Pathophysiology of ALF

The clinical signs and pattern of illness depend on the balance between three factors: the liver's ability to regenerate, the adverse metabolic consequences of the loss of a functioning liver, and the systemic effects of a wide range of toxic substances released into the serum from the necrotic liver. Although symptoms and signs of the different organ involvement are often considered separately, it is imperative to realize their interdependence ( Fig 1) and the central driving force of the primary liver injury. As an early consequence of the acute liver injury, host defenses to infection are severely compromised and with secondary bacterial infection there is endotoxemia, activation of macrophages, and release of cytokines and tumor necrosis factor. The resulting clinical picture is similar to that of septic shock, with hypotension and other circulatory changes leading to tissue hypoxia and damage to a number of organs as well as the gut, and with yet further ischemic injury to the liver.

Fig. 1 Vicious cycle of events forming the basis of multiple organ failure: TNF, tumor necrosis factor; MOF, multiple organ failure.

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