Ch 1 - Disease At Cell Level Flashcards
(131 cards)
0
Q
What is atrophy?
A
Wasting of tissues, organs, or entire body as from death and reabsorption of cells
Lessened function
0
Q
Necrosis vs apoptosis: nuclear changes?
A
Necrosis = pyknosis ->karyorrhexis -> karyolysis Apoptosis = nucleosome size fragments
1
Q
What is hypertrophy?
A
Increase in SIZE of cells
2
Q
What is hyperplasia?
A
Increase in NUMBER of cells (excluding tumor formation)
2
Q
Necrosis vs apoptosis: Plasma membrane?
A
Necrosis = Disrupted Apoptosis = Intact/altered
3
Q
What is hypoplasia?
A
Incomplete development of organ or tissue
3
Q
Necrosis vs apoptosis: Cell contents?
A
Necrosis = Enzymatically digested Apoptosis = Intact
4
Q
What is metaplasia?
A
Reversible replacement of one differentiated cell type with another mature differentiated cell type
4
Q
Necrosis vs apoptosis: Adjacent inflammation?
A
Necrosis = Frequent Apoptosis = NO
5
Q
What is Barrett’s esophagus?
A
Example of metaplasia - squamous mucosa grows into esophagus
5
Q
Necrosis vs apoptosis: Physiological or pathological?
A
Necrosis = Pathologic ONLY Apoptosis = Often physiological (can be pathologic)
6
Q
What is anaplasia?
A
Change in structure of cells and change in their orientation to each other
6
Q
Seven causes of cell injury?
A
- O2 deprivation 2. Physical agents 3. Chemical agents/drugs 4. Infectious agents 5. Immunilogic reactions 6. Genetic derangements 7. Nutritional imbalances
7
Q
What is aplasia?
A
Defective development or congenital absence of organ or tissue
7
Q
5 biochemical mechanisms of cell injury?
A
- ATP depletion 2. Mitochondrial damage 3. High intracellular Ca2+ 4. O2 deprivation and O2-derived free radicals 5. Defects in membrane permeability
8
Q
What is dysplasia?
A
Abnormal tissue growth with loss of cell orientation, shape, and size
8
Q
Hypoxia vs ischemia?
A
Hypoxia = inadequate oxygenation Ischemia = loss of blood supply
9
Q
Which cellular pathology is pre-cancerous?
A
Dysplasia
9
Q
What is MPT?
A
Mitochondrial Permeability Transition (leakage of cytochrome C into the cytosol)
10
Q
What happens when the limits of adaptive responses are exceeded?
A
Cell injury
10
Q
What is the outcome of decreased ATP due to cell injury?
A
Increased glycolysis -> Decreased glycogen, decreased pH => clumping of nuclear chromatin
11
Q
What are the two types of cell injury?
A
Reversible and irreversible
11
Q
Why does decreased ATP cause decreased pH?
A
Use anaerobic respiration, produces LACTIC ACID
12
Q
Cell swelling reversible vs irreversible injury?
A
Reversible = generalized cell swelling Irreversible = increased swelling
12
What causes free radical formation in the ER?
P-450 oxidases, B5 oxidases
13
Which type of cell injury has blebs?
Reversible
13
What causes free radical formation in the mitochondria?
P-450 oxidases, B5 oxidases, respiratory chain oxidation
14
Which type of cell injury has swelling of the ER?
Both
14
What causes free radical formation in the plasma membrane?
NADPH oxidase
15
Which type of cell injury has ribosome detachment from ER?
Reversible
15
What causes free radical formation in the cytosol?
Xanthine oxidase, transition metals (Cu, Fe)
16
What happens to the mitochondria in reversible cell injury?
Swelling
| Decreased oxidative phosphorylation => decreased ATP synthesis
16
What causes free radical formation in the peroxisomes?
Multiple oxidases
17
What happens to the mitochondria in irreversible cell injury?
Swollen with amorphous densities (vacuolization)
| Ca2+ influx due to membrane permeability
17
What causes free radical formation in the lysosomes?
Myeloperoxidases, NO synthase
18
What happens to nuclear chromatin in reversible cell injury?
Clumping
18
What are the 4 oxygen derived free radicals?
Hydrogen Peroxide, superoxide, hydroxyl radical, nitric oxide
19
What happens to nucleus in irreversible injury?
Condensation (pyknosis) -> fragmentation (karyorrhexis) -> nucleus dissolution (karyolysis)
19
How do free radicals cause cell injury?
Peroxidation of membrane lipids, DNA fragmentation, and/or protein cross-linking and fragmentation
20
Which type of cellular injury causes lysosome swelling and rupture?
Irreversible
20
How is superoxide neutralized?
Superoxide dismutase (SOD)
21
Which type of cell injury has low intracellular pH?
Both
21
How is hydrogen peroxide neutralized?
Catalase
22
What would you see under light microscopy with reversible cell injury?
Fatty change (steatosis)
22
How is hydroxyl radical neutralized?
Converted to H2O2 (2GSH --> GSSG using glutathione peroxidase)
23
What would you see under light microscopy with irreversible cell injury?
Calcification
23
What is used for free radical neutralization in membranes?
Vit. E + A, beta-carotene
24
Is nuclear clumping the same as nuclear condensation?
NO
24
What is used for free radical neutralization in mitochondria?
SOD, glutathione peroxidase
25
What are blebs?
Outpouchings of plasma membrane
25
What is used for free radical neutralization in Peroxisomes?
Catalase
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What is the ultimate result of cell injury?
Cell death
26
What is used for free radical neutralization in the cytosol?
SOD, Vit. C, glutathione peroxidase, Ferritin, Cerucoplasmin, Quercitin
27
What is necrosis?
Cell death
27
How is free radical injury initiated?
radiation exposure, metabolism of drugs, redox reaction, nitric oxide, transition metals, leukocyte oxidative burst
28
What is apoptosis?
Programmed cell death
28
How is free radical degradation produced?
enzymes, spontaneous decay, antioxidants
29
What enzyme do you check for in serum for MI?
Serum CK-MB
29
What is a major cause of injury after thrombolytic therapy?
Reperfusion after anoxia
30
Necrosis vs apoptosis: cell size?
Necrosis=enlarged
| Apoptosis = reduced
30
What are the 2 categories of toxins?
Direct and indirect
31
What are the subcellular responses to injury?
Induction (hypertrophy) of smooth ER, lysosomal catabolism, mitochondrial alterations, cytoskeletal abnormalities
32
What is the function of P-450 oxidases?
Neutralize toxins in liver (but produce free radicals)
33
What are the mitochondrial alterations with cellular hypertrophy?
Increased number (due to increased cellular processes)
34
What are the mitochondrial alterations with cellular atrophy?
Decreased number
35
What are the mitochondrial alterations with nutrient deficiency or EtOH liver disease?
Increased size (megamitochondria)
36
What is impaired (cytoskeleton) with cell injury?
Intracellular organelle/molecular transport, basic cell architecture/shape/polarity, signals to nucleus, tissue integrity/mechanical strength, cellular mobility, phagocytosis (SCAFFOLD/STRUCTURAL IMPAIRMENTS)
37
What are the roles of heat shock proteins (HSPs)?
1. Protein folding 2. Disaggregation of protein-protein complexes 3. Protein transport to cell organelles (CHAPERONES)
38
Where does coagulative necrosis occur?
Heart, liver, kidney
39
What is coagulative necrosis the result of?
Protein denaturation
40
What is coag. Necrosis characteristic of?
Hypoxic death
41
Is cell outline preserved in coag. Necrosis?
YES
42
Where does liquefactive necrosis occur?
Brain
43
What is liq. Necrosis a result of ?
Enzymatic digestion
44
What is liq. Necrosis characteristic of ?
bacterial infection, or hypoxic death w/in CNS (stroke)
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Is the basic architecture of cells preserved in liq. Necrosis?
NO - obliterated
46
Where does gangrenous necrosis occur?
limbs, GI tract
47
What is gangrenous necrosis?
Loss of blood supply & coag. Necrosis
48
What causes wet gangrene?
Coag. Necrosis plus liquefactive action of bacterial infection and attracted leukocytes
49
What is caseous necrosis characteristic of?
Tuberculosis
50
What is caseous necrosis?
a distinct form of coag. Necrosis
51
Is tissue architecture preserved with caseous necrosis?
NO - obliterated
52
What is seen microscopically with caseous necrosis?
amorphous granular debris of fragmented coag. Cell, enclosed w/in distinctive inflammatory border
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Where does fat necrosis occur?
Pancreas
54
What is fat necrosis?
Focal area of fat destruction (usually due to lipase release from pancreas)
55
What happens when fat necrosis combines with Ca2+?
Create grossly visible chalky areas
56
What is seen microscopically with fat necrosis?
Foci of shadowy outlines of fat cells w/ basophilic Ca2+ deposits, surrounded by inflammatory reaction
57
Where does fibrinoid necrosis occur?
Blood vessels
58
When does apoptosis occur?
embryogenesis, hormone induction (menstruation), immune cell-mediated death, injurious stimuli, regulation of cell pop. And tumor suppression, atrophy
59
What needs to be activated to initiate apoptosis?
Execution caspases
60
What do execution caspases do?
Activate endonucleases and induce catabolism of cytoskeleton
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What do endonucleases do?
DNA fragmentation
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What do catabolism of cytoskeleton and DNA fragmentation lead to in apoptotic pathways?
Formation of cytoplasmic bud
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What does the cytoplasmic bud become in apoptosis?
Apoptotic body
64
What happens to apoptotic bodies?
Phagocytosed by macrophages
65
What allows for cytochrome c to leak into cytosol in intrinsic apoptosis pathway?
MPT
66
What does cytochrome C do in the cytosol in intrinsic apoptosis p/way?
Activates caspases
67
How is extrinsic apoptosis pathway initiated?
Fas Ligand brings several Fas "death domains" in proximity -> Fas-associated death domain -> autocatalytic caspase activation
68
What are 4 general mechanisms for intracellular accumulations?
1. Abnormal metabolism (eg fatty change in liver) 2. Mutations causing alterations in protein folding and transport => defective molecules accumulate 3. Enzyme deficiencies = unable to break down compounds => accumulation in LYSOSOMES 4. inability to degrade phagocytosed particles
69
Where does intracellular accumulation of lipids usually occur?
Usually liver, also heart, muscles, kidney
70
What is steatosis?
abnormal TG accumulation in parenchymal cells
71
What is steatosis commonly caused by?
EtOH abuse, toxins, protein malnutrition, DM, obesity, anorexia
72
What is alcohol dehydrogenase used for?
Interconversion between alcohols and aldehydes/ketones
73
What is the appearance of cholesterol accumulation microscopically?
"Foamy" appearance due to phagocytes
74
Examples of cholesterol accumulations?
Atherosclerosis, xanthomas, inflammation, cholesterolosis, Niemann-Pick disease type C
75
What are reabsorption droplets?
protein accumulations in proximal renal tubules (kidney disease w/ protein loss)
76
What are Russell bodies?
protein accumulations in distended ER with large eosinophilic inclusions
77
What is amyloidosis?
aggregation of abnormal proteins
78
Examples of diseases involving protein accumulation?
Alzheimers, Huntington's, Parkinson's, maybe DM2
79
What supplement is used to "clean up clutter" in the brain in protein accumulation diseases?
Glutathione
80
What is "hyaline change" in regards to intracellular accumulations?
Variety of alteration - NOT a specific pattern of accumulation
81
Microscopic appearance of hyaline change?
homogenous, glassy, pink appearance
82
Intracellular examples of hyaline change?
reabsorption droplets, Russell bodies, Mallory alcoholic hyalin
83
Extracellular examples of hyaline change?
collagenous/fibrous tissue (old scars), arterial wall hyalinization (HBP or DM2)
84
What is the appearance of glycogen accumulation?
Clear vacuoles w/in cytoplasm
85
What are the causes of glycogen accumulation (2)?
Glucose metabolism disorders (DM), Genetic disorders (glycogen storage diseases)
86
What are 2 examples of exogenous pigment accumulations?
Carbon (coal), tattooing
87
What are 3 examples of endogenous pigment accumulation?
Lipofuscin (lipid peroxidation), melanin (eg. Alkaptonuria), Hemosiderin (hemoglobin derived: stored/eaten)
88
What is anthracosis?
Coal worker's pneumoconiosis (exogenous pigment accumulation)
89
What are the 2 types of pathologic calcification?
Dystrophic and metastatic
90
Where is calcium deposited in dystrophic calc.?
Locally in DYING tissue
91
What is the serum calcium level with dystrophic calc.?
NORMAL
92
Is there calcium metabolism pathology with dystrophic calc.?
NO
93
Examples of dystrophic calcification?
atherosclerosis of arteries, damaged heart valves
94
Where is calcium deposited in metastatic calcification?
In NORMAL tissue
95
What is serum calcium level with metastatic calc.?
ELEVATED
96
What is metastatic calcification usually due to?
Secondary hypercalcemia
97
What are the 4 principle causes of metastatic calc.?
1. increased PTH 2. Bone destruction (multiple myeloma, Paget disease) 3. Vit. D related (toxicity, sarcoidosis) 4. Renal failure (PO4 retention)
98
What does metastatic calc. principally affect?
Interstitial tissues of vasculature, kidneys, lungs, gastric mucosa
99
What is multiple myeloma?
Widespread lucencies in bone
100
What is distinctive to mult. Myeloma on x-rays?
Lucent, elliptical, subcortical shadows, especially in long bones = endosteal scalloping
