Regulation of pool size of bile acids in man

Various components of the enterohepatic circulation were investigated in 33 subjects to determine their effects on bile acid pool size. The pool size and secretion rates of bile acids were measured using an intestinal perfusion method, and bile acid synthesis was determined by fecal excretion. From these measurements, cycling frequency of the pool and intestinal absorption of bile acids were calculated. Results were analyzed for the group as a whole and for four subgroups based on incremental pool sizes (1 to 2 g, 2 to 3 g, 3 to 4 g, and >4 g). Factors that should regulate pool size are synthesis, absorption efficiency, and cycling frequency of the pool. In subjects with relatively low pools, steady state synthesis and absorption of bile acids were not reduced. However, two other factors appeared especially important in keeping pool sizes in the lower ranges - a high cycling frequency and overly sensitive feedback inhibition of bile acid synthesis. First, there was a significant inverse correlation between cycling frequency and pool size. Theoretically, a high cycling frequency should reduce pools in two ways - by suppressing synthesis and by increasing fecal losses. Second, in patients with low pools, transhepatic flux of bile acids was also reduced, and daily synthesis of bile acid, although being in the same ranges as those with larger pools, was inappropriate for the magnitude of the flux. With this overactive feedback on bile synthesis, these patients were unable to increase their bile acid synthesis to supranormal levels so as to cause a reexpansion of the pool to higher levels.