MSc Histopathology and Cytology
• General Pathology:
• Pathology is the study of disease. Pathology is a branch of medical
science that involves the study and diagnosis of disease through the
examination of surgically removed organs, tissues (biopsy samples),
bodily fluids, and in some cases the whole body (autopsy).
• Systemic pathology
• Systemic pathology is the study of the etiologies, the pathogenesis, and the
host response specific to a particular organ system.
What is the Disease?
It is the “State in which an individual exhibits an
anatomical, physiological, or biochemical deviation
from the normal.
•Disease may be defined as :
an abnormal alteration of structure or function in any part of the
What is Pathology
Pathology is the Scientific Study of Cell Injury and Disease.
Cell Injury and Disease: The structural and/or functional
changes in cells, tissues, and organs.
Scientific Study: applying one or more scientific methods to
reach a diagnosis.
What we study in Disease:
1. Etiology: cause of disease.
2. Pathogenesis: sequence of events from the initial stimulus to
ultimate expression of the disease (mechanisms).
1. Morphology: structural changes in cells and tissues (grossly and
2. Clinical significance: course (signs and symptoms) and prognosis
Four aspects of disease process
Aetiology (Causes of Injury and Disease)
1. Hypoxia (inadequate oxygenation of cells and tissues).
2. Physical agents (trauma, radiation, heat..).
3. Chemical agents (poisons, air pollutants, alcohol, cigarette
Is the mechanism by which a certain aetiological
factor causes disease (In Greek: pathos = disease,
genesis = development).
Clinical Significance of Disease
Course: progression of disease.
1. Symptoms: complaints of the patient.
2. Signs: features of disease detected by clinical
examination or investigations.
3. Prognosis: outcome of disease (good, poor, or unknown).
Clinical Symptoms & Signs
Clinical ssymptoms are the patient’s complain usually by its
own words as pain.
Clinical signs are seen only in the living individual as organomegaly.
Are the changes that occur in the cell tissue or organ as a result
of the pathological process.
Macroscopic appearance visible to the naked eye
Progression of a disease
Cell reacts to adverse influences by :
All forms of cell injury start with molecular or structural alterations in cells.
Under normal conditions, cells are in a homeostatic ‟steady state.”
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).
Cellular adaptation :
occurs when excessive physiologic stresses, or some pathologic stimuli,
preserves the viability of the cell.
1. Hypertrophy ( increase in mass of the cell).
2. Atrophy ( decrease in mass of the cell).
• Reversible cell injury:
Pathologic changes that can be reversed when the stimulus is removed
Pathologic changes that are permanent and cause cell death.
There are two morphologic patterns of cell death:
Necrosis: is more common type after exogenous stimuli and is manifested by:
a. Cell swelling.
c. Coagulation of proteins.
d. Breakdown of cellular organelles.
e. Cell rupture.
Apoptosis: ( programmed cell death ) is characterized by:
1) Occurs in single or small clusters of cells.
2) Results in elimination of unwanted cells during embryogenesis and in
various physiologic and pathologic states.
Causes of cellular injury:
1. Hypoxia (decrease of oxygen), due to :
a. Ischemia (loss of blood supply).
b. Inadequate oxygenation e.g., (cardiorespiratory failure).
c. Loss of oxygen- carrying capacity of the blood e.g (anaemia, carbon
2. Physical agent, including :
3. Chemical agents and drugs:
a) Therapeutic drugs (e.g., acetaminophen[Tylenol]).
b) Nontherapeutic agents (lead & alcohol).
4. Infections agents, including viruses, rickettsia, bacteria, fungi and
5. Immunologic reactions.
6. Genetic derangements
7. Nutritional imbalances.
There are 4 main structures that may be targeted by injury:
1. Cell membrane
2. Mitochondria (ATP production)
4. DNA (genetic material)
Biochemical Mechanisms of Cell Injury
Intracellular accumulation of calcium.
Accumulation of Oxygen-derived free radicals
Membrane damage with permeability loss
Hypoxia causes decreased ATP synthesis. This depletion
1. Failure of active transport by cell membrane and accumulation
of sodium and water into the cell.
1. Defects in protein synthesis, lipogenesis, and phospholipids
turnover, leading to loss of integrity of plasma membrane.
2-Intracellular accumulation of calcium.
Ischemia (deficient blood supply) increases concentrations of
cytosolic calcium leading to activation of catabolic enzymes
(phospholipase, protease, ATPase, and endonuclease). This
results in cell membrane damage, breakdown of proteins, ATP
depletion, and chromatin damage.
3-Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress)
• During generation of energy by cells, small amounts of reactive
oxygen forms and free radicals are produced.
• These forms are can damage lipids, proteins, and nucleic acids.
They are referred to as reactive oxygen species.
Cells have defense systems to prevent injury caused by these
products. An imbalance between free radical-generating and
radical scavenging systems results in oxidative stress, leading to
Important pathologic sources of free radicals include:
1. Prolonged ischemia (venous obstruction).
2. Bacterial infection
Oxygen and oxygen derived free radicals affect cells as follows:
1. Lipid per oxidation of cell membrane, leading to cell damage.
2. Oxidative proteins, leading to damage of proteins and enzymes.
3. DNA damage, leading to death or cancer
Free radicals- induced cell injury:
Free radicals are highly reactive, unstable species that interact
with proteins, lipids, and carbohydrates and are Involved in
cell injury induced by:
a) Absorption of radiant energy (UV light, X-ray).
b) Oxidative metabolic reactions.
c) Enzymatic conversion of oxygenous chemicals & drugs
d) O-derived radicals are toxic species (e.g. OH, H2O2, NO).
e) Superoxide (Ȯ2).
Mitochondria can be damaged by:
1. Increased cytosolic calcium.
2. Oxidative stress.
3. Breakdown of phospholipids.
5-Membrane damage with loss of Permeability
This can be due to:
1. ATP depletion
2. Loss of phospholipids due to activation of phospholipases by
3. Toxicity of oxygen derived free radicals.
4. Various infectious, chemical, or physical factors.
Definition: cells or tissues return to normal structure and function
after removal of the injurious factor.
1. Hydropic change: accumulation of water and sodium into the cell.
2. Fatty change: accumulation of fat into the cell.
Hypoxia results in ATP reduction, which affects the membrane Na-
K pump, leading to accumulation of water and sodium into the cell
and cellular swelling.
Affects all types of cells and considered the first sign of cell injury.
Hypoxia leads to release of fat from cell membrane,
which appear as small or large lipid vacuoles in
Irreversible cell injury
Definition: cells and tissues affected do not return to normal
structure and function.
1. Severe cytoplasmic vacuolation.
2. Mitochondrial damage.
3. Severe damage of cell components and membrane.
Definition: morphologic changes that follow cell death in
The morphologic appearance of necrosis is the result of
denaturation of intracellular proteins and enzymatic digestion
of the cell.
These enzymes are derived either from the lysosomes of the
dead cells themselves (autolysis), or from the lysosomes
leukocytes during inflammatory reactions (heterolysis).
Common types of necrosis:
1. Coagulative necrosis: common in the heart, kidney, and
spleen. The affected tissue is swollen, firm and yellow with
visible outlines of cells.
2. Liquefactive necrosis: results from rapid action of hydrolytic
enzymes , common in the brain and with bacterial infections.
The affected tissue is soft liquid-like with complete loss of
3.Caseous necrosis: chronic type of coagulative necrosis with fragile cheesy
appearance. It is characteristic for TB.
4. Gangrenous necrosis: it is a combination between coagulative and
liquefactive necrosis. Common in the legs.
5. Fat necrosis: due to action of activated lipases
common in fat of breast (traumatic) and peritoneum (alcoholic).
Definition: decreased cell size and functions due to reduced number of cell
1. Brain atrophy due to aging.
2. Pressure atrophy due to mass lesions.
3. Nutritional atrophy: starvation.
4. Atrophy due to febrile disease
Definition: decreased cell numbers due to failure of
proliferation during development
1. Dwarfism( hypo plastic tissues due to reduced levels of
growth hormone or lack of its receptors).
Definition: increased total mass of an organ due to increased number of cells by
frequent cell divisions.
1. Enlargement of breasts during pregnancy due to hormonal effects
2. Endometrial hyperplasia (pathological).
3. Bone marrow hyperplasia (compensatory).
Definition: increased total mass of an organ due to increased size of
cells without cell division.
1. Increased functional demand and hormonal stimuli result in
enlargement of uterine fibers during pregnancy.
2. Compensatory hypertrophy in renal donors.
Hyperplasia and hypertrophy frequently occur
together. For example , hormone-induced growth in
uterus during pregnancy involves both increased
number and size of smooth muscle and epithelial cells.
Definition: transformation of one type of differentiated tissue into
1. Cigarette smoking makes bronchial epith becomes squamous instead of
• Metaplasia of normal columnar (left) to squamous epithelium (right)
in a bronchus, shown (A) schematically and (B) histologically.