free radical basics Correct Ans-Cyt C oxidase transfers electrons to O2 during oxidative
phosphorylation, accepts 4 electrons O2 => O2- => H2O2 => OH- => H2O
pathologic generation of free radicals Correct Ans-ionizing radiation (H2O => OH- most
damaging radical)
inflammatio (neutrophils oxygen dependent killing: makes HOCl)
metals (Cu & Fe, Fenten rxn => OH-... Wilson's & Hemocromatosis (=> cirrosis of liver))
drugs/chemicals (tylenol by liver P450 => free radicals; CCl4)
free radical making enzymes Correct Ans-O2 => O2- = NADPH oxidase
O2- => H2O2 = superoxide dysmutase (SOD)
H2O2 => HOCl = myeloperoxidase
H2O2 => H2O + O2 (catalase)
OH- => H2O (glutathione peroxidase)
elimination of free radicals Correct Ans-antioxidants: Vit A, C, E
metal carrier proteins: transferrin carries Fe in blood; Ferratin binds Fe in liver (so radicals not
produced)
enzymes SOD, catalase, glutathione peroxidase
free radical injury Correct Ans-CCl4 dry cleaning industry
, Pathoma- Questions and Answers
liver P450 converts CCl4 = CCl3-, damaged hepatocyes
cellular swelling, RER swell, lose ribosomes => fail to synthecize protein (apolipoprotein) =>
fat can get in, but can't get out (function of liver) => fatty change of liver
reperfusion injury
MI, cells die. cath lab, O2 returns => hits inflammatory cells, make free radicals => further
damage to cardiac myocytes
amyloid Correct Ans-usually beta-pleated sheet
amyloid pics up Congo red stain, reveals apple-green birefringence under polarized light
systemic amyloidosis Correct Ans-primary amyloidosis: deposition of AL (light chain)
amyloid; plasma cell dyscrasia diseases => overproduction of light chain => deposits into
tissue
secondary amyloidosis: depositoin of AA (acute phase reactant) amyloid; SAA = acute phase
reactant => AA... in chronic inflammation, malignancy, familial mediterranean fever
(dysfunctional neutrophils
kidney most involved organ => nephrotic syndrome (> 3.5 g/24 hr proteinuria)
restrictive cardiomyopathy (amyloid => less compliant heart wall)
, Pathoma- Questions and Answers
localized amyloidosis Correct Ans-senile cardiac amyloidosis: non-mutated serum
transthyretin
familial amyloid cardiomyopathy: mutated serum transthyretin => restrictive cardiomyopathy
(5% blacks)
DM II: byproduct of insulin is amylin, deposits in islets of pancreas => burns out pancreas =>
insulin-dependent DM II
alzheimer disease: Abeta amyloid (beta-amyloid precursor protein Chr 21)
dialysis-associated amyloidosis: beta2-microglobulin (amyloid) structural support for MHC I...
gets filtered poorly => deposits in joints
medullary carcinoma of thyroid: tumor cells overproduce calcitonin, deposits => amyloid
(thyroid cancer in amyloid backgroudn = medullary carcinoma)
acute inflammation Correct Ans-edema + neutrophils
infection & tissue necrosis
acute inflammation factors Correct Ans-Tol-like Receptors (TLRs)
Arachidonic acid
Mast cells
Compliment
Hageman factor
TLRs Correct Ans-Tol-like receptors: recognize PAMPs, e.g. CD14 on macrophages recognize
LPS of gram neg bact => activate macrophage/dendritic cell =>immune reponse
, Pathoma- Questions and Answers
arachadonic acid Correct Ans-from phospholipase A2; acted upon by 1 of 2 pathways
COX pathway => prostaglandins => vasodilation & inc. vascular permeability (PGE2 => pain &
fever)
5-lipooxygenase pathway => leukotrienes => vasoconstriction, bronchospasm, & inc. vascular
permeability (pericytes within vessel endothelial cells) (LTB4 attacts & activates neutrophils
Hypoxia Correct Ans-Ischemia, Hypoxemia, Dec. O2-carrying capacity
ischemia Correct Ans-dec. blood flow through organ: block arterial flow to, or venous flow
from
budd-chiari syndrome Correct Ans-thrombosis of hepatic vein => infarction of hepatic
parenchyma (1 - poly-cythemia very, or 2 - lupus anticoagulant)
hypoxemia Correct Ans-PaO2 < 60, or SaO2 < 90
FiO2 dec: high altitude
PAO2 dec: high PACO2 (hypoventillation, OCPD), interstitial fibrosis
Dec. O2-carrying capacity Correct Ans-anemia (PaO2 & SaO2 normal), CO poisoning,
methemoglobinemia (tx. IV methylene blue)