Cell injury and cell adaptation--Mbbs / Bams 2nd year Pathology topic

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QUADRA INSTITUTE OF AYURVEDA
DEPARTMENT OF ROG NIDAN EVUM
VIKRATI VIGYAN
CELL INJURY
GUIDED BY
DR. MAYANK BISHNOI
[ H.O.D & ASSOCIATE PROFESSOR ]
DR. HIMADRI
[ ASSISTANT PROFESSOR ]
SUBMITTED BY
KRITIKAAGARWAL
BAMS [ 2021-26]

2. EDITED BY HKS 2
Outline

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Normal Cellular
Function
Metabolism
Protein Synthesis
Cell Division
Respiration
Ion Transport
Structural Support
Protection
Selective Barriers
Remember, understanding normal cellular
function is crucial for recognizing
deviations (such as cell injury) and
maintaining overall health

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Cell Injury
▪ Cell injury is defined as the effect of a
variety of stresses due to etiologic agents
a cell encounters resulting in changes in
its internal and external environment. In
general, cells of the body have inbuilt
mechanism to deal with changes in
environment to an extent.
▪ The cellular response to stress may vary
and depends upon following two
variables:
1. Host factors i.e. the type of cell and
tissue involved.
2. Factors pertaining to injurious agent i.e.
extent and type of cell injury.

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ETIOLOGY OF CELL INJURY
The cells may be broadly injured by two major ways:
• A. Genetic causes
• B. Acquired causes
The acquired causes of disease comprise vast majority of common diseases afflicting mankind. Based on underlying
agent, the acquired causes of cell injury can be further categorised as under:
• 1. Hypoxia and ischemia
• 2. Physical agents
• 3. Chemical agents and drugs
• 4. Microbial agents
• 5. Immunologic agents
• 6. Nutritional derangements
• 7. Ageing
• 8. Psychogenic diseases
• 9. Iatrogenic factors
• 10. Idiopathic diseases.

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Hypoxia and ischemia
Hypoxia :
Due to inadequate oxygenation of tissue.
Ischemia :
Decreased blood flow . It may be due to
thrombosis, embolism, atherosclerosis or
external compression of vessel.
Causes of hypoxia :
• Inadequate oxygenation of the blood
(hypoxemia)
– Due to pulmonary disease.
– Decreased perfusion of tissues ( cardiac failure,
hypotension shock) .
– Decreased oxygen-carrying capacity of the
blood ( anemia ).
– Severe blood loss.
Mechanism of injury:
Hypoxia causes cell injury by reducing aerobic oxidative respiration and decreasing the
synthesis of ATP.
Outcome:
Depending on the severity of the hypoxia, cells may adapt, undergo injury, or die.

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Different stages of cellular responses to stress/injury

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Cellular adaptation
Atrophy
Absence of growth
Associated with decrease size and decrease function
Hypertrophy
Increase size of cells leads to increase function of cells
Hyperplasia
Increase in number of cells
Metaplasia
Change in nature of cells in presence of stress factor.
A. Epithelial metaplasia In lungs smoking leads to squamous metaplasia (commonest example).
Ciliated columnar → squamous epithelium
B. Connective tissue metaplasia Myositis ossificans - after trauma due to haemorrhage the muscle is replaced by bone like tissue
Dysplasia
Disordered cell growth.
E.g. HPV infection in cervical epithelium → Mitosis occur
throughout the epithelial thickness with altered N: C ratio.

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Cellular adaptation

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REVERSIBLE CELL INJURY
Most common cause of cell injury at the level of cell → Hypoxia (↓↓ 02)
↓02 - Mitochondrial activity↓↓ - Cellular manifestations occur
A. Cell membrane:
• ATP↓ - Na+ accumulation (as Na-K Pump activity) - ↑water
(Hydropic Changes).
• Hydropic change (Cell swelling) is the 1st microscopic change.
• Outpouching occurs - Membrane blebs Formation.
B. Endoplasmic reticulum:
• Due to ↓ ATPs in Cell - ↓ RER activity→↓ Protein synthesis
• ATP degradation results in activity of SER - ↑↑ misfolded protein
accumulation
C. Nuclear changes:
• Clumping of chromatin.
• Due to excess H2O in cells, a part of Membrane from cell
organelle or cell membrane curling upon itself Appear as spiral
structure known as Myelin Figures

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IRREVERSIBLE CELL INJURY
Persistent hypoxia → decrease mitochondrial function → ↓↓↓ ATP leads to ↑↑ Ca² inside cell.
Increase calcium causes
1. Mitochondrial dysfunction:
• Mitochondrial/amorphous densities
• It leads to further decrease in concentration of
ATPs and the cycle continues.
2. Enzymes activation:
• Lysosomal enzymes → Autolysis (cell death)
• Phospholipase → Cell membrane damage
• Nucleases → Nuclear changes occur:
a. Nucleic acid condensation → Pyknosis (Ink-
dot nucleus)
b. Nucleic acid material fragment → Karyorrhexis
c. Complete breakdown of nuclear material →
Karyolysis (Nucleus disappear)

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Severity of nuclear damage
Normal cell Pyknosis
( Condensation and
clumping )
Karyorrhexis
( Fragmentation )
Karyolysis
( Dissolution )

13. If the cell is exposed to continuous injurious stimulus or if the injury
is severe, the cells undergo cell death.
Types of Irreversible Cell Injury
NECROSIS
Necrosis is defined as a localised area
of death of tissue followed later by
degradation of tissue by hydrolytic
enzymes liberated from dead cells; it is
invariably accompanied by
inflammatory reaction.
APOPTOSIS
Apoptosis is a form of ‘coordinated and
internally programmed cell death’
having significance in a variety of
physiologic and pathologic conditions .
Unlike necrosis, apoptosis is not
accompanied by any inflammation and
collateral tissue damage.
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NECROSIS
Morphological changes indicative of cell death in
a living tissue following harmful injury.
Necrosis is an “accidental” and unregulated form
of cell death.
Based on etiology and morphologic appearance,
there are 5 types of necrosis:
1. Coagulative necrosis
2. liquefaction (colliquative) necrosis
3. Caseous necrosis
4. Fat necrosis
5. fibrinoid necrosis.

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Types of Necrosis
1. Coagulative necrosis
• Most common type of necrosis.
• Most common cause ischemia
• Seen in all organs of the body except CNS.
• Neutrophilic infiltration seen in coagulative
necrosis.
• TOMBSTONE APPEARANCE (preservation
of cell outlines ) present.
Features seen.
• Increased Eosinophilia
• "Moth eaten" cytoplasm
• Glassy appearance
• Nucleus disappear

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Types of Necrosis
2. Liquefactive necrosis
(aka Colliquative necrosis)
• Hydrolytic enzyme activation leads to
damage to tissue structure.
• Seen with CNS ischemia and in
pancreas
• Tissue Architecture --> not present

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Types of Necrosis
3. Caseous necrosis
• It is like cheese-like necrotic
material.
• Combination of Coagulative necrosis
+ Liquefactive necrosis, but
coagulative necrosis is the most
predominant contributor.
• Found in Tuberculosis (due to Mycolic acid), fungal infection like
(histoplasmosis, coccidioidomycosis = valley fever) & syphilis.
• Granulomatous reaction is present.
• Macrophages (form Granuloma) & lymphocytes infiltration seen.
• Langerhans giant cells are associated with tubercular focus.

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Types of Necrosis
4. Fat necrosis
• Found in organs with excess fats (Non-
enzymatic) or with increased
concentration of lipases (Enzymatic).
• Found in injury to breast tissue or injury
to omentum tissue and pancreatitis.
• Appearance → Chalky white
Acute pancreatitis
• Gallstones or alcohol Lipase activation → lipids broken down into fatty acid.
• With Ca2+, Fat can form Chalk-like deposits.
• Fatty acid combines with Ca²+ → Serum Ca2+ level drops & it is an important prognostic factor to know the
severity of pancreatitis.
In Pancreatitis: 2 types of necrosis
1) Pancreas - Liquefactive necrosis.
2) Peri pancreatic fat - Fat necrosis.

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Types of Necrosis
5. Fibrinoid Necrosis
• Endothelial cell injury leads to immune complex
formation, damage to endothelial cells and deposition of
plasma protein in the vessels wall.
• Seen in Malignant hypertension , Rheumatic heart disease
, Immune complex disorder (or Type 3 hypersensitivity
reaction)
• Appearance → pink coloured fibrin like material is
deposited in the vessel wall

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Types of Necrosis
Characteristics Dry Wet
General features
Common site Limbs Bowels
Examples Gangrene due to
atherosclerotic narrowing
of blood vessel of lower
limb
Volvulus, intussusception
Etiological factors
Cause of ischemia Arterial obstruction Commonly venous
obstruction
Rate of obstruction Slow Abrupt
Gross features
Appearance of involved
part
Shriveled dry
(mummification) and
black
Swollen, soft and moist
Line of demarcation Clear cut Not clear cut
Spread Slow Rapid
6. Gangrene (Gangrenous Necrosis)
Types: Two types, namely dry and wet gangrene
❑ Gas gangrene
• Special type of wet gangrene caused by infection
with a gas forming anaerobic clostridia.
• These organisms enter into the tissues through open
contaminated wounds

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Apoptosis
Apoptosis is a type of caspade dependent
(programmed) cell death induced by a tightly regulated
suicide program.
Causes of Apoptosis
Apoptosis may be physiological or pathological.
Salient features of apoptosis
• Cell size decrease
• Chromatin condensation (HALLMARK)
• Inflammation ABSENT
• Gel electrophoresis → Step Ladder Pattern

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Causes of Apoptosis
Physiological Situations
• Removal of excess cells during embryogenesis
and developmental processes: For example,
disappearance of web tissues between fingers and
toes.
• Elimination of cells after withdrawal of
hormonal stimuli: For example, endometrial cell
breakdown during the menstrual cycle.
• Elimination of potentially harmful cells: In
immunology, the clones of self-reactive
lymphocytes that recognize normal self antigens
are deleted by apoptosis.

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Causes of Apoptosis
Pathological apoptosis
• DNA damage
• Viral infection of hepatitis - councilman body
• Accumulation of misfolded proteins -
Alzheimer's, Parkinson disease
• Duct obstruction → Atrophy

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Conclusion
▪ Overall cellular injury is the changes in structure and function of cells in the
human body. Thus, cellular injury provide clue to pathologists in
diagnosing of the disease.
▪ Knowledge about injury at the sub cellular organelle and molecular levels
is essential for development of new therapeutic strategies.

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