What causes failure to thrive in infants with cholestasis?

Updated: Aug 09, 2017
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: Carmen Cuffari, MD  more...
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Answer

One of the major clinical effects of cholestasis, particularly chronic cholestasis, is failure to thrive. The mechanisms of failure to thrive include malabsorption, anorexia, poor nutrient use, hormonal disturbances, and secondary tissue injury. Malabsorption in cholestatic liver disease results from reduced delivery of bile salts to the intestine, which results in inefficient digestion and absorption of fats. Digestion is affected because bile salts are important for the function of bile salt–dependent lipase activity and the stabilization of the lipase-colipase complex. In addition, bile salts are important in stabilization of lipid emulsions, which is important for increasing the surface area on which lipase works.

Absorption is inefficient because of reduced formation of intestinal micelles, which are important for removing the end products of lipolysis and effecting their absorption. The result of these events is the malabsorption of fat and fat-soluble vitamins.

Malabsorption of fat results in the loss of a source of calories that is important in infant nutrition. Furthermore, the delivery of fat into the colon can result in colonic secretion and diarrhea. Adults with fat malabsorption often experience anorexia. This may also occur in infants, but more often, infants take increased amounts of formula to compensate for loss of calories. Finally, the loss of fat into the stool also results in calcium wasting through the formation of calcium soaps of fatty acids. This may play an important role in bone disease in children and adults with chronic cholestasis.

The treatment of fat malabsorption principally involves dietary substitution. In older patients, a diet that is rich in carbohydrates and proteins can be substituted for a diet containing long-chain triglycerides. In infants, substitution may not be possible, and the substitution of a formula containing medium-chain triglycerides may improve fat absorption and nutrition.

The malabsorption of fat-soluble vitamins can result in vitamin deficiency states. Vitamins E, D, K, and A are all malabsorbed in cholestasis, and in that order. [7] Vitamin E deficiency can result in peripheral neuropathy and possibly hemolysis. Vitamin D deficiency results in osteomalacia and rickets. Vitamin K deficiency causes coagulopathy and possibly reduced brain development. Vitamin A deficiency does not result in clinical disease in cholestasis. In chronic cholestasis, careful attention must be paid to prevent fat-soluble vitamin deficiencies. This is accomplished by administering fat-soluble vitamins and monitoring the response to therapy.


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