Inflammation Flashcards
(105 cards)
1
Q
DNA laddering?
A
Sensitive indicator of apoptosis During karyorrhexis (nuclear fragmentation): endonucleases clear at internucleosomal regions yielding fragments in multiples of 180bp
2
Q
Radiation therapy induces?
A
Apoptosis, rapidly dividing cells are most susceptible
3
Q
Pro-apoptoic factors
A
BAX and BAK
4
Q
BAX and BAK increase leads to?
A
Increased mitochondrial permeability and cytochrome C release
5
Q
Anti-apoptotic factors
A
Bcl-2
6
Q
Bcl-2 increase leads to?
A
Decreased cytochrome C release by binding to and inhibiting Apaf-1
7
Q
Function of Apaf-1?
A
Induces activation of caspases
8
Q
What happens when Bcl-2 is over expressed?
A
Apaf-1 is overly inhibited leading to decrease in caspase activation and tumorigenesis (Follicular lymphoma)
9
Q
Ligand receptor interactions involved in extrinsic pathway apoptosis
A
FasL binding to Fas (CD95)
10
Q
Immune cell release what to acitivate the extrinsic pathway apoptosis?
A
cytotoxic T cell release of perforin and granzyme B
11
Q
Fas-FasL interactions are necessary for?
A
Thymic medullary negative selection
When Fas-FasL bind, they induce other Fas around them to activate FADD which activates caspases
12
Q
Defective Fas-FasL interactions contribute to?
A
Autoimmune disorders
13
Q
What type of necrosis is seen in brain infarcts?
A
Liquefactive
14
Q
Liquefactive necrosis due to
A
Neutrophil releasing lysosomal enzymes that digest the tissue (enzymatic degradation then protein denaturing)
Brain infarcts: liquefactive due to high fat content
15
Q
Coagulative necrosis due to
A
Ischemia or infarction; proteins denature, then enzymatic degradation
16
Q
Caseous necrosis due to
A
Macrophages wall off the infecting microorganism–>granular debris
17
Q
Fat necrosis due to
A
Damaged cells release lipase, which breaks down fatty acids in cell membranes–>vessel wall damage
18
Q
Fibrinoid necrosis due to
A
Immune complexes combine with fibrin–>vessel wall damage
Vessel walls are thick and pink on histology
19
Q
Gangrenous necrosis due to
A
Distal extremity after chronic ischemia
Dry: ischemia (coagulative)
Wet: superinfection (liquefactive)
20
Q
Is ATP depletion reversible with O2 or irreversible?
A
Reversible
21
Q
Is cellular/mitochondrial swelling (decreased ATP->decr. activity of Na/K pumps) reversible with O2 or irreversible?
A
Reversible
22
Q
Is lysosomal rupture reversible with O2 or irreversible?
A
Irreversible
23
Q
Is nuclear pyknosis, karryorrhexis, karyolysis reversible with O2 or irreversible?
A
Irreversible
24
Q
Is plasma membrane damage (degradation of membrane phospholipid) reversible with O2 or irreversible?
A
Irreversible
25
Is decreased glycogen reversible with O2 or irreversible?
Reversible
26
Is fatty change reversible with O2 or irreversible?
Reversible
27
Is ribosomal/polysomal detachment reversible with O2 or irreversible?
Reversible
28
Is membrane blebbing reversible with O2 or irreversible?
Reversible
29
Is nuclear chromatin clumping reversible with O2 or irreversible?
Reversible
30
Is mitochondrial permeability/vacuolization; phospholipid-containing amorphous densities within mitochondria
Irreversible
31
Which area is most susceptible to ischemia in the brain?
ACA/MCA/PCA boundary areas
32
Which area is most susceptible to ischemia in the heart?
subendochondral
33
Which area is most susceptible to ischemia in the kidney?
Straight segment of proximal tubule (medulla)
| Thick ascending limb (medulla)
34
Which area is most susceptible to ischemia in the liver?
Area around central vein (zone 3)
35
Which area is most susceptible to ischemia in the colon?
Splenic flexure, rectum (watershed zones)
36
Which organs get pale infarcts?
Heart, kidney, spleen
37
Which areas get red infarcts?
Venous occlusions
Tissues with multiple blood supplies: lungs, liver, intestine
Reperfusion: due to damage to free radicals
38
Chromatolysis
Axonal injury (changes reflect ^ in protein synthesis:
Round cellular swelling
Displavement of the nucleus to the periphery
Dispersion of Nissl substance throughout the cytoplasm
39
Dystrophic calcification
Ca2+ deposited into abnormal tissues secondary to injury or necrosis
40
Examples of dystrophic calcification
Calcific aortic stenosis, TB, lequefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, Monckeberg arteriolosclerosis, congenital CMV+toxoplasmosis, psammomma bodies
41
Metastatic calcification
Widespread deposition of Ca2+ into normal tissue secondary to hypercalcemia or high calcium-phosphate product levels
42
Examples of metastatic calcification
Ca2+ predominantly deposits into kidney, lung, gastric mucosa (these tissues lose acid quickly, ^pH favors deposition)
43
Calcium levels in patients with metastatic and dystrophic calcification
Metastatic: not normocalcemia
Dystrophic: normocalcemia
44
Proteins involved in margination and rolling of WBC
E-selectin
P-selectin
GlyCAM1, CD34
45
Proteins involved in tight binding of WBC
ICAM1
| VCAM1
46
Proteins involved in diapedesis of WBC
PECAM1
47
Proteins involved in migration of WBC
Chemotactic products: C5a, IL-8, LTB4, kallikrein, platelet activating factor
48
What is the defective on the WBC in leukocyte adhesion deficiency type 1
CD18 integrins: LFA1, MAC-1
49
What part of the WBC binds to E/P-selectins
Sialyl-lewis (during margination/rolling) (lewis=leukocyte)
50
What part of the WBC binds to GlyCAM/CD34
L-selectin "leukocyte-selectin"
51
What part of the WBC binds to ICAM1
CD11/CD18 integrins: LFA1/MAC1 (I=leukocyte)
52
What part of the WBC binds to VCAM1
VLA-4 integrin (I=leukocyte)
53
How do free radicals damage cells?
Membrane lipid peroxidation
Protein modification
DNA breakage
54
Scavenging enzymes purpose and types
Eliminate free radicals.
Catalase
Superoxide dismutase
Glutathoine peroxidase
55
Types of free radical elimination
Scavenging enzymes
Spontaneous decay
Antioxidants (Vit. A, C, E)
Certain metal carrier proteins (transferrin, ceruloplasmin)
56
Free radical injury due to carbon tetrachloride
Liver necrosis (fatty change)
57
Free radical injury due to acetaminophen overdose
Fulminant hepatitis, renal papillary necrosis
58
Free radical injury due to iron overload
Hemochromatosis
59
Free radical injury due to reperfusion injury
Esp. due to thrombolytic therapy
60
Tissue mediators that facilitate angiogenesis
VEGF
TGF-B
FGF
61
Tissue mediators that facilitate tissue remodeling
Metalloproteinases
62
Tissue mediators that stimulate cell growth
EGF (via tyrosine kinases (EGFR))
63
Tissue mediators that stimulate vascular remodeling and smoother muscle cell migration
PDGF
64
Tissue mediators that stimulate fibroblast growth for collagen synthesis
PDGF (TGF-B stimulates fibrosis)
65
Tissue mediators that stimulate cell cycle arrest
TGF-B
66
PDGF role
Activated platelets and macrophages secrete to:
Induce remodeling and smooth muscle cell migration
Stimulates fibroblast growth for collagen synthesis
67
FGF role
Stimulates angiogenesis
68
EGF role
Stimulates cell growth via tyrosine kinases
69
TGF-B role
Angiogenesis, fibrosis, cell cycle arrest
70
Metalloproteinases role
Tissue remodeling
71
VEGF role
Stimulates angiogenesis
72
1st phase of wound healing
0-3 days. Inflammatory: clot formation, increase vessel permeability and PMN migration, macrophages clear out debris
73
2nd phase of wound healing
3 days-weeks. Proliferative: Deposition of granulation tissue and collagen, angiogenesis, wound contraction (myofibroblasts)
74
3rd phase of wound healing
1 week-months. Remodeling: Type III collagen replaced by type 1 collagen
^ tensile strength of tissue
75
Granulomatous disease mechanism
Th1 cells secrete IFN-g, activating macrophages
| TNF-a from macrophages induces and maintains granuloma formation
76
What should you always test for being starting anti-TNF therapy?
Tuberculosis (TNF-a breaks down the granuloma and can cause full dissemination of the disease)
77
Examples of disease with granulomas
```
Bartonellas
Listeria
M. Leprae
M. tuberculosis
Treponema pallidum (tertiary)
Schistosomiasis
Fungal infections
Sarcoidosis
Berylliosis
Eosinophlic granulomatosis with polyangitis (Churg-strauss)
Granulomatosis with polyangitis (Wegeners)
Crohn diease
Foreign device
```
78
Exudate contents
Cellular, protein rich, ^specific gravity (1.020+)
79
Reasons for exudate
Lymphatic obstruction
Inflammation/ infection
Malignancy
80
Transudate contents
Hypocellular, protein-poor, decrease specific gravity (less than 1.012)
81
Reasons for transudate
Increased hydrostatic pressure
Decreased oncotic pressure (cirrhosis, nephrotic syndrome)
Na+ retention
82
ESR measures what?
Products of inflammation coat RBCs and cause aggregation. The denser the RBC, the faster it falls
83
Elevated ESR associated with
```
Most anemia
Infection
Inflammation (termporal arteritis)
Cancer
Pregnancy
Autoimmune disorders (SLE)
```
84
Decreased ESR associated with
```
Sickle cell anemia
Polycythemia
HF
Microcytosis
Hypofibrinogenemia
```
85
AL amyloidosis consists of
Ig Light chains (aL for light chain)
| Multiple myeloma or other plasma cell disorders
86
AA amyloidosis consists of
serum Amyloid A (AA)
| Seen in chronic inflammatory conditions: RA, IBD, spondyloarthropathy, protracted infection
87
Dialysis related amyloidosis consists of
Fibrils composed of B2-microglobulin in patients with ESRD
88
Heritable amyloidosis consists of
Heterogenous group of disorders: familiar amyloid polyneuropathies
Transthyretin gene mutation
89
Age-related (senile) systemic amyloidosis
Deposition of normal transthyretin in myocardium
| Slow cardiac progression than AL
90
Amyloidosis on histology
Congo red stains with apple green birefringence
91
Lipofuscin
Signs of normal aging
Yellow-brown wear and tear pigment
Oxidation and polymerization of autophagocytoseed organellar membranes
Autopsy of elderly person will reveal deposits in heart colon, liver, kidney, eye etc.
92
P-glycoprotein aka
Multidrug resistance protein 1 (MDR1)
93
What is the function of MDR1/P-glycoprotein?
A function of cancer cells that is used to pump out toxins including chemotherapy (ATP dependent)
94
What type of protein is MDR1/P-glycoprotein?
ATP-dependent protein efflux pump
95
What cancer classically has MDR1/P-glycoprotein?
Adrenal cell carcinoma
96
Anaplasia
Loss of structural differential and function of cells
Resemblings primitive cells of same tissue
May see giant cells with single large nucleus
97
Desmoplasia
Fibrous tissue formation in response to neoplasm
| Ex. linitis plastica in diffuse stomach cancer)
98
Cancer grade
Degree of cellular differentiation and mitotic activity on histology
99
Cancer stage
Degree of localization/spread based on primary lesion
TNM: Tumor size, node involvement, metastases
**Best indicator of prognosis!!
100
Most carcinomas spread?
Lymphatically
101
Most sarcomas spread?
Hematogenously
102
Hamartoma definition and example
Disorganized overgrowth of tissues in their native location
| Ex. Peutz-Jeghers polyps
103
Choristoma definition and example
Normal tissue in a foreign location
| Gastric tissue located in the small bowel in Meckel diverticulum
104
Cachexia definition
Weight loss, muscle atrophy, and fatigue that occurs in chronic disease (cancer, AIDS, heart failure, TB)
105
What mediates cachexia
TNF-a (also IFN-g, IL-1, IL-6)
