Chapter 1/2/3 Flashcards
1
Q
mechanism of hypertrophy
A
gene activation, protein synthesis and production of organelles
2
Q
mechanism of hyperplasia
A
increase in cells from stem cells
3
Q
permanent tissues can not undergo…..
A
hyperplasia
4
Q
permanent tissue of body
A
cardiac/skeletal muscle and nerves
5
Q
exception of hyperplasia to dysplasia
A
BPH
6
Q
decrease in number of cells occurs by…
A
apoptosis
7
Q
decrease in size of cells occurs by…
A
- ubiquitin proteasome degradation pathway
- autophagy (in vacuoles with lysosomes)
8
Q
mechanism for metaplasia
A
reprogramming of stem cells
- reversible by removing stress
9
Q
exception for metaplasia to cancer
A
apocrine metaplasia
10
Q
______ deficiency can result in metaplasia
A
vitamin A (necessary for special epithelium) - results in thickening of conjunctiva
11
Q
example of mesenchymal tissue metaplasia
A
myositis ossificans
- skeletal muscle converts to bone after trauma
- can be confused with osteosarcoma (not connected to bone)
12
Q
is dysplasia reversible
A
YES
13
Q
point where changes are irreversible
A
carcinoma
14
Q
most common cause of Budd Chiari
A
polycythemia vera (also lupus)
15
Q
what is decreased in CO poisoning
A
oxygen saturation (can’t bind to hemoglobin)
16
Q
classic finding of CO poisoning
A
cherry red skin (also headache is early sign)
17
Q
what is decreased in methemoglobinemia
A
oxygen saturation (iron is in Fe3+ state and cant bind to hemoglobin)
18
Q
cause of methemoglobinemia
A
oxidant stress (sulfa and nitrate drugs) or in newborns (immature deoxidants)
19
Q
classic finding in methemoglobinemia
A
cyanosis and chocolate colored blood
20
Q
treatment of methemoglobinemia
A
methylene blue
21
Q
findings of reversible injury
A
cellular swelling (water follows sodium)
- loss of microvilli, membrane blebbing(from cytoskeletal damage) and swelling of RER
22
Q
hallmark of irreversible damage
A
membrane damage
23
Q
apoptosis activator
A
cytochrome C
24
Q
three membranes damages in cell injury
A
plasma, mitochondrial, lysosome
25
hallmark of cell death
loss of nucleus
26
pyknosis
shrinking of nucleus
27
karyorrhexis
breaking up of nucleus
28
karylosis
lysing of nucleus
29
what follows necrosis
acute inflammation
30
coagulative necrosis
- necrotic tissue remains firm, structure remains
- nucleus disappears
- a result of ischemic infarction (expect brain)
31
red infarction
if blood re enters tissue after infarction
32
liquefactive necrosis
- dead tissue becomes liquid by enzymatic destruction
33
liquefactive necrosis seen in....
- brain infarction (microglial cell mediated)
- abscess (neutrophils have hydrolytic enzymes)
- pancreatitis (of pancreas itself)
34
gangrenous necrosis
- ischemia of lower limb**
- can be GI tract
- usually in diabetics
- resembles mummified tissue
35
caseous necrosis
- soft friable necrotic tissue
- combination of coagulative and liquefactive necrosis
- TB and fungal infections
36
fat necrosis
- adipose tissue
- fatty acids bind with calcium (saponification)
- happens in pancreatitis (peripancreatic fat) and trauma to breast
37
saponification
fatty acids combining with calcium
| - example of dystrophic calcification (nidus)
38
metastatic calcification
calcium or phosphate levels are high (does not mean there is cancer)
- calcium deposits in tissue
39
fibrinoid necrosis
- necrotic damage of blood vessel wall, leaking of proteins
- bright pink staining
- characteristic of malignant hypertension and vasculitis
40
preeclampsia leads to....
fibrinoid necrosis of placenta
41
apoptosis is mediated by....
caspases
- proteases to break down cytoskeleton
- endonucleases break down DNA
42
intrinsic mitochondrial pathway
- caused by cell injury, DNA damage or decreased hormone
| - mediated by cytochrome C
43
Bcl2
stabilized mitochondria so cytochrome C stays in membrane
44
extrinsic apoptotic pathway
- FAS ligand binds FAS receptor on target cell
- TNF binds TNF receptor
- causes apoptosis
45
molecules CD8 cells use
perforin and granzymes
46
physiologic generation of free radicals
- cytochrome c oxidase transfers electrons to oxygen
| - partial reduction leads to free radicals
47
most damaging free radical
OH
48
enzyme for producing free radical in neutrophil
NADPH oxidase
49
results of free radical damage
- peroxidation of lipids
| - oxidation of DNA and proteins
50
enzymes of free radical removal
- super oxide dismutase (O2-)
- glutathione peroxidase (OH-)
- catalase (H2O2)
51
amyloid
misfolded protein that deposits in extracellular space
52
common characteristics of amyloid
- beta pleated sheets
| - congo red stain with apple green birefringence on polarized light
53
primary amyloidosis
- AL amyloid derived from Ig light chain
| - associated with plasma cell dyscrasias
54
secondary amyloidosis
- AA amyloid from SAA
| - acute phase reactant from inflammation, malignancy, familial Mediterranean fever
55
familial Mediterranean fever
- dysfunction of neutrophils
- leads to fever and serosal inflammation
- High SAA during attacks and deposits of AA
56
findings of amyloidosis
- nephrotic syndrome (kidney most common)
- restrictive cardiomyopathy
- tongue enlargement, malabsorption
57
senile cardiac amyloidosis
- serum transthyretin in heart
| - asymptomatic
58
familial amyloid cardiomyopathy
- mutated serum transthyretin
| - restrictive cardiomyopathy
59
by product of insulin
amylin deposits in pancrease
60
alzheimer disease
Abeta deposits derived from beta-amyloid precursor protein (seen in down syndrome)
61
dialysis associated amyloidosis
beta-2 microglobulin in joints
| - not filtered well from blood
62
medullary carcinoma of thyroid
- calcitonin deposits in tumor
- c cells
- classic for tumor cells and amyloid
63
hallmarks of acute inflammation
neutrophils and edema
64
CD14
on macrophages, recognizes LPS on gram negative bacteria
65
NF-KB
- TLR binding uses this to activate immune response
66
cyclooxygenase produces...
prostaglandins
67
PGI2, PGD2, PGE2
vasodilation and increased permability
68
PGE2
Feeever and pain
69
LTB4
attracts and activates neutrophils
70
LTC4, LTD4, LTE4
vasoconstriction, bronchospasm, and increase vascular permeability (pericyte contraction)
- smooth muscles contraction
71
mast cell activated by...
- tissue trauma
- C3a and C5a (anaphylatoxins)
- IgE crosslinking
72
histamine
- vasodilation of arterioles
| - increased vascular permeability of post capillary venule
73
what is necessary for delayed response of mast cells
leukotrienes, second phase of mast cell response
74
classical pathway
C1 binds to IgG of IgM bound to antigen
75
alternative pathway
microbial products directly activate
76
C5a
chemotactic for neutrophils
77
C3b
opsonin for phagocytosis
78
4 things that attract neurotphils
- LTB4
- C5a
- IL8
- bacterial products
79
Hageman factor
- activated on exposure to subendothelial or tissue collagen
- important role in DIC
- activates coag and fibrinolytic system
- complement and kinin system
80
kinin
like histamine and pain
81
pain mediated by...
PGE2 and bradykinin
82
fever cytokines
IL1 and TNF (macrophages), increase in COX
| - PGE2 raises temp
83
molecules in rolling
selectins on endothelial cells bind to neutrophils
84
P selectin
from Weibel-Palade bodies, mediated by histamine
85
E selectin
induced by TNF and IL1
86
sialyl Lewis X
on leukocytes, binds to selectins during rolling
87
neutrophil adhesion
cellular adhesion molecules on endothelial cells bind integrins on neutrophils
88
defect in leukocyte adhesion deficiency
CD18 deficiency (integrins)
89
clinical features of LAD
- delayed separation of umbilical cord (no acute inflammation)
- increased circulating neutrophils
- recurrent infections that lack pus
90
disease with delayed separation of umbilical cord
LAD
91
chediak higashi syndrome
- protein trafficking defect
| - microtubule defect can't traffic lysosome
92
clinical features of chediak higashi syndrome
- increased infection
- neutropenia (cant divide properly)
- giant granules in leukocytes
- defective primary hemostasis (dependent on platelets)
- albinism (pigment by melanocytes cant be handed off)
- peripheral neuropathy (lack of transport)
93
pseudomonas cepecia
in CGD because of catalase positivity
94
MPO deficiency
increase of candida infection
| NBT test is positive
95
cytokines for resolution and healing
IL10 and TGF-beta (shut down inflammatory process)
96
mechanisms for continued acute inflammation
IL8
97
B7
on APC, binds to CD28 on CD4 T cells
28/7 = 4
98
TH1
```
Helps CD8 T cells (via IL2)
helps macrophages (via IFN-gamma)
```
99
TH2
```
IL4 (IgG to IgE)
IL5 (eosinophil activation, plasma cells, IgA class switching
IL10 (downregulates TH1)
```
100
second signal of B cell binding
CD40 and CD40L
101
defining feature of granuloma
epithelioid histiocytes
102
steps in granuloma formation**
- macrophages present antigen to MHC II to helper T cells
- IL12 convert TH1
- IFN gamma convert macrophages to histiocytes
103
diGeorge syndrome
- failure of 3/4 pharyngeal pouch
| - no thymus or parathyroids
104
SCID
- both cell mediated and humoral immunity
| - infections (no live vaccines)
105
etiologies of SCID
- cytokine receptor defects
- ADA deficiency (toxicity to lymphocytes)
- MHC II deficiency
106
X-linked agammaglobulinemia
- lack Ig
- disordered B cell maturation
- Bruton tyrosine kinase
- Bacterial enterovirus and giardia***
107
CVID
- low Ig
- B or T cell defect
- bacteria, enterovirus, giardia
- risk for autoimmue and lymphoma
108
IgA deficiency
- most common
| - mucosal and infections, especially viral
109
hyper IgM syndrome
- mutation in CD40 or CD40L
- can not class switch
- recurrent pyogenic infections at mucosal surfaces
110
Wiskott- Aldrich syndrome
- thrombocytopenia
- eczema
- immune deficiency
111
C5-C9 deficiency
Neisseria infections
112
C1 inhibitor deficiency
angioedema and mucosal surfaces (periorbital)
113
autoimmune polyendocrine syndrome
AIRE mutation (lack of central tolerance)
114
AIRE
transcription of self antigens in thymus
115
ALPS (autoimmune lymphoproliferative syndrome)
Fas apoptosis pathway mutation, lack of peripheral tolerance
116
CD95
same as Fas (for apoptosis)
117
CTLA4
binds B7, turns off system
118
negative cytokines
IL10 and TGF beta
119
CD 4 and CD 25 positive
Treg (also FoxP3)
120
CD 25 polymorphisms
no IL2 receptor (leads to MS and type 1 DM)
121
IPEX syndrome
FOXP3 mutation
122
PTPN22
associated with autoimmunity (tyrosine phosphatase)
123
lupus (SLE)
- immune complexes activate complement
| - early complement deficiency (C2)
124
findings in SLE
- fever, weight loss and fatigue
- LAD Raynaud
- Malar butterfly rash
- oral/nasopharyngeal ulcers
- arthritis and serositis
- CNS problems
- renal damage
- anemia, thrombocytopenia
- Libman-Sacks endocaditis
125
antibodies in SLE
- ANA (sensitive)
| - anti-dsDNA or anti-Smith (specific)
126
false positive syphilis test
anticardiolipin antibodies
127
antiphospholipid antibody syndrome
- antiphospholipid antibody plus hypercoagulable state
| - associated with lupus but not necessary
128
drugs associated with lupus
- hydralazine, procainamide and isoniazid
- ANA+
- removal of drugs end disease
129
most common causes of death in lupus
- renal failure and infections
130
sjogrens syndrome
- type 4 hypersensitivity to lacrimal and salivary glands
- dry mouth, dry eyes, dental caries
- associated with RA
131
anti-ribonucleoprotein antibodies
Sjogren's
- anti SSA and SSB
- can cross placenta (neonatal lupus and congenital heart block)
132
three criteria for sjogrens
- dry eyes
- Anti ANA, anti SSA, anti SSB
- lymphocytic siadelnitis
133
increased risk for......in Sjogrens
B-cell lymphoma
134
Scleroderma
- activation of fibroblasts leading to increased collagen deposition
- produce endothelin, PDGF
135
CREST
```
Calcinosis (anti-centromere)
Raynaud
Esophageal
Sclerodactyly
Telangiectasias
```
- limited type shows limited skin imvolement
136
diffuse scleroderma
CREST plus other organs
| - pulmonary most common cause of death
137
antibodies to diffuse and limited scleroderma
diffuse - DNA topoisomerase I
limited - anti-centromere antibodies
138
antibodies in mixed connective tissue disease
ANA with serum antibodies against U1 ribonucleoprotein
139
initial phase of repair
granulation tissue
140
colagenase (and cofactor)
removes type 3 collagen and requires zinc
141
TGF-alpha
epithelial and fibroblast growth factor
142
TGF-beta
- epithelial and fibroblast growth factor
| - inhibits inflammation
143
PDGF
- endothelium, smooth muscle and fibroblast growth factor
144
FGF
*angiogenesis*, skeletal development
145
VEGF
angiogenesis
146
mechanism for scar shrinking
myofibroblasts
147
keloid
characterized by type 3 collagen
| - classically in earlobe
148
G6PD isoforms
used to determine clonality in neoplasia (can also be androgen receptor isoforms)
149
aflatoxins
- causes hepatocellular carcinoma
| - from aspergillus from stored grains
150
alkylating agents
- causes leukemia/lymphoma
| - side effect of chemo
151
alcohol
- causes SCC or oral cavity, pancreatic carcinoma and hepatocellular carcinoma
152
arsenic
- causes squamous cell carcinoma of skin, lung and angiosarcoma
- in cigarette smoke
153
asbestos
- causes lung carcinoma and mesothelioma
| - more likely to cause lung cancer
154
cigarette smoke
- carcinoma of oropharynx, esophagus, lung, kidney and bladder (toxins concentrated in urine)
- polycyclic hydrocarbons
155
nitrosamines
- causes stomach cancer (intestinal type)
| - in smoked food
156
napththylamine
- causes urothelial carcinoma of bladder
| - from cigarette smoke
157
vinyl chloride
- causes angiosarcoma of liver
| - used to make PVC
158
nickel, chromium, beryllium or silica
- causes lung carcinoma
| - occupational exposure
159
HHV-8
Kaposi sarcoma
160
EBV
- chinese male and african
| - neck mass, Burkitt lymphoma and CNS lymphoma in AIDS
161
HTLV-1
Adult T-cell leukemia/lymphoma
162
high risk HPV
16,18,31,33
163
ionizing radiation
AML, CML and papillary carcinoma of thyroid
| - generates hydroxyl free radicals
164
non-ionizing radiation
- basal/squamous cell carcinoma and melanoma
| - causes pyrimidine dimers which are excised by endonucleases
165
PDGF-B (cancer)
- growthy factor
| - in astrocytoma, self activation (autocrine)
166
ERBB2 (HER2/neu)
- epidermal growth factor receptor
| - breast carcinoma
167
RET (cancer)
- neural growth factor receptor
| - MEN 2A, MEN2B, sporadic medullary carcinoma of thyroid
168
KIT (cancer)
- stem cell growth factor receptor
| - gastrointestinal stromal cancer
169
RAS (cancer)
- GTP binding protein
| - carcinoma, melanomas, and lymphomas
170
ABL
- tyrosine kinase
| - CML and some types of ALL
171
c-myc
- transcription factor t(8:14) involving IgH
| - Burkitt lymphoma
172
n-myc
- transcription factor
| - neuroblastoma
173
l-myc
- transcription factor
| - lung carcinoma
174
CCND1
- cyclin t(11:14) involving IgH
| - mantle cell lymphoma
175
CDK4
- cyclin dependent kinase
| - melanoma
176
cyclin D
allows cell to go from G1 to S
177
Rb
binds to E2F, when Rb is phosphorylated, E2F is released and G1 goes to S
178
Bcl2
stabilizes mitochondrial membrane, prevents apoptosis
179
what is overexpressed in follicular lymphoma
Bcl2, prevention of apoptosis (only place where you want a lot of apoptosis)
180
downregulation of E-cadherin
allows tumor cells to detach from each other
181
steps for tumor cells to escape
1. downregulation of E-cadherin
2. attach to laminina and destroy BM
3. attach to fibronectin in ECM
4. entrance into vessels
182
carcinomas spread via.....
lymphatics
183
sarcomas spread via....
hematogenous route
184
carcinomas that go in blodd
- Renal cell carcinoma (renal vein)
- hepatocellular carcinoma (hepatic vein)
- follicular carcinoma of thyroid
- choriocarcinoma
185
how does ovarian cancer spread
seeding
186
keratin
epithelium
187
vimentin
mesenchyme
188
desmin
muscle
189
GFAP
neuroglia
190
neurofilament
neurons
191
PSA
prostatic epithelium
192
ER (estrogen receptor)
breast epithelium
193
thyroglobulin
thyroid follicular cells
194
chromogranin
neuroendocrine cells
195
S-100
melanoma
