)

Providing accurate information to families requires
A) Specific Condition or Conditions
If a specific diagnosis is made and confirmed, that should be discussed with the family and
information should be provided in writing. However, often the disorder fits into a spectrum (e.g., one
of many types of arthrogryposis) or the diagnosis is clinical rather than laboratory based. In those
situations, the family needs to understand the limits of present knowledge and that additional
research will probably lead to better information in the future.
B) Knowledge of the Diagnosis of the Particular Condition
Although it is not always possible to make an exact diagnosis, having a diagnosis as accurate as
possible is important. When a specific diagnosis cannot be made (as in many cases of multiple
congenital anomalies), the various possibilities in the differential diagnosis should be discussed
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with the family and empirical information should be provided.
C) Natural History of the Condition
It is very important to discuss the natural history of the specific genetic disorder in the family.
Affected persons and their families have questions regarding the prognosis and potential therapy
that can be answered only with knowledge of the natural history. If there are other possible diagnoses,
their natural history may also be discussed. If the disorder is associated with a spectrum of clinical
outcomes or complications, the worst and best scenarios, as well as treatment and referral to the
appropriate specialist, should be addressed.
D) Genetic Aspects of the Condition and Recurrence Risk
The genetic aspects and risk of recurrence are important because all family members need to be
aware of their reproductive choices. The genetics of the disorder can be explained with visual aids
(e.g., diagrams of chromosomes). It is important to provide accurate occurrence and recurrence
risks for various members of the family, including unaffected individuals. Counselling should give
patients the necessary information to understand the various options and let the patients make their
own informed decisions regarding pregnancy, adoption, artificial insemination, prenatal diagnosis,
screening, carrier detection, and termination of pregnancy. It may be necessary to have more than 1
counselling session.
E) Prenatal Diagnosis and Prevention
Many different methods of prenatal diagnosis are available, depending on the specific genetic
disorder. The use of ultrasonography allows prenatal diagnosis of anatomic abnormalities such as
congenital heart defects. Amniocentesis and chorionic villous sampling are used to obtain fetal
tissue for analysis of chromosomal abnormalities, biochemical disorders, and DNA studies.
Maternal blood or serum sampling is used for some types of screening. Fetal cells can be retrieved
from the umbilical cord or from maternal blood (free fetal DNA) for testing, although mothers might
harbour cells from all previous pregnancies.
F) Therapies and Referral
A number of genetic disorders require the care of a specialist. Girls with Turner syndrome usually
need to be evaluated by an endocrinologist. Prevention of known complications is a priority. The
psychologic adjustment of the family might require specific intervention. When to discuss the
diagnosis of a chronic disease with the patient is always a difficult decision. The decision to do so
should always involve the parents and an assessment of the maturity and capacity of the child or
adolescent.
Alternative medicines or non-traditional therapies are often brought to attention by parents after
exhaustive Internet searches. Such treatments should not necessarily be dismissed out of hand
because the physician and counsellor should serve as an important resource for helping parents
navigate the maze of nonstandard treatments. Instead, the relative merits of treatments should be
framed in the context of cost and benefit, scientific rationale, evidence from controlled and/or
observational studies, the placebo effect, safety of the treatment, and the gaps on our own scientific
knowledge base.
G) Support Groups
A large number of community lay support groups have been formed to provide information and to
fund research on specific genetic and non genetic conditions. An important part of genetic
counselling is to give information about these groups to patients and to suggest a contact person for
the families. Many groups have established websites with very helpful information.
H) Follow-up
Families should be encouraged to continue to ask questions and keep up with new information about
the specific disorder. New developments often influence the diagnosis and therapy of specific
genetic disorders. Lay support groups are a good source of new information.
I) Nondirective Counselling
Genetic counselling is usually nondirective; choices about reproduction are left to the family to
decide what is right for them. The role of the counsellor (physician, genetic counsellor, nurse,
medical geneticist) is to provide information in understandable terms and outline the range of options
available.

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2. Cytogenetics: Clinical cytogenetics is the study of chromosomes: their structure, function,
inheritance, and abnormalities.
Chromosome analyses are indicated in persons presenting with
1. Multiple congenital anomalies, dysmorphic features, and/or mental retardation with or without
associated anatomic abnormalities.
2. Advanced maternal age (>35 yr)
3. Multiple abnormalities on fetal ultrasound (prenatal testing), multiple congenital anomalies,
unexplained growth retardation in the fetus.
4. Postnatal problems in growth and development
5. Ambiguous genitalia
6. Primary amenorrhea or infertility, recurrent miscarriages (≥3) or prior history of stillbirths and
neonatal deaths
7. A 1st-degree relative with a known or suspected structural chromosome abnormality
8. Clinical findings consistent with a known anomaly, some malignancies, and chromosome breakage
syndromes (Bloom syndrome, Fanconi anemia).
Cytogenetic studies are usually performed on
1. Peripheral blood lymphocytes, although cultured fibroblasts may also be used.
2. Prenatal (fetal) chromosome studies are performed with cells obtained from the amniotic fluid,
chorionic villus tissue, and fetal blood.
3. Preimplantation diagnosis, by analysis of a blastomere.
4. Cytogenetic studies of bone marrow have an important role in tumor surveillance, particularly
among patients with leukemia.
Methods:
Karyotyping - Banding (G, Q, C, R)
Molecular cytogenic techniques: FISH, Genomic array hybridization studies, Spectral
karyotyping (SKY), multicolour FISH (M-FISH), RFLP, Linkage analysis and Comparative genomic
hybridization (CGH).
FISH:

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Fluorescence in situ hybridization (FISH) involves

Denaturation of double-stranded DNA as present in metaphase chromosomes or interphase nuclei

on cytogenetic slide preparations (A) into single-stranded DNA (B).

The slide-bound (in situ) DNA is then renatured or reannealed in the presence of excess copies of a
single-stranded, fluorochrome-labeled DNA base-pair sequence or probe (C).

The probe anneals or “hybridizes” to sites of complementary DNA sequence (D) within the
chromosomal genome.

Probe signal is visualized and imaged on the chromosome by fluorescent microscopy.

Advantages: FISH can reliably detect deletions as small as 50 to 200 kb of

DNA. This has allowed the clinical characterization of a number of microdeletion syndromes.

Disadvantages: FISH requires the clinical

knowledge and tests only 1 area at a time. Needs cell culture to generate sufficient DNA.

Applications:

1. Preimplantation chromosomal analysis

2. Pre and post natal diagnosis

3. Chromosomal microdeletion syndromes

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4. Age related losses

5. Oncology

6. Chromosomal structure study

7. Specific probe preparation

Dialysis/ renal replacement therapy:

Principle of excess water and solute removal by running it through a semipermeable membrane and
discarding the waste products.
Clinical indications Biochemical indications

Refractory fluid overload GFR falls to <15ml/min/1.73m2

Pulmonary oedema Serum creatinine of more than 4.0 mg/dL,

Uncontrollable hypertension Intractable metabolic acidosis,

Persistent vomiting, drowsiness and Refractory hyperkalemia

Convulsions with no definable cause
Hyponatremia with serum sodium of less
Growth failure than 120 mEq/L.

Drug intoxication Hyperphosphatemia

TYPES
EXTRA CORPOREAL DIALYSIS INTRA CORPOREAL DIALYSIS
a) manually- continuous ambulatory
a) Continuous RRT (CVVH, CVVHD) peritoneal dialysis (CAPD)

b) Intermittent Hemodialysis (IHD) b)automated devices- continuous cycling

peritoneal dialysis (CCPD)

Hemodialysis Peritoneal dialysis

Principle See pic in hematuria article See pic in hematuria article
Advantages Ability to accurately Safe and simple
regulate volume control Uremic toxins are better removed
No need for technician or vascular access or
Ultra filtration and solute water.
removal can be isolated Fluid and dietary intake is quite liberal
Child can continue his daytime routine
Exact amount of Less mortality
ultrafiltration can be
programmed and achieved
Complications Steal syndrome Pain shock
Dev of aneurysm Leakage from the catheter enter site
Infections Perforation of the viscera
Dialysis disequilibrium Respiratory distress
Peritonitis Hypothermia
Recurrent thrombosis, Dyselectrolytemia
stenosis and recirculation. Protein loss- malnutrition
Dialysis disequilibrium syndrome (DDS)
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 Over anticoagulation Seizures Catheter malfunctioning
limitations Hemodynamic instability Clearance of small molecules is inadequate
Need for anticoagulation Risk of peritonitis
Risk of bleeding
Technical challenges
Need for NG feeding
Available only at specialised
centers

ADHD:
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of
childhood, among the most prevalent chronic health conditions affecting school-aged children, and
the most extensively studied mental disorder of childhood.
DIAGNOSTIC CRITERIA FOR ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
A Either 1 or 2
1 Six (or more) of the following symptoms of inattention have persisted for ≥6 mo to a degree that is
maladaptive and inconsistent with development level:
Inattention
a Often fails to give close attention to details or makes careless mistakes in schoolwork, work,
or other activities
b Often has difficulty sustaining attention in tasks or play activities
c Often does not seem to listen when spoken to directly
d Often does not follow through on instructions and fails to finish schoolwork, chores, or duties
in the workplace (not due to oppositional behavior or failure to understand instructions)
e Often has difficulty organizing tasks and activities
f Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort
(such as schoolwork or homework)
g Often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils,
books, tools)
h Is often easily distracted by extraneous stimuli
i Is often forgetful in daily activities
2 Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for ≥6 mo to
a degree that is maladaptive and inconsistent with developmental level:
Hyperactivity
a Often fidgets with hands or feet or squirms in seat
b Often leaves seat in classroom or in other situations in which remaining seated is expected
c Often runs about or climbs excessively in situations in which it is inappropriate (in
adolescents or adults, may be limited to subjective feelings of restlessness)
d Often has difficulty playing or engaging in leisure activities quietly
e Is often “on the go” or often acts as if “driven by a motor”
f Often talks excessively
Impulsivity
g Often blurts out answers before questions have been completed
h Often has difficulty awaiting turn
i Often interrupts or intrudes on others (e.g., butts into conversations or games)
B Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before 7 yr
of age
C Some impairment from the symptoms is present in 2 or more settings (e.g., at school [or work] or at
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 home)
D There must be clear evidence of clinically significant impairment in social, academic, or occupational
functioning
E Symptoms do not occur exclusively during the course of a pervasive developmental disorder,
schizophrenia, or other psychotic disorder, and are not better accounted for by another mental disorder
(e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder)

Etiology:
1. Maternal smoking and alcohol use during pregnancy and prenatal period.
2. Postnatal exposure to lead.
3. Food colourings and preservatives have inconsistently been associated.
4. There is a strong genetic component to ADHD. Genetic studies have primarily implicated
2 candidate genes, the dopamine transporter gene (DAT1) and a particular form of the
dopamine 4 receptor gene (DRD4), in the development of ADHD.
5. Structural (functional) abnormalities include dysregulation of the frontal subcortical
circuits, small cortical volumes in this region, widespread small-volume reduction
throughout the brain, and abnormalities of the cerebellum.
6. Psychosocial family stressors.
Treatment:
MEDICATIONS USED IN THE TREATMENT OF
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
GENERIC DOSAGE
SIDE EFFECTS
NAME RANGE
Moderate appetite suppression, mild sleep disturbances, transient
methylphenidate 5, 10, 20 mg tabs
weight loss, irritability, emergence of tics

dexmethylphenidat 2.5, 5, and 10 mg Moderate appetite suppression, mild sleep disturbances, transient
e tabs weight loss, irritability, emergence of tics
dextroamphetamin 5, 10, and 15 mg Moderate appetite suppression, mild sleep disturbances, transient
e tabs weight loss, irritability, emergence of tics
Nervousness, sleep problems, fatigue, stomach upset,
10, 18, 25, 40, 60 dizziness, dry mouth
atomoxetine
mg caps Can lead in rare cases to severe liver injury or to
suicidal ideation
100, 150, 200 mg
Bupropion Difficulty sleeping, headache, seizures
tabs
Nervousness, sleep problems, fatigue, stomach upset, dizziness,
Imipramine
dry mouth, accelerated heart rate
3-10 mcg/kg/day Sedation, depression, dry mouth, rebound hypertension on
Clonidine
bid-qid discontinuing, confusion
Guanfacine Hypotension, lightheadedness

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 High risk pregnancy:
Def: High-risk pregnancies are those that increase the likelihood of abortion, fetal death, premature
delivery, intrauterine growth restriction, poor cardiopulmonary or metabolic transitioning at birth,
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fetal or neonatal disease, congenital malformations, mental retardation, or other handicaps.
Causes:
Economic: Cultural- behavioural Biologic and genetic
Poverty unemployment Unmarried Short stature
Poor access to prenatal care short inter pregnancy interval Consanguinity
uninsured Age < 20 and > 40 Poor maternal birth weight
Lack of support group Poor weight gain in pregnancy
Low educational level Previous low birth weight baby or
Poor health care attitudes pre term baby
Cigarette alcohol and illicit drug use
Reproductive: Medical
Previous caesarean section Diabetes mellitus
Prolonged gestation Hypertension
Prolonged labour Torch infection
Previous infertility Sexually transmitted infections
Previous baby with cerebral palsy Congenital heart disease
Multiple gestation, prom, breech Maternal hypercoagulable state

Fetal distress:see notes

Pain in new born:

Pain in neonates may be unrecognized and/or undertreated.

Causes: The intensive care of neonates may involve a number of painful procedures,

including blood sampling (heelstick, venous or arterial puncture)

Endotracheal intubation and suctioning,

Mechanical ventilation, and insertion of chest tubes and intravascular catheters.

Pain in neonates results in obvious distress and acute physiologic stress responses, which may have
developmental implications for pain in later life.

Treatment:

The most frequently used drugs are intermittent or continuous doses of opioids (morphine, fentanyl)
and benzodiazepines (midazolam, lorazepam).

Although the long-term effects of opioids and sedatives are not well established, the 1st concern
should be the treatment and/or prevention of acute pain.

Some minor but painful procedures performed in well neonates can be managed with oral sucrose
solutions.

Prevention:

Pain and discomfort are potentially avoidable problems during the treatment of sick infants.

Preemptive relief from painful stimuli should be provided before pain or anxiety develops.

Educational programs to increase the skills of health care professionals in the assessment and
management of stress and pain in neonates should be provided.

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Health care institutions should develop and implement patient care policies to assess, prevent, and
manage pain in neonates.

Further research is needed to develop and validate neonatal pain assessment tools that are useful in
the clinical setting; to determine optimal behavioral and pharmacologic interventions; and to study
long-term effects of pain and pain management.

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