Cell Injury and Free Radical Mediation

Free Radical Mediation of Cell Injury

• Free radicals are unstable molecules with an unpaired electron.
• They readily react with organic and inorganic chemicals.
• Free radicals are implicated in chemical, radiation, and oxygen toxicity, cellular aging, microbial killing, inflammatory damage, and tumor killing.
• They are generated during normal physiological processes and by exposure to radiation and certain chemicals.
• Free radical generation occurs through the reduction of oxygen, enzymatic catabolism, absorption of radiant energy, and reactions with metals like copper and iron.
• Free radicals can damage lipid, DNA, and proteins.

Reversible Cell Injury

• Light microscopic changes include cell swelling, cytoplasmic eosinophilia, and fatty change.
• Ultrastructural changes involve the plasma membrane, mitochondria, endoplasmic reticulum, and nucleus.

Necrosis

• Characterized by morphological changes that follow cell death.
• Manifestations result from enzymatic digestion and protein denaturation.
• Types include coagulative, liquefactive, gangrenous, caseous, and fat necrosis.

Coagulative Necrosis

• Cell structure is preserved, but enzymes are denatured.
• Common in myocardial infarction.
• Occurs in hypoxic tissues except the brain.

Liquefactive Necrosis

• Results from bacterial or fungal infection.
• Occurs in the CNS due to hypoxia.
• Leads to the formation of a liquid mass.

Gangrenous Necrosis

• Ischemic coagulative necrosis with superimposed infection.
• Often referred to as "wet gangrene".

Caseous Necrosis

• Characterized by a cheese-like appearance.
• Seen in tuberculosis.
• Microscopically composed of granular debris within granulomatous inflammation.

Fat Necrosis

• Caused by the release of pancreatic enzymes.
• Occurs in the peritoneum following pancreatitis.
• Leads to the hydrolysis of triglyceride esters within fat cells.

Apoptosis

• Programmed cell death.
• Seen in physiological and pathological conditions.
• Apoptosis involves single cells or clusters of cells and can be initiated by withdrawal of growth factors, engagement of specific receptors, injury, and intrinsic protease activation.

Intracellular Accumulations

• Normal cells may accumulate abnormal substances.
• Accumulations can be normal endogenous substances, abnormal endogenous substances, or abnormal exogenous substances.
• Accumulations may be harmful or injurious.

Fatty Change (Steatosis)

• Accumulation of triglycerides within cells.
• Most commonly seen in the liver, although it can occur in other organs.

Cholesterol and Cholesterol Esters

• Accumulation can lead to fatty cells, atherosclerosis, and xanthomas.

Proteins

• Uncommon accumulation, but can be observed in glomerular diseases.

Glycogen

• Accumulates in cases of abnormal glucose or glycogen metabolism.

Pigments

• Colored substances either exogenous or endogenous.
• Examples include melanin, hemosiderin.

Pathologic Calcification

• Abnormal deposition of calcium salts.
• Dystrophic calcification occurs in dead or dying tissues.
• Metastatic calcification occurs in normal tissues due to hypercalcemia.

Cell Adaptations of Growth and Differentiation

• Cells adapt to changes in their environment.
• Physiological adaptations are responses to hormones or endogenous chemicals.
• Pathological adaptations are often responses to stress or injury.

Atrophy

• Shrinkage in cell size.
• Can involve the entire organ.
• Causes include decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, and aging.

Hypertrophy

• Increased cell size.
• Results from increased synthesis of structural proteins and organelles.
• Associated with increased workload.