The clinical course of sepsis depends on the type and resistance of the infectious organism, the site and size of the infecting insult, and the genetically determined or acquired properties of the host's immune system.
The pathogenesis of sepsis can be discussed as follows [2][3][4][5]
This response by complement system helps the B lymphocyte to produce memory cells in case of future infection and is responsible for the increased production and chemotaxis of more T helper cells.
The vascular endothelium plays a major role in the host's defense to an invading organism, but also in the development of sepsis.
Activated endothelium not only allows the adhesion and migration of stimulated immune cells but becomes porous to large molecules such as proteins, resulting in the tissue edema.
Through vasodilatation (causing reduced systemic vascular resistance) and increased capillary permeability (causing extravasation of plasma), sepsis results in relative and absolute reductions in circulating volume.
Relative and absolute hypovolemia are compounded by reduced left ventricular contractility to produce hypotension.
Initially, through an increased heart rate, cardiac output increases to compensate and maintain perfusion pressures, but as this compensatory mechanism becomes exhausted, hypoperfusion and shock may result.
Impaired tissue oxygen delivery is exacerbated by pericapillary edema.
It makes oxygen to diffuse a greater distance to reach target cells.
There is a reduction of capillary diameter due to mural edema and the procoagulant state results in capillary microthrombus formation.
Decreased blood flow through capillary beds, resulting from a combination of shunting of blood through collateral channels and an increase in blood viscosity secondary to loss of red cell flexibility.
As a result, organs become hypoxic, even with increased blood flow.
Cellular energy levels fall as metabolic activity begins to exceed production.
However, cell death appears to be uncommon in sepsis, implying that cells shut down as part of the systemic response.
This could explain why relatively few histologic changes are found at autopsy, and the eventual rapid resolution of severe symptoms, such as complete anuria and hypotension, once the systemic inflammation resolves.
↑ 4.04.1Cunneen J, Cartwright M (2004). "The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment". AACN Clin Issues. 15 (1): 18–44. PMID14767363.