Pathology-

Introduction
What is pathology ?

 Pathology is the branch of medical science that

studies the origin, cause, nature, progression,
course and consequence of disease
Importance of studying pathology
 To have an in-depth understanding of pathology in order to
interpret the pathologic basis of diseases and hence to treat
the patients appropriately
 Understanding the cause of the disease
 Knowledge about progression of the disease
 Early and effective diagnosis
 Prevention of the disease
 Helps in effective management and care of patients
Terminologies
 Lesions

An area of abnormal or damaged tissue caused by

injury, infection, or disease.
A lesion can occur anywhere in or on the body,
such as the skin, blood vessels, brain, and other
organs.
 Examples of lesions include wounds, ulcers,
abscesses, sores, cysts, and tumors. A lesion may
be benign (not cancer) or malignant (cancer).
Terminologies

 Etiology; cause

 Pathogenesis: is the mechanism of disease evolution

and progression
 Morphology: is the structural changes in cells and
organs
 Prognosis:
The likely outcome or course of a disease;
the chance of recovery or recurrence.
Cellular adaptation
 Cellular adaptation refers to the ability of cells to
adjust to changes in their environment to maintain
homeostasis.
 When faced with different types of stressors, cells
may undergo various forms of adaptation to survive
and continue functioning.
 These adaptations can be physiological (normal) or
pathological (abnormal) responses to changes such
as increased workload, decreased blood supply, or
chronic irritation.
Types of cellular adaptation
 1. Hypertrophy

• Definition: Increase in cell size, leading to an

increase in the size of the organ.
• Causes: Commonly occurs due to increased
workload or demand. It is often seen in muscle cells,
such as the heart or skeletal muscles.
• Examples: Hypertrophy of the heart muscle due to
high blood pressure or increased muscle size in
bodybuilders.
2. Hyperplasia

• Definition: Increase in the number of cells

in an organ or tissue, leading to an increase
in tissue mass.
• Causes: Usually occurs as a response to a
stimulus and can be hormonal or
compensatory.
• Examples: Hormonal hyperplasia in the
uterus during pregnancy or compensatory
hyperplasia in the liver after partial removal.
3. Atrophy
• Definition: Decrease in cell size, which can result in
a reduction in the size of an organ or tissue.
• Causes: Can occur due to decreased workload, loss
of innervation, diminished blood supply, inadequate
nutrition, or aging.
• Examples: Muscle atrophy due to immobilization
(e.g., wearing a cast) or brain atrophy in Alzheimer’s
disease.
4. Metaplasia

• Definition: Reversible change in which one adult cell

type is replaced by another adult cell type.

• Causes: Often a response to chronic irritation or

inflammation.

• Examples: Squamous metaplasia in the respiratory tract

of smokers, where normal columnar epithelial cells are
replaced by squamous cells.
 5. Dysplasia

• Definition: Abnormal changes in the size, shape, and

organization of mature cells.
• Causes: Often considered a precursor to cancer and
is associated with chronic irritation or inflammation.
• Examples: Cervical dysplasia caused by human
papillomavirus (HPV) infection.
 These adaptations are crucial as they help cells
survive under adverse conditions. However, if the
stressor persists or is too severe, the adaptive
mechanisms may fail, leading to cell injury or death.
Cell injury

 Cell injury: Sequence of events that occurs when

stresses exceed ability of cells to adapt. Responses are
initially reversible, but may progress to irreversible
injury and cell death.
 Cell death: Results when continuing injury becomes
irreversible, at which time the cell cannot recover.
Causes of Cell injury
 Hypoxia
 Hypothermia can mitigate hypoxic injury by decreasing cellular
metabolism and slowing reperfusion
 Ischemia
 Toxin-induced (e.G., Ethanol and cigarette smoking)
 Infectious agents
 Genetic abnormalities
 Aging
 Imbalances in nutrition
 Physical causes (e.g., trauma)
Cell injury can be categorized into reversible and irreversible
types:

 1. Reversible Cell Injury:

• The cell can recover if the harmful stimulus is removed.

• Common features include:
• Cellular swelling: Due to failure of ion pumps, leading to
water accumulation inside the cell.
• Fatty change: Seen in cells that metabolize lipids, such
as liver cells, where fat accumulates within cells.
 2. Irreversible Cell Injury:

• Occurs when the damage is beyond the cell's repair

mechanisms.
• Leads to cell death, either through:
• Necrosis: Uncontrolled cell death, causing
inflammation.
• Apoptosis: Programmed cell death, a controlled
process without inflammation.
 Mechanisms of Cell Injury:

Injury/Stress
↓
Key Mechanisms Activated:
1. ATP Depletion ↓
• Ion pump failure
• Cell swelling
2.Reactive Oxygen Species (ROS) ↓
• Oxidative damage to proteins, DNA, and lipids
3. Calcium Influx ↓
• Activation of damaging enzymes (e.g., proteases, phospholipases)
• Membrane damage
 4. Mitochondrial Damage ↓
• Loss of ATP
• Release of pro-apoptotic factors
5. Membrane Damage ↓
• Loss of cell integrity

 Each of these mechanisms converges toward irreversible

injury and may lead to necrosis or apoptosis depending on
the context of the injury.
Cell death
There are TWO principle types of
cell death:
 1. Necrosis -
 Death of cells in living tissues characterized by the
breakdown of cell membranes. These changes occur
because of digestion and denaturation of cellular
proteins, largely by release of hydrolytic enzymes from
damaged lysosomes.
 There are many subtypes / morphological patterns of
necrosis: Coagulative; Liquefactive; Caseous; ;
 Haemorrhagic; Suppurative; Gangrenous; Fat; Fibrinoid
 2. Apoptosis -
 Defined as programmed cell death characterized by
nuclear dissolution, fragmentation of the cell without
complete loss of membrane integrity, and rapid
removal of the cellular debris.
 Apoptosis can be physiological or pathological
Necrosis
 Necrosis is a form of cell death that occurs when cells are
exposed to severe or prolonged damage, leading to the
uncontrolled breakdown of cellular structures. Unlike apoptosis,
which is a regulated and programmed process, necrosis is often
associated with inflammation and further injury to surrounding
tissues.
Characteristics of Necrosis:

 Uncontrolled Process: Occurs due to severe cell injury.

 Loss of Cell Membrane Integrity: Results in the
leakage of cellular contents into the surrounding tissue.
 Inflammatory Response: The release of cell contents
triggers an inflammatory response in the surrounding
tissue.
 Swelling and Rupture: Cells often swell before
bursting, releasing enzymes that degrade nearby tissue.
Types of Necrosis:

1. Coagulative Necrosis:
o Most common type.

o Often caused by ischemia (lack of blood flow) in solid organs like the heart,
kidneys, or spleen.
o Characterized by firm tissue where the underlying architecture is preserved
for a few days before being broken down.
2. Liquefactive Necrosis:

o Seen in brain infarcts and bacterial infections.

o Enzymatic digestion of cells results in a liquid, viscous mass.
 Oftenforms pus due to the accumulation of dead cells and
enzymes.
3. Caseous Necrosis:
o Seen in tuberculosis and some fungal infections.
o Tissue has a cheese-like appearance (soft and white).
o A mixture of coagulative and liquefactive features.

4. Fat Necrosis:
o Occurs in areas of fatty tissue, such as the pancreas and breast.
o Enzymatic digestion of fat cells leads to the formation of chalky
deposits (soap-like).
 Often seen in pancreatitis due to the release of pancreatic enzymes.
5. Gangrenous Necrosis:
o Typically affects extremities like limbs due to severe ischemia.

o Can be dry or wet:

 Dry Gangrene: Coagulative necrosis with dried, shrunken tissue.

 Wet Gangrene: Superimposed bacterial infection leads to liquefactive

necrosis.

6. Fibrinoid Necrosis:
o Seen in immune-mediated vascular damage (e.g., autoimmune diseases).

o Characterized by the deposition of immune complexes and fibrin-like material

in blood vessel walls.
Pathological Consequences of Necrosis:

 Tissue Damage: Necrosis often results in significant damage to

surrounding tissues.
 Inflammation: Attracts immune cells to the site, which may further
damage surrounding cells.
 Scarring or Fibrosis: Chronic necrosis can lead to the formation of scar
tissue as part of the healing process.
 Necrosis is often associated with pathological
conditions like heart attacks, strokes, infections, and
trauma. Its unregulated nature makes it damaging to
tissues, which can impair organ function and healing.
 Gangrene is a serious condition that occurs when body tissue dies due to a loss of
blood supply or severe infection. It most commonly affects the extremities, such as
toes, fingers, and limbs, but can also occur in internal organs. It results from a
combination of ischemia (lack of blood flow) and infection, leading to tissue necrosis.
Types of Gangrene:

1. Dry Gangrene:
o Occurs due to a gradual reduction in blood flow to an area, often from
conditions like atherosclerosis (narrowing of arteries).
o The tissue becomes dry, shrivelled, and dark brown or black.
o The affected area often has a clear line of demarcation between healthy and
dead tissue.
o Common in patients with diabetes, peripheral arterial disease, or frostbite.
o Usually does not involve bacterial infection.
o Progresses slowly and is less likely to cause sepsis compared to other types.
2. Wet Gangrene:
o Occurs when there is a sudden loss of blood flow to a tissue, usually
accompanied by a bacterial infection.
o Tissue appears swollen, soft, and may produce a foul odor due to
bacterial growth.
o Often results from severe burns, injuries, or infections.
o Rapidly spreads and can lead to sepsis (a life-threatening systemic
infection).
o Requires immediate medical intervention, such as antibiotics and
surgical removal of the affected tissue.
3. Gas Gangrene:
o Caused by infection with certain types of bacteria, particularly
Clostridium species.
o Bacteria produce gas and toxins within the infected tissue.
o Affected area may appear swollen and crackle when touched due to
gas bubbles beneath the skin.
o Progresses quickly, leading to tissue death and systemic infection.
o Requires prompt treatment, including antibiotics, surgical removal
of dead tissue, and sometimes hyperbaric oxygen therapy to inhibit
bacterial growth.
4. Internal Gangrene:
o Affects internal organs such as the intestines, gallbladder, or
appendix.
o Occurs when blood flow to an internal organ is blocked, often due
to a hernia, blood clot, or bowel obstruction.
o Symptoms may include severe pain, fever, and swelling.
o Can be life-threatening and usually requires emergency surgery.
5. Fournier’s Gangrene:
o A rare but severe form of wet gangrene that affects the genital
area, perineum, and sometimes the lower abdomen.
o It is more common in men and associated with diabetes or immune
suppression.
o Rapidly progressive and requires aggressive treatment with
antibiotics and surgical removal of infected tissue.
Inflammation
Inflammation

 Inflammation is a natural biological response by the

body's immune system to harmful stimuli such as
pathogens (e.g., bacteria, viruses), damaged cells, or
irritants. It serves as a protective mechanism aimed at
removing harmful agents and initiating tissue repair.
 Inflammation can be categorized into two main types:
acute and chronic.
Acute inflammation

 Acute inflammation is the body's initial response to harmful stimuli, such as

infection or injury. It is a protective mechanism that aims to eliminate the
cause of cell injury, clear out damaged cells, and initiate the process of tissue
repair. Acute inflammation is characterized by rapid onset and relatively short
duration, typically lasting from a few minutes to a few days.
Stages of Acute Inflammation:
 Acute inflammation involves both vascular events and
cellular events, which work together to combat
infection or injury and promote tissue repair.
 1. Vascular Events in Acute Inflammation:
 These events involve changes in the blood vessels at the site of injury or
infection, primarily to increase blood flow and allow immune cells and proteins
to reach the affected area.
 Vasodilation:
o Initiated by chemical mediators like histamine and nitric oxide.
o Causes the widening of blood vessels (arterioles), leading to increased
blood flow to the site of injury.
o Results in redness (rubor) and heat (calor).
 Increased Vascular Permeability:
o The blood vessels become more permeable, allowing plasma
proteins and fluid to leak into the tissue.
o This leakage contributes to swelling (tumor) or edema in the
affected area.
o Mediators like histamine, bradykinin, and leukotrienes
contribute to this increased permeability.
 Exudation:
o The fluid that leaks out is rich in proteins, antibodies, and immune
cells.
o The exudate helps dilute toxins and delivers immune cells to the
site.
o This can result in pain (dolor) due to the increased pressure on
nerve endings.
 Stasis:
o As fluid leaves the blood vessels and enters the tissue, the flow of
blood slows down in the vessels.
o This slowdown allows leukocytes (white blood cells) to come into
contact with the blood vessel walls, facilitating their movement
out of the bloodstream into the affected area.
 Cellular Events in Acute Inflammation:

 These events focus on the recruitment, activation, and action of immune cells, particularly
leukocytes, which help to clear the injury or infection.

 Leukocyte Recruitment:

o Margination: Due to stasis, leukocytes move closer to the blood vessel walls.

o Rolling: Leukocytes roll along the inner surface of the blood vessels, slowed down by
selectin molecules on endothelial cells.
o Adhesion: Integrins on leukocytes bind tightly to adhesion molecules (like ICAM-1) on
endothelial cells, causing the leukocytes to adhere firmly to the vessel wall.
o Diapedesis (Transmigration): Leukocytes squeeze through the gaps between
endothelial cells to exit the blood vessel and enter the tissue.
Chemotaxis:
o After exiting the bloodstream, leukocytes move toward the
site of injury or infection in response to chemotactic signals.
o These signals include chemokines, bacterial products, and
complement fragments (e.g., C5a).
o Chemotaxis ensures that immune cells reach the exact
location of the threat.
 Phagocytosis:

o Neutrophils and macrophages are the primary phagocytic cells involved in acute
inflammation.
o The steps of phagocytosis include:

 Recognition and Attachment: The immune cells recognize pathogens or debris

through opsonins (like antibodies or complement proteins).
 Engulfment: The leukocyte surrounds the target, engulfing it into a phagosome.
 Killing and Degradation: The phagosome fuses with lysosomes, forming a
phagolysosome that uses enzymes and reactive oxygen species (ROS) to destroy the
ingested material
 Release of Inflammatory Mediators:

o Activated immune cells release cytokines (e.g., IL-1, TNF-α),

prostaglandins, and leukotrienes.
o These mediators amplify the inflammatory response, recruit more
leukocytes, and help to eliminate the source of injury.
Interaction Between Vascular and Cellular Events:

 The vascular changes create the conditions needed for leukocytes to migrate
from the bloodstream into the tissue.
 Increased permeability allows proteins and complement to enter the tissue,
supporting leukocyte action.
 Leukocytes then follow chemotactic signals and use the increased vascular
permeability to reach the area of injury or infection more effectively.
 These coordinated vascular and cellular events are crucial for the rapid
response of acute inflammation, aiming to neutralize the injurious agent,
limit tissue damage, and initiate the repair process.

 However, if these processes are excessive or poorly regulated, they can

contribute to further tissue injury and inflammation.

Clinical manifestations of Acute Inflammation:

1. Rapid Onset: Begins quickly after injury or infection.

2. Short Duration: Lasts from a few minutes to a few days.

3. Cardinal Signs: The classic signs of acute inflammation are:

o Redness (Rubor): Due to increased blood flow to the area.

o Heat (Calor): Resulting from increased blood flow and local metabolic activity.

o Swelling (Tumor): Due to the accumulation of fluid (edema).

o Pain (Dolor): Caused by the release of chemicals like prostaglandins and

bradykinin.
o Loss of Function (Functio Laesa): Swelling and pain may restrict movement and
function.
Effect of Acute Inflammation:

1. Resolution:
o Complete healing and restoration of normal tissue architecture.

o Occurs when the injury is mild and the body can eliminate the cause quickly.

2. Suppuration (Formation of Pus):

o Accumulation of dead neutrophils, bacteria, and tissue debris.

o Leads to abscess formation, which may need drainage for healing.

3. Chronic Inflammation:
o If the injurious stimulus persists, acute inflammation can evolve into
chronic inflammation.
o Characterized by a longer duration and involvement of different immune
cells, like macrophages and lymphocytes.
4. Fibrosis:
o When there is significant tissue damage, healing may occur through scar
formation.
o Fibroblasts deposit collagen, which replaces normal tissue with fibrous
tissue.