Cell Injury and Adaptation

Cell Injury Definition

• Cell injury is the effect of various stresses from etiologic agents on a cell.
• Cell injury leads to changes in a cell's internal and external environment.

Cell Response to Stress

• With increased functional demand, cells may adapt and revert to normal when the stress is removed.
• With mild to moderate stress, cells may recover, resulting in reversible cell injury.
• Persistent and severe cell injury can cause cell death, leading to irreversible cell injury.

Cell Adaptations

• Atrophy involves decreased cell size.
• Hypertrophy involves increased cell size.
• Hyperplasia involves increased cell number.
• Metaplasia is the conversion of one cell type to another.
• Dysplasia is the term for the presence of disorderly growth.

Causes of Cell Injury

• Genetic factors include developmental defects and chromosomal abnormalities.
• Acquired factors can also cause cell injury.

Acquired Causes of Cell Injury

• Ischemia is a reduced blood supply.
• Hypoxia is a reduced oxygen supply.
• Physical agents can cause cell injury and include:
  • Mechanical trauma.
  • Excessive heat or cold.
  • Electricity.
  • Radiation.
  • Rapid changes in atmospheric pressure.
• Chemical substances such as:
  • Cyanide.
  • Arsenic.
  • Mercury.
  • Strong acids and alkalis.
  • Environmental pollutants.
  • Alcohol.
• Microbial agents, including bacteria, viruses, fungi and parasites.
• Immunological agents like hypersensitivity reactions and autoimmune diseases.
• Nutritional factors, including deficiencies and excesses.

Reversible Cell Injury: Morphologic Forms

• Hydropic change
• Fatty change
• Hyaline change
• Mucoid change

Hydropic Change

• Represents the earliest form of injury from almost all causes.
• Bacterial toxins, chemicals, poisons, burns and high fever may induce it
• Organs involved: kidney, liver and pancreas.

Fatty Change

• Involves the accumulation of neutral fat within parenchymal cells.
• Organs involved: liver, heart, skeletal muscle and kidney
• Etiology of fatty liver:
  • Hyperlipidaemia
    • Obesity
    • Diabetes mellitus
    • Congenital hyperlipidaemia
  • Liver cell damage
    • Alcoholic liver disease
    • Starvation

Hyaline Change

• Involves the deposition of glassy, homogenous material.
• Types:
  • Intracellular
    • Renal tubules
    • Hepatocytes with Mallory hyaline
    • Viral infections
  • Extracellular
    • Leiomyoma of uterus
    • Old scar of fibrocollagenous tissue

Necrosis

• Necrosis is a localized area of tissue death followed by degradation by hydrolytic enzymes from dead cells.
• It is invariably accompanied by an inflammatory reaction.
• Causes:
  • Hypoxia which is the most common cause, leading to ischemia.
  • Physical injury.
  • Chemical injury.
  • Microbial toxins.

Types of Necrosis

• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fat necrosis/adipocytic necrosis
• Fibrinoid necrosis

Coagulative Necrosis

• Architecture of dead tissue is preserved for days.
• Example: solid organ infarcts, except in the brain.

Liquefactive Necrosis

• Necrotic tissue liquefies into a viscous liquid.
• Shape is not maintained
• Example: brain infarct

Caseous Necrosis

• A combination of coagulative and liquefactive necrosis.
• Characteristic of granulomatous inflammation from tuberculous or fungal infections.
• Examples: tuberculosis, histoplasmosis and nocardia infection

Fat Necrosis

• Also known as adipocytic necrosis.
• Occurs in fatty tissue.
• Grossly visible as chalky white areas.
• Most commonly seen in the pancreas, breast and omentum.

Fibrinoid Necrosis

• A special form of vascular damage usually seen in immune-mediated tissue injury.
• Associated conditions include hypertension, peptic ulcer, polyarteritis nodosa, rheumatic carditis and hyperacute graft rejection.
• Fibrin, or fibrin-like material, is deposited in the tissue.

Gangrene

• Gangrene is tissue necrosis associated with superadded putrefaction.
• There are 2 main types of gangrene: dry and wet
• Gas gangrene is a variant of wet gangrene

Dry Gangrene

• Begins in the distal part of a limb due to ischemia.
• A typical example is dry gangrene in the toes and feet from severe atherosclerosis.
• Spreads slowly upwards until it reaches adequate blood supply.
• A line of separation forms to delineate the gangrenous and viable parts.

Wet Gangrene

• Occurs in naturally moist tissues and organs such as the bowel, lung, mouth, cervix and vulva.
• Other examples:
  • Diabetic foot from high glucose content in necrotic tissue, this supports bacteria growth.
  • Bed sores in bed-ridden patients due to pressure on the sacrum, buttocks and heel.
• Toxic bacterial products are absorbed, causing septicaemia and death.
• Spreading wet gangrene lacks a clear-cut demarcation line.

Gas Gangrene

• A special form of wet gangrene caused by gas-forming clostridia.
• Clostridia enters tissues through open contaminated wounds, especially in muscles, or as a complication of colon surgery.
• The affected area is swollen, oedematous painful and crepitant due to carbon dioxide accumulation.
• Carbon dioxide is formed by the fermentation of sugars by bacterial toxins.

Pathologic Calcification

• Deposition of calcium salts in tissues other than osteoid or enamel.
• Types: dystrophic and metastatic.
• Special stains: von-kossa which stains black and alizarin red S which stains red.

Dystrophic Calcification

• Serum calcium levels are within normal limits.
• Calcification occurs in dead tissue.
• Occurs in degenerated tissue such as in tuberculosis, abscess, fat necrosis, infarcts, thrombi, hematoma, dead parasite and breast cancer.

Metastatic Calcification

• Occurs in normal tissue due to hypercalcemia.
• The causes of hypercalcaemia include:
  • Excessive mobilization of calcium from bone.
  • Hyperparathyroidism
  • Bony destructive lesions.
  • Prolonged immobilization.