If the underlying causes are not corrected, shock passes imperceptibly to the progressive phase, which as noted is characterized by widespread tissue hypoxia. In the setting of persistent oxygen deficit, intracellular aerobic respira- tion is replaced by anaerobic glycolysis with excessive pro- duction of lactic acid. The resultant metabolic lactic acidosis lowers the tissue pH, which blunts the vasomotor response; arterioles dilate, and blood begins to pool in the microcir- culation. Peripheral pooling not only worsens the cardiac output but also puts endothelial cells at risk for the devel- opment of anoxic injury with subsequent DIC. With wide- spread tissue hypoxia, vital organs are affected and begin to fail. #401 | | |
In the absence of appropriate intervention, or in severe cases, the process eventually enters an irreversible stage. Widespread cell injury is reflected in lysosomal enzyme leakage, further aggravating the shock state. Myocardial contractile function worsens, in part because of increased NO synthesis. The ischemic bowel may allow intestinal flora to enter the circulation, and thus bacteremic shock may be superimposed. Commonly, further progression to renal failure occurs as a consequence of ischemic injury of the kidney (Chapter 14), and despite the best therapeutic interventions, the downward spiral frequently culminates in death. #402 | | |
Fig. 4.19 Major pathogenic pathways in septic shock. Microbial products activate endothelial cells and cellular and humoral elements of the innate immune system, initiating a cascade of events that lead to end-stage multiorgan failure. Additional details are provided in the text. DIC, Disseminated intravascular coagulation; HMGB1, high-mobility group box 1 protein; NO, nitric oxide; PAF, platelet-activating factor; PAI-1, plasminogen activator inhibitor-1; PAMP, pathogen- associated molecular pattern; STNFR, soluble tumor necrosis factor receptor; TF, tissue factor; TFPI, tissue factor pathway inhibitor. #403 | | |
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The cellular and tissue effects of shock are essentially those of #405 | | |
hypoxic injury (Chapter 2) and are caused by a combination of hypoperfusion and microvascular thrombosis. Although any organ can be affected, the brain, heart, kidneys, adrenals, and gastrointestinal tract are most commonly involved. Fibrin thrombi can form in any tissue but typically are most readily visualized in kidney glomeruli. Adrenal cortical cell lipid depletion is akin to that seen in all forms of stress and reflects increased use of stored lipids for steroid synthesis. Whereas the lungs are resistant to hypoxic injury in hypovolemic shock occur- ring after hemorrhage, sepsis or trauma can precipitate diffuse alveolar damage (Chapter 13), leading to so-called “shock lung.” Except for neuronal and cardiomyocyte loss, affected tissues can recover completely if the patient survives. #406 | | |
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The clinical manifestations of shock depend on the pre- #408 | | |
cipitating insult. In hypovolemic and cardiogenic shock, patients exhibit hypotension, a weak rapid pulse, tachy- pnea, and cool, clammy, cyanotic skin. As already noted, in septic shock, the skin may be warm and flushed owing to periph- eral vasodilation. The primary threat to life is the underlying initiating event (e.g., myocardial infarction, severe hemor- rhage, bacterial infection). However, the cardiac, cerebral, and pulmonary changes rapidly aggravate the situation. If patients survive the initial period, worsening renal func- tion can provoke a phase dominated by progressive oligu- ria, acidosis, and electrolyte imbalances. #409 | | |
Prognosis varies with the origin of shock and its dura- tion. Thus, more than 90% of young, otherwise healthy patients with hypovolemic shock survive with appropriate management; by comparison, septic or cardiogenic shock is associated with substantially worse outcomes, even with state-of-the-art care. #410 | | |
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Shock is defined as a state of systemic tissue hypoperfusion resulting from reduced cardiac output and/or reduced effective circulating blood volume. #414 | | |
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The major types of shock are cardiogenic (e.g., myocardial infarction), hypovolemic (e.g., blood loss), and septic (e.g., infections). #416 | | |
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Shock of any form can lead to hypoxic tissue injury if not corrected. #418 | | |
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Septic shock is caused by the host response to bacterial or fungal infections; it is characterized by endothelial cell activa- tion, vasodilation, edema, disseminated intravascular coagula- tion, and metabolic derangements. #420 | | |
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