What is Sepsis?  Hypotension

Peripheral Vascular Failure and Capillary Leak in Sepsis

The microcirculation is the main site of injury in systemic sepsis (12). There are two stages in the process, the first compensatory phase (physiologic reserve) and the second – a phase of decompensation, when reserve runs out or the inflammatory process goes out of control (figures 9 –10).

Stage 1: compensation

In response to intravascular volume depletion (distributive or hypovolemic shock), the pre capillary arterioles and post capillary venules vasoconstrict: this helps maintain systemic blood pressure. Due to narrowing of the entrance to the microcirculation, the velocity of blood passing through it increases, increased hydrostatic pressure in the capillaries. This has the effect of sucking fluid in from the interstitium (a net influx of fluid into the circulation). This is known as "transcapillary refill". Fluid effectively shifts from the extravascular to the intravascular space. The extrinsic system of volume control acts in parallel to this (see the tutorial on oliguria). This situation persists until the extravascular volume is restored by fluid resuscitation.

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Stage 2: decompensation

In sepsis, due to sustained release of nitric oxide and dysfunctional oxygen extraction by the tissues, accumulation of hydrogen ions, lactic acid, increased PaCO2 & vasoactive substances, occurs. These cause precapillary sphincters to relax, presumably due to cellular hyperpolarization from activation of potassium channels in smooth muscles. Conversely, the post capillary venules become unresponsive and vasoconstrict. Fluid drains into the capillary bed, but is very slow to move out of it. Simultaneously, there is widespread destruction of the capillary endothelium, due to the systemic inflammatory response – the capillaries become leaky. Blood "sieves" out of the capillary bed: fluid rich in albumin extravascates, leaving cellular material behind.  This causes interstitial edema, hemoconcentration and increased blood viscosity. Parallel activation of the coagulation system (and inhibition of fibrinolysis) leads to sticky clotting blood blocking up the small blood vessels, leading to ischemic injury. The combination of ischemia due to clot, the inability to extract oxygen and the compression effects of tissue edema may lead to macroscopic organ injury and organ failure. This is probably the mechanism of development of MODS. When clotting factors run out, the patient develops a bleeding tendency, and thrombosed areas may reperfuse. Such reperfusion may lead to the development of oxygen free radicals, which further organ injury.

THIS TUTORIAL BY PATRICK NELIGAN MD, UNIVERSITY OF PENNSYLVANIA

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