Porth's Essentials of Pathophysiology, 4e

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Circulatory Function

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Persons with severe sepsis and hyperglycemia (two consecutive blood glucose readings > 180 mg/dL) should receive insulin therapy following a protocol to maintain their blood glucose levels at a target level of ≤ 180 mg/dL. 67 Ongoing assessment of CVP, mixed venous or arterial oxygen saturation, mean arterial pressure, urinary out- put, and laboratory measurements of blood chemistries, serum lactate, base deficit, and pH are used to evalu- ate the progression of sepsis and adequacy of treatment as well as the need for other supportive therapies. This group of interventions lists the sepsis “bundle” that when implemented together produce better outcomes than when implemented individually. 67,68 Complications of Shock As the late Carl Wiggers, a noted circulatory physiolo- gist, once stated, “shock not only stops the machine, but it wrecks the machinery.” 72 Many body systems are wrecked by severe shock. Five major complications of severe shock are lung injury, acute kidney failure, gas- trointestinal complications, disseminated intravascular coagulation, and multiple organ dysfunction syndrome. These complications of shock are serious and often fatal. Acute Lung Injury/Acute Respiratory Distress Syndrome Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a potentially lethal form of pulmonary injury that may be either the cause or result of shock (see Chapter 23). Acute lung injury/acute respiratory distress syndrome represents a spectrum of acute respi- ratory failure with ARDS being the more severe form, associated with greater hypoxemia and mortality. Acute lung injury/acute respiratory distress syndrome is marked by the rapid onset of profound dyspnea that usually occurs after an initiating event, such as trauma, aspiration, or pancreatitis. The respiratory rate and effort of breathing increase. Arterial blood gas analysis establishes the presence of profound hypoxemia that is refractory to supplemental oxygen. The hypoxemia results from impaired matching of ventilation and per- fusion and from the greatly reduced diffusion of blood gases across the thickened alveolar membranes. 6 The exact cause of ALI/ARDS is unknown. Neutrophils are thought to play a key role in its pathogenesis. A cytokine-mediated activation and accumulation of neu- trophils in the pulmonary vasculature and subsequent endothelial and epithelial injury are thought to cause leaking of fluid and plasma proteins into the interstitium and alveolar spaces. 73 The fluid leakage causes atelectasis, impairs gas exchange, and makes the lung stiff (poor com- pliance) and more difficult to inflate. Abnormalities in the production, composition, and function of surfactant may contribute to alveolar collapse and gas exchange abnor- malities. Inappropriate vasodilation and vasoconstriction worsen the ventilation and perfusion mismatch. Interventions for ALI/ARDS focus on increasing the oxygen concentration in the inspired air and support- ing ventilation mechanically to optimize gas exchange

while avoiding oxygen toxicity and preventing further lung injury. Despite the delivery of high levels of oxy- gen using high-pressure mechanical ventilatory support and positive end-expiratory pressure, many persons with ALI/ARDS remain hypoxic, often with a fatal outcome. 74 Acute Kidney Injury Acute kidney injury (AKI), formerly known as acute renal failure, often occurs in the context of sepsis and multiple organ failure. 75 The renal tubules are particu- larly vulnerable to ischemia, and AKI is an important factor in mortality due to severe shock. Most cases of AKI are due to impaired renal perfusion in response to decreased intravascular volume. 75 The degree of renal damage is related to the severity (or stage) and duration of shock. The renal dysfunction most frequently seen with progressive to severe shock states is acute tubu- lar necrosis. Acute tubular necrosis usually is revers- ible, although return to normal renal function may require weeks or months (see Chapter 25). Continuous monitoring of urinary output during shock provides a means of assessing renal blood flow. Frequent monitor- ing of serum creatinine and blood urea nitrogen lev- els also provides valuable information regarding renal status. Gastrointestinal Complications The gastrointestinal tract is particularly vulnerable to ischemia because of the changes in distribution of blood flow to its mucosal surface. In shock, there is widespread constriction of blood vessels that supply the gastrointes- tinal tract, causing a redistribution of blood flow and a severe decrease in mucosal perfusion. Proton pump inhibitors or histamine 2–receptor antagonists may be given prophylactically to prevent gastrointestinal ulcer- ations and bleeding in persons with shock who have risk factors for bleeding. 67 Disseminated Intravascular Coagulation Disseminated intravascular coagulation (DIC) is char- acterized by widespread activation of the coagulation system with resultant formation of fibrin clots and thrombotic occlusion of small and mid-sized vessels (see Chapter 12). The systemic formation of fibrin results from increased generation of thrombin, the simultaneous suppression of physiologic anticoagulation mechanisms, and the delayed removal of fibrin as a consequence of impaired fibrinolysis. Clinically overt DIC is reported to occur in as many as 30% to 50% of persons with Gram negative sepsis. 76 As with other systemic inflam- matory responses, the derangement of coagulation and fibrinolysis is thought to be mediated by inflammatory mediators and cytokines. The contribution of DIC to morbidity and mortality in sepsis depends on the underlying clinical condition and the intensity of the coagulation disorder. Depletion of the platelets and coagulation factors increases the risk of bleeding. Deposition of fibrin in the vasculature of organs contributes to ischemic damage and organ failure.