Abstract: . . .  M&CP Lecture 11 PART I Shock, Hemorrhage & Thrombosis Dr. Lefkowitch PART II Shock Dr. Marcantonio transcriber: Maria Bradley-Moore (mdb143) September 23, 2004 Thanks to adobe acrobat most of this was copied from last years transcript which was verbatim. PART I SHOCK : Low perfusion circulatory insufficiency that results in an imbalance between the metabolic needs of vital organs and . . .
. . .  formation of LPS-LPB (LPS binding protein complex) in blood) (3) monocyte/macrophage binding of complex at CD 14 receptor (4) trigger cytokine secretion ( TNFa, IL-1 ) (5) endothelial cell secretion of cytokines, can lead to endothelial injury which leads to DIC Time course of cytokine induction (hrs) (fig 4-19) LPS in bloodstream then TNF then IL-1 then IL6, IL8 note: drugs that target TNF have not succeeded in part due to the quick rate of events. Pathogenesis of shock LPS Signaling : - target cells are macrophages and monocytes - CD 14 on cells and in the plasma binds LPS - Other cell surface receptors, such as CCR chemokine receptors and integrins may also bind LPS - Toll-like receptors (TLR) are the actual signaling receptors -> activate Nf kappaB to initiate massive cytokine synthesis (positive feedback . . .
. . .  Signaling : - target cells are macrophages and monocytes - CD 14 on cells and in the plasma binds LPS - Other cell surface receptors, such as CCR chemokine receptors and integrins may also bind LPS - Toll-like receptors (TLR) are the actual 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 . . .
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