Ileal resection

Antibiotics have been studied based on the rationale that they may interrupt the inflammatory response directed against endogenous bacterial flora. Metronidazole and ciprofloxacin have been the two most widely-studied agents.32 Metronidazole may benefit some patients with pouchitis (inflammation of surgically-created intestinal pouches) and patients with CD who have had ileal resection or have perianal fistulas. Ciprofloxacin has shown some efficacy in refractory active CD. Both drugs may cause diarrhea, and long-term use of metronidazole is associated with the development of peripheral neuropathy. 

Rutgeerts P, Hiele M, Geboes K, Peeters M, Penninckx F, Aerts R, Kerremans R Controlled trial of metronidazole treatment for prevention of Crohn s recurrence after ileal resection. Gastroenterology 1995 108 1617-1621. 

Secondly, ileal resection disrupts enterohepatic circulation of bile acids due to loss of the ileal sodium-dependent bile acid transporter (ISBT) leading to... 

J. E. Oscarson, H. F. Veen, J. S. Ross and R. A. Malt, Ileal resection potentiates 1,2-dimethylhydrazine-induced colonic carcinogenesis, Ann. Surg., 1979, 189, 503. 

Chologenic diarrhea results when bile acids fail to be absorbed in the ileum (e.g., after ileal resection) and enter the colon, where they cause enhanced secretion of electrolytes and water, leading to the discharge of fluid stools. 

Failure of the terminal ileum to reabsorb bile salts may result from Crohn s disease, or ileal resection,... 

Intestinal malabsorption of vitamin B12 may be caused by gastrectomy or ileal resection, with an inverse relationship between the length of ileum resected and the absorption of vitamin B12. Other causes of malabsorption are tropical sprue, inflammatory disease of the small intestine, intestinal stasis with overgrowth of colonic bacteria, which consume the vitamin 6,2 ingested by the host, and HIV infection. Another cause of vitamin B malabsorption is failure to extract cobalamin from food. Some patients fail to absorb cobalamin bound to food, whereas absorption of nonfood-bound cobalamin in the Schilling test is unimpaired. This is particularly a problem in patients with compromised gastric status or early in the course of development of pernicious anemia. 

Cobalamin (Bi 2) Pernicious anemia, glossitis, spinal cord degeneration, peripheral neuropathy Serum Bi 2 Decreased absorption in the elderly, distal ileal resection, loss of gastric intrinsic factor... 

Patients with ileal resection commonly develop vitamin Bu deficiency, necessitating therapy with parenteral cyano-cobalamin. 

The adaptation process of the residual small intestine to compensate for the resected area begins 12 to 24 hours after bowel resection. The changes in the GIT to compensate for the lost absorptive area are gradual and may continue to occur for 1 to 2 years. Factors that act as stimuli for adaptation include luminal nutrients, pancreaticobiliary secretions, and intestinal hormones. The ability of the remaining intestine to adjust after resection is also influenced by the area of bowel loss. The jejunum is the primary site for absorption of most nutrients, but if it is removed the ileum usually can accommodate and take on the structural characteristics and functional roles. Even with this compensation, patients with less than 50 to 60 cm of jejunum will typically need indefinite PN. With ileal resection, the jejunum has a decreased capacity to adapt and perform the functions of the ileum. ... 

Patients with ileal resection commonly develop vitamin B12 deficiency, necessitating therapy with parenteral cyanocobalamin. Most other water-soluble vitamins are absorbed in the proximal jejunum, and deficits of these vitamins are found only in more severe SBS. Small bowel bacterial overgrowth can contribute to diminished vitamin B12 because bacteria may metabolize the nutrient within the intestine, decreasing its availability for absorption. SBS patients with fat malabsorption can acquire deficiencies in vitamins A, D, E, and K. These fat-soluble vitamins depend on bile salt micelles for effective absorption, and malabsorption with depletion of the bile salt pool can lead to their deficits. ... 

C25. Compston, J. E., and Horton, L. W. L., Oral 25-hydroxy-vitamin Dj in the treatment of osteomalacia associated with ileal resection and cholestyramine therapy. Gastroenterology 74, 900-902 (1978). 

BILE ACID SEQUESTRANTS Cholestyramine, colestipol, and colesevalam effectively bind bile acids and some bacterial toxins. Cholestyramine is useful in the treatment of bile salt-induced diarrhea, as in patients with resection of the distal Ueum. In these patients, there is partial interruption of the normal enterohepatic circulation of bile salts, resulting in excessive concentrations reaching the colon and stimulating water and electrolyte secretion (see below). Patients with extensive ileal resection (usually >100 cm) eventually develop net bile salt depletion, which can produce steatorrhea because of inadequate micellar formation required for fat absorption. In such patients, the use of cholestyramine will aggravate the diarrhea. 

The most common situations in which bile salts are deficient in the small intestine are (1) T-tube drainage of the common bile duct and (2) partial or complete interruption of ileal absorption, as in regional enteritis or ileal resection or bypass. In the former group, bile drainage is usually incomplete and temporary, so that most patients tolerate this period well without... 

The efficient intestinal absorption of bile acids involves both active and passive absorption, but little information on the relative sites and mechanisms of absorption and on their contribution to the entire enterohepatic cycle of bile acids exists. Although the contribution of passive and active absorption of bile acids in the rat small intestine has been measured (20), no data are available for other species. The major site of absorption in all vertebrates appears to be the ileum, where an active transport site exists (14,15). Free bile acids are absorbed passively in the jejunum by nonionic diffusion, dihydroxy acids being absorbed more rapidly than trihydroxy acids (21,22). Perfusion studies in the human jejunum have suggested that glycine dihydroxy bile acids may be absorbed to some extent, and additional evidence for jejunal absorption of bile acids has been obtained in patients and animals with ileal resection (97,98). No information exists on the importance of jejunal bile acid absorption in health in man. Taurine-conjugated bile acids do not appear to be absorbed in the human jejunum (24). 

It seems evident that (1) if bile acid elimination is inhibited or impaired as a primary phenomenon, e.g., in biliary obstruction and hypercholesterolemia, a decreased catabolism of cholesterol leads to hypercholesterolemia and reduced cholesterol synthesis (2) if bile acid elimination is primarily augmented, e.g., after an external bile fistula, ileal bypass, ileal resection, cholestyramine treatment, or perhaps a diet rich in fibrous material, conversion of cholesterol to bile acids is enhanced, leading almost always, despite stimulated cholesterol synthesis, to a fall in serum cholesterol (3) if endogenous cholesterol production is primarily increased, e.g., by obesity and excess of calories, bile acid synthesis and elimination are augmented, preventing together with increased neutral sterol elimination in some but not all cases the increase of serum cholesterol. This suggests that removal, not production, of cholesterol is the primary factor which determines serum cholesterol level. 

Cholesterol and fat-soluble vitamins require bile acid induced micellar solubilization for absorption, which takes place in the upper small intestine (c/. 32,116-118). Accordingly, in bile salt deficiency states, cholesterol absorption should be markedly impaired and fecal neutral sterol excretion increased. The fact that fecal neutral steroid excretion on a low-cholesterol diet is actually normal, as after ileal resection, ileal bypass, and cholestyramine treatment, or even decreased, as in cirrhosis of the liver or biliary occlusion (11), is due to a markedly reduced biliary secretion of cholesterol. In gluten enteropathy, in which no excessive bile salt loss usually exists, fecal neutral sterol excretion is markedly augmented (119). However, in occasional cases in which fecal bile salt elimination is markedly enhanced, the fecal neutral steroid excretion is quite normal, probably owing to decreased biliary cholesterol secretion as a consequence of low biliary bile salt secretion. Detailed information on the role of bile salts in both intraluminal and mucosal phases of fat and sterol absorption is presented in many recent reviews (6,10,113,114,117). 

Fig. 4. Correlation of fecal bile acid excretion with the following 1, fecal fat, 2, 3, and 4, jejunal micellar fat and bile acids, and jejunal total cholesterol, respectively, calculated for amounts found in the intestinal pool in which 136 mg of )5-sitosterol administered in the test meal was dispersed. 5, Serum methyl sterol (diunsaturated dimethyl sterol), used as an indicator of augmented cholesterol synthesis (see reference 11). 6, Serum cholesterol., Patients with incomplete ileal resection (25-50 cm of the very terminal ileum intact, 1-2 m of the more proximal gut removed) , complete ileal resection 4, extensive intestinal resections with severe malnutrition (the values omitted from calculations in 5).

It is partly owing to adaptation of the remaining small intestine to reabsorb bile acids that the length of ileal resection is not correlated with fecal bile acid excretion (64,101). In addition, accompanying malnutrition may limit the capacity of the liver to enhance its bile acid synthesis, so that in patients with extensive intestinal resections fecal bile acid excretion may be only moderately increased (64,101). In these cases, serum cholesterol is usually very low and depletion of body cholesterol in the presence of insufficiently enhanced cholesterol synthesis may be one factor for limited bile salt production. 

For diarrhea in ileopathy, see Section VD. Ineffectiveness of cholestyramine on diarrhea in patients with extensive ileal resection has been explained by the presence of hydroxy fatty acids and a low level of solubilized bile salts in feces (268). 

Since intestinal mucosa, especially in ileum, appears to synthesize cholesterol at a high rate even in man and since this synthesis is increased by the absence of bile acids (223), it is to be expected that in patients with intestinal bypass mucosal cholesterol production is markedly increased in the bypassed portion of the gut and should contribute to serum cholesterol. Ileal or more extensive intestinal resections, on the other hand, prevent this increase in synthesis and should reduce serum cholesterol more effectively than the sole bypass does. However, animal experiments indicate that in monkeys prevention of dietary-induced hypercholesterolemia is less effective by ileal resection... 

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-... 

Genetic variations in P450 7A1 have also been related to gallstone disease [1797], bile acid synthesis rates following ileal resection [1798], risk of neuromyelitus optica [1799], and hypertension [1800]. 

Lenicek M, Komarek V, Zimolova M, Kovar J, Jir-sa M, Lukas M, Vitek L (2008) CYP7A1 promoter polymorphism -203 A>C affects bile salt synthesis rate in patients after ileal resection. J Lipid Res 49 2664-2667... 

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