Cell injury-1

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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

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.

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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.

Hypoxic cell injury

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- 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

Na pump

Influx of Na, H2O

& Ca2+

Efflux of K

Cell Swelling

Glycolysis

Lactic acid

pH

Ribosomal Detachment

ProteinSynthesis

Nuclear chromatinclumping

↓↓ ATP

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* 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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Endoplasmic reticulum

MitochondriaNucleus

Lysosome

Normal cell

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Normal cell Normal cell

Rev

ersi

ble

inju

ry

Injury (hypoxia) Recovery

Cell swelling,Swelling of

ER andmitochondria

Chromatin clumping

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Cell swelling - Light Microscopy

Normal epitheliu

m

Cellular Swelling= hydropic

change

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Myocardium: cell swelling= hydropic change

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Normal liver histology

Hepatocytes showing fatty change

Good luck