Abstract: . . .  signaling receptors -> activate Nf kappaB to initiate massive cytokine synthesis (positive feedback loop) *potential therapeutic target* - TLR4 gram negative shock, TLR2 gram positive sepsis highly specific. (TLR4 KO mice do not develop shock even when injected with high levels of endotoxins) slide w/ nutmeg liver : massive amount of congestion Main culprit for low bp: NITRIC OXIDE 1. produced by endothelium and macrophages 2. NO Synthetase is induced in macrophages by numberous cytokines (iNOS) 3. deletion of cNOS (constitutive) from mice leads to systemic hypertension Mechanism : NO made by endothelial cells/macrophages diffuses through basement membrane due to gaseous properties relaxes vascular smooth muscle hypotension  . . .
. . .  red color, surrounded by neutrophils. slide w/ splenic infarct : result of arterial thrombotic occlusion (e.g. thromboembolus from a mitral valve , or local thrombosis due to sickle cell disease ). Yellow portion typical of necrotic tissue. slide w/ pulmonary embolus: in pulmonary artery, total infarction of upper lobe evident compared to other lobes. DISSEMINATED INTRAVASCULAR COAGULATION (DIC): Widespread thrombosis in the microcirculation with platelets and fibrin (few RBC) in capillaries. Activation of intrinsic pathway of coagulation. (Think sepsis or cancer) DIC mechanism : activation of intrinsic pathway Clinical findings: shock , respiratory distress, CNS depression, heart/renal failure Pathophysiology : rapid consumption of fibrinogen, platelets, prothombin, factors V, VIII, X, and at same time generation . . .
. . .  TLR4 gram negative shock, TLR2 gram positive sepsis highly specific. (TLR4 KO mice do not develop shock even when injected with high levels of endotoxins) slide w/ nutmeg liver : massive amount of congestion Main culprit for low bp: NITRIC OXIDE 1. produced by endothelium and macrophages 2. NO Synthetase is induced in macrophages by numberous cytokines (iNOS) 3. deletion of cNOS (constitutive) from mice leads to systemic hypertension Mechanism : NO made by endothelial cells/macrophages diffuses through basement membrane due to gaseous properties relaxes vascular smooth muscle hypotension  . . .
--2695,3,449,2691,13474