Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids
M. Pittiruti, J. H. Siegel, G. Sganga, B. Coleman, C. E. Wiles 3rd and R. Placko
Maryland Institute for Emergency Medical Services Systems (MIEMSS), University of Maryland, Baltimore 21201.
The major determinants of urea production were investigated in 26 patients
with multiple trauma (300 studies). The body clearances (CLRs) of ten amino
acids (AAs) were estimated as a ratio of muscle-released AAs plus total
parenteral nutrition-infused AAs to their extracellular pool. While
clinically septic trauma (ST) patients without multiple-organ failure
syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/-
13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/-
7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per
day), in all groups urea N production was found to be a function of muscle
protein degradation (catabolism), total parenteral nutrition-administered
AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P
less than .0001). Since tyrosine is cleared almost exclusively by the
liver, the L/T ratio may be regarded as an index of hepatic function. The
significant differences between urea N production in ST and NST patients
lay in an increased positive dependence on muscle catabolism and increased
negative correlation with L/T in the ST group. At any L/T ratio, urea N
production was increased in ST patients over NST patients, but in ST
patients with MOFS, it fell to or below levels of NST patients. These data
show that the ST process is associated with enhancement of ureagenesis, due
to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis
with MOFS, a marked inhibition of urea synthesis occurs, partially
explained by a decreased hepatic CLR of non-branched-chain AAs.
