Pathophysiology of remote organ dysfunction

The clinical course of severe acute pancreatitis can be divided into an early 'toxemic' phase (0-15 days), characterized by the emergence of distant organ damage, and a later 'necrotic' phase when local complications prevail (Table2). However, the two phases are often superimposed, particularly when necrosis becomes infected early on.

Table 2 Clinical manifestations of severe acute pancreatitis: a model of multiple organ dysfunction syndrome

Systemic complications characterizing the toxemic phase, in particular cardiocirculatory and respiratory failure, contribute significantly to morbidity and mortality. Most are mediated by spillage into the systemic circulation of pancreatic enzymes and toxic substances including proinflammatory cytokines generated retroperitoneally by the inflammatory reaction and the necrotizing process. Among the various routes of autointoxication of the organism (pancreatic veins, transperitoneal and transpleural absorption), retroperitoneal and peripancreatic lymphatics which enter the thoracic duct play a predominant role.

The hemodynamic profile of the early phase of severe acute pancreatitis is usually hyperdynamic, although severe myocardial depression occasionally occurs. Contributory factors include intravascular volume depletion secondary to increased vascular permeability, abdominal fluid sequestration and/or gastrointestinal and retroperitoneal hemorrhage, direct or proteolytic activation of the contact system, a myocardial depressant factor synthesized by acinar cells, and release of prostanoids (platelet-activating factor) and cytokines by activated leukocytes in the necrotic areas.

Metabolic sequelae include an increase in resting energy expenditure averaging 125 per cent of predicted values, elevated protein catabolism, unsuppressed hepatic gluconeogenesis, and peripheral insulin resistance. Hepatic and peripheral insulin resistance, b-cell dysfunction, and hyperglucagonemia result in hyperglycemia. Diabetic ketoacidosis or non-acidotic diabetic coma may be presenting features, particularly in patients with hyperlipidemia. Hypocalcemia and hypertriglyceridemia are also seen.

Respiratory complications commonly arise from pleural effusions and elevated/limited excursion of the diaphragm due to pain/ileus with secondary pulmonary atelectasis, hypoxemia, and pulmonary infection. All patients with severe acute pancreatitis develop pleural effusions, and 20 per cent suffer early acute respiratory distress.

Disseminated intravascular coagulation mostly results from the proteolytic effects of circulating free trypsin, although it is usually clinically silent. Oliguria and mild azotemia are usually attributed to intravascular volume depletion, although histological studies have shown deposits of fibrin and fibrinogen in the glomerular capillaries. Thus impaired renal perfusion and ischemia may be related to a trypsin-induced hypercoagulable state.

Central nervous system disorders include psychosis, confusion, coma, and seizures. Alcohol withdrawal, fat embolism, intravascular coagulation, hypoxemia, and hyperosmolarity have all been incriminated.

The multiple organ dysfunction syndrome seen with severe acute pancreatitis is indistinguishable from that seen in septic shock or following extensive tissue injury. It supports a final common pathway and reflects the capacity of the necrotizing inflammatory process to produce and release multiple mediators, enzymes, and vasoactive substances into the systemic circulation (Gio§s...§t§/ 199.3).

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