1. Hypoxia (lack of oxygen

2. Physical agents

3. Chemical agents and drugs

4. Biologic agents

5. Immunologic reactions

6. Genetic derangements

7. Nutritional imbalance

1. ATROPHY

Decrease in size and function of a cell. The decrease in structural components of the cell (decrease of mitochondria, myofilaments, endoplasmic reticulum) causes shrinkage in cell size. If many cells are involved, atrophy of tissues or organs ensues.

Etiology: Decrease in: workload, innervation, blood supply, nutrition, endocrine stimulation. Prolonged pressure in inappropriate locations. Aging

Pathogenesis: not well understood: decreased protein synthesis, increased catabolism.

Increase in size of cells. If many cells are involved, increase in size of tissue or organ ensues. Increased synthesis of structural components (more RNA synthesis, protein synthesis, mitochondria, myofibrils). Stress results in increased signals followed by upregulated gene expression and increase in size.

Etiology: Physiologic. Pathologic

Increase in the number of cells: cells divide more.

Etiology: Physiologic. Pathologic

Change from one adult cell type (epithelial or mesenchymal) to another adult cell type. The most common case is glandular epithelium replaced by squamous. The change is reversible if injury stops.

Change characterized by proliferation and cell alterations (size and shape), so that the regular arrangement of cells within a tissue is altered. Cells vary in size, shape, size of nuclei, chromatin density. Occurs most commonly in hyperplastic squamous epithelium (e.g. actinic keratosis caused by exposure to sunlight) and in areas of squamous metaplasia (bronchus, cervix).

Reversible lesions are caused by brief injury (and/or lesser intensity of injury). When the stress disappears, the cell returns to its normal state.

Morphology:

Light microscopy: Cellular swelling. Fatty change. Hyaline droplet formation, glycogen depletion, various accumulations in the cell.

Electron microscopy: Alterations of plasma membrane: cell swelling, blebs. Mitochondrial changes: swelling, densitities (calcium). Endoplasmic reticulum: dilated, detachment of ribosomes, development of small inclusions (liposomes). Nucleus: clumping of chromatin to nuclear membrane

Irreversible lesions are caused by severe injury and/or longer duration of injury ---> cell death.Two patterns of cell death can be observed: necrosis and apoptosis.

a. Necrosis: Cytoplasmic and nuclear changes

Types of necrosis:

Coagulation necrosis (coagulative necrosis). Liquefaction necrosis (liquefactive necrosis). Fat necrosis. Caseous necrosis. Gangrenous necrosis. Fibrinoid necrosis

b. Apoptosis: Cytoplasmic and nuclear changes

It is observed when cell death is part of organized tissue reactions in: Embryogenesis, metamorphosis. Endocrine-dependent tissue atrophy. Regressing tumors. In lymphoid organs. Immunologically mediated killing

The situation may not be so stereotyped: Mild degrees of hypoxia, toxic injury, heat shock may cause apoptosis. More severe degrees result in necrosis

PATHOGENESIS (mechanisms) OF CELL INJURY

1. Mechanism of necrosis: They include release of lysosomal enzymes (this occurs at later stages of injury), generation of toxic oxygen radicals (superoxide, hydrogen peroxide), depletion of cellular ATP (this occurs but does not induce death in the absence of extracellular Ca2+), activation of calcium-dependent phospholipases (movements of Ca2+ activate endogenous, membrane bound, Ca2+ dependent phospholipases, causing lethal disruption of cellular membranes by both direct enzyme action and the detergent action of accumulated fatty acylesters).

2. Mechanisms of apoptosis: Apoptosis is characterized by endogenous endonuclease activation. For these reasons, apoptosis is also called "programed cell death" or "cellular suicide" because it results from the induction of active processes within the cell.

Intracellular storage of lipids, proteins, glycogen, pigments

Deposition of calcium salts intra- and extra-cellular.

a. Dystrophic

b. Metastatic

Amyloid is a fibrillar substance:

1. AL amyloid light chain derived from immunoglobulin (Ig) light chains (e.g., in multiple myeloma)

2. AA (amyloid associated), non Ig, synthesized by liver (secondary amyloidosis, e.g., in chronic inflammation, as observed in rheumatoid arthritis)