Pathogenesis of irreversible shock

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Pathogenesis of irreversible shock

INTRODUCTION — Shock is a physiologic state characterized by a significant, systemic reduction in tissue perfusion, thereby resulting in decreased tissue oxygen delivery. Three broad mechanisms of shock are recognized, each of which is characterized by one primary physiologic derangement :

Pathophysiology and hemodynamic profile of shock states

Physiologic variable	Preload	Pump function	Afterload	Tissue perfusion
Clinical measurement	Pulmonary capillary wedge pressure	Cardiac output	Systemic vascular resistance	Mixed venous oxygen saturation
Hypovolemic	decreased	decreased	increased	decreased
Cardiogenic	increased	decreased	increased	decreased
Distributive	decreased or same	increased	decreased	increased

• Hypovolemic — fall in intravascular volume
• Cardiogenic — fall in cardiac output
• Distributive, most often due to sepsis — fall in systemic vascular resistance

Shock may progress through a series of stages if not successfully treated, culminating in end-organ damage, irreversible shock, and death. The pathogenesis of irreversible shock will be reviewed here. A general overview of shock and discussions of the different types of shock are presented elsewhere.

PATHOGENESIS — Early correction of the volume deficit is essential in hypovolemic shock to prevent the decline in tissue perfusion from becoming irreversible. In experimental animals, for example, hemorrhagic shock can be reversed if the blood that has been removed is reinfused within two hours . In comparison, there is only a transient increase in blood pressure if return of the shed blood is delayed for four hours or longer. A similar phenomenon appears to occur in humans, although substantially more than four hours may be required before volume repletion becomes ineffective .
Irreversible shock seems to be associated with pooling of blood in the capillaries and tissues, leading to a further impairment in tissue perfusion . Several factors may contribute to the vasomotor paralysis in this setting including:

• Hyperpolarization of vascular smooth muscle cells as ATP depletion or acidemia leads to opening of ATP-dependent potassium channels, which are normally closed by ATP [4]. Hyperpolarization decreases calcium entry into the cell through voltage-dependent calcium channels. The ensuing reduction in cell calcium concentration is responsible for the persistent vasodilatation. In experimental models of shock, for example, the administration of the sulfonylurea glyburide, an inhibitor of the ATP-dependent potassium channel, can lead to both vasoconstriction and an elevation in systemic blood pressure . The clinical applicability of this observation remains to be proven.
• Plugging of the capillaries by activated circulating neutrophils .
• Cerebral ischemia impairs central vasomotor regulation, resulting in reversal of the initial increase in peripheral sympathetic ton.
• Increased generation of the vasodilator nitric oxide; in experimental animals, the vascular unresponsiveness in irreversible shock can be overcome by administration of an inhibitor of nitric oxide synthase . There is, however, a potential risk with this regimen when hypotension is induced by endotoxin. Nitric oxide is also an inhibitor of platelet aggregation; as a result, inhibition of its formation may enhance the tendency to intravascular coagulation associated with endotoxemia [8].
• Generation of iron-dependent, oxygen-derived free radicals . Resuscitation with a free radical-scavenger conjugate of starch and deferoxamine may attenuate derangements in microvascular blood flow.
• Vasopressin deficiency, due to exhaustion of hypophyseal stores and rapid degradation of vasopressin in plasma . Low-dose infusion of vasopressin has been useful in animal models and some patients with otherwise irreversible shock, but this treatment strategy has not been examined in controlled clinical trials.

Regardless of the mechanism, the net effect is that administered fluid is sequestered in the capillary circulation. The ensuing elevation in the capillary hydraulic pressure favors the movement of fluid out of the vascular space into the interstitium . An increase in capillary permeability also may contribute to this process, as toxic products released from injured tissues or from the local accumulation of neutrophils can damage the capillary wall .

In this setting, fluid may also be sequestered within cells. Tissue ischemia diminishes cellular Na-K-ATPase activity, thereby reducing the active transport of sodium out of cells. The ensuing increase in cell sodium concentration promotes the entry of water into cells via an osmotic gradient.

节自"与时并进" 2009 三月