Liver failure pathophysiology

Sen, S., Williams, R., Jalan, R. The pathophysiological basis of acute-on-chronic liver failure. Liver 2002 22 (Suppl. 2) 5-13... 

Hepatorenal syndrome, functional renal failure in the setting of cirrhosis in the absence of intrinsic renal disease, occurs in patients with cirrhosis as a result of intense vasoconstriction within the renal cortical vasculature. It is common and develops in approximately 40% of patients with cirrhosis and ascites within 5 years. The resultant reduction in blood supply to the kidneys causes avid sodium retention and oliguria. The vasoconstriction that occurs in the kidneys is in stark contrast to the state of systemic vasodilation that is characteristic of chronic liver failure. The pathophysiologic mechanism responsible for these effects is unknown, but is linked to the systemic vasodilation, hypovolemia, and hyperkinetic circulation seen in chronic liver failure. ... 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

The higher polyamines, spermine in particular, play important physiological roles in protection from oxidative stress. Enhanced polyamine catabolism reduces this protection while concomitantly generating ROS and toxic aldehyde by-products. As a result, increased polyamine catabolism, resulting from the stimuli just mentioned, has been implicated in several pathophysiological conditions, including neurological and liver disease, stroke, kidney failure, and cancer. 

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