Cell Injury and Death

Question 1

types of cell death

Answer 1

necrosis and apoptosis

Question 2

major causes of cell injury and death

Answer 2

hypoxi/anoxic injury, physical agents, chemical agents, infectious agents, immune system, genetic disease, nutritional abnormalities

Question 3

necrosis

Answer 3

local death of groups of cells in a living organism, all forms are pathologic

cells die quickly after the “tipping point” 4-12 hours after injury

Question 4

Identify the variants of necrosis.

Answer 4

coagulative, liquefaction, caseous, fat, gangrenous, tumor

Question 5

cellular changes in necrosis

Answer 5

cell swelling

increased eosinophilia due to loss of RNA

glassy homogeneous pattern due to degradation of protein/organelles

loss of nuclear material: random DNA breaks, DNase activity, karyolysis, pyknosis, karyorrhexis (fragmentation)

ghost like appearance

inflammatory response

Question 6

coagulative necrosis

Answer 6

most commonly after a severe cell injury from ischemia, due to exposure of toxic agents

opaque and drier than surrounding normal tissue, nuclei may be absent, but cell outlines and cytoplasm are still discernible

Question 7

liquefaction necrosis

Answer 7

a form of coagulative necrosis

necrotive area rapidly liquiefied due to extensive lysis

most fequently seen in the brain after ischemic injury from arterial occlusion

necrotic area is soft and the center becomes liquefied as the result of release and activation of hydrolytic enzymes

Question 8

caseous necrosis

Answer 8

commonly associated with foci of tuberculous infection in tissues, whitish-gray, sharply demarcated from surrounding non-necrotic tissue

reminiscnent of dry cheese, center of these lesions undergo liquefaction

hallmark is granuloma formation

Question 9

fat necrosis

Answer 9

almost exclusively found in adipoe tissue contiguous to the pancreas and more rarely at distant sites

result of leakage of lipase and other hydrolytic enzymes form acutely injured acinar cells of the pancreas

calcium sinks due to saponification, which leads to hypocalcemia and tetany

Question 10

process of pancreatic fat necrosis

Answer 10

Question 11

gangrenous necrosis

Answer 11

a variant of coagulation necrosis, localized to soft tissue of lower limbs that have been compromised by protracted hypoxia and ischemia

Question 12

tumor necrosis

Answer 12

tumors may outgrow their blood supply and create hypoxic zones, these cells will die through necrosis

therapy can lead to necrosis as well as abnormal production of pro-angiogenic factors secreted by the tumor cells causing the tration of immune system cells

apoptotic factors produced by dying cells can also trigger necrosis

Question 13

Name the general mechanisms that can lead to necrosis

Answer 13

ATP depletion, loss of calcium homeostasis, free radical generation, loss of membrane permeability, damage to DNA and protein

Question 14

ATP depletion

Answer 14

absence of oxygen, ATP synthesis stops, allowing the emitochondreal permeability transition pore to open

drop in pH leads to lactate and NADH accumulates, inhibiting anaerobic glycolysis

membrane damage, leakiness and cell swelling

early changes can be reversible

Question 15

loss of calcium homeostasis

Answer 15

dead cells accumulate calcium due to influx of calcium into the cell and the mitochondria

uncontrolled calcium entry can cause death by activating degradative enzymes

prevents contraction in contractile cells such as heart muscle

Question 16

free radical generation

Answer 16

adding electrons to molecular oxygen as well as modifications to L-Arginine can cause ROSs to form

can cause significant damage to proteins, nucleic acids, and lipids

anit-oxidants and recuding enzymes help reduce ROS buildup under normal conditions

anti-oxidants lost during ATP or nutrient depltion, and a pulse of free radicals can occur during reperfusiuon/reoxygenation

Question 17

loss of membrane permeability

Answer 17

increase of intracellular calcium levels in the cytoplasm triggers phospholipase activation, resulting phospholipid loss would result in membrane damage

Question 18

three “vital systems” of cell structure and function

Answer 18

boundary functions

energy metabolism

protein synthesis

Question 19

mechanisms of free radical damage

Answer 19

DNA damage and lipid peroxidation

Question 20

apoptosis

Answer 20

death of a signle cell, programmed and responsible for many developmental processes

activated through the intrinsic and extrinsic pathways

dysregulation is critical for cancer development and tumor cell survival

Question 21

processes during apoptosis

Answer 21

loss of contact with adjacent cells, loss of water and electrolytes (dehydration), chromatin condensation and DNAfragmentation, blebbing of cytoplasm, fragmentation of the nucleus, phagocytosis

no inflammatory response

Question 22

physiologic causes of apoptosis

Answer 22

developmental programming, hormone withdrawal, removal of self-reactive lymphocytes

Question 23

pathologic causes of apoptosis

Answer 23

DNA damage, misfolded protein accumulation, infections, immune-related

Question 24

caspases

Answer 24

important set of cystein proteeases with specificity for aspartic acid residues

the ones known are 3,7,8, and 9, reside in cells as procaspase precursors until needed

Question 25

intrinsic pathway of apoptosis

Answer 25

triggered by p53 in response to DNA damage and other types of severe cell stress

p53 activates pathway by upregulating proteins such as PUMA and BAX

BAX causes the release of cytochrome c which activates caspase 9, activating other caspases that destroy the cell

Question 26

extrinsic pathway of apoptosis

Answer 26

TNFr and Fas receptors are pro-apoptotic when activated

pathway stimulates apoptosis independently of p53

assembly of death-inducing signaling complex (DISC) and recruitment of initiator caspases 8 and 10 through the Fas-associated death domain (FADD)

caspases 8 and 10 activate effector caspases 3, 6, and 7, leading to apoptosis

Question 27

fatty liver disease

Answer 27

alcoholic and non-alcoholic, caused by alcohol or obesity

macrovesicular change - fat deposits large in comparison to hepatocyte size, many hepatocyte replaced

microvesicular change - lipid droplets are smaller than hepatocytes