FA Pathology

eesohbel's version from 2015-07-27 02:43

Apoptosis and necrosis

Question Answer
Characteristics of apoptosiscell shrinkage
nuclear shrinkage (pyknosis) and basophilia
membrane blebbing
nuclear fragmentation (karyorrhexis)
formation of apoptotic bodies - later phagocytosed
When is the intrinsic pathway for apoptosisTissue remodeling in embryogenesis
exposure to injurious stimuli
via inc. mitochondria permiability and cytochrome c release. BAX and BAK are proapoptotic. Bcl2 is antiapoptotic
Extrinsic pathways (2)Ligand receptor interactions - Fas ligand binding to Fas [CD95]
Immune cell - cytotoxic T-cell release of perforin and granzyme B
Coagulative necrosisinfarcts/ischemia in most tissues (except brain)
Liquefactive necrosisbrain, bacterial abscess, pleural effusion
Caseating necrosisTB, systemic fungi
Fatty necrosisperipancreatic fat (saponification via lipase) and breast trauma
Fibrinoid necrosisimmune reactions at vessels
Gang necrosiscommon in limbs and GI tract

Cell injury

Question Answer
decreased ATP synthesisreversible
cellular swelling (no ATP, impaired Na/K pump)reversible
nuclear chromatin clumpingreversible
decreased glycogenreversible
fatty changereversible
ribosomal detachment (decreased protein synthesis)reversible
nuclear pyknosis, karyolysis, karyorrhexisirreversible
calcium influx, caspase activationirreversible
plasma membrane ruptureirreversible
lysosomal ruptureirreversible
mitochondrial permeabilityirreversible

Areas susceptible to hypoxia and ischemia/infarcion

Question Answer
brain ischemia susceptibilityACA/MCA/PCA boundary areas
heartsubendocardium (LV)
kidneystraight segment of proximal tubule (medulla), thick ascending limb (medulla)
liverarea around central vein (zone III)
colonsplenic flexure, rectum
hypoxic ischemic encephalopathy (HIE) affectspyramidal cells of hippocampus and Purkinje cells
reperfusion injury is due to damage byfree radicals
Red infarctsdue to hemorrhage
in loose tissues with collaterals: liver, lungs, intestine, or following reperfusion
Pale infarctsin solid tissues with a single blood supply: heart, kidney, and spleen
hypovolemic/cardiogenic shocklow-output failure, high TPR, low cardiac output, cold and clammy patient
septic shockhigh-output failure, low TPR, dilated arterioles and high venous return, hot patient

Atrophy & Inflammation

Question Answer
atrophy due to decreased hormonesuterus/vagina
atrophy due to decreased innervationmotor neuron damage
atrophy due to increased pressurenephrolithiasis
atrophy due to occlusion of secretory ductscystic fibrosis
vascular component of inflammationincreased vascular permeability, vasodilation, endothelial injury
cells mediating acute inflammationneutrophil, eosinophil, antibody
potential outcomes of acute inflammationresolution, abscess, progression to chronic inflammation
cells mediating chronic inflammationmononuclear cells
granulomanodular collections of epithelioid macrophages and giant cells
potential outcomes of chronic inflammationscarring, amyloidosis
chronic inflammation associated with blood vesselproliferation, fibrosis

Leukocyte extravasation

Question Answer
vascular rolling proteinsE-selectin, P-selectin
neutrophil rolling proteinSialyl-LewisX
vascular tight binding proteinICAM-1
neutrophil tight binding proteinLFA-1 ("integrin")
vascular diapedesis proteinPECAM-1
neutrophil diapedesis proteinPECAM-1
neutrophil chemotactic agentsbacterial products, C5a, IL-8, LTB4, Kallikrein (CILK)

Free radical injury

Question Answer
mechanisms of free radical damage to cellslipid peroxidation, protein modification, DNA breakage
antioxidant vitaminsA, C, E
enzymes that eliminate free radicalscatalase, superoxide dismutase, glutathione peroxidase

Wound healing

Question Answer
cell mediators of inflammatory phase of wound healingplatelets
macrophages (clear debris after 2 days)
cell mediators of proliferative phase of wound healingfibroblasts
myofibroblasts (mediate wound contraction)
endothelial cells
things that happen in proliferative phase of wound healingdeposition of granulation tissue and collagen
epithelial cell proliferation
clot dissolution
cell mediators of remodeling phase of wound healingfibroblasts
things that happen in remodeling phase of wound healingtype III collagen replaced by type I collagen
increasing tensile strength of tissue
Order/timing of wound healing phasesInflammatory - immediate
Proliferative - 2-3 days after wound
Remodeling - 1 week after wound

Granulomatous diseases

Question Answer
infectious granulomatous diseasesM. tuberculosis
fungal infections
autoimmune granulomatous diseasessarcoidosis
Crohn's disease
granulomatosis with polyangiitis (Wegner's)
environmental granulomatous diseasesberylliosis, silicosis
TH1 cells activate macrophages by secretingγ-interferon
released from macrophages to induce and maintain granuloma formationTNF-α
side effect of anti-TNF drugsbreak down granulomas, disseminating disease

Transudate vs Exudate & ESR

Question Answer
specific gravity of transudate< 1.012
specific gravity of exudate> 1.020
causes of transudateincreased hydrostatic pressure (ex.HF), decreased oncotic pressure (ex.cirrhosis, nephrotic syndrome), sodium retention
causes of exudatelymphatic obstruction, inflammation
causes of increased ESRinfections, inflammation, cancer, pregnancy, SLE
causes of decreased ESRsickle cell, polycythemia, CHF

Iron poisoning

Question Answer
mechanism of iron poisoningperoxidation of membrane lipids leads to cell death
symptoms of acute iron poisoninggastric bleeding
symptoms of chronic iron poisoningmetabolic acidosis, scarring leading to GI obstruction


Question Answer
macroscopic appearance of tissue in amyloidosiswaxy
microscopic appearance of tissue in amyloidosisapple-green birefringence (Congo red stain) of amyloid deposits
AL (primary) amyloidosis due to deposition ofIg light chains
AL amyloidosis associated withmultiple myeloma, plasma cell disorder
organ systems involved in AL amyloidosisnephrotic syndrome
cardiac (heart failure, arrhythmia)
hematologic (easy bruising)
hepatomegaly and neuropathy
composition of protein in AA amyloidosisserum amyloid A
AA amyloidosis associated withchronic diseases; RA, IBD, spondyloarthropathy, chronic infections
AA amyloidosis effect on organ systemssame as AL; nephrotic syndrome, cardiac (heart failure, arrhythmia), hematologic (easy bruising), hepatomegaly and neuropathy
dialysis-related amyloidosisbeta-2-microglobulin
dialysis-related amyloidosis often presents ascarpal tunnel syndrome and other joint issues

Precursor Proteins for Organ Specific Amyloid

Question Answer
cardiac atriaANP
pancreasislet amyloid polypeptide

Disease conditions associated with neoplasms

Question Answer
barrett esophagusprecursor to esophageal adenocarcinoma
chronic atrophic gastritispredisposes to gastric adenocarcinoma
cirrhosispredisposes to HCC
UCpredisposes to colon adenocarcinoma
actinic keratosisprecursor to squamous cell carcinoma of the skin
dermato and polymyositispredisposes to visceral malignancies, particulalry genitourinary
dysplastic nevusprecursor to malignant melanoma
Paget diseaseosteosarcoma and fibrosarcoma
Plummer Vinsonsquamous cell carcinoma of the esophagus
tuberous sclerosismanifests with multiple hamartomas including giant cell astrocytomas, renal angiomyolipomas, cardiac rhabdomyomas that may become malignant
xeroderma pigmentosumpredisposes to squamous cell, basal cell, melanoma
DownALL and AML

Oncogenes, gain of function increases cancer risk. need damage to only 1 allele.

Question Answer
number of damaged oncogene alleles needed to increase cancer risk1
abl cancerCML
abl gene producttyrosine kinase
c-myc cancerBrukitt's lymphoma
c-myc gene producttranscription factor
bcl-2 tumorfollicular and undifferentiated lymphoma
bcl-2 gene productanti-apoptotic molecule
HER2/neu tumorbreast, ovarian and gastric carcinomas
HER2/neu gene producttyrosine kinase
ras tumorcolon carcinoma
ras productGTPase
L-myc tumorlung tumor
L-myc producttranscription factor
N-myc tumorneuroblastoma
N-myc producttranscription factor
ret tumorMEN 2A and 2B
ret producttyrosine kinase
c-kit tumorgastrointestinal stromal tumor (GIST)
c-kit productcytokine receptor

Tumor suppressor genes. loss of function. both alleles must be lost to cause expression

Question Answer
number of damaged tumor suppressor gene alleles necessary to express disease2
Rb tumorretinoblastoma, ostersarcoma
Rb productinhibits E2F; blocks G1 to S phase
p53 tumormost cancers, Li-Fraumeni syndrome
p53 producttranscription factor for p21, blocks G1 to S phase
BRCA1 tumorbreast and ovarian cancer
BRCA1 productDNA repair protein
BRCA2 tumorbreast and ovarian cancer
BRCA2 productDNA repair protein
p16 cancermelanoma
BRAF tumormelanoma
BRAF productB-raf
APC tumorcolorectal cancer (associated with FAP)
WT1 tumorWilms' tumor (nephroblastoma)
NF1 tumorneurofibromatosis type 1
NF1 productRAS GTPase activating protein (RAS-GAP)
NF2 tumornerofibromatosis type 2
NF2 productmerlin (schwannomin) protein
DPC4 tumorpancreatic cancer
DCC tumorcolon cancer

Oncogene vs. tumor suppressor genes

Question Answer
HER2/neu (c-erbB2)oncogene
RbTumor suppressor gene
p53Tumor suppressor gene
BRCA1Tumor suppressor gene
BRCA2Tumor suppressor gene
p16Tumor suppressor gene
BRAFTumor suppressor gene
APCTumor suppressor gene
WT1Tumor suppressor gene
NF1Tumor suppressor gene
NF2Tumor suppressor gene
DPC4Tumor suppressor gene
DCCTumor suppressor gene

Tumor markers

Question Answer
PSAprostate carcinoma. can be elevated in BPH and prostatits
prostatic acid phosphataseprostate carcinoma
CEAnon-specific for colorectal and pancreatic cancers; also produced by gastric, breast, and medullary thyroid cancer
alpha-fetoproteinhepatocellular carcinoma, non-seminomatous germ cell tumors
beta-hCGhydatidiform moles and choriocarcinomas
CA-125ovarian cancer
S-100melanoma, neural tumors, schwannomas
alkaline phosphatasemetastases to bone, liver, Paget's disease of bone
bombesinneuroblastoma, lung and gastric cancer
TRAPhairy cell leukemia (stands for Tartrate-Resistant Acid Phosphatase)
CA-19-9pancreatic adenocarcinoma
Calcitoninmedullary thyroid carcinoma
AFPuseful makrer in evaluation of cirrhotic patients who are at increased risk for HCC

Oncogenic microbes

Question Answer
HTLV-1adult T-cell leukemia/lymphoma
HBV, HCVhepatocellular carcinoma
EBVBurkitt's lymphoma
Hodgkin's lymphoma
nasopharyngeal carcinoma
CNS lymphoma (in immunocompromised)
HPVcervical carcinoma (16, 18), penile/anal carcinoma, upper respiratory SCC
HHV-8Kaposi's sarcoma
body cavity fluid B-cell lymphoma
H. pylorigastric adenocarcinoma
Shistosoma haematobiumbladder cancer (squamous cell)
Liver fluke (clonorchis sinensis)cholangiocarcinoma

Chemical carcinogens

Question Answer
arsenicangiosarcoma/lung cancer/ squamous cell carcinoma
asbestosbronchiogenic carcinoma greater than mesothelioma
ionizing radiationpapillary carcinoma of the thyroid
nitrosaminesgastric cancer
radonlung (2nd leading cause after cigarette smoke)
vinyl chlorideangiosarcoma
ethanolsquamous cell carcinoma of esophagus and HCC

Paraneoplastic syndromes

Question Answer
ACTHsmall cell lung carcinoma, renal cell carcinoma
ADHsmall cell lung carcinoma, intracranial neoplasm
antibodies against pre-synaptic calcium channels at NMJ (aka lambert eaton)small cell lung carcinoma
erythropoietinrenal cell carcinoma, hemangioblastoma, HCC, leiomyoma, pheo
PTHrPsquamous cell lung carcinoma, renal cell carcinoma, breast cancer
psammoma bodiesPSaMMoma (Papillary carcinoma of thyroid, Serous papillary cystadenocarcinoma, Meningioma, Malignant Mesothelioma)

Cancer epidemiology

Question Answer
Most common (incidence) - male cancersProstate
Most common (incidence) - Female cancersBreast
Male cancers with highest mortalityLung
Female cancers with highest mortalityLung
1st and 2nd leading cause of death in the USHeart disease

Common metastases

Question Answer
most brain tumors are frommetastases
typical location of brain tumorgray/white junction, well circumscribed
tumors that metastasize to brainlung
most common sites of metastasis, after regional lymph nodesliver and lung
tumors that metastasize to livercolon >> stomach > pancreas
lung → bone mets arelytic
prostate → bone mets areblastic
breast → bone mets arelytic and blastic
tumors that metastasize to boneprostate
breast > lung > thyroid

Collagen synthesis

Question Answer
type Idermis, bone, tendons, ligaments, dentin, cornea, blood vessels and scar tissue
diseases associated with type I collagenosteogenesis imperfecta
type IIcartilage, vitreous humor, nucleus pulposus
type IIIskin, lungs, intestines, blood vessels, bone marrow, lymphatics and granulation tissue
type Iv collagenbasement membrane
associated diseases with type IV collagenalport syndrome

You should know these

Question Answer
Neurofibromatosis 1Cafe-au-lait spots
Lisch nodules
Optic gliomas
Neurofibromatosis 2Bilateral acoustic schwannomas

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