LPS can give septic shock: O-specific side chain is antigenic but not toxic; core region; Lipid A part is toxic. Basically an exaggerated, maladaptive inflammatory response. LPS activates macrophages via CD14; it also activates coagulation system -- hence DIC.
TLRs: family of 11 proteins; distinct extracellular domains, but similar intracellular domains; form heterodimers when activated. Activated by things like peptidoglycan, lipoteichoic acid, fungal glucan, viral RNA, LPS, oxLDL, flagellin, bacterial CpG DNA. Not just bacterial products but fungal and viral and even parasites! Bacterial TLRs on outer membrane, but also intracellular receptors for viral infections. Macrophages are primary responders to bacterial products.
Cytokines and other mediators. Macrophages release a lot of shit. Endothelial cells produce a lot of cytokines, plus NO (contributes to vasodilation, reduction in systemic vascular resistance, shock).
Tachypnea (respiratory alkalosis), fever --> compensated metabolic acidosis, hypotension, DIC --> ARDS, renal failure, hepatic damage. DIC: Consumption of platelets and coagulation factors. Microinfarcts. Hemorrhage due to consumption. DIC is major contributor to renal failure in septic shock. ARDS: Lungs fill up with fluid due to endothelial damage, may require intubation.
Can be gram positive, gram negative, mixed, or fungal, even viral in kids.
Risks factors: central venous catheter, malignancy causing neutropenia, HIV infection, old age, patients post-op for GI problem.
Treatment: First priority is keeping blood pressure up: fluid replacement, and pressors to keep BP above 90; start broad spectrum antibiotics promptly. Anti-inflammatory drugs don't work. Activated Protein C somewhat effective: reduces clotting, general anti-inflammatory effect.
Matching questions (on test?)
TLR2 -- peptidoglycan, glucan
TLR4 -- LPS
TLR5 -- Flagellin
CD14 -- LPS
Dectin -- Glucan (fungal)
No comments:
Post a Comment