Il8o HANDBOOK OF PHYSIOLOGY — CIRCULATION II 



HO \"^ ^"-""^ OH 



CHENODEOXYCHOLIC ACID 



I 

 INTESTINAL 

 BACTERIA 



OH 



CHOLIC ACID 



I 

 INTESTINAL 

 BACTERIA 



* 



OH 



COOH 



LITHOCHOLIC ACID 

 I 



DEOXYCHOLIC ACID 



C-NH-CH 2 -C00H (GLYCINE CONJUGATES) 

 ■NHCH,-CH,-SO,OH (TAURINE ' ) 



I CONJUGATION IN LIVER 



fig. 6. Formation of "primary" and "secondary" bile acids 

 in man. (From Van Itallie & Hashim, M. Clin. North America. 

 In press.) 



excreted as bile acids, and a portion of the remainder 

 is excreted in the feces as cholesterol, coprostanol, 

 cholestanol, and other nonacidic sterols. The newly 

 formed bile acids are excreted into the small intestine 

 and participate in an enterohepatic cycle through 

 which 20 to 30 g of bile acids circulate per day 

 (fig. 7). The net loss of bile acids in the feces nor- 

 mally corresponds to the amount converted from 

 cholesterol in the liver. 



That bile acids are the major catabolic products of 

 cholesterol has been suspected for about a century. 

 However, this fact was clearly established in 1943 by 

 Bloch et al. (26) who demonstrated that, when choles- 

 terol labeled with deuterium was administered to 

 dogs, a minimum of two-thirds of the label appeared 

 in the excreted bile acids. These observations have 

 now been amply confirmed by studies involving use 

 of C'Mabeled cholesterol, notably by Siperstein et al. 

 (191, 192), Bergstrom et al. (17, 18), and others. 



The behavior of the enterohepatic cycle of bile 

 acids profoundly affects the rate of cholesterol con- 

 version to bile acids. This rate in turn appears to 

 influence plasma cholesterol concentration. Rats with 



approx 0.8gm/day 

 in feces 



fig. 7. Enterohepatic cycle of bile acids. [Adapted from 

 Bergstrom (18).] 



indwelling cannulae in the common bile duct exhibit 

 a 10-fold to 15-fold increase in bile acid output 

 through the externalized cannulae compared with 

 the fecal bile acid output of intact rats (18). This also 

 has been observed clinically in patients with common 

 duct intubation. Conversely, in animals with experi- 

 mental ligation of the common duct (41), and in 

 patients with cholestasis (202), the rate of conversion 

 of cholesterol to bile acids decreases. Moreover, in 

 such situations cholesterol synthesis actually may 

 increase, sometimes with marked elevation of serum 

 cholesterol. 



FACTORS THAT INFLUENCE SERUM LIPIDS 



Serum lipid levels result from a complex interaction 

 between host and environment (157). Genetic dis- 

 orders such as familial hypercholesteremia and essen- 

 tial hyperlipemia are associated with gross abnormali- 

 ties of serum lipids. Among the environmental factors, 

 diet and "stress" have attracted particular attention. 

 Certain diseases also have conditioning effects on 

 serum lipids. Included in this category are nephrosis, 

 hypothyroidism, biliary cirrhosis, diabetes mellitus, 

 pancreatitis, and others. In addition, such factors 

 as age, sex, race, culture, occupation, exercise, body 

 composition, and cigarette smoking have been 



