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23 Cards in this Set

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Apoptosis
ATP required; activation of caspases; DNA laddering 180-bp; no inflammation

Intrinsic--Bcl-2 prevents cytochrome c release; dec IL-2 after completed immunological rxn triggers apoptosis

Extrinsic--FAS or T-cell release of perforin & granzyme
*FAS mutation-->autoreactive lymphocytes-->autoimmune disease
Hypoxic ischemic encephalopathy

Red neuron
Affects pyramidal cells of hippocampus and purkinje cells of cerebellum

Red neuron: a neuron responding to irreversible injury, typically evident 12-24 hrs after injurious event; eosinophilic cytoplasm, pyknotic nucleus, loss of nissl substance
Areas susceptible to ischemia:
Brain
Heart
Kidney
Liver
Colon
B: ACA/MCA/PCA boundary areas
H: subendocardium
K: PCT and thick loop
L: zone III (area around central vein)
C: splenic flexure, rectum

**CNS & neurons most susceptible; ischemia causes liquefactive necrosis and cystic astroglial scar
Dystrophic versus Metastatic calcification
Dy: localized calcium deposition in tissues secondary to necrosis; pancreatic saponification, breast trauma; pts are normally normocalcemic!!

Me: widespread deposition of calcium secondary to hypercalcemia; favors kidney, lungs, and GI due to increased pH; pts are hypercalcemic
Axonal rxn~chromatolysis
Seen in neural cell body following axonal injury-->increased protein synthesis and repair

Round cellular swelling
Displacement of nucleus to periphery
Dispersion of Nissl substance throughout cytoplasm
Leukocyte extravasation
Margination
Tight-binding
Diapedesis
Migration
Occurs at postcapillary venule

M: endothelial selectin interacts with leukocyte sialyl-lewisX protein; essentially speed bumps

T: interaction btw endothelial ICAM/VCAM and leukocyte CD18/integrin/LFA-1

D: actually exits blood vessel; PECAM to PECAM

M: C5a, IL-8, LTB4 are main chemotactic products
Free Radicals Pathologies

Radiation tx
Retinopathy of prematurity
Bronchopulmonary dysplasia
Iron overload (hemochromatosis)
Reperfusion injury (ypac post tPA tx)
**Acetaminophen OD (fulminant hep, renal papillary necrosis)
**CCl4-->RER swelling (free radical damage)->dec protein synthesis->dec apolipoproteins-->fatty liver necrosis

RTX: induces dsDNA break and forms free radicals
Wound healing mediators
PDGF
FGF
EGF
TGF-b
Metalloproteinases
PDGF: secreted by activated platelets and M0's; vascular remodeling and smooth muscle recruitment

**FGF: stimulates all aspects of angiogensis

EGF: stimulates cell growth via tyrosine kinase

TGF-b: angiogenesis, fibrosis, cell cycle arrest

**Metalloproteinases (collagenase, hydrolase): degrades collagen during tissue remodeling; **also used by invasive Ca to invade basement membrane
Granulomatous disease
TH1 cells secrete IFN-g to activate M0's. TNF-a from M0's maintains granuloma formation.

Anti-TNF drugs can cause granuloma breakdown-->disseminated disease. Always screen for latent TB before starting anti-TNF tx
ESR elevation

Common causes
Products of inflammation (fibrinogen) coat RBCs and cause aggregation--RBCs group (rouleax) and fall at faster rate

Anemia, infection, inflammation, cancer, pregnancy, autoimmune disorders
Iron poisoning
Mechanism
Sx's
Tx
Iron kills cells by peroxidation of membrane lipids

n/v, gastric bleeding

chelation (deferoxamine) and dialysis
Amyloidosis
AL (primary)
AA (secondary)
Dialysis-related
Heritable
Organ-specific
Due to misfolded proteins; stains congo red, apple green birefringence
AL--Ig Light chain; common in multiple myeloma or other plasma cell disorder
AA--acute phase reactant, seen in chronic conditions like RA
D: b2-microglobulin; may present as carpal tunnel syndrome
H: often due to transthyretin gene mutation-->cardiac amyloidosis and restrictive CM
O: amyloid-b protein in alzheimer; amylin in DM type II
P-glycoprotein
AKA multidrug resistance protein 1 (MDR1)

Expressed by some cancer cells to pump out toxins & chemotherapeutic agents. One mechanism of resistance to CTX.
Tumor Grade versus Stage
G: determined by degree of cellular differentiation and mitotic activity; low grade (well differentiated), high grade (anaplastic)

S: based on site and size of primary lesion, spread to lymph nodes and mets
Cachexia
Weight loss, muscle atrophy, and fatigue that occur in chronic disease (Ca, AIDS, CHF, TB). Mediated by TNF-a, IFN-g, and IL-6.
PSaMMoma bodies
Laminated, concentric, calcific spherules

Papillary thyroid carcinoma
Serous papillary cystadenocarcinoma of ovary
Meningioma
Malignant mesothelioma
Carcinogens--
Alfatoxins (aspergillus)
Alkylating agents
Aromatic amines (naphthylamine)
Asbestos
CCL4
Cigaretter smoke
Alf: liver-HCC
Alk: blood-leukemia, lymphoma
Aro: bladder-transitional cell carcinoma
Asbestos: lung-bronchogenic>mesothelioma
CCL4: liver-centrilobar necrosis, fatty change
Cigs: transitional CC; esophagus-squamous & adenocarcinoma; RCC; larynx-squamous; lung-squamous & small CC; pancreas-adenocarcinoma
Carcinogens--
Ethanol
Ionizing radiation
Nitrosamines (smoked foods)
Vinyl chloride
Eth: liver-HCC
Ion: thyroid-papillary thyroid carcinoma
Nit: stomach-gastric Ca
Vin: liver-angiosarcoma
Oncogenic Microbes
HBV, HCV
H. pylori
Liver fluke (Clonorchis sinensis)
Schistosoma haematobium
HBV, HCV--HCC
H. pylori--gastric adenocarcinoma & MALT lymphoma
Clonorchis--cholangiocarcinoma, pigmented gall stones; tx praziquantel
Schistosoma--bladder Ca (squamous), painless hematuria, snails are host; tx praziquantel
Oncogenes--
BCR-ABL
bcl-2
BRAF
c-kit
c/n/l myc
Her2-neu (c-erbB2)
ras
ret
Cause gain of fxn; need to damage only 1 allele

BCR-ABL--TK; CML & ALL
bcl-2--anti-apoptosis
BRAF--melanoma
c-kit--GIST GI stromal tumor
c/n/l myc--transcription factor; burkitt, lung tumor, neuroblastoma
Her2-neu (c-erbB2)--TK; breast, ovarian
ras--GTPase; colon, lung, pancreatic Ca
ret--TK; MEN 2A & 2B
Tumor suppressor genes--

APC
DCC
NF1
NF2
p53
Rb
Loss of fxn; both alleles must be lost--two hits
Loss of heterogeneity--"first hit"

APC: colorectal Ca (associated w/FAP)
BRCA1/2: DNA repair protein
DCC: deleted in colon Ca
NF1: RAS GTPase activating protein
NF2: merlin protein
p53: Li-Fraumeni syndrome; TF for p21; blocks G1 to S
Rb: retinoblastoma, osteosarcoma; inhibits E2F, blocks G1 to S
Tumor markers
Alkaline phosphatase
AFP
b-HCG
CA-19-9
CA-125
CEA
S-100
TRAP
ALP: mets to bone, liner, paget disease of bone, seminoma (placental ALP)
AFP: HCC, yolk sac tumor, testicular cancer, mixed germ cell tumors; normally made by fetus (commonly elevated due to underestimation of gestational age)
b-HCG: hydatidiform moles & choriocarcinomas
CA-19-9: pancreatic adenocarcinoma
CA-125: ovarian cancer
CEA: nonspecific; colorectal, pancreatic Ca
S-100: neural crest origin (melanomas, neural tumors, schwannomas), langerhans cell histiocytosis (tennis racket)
TRAP: Tartrate-Resistant Acid Phosphatase; hairy cell leukemia (B-cell neoplasm)
Tumor nomenclature
Carcinoma versus Sarcoma
Method of spread & exceptions
C: implies epithelial origin
S: implies mesenchymal origin

Carcinomas typically spread via lymphatics, while sarcomas spread via blood

Notable exceptions: RCC (renal vein); HCC (hepatic vein); follicular carcinoma of thyroid, and choriocarcinoma