Cell Injury & Death Flashcards
1
Q
define hyperplasia
A
increase in cell number
2
Q
define hypertrophy
A
increase in cell size
3
Q
define atrophy
A
decrease in cell size and number
4
Q
define metaplasia
A
adult cell changes into another cell type
5
Q
T/F hyperplasia and hypertrophy both can be physiological or pathological
A
True
6
Q
during atrophy, how are proteins degraded?
A
- cytoskeleton broken down by proteasome
- cellular components are “self-eaten” (autophagy)
7
Q
examples of metaplasia
A
- smokers from resp. epith. to squam. epith.
- gastric reflux from squam. epith. to gastric/intestinal eptih.
- vitamin A deficiency = squamous lining begins to keratinize
- myositis ossificans = m tissue changing to bone after trauma
8
Q
what is hypoxia caused by
A
- ischemia
- hypoxemia
- decreased O2 carrying capacity of blood
9
Q
what is ischemia
A
decreased blood flow to a tissue/organ
- shock = generalized drop in BP causing poor tissue perfusion
10
Q
what is hypoxemia
A
low partial P of Oxygen (PaO2) in arterial blood
11
Q
what causes hypoxemia
A
- high altitude = decreased PaO2
- hypoventilation = increased PaCO2 –> decreased PaO2
- diffusion defect
- blood bypasses the lung or oxygenated air can’t reach the blood
12
Q
what is anemia
A
decrease in RBC mass - PaO2 and SaO2 are normal
13
Q
what can cause decreased OXYGEN carrying capacity
A
anemia
carbon monoxide poisoning
methemoglobinemia
14
Q
does CO or OXYGEN bind Hb better
A
CO binds better = carbon monoxide poisoning
15
Q
what is methemoglobinemia
A
iron in heme is oxidized to F3+ which can’t bind O2
16
Q
what are the four general mechanisms that lead to cell injury
A
- ATP depletion and production of ROS
- Ca2+ influx into cytoplasm
- cell mem. damage
- DNA damage and protein misfolding
17
Q
what happens in the cell when there is decreased ATP
A
- Na+K+ pump stops working –> increased Na+ and water in the cytosol = cell swelling
- Ca2+ pump stops working –> increased Ca2+ in cytosol
- switch to anaerobic glycolysis –> lactic acid buildup lowers the pH = denatures protein and precipitates DNA
18
Q
three things ROS can cause
A
- peroxidized lipids –> membrane damage
- oxidation of DNA –> mutations
- oxidation of proteins –> protein breakdown/misfolding
19
Q
how are ROS made
A
- during mitochondrial respiration due to imperfect rx of OXYGEN to water which forms (superoxide) O2-
- in phagosome of phagocytes as part of the respiratory (oxidative) burst
20
Q
what does superoxide get converted to and by what
A
converted to hydrogen peroxide by superoxide dismutase
21
Q
what can superoxide combine with and what does that produce
A
nitric oxide (NO) —> peroxynitrite ONOO-
22
Q
what can hydrogen peroxide be converted to and by what
A
converted to hypochlorite (HOCl) by myeloperoxidase
23
Q
damage caused by ROS is called what
A
oxidative stress
24
Q
free radicals and ROS decay spontaneously and are broken down by what
A
- superoxide dismutase
- glutathione peroxidases in cytoplasm and catalase in peroxisome both convert hydrogen peroxide to water
25
what do antioxidants do
block free radical formation or scavenge them
26
ischemia causes release of what
intracellular Ca2+ stores into the cytosol then later influx across the plasma membrane
27
what happens when there is elevated cytosolic Ca2+
- activates enzymes which damage membranes, proteins, DNA and ATP
- can also induce apoptosis by activation of caspases and increasing mitochondrial permeability (cytochrome c release)
28
what does plasma membrane damage lead to
- cytosolic enzymes leaking into serum (e.g. cardiac troponin)
- calcium influx
29
what does mitochondrial membrane damage lead to
- loss of ETC
- cytochrome c leaking into cytosol (activates apoptosis)
30
what does lysosome membrane damage lead to
hydrolytic enzymes leaking into the cytosol which are activated by high intracellular calcium
31
define hydropic degeneration
accumulation of water droplets in cytoplasm. causes organs to appear pale/swollen
32
define fatty change (degeneration)
in cells involved in fat metabolism - lipid vacuoles in cytoplasm. cause organs to appear yellow/greasy
33
T/F for reversible injury if the stimulus is removed, the tissues return to normal
T
34
what are two examples of reversible cell injury
- hydropic degeneration
- fatty change
35
what are two predictors of irreversible injury
- cell can no longer make ATP
- membranes lose their integrity
36
T/F cells lost function after they change morphology or die
False. Cells lose their function long before they change morphology or die
37
what are the two main mechanisms of cell death
necrosis and apoptosis
38
what is the main histologic change in cell death
loss of the nucleus
39
what are the three ways a cell can lose its nucleus
- condensation (pyknosis)
- fragmentation (karyorrhexis)
- dissolution (karyolysis)
40
what are the three main types of necrosis
coagulative, liquefactive, and caseous
41
define necrosis
death of a group of cells --> release of cellular components --> acute inflammatory response
42
define coagulative necrosis
cell shape and organ structure preserved due to coagulation of proteins but nucleus disappears
43
coagulative necro pattern is seen when
with ischemic infarction (obstruction of blood leading to cell/tissue death) of any organ except the brain
44
clinical feature of coagulative necro
- area of infarcted tissue is pale and wedge-shaped (pointing to focus of vascular occlusion)
- red infarction arises if blood re-enters a loosely organized tissue (pulmonary or testicular infarction)
45
define liquefactive necro
necrotic tissue becomes liquefied: enzymatic lysis of cells and protein results in liquefaction
46
liquefactive necro is characteristic of what
- brain infarction = proteolytic enzymes from microglial cells liquefy the brain
- abscess = proteolytic enzymes from neutrophils liquefy tissue
47
gangrenous necro is a type of which necro
coagulative necro
48
gangrenous necro resembles what kind of tissue
mummified tissue (dry gangrene)
49
gangrenous necro is characteristic of what
ischemia of lower limb and GI tract
50
with gangrenous necro, if superimposed infection of dead tissues occur, what happens next
liquefactive necro ensues (wet gangrene)
51
define caseous necro
soft and friable with cheese-like appearance
52
caseous necro is characteristic of what
- tuberculosis
- deep fungal infections
53
what happens to tissue architecture during caseous necro
tissue architecture replaced by define foci of granulomatous inflammation (contain granulomas)
54
define fat necro
focal areas of fat destruction from trauma or enzymatic breakdown
55
ex. of fat necro
acute pancreatitis releases pancreatic enzymes:
---> break down membranes and fats of adjacent adipose tissue in the peritoneum
---> fatty acids released combine with Ca2+ to form chalky white areas (fat saponification)
56
define fibrinoid necro
necrosis of a vessel wall leading to leakage of fibrin and other proteins into the wall which stains bright pink on H&E
57
what is fibrinoid necro caused by
immune reactions (vasculitis) and malignant hypertension
- (inflammatory response to blood vessel itself)
58
define apopto
ATP dependent "programmed" cell death of a single or small group of cells
59
purpose of apoptosis is to eliminate what
- unneeded structures- embryogenesis, stopping the immune response
- old, non-functional cells - intestine turnover, menstrual cycle
- potentially harmful cells - virus-infected, cancer cells
- cells with DNA damage that can't be repaired - radiation, drugs etc.
60
what is apopto initiated by
caspases which activate endonucleases (degrade DNA) and proteases (degrade cytoskeleton)
61
what happens during apopto as the dying cell shrinks
- cytoplasm becomes more eosinophilic and the nucleus condenses and fragments
- fragments of the cell break off with intact cell membranes
- phagocytes engulf the fragments
62
is there an inflammatory response to apopto?
little to no inflammatory response
63
what are the two kinds of apopto
intrinsic (mitochonndrial) and extrinsic (death receptor)
64
what initiates the intrinsic apopto pathway
cell injury, DNA damage or lack of growth signals
65
intrinsic pathway steps
- decrease in BCL-2 protein family (anti-apoptotic)
- which allows cytochrome c to leak from the mitochondria into the cytoplasm
- activates caspases leading to apoptosis
66
extrinsic apopto pathway cells express what
death receptors
- TNF receptor family
- Fas (CD95)
67
extrinsic apopto pathway steps
Fas ligand (FasL), mainly on activated T cells, binds to Fas and activated caspases leading to apopto
68
how are intracellular accumulations acquired?
- inadequate removal of nermal substance from cell
- genetic or acquired defect in protein folding or transport
- enzyme deficiency leads to accumulation of metabolites
- accumulation of exogenous substances
69
pigments can be ____ or _____
exogenous or endogenous colored substances
70
what is the most common exogenous pigment
carbon. in coal dust and urban air. aggregates in the lung
71
what are the four pigments that we need to know
-carbon
-lipofuscin
- melanin
- hemosiderin
72
define lipofuscin
'wear and tear' brownish-yellow complex of lipid and protein
73
what is lipofuscin derived from
previous free radical damage of membranes
74
how does lipofuscin accumulate
with age or atrophy in heart, liver and brain
75
what is melanin
brown/black pigment made by melanocytes that screens against UV damage
76
what is hemosiderin
golden yellow/brown, hemoglobin derived pigment present where there is excess of iron
77
what is pathologic calcification
abnormal tissue deposition of calcium salts
78
if pathologic calcification occurs in dead or dying tissues they are called what
dystrophic calcifications
79
if pathologic calcification occurs in normal tissues they are called what
metastatic calcifications
80
what are metastatic calcifications caused by
elevated calcium caused by:
- renal failure
- increased PTH
- bone destruction
- vitamin D disorders
81
what slows cell aging
calorie restriction and physical activity
82
why do cells age
- accumulation over time of unrepaired DNA damage
- decreased cellular replication
- defective proteins
- increasing inflammation
83
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