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Flashcards in Cell Injury Deck (38):
1

hypoxia

oxygen deprivation due to inadequate oxygenation of the blood (cardiorespiratory failure, CO poisoning)

2

Ischemia

loss of blood supply. more rapidly injurious than hypoxia bc of loss of both oxygen and nutrients. No glycolytic energy production can occur (as in hypoxia)

3

cellular adaptations

physiologic and morphologic cellular changes leading to a new but altered steady state. caused by excessive stress or pathologic stimuli. REVERSIBLE

4

four types of cellular adaptations

hyperplasia, hypertrophy, atrophy, metaplasia

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hyperplasia

an increase in the number of cells in an organ or tissue due to an increased demand for function

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types of hyperplasia

normal hormonal (uterus during pregnancy), compensatory (regeneration), pathologic (excessive hormonal stimulation to divide)

7

hypertrophy

an increase in cell size due to increased protein synthesis (not due to cell swelling). caused by in increased demand for function, mechanically or hormonally.

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types of hypertrophy

skeletal muscle (exercise, steroids), cardiac (hypertension, valvular stenosis)

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atrophy

decrease in cell size. caused by decreased workload, decreased blood supply, inadequate nutrition, loss of endocrine stimulation, denervation

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metaplasia

a reversible change in the differentiation program of tissue stem cells to a different mature cell type

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classic example of metaplasia

protective change from psuedostratified to squamous metaplasia of the respiratory tract due to smoking. loss of mucus production/cilia. also metaplasic changes may predispose to neoplastic formation and cancer

12

which cells are most susceptible to ischemic injury?

neurons>myocardium, hepatocytes, renal epithelia>fibroblast, epidermis, skeletal muscle

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consequences of ischemia

decreased oxphos=decreased ATP=decreased Na pump (swelling), increased glycolysis (acidosis), decreased protein synthesis (lipid deposition)

14

what is generally indicative of irreversible cell injury

large increase in intracellular Ca2+ (after damage to membrane. activates proteases and leads to lysosomal lysis which damages membranes)

15

how does mitochondrial dysfunction lead to cell injury?

via formation of free radicals

16

defenses against free radicals

antioxidants, superoxide dismutase, catalase, glutathione peroxidase, ferritin

17

ferritin

an iron is an iron storage and detoxifying protein. limits toxicity due to iron donating electrons to H2O2--> OH*

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which nucleic bases do free radicals react with?

A & T, cause single chain breaks

19

lipid peroxidation

free radicals interact with the double bonds in poly-unsaturated fatty acids resulting in lipid peroxides, which react with O2 which ultimately produces lipid hydroperoxides. (chain rxn of radical formation)

20

carbon tetrachloride

dry cleaning solvent. converted by cytochrome P-450 to highly reactive free radical. Causes lipid peroxidation (a chain rxn). ER in liver is affected=decreased protein synthesis and fat export (hepatocyte fat accumulation=cell death)

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necrosis

morphological changes that follow cell death due to the degradative actions of enzymes and protein denaturation

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three types of necrosis

coagulative, caseous, liquefactive

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coagulative necrosis

most common type of necrosis, proteins denature & coagulate, cytoplasm becomes eosinophilic, cellular architecture is preserved. characteristic pattern of irreversible ischemic injury to solid organs.

24

why is coagulative necrosis surrounded by red border?

RBCs pile up since their entry into the necrotic area is impaired

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liquefactive necrosis

hydrolytic enzymes predominate over protein denaturation. rapid softening with loss of cell outlines. characteristic of brain tissue and inflammatory rxns.

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caseous necrosis

combination of coagulative and liquefactive. principally associated with TB. cells aren't totally liquefied, but outlines are not preserved and necrotic areas is surrounded by granulomatous inflammatory wall.

27

apoptosis

morphological manifestation of programmed cell death, which is designed to eliminate unwanted cells through the activation of a coordinated set of regulatory and effector proteins

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morphological changes associated with apoptosis

cell shrinks, chromatin condenses, cytoplasmic blebs break off, macrophages phagocytose blebs, membrane remains in tact, doesn't elicit inflammation

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p53

normally delays cell cycle allowing for DNA damage repair, but stimulates apoptosis when repair fails. mutated in tumors

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extrinsic pathway of apoptosis (death receptor pathway)

initiated by binding of FasL from CTLs to Fas death receptor. multimerization in induced and activates FADD protein, which activates pro-caspase 8, the executioner proteins.

31

Bcl-2 protein family function

regulates outer membrane permeability. consist of BH genes

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apoptotic mitochondrial pathway

outer mitochondrial membrane becomes permeable and pro-apoptotic proteins (cytochrome c) are released, which neutralize apoptotic inhibitors in cytosol. Forms apoptosome, which activates caspases

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caspase

the executioner proteins of apoptosis that process substrates leading to DNA degradation, chromatin condensation, and membrane blebbing

34

what is required for the apoptosome formation?

ATP

35

multi domain, anti apoptotic protein in Bcl-2 family

Bcl-2 (inhibits permeability)

36

which Bcl-2 gene on its own is pro-apoptotic?

BH3 (enhances permeability)

37

multi-domain, pro apoptotic protein in Bcl-2 family

Bak, Bax (enhances permeability)

38

what sets the threshold of susceptibility to apoptosis for the mitochondrial/intrinsic pathway?

ratio of anti to pro apoptotic proteins in the membrane