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177 Cards in this Set
- Front
- Back
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apoptosis requires _
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ATP
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intrinsic pathway of apoptosis mechanism (3)
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changes in levels of anti- and pro- apoptotic factors
--> -- ^ mitochondrial permeability -- release of cytochrome c |
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when does apoptosis intrinsic pathway happen? (4)
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embryogenesis
hormone induction e.g. menstruation atrophy e.g. endometrial lining in menopause injurious stimuli e.g. --radiation --toxins --hypoxia |
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extrinsic pathway of apoptosis mechanism
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--FasL binding to Fas (CD95)
--killer T cell release of perforin and granzyme B |
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both intrinsic & extrinsic apoptosis pathways lead to
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activation of cytosolic caspases -->
cellular breakdown |
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apoptosis histopathology
3 + 4 |
--cell shrinkage
--membrane blebbing --apoptotic bodies which are phagocytosed nuclear: --shrinkage --pyknosis --karyorrhexis --karyolysis |
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pyknosis
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irreversible condensation of chromatin in the nucleus
--> basophilia |
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karyorrhexis
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pyknotic nuclear fragmentation
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karyolysis
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nuclear fading
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types of necrosis
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coagulative
liquefactive caseous fatty fibroid gangrenous |
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coagulative necrosis is @
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heart
liver kidney |
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liquefactive necrosis is @
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brain
bacterial abscess pleural effusion |
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caseous necrosis is @
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TB
systemic fungi |
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fatty necrosis is @
and involves |
pancreas
saponification |
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fibroid necrosis is @
involves |
blood vessels
immune-mediated damage |
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gangrenous necrosis is @
types |
limbs
GI tract dry (ischemic) wet (bacteria) |
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necrosis involves (4)
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exogenous injury -->
enzymatic degradation, protein denaturation intracellular components extravasate inflammatory process |
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intrinsic apoptosis:
_ is pro-apoptotic _ is anti-apoptotic |
Bax
Bcl-2 |
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cell injury that's reversible with O2 (6)
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v ATP synthesis
cellular swelling chromatin clumping v glycogen fatty change ribosomal detachment (v protein synthesis) |
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cell injury that's irrreversible (7)
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nuclear
--pyknosis --karyolysis --karyorrhexis ca2+ influx --> caspase activation membrane damage lysosomal rupture mitochondrial permeability |
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red infarcts occur when/where?
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loose tissues with collaterals e.g.
liver lungs intestine or following reperfusion |
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reperfusion injury is due to damage by
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free radicals
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pale infarcts occur where/when?
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solid tissues with single blood supply e.g.
heart kidney spleen |
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atrophy is _
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reduction in size or number of cells
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6 causes of atrophy
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v hormones (uterus/vagina)
v innervation (motor neurons) v blood flow v nutrients ^ pressure (nephrolithiasis) occlusion of secretory ducts (cystic fibrosis) |
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inflammation:
abscess-- |
fibrosis surrounding pus
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inflammation:
granulation tissue-- |
highly vascularized
fibrotic |
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mediators of
acute vs. chronic inflammation |
neutrophil
eosinophil antibodies mononuclear cells |
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chronic inflammation characterizations/associations
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persistent destruction & repair
vessel proliferation fibrosis granulomas |
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leukocyte extravasation steps (4)
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rolling
tight binding diapedesis migration |
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leukocyte extravasation
vasculature/stroma vs. leukocyte molecules involved in rolling |
e-selectin
p-selectin sialyl lewis |
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leukocyte extravasation
vasculature/stroma vs. leukocyte molecules involved in tight binding |
ICAM-1
LFA-1 ("integrin") |
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leukocyte extravasation
vasculature/stroma vs. leukocyte molecules involved in diapedesis |
PECAM-1
PECAM-1 |
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leukocyte diapedesis is
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leukocyte travels between endothelial cells and exits blood vessel
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leukocyte migration is
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travels through interstitium
to injury or infection site guided by chemotactic signals |
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leukocyte extravasation
vasculature/stroma vs. leukocyte molecules involved in |
--bacterial products
"CILK" C5a IL-8 LTB4 Kallikrein ---------------------------- various |
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free radicals damage cells via (3)
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membrane lipid peroxidation
protein modification DNA breakage |
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free radical injury is initiated by (6)
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radiation
phase I metabolism of drugs transition metals redox rxns NO leukocyte oxidative burst |
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free radicals --> pathologies...
(6) |
preemies:
--retinopathy of prrematurity --bronchopulmonary dysplasia CCl4 acetaminophen iron overload reperfusion |
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CCl4 -->
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liver necrosis (fatty change)
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reperfusion free radical injury involves _
esp occurs when? |
superoxide
after thrombolytic rx |
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granulomatous diseases (8)
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tuberculosis
leprosy fungal infections (e.g. histoplasmosis) syphilis sarcoidosis berylliosis cat scratch fever Crohn's |
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mechanism of granuloma formation/maintenance
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Th1 cells: gamma-interferon -->
+ macrophages: TNF-alpha |
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a bad juju that happens with anti-TNF drugs...
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break down granulomas
--> disseminated disease |
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a drug that can break down granulomas
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anti-TNF
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transudate vs. exudate
cellularity protein specific gravity |
hypocellular vs. cellular
poor vs. rich < 1.012 > 1.020 |
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transudate vs. exudate
due to: |
^ hydrostatic pressure
v oncotic pressure Na+ retention lymphatic obstruction inflammation |
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ESR: RBCs fall at a faster rate within the test tube because...
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products of inflammation e.g. fibrinogen
coat RBCs --> aggregation |
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a surprise cause of ^ ESR
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pregnancy
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(3) cause v ESR
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sickle cell (altered shape)
polycythemia (too many) CHF |
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iron poisoning epi
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one of the leading causes of toxicologic fataly in children
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iron poisoning moa
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cell death 2^ peroxidation of membrane lipids
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iron poisoning sxs
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acute: gastric bleeding
chronic: --metabolic acidosis --scarring --> GI obstruction |
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amyloidosis
--in a word |
beta-pleated sheet
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amyloidosis
--lab |
apple-green birefringence of
Congo-red stain under polarized light |
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amyloidosis
--gross clinical |
tissue has waxy appearance
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primary amyloidosis
--protein --derived from |
AL
Ig light chains (multiple myeloma) |
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secondary amyloidosis
--protein --derived from |
AA
serum amyloid-associated protein (chronic inflammatory disease) |
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senile cardiac amyloidosis
--protein --derived from |
transthyretin
AF |
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diabetes II amyloidosis
--protein --derived from |
amylin
AE |
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medullary thyroid carcinoma amyloidosis
--protein --derived from |
A-CAL
calcitonin |
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Alzheimer's amyloidosis
--protein --derived from |
beta-amyloid
amyloid precursor protein (APP) |
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dialysis-associated amyloidosis
--protein --derived from |
beta-2 microglobulin
MHC class I |
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types of amyloidosis
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primary
secondary senile cardiac alzheimer's medullary thyroid carcinoma diabetes II dialysis-associated |
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hypovolemic/cardiogenic vs. septic shock
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low-output
^ TPR low cardiac output cold, clammy -- high-output -- v TPR -- dilated arterioles, high venous return -- hot |
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neoplastic progression:
hyperplasia |
increase in number of cells
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neoplastic progression:
dysplasia |
abnormal proliferation
loss of size shape orientation |
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neoplastic progression:
carcinoma in situ/preinvasive |
--have not invaded basement membrane
--neoplastic cells encompass entire thickness --high nuclear/cytoplasmic ratio --clumped chromatin |
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neoplastic progression:
invasion of the basement membrane occurs by using _ |
collagenases
hydrolases |
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metastasis, to occur, must survive
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immune attack
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metastasis molecular changes {{on the surface of cancer cells??}}
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v cadherin
^ laminin, integrin receptors |
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hyperplasia
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^ number of cells
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metaplasia (3)
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one adult cell type is replaced by another
often 2^ irritation or exposure e.g. squamous metaplasia in trachea and bronchi of smokers |
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dysplasia
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abnormal growth
loss of orientation shape size |
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reversible plasias vs. irreversible plasias
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hyperplasia
metaplasia dysplasia anaplasia neoplasia desmoplasia |
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anaplasia
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"undifferentiated malignant neoplasms"
lacking differentiation, like that tissue's primitive cells little or no resemblance to tissue of origin |
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neoplasia
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clonal proliferation that's
uncontrolled and excessive |
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desmoplasia
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fibrous tissue formation
in response to neoplasm |
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tumor grade vs. stage
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diffferentiation
spread |
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_ _ _ staging system
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TNM
size of tumor node involvement metastasis |
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_ is often more predictive of cancer prognosis than _
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stage
grade |
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epithelial tumors
benign malignant |
adenoma
papilloma adenocarcinoma papillary carcinoma |
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blood vessel tumors:
benign malignant |
hemangioma
angiosarcoma |
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skeletal muscle tumors:
benign malignant |
rhabdomyoma
rhabdomyosarcoma |
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tumors with
> 1 cell type |
benign:
--mature teratoma (women) malignant: --immature teratomas --mature teratoma (men) |
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_ implies epithelial origin of a malignant tumor
_ implies mesenchymal origin of a malignant tumor |
carcinoma
sarcoma |
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neoplasms associated with
down syndrome |
ALL ("we all fall down")
AML |
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neoplasms associated with
xeroderma pigmentosum & albinism |
melanoma
basal cell carcinoma squamous cell carcinomas esp |
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gastric adenocarcinoma is associated with (3)
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chronic atrophic gastritis
pernicious anemia postsurgical gastric remnants |
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tuberous sclerosis = (3)
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facial angiofibroma
seizures mental retardation |
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neoplasms associated with
tuberous sclerosis |
astrocytoma
angiomyolipoma cardiac rhabdomyoma |
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neoplasms associated with
actinic keratosis |
squamous cell carcinoma of skin
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barrett's esophagus is associated with _ cancer
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esophageal adenocarcinoma
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neoplasms associated with
plummer vinson syndrome |
squamous cell carcinoma of esophagus
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plummer vinson triad
cause? |
iron deficiency -->
atrophic glossitis esophageal webs anemia |
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(3) --> hepatocellular carcinoma
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cirrhosis 2^ alchol, hep b, hep c
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neoplasms associated with
ulcerative colitis |
colonic adenocarcinoma
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neoplasms associated with
paget's disease of the bone |
2^ osteosarcoma
fibrosarcoma |
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neoplasms associated with
immunodeficiency |
lymphomas
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autoimmune diseases e.g. (2)
--> lymphoma |
hashimoto's thyroiditis
myasthenia gravis |
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neoplasms associated with
acanthosis nigricans |
BLUStering malignancy
breast lung uterus stomach |
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acanthosis nigricans = (2)
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hyperpigmentation
epidermal thickening |
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malignant melanoma is associated with _ of the skin
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dysplastic nevus
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neoplasms associated with
radiation exposure (2) |
sarcoma
papillary thyroid cancer |
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tumor and gene product associated with
abl |
CML
tyrosine kinase |
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tumor and gene product associated with
c-myc |
Burkitt's lymphoma
transcription factor |
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tumor and gene product associated with
bcl-2 |
follicular and undifferentiated lymphomas
inhibits apoptosis |
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tumor and gene product associated with
erb-B2 |
breast
ovarian gastric carcinomas tyrosine kinase |
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tumor and gene product associated with
ras |
colon carcinoma
GTPase |
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tumor and gene product associated with
L-myc N-myc |
Lung tumor
Neuroblastoma transcription factor transcription factor |
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tumor and gene product associated with
ret |
MEN II and III
tyrosine kinase |
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tumor and gene product associated with
c-kit |
gastrointestinal stromal tumor aka GIST
cytokine receptor |
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oncogenes whose product is a tyrosine kinase
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abl
erb-B2 ret |
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oncogenes whose product is a transcription factor
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c-myc
L-myc N-myc |
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an oncogene whose product is an anti-apoptotic molecule
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bcl-2
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an oncogene that's a GTPase
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ras
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ras's gene product is a _
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GTPase
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9 oncogenes
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c-myc
L-myc N-myc abl bcl-2 erb-B2 ret ras c-kit |
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11 tumor suppressor genes
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Rb
p53 p16 BRCA1 BRCA2 APC DPC DCC WT1 NF1 NF2 |
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tumor and gene product associated with
Rb |
retinoblastoma
osteosarcoma blocks G1 --> S phase |
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tumor and gene product associated with
p53 |
most human cancers
Li-Fraumeni syndrome blocks G1 --> S phase |
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tumor suppressor genes whose products block
G1 --> S phase |
Rb
p53 |
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tumor and gene product associated with
BRCA1 BRCA2 |
breast and ovarian
breast -------------------------- DNA repair protein |
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tumor associated with p16
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melanoma
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tumorr associated with APC
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colorectal cancer (FAP)
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pancreatic cancer is associated with _ gene
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DPC
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colon cancer is associated with (2) tumor suppressor genes
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APC
DCC |
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Rb chromosome
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13q
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p53 chromosome
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17p
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BRCA1
BRCA2 chromosomes |
17q
13q |
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p16 chromosome
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9p
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APC chromosome
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5q
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WT1 chromosome
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11p
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NF1
NF2 chromosomes |
17q
22q |
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DPC
DCC chromosomes |
18q
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tumor markers:
PSA prostatic acid phosphatase |
prostate carcinoma
BPH prostatitis ------------------------ prostate carcinoma |
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tumor markers:
CEA |
carcinoembryonic antigen
nonspecific 70% of colorectal and pancreatic cancers also in cancers of: --gastric --breast --thyroid medullary |
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tumor marker:
alpha-fetoprotein (3) |
mormally made by fetus
hepatocellular carcinomas nonseminomatous germ cell tumors of the testis (e.g. yolk sac tumor) |
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tumor marker
CA-125 |
ovarian
malignant epithelial tumors |
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tumor marker
S-100 |
melanoma
neural tumors astrocytomas |
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tumor marker
alkaline phosphatase |
metastases to bone
obstructive biliary disease Paget's disease of bone |
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tumor marker
bombesin |
neuroblastoma
lung gastric |
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tumor marker
TRAP (tartrate-resistant acid phosphatase) |
hairy cell leukemia
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hairy cell leukemia is a neoplasm of _ cells
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B cells
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tumor markers:
CA-19-9 |
pancreatic adenocarcinoma
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HHV-8 --> ____ cancers
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--Kaposi's sarcoma
--body cavity fluid B-cell lymphoma |
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H pylori causes _ gastric cancer
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gastric adenocarcinoma
gastric lymphoma |
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aflatoxins are notably produced by _
cause what? |
aspergillus
hepatocellular carcinoma |
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vinyl chloride C2 H3 Cl -->
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angiosarcoma
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_ carcinogens causes angiosarcoma
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vinyl chloride
asbestos |
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nitrosamines cause cancer @
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esophagus
stomach |
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cigarette smoke causes _ cancers
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larynx
--squamous cell carcinoma lung --squamous cell carcinoma --small cell carcinoma kidney --renal cell carcinoma bladder --transitional cell carcinoma |
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CCl4 -->
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liver
--centrilobular necrosis --fatty change |
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asbestos -->
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mesothelioma
bronchogenic carcinoma |
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arsenic -->
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skin
--squamous cell carcinoma liver --angiosarcoma |
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naphthaleene (aniline) dyes -->
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bladder
--transitional cell carcinoma |
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alkylating agents -->
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leukemia
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paraneoplastic effects
___ --> ACTH or ACTH-like peptide |
small cell lung carcinoma
|
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paraneoplastic effects
____ --> ADH |
small cell lung carcinoma
intracranial neoplasms |
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small cell lung carcinoma --> ___ paraneoplastic products
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ACTH
ADH |
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hypercalcemia as a paraneoplastic effect
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squamous cell lung
renal cell carcinoma breast carcinoma --> PTH-related peptide TGF-beta TNF IL-1 --> hypercalcemia |
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cushing syndrome as a paraneoplastic effect
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small cell lung carcinoma
--> ACTH or ACTH-like peptide |
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SIADH as a paraneoplastic effect
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small cell lung carcinoma
intracranial neoplasms --> ADH --> SIADH |
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polycythemia as a paraneoplastic effect
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renal cell carcinoma
hemangioblastoma --> erythropoietin |
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hemangioblastoma is ____
|
spinal
brain stem cerebellar very vascular |
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gout
urate nephropathy as paraneoplastic effects |
leukemias
lymphomas --> hyperuricemia due to excess nucleic acid turnover (i.e., cytotoxic therapy) |
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psammoma bodies
(image) |
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psammoma bodies are _
|
laminated
concentric calcific spherules |
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psammoma bodies are seen in (4)
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PSaMMoma:
1. Papillary adenocarcinoma of thyroid 2. Serous papillary cystadenocarcinoma of ovary 3. Meningioma 4. Malignant mesothelioma |
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cancer epidemiology:
|
male, female
incidence: prostate 32%, breast 32% lung 16%, 13% colon and rectum 12%, 13% --------------------------------- mortality: lung 33%, 23% prostate 13%, breast 18% |
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tumors that metastasize to brain
|
Lots of Bad Stuff Kills Glia
lung breast skin (melanoma) kidney (renal cell carcinoma) GI |
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two general comments about cancer that metastasizes to the brain
|
approximately 50% of brain tumors are from metastases
multiple well-circumscribed tumors @ gray/white matter junction |
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the most common sites of metastasis
|
1. regional lymph nodes
2. lung & liver |
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the most common tumors that metastasize to the liver
|
Cancer Sometimes Penetrates Benign Liver
Colon > Stomach > Pancreas > Breast > Lung |
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these 1^ tumors metastasize to bone
|
P.T.T. Barnum Loves Kids
**Prostate Thyroid Testes **Breast Lung Kidney ** most common |
|
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bone tumors: 1^ or metastatic are more common?
liver? brain? |
metastatic are far more common
metastatic >> 1^ 50% / 50% |
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two types of bone metastases
which organs do they come from? |
lung --> lytic
prostate --> blastic breast --> lytic and blastic |
