Blast from the past: the hepatorenal reflex revisited

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How does sodium retention occur in liver cirrhosis? Most of us accept Schrier’s peripheral arterial vasodilation hypothesis. This hypothesis postulates that overproduction of vasodilatory substances in the splanchnic circulation in cirrhosis leads to splanchnic pooling and decreased “effective” arterial blood volume which will trigger the activation of sodium and water retaining mechanisms (i.e. renin-angiotensin-aldosterone)

However, this hypothesis has come under scrutiny recently. In elegant studies done in dogs with experimental liver cirrhosis, Levy et al. observed that sodium retention and plasma volume expansion precede the development of systemic vasodilation, suggesting that systemic vasodilation in cirrhosis is likely a homeostatic response to ECF volume expansion.

Experimental evidence collected over several decades point towards the existence of an intrahepatic vascular sensor involved in ECF volume regulation: the hepatorenal reflex. Under normal conditions, hepatic sensors would respond directly or indirectly to a decrease in ECF volume in the intrahepatic circulation and will activate renal sympathetic nerves to produce sodium retention and maintain sodium balance. Along this line of thinking, hepatic denervation abolishes this reflex.

The hepatorenal reflex has been implicated in the pathophysiology of sodium and water retention in liver cirrhosis. Apparently, the distorted liver architecture and abnormal intrahepatic circulation in cirrhosis will produce changes in portal venous flow that will pathologically activate this reflex with the subsequent development of sodium retention. Adenosine plays a central role in this reflex. Adenosine receptor blockers were shown to exert a natriuretic effect, prevent the decline in creatinine clearance and to decrease mortality in an animal model of liver cirrhosis. More studies are needed to clarify whether adenosine antagonists could be clinically beneficial in these patients.

Helbert Rondon, MD, FACP, FASN

1 comment

  1. Nice, citations from 1970's love it.

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