Cell Injury PDF

Cell injury Intended learning objectives Define homeostasis and cell injury List causes of cell injury. What are types of cell injury. Explain fatty change Analyze the mechanisms of hemochromatosis and pathologic calcification Describe amyloidosis, necrosis and apoptosis ...

Cell injury Intended learning objectives Define homeostasis and cell injury List causes of cell injury. What are types of cell injury. Explain fatty change Analyze the mechanisms of hemochromatosis and pathologic calcification Describe amyloidosis, necrosis and apoptosis  Cell injury Homeostasis: is the ability of the cells to adjust their functions with different environmental stress. Cell injury: is a condition when the changes in the environmental stress exceed the ability of the cell to adapt. Causes of cell injury (Stress): - Hypoxia: chronic heart failure and anemia. - Physical agents: trauma and burns. - Chemical agents: poisons and industrial chemicals. - Inflammation: bacteria and viruses. - Antigen-antibody reaction. - Genetic abnormality: gene mutations. - Nutritional imbalances: deficiencies of vitamins.  Types of cell injury - Reversible cell injury (degeneration): they are pathological changes in which the cells can return to normal state when the stimulus stops. Degeneration: It is a reversible deterioration in the cell function leads to change of tissue to less functionally active one. - Irreversible cell injury: The injury cannot adapt by the cells and the cells cannot return to normal state. Irreversible injuries lead to cell death either by necrosis or apoptosis.  Fatty change (steatosis) Definition: It is a reversible intra-cytoplasmic accumulation of triglycerides either due to excessive entry or defective metabolism and release. Sites: liver, heart, muscles and kidney. Causes: Alcohol- Diabetes- Obesity  Fatty change (steatosis) Gross picture: The organ is enlarged, yellow, soft and greasy. Microscopically: H&E stain: The affected cells appear vacuolated. The fat droplets push the nucleus to one side giving signet ring appearance. Complications: fatty change is a reversible condition but it can lead to inflammation and fibrosis. Fatty change  Primary hemochromatosis (Bronzed diabetes) Definition: iron overload due to an inborn error characterized by increase absorption of dietary iron. It mainly affects males and is rare in females (due to physiological loss of iron in menses and pregnancies). Sites: The pigment is deposited in the cells of liver, pancreas, heart and skin. Gross: the organs appear enlarged, brown and hard. Microscopically: the affected cells undergo necrosis and fibrosis. Effects: Liver: cirrhosis and liver cell carcinoma. Pancreas: fibrosis replaces islet cells leads to diabetes mellitus. Heart: fibrosis leads to heart failure. Skin: bronzed color due to increased melanin and hemosiderin deposition.  Pathological calcification: Abnormal soft tissue deposition of calcium salts. 1- Dystrophic calcification: Definition: it is calcification of dead or damaged tissues in spite of a normal blood calcium level. Psammoma bodies: single necrotic cells around which calcium is deposited. Psammos is Greek for sand. Psammoma bodies are common in papillary carcinomas of thyroid glands. 2- Metastatic calcification: Definition: it is calcification of normal tissues due to hypercalcemia. It occurs widely throughout the body: (metastatic) Examples: gastric mucosa, kidney tubules (nephrocalcinosis) and lung alveoli.  Amyloidosis Definition: It is extracellular deposition of an insoluble protein substance in between cells and walls of blood vessels. Amyloid deposition leads to pressure atrophy to adjacent tissue. Characters: Stains positively with Congo red. Causes: Multiple myeloma- Rheumatoid arthritis Congo red  Necrosis Definition: it is a form of cell injury which results in premature death of cells in a living tissue by autolysis or heterolysis. Autolysis: digestion of cell by its own lysosomal enzymes. Heterolysis: digestion of cell by lysosomal enzymes of leukocytes.  Types of necrosis 1- Coagulative necrosis: necrotic tissue remains firm. Examples: Infarction of heart, kidney, and spleen 2- Liquefactive necrosis: digestion of tissues by proteolytic enzymes. Examples: A) Infarction of brain: lysosomal enzymes from microglial cells or necrotic cells liquefy the brain. B) Abscess and cellulitis (proteolytic enzymes from neutrophils liquefy infected tissues forming pus).  Types of necrosis 3- Gangrenous necrosis: it starts as coagulation necrosis due to cut of blood supply leads to dry gangrene. By time, liquefaction of necrotic tissue occurs due to the action of putrefactive bacteria resulting in wet gangrene. 4- Caseation necrosis: the necrotic tissue is soft, friable and cheesy. Causes: reaction between macrophages and T lymphocytes with bacterial antigen. Example: Tuberculosis. Gangrenous necrosis Caseation necrosis  Types of necrosis 5- Fat necrosis: it is seen in adipose tissue. Examples: 1- Enzymatic necrosis of omental fat: In acute hemorrhagic pancreatitis. Causes: It is due to lipase enzyme released from injured pancreatic cells. 2- Traumatic fat necrosis of female breast. 6- Fibrinoid necrosis: Pattern of necrosis occurs in: A- Deposition of immune complex protein (Ag-Ab) and fibrin in arterial wall Examples: immune vasculitis as in SLE B- Deposition of non-immune protein (plasma proteins). Examples: malignant hypertension. Fibrinoid necrosis  Apoptosis Definition: it is an energy dependent genetically programmed cell death that involves single cells. Characters: 1- Apoptosis is a cell suicide program. 2- This type of cell death is under the influence of hormones, growth hormone and cytokines. 3- Apoptosis is not harmful to the host and doesn’t result in inflammation. The died cell doesn’t rupture and intracytoplasmic granules are not released outside the cell.