Cell Injury- Calcification and Amyloidosis

Question 1

Disease

Answer 1

abnormal body process with a characteristic set of signs or symptoms that may affect the whole body or any of its parts. The fundamental disease process regardless of etiology begins at the molecular and cellular level.

Question 2

Injury

Answer 2

refers to damage or pathologic alterations in molecules and structure can occur in cells and extracellular components of tissue. Injury to a cell can result in loss of normal cell functions and loss of tissue function.

Question 3

adaptation

Answer 3

changes in function and structure that maintain a homeostatic state and maintain cell viability. Cells may revert to previous structure and function when the stress or injury is removed.

Question 4

Reversible injury

Answer 4

pathologic alterations in cell molecules and structure that are associated with abnormal function and with loss of homeostatic state. Removal of stress or injury results in cell recovery and return to normal function.

Question 5

Irreversible injury and cell death

Answer 5

damage to cell reaches magnitude or duration where the cell passes a “point of no return.” Despite removal of injury or stress, the cell cannot recover and dies.

Question 6

Necrosis

Answer 6

a pattern of cell death that often follows hypoxic, toxic and some microbial injuries and that is characterized by cell swelling and membrane changes as well as nuclear changes such as pyknosis and karyorrhexis.

Question 7

Apoptosis

Answer 7

a pattern of cell death that is induced by a tightly regulated intracellular program in which cells induced to die activate enzymes that degrades the cells’ own nuclear DNA and nuclear and cytoplasmic proteins leading to nuclear fragmentation without loss of plasma membrane integrity.

Question 8

Hypoxia/hypoxemia

Answer 8

cardio respiratory failure and neuronal necrosis. Renal vein thrombosis and renal tubular necrosis.

Question 9

Physical agents

Answer 9

trauma. Thermal induced skin necrosis.

Question 10

Chemicals/drugs

Answer 10

lead toxicity and neuronal and renal tubular necrosis. Glucocorticoid- induced lymphocyte apoptosis.

Question 11

Infectious agents

Answer 11

adenovirus-induced epithelial cell necrosis. Endotoxin-induced apoptosis of lymphocytes and hepatocytes in gram-negative bacteremia.

Question 12

Immunologic reactions

Answer 12

complement-mediated hemolysis in autoimmune hemolytic anemia in dogs. T-lymphocytes-induced cell apoptosis in viral infection.

Question 13

Genetic defects

Answer 13

copper storage disease of bedlington terrier dogs results in hepatocyte necrosis. Purkinje cells necrosis in cerebellar abiotrophy of calves.

Question 14

Nutritional inbalances

Answer 14

vitamin E deficiency and hepatocellular necrosis in pigs. High dietary copper and hemolysis in sheep.

Question 15

Swelling

Answer 15

Gross morphology: organ may be enlarged, pale or discolored.
Light microscopic morphology: lipidosis may occur because of decreased protein synthesis.
Electron microscopic changes: cell swelling with ER dilation

Question 16

Pyknosis

Answer 16

nuclear shrinkage with increased basophilia

Question 17

Karyorrhexis

Answer 17

fragmentation of chromatin

Question 18

karyolysis

Answer 18

dissolution of chromatin

Question 19

Gangrenous necrosis

Answer 19

ischemic necrosis of distal extremities toes, feet, ears

Question 20

Fat necrosis

Answer 20

necrosis of adipocytes and chalky-white lesions in fat characterized by cleaveage of neutral fat by lipase to triglycerides and FA and precipitation of the FA by calcium to form FA soaps.

Question 21

Patterns of necrosis

Answer 21

coagulative, liquefactive, caseous.

Question 22

Physiologic apoptosis

Answer 22

embryogenesis and development involution. Hormone dependent cycling. Cell depletion in proliferating populations. Deletion of autoreactive Tcells.

Question 23

Pathologic induction of apoptosis

Answer 23

endotoxin-induced apoptosis of lymphocytes and hepatocytes. Corticosteroid-induced apoptosis of lymphocytes. Lentiviral-induced apoptosis of lymphocytes. Tumor necrosis factor of apoptosis in many cells.

Question 24

Pathologic inhibition of apoptosis

Answer 24

the failure of cells to undergo apoptosis is a feature of many neoplastic diseases. Inhibition of apoptosis is an important feature of several viral diseases that induce proliferative lesions.

Question 25

Initiation of apoptosis

Answer 25

Extrinsic (death receptor initiated) pathway- TNF receptor, Fas. Intrinsic (mitochondrial pathway)- increases in mitochondria permeability release pro-apoptotic molecules such as cytochrome c, inhibitors of apoptosis at this level (Bcl-2, Bcl-X), promoters of apoptosis (Bak, Bax).

Question 26

Execution phase of apoptosis

Answer 26

caspase cascade activation and activation of DNase. Removal of dead cells by phagocytic cells.

Question 27

Morphologic features of apoptosis

Answer 27

chromatin condensation and fragmentation occur due to endogenous endonuclease (first change). Formation of membrane blebs. Cell fragments (apoptotic bodies) are phagocytosed by adjacent parenchymal cells or phagocytes.

Question 28

Necroptosis

Answer 28

a form of programmed necrosis. Similar mechanisms to TNF-induced apoptosis are associated with its initiation However, caspase 8 is not activated in the sequence and activation of receptor associated kinase 1 and 3 are activated and lead to mitochondrial damage and reduction of ATP with resultant cell swelling.

Question 29

Pyroptosis

Answer 29

characterized by cell swelling. It is initiated by intracellular microbial product interaction with NOD-like receptors to activate the inflammasome with subsequent activation of caspase-1 and caspase-11, release of IL-1 and loss of membrane integrity.

Question 30

Autolysis

Answer 30

refers to hydrolytic changes that occur to cells and tissues after somatic death. Occurs diffusely in the body. Necrosis may affect sharply demarcated areas of tissue. From a diagnostic histopathology perspective, necrosis induces an inflammatory response in viable tissue, whereas no inflammatory reaction occurs in autolysis.

Question 31

4 common mechanisms that induce necrosis

Answer 31

Hypoxia/ischemia inhibit aerobic respiration: ATP depletion.
Generation of reduced oxygen species: free radicals.
Defects in membrane permeability: membrane damage.
Disruption of calcium homeostasis: calcium influx.

Question 32

Ischemic and hypoxic injury

Answer 32

lack of oxygen decreases mitchondrial aerobic respiration and ATP generation slows down or stops entirely. No ATP= no K/Na pump- cell swells.