Shock is the clinical syndrome that results from inadequate tissue perfusion. Irrespective of cause, the hypoperfusion-induced imbalance between the delivery of and requirements for oxygen and substrate leads to cellular dysfunction. The cellular injury created by the inadequate delivery of oxygen and substrates also induces the production and release of damage-associated molecular patterns (DAMPs or "danger signals") and inflammatory mediators that further compromise perfusion through functional and structural changes within the microvasculature. This leads to a vicious cycle in which impaired perfusion is responsible for cellular injury that causes maldistribution of blood flow, further compromising cellular perfusion; the latter ultimately causes multiple organ failure (MOF) and, if the process is not interrupted, leads to death. The clinical manifestations of shock are also the result, in part, of autonomic neuroendocrine responses to hypoperfusion as well as the breakdown in organ function induced by severe cellular dysfunction (Fig. 270-1).
Shock-induced vicious cycle.
When very severe and/or persistent, inadequate oxygen delivery leads to irreversible cell injury; only rapid restoration of oxygen delivery can reverse the progression of the shock state. The fundamental approach to management, therefore, is to recognize overt and impending shock in a timely fashion and to intervene emergently to restore perfusion. This often requires the expansion or reexpansion of intravascular blood volume. Control of any inciting pathologic process (e.g., continued hemorrhage, impairment of cardiac function, or infection), must occur simultaneously.
Clinical shock is usually accompanied by hypotension (i.e., a mean arterial pressure (MAP) <60 mmHg in previously normotensive persons). Multiple classification schemes have been developed in an attempt to synthesize the seemingly dissimilar processes leading to shock. Strict adherence to a classification scheme may be difficult from a clinical standpoint because of the frequent combination of two or more causes of shock in any individual patient, but the classification shown in Table 270-1 provides a useful reference point from which to discuss and further delineate the underlying processes.
Table 270–1. Classification of Shock
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Table 270–1. Classification of Shock
Normally when cardiac output falls, systemic vascular resistance rises to maintain a level of systemic pressure that is adequate for perfusion of the heart and brain at the expense of other tissues such as muscle, skin, and especially the gastrointestinal (GI) tract. Systemic vascular resistance is determined primarily by the luminal diameter of arterioles. The metabolic rates of the heart and brain are high, and their stores of energy substrate are low. These organs are critically dependent on a continuous supply of oxygen and nutrients, and neither tolerates severe ischemia for more than brief periods (minutes). Autoregulation (i.e., the maintenance of blood flow over a wide range of perfusion pressures), is critical in sustaining cerebral and coronary perfusion despite significant hypotension. However, when MAP drops to ≤60 mmHg, blood flow to these organs falls, and their function deteriorates.
Arteriolar vascular smooth muscle has both α- and β-adrenergic receptors. The α1 receptors mediate vasoconstriction, while the β2 receptors mediate vasodilation. Efferent sympathetic fibers release norepinephrine, which acts primarily on α1 receptors as one of the most fundamental compensatory responses to reduced perfusion pressure. Other constrictor substances that are increased in most forms of shock include angiotensin II, vasopressin, endothelin 1, and thromboxane A2. Both norepinephrine and epinephrine are released by the adrenal medulla, and the concentrations of these catecholamines in the bloodstream rise. Circulating vasodilators in shock include prostacyclin [prostaglandin (PG) I2], nitric oxide (NO), and, importantly, products of local metabolism such as adenosine that match flow to the tissue's metabolic needs. The balance between these various vasoconstrictors and vasodilators influences acting upon the microcirculation determines local perfusion.
Transport to cells depends on microcirculatory flow; capillary permeability; the diffusion of oxygen, carbon dioxide, nutrients, and products of metabolism through the interstitium; and the exchange of these products across cell membranes. Impairment of the microcirculation that is central to the pathophysiologic responses in the late stages of all forms of shock, results in the derangement of cellular metabolism that is ultimately responsible for organ failure.
The endogenous response to mild or moderate hypovolemia is an attempt at restitution of intravascular volume through alterations in hydrostatic pressure and osmolarity. Constriction of arterioles leads to reductions in both the capillary hydrostatic pressure and the number of capillary beds perfused, thereby limiting the capillary surface area across which filtration occurs. When filtration is reduced while intravascular oncotic pressure remains constant or rises, there is net reabsorption of fluid into the vascular bed, in accord with Starling's law of capillary interstitial liquid exchange. Metabolic changes (including hyperglycemia and elevations in the products of glycolysis, lipolysis, and proteolysis) raise extracellular osmolarity, leading to an osmotic gradient that increases interstitial and intravascular volume at the expense of intracellular volume.
Interstitial transport of nutrients is impaired in shock, leading to a decline in intracellular high-energy phosphate stores. Mitochondrial dysfunction and uncoupling of oxidative phosphorylation are the most likely causes for decreased amounts of adenosine triphosphate (ATP). As a consequence, there is an accumulation of hydrogen ions, lactate, and other products of anaerobic metabolism. As shock progresses, these vasodilator metabolites override vasomotor tone, causing further hypotension and hypoperfusion. Dysfunction of cell membranes is thought to represent a common end-stage pathophysiologic pathway in the various forms of shock. Normal cellular transmembrane potential falls, and there is an associated increase in intracellular sodium and water, leading to cell swelling that interferes further with microvascular perfusion. In a preterminal event, homeostasis of calcium via membrane channels is lost with flooding of calcium intracellularly and a concomitant extracellular hypocalcemia. There is also evidence for a widespread but selective apoptotic (programmed cell-death) loss of cells, contributing to organ and immune failure.
Hypovolemia, hypotension, and hypoxia are sensed by baroreceptors and chemoreceptors that contribute to an autonomic response that attempts to restore blood volume, maintain central perfusion, and ...