Hypertyraminemia in Cirrhotic Patients

Abstract

To evaluate the role of tyramine in hepatic disorders, we used a radioimmunoassay to study plasma concentration of tyramine in eight healthy subjects, 20 hospitalized patients without liver disease, and 13 cirrhotic patients of whom seven had hepatic encephalopathy. The effect of increasing dietary protein on tyramine level of cirrhotic patients was also assessed. No significant difference in plasma tyramine concentration was seen between normal subjects, 1.3 +/- 0.1 ng per milliliter (average +/- S.E.), hospitalized patients without hepatic disease (1.4 +/- 0.1 ng per milliliter) and cirrhotic patients without encephalopathy (2.7 +/- 0.5 ng per milliliter). However, the tyramine level in cirrhotic patients with encephalopathy, 6.4 +/- 0.1 ng per milliliter, was significantly (P less than 0.001) higher than in normal subjects or in cirrhotic patients without encephalopathy. Increasing dietary protein from 40 to 80 g per day raised fasting tyramine concentration by 30 to 70 per cent within three days in both encephalopathic and non-encephalopathic cirrhotic patients. Concentration of plasma tyramine in cirrhotic subjects was significantly correlated with that of plasma tyrosine (P less than 0.001).

Tyramine kinetics and metabolism in cirrhosis.

“…Further support for this hypothesis comes from our demonstration of impaired metabolism of both 4-hydroxyphenylpyruvic and homogentisic acids in hypertyraminemic cirrhotics, compatible with blocks at the levels of the two corresponding hepatic oxidases (25). Finally, when dietary tyrosine is increased in cirrhotics, plasma tyrosine and plasma tyramine rise in parallel (1).…”

“…This same pattern was found in the cirrhotics. Tables I and II. tyramine, and its f8-hydroxylated derivative octopamine, have also been found in cirrhotics (1)(2)(3)(4)(5). The objective of this study is to determine whether tyramine accumulation in plasma is the result of accelerated production or decreased elimination.…”

“…Tyramine concentration is abnormally elevated in the plasma of cirrhotic patients (1). Tyramine is the precursor of octopamine.…”

“…Octopamine acts as a central "false neurotransmitter" and tyramine acts as an indirect sympathomimetic agent. Both have potent ef-fects on circulatory and neurologic functions, which are often disturbed in cirrhotics (1)(2)(3)(4)(5). An understanding of the mechanism of the hypertyraminemia of cirrhotic patients is therefore desirable.…”

Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans

“…High concentrations of tyramine, well above endogenous plasma levels of Ϸ7.5 nmol/L in healthy subjects, 28 were required to produce a vasoconstrictive response in subjects in the present study (Figure 2). Their responses were seen over local 0.129-to 25.8-mmol/L concentrations in a dorsal hand vein, and the EC 50 (threshold concentration) was estimated at Ϸ9 mmol/L tyramine, consistent with the viewpoint that tyramine acts as a sympathomimetic amine, which functions only indirectly by displacing NE from storage vesicles, allowing the nonexocytotic release of the transmitter into the synaptic cleft.…”