Do increased catecholamines and plasma methionine enkephalin in cirrhosis promote bleeding oesophageal varices?

Increased sympathetic tone and adrenal medullary activity in hepatic cirrhosis may promote portal hypertension. We suggest that they may be imperfect homeostatic mechanisms attempting to maintain systemic arterial pressure in response to chronic vasodilatation and that small, endogenous opioid peptides may play a part in this vasodilatation. As initial investigation of this hypothesis, we measured noradrenaline (an indicator of sympathetic tone), adrenaline and methionine enkephalin in the plasma of patients with cirrhosis with oesophageal varices which had or had not bled previously, patients with cirrhosis without varices, patients with acute liver disease and controls. In patients with cirrhosis, noradrenaline, adrenaline and methionine enkephalin were all greatest in those with oesophageal varices which had previously bled. In this group, noradrenaline correlated strongly with the widely used prognostic guide, Pugh's modification of Child's classification. In patients with acute liver disease, methionine enkephalin and adrenaline were increased six- and four-fold respectively. However, noradrenaline was normal, suggesting that increased sympathetic tone in cirrhosis may develop gradually. The use of opioid antagonists may enable determination of whether elevated plasma opioid peptides in cirrhosis stimulate the increase in sympathetic tone and plasma adrenaline, and promote bleeding oesophageal varices.