Shock Syndromes I

Vasodilatory shock occurs because of a failure of the vascular smooth muscle cells to constrict, whether

from a failure of vasoconstriction methods or the inappropriate activation of vasodilatory mechanisms.

In most cases (except for neurogenic shock), this failure occurs despite high plasma concentrations of

endogenous vasoconstrictors (e.g., norepinephrine, epinephrine, and angiotensin II).

Activation of cellular ATP-dependent potassium channels leads to hyperpolarization of the

vascular smooth muscle cell through potassium efflux, which prevents extracellular calcium influx

by voltage-gated calcium channels. As a result, cellular depolarization is prevented, high cytosolic

calcium concentrations needed for vasoconstriction are not achieved, and vasodilation occurs.

Increased expression of inducible nitric oxide synthase leads to increased intracellular nitric

oxide concentrations and resultant vasodilation by a cyclic guanosine monophosphate–mediated

mechanism. Nitric oxide may also induce vasodilation by activating potassium channels in the

plasma membrane, leading to cellular hyperpolarization, as described earlier.

Inappropriately low plasma vasopressin concentrations despite the level of shock (“relative

vasopressin deficiency”) may contribute to the inability of the vascular smooth muscle cell to

contract. Although initial plasma vasopressin concentrations may be high in the initial setting of

shock, vasopressin concentrations may decrease to physiologic concentrations as quickly as 1 hour

after the onset of hypotension.

The pathogenesis of vasodilation depends on the underlying cause.

Septic shock involves complex interactions between an infecting pathogen and the host

inflammatory, immune, and coagulation response. The pattern-recognition (e.g., toll-like) receptors

on innate immune system cells recognize specific molecules present in microorganisms and signal

the release of nuclear factor B, which leads to the transcription of both proinflammatory cytokines

(e.g., interleukin-1, interleukin-6, tumor necrosis factor alpha) and anti-inflammatory cytokines

(i.e., interleukin-10). These proinflammatory cytokines activate neutrophils and endothelial cells,

leading to an increased expression of inducible nitric oxide synthase and subsequent vasodilation.

Neurogenic shock involves a decrease in sympathetic outflow from the central nervous system with

unopposed parasympathetic activity. As such, vascular tone is lost, resulting in a decrease in SVR

and venous pooling of blood with a subsequent decrease in preload. Concomitant bradycardia is

common, and decreased CO (even after fluid administration) may occur because of the interruption

of cardiac sympathetic innervation, further contributing to hypotension. This shock type classically

occurs as a complication of an acute spinal cord injury at the level of the thoracic or cervical

vertebra, most commonly when the injury is above the fifth cervical vertebra.

Immune-mediated (anaphylactic) shock occurs because of reexposure to a sensitizing foreign

pathogen that stimulates immunoglobulin E–mediated mast cell or basophil degranulation and

resultant cytokine (e.g., histamine and tryptase) release. The mechanism of vasodilation is complex

and multifaceted; however, for example, the binding of histamine to the histamine-1 receptor can

activate nitric oxide synthase with resultant increases in nitric oxide and vasodilation.

Profound vasodilation leads to ineffective circulating plasma volume (either from venodilation [“venous

pooling”] or from fluid shifts because of increased vascular permeability) and resultant decreases in

cardiac preload and CO.

Resuscitation and treatment of patients specifically with sepsis and septic shock is covered later in the

chapter.

Septic shock requires rapid (within 1 hour of disease recognition) administration of antimicrobials

with activity against all likely pathogens.