HOMEOSTASIS & CELLULAR

ADAPTATIONS
CELLULAR RESPONSES TO STIMULI

STIMULI – WHICH IS GOOD OR BAD?

• PHYSIOLOGICAL

– Good stimulus, part of body’s normal function

• PATHOLOGICAL

– Bad stimulus, can affect or cause harm to body structure

and/or function

SUMMARY OF CELLULAR RESPONSES

HOMEOSTASIS
• CELLULAR ADAPTATION – reversible changes in
• A cell is normally in Homeostasis (Steady state).
structure & function
• At this state, the cell is limited to a narrow range of • CELLULAR INJURY – damage that occurs when the
function and structure & capable of handling physiologic limits of adaptive responses are exceeded; can still be
demands. reversible if mild or not persistent
• CELL DEATH – end result of progressive injury
where the cell ultimately gets killed or kills itself
• CELLULAR ACCUMULATIONS – accumulation of
EXCESSIVE STIMULATION/STRESS substances inside the cell that occur in response to stress
and injury
• With excessive physiological stimulation/stress or with
pathologic (harmful) stimuli, the cell undergoes a series
of events or phenomenon called Cellular Adaptation.
• In order to achieve a new altered steady state to survive ALWAYS REMEMBER
and continue to function.
• How a cell responds depends on the NATURE &
SEVERITY of stress, and other variables affecting the cell
itself – whether it will be an adaptive response, reversible
HOMEOSTASIS, ADAPTATION & INJURY injury, or cell death.

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 CELLULAR ADAPTATIONS MECHANISMS OF ADAPTIVE CHANGE

• Reversible changes in structure (size, number) and • Regulation of specific cellular receptors
function (metabolic activity, phenotype) in – Upregulation (adds more receptors)
response to stimuli from the environment. – Downregulation (removes)
• During this time, new but altered steady states are • Induction of new proteins
achieved, allowing the cell to survive and continue – Switching of one type of protein to
to function. another

ADAPTATION = REVERSIBLE

• It is important to note that these changes are

reversible!
• Once stress or injurious stimulus is eliminated, the
cell can recover back to its original state without
suffering any harmful consequences

1. ATROPHY

• Reduced size of an organ or tissue due to a

• decrease in cell size and loss of cell contents.
• Cells shrink but are not dead
• Can be physiologic or pathologic.

PHYSIOLOGIC ATROPHY

• Occurs during embryonic development where

embryonic structures not useful in life are removed
• Occurs shortly after delivery of the baby where the
uterus shrinks back to near nonpregnant size

PATHOLOGIC ATROPHY

Common causes:

1. Decreased workload (atrophy of disuse)

2. Loss of nerve supply (denervation atrophy)

3. Diminished blood supply

4. Inadequate nutrition

5. Loss of endocrine stimulation

6. Pressure

7. Aging (senile atrophy)

EXAMPLES OF ATROPHY

TESTICULAR ATROPHY

• Shrinkage of the testis due to reduced

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hormonal stimulation and/or blood supply • Occurs when the cell is capable of dividing
• Proliferation of cells due to growth factor, or increased
formation of cells from stem cells
• Can either be physiologic or pathologic

PHYSIOLOGIC HYPERPLASIA

• Response to a normal functional stimulus

• Can either be hormonal or compensatory
• HORMONAL HYPERPLASIA
– Response to hormone stimulation
– Ex. Enlargement of the breast during
CEREBRAL ATROPHY puberty & pregnancy

• Shrinkage of brain tissue, causing deepening and • COMPENSATORY HYPERPLASIA

widening of the depression (sulcus) and narrowing of
the folds (gyri)  Occurs after damage or partial removal of
a tissue
 Ex. Regeneration of the liver after
damage/surgical removal
ATROPHY OF DISUSE
TRIVIA:
• Shrinkage of muscles after prolonged immobilization or
loss of use/function As punishment for stealing the secret of fire from the gods,
• e.g. leg of stroke patients with one-sided paralysis Prometheus was chained to a mountain and his liver was
devoured daily by an eagle, only to regenerate anew every
night
2. HYPERTROPHY

• INCREASE IN SIZE of the cell increased size of

PATHOLOGIC HYPERPLASIA
organ or tissue
• Increased production of proteins in the cell Response to excess hormones or growth factors.
• Can be physiologic or pathologic
• Caused by increased functional demand or by • Benign Protatic Hyperplasia
stimulation by hormones/growth factors  Enlargement of prostate from excess
• Most common stimulus is increased workload testosterone
• No new cells, just larger ones • Endometrial Hyperplasia
 Thickening of the uterine wall (endometrium)
from excessive estrogen
EXAMPLES OF HYPERTROPHY
• Keloid formation
• Uterine smooth muscle – increase in size of the uterus  Excessive skin/connective tissue on scars
in response to hormones of pregnancy (e.g. estrogen)
• Cardiac muscle – enlargement of the heart & its
cardiac muscle fibers due to prolonged increased ENDOMETRIAL HYPERPLASIA
workload caused by long standing hypertension or
faulty heart valves • Occurs when the cycle of estrogen and progesterone
• Skeletal muscle – increase in muscle mass in response
to increased demand from weight lifting or other is disrupted and estrogen levels increase excessively
exercises
• Common cause of abnormal uterine bleeding

• If estrogen stimulation is removed, the uterine lining

3. HYPERPLASIA
returns to its normal thickness
• INCREASE IN NUMBER of cells
• increased growth and mass of organ or tissue
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KELOID FORMATION “CHANGE OF PATH”

• In wound healing, granulation tissue formation occurs • In a metaplastic change, precursor cells mature along a
to fill the “gaps” of a wound. different pathway
• Excess in mitogenic growth factor in certain people
cause excessive growth of fibroblasts & connective
tissue- keloid formation
COLUMNAR-TO-SQUAMOUS METAPLASIA

• Most common form of metaplasia

HYPERTROPHY & HYPERPLASIA • Mucus-secreting columnar epithelium is replaced
by the protective stratified squamous epithelium
• Hypertrophy & Hyperplasia can occur together • Examples:
• Ex. Pregnant uterus – both the uterine endothelium and – In the respiratory tract in response to
uterine smooth muscle cells undergo increased DNA prolonged
synthesis & enlargement of cells • irritation (e.g. smoking) or Vitamin A deficiency
– In the ducts of glands, pancreas or bile tree
in response to unremoved stones

CANCER VS. HYPERPLASIA?

• Hyperplasia is distinct from cancer. The normal lining of ducts & respiratory tract is composed
• Pathologic hyperplasia however constitutes a fertile soil of simple or pseudostratified columnar cells that secretes
for cancerous proliferation to arise. mucus and contains cilia.
– Those with endometrial hyperplasia are at
an increased risk of developing In squamous metaplasia, the more protective stratified
endometrial cancer squamous epithelium takes over.

DIVIDING vs. NON-DIVIDING CELLS

• Non-dividing cells
– Cells of brain, kidneys, muscle, nerves and
heart
– Respond to stress by increasing tissue
mass through hypertrophy.

Cells capable of dividing

• Lining cells of the mouth, stomach and intestines

red blood cells
• Respond to stress by undergoing both hypertrophy
and hyperplasia.
SQUAMOUS-TO-COLUMNAR METAPLASIA

4. METAPLASIA • May occur, as in Barrett’s esophagus

• Esophageal squamous epithelium is replaced by
• Reversible change in phenotype intestinal-like columnar epithelium in prolonged
• One mature cell type is replaced by another exposure to gastric acid reflux
• It may be an adaptive replacement of a weaker
stress-sensitive type by a more resistant type.
• Can be a result of reprogramming of stem cells
CONNECTIVE TISSUE METAPLASIA
existing in normal tissue, or by undifferentiated
mesenchymal cells. • Formation of mesenchymal tissues such as
cartilage, bone or adipose in tissues that normally
do not contain these elements
• Ex. Myositis ossificans

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SEQUELAE OF METAPLASIA • Injuries may progress through a reversible stage,
and may culminate in cell death.
• Change to metaplastic squamous epithelium comes
with a price. REVERSIBLE INJURY
• Although becoming tough and protective,
important mechanisms of protection against • Occurs in early stages or mild forms of injury
infection become lost
• Changes are reversible if stimulus is removed

• Hallmarks of this stage:

DYSPLASIA
 Reduced oxidative phosphorylation
• NOT a true adaptation o with depletion of energy stores (ATP)
• Refers to an abnormal development of cells causing  Cellular swelling
abnormal changes in shape, size and/or o caused by changes in ion concentrations
organization and water influx
• Thought to be related to hyperplasia, and is
sometimes called “Atypical hyperplasia” CELL DEATH
• Can be seen in the lining of squamous epithelium
Two principal types:
thickened by hyperplasia of basal cells with
abnormal maturation of cells • Necrosis – severe damage with self-digestion &
• Dysplatic changes (e.g. mitotic figures, abnormally release of cell contents
large nuclei, abnormally large cells) can act as a • Apoptosis – cell suicide
precursor to cancer. • Can also be an end result of autophagy
 A.K.A. Stage 0 cancer
 This is still REVERSIBLE at this point!

DYSPLASIA of the CERVIX

(Cervical Intraepithelial Neoplasia or CIN)

• Cells appear different in size, shape and nuclear

appearance

NECROSIS vs. APOPTOSIS

• Necrosis is always pathologic

• Apoptosis serves many normal functions and is not
necessarily associated with cell injury.
• Both may be seen in response to the same insult
only at different stages.
CELL INJURY & CELL DEATH • Apoptosis can progress to necrosis

CELL INJURY

Results when cells:

• Are severely stressed that they can no longer be

able to adapt
• Are exposed to naturally damaging agents
• Suffer from genetic abnormalities

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 INFECTIOUS AGENTS

• Cause harm to the cell by producing harmful toxins

or using mechanisms to destroy the cell and enter
the body.
• Examples include:
 Viruses
 Rickettsiae
 Bacteria
 Fungi
OXYGEN DEPRIVATION (HYPOXIA)  Parasites

• Reduces (O2 dependent) aerobic metabolism IMMUNOLOGIC REACTIONS

• Causes include: • Although essential in the defense against

infections, these reactions can also cause injury
 Reduced blood flow (ischemia) (e.g. heart attack,
• Autoimmune diseases
stroke)
 own antibodies attack cells causing cell injury
 Inadequate oxygenation of the blood
 e.g. antiphospholipid antibody syndrome, SLE
 Decreased oxygen-carrying capacity of the blood
• Immune reactions against microbes or some
(e.g. anemia, severe blood loss)
substances can damage normal tissues

GENETIC ABNORMALITIES
PHYSICAL AGENTS
• Cause injury due to deficiency of functional
• Mechanical trauma proteins, or by accumulation of damaged DNA or
• Extremes of temperature (burns, severe cold) misfolded proteins that are beyond repair.
• Pressure changes • Examples include:
• Radiation  Chromosomal anomalies
• Electric shock e.g. Trisomy 21 or Down syndrome
 Sickle cell anemia
Single amino acid substitution in hemoglobin
causing decreased life span of red blood cells
CHEMICAL AGENTS & DRUGS
NUTRITIONAL IMBALANCES
Salt and glucose in cause derangements in
hypertonic solutions electrolyte balance in • Includes undernutrition, overnutrition, or
cells cellular swelling imbalanced composition of the diet
• Examples:
causes toxic free radical
Oxygen at high  Protein-calorie malnutrition
formation
concentrations  Vitamin deficiencies
 Self-imposed nutritional problems
Trace amounts of poisons e.g. arsenic, cyanide or
mercury  Excess cholesterol & obesity

Environmental and air

pollutants, insecticides &
herbicides

Industrial & occupational e.g. carbon monoxide,

hazards asbestos

Some therapeutic drugs e.g. chemotherapy

or medicine
Recreational drugs e.g. alcohol, cocaine
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  Seen mainly in cells involved in & dependent on
fat metabolism, such as hepatocytes and
myocardial cells.
 Appears as clear lipid vacuoles in the cytoplasm

ULTRASTRUCTURAL CHANGES OF REVERSIBLE

CELL INJURY

• Plasma membrane alterations

 Blebbing, blunting, and loss of microvilli

• Mitochondrial changes

MORPHOLOGIC CHANGES IN CELL  swelling & appearance of amorphous densities

INJURY
• Dilation of the ER
REVERSIBLE INJURY
 with detachment of ribosomes
Characterized by:
• Nuclear alterations
• Generalized swelling of the cell and organelles
• Blebbing of the plasma membrane  disaggregation of granular and fibrillar elements
• Detachment of ribosomes from the ER
• Clumping of nuclear chromatin. • Plasma membrane alterations

– Blebbing
– Blunting
Mechanisms of injury: – Loss of microvilli

• Decreased generation of ATP • Mitochondrial changes

• Loss of cell membrane integrity
• Defects in protein synthesis • Dilation of the ER
• Cytoskeletal damage
• Nuclear alterations
• DNA damage.

IRREVERSIBLE CELL INJURY

REVERSIBLE INJURY: TWO PATTERNS OF
REVERSIBLE CELL INJURY • Persistent or excessive injury causes cells to pass
the “point of no return” into irreversible injury and
1. Cellular swelling
cell death.
• A.K.A. Hydropic change or Vacuolar degeneration
• Failure of energy-dependent ion pumps in the
cell membrane causing loss of balance of fluids & CRITERIA THAT CHARACTERIZE
ions IRREVERSIBILITY
• Causes pallor, increased turgor or swelling of
organ • Inability to reverse mitochondrial dysfunction even after
• Appears as small clear vacuoles within the resolution
cytoplasm
of the original injury

• Profound disturbances in membrane function

2. Fatty change

 Occurs in hypoxic injury & toxic/metabolic injuries

NECROSIS

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• Principal outcome in many common injuries Nuclear changes Nuclear breakdown
• Result of denaturation of intracellular proteins and
enzymatic digestion of the injured cell Nuclear shrinkage
• Necrotic cells cannot maintain membrane integrity and
contents may leak out, and elicit inflammation in the Nuclear fragmentation
surrounding tissue.

MORPHOLOGIC CHANGES IN NECROSIS

Increased loss of cytoplasmic RNA

eosinophilia
increase in denatured
cytoplasmic proteins

loss of glycogen
Glassy homogenous
appearance

enzymatic digestion of
Vacuoles or moth-
cytoplasmic organelles
eaten appearance
COAGULATIVE NECROSIS
Myelin figures whorls of phospholipids from
dead cell membranes – Architecture of dead tissues is preserved for days
after injury.
Can generate calcium salts and – Opaque acidophilic ghost cells.
accumulate calcium – Commonly occurs during decreased blood flow in
end-organs (e.g. kidneys, heart, adrenals)
Nuclear Karyolosis

karyo for nucleus, lysis for

breakdown LIQUEFACTIVE NECROSIS

Loss of DNA from enzymatic • Digestion of cells, transforming the tissue into a liquid
degradation & basophilia viscous mass that is usually cream yellow due to
presence of dead leukocytes (i.e. pus)
• It can be seen in:
Pyknosis – Focal bacterial infections & fungal infections
– Hypoxic cell death of cells within the central
Nuclear shrinkage and nervous system (e.g. brain)
increased basophilia

Condensation (pykno) of GANGRENOUS NECROSIS

chromatin into a dense mass
• Not a specific pattern of cell death
• Applies to a limb that lost blood supply and undergone
Karyorhhexis
necrosis involving multiple layers
-rrhexis for rupture • Types of gangrene include:
– Dry gangrene (coagulative necrosis)
fragmentation of the nucleus – Wet gangrene (liquefactive necrosis with
superimposed bacterial infection &
Increased – pus formation)
eosinophilia

Appearance of
vacuoles CASEOUS NECROSIS
Myelin figures

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• Characterized by a cheese-like (casein-like) gross
appearance of necrotic area
• Commonly seen in tuberculous infections.
• Appears as collection of fragmented cells and
amorphous granular debris enclosed with an
inflammatory border (granuloma).

FAT NECROSIS

• Focal areas of fat destruction

• Appears like adipose tissue with necrotic changes
• Basophilic calcium deposits with inflammation
• Different causes include:
– Enzymatic fat necrosis
• Leaked enzymes digest and liquefy the
membranes of fat cells
• Fatty acids are released in the process & cause
saponification IMPORTANCE OF APOPTOSIS
– Traumatic fat necrosis
• Programmed destruction of cells during embryonic
• Occurs in blunt trauma of adipose tissue
development
• Involution of hormone-dependent tissues on
hormone withdrawal
FIBRINOID NECROSIS • Cell loss in proliferating cell populations
• Elimination of potentially harmful self-reactive
• Pattern wherein immune complexes (antigens and lymphocytes
antibodies) are deposited in walls of arteries and • Death of host cells that have serve their useful
interact with fibrin outside vessels purpose
• Seen in immune reactions involving blood vessels
• Appears as bright pink (fibrin-like) deposits

EXAMPLES OF APOPTOSIS

APOPTOSIS • DNA damage

– Radiation, anticancer chemotherapy, and
• A pathway of cell death induced by a tightly regulated hypoxia
suicide program, in which cells destined to die activate – If repair mechanisms cannot cope with the injury,
enzymes that degrade their own nuclear DNA and cells trigger apoptosis
proteins. – “Elimination of the cell is a better option than
• Occurs normally both during development & adulthood, risking mutations in the
serving to eliminate unwanted, old, or potentially – damaged DNA”
harmful cells.
• It can also be a pathologic event when diseased cells • Accumulation of misfolded proteins
become damaged beyond repair. – May arise because of mutations in genes or
• Characterized by the absence of membrane loss, because of free radical
enzymatic digestion of cells, leakage of cellular – Excessive accumulation of these in the ER leads to
contents, and an inflammatory reaction. ER stress, which leads to apoptotic cell death.\
– Apoptotic cells break up in fragments, called
apoptotic bodies. • Cell death in certain infections
– Membrane of the apoptotic bodies remains intact – Especially viral infections
but become “tasty” targets for phagocytes. – Loss of cells is largely due to apoptosis induced by
– Phagocytes quickly devour fragments before the virus (e.g. adenovirus, HIV) or by the host
contents leak out and incite an inflammation. immune response (e.g. viral hepatitis)
– Cytotoxic T cells specific for viral proteins can also
induce apoptosis of infected cells in an attempt to
eliminate reservoirs of infection.
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• Pathologic atrophy in organs after duct obstruction

MORPHOLOGIC CHANGES IN APOPTOSIS

• Cell shrinkage
– cytoplasm becomes dense & organelles become
tightly packed
• Chromatin condensation
– the most characteristic feature of apoptosis
chromatin aggregates into dense masses of various
shapes & sizes; the nucleus may fragment ATP DEPLETION
• Formation of cytoplasmic blebs & apoptotic bodies
• Phagocytosis of apoptotic cell or cell bodies by • Major causes of ATP depletion include:
macrophages 1. Low supply of oxygen & nutrients
2. Mitochondrial damage
3. Actions of some toxins
• Depletion of ATP down to 5-10% of normal levels has
MECHANISMS OF CELL INJURY
widespread effects on many critical cellular systems
1. Response to injurious stimuli depends on the • Reduced activity of the plasma membrane sodium
nature, duration and severity of injury potassium pump
2. Consequences of cell injury depends on the type,
state & adaptability of the cell.
3. Any injurious stimulus may trigger multiple
interconnected mechanisms that damage cells.
4. Cell injury results from biochemical mechanisms
acting on several essential cellular components.

1. Response to injurious stimuli depends on the nature,

duration and severity of injury

• Small doses of a toxin or brief periods of reduced blood

flow may cause reversible injury
• Large doses of the same toxin or prolonged reduction in
blood flow results in instant death or in irreversible • Cellular energy metabolism is altered
injury leading to cell death. • Failure of calcium ion pump
• Disruption of protein synthesis
2. Consequences of cell injury depend on the type, state • Proteins may become misfolded
& adaptability • Irreversible damage to mitochondrial & lysosomal
membranes
of the cell.

• Responses differ between cells

• A certain dose can be lethal to one cell but could have MITOCHONDRIAL DAMAGE
no effect on another
• Due to genetic variations affecting enzymes.

3. Cell injury results from biochemical mechanisms

acting on several essential cellular components

Page 10 of 16
 DAMAGE TO DNA & PROTEINS

• Damage to DNA that is severe enough for repair

mechanisms to correct leads to the initiation of a suicide
program  apoptosis
• Presence of misfolded proteins from genetic mutations
or free radical exposure also leads to apoptosis.

INTRACELLULAR ACCUMULATIONS
• A manifestations of metabolic imbalance in cells is the
accumulation of various substances belong to one of
two categories:
1. Normal constituent
• Formation of the mitochondrial permeability transition
2. Abnormal substance
pore
o Exogenous
• Leakage of proteins such as cytochrome into the cytosol
o Endogenous

LOSS OF CALCIUM HOMEOSTASIS

CATEGORIES OF ACCUMULATIONS
• Elevated intracellular Ca2+ causes cell injury by:
– Activating enzymes 1. Normal endogenous substance at normal rate of
o proteases, ATPases, endonucleases & production, but slow rate of removal
phospholipases 2. Abnormal endogenous substance accumulating from
o that cause breakdown of cellular structures defects in folding, transport & degradation
• Opening of the mitochondrial permeability
transition pore
– due to Ca2+ accumulation in mitochondria, causing
loss of potential and failure of ATP synthesis
• Activating caspases that promote apoptosis

ACCUMULATION OF OXYGEN-DERIVED
FREE RADICALS
• Read on the mechanism of Free radical formation &
removal

DEFECTS IN MEMBRANE PERMEABILITY

• Early loss of membrane permeability leading to

membrane damage is a consistent feature of most forms
of cell injury.
• May be the result of:
– ATP depletion and calcium-mediated activation of LIPIDS
enzymes that breakdown phospholipids
LIPID ACCUMULATIONS
– Direct damage by bacterial toxins, viral proteins,
lytic cell components, and variety of physical and • All major classes of lipids can accumulate in cells
chemical agents – Triglycerides, Cholesterol, Phospholipids
• Most important sites of membrane damage: • Abnormal complexes of lipids and carbohydrates can
– Mitochondria also accumulate in certain diseases.
– Plasma membrane
– Lysosomes

STEATOSIS
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• A.K.A. Fatty change • Smooth muscle cells & macrophages within the layer of
• Abnormal accumulation of triglycerides within aorta and large arteries become filled with lipid
parenchymal cells of organs vacuoles
– Liver, the major organ involved in fat metabolism • Foam cells
– Heart, muscle & kidney • Atheromas
• Causes include:
– Toxins
– Protein malnutrition XANTHOMAS
– Diabetes Mellitus
• Intracellular accumulation of cholesterol within
– Obesity
macrophages
– Anoxia
• Presents as tumorous masses composed of clusters of
• In developed nations, the most common causes of
foamy cells found in the connective tissue of the skin &
significant fatty liver are alcohol abuse and
tendons
nonalcoholic fatty liver disease (NAFLD)

FATTY LIVER

• Excess accumulation of triglycerides within the liver

may result from excessive entry or defective
metabolism and export of lipids.
– Hepatotoxins, such as alcohol/ethanol
o Reduces lipid breakdown CHOLESTEROLOSIS
o Increases lipid synthesis
– Protein malnutrition • Focal accumulations of cholesterol-laden (light)
o Reduced synthesis of apoproteins macrophages in the lamina propia of gallbladder
– Hypoxia
o Impairs fatty acid metabolism (oxidation)
PROTEIN
PROTEIN ACCUMULATION
LIPID ACCUMULATION: MORPHOLOGY
• Intracellular accumulations of proteins usually appear
• Most often seen in the liver and heart
as rounded eosinophilic (red) droplets, vacuoles, or
• In all organs, fatty change appears as clear vacuoles
aggregates in the cytoplasm.
within the parenchyma.
• Excess proteins within cells have various causes
– Reabsorption droplets in kidney tubules

HYALINE

HYALINE ACCUMULATION

• “Hyaline” refers to a change within cells or

extracellular space that give it a glassy homogenous,
bright pink appearance in slides.
• Produced by a variety of alterations.
• Does not represent a specific pattern of accumulation.

GLYCOGEN
ATHEROSCLEROSIS • Glycogen is a readily available source of energy in the
cytoplasm of healthy cells.
ATHEROSCLEROTIC PLAQUE

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• Excessive intracellular deposits of glycogen are seen in • phospholipids bound to protein.
patients with abnormality in glycogen or glucose • Known as the wear-and-tear pigment.
metabolism. – Not harmful but can be a sign of free radical injury
– Diabetes Mellitus is an example of a disorder of and lipid peroxidation.
glucose metabolism with glycogen deposits in – Often seen in slowly-regressing cells of the liver
multiple organs and heart of aging patients, and can also be seen in
• Masses of glycogen appear as clear vacuoles within severe malnutrition or cancer.
the cytoplasm. • Appears as a yellow-brown, finely granular
cytoplasmic (often perinuclear) pigment

PIGMENT
MELANIN
PIGMENT ACCUMULATION
• An endogenous, brown-black pigment formed from
• Pigments are colored substances, some of which are oxidation of tyrosine in melanocytes.
normal constituents of cells, whereas others are • The only endogenous black-brown pigment.
abnormal and accumulate in cells in certain • Normally seen in melanocytes of the stratum basale of
circumstances. the skin but can accumulate in areas of stress.
• Exogenous pigments come from outside of the body. • Granular appearance
• Endogenous pigments are synthesized within the body
itself.
HEMOSIDERIN

• A hemoglobin-derived, golden yellow-to-brown,

granular or crystalline pigment that serves as one of the
major storage forms of iron.
EXOGENOUS PIGMENTS: CARBON • Hemosiderin pigment represents aggregates of ferritin
(iron) micelles.
• The most common exogenous pigment, also known as
• Can be seen normally in small amounts in the
“Coal Dust” from its black color
mononuclear phagocytes of the bone marrow, spleen &
• When inhaled, carbon pigments become picked up by
liver.
macrophages within the alveoli.
• Accumulations blacken the tissues of the lungs
(anthracosis) and lymph nodes.
HEMOSIDEROSIS
EXOGENOUS PIGMENTS
• Deposition of hemosiderin pigment in many organs and
• Tattooing is a form of localized, exogenous tissues during state of iron overload.
pigmentation of the skin. • Main causes:
• The ink pigments are taken up by dermal macrophages, – Increased absorption of dietary iron
which reside in the skin for the remainder of the life. – Hemolytic anemias, with iron released from RBCs
– Repeated blood transfusions

ENDOGENOUS PIGMENTS
BILIRUBIN
• Endogenous pigments are derived from by-products of
processes within the cell. • Normally the major pigment found in bile that is
• Examples: derived from hemoglobin but contains no iron.
– Lipofuscin • Jaundice is a common clinical disorder caused by
– Melanin excesses of bilirubin within cells and tissues.
– Hemosiderin – Hepatitis
– Bilirubin – Biliary flow obstruction

BILIARY OBSTRUCTION/CHOLESTASIS
LIPOFUSCIN

• A brown insoluble pigment, composed of lipids and

Page 13 of 16
 • where a BMI less than 16kg/m2 is considered
• malnourished.
WHAT IS AN “APPROPRIATE DIET”? – But we have to consider other factors as well such
as edema, fat stores, muscle mass, and blood
• Sufficient source of energy/calories proteins.
– In the form of carbohydrates, fats & proteins
– Needed for body’s daily metabolism PEM SYNDROMES
• Amino acids & fatty acids
– Used as building blocks for synthesis of structural • A spectrum of syndromes, all characterized by a dietary
& functional proteins and lipids intake of protein and calories inadequate to meet the
• Vitamins & minerals body’s needs.
– Function as coenzymes or hormones in metabolic • The two ends of the spectrum of PEM syndromes are
– pathways, and also as structural components known as marasmus & kwashiorkor.
• May affect the somatic (muscle) component, or the
visceral (organs) component

MALNUTRITION

• A.K.A. Protein Energy Malnutrition (PEM) MARASMUS

• Consequence of inadequate intake of proteins and
calories, or deficiency in digestion of absorption of • Considered when a child’s weight falls below 60% of
proteins. normal for sex, height and age.
• Results in loss of fat & muscle tissue, weight loss, • A marasmic child suffers growth retardation, and loss of
lethargy & generalized weakness. muscle and subcutaneous fat.
• Millions of people in developing nations are • Visceral protein & blood protein levels are however
malnourished & starving. normal or only slightly reduced.

PRIMARY MALNUTRITION

• Inadequate supply of at least one or all of the nutrients

in the diet
• Ex. Marasmus, kwashiorkor With such losses of muscle and subcutaneous fat, the
extremities are emaciated. The head appears too large for
SECONDARY MALNUTRITION
the body. Anemia and manifestations of multiple vitamin
• Supply of nutrients is adequate, but there is insufficient deficiencies are present, and there is evidence of immune
intake, absorption, utilization, storage, excess loss, or deficiency
increased need for nutrients

KWASHIORKOR
Conditions that lead to Dietary Insufficiency
• Occurs when marked protein deprivation is greater
• Poverty than the reduction in total calories, and is associated
• Infections with severe loss of visceral protein.
• Acute or chronic illnesses • Resultant low albumin levels in the blood causes
• Chronic alcoholism generalized edema, which masks weight loss.
• Ignorance & failure of diet supplementation • Subcutaneous fat and muscle mass is spared.
• Self-imposed dietary restriction

PROTEIN ENERGY MALNUTRITION (PEM)

• A serious & often lethal disease affecting children

• Determined according to body mass index (BMI)
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Children with kwashiorkor have characteristic “flaky paint”
appearance.

Hair changes include overall loss of color or alternates. ANOREXIA NERVOSA

Other features that differentiate kwashiorkor from marasmus
• Condition characterized by self-induced starvation,
include an enlarged, fatty liver, development of apathy,
resulting in marked weight loss.
listlessness, and loss of appetite. Vitamin deficiencies,
• Clinical findings similar to those in severe PEM, but
defects in immunity and secondary infections may also occur
additional effects amenorrhea, anemia, hypothyroidism,
dehydration & electrolyte imbalance
• Highest death rate of any psychiatric disorder
SECONDARY PEM – Increased susceptibility to sudden cardiac death
from low potassium levels (due to poor intake)
• Occurs in chronically ill, elderly, bedridden patients.
ANOREXIA NERVOSA

Eating disorders (anorexia, bulimia) occur primarily in

previously healthy young women who have developed an
obsession with body image and thinness.

BULIMIA

• A condition in which the patient binges on food and

CACHEXIA
then induces vomiting.
• Protein energy malnutrition occurring in patients with • Large amounts of food, principally carbohydrates, are
AIDS or advanced cancer (around 50%). ingested, to be followed by induced vomiting.
• Highly debilitating condition characterized by extreme • Major medical complications relate to continual
weight loss, fatigue, muscle atrophy, anemia, anorexia induced vomiting, and the use of laxatives and diuretics
and edema. (electrolyte imbalances, lung aspiration)
• Death is usually caused by the atrophy of the
diaphragm.
OBESITY

• A disease of caloric imbalance (and excess fat storage)

CANCER-RELATED CACHEXIA
that results from an excess intake of calories above their
The lesser the physiological reserve (proteins, fats, etc) the consumption by the body
lower the chances of survival in these disease states. Hence • Has become a major public health problem in the
nutritional upbuilding is very important. industrial world, and even developing nations.
• Associated with the development of diseases such as
diabetes and atherosclerosis, that complicate into heart
attacks, stroke, and death.

BODY MASS INDEX (BMI)

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• The normal BMI range is 18.5 to 25 kg/m2, although
this may differ for different countries.
• Individuals with BMI between 25 kg/m2 and 30 kg/m2
are considered to be overweight.
• Individuals with BMI above 30 kg/m2 are classified as
obese.

Other means of assessing body fat

• Body fat may also be measured by:

– triceps skinfold thickness
– mid-arm circumference, and
– ratio between waist and hip circumferences

CENTRAL OBESITY (Visceral Obesity)

• Condition in which fat accumulates in the trunk and in

the abdominal cavity (in the mesentery and around
viscera).
• Is associated with a much higher risk for several
diseases than is excess accumulation of fat diffusely in
subcutaneous tissue.

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