Cell injury-1
 Cells are constantly exposed to a variety of
stresses.
 At first cells try to adapt themselves to
overcome this stressful condition, but When
stress is too severe or for prolonged duration,
injury results.
Injury of the cell may be;
1. Reversible: if the affected cells recover from
the injury.
2. irreversible: injury: cell may die
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* Causes of cellular injury:
 Physical agents: Hypoxia, mechanical trauma, burns, radiations,
electric shock
 Chemical agents: poisons (toxins), insecticides, alcohol, tobacco.
 Infectious agents: viruses, bacteria, fungi, parasites.
 Immunologic reactions: anaphylaxis, autoimmune disease.
 Genetic derangements: abnormal proteins
(hemoglobinopathies), abnormal or absent enzymes (storage
disorders).
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- The cellular response to injurious stimuli
depends on :
1. Type, duration and severity of injurious agent.
2. The type, status, adaptability of the injured
cell.
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Adaptation
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a. Hyperplasia: increase in cell number e.g.
compensatory hyperplasia of the kidney after
nephrectomy.
b. Hypertrophy: increase in cell size.
Hypertrophy of the left ventricle due to aortic
stenosis of systemic hypertension.
c. Atrophy: decrease in cell number and/ or size
e.g. atrophy of the female breast after
menopause.
d. Metaplasia: change of type of cell to another
type of the same category (epithelial to epithelial
or connective tissue to connective tissue e.g.
squamous metaplasia of urinary bladder
epithelium in case of bilharziasis.
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Reversible cell injury
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* Mechanisms of reversible cell injury:
1. Cell membrane damage: leading to Loss of structural
integrity and Loss of function.
2. Mitochondrial damage: leading to decreased energy
production (decrease ATP).
3. Ribosomal detachment: leading to decreased protein
synthesis.
4. Production of oxygen derived free radicals.
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Hypoxic cell injury
- The most common cause of cell injury.
* Definition: inadequate oxygenation of tissue.
* Causes:
1. Ischemia: decreased arterial blood flow to tissues.
– Most common cause of hypoxia.
– Ex: Atherosclerosis (lesion in intima = atheroma) in coronary
arteries.
2. Hypoxemia: decrease in the amount of oxygen dissolved in
plasma. Seen in: Atelectasis, pulmonary embolus and interstitial
fibrosis of lung.
3. Hemoglobin related abnormalities
– Anemia
– Carbon monoxide poisoning (CO has high affinity for
hemoglobin).
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* Consequences of tissue hypoxia:
•
Decreased synthesis of ATP by oxidative phosphorylation causing ATP
depletion.
•
This leads to;
1. Impaired Na+/K+-ATPase pump:
–
Diffusion of Na+ and water into cells  cellular swelling.
2. Shifting to anaerobic glycolysis: leads to;
•
Accumulation of lactic acid.
•
Decrease in intracellular pH  denaturation of proteins 
decreased activity of many enzymes  clumping of nuclear
chromatin.
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3. Ribosomal detachment:
Leads to decreased protein synthesis.
- ↓protein synthesis leads to ↓ synthesis of
apolipoproteins (lipid carriers in blood)  accumulation
of lipid in the cell (fatty change).
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Ischemia
↓ oxidative phosphorylation
↓↓ ATP
 Na pump
Glycolysis
Influx of Na,
H2O
& Ca2+
Efflux of K
 Lactic acid
Cell Swelling
Nuclear chromatin
clumping
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 pH
Ribosomal Detachment
 Protein
Synthesis
* Morphology of reversible cell Injury:
1. Cell Swelling:
1. The first manifestation of cell injury.
2. Occurs when cells fail to maintain ionic and fluid
homeostasis.
3. Manifests as small clear vacuoles inside the cytoplasm.
4. Also known as hydropic change.
2. Fatty change:
1. Manifested by appearance of lipid vacuoles in the
cytoplasm.
2. Seen in kidney, heart and liver.
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Normal cell
Lysosome
Nucleus
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Endoplasmic
reticulum
Mitochondria
Normal cell
Normal cell
Reversible injury
Injury (hypoxia)
Cell swelling,
Swelling of
ER and
mitochondria
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Recovery
Chromatin
clumping
Cell swelling - Light Microscopy
Cellular Swelling
= hydropic change
Normal
epithelium
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Myocardium: cell swelling= hydropic change
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Normal liver histology
Hepatocytes showing fatty change
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