Endotoxin, Bacteremia, Septicemia
Xigris
manufactured protein C which can be activated and admin IV to deminish inflam response in severe sepsis and works at the level of endothelium
systemic inflammatory response syndrome
2+ of fever >38, tachypnea >20, tachycardia >90, leuckocytosis >12,000
Endotoxin
Lipopolysaccharide, OM, not denatured by heat, antigenic, no toxoid, low potency, low specificity, no enzymatic, pyrogenic
gram negative bacteria
O polysaccharide with O antigen on OM core polysaccharide with 2keto3deoxyoctonate to stabilize the lipid A and required for potency lipid A: the active center, string of myristic acid responsible for endotoxic effect periplasmic aspace: contains B lactamases here
sepsis
SIRS with proven microbial etiology and severe sepsis includes involvement of >1sign of organ failure
D dimers
degradation product of fibrin and levels elevate after clot formation...test if suspect DVT, PE, DIC factor XIII crosslinks E element to 2 D elements to make a thrombus
endotoxin on body
induction of fever, acute inflam, tissue destruction, RDS, damage capillaries, DIC, hypotension, irreversible shock, decr cardiac fxn, diarrhea
signs of septic shock
low arterial BP, weak rapid pulse, cold, pale, sweaty skin, rapid breathing, dry mouth, reduced urine output, anxiousness due to a loss of homeostasis with increased coagulation and decreased fibrinolysis infection/trauma...inflam...coag abnorm...microthrombi...microvascular dysfxn...organ failure decrease of Protein C with increase of D-dimer
endotoxin mechanism
lysis of gram neg cells releases LPS...binds LPS binding protein in blood...binds CD14 R on macrophages...release IL1, IL6, IL8, TNFa, PAF...binds cytokine R....initiate inflammation, activates complement, coagulation...blood clot, inflam, MAC lysis
bacteremia
presence of bacteria circulating in blood stream not necessarily causing bad effect but may cause septicemia
septicemia
presence of microbes in blood, systemic dz leading to septic shock
Exotoxin
protein, extracellular, denatured by heat, antigenic, toxoid, high potency, high specificity, enzymatic, sometime pyrogenic
gram positive bacteria
thick peptidoglycan layer with teichoic acid generally produce exotoxin
Protein C
vitamin dependent serine protease enzyme activated by thrombin to form activated protein C and is an anticoagulant inhibits factors V and VIII to inhibit thrombin inhibit PAI1 so profibrinolytic less TNF, IL1 to be anti inflam