PATHOLOGY

Pabitra Subadi
What Is Pathology
• Pathology literally is the study (logos) of suffering (pathos)
• Pathology is the scientific study of disease.
• Pathology is the foundation of medical science & practice.
• Pathology is a result of disease and changes in homeostasis.
• Pathology is a bridging discipline devoted to the study of the structure & functional changes in cells, tissues
& organs that underlie diseases. Pathology attempts to explore the “ whys” and “wherefores” of the signs
and symptoms of diseases
• Pathology much of it has a visible expressions
- Radiographs
- CT-scans
- MRI (magnetic resonance imaging)
- Ultrasound
- Clear drawings
 Four aspects of a disease process that form the core of pathology

Pathology

Etiology Pathogenesis Morphological Clinical

Changes Menifestation
its cause Mechanisms of its
Structural alterations
development Functional
induced in cells &
consequences of
organs
the morphologic
ETIOLOGY changes
•Study of the cause of diseases.
•Unknown causes of some diseases (idiopathic)
PATHOGENESIS
• Refers to the sequence of events in the response of the cells or tissues to the etiologic agent, from
the initial stimulus to the ultimate expression of the disease.
• The mechanism through which the etiology (cause) operates to produce the pathological and
clinical manifestations.
• Examples include: inflammation, degeneration, carcinogenesis, immune reactions.
Pathogenesis
• Tobacco smoking is the main risk factor for COPD, although other inhaled
noxious particles and gases may contribute.
• In addition to inflammation, an imbalance of proteinases and antiproteinases
in the lungs, and oxidative stress are also important in the pathogenesis of
COPD

Pathophysiology
• The different pathogenic mechanisms produce the pathological changes
which, in turn, give rise to the physiological abnormalities in COPD:
- mucous hypersecretion and ciliary dysfunction,
- airflow limitation and hyperinflation,
- gas exchange abnormalities,
- pulmonary hypertension,
- systemic effects.
MORPHOLOGICAL CHANGES
• Structural changes  includes biological changes (enlargement of organs, rupture of
blood vessels  as seen in typhoid)

CLINICAL MENIFESTATION
• Signs and symptoms of certain diseases.
• Sign  objective evidence of disease.
• Symptoms  subjective evidence of disease.
• Therefore, a symptom is a phenomenon that is experienced by the individual affected by
disease, while a sign is a phenomenon that can be detected by someone other than the
individual affected by disease.
• For examples  tiredness, pain, itching are symptoms while rashes, bloody nose,
swelling of glands, fever, high blood pressure are signs.
• Various physiologic arrangements which serve to restore the normal state, once it has
been disturbed  Homeostasis
• Excess physiologic or pathologic stress may force the cell to a new steady state 
Adaptation
• Too much stress exceeds the cell’s adaptive capacity  Injury
• Cell injury is defined as a variety of stresses a cell encounters as a result of changes in
its internal and external environment.
• The cellular response to stress may vary and depends upon the following:
- the type of cell and tissue involved
- extent and type of cell injury

Dr. Prayas Ghimire, Pharm D.(PB)

 Causes of Cell Injury
1. Hypoxia
 oxygen supply
 most common cause
 Hypoxia may be due to
a) Ischemia  decrease in blood supply (e.g. Atherosclerosis)
b) Loss of O2 carrying capacity of blood (e.g. Anemia)
c) Inadequate oxygenation of blood (e.g. Asthma)

2. Physical agents
 Mechanical trauma
 Radiation
 Electric shock
 Extremes of temperature (burn and cold)
 Sudden change in atmospheric pressure
3. Chemical agents
Acids & Alkalis
Poisons (e.g. arsenic, cyanide, mercury)
Environmental & air pollution (e.g. insecticides, CO, alcohol, asbestos)
Normal body compound in high concentration (e.g. hypertonic solution of glucose, NaCl)

4. Biological agents
Bacteria
Viruses
Fungi
Parasites (e.g. roundworm, hookworm)
5. Immunological reactions
Type-1 hypersensitivity reaction (Anaphylactic reaction)
Autoimmune diseases ( e.g. Rheumatoid Arthritis)

7. Nutritional Imbalances
 Nutrition (e.g. excess lipids  Atherosclerosis)
 Nutrition (e.g. protein calorie malnutrition  Kwashiorkor)
Vit C deficiency  Scurvy
Vit D deficiency  Ricket
 Cell Adaptation
• Change in size and number of cells to maintain homeostasis.
• To be in normal  they change to become adapted in environment around.
• Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or
functions of cells in response to changes in their environment.
• Cells must constantly adapt, even under normal
• Cells must constantly adapt, even under normal conditions, to changes in their
environment.
• These physiological adaptations usually represent responses of cells to normal stimulation
by hormones or endogenous chemical substances.
• For example, as in the enlargement of the breast and induction of lactation by pregnancy.
• Cellular adaptation is a state that lies intermediate between the normal, unstressed cell
and the injured, overstressed cell.
• Cell can adapt themselves by undergoing 5 different conditions
1. Hyperplasia
2. Hypertrophy
3. Atrophy
4. Metaplasia
5. Dysplasia

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 Hyperplasia
• Increased number of cells resulting in increased mass of the organ or tissue.
• Takes place in cells capable of dividing.

Physiological hyperplasia
- Uterine enlargement during pregnancy
- Female breast in puberty & lactation
Pathological hyperplasia
- Hyperplasia of the endometrium (excessive hormone stimulation).
- Prostatic hyperplasia

Pathologic hyperplasia can be a fertile soil for development of neoplasia (maglignancy).

 Atrophy
• Acquired loss of size due to reduction of cell size or number of parenchyma cells in an
organ.

Physiologic
- Embryonic development.
- Gravid uterus involution.
- Hormonal withdrawal after menopause.
Pathologic
- Decreased workload (Disuse atrophy)
- Diminished blood supply.
-Inadequate nutrition.
- Loss of endocrine stimulation.
 Hypertrophy
• Hypertrophy is an increase in cell size resulting in an increase in the size of the organ.
Types
Physiologic: physiologic growth of the uterus during pregnancy involves both hypertrophy
and during pregnancy involves both hypertrophy and hyperplasia.
Pathologic causes: increased workload, hormonal stimulation and growth factors
stimulation.
e.g. hypertrophy of heart the most common stimulus is chronic hemodynamic
overload

There is a limit for hypertrophy, beyond which the muscle is no longer able to
compensate for the increased burden.
 Metaplasia
• Metaplasia is a reversible change in which one adult cell type is replaced by another
adult cell type.
• New cell type is better in dealing with the current stress or irritation.
• Persistence of factors causing metaplasia may lead to progression into malignant
transformation.
• Causes:
- Changes in environment
- Irritation or inflammation
- Nutritional
• Example: Replacement of ciliated columnar epithelium with stratified squamous
epithelium in the respiratory tract of a smoker.
 Dysplasia
• Loss of uniformity of individual cells and loss of their architectural orientation (gall bladder,
cervix etc.)
• Pleomorphism
• Occurs most commonly in epithelial cells
• Epithelial dysplasia is characterized by cellular proliferation and cytologic changes.
• Chances of becoming cancer are high
• Causes:
- Chronic irritation, chronic inflammation
- Chronic infection
 Cell Death
Necrosis
• Necrosis is a sequence of morphological changes that follow cell death mainly resulting
from degenerative action of enzymes on lethally injured cells.
• It is the death of cells with morphological evidence of death.
• Causes of cell necrosis: most common causes of cell death are: viruses, ischaemia,
bacterial toxins, hypersensitivity, and ionizing radiation.
• Necrosis results from:
- enzymatic digestion of cells
- degeneration of proteins (enzymes)
• Cytoplasm of necrotic cell untergoes following changes:
- Swelling and granularity of the cytoplasm
- Loss of cellular membrane
- Fusion of cells
• Nucleus of necrotic cell undergoes destructive changes (occurs due to hydrolysis of
nuclear proteins)
- Pyknosis  the nucleus becomes shrunken condensed and deeply stained.
- Karyorrhexis  rupture of nuclear membrane with fragmentation of the nucleus.
- Karyolysis  the nucleus dissolves and disappears.
 Types of Necrosis
1. Coagulative necrosis
- Cause  ischemia; less common bacterial/chemical
- The protein of the affected tissue becomes denaturated.
- The infarct area is surrounded by narrow zone of inflammation and congestion.
- Organ commonly encountered  heart, kidney & spleen
- Gross appearance of tissue  foci of coagulative necrosis occurs as pale, firm and slightly
swollen
- Microscopically, the structural outline of the affected tissue is preserved but the cellular
details are lost (Tombstone appearance)
- Affected tissue is firm
- Cell degradation & liquefaction is not seen in coagulative necrosis (cell outline is still
remaining intact)
- at the end of necrosis  the necrotized cells are infiltrated by inflammatory cells and then
phagosized.
2. Liquifactive necrosis
- The necrotic tissue undergoes rapid softening e.g. infarction of the nervous tissue which
has abundant lysosomal enzymes.
- the tissue becomes liquid viscous mass  there is degradation of cells  due to
powerful hydrolytic enzymes released from dead cells.
- material is creamy yellow in color.
- seen in brain and abscess.

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- Caused by: ischemia/bacteria/fungi
- Organ: Infract brain & Abscess cavity
- Gross appearance: soft with central liquid material  as time progress  cystic lining
is formed surrounding the liquid materials
- Microscopic characters:
- cystic cavity contains numerous necrotic products and macrophages
- peripheral cystic lining contains proliferating capillaries and inflammatory cells
3. Caseous necrosis
- It is characteristic of tuberculosis.
- commonly found in central foci of tuberculi infection.
- has feature of both coagulative and liquifactive necrosis.
- Unlike coagulative necrosis, the necrotic cells do not retain their cellular outlines, and do not
disappear by lysis, as in liquifactive necrosis.
- The cause of necrosis in TB is hypersensitivity reaction caused by the tuberculoprotein
content of the cell wall of Mycobacterium.
- The necrotic tissue undergoes slow partial liquefaction forming yellow cheesy material.
- Grossly, the caseous material resembles clumpy cheese, hence the name caseous necrosis.
- Microscopically, it shows amorphous granular eosinophilic material lacking the cell outlines.
4. Fat necrosis
- it is necrosis of adipose tissue including two types:
a) Traumatic: caused by trauma to adipose tissue e.g. breast and subcutaneous tissue.
b) Enzymatic: which occurs in case of acute haemorrhagic pancreatitis  Obstruction
of the pancreatic duct leads to release of lipase which splits the fat cells of the omentum
into fatty acid (combine with Ca giving chalky white calcification) and to glycerol which
is absorbed in the circulation.
- Organs: pancreas (when there is acute pancreatic necrosis) & breast ( traumatic fat
injury)
- Grossly, yellowish white & texture is firm (due to chalky white calcification)
- Microscopically, cloudy apperanace (due to necrotized fat cells) & Ca salt apperas as
amorphous, granular and basophilic.
5. Fibrinoid necrosis
- This is characterized by swelling, fragmentation, increased collagen fibers and
accumulation of mucopolysaccharides and fibrin due to vascular exudation of fibrinogen at
the site of lesion.
- characterized by  deposition of fibrin like material
- seen in immunologic cell injury, hypertension, peptic ulcer.
- microscopically, necrotic materials seems to be having brightly eosinophilic, hyaline like
deposition surrounded by nuclear materials of neutrophils which is called leucocytoclasis.
 Apoptosis
• Apoptosis, or programmed cell death, is a highly regulated process that allows a cell to self-degrade in
order for the body to eliminate unwanted or dysfunctional cells.
• During apoptosis, the genome of the cell will fracture, the cell will shrink and part of the cell will
disintegrate into smaller apoptotic bodies.
• Between 50 and 70 billion cells die each day due to apoptosis in the average human adult. For an average
child between the ages of 8 and 14, approximately 20 billion to 30 billion cells die a day.
• Apoptosis has since been recognized and accepted as a distinctive and important mode of “programmed”
cell death, which involves the genetically determined elimination of cells.
• Apoptosis is essential to embryonic development and the maintenance of homeostasis in multicellular
organisms.
• In humans, for e.g., During fetal development, cell death helps sculpt body shape and making the right
neuronal connections
• Tissue homeostasis mainly depends on the balance between cell proliferation and cell death.
• Programmed cell death or apoptosis is an intrinsic death program that occurs in various physiological
and pathological situations.
• Apoptosis or self destruction is necessary for normal development and homeostasis of multicellular
organisms.
• Apoptosis plays a major role in many diseases like cancer, AIDS and neurodegenerative disorders.
Dr. Prayas Ghimire, Pharm D.(PB) 32
 Need Of Apoptosis
• Apoptosis is needed for proper development
Examples:
The resorption of the tadpole tail
The formation of the fingers and toes of the fetus
The formation of the proper connections between neurons in the brain
• Apoptosis is needed to destroy cells
Examples:
Cells infected with viruses
Cells with DNA damage
Cancer cells
 Difference between Necrosis & Apoptosis
Features NECROSIS APOPTOSIS

Definition Cell death occuring through activation of lysosomal Programmed cell death occuring through
hydrolytic enzymes activation of caspases

Cell size Cells are swollen Cells are shrunken

Nucleus Condensation of nucleus Fragmentation of nucleus

Organelle Swollen organelles Normal looking organelles but tightly packed

Cell membrane Disrupted; Marked membrane damage Intact membrane till end

Stimulus Invariably pathological Both physiological and pathological

Inflammatory reaction in Present Absent

surroundings

No. of cells undergoing death Death of usually single cell or small cluster of cell at Death of many cells at a time
a time Dr. Prayas Ghimire, Pharm D.(PB) 34