IntroPathologySSN Flashcards
(253 cards)
1
Q
Postmitotic
A
heart, nerve. Replaced by scar when injured
2
Q
intermitotic
A
divide all the time. Rapid turnover. Intestine, epithelial, skin, bone marrow
3
Q
reverting mitotic
A
usually don’t divide but can when injured. Hepatocytes, renal tubular eptothelium
4
Q
lipofuscin
A
old age/wear-and-tear pgment in liver and heart
5
Q
free radical injury
A
physical, radiation: breaks chromosomes, diarrhea, hair loss, low blood count
6
Q
free radical damage in
A
S and G2, intermitotic cells particularly
7
Q
types of free radicals
A
lipid peroxidation, protein cross-linking, DNA mutation, superoxide, hydroxyl, peroxide
8
Q
cytopathic viral infections
A
interfere with cel metabolism
9
Q
Immune-mediated viral damage
A
against virus or virus-altered cells
10
Q
cytomegalovirus
A
in immune-supressed pt., cell becomes huge
11
Q
two ways chemicals damage
A
directly combine with molecule or organelle, or reactive metabolite binds membrane protein or lipid
12
Q
hypoxia/ischemia
A
lactic acid causes pH drop, causes ATPase disfunction, Na influx, swelling
13
Q
reversible hypoxia
A
ER swells, mitochondria condense, ribosomes disaggregate, glycogen stores used up.
14
Q
irreversible hypoxia
A
cell rupture
15
Q
necrosis triggers
A
neutrophils
16
Q
test for necrosis with
A
trypan blue binds cells in lab (not diagnostic)
17
Q
gross necrosis
A
plase area with yellow and hemorrhage Nuclei disappear, incoming neutrophils, hypereosinophilic
18
Q
caseous necrosis
A
whitelooking areas of necrosis
19
Q
nuclear breakdown
A
pyknosis (enlarged), karyorrhexis (nucleus breakdown) karyolysis (small bits)
20
Q
mitochondrial apoptosis
A
release superoxides, mito pores releases cytochrome C, causes caspase 9 and activates DNAases
21
Q
Death-receptor apoptosis
A
cytoplasmic caspace 8 activation. T-cells bind FAS. Chromatin forms DNA ladders, Blebs form apoptotic bodies
22
Q
acute inflammation: vascular phase
A
Dolor, rubor, calor, tumor, functio laesa
23
Q
dolor (pain)
A
fleeting vasoconstriction (seconds); mediated by nerve endings
24
Q
rubor (red) and calor (heat)
A
progressive vasodilation of arterioles, cap bed and venules increases blood flow
25
histamine, leukotrienes, bradykinin
rela arteriole smooth muscle
26
tumor and functio laesa
increase vascular permeability and hydrostatic pressure; leakage of fluids into interstitial space; edema
27
transudate
low cells, low protein. Duration of leak depends on endothelial injury
28
exudate
transudate after cellular phase. Cell and protein rich
29
assume neutrophils in exudate unless
allergy, drug rxn, parasite (eosinophil), or viral (lymphocyte)
30
acute inflammation: cellular phase
margination, rolling with transient adhesions. Firm adhesion, transmigration
31
margination
vasodilation slows blood flow, nuetrohils migrate to flow periphery
32
rolling with transient adhesions: P-selectin endothelia
histimine, thrombin, sialyl-Lewis X oligosaccharides, LAD-2 disease
33
rolling with transient adhesions: E-selectin endothelia
TNF, IL-1, sialyl-lewis X oligosaccharides, LAD-2 disease
34
firm adhesion: ICAM-1 endothelia
TNF, IL-1, LFA-1 (integrin), LAD-1 disease
35
firm adhesion: VCAM-1 endothelia
TNF, IL-1, VLA-4 (integrin)
36
transmigration PECAM-1 (CD-31) endothelia
collagenases (from neutrophils)
37
opsinization
how antibodies coat patholgens
38
opsonins
help host phagocytotic cells bind and destroy pathogen
39
TLRs
toll like receptors, are pattern recognition receptors that let innate immune cells (neutrophils) bind molecular motifs common to pathogens
40
PAMPS
pathogen associated molecular patterns, what TLRs on neutrophils recognize
41
neutrophil receptors
FcR, CR1, CR3, C1q, TLR4
42
FcR ligand
IgG (opsonin)
43
CR1, CR3 ligand
C3 (opsonin)
44
C1q ligand
Collectins (opsonin)
45
TLR4 ligand
LPS (a PAMP)
46
steps of opsination and destruction
1. recognition and attachment 2. engulfment 3. phagosome 4. phagolysosome 5. destruction via reactive oxygen species
47
O2 to Superoxide, hydrogen peroxide, hydroxyl radical: enzymes and location
NADPH oxidase, mitochondria
48
Nitric Oxide (NO) enzyme and location
iNOS (+arginine) in cytoplasm
50
acute inflammation outcomes
resolve, abscess, turn to chronic inflammation (hours or days)
51
fibrinous exudate
forms on inflammed organs b/c tissue factos are released, causing extrinsic coagulation cascade
52
green in pus
comes from heme component of MPO
53
cytokines
mediate inflammation and immune response
54
TNF & IL-1
cytokines produced by macrophages that activate the endothelium
55
chemokines
recruit leukocytes (in inflammation states) and organize B and T-cells in the spleen and lymph nodes (in normal tissue)
56
Chemokine examples
**CC (adjacent cysteine residues) and CXC (cysteines separated by another amino acid)
57
lysosomal enzymes of leukocytes
mediate acute inflammation: proteases which act on kininogen and complemet proteins (c3, c5)
58
neuropeptides
small substances initiate inflammatory response
59
Nitric Oxide (NO) enzyme and location
Short-lived soluble free radical gas, causes smooth muscle relaxation and vasodilation
60
plasma protein derived mediators
produced in liver and present in blood inactive. Complement activation ( C3a, C5a, C3b, C5b-9) and factor XII (kinin system)
61
plasma proteins
C1-C9 play role in host defense and inflammation
62
membrane attack complex
C5-C9, degrade membrane for cell lysis
63
complement activation pathway: classical
Ag-Ab complexes; IgG/IgM
64
complement activation pathway: alternative
bacterial polysaccharides
65
complement activation pathway: lectin
binds mannose residues microbes
66
systemic effects of inflammation: exogenous pyrogens
macrophages release TNF and IL-1 ->cyclooxygenase increase, prostaglandin production
67
systemic effects of inflammation: increase in acute phase proteins
liver production of C reactive protein, serum amyloid A, fibronogen
68
C reactive protein
CRP, opsonization
69
serum amyloid A
SAA, opsonization
70
fibrinogen
increases erythrocyte sedimentation rate
71
systemic effects of inflammation: leukocytosis
increase of WBCs from bone marrow
72
chronic inflammation causes
caused by infection or de novo from chronic disease
73
chronic inflammation involves
lymphocytes, plasma cells and macrophages (not neutrophils of acute)
74
granulomas
activated macrophages plus T-cells, eosinophils, around an indigestible antigen or as part of a type IV hypersensitivity response
75
granulomas lead to
chronic scarring/fibrosis/calcification
76
granuloma serious clinical problems
schistosomiasis, sarcoidosis, inflammatory bowel disease
77
types of granuloma
infectious (parasitic, fungal, bacterial), foreign body, unknown, miscellaneous
78
caseating granulomas
necrotizing, as in TB, less clear borders, denucleiated ded cells
79
noncaseating granulomas
as in sarcoidosis, macrophages, giant cells, clear border (surrounded by lymphocytes)
80
platelets
bud off megakarocytes. Replace every 10 days. 6 day shelf life.
81
platelets cause vasoconstriction
by releasing ADP/thromboxane A2 (TxA2)
82
thrombocytopenia
less than 150,000 platelet count, need transfusion
83
platelet plug formation
adhesion, activation, aggregation
84
vWF (adhesion)
Cross-linked dimers bind collagen and platelets
85
A3 domain
where vWF binds collagen exposed at site of injury
86
Gp1b receptor (A1 domain)
where vWF binds platelet
87
ADAMTS13
cleaves vWF multimers at A2 (to minimize clot size
88
defects in vWF
von Willebrand disease: easy bruising, nosebleeds, dental bleeding, menorrhagia
89
von Willebrand type I
low vWF. Most common form
90
von Willebrand type II
AD or AR, may not bind VIII, platelets correctly
91
vonW type 2M
A1 loF mutation. Platelets can't bind. (GeI=NL; ristocetin=no clumping)
92
vonW type 2A
defects in A2/crosslinking
93
vonW type 2B
A1 GoF (increased A1/Gp1b interaction). Clotting in general circulation, less avail for injury
94
vonW type 2N
poor binding to VIII
95
von Willebrand type 3
AR, no vWF syth so VIII is very low. Rare.
96
thrombotic thrombocytopenic purpura (TTP)
lack of ADAMTS13 leads to spontaneous clotting
97
5 signs of TTP
microangiopathic hemolytic anemia, low platelets, neuro, renal, fever.
98
TTP affects
Young adults, mainly female. High mortality if untreated
99
Congenital TTP
AR, rare, no ADAMTS13. Neonatal jaudice, some present as adults. Give FFP (contains ADAMTS13)
100
acquired TTP
autoimmune, Abs to ADAMTS13. Treat with plasmapheresis
101
acquired TTP induced by
clopidogrel
102
platelet activation
stabilizes adhesion. Platelets spread on top of wound
103
major platelet activators
Thrombin/collagen+TxA2/ADP
104
platelet GpVI
binds exposed collagen, transmit IC signals to increase Ca, release TxA2/ADP (promotes aggregation)
105
platelet PAR1
binds with thrombin, transmit IC signals to increase Ca, release TxA2/ADP (promotes aggregation)
106
ADP binds
P2Y12 receptor on platelets
107
TxA2 binds
TxA2 receptor on platelets
108
clopidogrel blocks
P2Y12 receptor on platelets
109
ASA blocks
TxA2 production
110
Hermansky Pudlak syndrome
platelets lack ADP granules. Lower platelet activation, bleeding.
111
integrins
transmembrane domains that require conformational change to bind ligand
112
GpIIb/IIIa
integrin on platelets essential for aggregation. EC is fibrinogen receptor.
113
GpIIb/IIIa requires activation by
ADP/thrombin
114
Glanzmann's thrombasthenia
AR. abnormal GpIIb/IIIa, fibrinogen can't bind/stabilze clot. Bleeding.
115
aggregation balance between
ADP/TxA2 (pro-aggregation, from platelets) & PGI2/NO (anti-thrombotic, from endothelium)
116
Atherosclerosis & clotting
damaged endothelium can't release antithrombic factors easily (low cAMP, high Ca, high platelet activation)
117
primary hemostasis
platelet plug
118
secondary hemostatis
clotting cascade
119
tertiary hemostasis
clot degeneration by plasmin as injury heals
120
fibrin
glue that holds platelets together (goal of clotting cascade)
121
clotting system max rate depends on
tenase, prothrombinase complexes
122
extrinsic clotting pathway
tissue factor (TF) exposed(+VII); Xa(+Va)=prothrombinase; early thrombin (IIa) burst activates intrinsic pathway (via XI, VIII & V)
123
intrinsic clotting pathway
XII activates at negatively charged surface; Xia;IXa(+VIIIa)=tenase; Xa
124
common clotting pathway
Xa+Va; IIa (thrombin); Ia (fibrin); crosslinked by XIIIa
125
anticoagulants: TFPI
inhibits VIIa/TF/Xa complex
126
anticoagulants: ATIII-Heparin
inactivates thrombin, Xa, Ixa
127
anticoagulants: Protein C,S, thrombomodulin
Cleaves Va, VIIIa
128
anticoagulants: Plasmin
cleaves fibrin, V, VIII
129
50% defect of any anti-coagulant
increase risk of thrombosis
130
100% defect of any anti-coagulant
neonatal purpura fulminans: cutaneous haemorrhage and necrosis, low blood pressure, fever and disseminated intravascular coagulation
131
HIF
Hypoxia-inducible factor
132
HIF major effects
POG: decrease cell proliferation, increase oxygen delivery, increase glucose metabolism
133
HIF-1
heterodimer, expressed by all cells, metabolism and glycolysis
134
HIF-1 alpha subunit
constantly made, degraded if O2 is present
135
HIF-1 beta subunit
combines with alpha when hypoxic; activation
136
HIF-2
oxygen delivery. Expressed by endothelium, lungs, kidney and macrophages
137
HIF-2 acts on
EPO, VEGF, transferrin
138
VHL: Von Hippel-Lindau tumor suppressor
protein, forms complex that breaks down HIF (by ubiquination).
139
Vin Hippel-Lindau syndrome
AD loss of VHL function=more cancers (esp. renal cell carcinoma, pheochromocytoma, hemangioblastoma)
140
chuvash polycythemia
AR mutation in VHL=higher HIF expression, overproduction of red cells, increase risk of thrombosis
141
Chuvash and erythropoietin sensitivity
HIF is more stable, so EPO is overproduced in kidney=polycythemia. Mutant VHL also can't inhibit JAK2-STAT5 pathway in erythroid porgentiors=more proliferation in response to erythropoetin
142
Warburg effect
cancer cells mostly make energy by lactic acid fermentation even when O2 is present.
143
cause of Warburg effect
tumor makes lots of HIF-1, up-regulates LDHA, inactivates PDH
144
upregulated LDHA
converts more pyruvate to lactate
145
inactivated PDH
shunts pyruvate out of TCA cycle
146
altitude sickness
too much hemoglobin increases blood viscosity, which reduces tissue oxygenation
147
Why do Tibetans have normal hemoglobin levels?
mutations reduce HIF-2 expression.
148
shock
circulatory perfusion insufficient for oxygenation and waste removal
149
3 major types of shock
cardiogenic (MI or CHF), hypovolemic (hemorrage or dehydration), redistributive (sepsis, anaphylaxis, toxins, drugs, neurogenic)
150
5 signs of shock
CHOMM: cool clammy skin, hypotension, oliguria, mental status, metabolic acidosis
151
cool clammy skin
skin vasoconstricts, trying to compensate for hypovolemia
152
hypotension
absolute (systolic < 90mmHg) or relative (systolic drop > 40 mmHg)
153
oliguria
low urine output because kidneys aren't being perfused
154
mental status
agitation; confusion and delirium; coma
155
metabolic acidosis
liver, kidney and muscles not clearing lactic acid
156
3 stages of shock
initial, Day 2-6, day 10-14
157
initial shock
electrolyte imbalance (from acidosis, low output)
158
Day 2-6 shock
renal dysfunction and necrosis, fluid overload, edema, acidosis, uremia, oliguria, may see manifestations of brain damage
159
Day 10-14 shock
kidneys heal: diuretic/resolution phase
160
hemorrhage percents
15% is mostly tolerable, 40% will kill without aggressive resuscitation
161
hematoma
massive clot
162
hemo-[location]
blood where blood should not be. (hemopericardium, hemothorax)
163
bleeds into skin
petechia
164
hemorrhage treatment goals
restore volume, maintain oxygenation, reverse or prevent coagulopathy, eliminate cause
165
edema
transudate (SG 1.020). only exudate is inflammatory
166
virchow traid (thrombosis)
endothelial injury, abnormal blood flow, hypercoagulability
167
thrombosis: arterial origin
coronary, cerebral, aortic
168
thrombosis: venous origin
90%! deep leg, peri-uterine, peri-prostatic
169
thrombosis: mural origin
clot forms along wall of damaged heart
170
DIC: disseminated intervascular coagulation
small petechia in capillaries. Sepsis, childbirth (amniotic fluid TF in maternal blood), glandular cancers (when TF is produced)
171
DIC diagnosis
D-dimer measures breakdown products of fibrin
172
acute inflammation outcomes
Minimal necrosis, if stimulus is destroyed. Necrosis is stimulus is not destroyed.
173
minimal necrosis outcomes
normal tissue & mild burn if exudate is resolved, scarring & fibrinoprurulent percarditis, peritonitis if exudate is organized
174
necrosis outcomes
labile or stable cells, or permanent cells
175
permanent necrotic cells
scar from MI
176
labile or stable necrosis
framework intact: normal tissue, lobar pneumonia. Framework destroyed: scar, bacterial abscess
177
keloids
excessive scar (TIMP unchecked)
178
contractures
tightening of skin after burns
179
inadequate scar
dehiscence (wound comes apart), ulceration
180
stages of wound healing
hemostasis, inflammation, proliferation, remodeling
181
inflammation in wound healing
neutrohils and macrophages. After hemostasis (platelets and clotting factors)
182
neutrophils in wound healing
arrive first (72 hours), remove debris
183
macrophages in wound healing
remove debris, screte cytokines and Gfs that signal angiogenesis and ECM remodeling
184
proliferation
3-7 days, remove fibrin clot, angiogenesis (VEGF!), re-epithelialize, matrix deposited (granulation tissue!)
185
remodeling
weeks. Collagen remodeling (balance of MMP and TIMP), wound contraction (myofibroblasts)
186
neoplasia
new growth
187
anaplasia
neoplasm with dedifferentiation. Not good.
188
dysplasia
disorderly maturation (HPV-cervix, smoking-lungs, GERD-esophagus)
189
grading
looking at cells
190
staging
T: where primary tumors are, N: region lymph nodes, M: metastasis
191
-oma
benign
192
-sarcoma, -carinoma
malignant (exception: invasive meningioma, melanoma)
193
AR diseases of defective DNA repair
Xeroderma pigmentosum, ataxia telangiectasia, bloom sydrome, Fanconi anemia
194
xeroderma pigmentosum
severe sunburn, discoloring, skin cancers
195
ataxia telangiectasia
ataxia, mental development decrease, discolored skin, x-ray sensitivity
196
bloom syndrome
short stature and tendency to develop cancers
197
fanconi anemia
ashkenazi Jews and afrikaners. Acute myelogenous leukemias, bone marrow failure, and developmental disabilities
198
Stain: CK7+CK20-
tracheal cancer
199
Stain: CK7-CK20+
colon cancer
200
Stain EGFR
lung cancer
201
metastasis dissemination
seeding of body cavities (ovarian), lymphatic spread (carinoma), hematogenous spread (sarcoma)
202
metastasis steps: detachment
through E-caherin loss
203
metastasis steps: ECM degradation
via MMP and TIMP collagenases. Then attach to new ECM
204
metastasis steps: migration
cytokine, autocrine, or paracrine stimulated motility
205
metastasis steps: travel as tumor emboli
selectin selection, ICAM and VCAM for locale stabilization, then diapedesis and invasion of endothelial cells
206
homing of tumor to certain locales
CXCR4, 7 in breast cancer, CDCL12 and CCL21 elsewhere
207
tissue architecture: benign
well circumscribed, encapsulated
208
tissue architecture: malignant
poorly circumscribed, lack of cell polarity and epithelial connections
209
cytologic features: benign
small uniform cells, no visible nucleoli
210
cytologic features: malignant
large, pleomorphic, larger hyperchromatic nuclei. Nucleus as big as cytoplasm
211
differentiation: benign
well differentiated, resembles cell of origin
212
differentiation: malignant
well differentiated if metastasized, otherwise numerous bizarre mitoses
213
rate of growth: benign
slow, some dependence on hormones
214
rate of growth: malignant
rapid, areas of necrosis from outgrowing blood supply
215
local invasion: benign
encapsulation, does not invade
216
local invasion: malignant
can invade and destroy adjacent tissue w/MMP, metastasize
217
biomarker: CEA
colon cancer
218
biomarker: AFP
Hepatoma
219
biomarker PSA
prostate cancer
220
biomarker Ca-125
Ovarian cancer
221
biomarker CA19-9
bile cancer
222
biomarker HCG
testis and placenta cancer
223
biomarker calcitonin
medullary cancer
224
asbestos causes
mesothelioma (cancer of protective lining of organs)
225
benzene causes
leukemia, hodgkin lymphoma
226
UV causes
Xeroderma pigmentosum
227
Most common cancer incidence
1. breast/prostate 2. lung 3. colon
228
Highest mortality cancer
1. lung 2. breast (F), colon (M) 3. Colon (F), Prostate (M)
229
cancer symptoms
TNF, Paraneoplastic syndrome, trousseau phenomenon
230
TNF & IL-1
Cachexia, suppresses fatty acid metabolism, catabolism
231
paraneoplastic syndrome
ectopic hormones (PTH-rP-hypercalcemia, ADH waterlogging)
232
trousseau phenomenon
miniclots all over the body
233
Making Cancer
1. self-sufficient growth signals 2. insensitivity to anti-growth factors 3. tissue invasion/metastasis 4. limtless replication potential 5. sustained angiogenesis 6. evading apoptosis
234
Self-sufficient growth factors: glioblastoma
PDGF/PDGFR
235
Self-sufficient growth factors: sarcoma
TGFalpha/TGFalphaR
236
SS receptor: squamous cell lung cancer
increased ERBB1 (EGFR)
237
SS receptor: breast cancer
increased Her2/ERBB2
238
2nd messengers: neurofibromatosis
RAS GTPase (inactivating) is mutated. Leads to elephant man
239
2nd messenger: ACR-ABL kinase
chromosome translocation leads to uninhibited tyrosine kinase
240
limitless replication
overexpression of telomerase , overrides p53/RB checkpoints
241
HPV16, 18
carcinoma of cervix
242
HHV8 virus
kaposi sarcoma
243
HBV, HCV virus
hepatocellular carcinoma
244
EBV virus
B-cell and nasopharyngeal cancer
245
nonlethal damage to cancer?
Proto-oncogenes, tumor suppressors, apoptosis related, DNA repair genes
246
rolling: selectins
| induced by
histimine, thrombin, TNF and IL-1
247
adhesion: integrins
| pairing
IFA to ICAMS
| VFA to VCAMS
248
FcR and complement bind what why?
IgG, C3, collectins
| to opsonize antigen!
249
LAD 1
adhesion defect (LFA)
250
LAD 2
```
rolling defect
(P selectin)
```
251
chronic granulomatous disease
NADPH oxidase deficient
252
Chediak-Higashi
can't deliver bacteria to lysosomes
253
high in cell
K, glucose, negative charge
254
low in high
Na, Cl-
