Pathology Flashcards
1
Q
neurons most vulnerable to hypoxic-ischemic insults
A
purkinje cells of cerebellum
pyramidal cell of hippocampus and neocortex (zones 3, 5, 6)
2
Q
histology of caseous necrosis
A
fragmented cells and debris surrounded by lymphocytes and macrophages (granuloma)
3
Q
what is primary systemic amyloidosis associated with
A
plasma cell dycrasias (MM)
4
Q
what is secondary systemic amyloidosis
A
systemic deposition of serum amyloid A (AA)
seen in chronic inflammatory conditions (RA, IBD, familiar mediterranean fever, protracted infection, cancer)
5
Q
Fever mechanism
A
- pyrogens (LPS) induce macrophages to release IL-1 and TNF
- increase COX in perivascular cells of hypothalamus
- increase PGE2
- increase temp set point
6
Q
which bcl-2 proteins are proapoptotic
A
BAX
BAK
form pores in mitochondrial membrane –> release cytochrome C (inner mito) into cytoplasm –> activation of capsases
7
Q
the two pathways of extrinsic (death receptor) path
A
- ligand receptor interactions (FasL binding to Fas [CD95] or TNF alpha bind to receptor)
- immune cell (cytotoxic T-cell release of perforin and granzyme B)
8
Q
Fas-FasL interaction is necessary in
A
thyme medullary negative selection
9
Q
What kind of necrosis is seen with distal extremity and GI tract after chronic ischemia
A
gangrenous
10
Q
caseous necrosis is d/t
A
macrophages
-wall off infecting microorganism –> granular debris
11
Q
How is apoptosis different from necrosis
A
apoptosis does not have local inflammatory reaction
12
Q
area of liver most vulnerable to ischemia
A
area around central vein (zone III)
13
Q
histology of wet gangrene
A
liquefactive superimposed on coagulative
liquefactive: neutrophils and cell debris seen with bacterial infection
coagulative: preserved cell structure w/no nuclei, increased eosin staining, PMNs later to clean up
14
Q
what does bcl-2 do
A
keeps mitochondrial membrane impermeable
prevents cytochrome C from leaking
15
Q
what is primary systemic amyloidosis
A
systemic deposition of AL amyloid derived from Ig light chain
16
Q
acute phase proteins are notably induced by
A
IL-6
17
Q
rubor (redness) and color (warmth) is mediated by
A
histamine PG bradykinin NO vasodilation (SM relaxation)
18
Q
MC see coagulative necrosis in what organs
A
heart liver spleen kidneys organs that use a lot of oxygen
19
Q
Aschoff bodies in acute rheumatic heart disease is an example of what kind of necrosis
A
fibrinoid necrosis
(type II hypersensitivity)
lymphocytes in heart muscles layers
20
Q
what does fat necrosis look like on H&E stain
A
dark blue
-saponification of fat with Ca
21
Q
familial ventricular endomyocardium deposition of amyloid causes
A
restrictive cardiomyopathy and arrhythmia
22
Q
what kind of necrosis do you see in brain infarcts and pancreas
A
liquefactive
23
Q
tumor (swelling) is mediated by
A
endothelial contraction leukotrienes C4, D4, E4 histamine serotonin increase vascular permeability and interstitial oncotic pressure
24
Q
what kind of necrosis will you see in immune vascular reactions (PAN)
A
fibrinoid necrosis
25
what is familial mediterranean fever
AR
dysfunction of neutrophils
acute fever and serousal inflammation
high SAA during attacks that deposit as AA amyloid
26
opsonin
fixes complement and facilitates phagocytosis
measured clinically as nonspecific sign of ongoing inflammation
CRP (positive, upregulated)
27
definition of pseudocyst (seen in pancreas)
cavity of fluid lined by necrotic tissue
28
intrinsic and extrinsic apoptosis mediated by
capsases (cytosolic proteases)
29
Part of kidney most vulnerable to ischemia
straight segment of proximal tubule (medulla)
| thick ascending limb (medulla)
30
GI manifestations of systemic amyloidosis
macroglossia
hepatomegaly
malabsorption from bowel thickening
31
histology of dry gangrene
same as coagulative
- preserved cell architecture
- nuclei disappear
- increase cytoplasmic binding of eosin stain
- neutrophils will come in to clean up later on
32
liquefactive necrosis histology
early: cellular debris and macrophages
late: cystic spaces and cavitation (brain), neutrophils and cell debris seen with bacterial infection
33
MC organ affected by amyloid
kidney
34
general characteristics of reversible cell injury
- ribosomal/polysomal detachment (decrease protein synthesis)
- plasma membrane changes (blobbing)
- nuclear changes (chromatin clumping)
- rapid loss of function (myocardial cells are non contractile after 1-2 min of ischemia)
35
general characteristics of irreversible cell injury
- mitochondrial damage/dysfunction
- rupture of lysosomes --> autolysis
- nuclear degradation
36
Intrinsic pathway regulated by what family of proteins
bcl-2
37
neurologic manifestations of systemic amyloidosis
neuropathy
38
examples of localized amyloidosis
```
alzheimer dz
T2DM
medullary thyroid cancer
isolated atrial amyloidosis
systemic senile (age related) amyloidosis
```
39
autoimmune lymphoproliferative syndrome is caused by
defective Fas-FasL interactions
40
MSK manifestations of systemic amyloidosis
carpal tunnel syndrome
41
amyloidosis Dx requires
biopsy
| abdominal fat pad or rectum are easy
42
transudate is d/t
increase hydrostatic pressure (HF, Na retention)
| decrease oncotic pressure (cirrhosis, nephrotic syndrome)
43
MC type of necrosis
coagulative
- seen in ischemia/infarcts (except in brain)
- injury denatures enzymes (proteolysis blocked)
44
Where do you see caseous necrosis (cottage cheese)
TB
systemic fungi (histoplasma capsulatum)
nocardia
45
Definition of a cyst
cavity of fluid lined by epithelium
46
histology of coagulative necrosis
- preserved cell architecture
- nuclei disappear
- increase cytoplasmic binding of eosin stain
- neutrophils will come in to clean up later on
47
area of colon most vulnerable to ischemia
splenic flexure
| rectum
48
When do red infarcts occur
venous occlusion
tissues with multiple blood supplies (liver, lung, intestine, testes)
reperfusion (after angioplasty)
49
apoptotic cell characterized by
ATP dependent programmed cell death
eosinophilic cytoplasm
basophilic nucleus
pyknosis (nuclear condensation)
karyorrhexis (nuclear fragmentation)
DNA laddering (fragments in multiples of 180 bp)
cell membrane typically intact w/o significant inflammation
50
beta 2 microglobulin is associated with
supports MHC class I transmembrane function
51
histology of fat necrosis
outlines of dead fat cells w/o peripheral nuclei
52
what are the two inherited amyloidoses
familial amyloid cardiomyopathy (5% in AA)
familial amyloid poly neuropathies
both mutated transthyretin (ATTR)
53
lipofuscin is formed by
oxidation and polymerization of autophagocytosed organelles membranes
54
what cell predominates the late stages of acute inflammation
macrophages
peak 2-3 days after onset
influence outcomes by secreting cytokines
55
where do you see systemic senile amyloidosis
cardiac ventricles
increased transthyretin (TTR, normal wild type)
cardiac dysfunction more insidious than in AL amyloidosis
asymptomatic
56
what coats RBCs during inflammation
fibrinogen
makes them less negative and stick together
increases ESR
57
Biochemical basis of reversible cell injury
decrease ATP --> decrease activity of calcium and Na/K pumps --> cellular swelling (earliest) --> mitochondrial swelling
58
what kind of necrosis will you see in hypertensive emergency and preeclampsia (non-immune vascular reaction)
fibrinoid necrosis
59
deposition of beta 2 micro globulin in joints
dialysis-related amyloidosis
60
pale infarcts occur when
solid organs with single blood supply (heart, kidney)
61
- tissue remodeling in embryogenesis
- withdrawn regulating factor from proliferating cell population
- after exposure to injurious stimuli (radiation, toxins, hypoxia)
intrinsic pathway (mitochondrial)
62
fibrinoid necrosis is d/t
- immune complex deposition (type III)
| - plasma protein (fibrin) leakage from damaged vessel
63
which bcl-2 proteins are antiapoptotic
bcl-2
| bcl-xL
64
what triggers activation of capsases in intrinsic pathway
cytochrome C release from inner mitochondrial
65
over expression of bcl-2 is associated with what cancer
follicular lymphoma t[14, 18]
| -decrease capsize activation = tumorigenesis
66
on H& E stain, calcium deposits appear
basophilic
67
what kind of necrosis do you see in bacterial abscesses
liquefactive
68
characteristics of dysplasia
disordered precancerous epithelial cell growth
not truly adaptive response
-loss of uniformity (pleomorphism)
-loss of tissue orientation
-nuclear changes (increase nuclear:cytoplasm ratio, clumped chromatin)
69
AL deposition
primary systemic amyloidosis
70
nuclear changes in irreversible cell injury
nuclear degradation
1. pyknosis (nuclear condensation)
2. karyorrhexis (nuclear fragmentation caused by endonuclease by endonuclease mediated cleavage
3. karyolysis (nuclear dissolution)
71
Coagulation factor
promotes endothelial repair
correlates with ESR
acute phase reactant
fibrinogen (positive, upregulated)
72
necrosis seen with traumatic injury
non enzymatic fat necrosis
| -injury to breast tissue
73
wet gangrene is d/t
superinfection
74
cardiac manifestations of systemic amyloidosis
restrictive cardiomyopathy
| arrythmia
75
biochemical basis of irreversible cell injury
breakdown plasma membrane --> cytosolic enzymes leak into serum (troponin) --> influx of Ca --> activation of degradative enzymes
76
reduction conserves amino acids for positive reactants
albumin (negative, down regulated)
| acute phase reactant
77
organs with amyloid deposition can only be cured with
transplant
| cannot be removed
78
isolated atrial amyloidosis commonly seen in
normal aging
increase risk of a-fib
increased ANP
79
What is amyloid
misfiled protein that deposits in extracellular space and damages tissues
80
examples that decrease ESR
```
-sickle cell (altered shape)
polycythemia (increase RBC "dilute" aggregation factors)
-HF
-microcytosis
-hypofibrinogenemia
```
81
acute phase proteins are made by
the liver in both acute and chronic inflammation
82
Alzheimer dz is d/t
increased beta-amyloid protein
| cleaved from amyloid precursor protein (APP)
83
serum amyloid A
secondary systemic amyloidosis
84
amyloid tends deposits around
blood vessels
85
histology of fibrinoid necrosis
vessel walls are thick and pink
86
amyloid in DM is d/t
deposition of amylin in pancreatic islets
| will see increased islet amyloid polypeptide (IAPP)
87
Dolor (pain) is mediated by
bradykinin
PGE2
histamine
sensitization of sensory nerve endings
88
attack of increased SAA and deposition of AA amyloid
familial mediterranean fever
89
Why doesn't the brain experience coagulative necrosis
less fibroblasts
90
Dry gangrene is d/t
ischemia
91
mutations in Fas causes
increase numbers of circulating self-reacting lymphocytes d/t failure of clonal deletion
92
liquefactive necrosis is d/t
```
neutrophil release (heterolysis)
lysosomal enzymes that digest tissue (autolysis)
```
93
- decrease in tissue mass d/t decrease in size
- increase cytoskeleton degradation via ubiquitin-proteasome path and autophagy, decrease protein synthesis
- apoptosis
atrophy
94
renal manifestations of systemic amyloidosis
nephrotic syndrome
95
Exudate is due to
lymphatic obstruction
inflammation/infection
malignancy
96
SAA is an example of an
acute phase reactant
| increased in chronic inflammation, malignancy, familial mediterranean fever
97
what is lipofuscin
"wear and tear" pigment
yellow-brown
associated with normal aging
see in heart, colon, liver, kidney, eye, other
98
what is dialysis related amyloidosis
systemic amyloidosis with deposition of beta 2 micro globulin
seen in ESRD and/or long term dialysis
99
necrosis seen in acute pancreatitis
enzymatic fat necrosis
- saponification of peripancreatic fat
- damaged pancreatic cells release lipase --> breaks down TG
- liberated FA's bind Ca = saponification (chalky white appearance)
100
hematologic manifestations of systemic amyloidosis
easy bruising
| splenomegaly
