LECTURE #2: CELL INJURY, CELL DEATH, AND ADAPTATIONS

1. Cause (etiology)

2. Biochemical, molecular mechanisms of its development (pathogenesis)

3. Structural alterations induced in cells and organs (morphologic changes)

4. Consequences of changes (clinical manifestations)

FOUR ASPECTS OF DISEASE

Hypertrophy

Increase in size of cells

Hyperplasia

Increase in number of cells

Atrophy

Decrease in size of cells

Metaplasia

Change in phenotype of cells. One cell type is replaced by another cell type

1. Oxygen deprivation

2. Physical agents: trauma burns temperature radiation, electric shock

3. Chemicals and Drugs

4. Infectious agents

5. Immune reactions

6. Genetic

7. If limits of adaptive response is exceeded then there is cell injury

8. Cell injury is reversible up to a certain point.

9. If stimulus is severe or prolonged enough there is irreversible injury and ultimately cell death.

CAUSES OF CELL INJURY:

Cellular Swelling, Fatty Change

RESERVABLE INJURY:

Two features seen under light microscope

Necrosis, Apoptosis

CELL DEATH

TWO TYPES

NECROSIS

Unregulated death. Cell contents leak out and illicit inflammation

APOPTOSIS

Programed cell death. Maybe physiological. Nuclear dissolution and fragmentation without loss of membrane integrity.

TISSUE PATTERNS OF NECROSIS

1. Coagulative Necrosis

2. Liquefactive Necrosis

3. Gangrenous Necrosis

4. Caseous Necrosis

5. Fat Necrosis

6. Fibrinoid Necrosis

COAGULATIVE

• Architecture if dead cells is preserved.

• Tissue exhibit firm texture

LIQUEFACTIVE

• Dead cells are digested resulting into liquid viscous mass

• Common in Central Nervous system

CASEOUS

Cheese like, Tuberculosis. Microscopic amorphous granular debris

FAT NECROSIS

Areas of fat destruction. Acute pancreatitis

FIBRINOID NECROSIS

Special form of necrosis usually seen in immune reactions involving blood vessels.

Apoptosis, Causes - Physiologic

• Destruction during embryogenesis

• Involution of hormone dependent tissues upon withdrawal

• Cell loss in Proliferative cell populations

• Eliminating self-reactive lymphocytes

Apoptosis, Causes - Pathologic

• DNA damage: anticancer drugs

• Accumulating misfolded proteins

• Infections

• Pathologic atrophy in organs after obstruction

Apoptosis, Morphological Changes

• Cell shrinkage

• Chromatin condensation: most characteristic feature

• Formation of cytoplasmic blebs and apoptotic bodies

• Phagocytosis of apoptotic bodies by macrophages

PATHOLOGICAL CALCIFICATION

Abnormal tissue deposition of calcium salts, small amounts of iron, magnesium, and other mineral salts.

• Dystrophic Calcification

• Metastatic Calcification

Two forms of pathologic calcification:

Dystrophic Calcification

• Encountered in areas of necrosis

• Seen in damaged heart valves, atherosclerosis

• Serum calcium is normal

Metastatic Calcification

Occurs in normal tissues whenever there is hypercalcemia

• Increased Parathyroid Hormone Levels

• Reabsorption of Bone due to Bone Tumors

• Vitamin D related disorders

• Renal Failure

Four principal causes of hypercalcemia: