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III. MUCOSAL INTEGRITY Studies of gastrointestinal physiology reveal an intricate interaction between central and peripheral nerves, hormones, and peptides inside and outside the intestinal cell. This is exempliﬁed by the different phases of vagal stimulation, made known to the rest of the world by Pavlov’s classic studies in dogs in the 19th century. To use a slight understatement: Our knowledge has expanded since the work of Pavlov. We know now that physiological intestinal homeostasis is mediated through several mechanisms, whereby the way in which cellular mucosal defense is achieved is of utmost importance for maintaining mucosal integrity and thus also very relevant to drug absorption.
2. 3. If there is an impaired secretion of bile acids into the lumen (obstructive jaundice, intrahepatic cholestasis, primary biliary cirrhosis) If there is an extensive bile acid loss from the lumen, higher than the synthetic capacity in the liver If bile acids are deconjugated in the intestinal lumen owing to bacterial overgrowth syndrome An increased enteral bile acid loss occurs most frequently in Crohn’s disease with ileal involvement, and after surgical resection of the ileum. If less than 1 m of ileum is removed or functionally impaired, a compensated chologenic diarrhea occurs, and it can be efﬁciently treated with ionexchangers (cholestyramine, cholestipol).
Malabsorption can also occur. Correction of the underlying hypothyroidism also leads to the improvement of malabsorption. Amyloidosis, scleroderma, and dermatomyositis can be accompanied by malabsorption syndrome. The etiology is a motility disorder resulting in bacterial overgrowth in the small intestine. Systemic vasculitis with small-intestinal involvement may inﬂuence drug absorption owing to either altered motility or mucosal damage. The decreased absorption of diazepam, phenytoin, and acetaminophen was attributed to inﬂammatory and vascular changes in the duodenum in Behcet’s syndrome, even in the absence of clinical evidence for a malabsorption syndrome (12).