1- Introduction of

Pathophysiology
By: Dr Tarek Atia

Pathology of disease is studied under four subdivisions:

Etiology: Study of causes or causative agents of

disease
Pathogenesis: Study progression or development of a
disease .
Morphology: Study of structural changes in diseased
tissue or organ (macroscopic & microscopic)
Clinical Significance: Study of how clinical features
are related to changes.

Major groups of diseases are

Inflammatory, Degenerative & Neoplastic

Inflammatory disorders are due to damage to tissues by
various injuries (physical, chemical, infections etc.)
Degenerative disorders are due to lack of growth or
ageing.
Neoplastic disorders are due to excess cell division
forming tumors.

Cell Injury
Damage or alteration of one or more cellular components

Many types of injury are tissue-specific because of

anatomic relationships and tissue response to chemical
and infectious agents.
Cell injury disrupt cell physiology; so the cell does not
function at full capacity.

Stages in the cellular response to stress and

injurious stimuli

Cell Injury Produces

Symptoms:
experienced

complaints
by

the

patient.

Signs: abnormal physical

findings.

Outcomes from cell injury depend upon:

Type of injury
Severity of the injury
Duration of the injury
Type of cell being injured: Some types sustain

injury better than others; some tissues (e.g.

liver) have a capacity to regenerate.

Consequences of Injury

(Reversible): No long term effects- the cell

damage is repaired, the effects of the injury
are reversible.

The cell adapts to the mild damaging

stimulus.

(Irreversible): The cell dies, undergoing

necrosis. The damage is irreversible.

Adaptation to injury
1. Atrophy: decrease in the size and functional
capacity of the cell, after normal growth has
been attained . ( O2, blood, nerve supply)
2. Hypertrophy: an increase in the size of the cell

secondary to an increase in cell function.

Causes of Cell Atrophy

1. Loss of blood supply or innervations
2. Loss of endocrine factors (hormone)
3. Decrease in the workload
4. Aging, chronic illness

3. Hyperplasia: an increase in the number of cells of

tissue in response to a stimulus or injury.

4. Metaplasia: replacement of one type of tissue with

another type in response to an injury.
4. Hypoplasia: incomplete development of an organ /

tissue.
6. Aplasia: lack of development of an organ or tissue.

Muscular hypertrophy

Metaplasia

Cell Death
Apoptosis

Necrosis

Apoptosis: Programmed cell death:

It plays an important role in many physiological and
diseased conditions.
Death of aged cells.
Embryonic remodeling.

 The apoptotic cells undergo series of changes including

membrane blebbing, and fragmentation of DNA
creating a vacuolar nucleus.
Apoptotic cells shrink in size, break into smaller pieces
called apoptotic bodies that are recognized by

phagocytes.

Membrane blebbing

Cell shrink

Cell
fragmentation

Morphology of Necrotic nucleus

1- Pyknosis
Shrunken nucleus
with dark staining
Seen in a necrotic
(dead) cell

Karyorrhexis
Fragmentation of pyknotic nucleus

Karyolysis
Extensive hydrolysis of
pyknotic nucleus with
loss of staining
Represents breakdown
of

the

chromatin

denatured

Types of tissue necrosis

Cardiac muscle fibers

1- Coagulative Necrosis
Dead

cells

ghost-like

remain

as

remnants

of

their former self

Classically seen in an
Myocardial Infarction

Kidney (necrotic renal tubules)

2- Liquefactive Necrosis
The

dead

cells

undergo

extensive autolysis, caused by

the

release

of

lysosomal

enzymes (proteinases, DNases,

RNases, lipases, etc.)
Seen classically in the spleen
and brain following infarction.

(A) Coagulative vs. (B) Liquefactive Necrosis

3- Caseous Necrosis (Caseum - Cheesy)

Resembles cottage cheese
Soft, friable, whitish-grey
Present within infected tissues
Seen in Tuberculosis (Mycobacterium
tuberculosis)

4- Fat Necrosis
Leakage of lipases from dead cells

attack

triglycerides

surrounding

fat

tissue

in
and

generate free fatty acids and

calcium soaps
These soaps have a chalky-white
appearance
Seen in the pancreas following
acute inflammation

Injury

Acute inflammation

Chronic inflammation

Resolution

Repair

 Time course
Acute inflammation: Less than 48 hours
Chronic inflammation: Greater than 48 hours
(weeks, months, years)

Cell type
Acute inflammation: Polymorph-nuclear leukocyte

or neutrophils
Chronic

inflammation:

Mononuclear

(Macrophages, Lymphocytes, Plasma cells).

cells

Pathogenesis: Three main processes occur at the site

of inflammation, due to the release of chemical
mediators :

Increased blood flow (redness and warmth).

Increased vascular permeability (swelling,

pain & loss of function).

Leukocytic Infiltration.

Mechanism of Inflammation
1. Vaso dilatation
2. Exudation - Edema
3. Emigration of cells
4. Chemotaxis

Chronic Inflammation:
An immune reaction to some mild but persistent
antigen producing proliferation of lymphocytes
and/or plasma cells.
There are usually no pain, redness, swelling, or
warmth.

Cells of Chronic Inflammation

Histologically, chronic inflammation includes:
Macrophages, Lymphocytes, and Plasma cells.
Proliferation of fibroblasts and small blood vessels

(revascularization).
Increased connective tissue (fibrosis)
Tissue destruction.

 Multinucleate giant cells: huge cells with many

nuclei formed by fusion of macrophages. They are
associated with foreign materials or accompany reactions
to certain organisms as TB.

Fibroblasts and collagen: Collagen production is a

common feature of chronic inflammation. Chemical
mediators stimulate collagen secreting cells and fibrosis.

Chronic inflammation

Acute inflammation

A: Chronic inflammation in the lung, showing all three characteristic histologic features: (1)
collection of chronic inflammatory cells, (2) destruction of parenchyma (alveoli are replaced
by spaces lined by cuboidal epithelium, arrowheads), and (3) replacement by connective
tissue (fibrosis, arrows).
B: By contrast, in acute inflammation of the lung (acute bronchopneumonia), neutrophils fill
the alveolar spaces and blood vessels are congested.