Ileal dysfunction

Therapeutically effective doses of colchicine in gout are 2-3 mg per patient on day 1 with smaller doses later, and 0.5-1 mg/day for 1-3 years given orally in familial Mediterranean fever (131). Side effects such as ileal dysfunction, decreased vitamin Bi2 absorption, and an increased absorption of steroids occur after intake of 7-10 mg/day, which if continued for 4-5 days result in dehydration and renal shutdown (96). The three congeners of allocolchicine, jerusalemine, salimine, and suhailamine, which all had (—)-rotations were isolated from Colchicum decaisnei Boiss. (141). 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

In contrast to many earlier studies using less specific procedures cf, 55), the chemical methods, which apparently give the most reliable results, have shown that the daily bile acid synthesis is normally relatively low in man, being about 250 mg/day (range from about 100 to 400 mg/day), i.e., about one-third of total cholesterol catabolism. Dietary factors, and especially body size and obesity, affect the values sensitively impaired liver function and hypercholesterolemia decrease, and malabsorption, especially ileal dysfunction, increases markedly the fecal bile acid elimination (11,62,63). Determination of the fecal bile salt excretion is a sensitive method for detection of ileal dysfunction (64). 

Measurement of fecal excretion of isotopic bile acids (65) gives only the half-life of the labeled bile acid used. The isotope is injected intravenously, and the daily fecal excretion of radioactivity is measured. According to this procedure, the fractional excretion rate of cholic acid in man is normally about 12-13% per day (66,67). Disadvantages of the method are that the absolute values are not obtained, the cholic and chenodeoxycholic acid excretions must be measured separately or a double label method must be used, and the fecal flow should be regular, though an unabsorbable fecal marker can be used. The method appears to be suitable for screening of ileal dysfunction. 

Cholestyramin is a basic anion exchange resin which is used to ameliorate watery diarrhea in cases of ileal dysfunction, ileal resection, and vagotomy. It is also used to relieve pruritus due to elevated serum and skin levels of bile salts in patients with intrahepatic cholestasis and to lower cholesterol levels in familial hypercholes-... 

Fig. 1. Gas-liquid chromatographic runs of fecal bile acids on OV-1 capillary column. Identifications according to retention times of available standards 1. isolithocholic acid, 2. cholic acid, 3. isodeoxycholic acid, 4. deoxycholic acid, 5. chenodeoxycholic acid, 6. cholic acid, 7. ursodeoxycholic acid. Run from a patient with ileal dysfunction (lower panel on right hand side) shows presence of mainly primary bile acids and derivatives without 7-dehydroxylation. Increase of sensitivity by a factor of four indicated by small arrows. 

Finally, the existence in CF of a primary ileal mucosal defect for BA absorption has been recently investigated. The ileal mucosal uptake of taurocholate in vitro was found to be reduced in CF patients and comparable to those for passive jejunal taurocholic acid uptake in controls. An incapacity of the ileus to actively transport BA in CF has therefore been suggested, similarly to other small bowel mucosal dysfunctions previously described in this disease. 

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