Question

What is the pathophysiology of Sepsis?

Answer 1

Sepsis is the final common pathway for a number of potentially lethal clinical events, including severe hemorrhage, extensive trauma or burns, large Myocardial Infarction, massive pulmonary embolism and microbial sepsis.

What ever is the pathology sepsis leads to systemic hypoperfusion, it is caused due to either reduced cardiac output or by reduced effective circulating blood volume.

Pathophysiology

Three types of shock

1) Cardiogenic shock: failure of cardiac pump

Caused by Myocardial damage, ventricular arrythmia

2) Hypovolemia shock: loss of blood or plasma volume

Caused by hemorrhage, fluid loss from severe burns or trauma.

3) septic shock: by microbial infection

Mostly by gram negative infection ( endotoxic shock)

Host inflammatory responses to local extravascular infections

All of the cellular and hemodynamic effects of sepsis are due to LPS, it binds to protein and binds to a specific receptor (CD14) on monocytes, macrophages, and neutrophils. CD 14 signelling results in profound activation of mononuclear cells and production of cytokines such a IL 1 and TNF

And these cytokines act on endothelial cells leading to reduced synthesis of anticoagulation factors such as tissue factor pathway inhibitor and thrombomodulin.

TLR mediated activation trigger the innate immune system but department on the dosage and extend of immune and vascular activation the secondary effects of LPS release leading to shock

Finally LPS high levels lead to:

Systemic vasodilation( hypotension)

Reduced മൈക്കോ contractility

Widespread endothelial injury

Activation of coagulation system leading to DIC

The hypoperfusion is due to effect of vasodilation, Myocardial failure, DIC leads to multiorgan failure

Abbreviation:

LPS : Lipopolysaccharide

DIC: dissemiated intravascular coagulation

TNF: Tumor necrosis factor