Malabsorption Syndromes

Here we'll learn about select malabsorption syndromes; be aware that many other disorders are associated with GI malabsorption, but they are discussed in other contexts (i.e., cholestasis, inflammatory bowel disease). Malabsorption is the failure to assimilate one or more nutrient types due to defects in digestion, absorption, or transport. Failure is due to:

• Deficient digestive agents (i.e., pancreatic enzymes)
• Abnormal gastrointestinal epithelium
• Impaired transport
• Short bowel (for example, after re-sectioning in inflammatory bowel treatment)
• Inadequate mixing in the stomach

Signs and symptoms: Diarrhea, steatorrhea, weight loss, weakness, anemia, and vitamin and mineral deficiencies. Malnutrition can lead to musculoskeletal, neurologic, and cardiac complications (i.e., night blindness in Vitamin A deficiency, peripheral neuropathy due to deficiencies in Vitamins B1, B6, B12, edema in protein deficiency, etc.). Diagnosis:

• Patient history (stool type & frequencies, weight loss, etc.)
• Blood tests to determine specific nutrient deficiencies (which may point to the specific disorder)
• Fecal fat tests and Sudan III staining to confirm malabsorption
• Investigation into the root cause, which can involve endoscopy and colonoscopy with or without biopsy, breath tests, or small bowel x-rays.

EPI causes malabsorption of fats and fat-soluble vitamins (A, D, E, K, and B12) when more than 90% of the pancreatic enzyme function is lost. Top causes: Pancreatitis (often due to excess alcohol consumption in adults), cystic fibrosis (the most common cause in children), and tumors that obstruct pancreatic enzyme transport to the small intestine. You may recall that the pancreas secretes amylase, protease, and lipase, and wonder why pancreatic insufficiency causes fat malabsorption but doesn't usually affect carbohydrate or protein absorption. This is because carbohydrate and protein digestion and absorption are typically maintained by amylase and protease secreted by other organs (salivary glands, stomach, small intestine). Signs and symptoms: The feces of patients with EPI are loose, bulky, oily, and pale – the stool often floats because of the oil content. Patients with pancreatitis have pain that starts in the left epigastric area and radiates to the back. Diagnosis: Reduced duodenal pH and fecal elastase-1 (FE-1), which is an enzyme marker of pancreatic secretion. Treatment: Lifestyle modifications (alcohol cessation), vitamin supplements, and exogenous pancreatic enzyme administration. Caused by deficient activity of lactase, which is an intestinal enzyme that breaks down lactose; lactose is a carbohydrate found in dairy products. Lactose intolerance prevalence worldwide is estimated to be more than 65%. Prevalence varies widely according to population: ~30% in Europe, ~50% in the United States, ~70% in Asian countries, and nearly 100% in Africa; variability likely reflects genetic adaptations in populations heavily reliant on dairy products). Symptoms of lactose intolerance vary according to the extent of the deficiency and other factors. Causes: We can break down the causes of lactase deficiency into three groups: Congenital lactase deficiency is a rare autosomal recessive disorder with deficient enzyme activity from birth. Primary lactose intolerance (adult-type lactase deficiency) is the common condition resulting from downregulated lactase gene expression over the course of normal human development (also an autosomal recessive trait). Secondary lactase deficiency is transient state due to intestinal damage caused by infections, food allergies, etc. In these cases, the intestinal villi will appear damaged, whereas the intestinal villi in primary lactose intolerance appear normal. Lactase: We show what happens in the intestines in the presence and absence of lactase: In the presence of lactase, lactose is broken down to form galactose and glucose, which are absorbed into the blood stream. However, in the absence of lactase, the lactose remains in the intestines with the following outcomes: The undigested lactose produces pulls water into the intestines, causing osmotic diarrhea. Bacterial enzymes ferment lactose and produce short-chain fatty acids and gas with abdominal pain, bloating, and flatulence. Diagnosis: We often use a hydrogen breath test to diagnose lactose intolerance. To administer the test, we collect baseline levels of hydrogen in the breath, then administer a lactose solution. In the setting of lactase deficiency, hydrogen production will increase from bacterial fermentation in the colon. If hydrogen increases more than 20 ppm (parts per million) above baseline, the patient has lactase deficiency. We can also use blood glucose tests, DNA tests, and stool acidity tests to determine lactase status. It is recommended that patients reduce consumption of lactose-rich foods; patients may need to experiment to find out how much lactose they can "tolerate," as this varies by person. Be aware that lactose intolerance is different from "milk allergy," which is an immune-mediated reaction to cow's milk proteins. CD is an autoimmune-mediated inflammatory disorder of the small bowel; it is triggered by gliadin, which is a gluten protein found in wheat, barley, and rye. Celiac disease is also referred to as gluten-induced enteropathy, non-tropical sprue, and celiac sprue. Celiac disease affects 1% of US adults. Diagnosis: To screen for celiac disease we can use serological markers: IgA anti-tissue transglutaminase (tTG-IgA, tTG-IgG), deamidated gliadin peptide antibodies, and anti-endomysial antibodies (EMA-IgA). Serological screening can suggest, but not diagnose, celiac's disease. Diagnosis requires endoscopy with small bowel biopsy. We look for histologic changes concurrent with gluten-containing diet and clinically significant improvement when the gluten-containing diet is stopped. On gross inspection, we see "scalloping" of the duodenal folds and increased vascularity. Scalloping is not specific to celiac disease, but reflects the villous atrophy and edema of duodenal injury. Celiac disease histopathology is characterized by increased lymphocytes, mucosal inflammation, villous atrophy, and crypt hyperplasia upon exposure to gluten, all of which diminish when gluten is removed from the diet. See below for image references. Genetic markers include haplotypes HLA-DQ2 and HLA-DQ8 (which are common in the general population, so are only useful for ruling out Celiac's disease). Other common associations include dermatitis herpetiformis (approximately 10% of patients with CD), reduced bone density due to calcium deficiency, and increased risk of malignancy. Treatment: Gluten-free diet. A rare disorder of uncertain origins (likely infectious or environmental causes) that occurs in some tropical regions (i.e., parts of India and Pakistan, Puerto Rico, Haiti, and Cuba). It is characterized by malabsorption of folic acid and Vitamin B12, and, therefore, development of megaloblastic anemia. Diagnosis: Upon biopsy we'll see villous atrophy, increased crypt depth, epithelial cell enlargement, and increased lymphocytic and inflammatory cells. Since Tropical Sprue and celiac disease have similar histopathology, we use serologic tests to rule out Celiac's disease. Treatment: Tropical sprue with folic acid and Vitamin B12 supplementation and antibiotics (tetracycline, ampicillin, etc.). A rare bacterial disease caused by Tropheryma whipplei. These bacteria are gram-positive and periodic acid-Schiff (PAS)-positive bacilli that are ubiquitous in the environment. It seems that some individuals are more genetically susceptible to infection and disease than others. Whipple disease is most common in older males of European descent with immune defects. Patients with Whipple disease suffer a range of multisystemic symptoms. Clinical presentation: Starts with arthralgias, but can also include neurologic symptoms (dementia, for example), and endocarditis, in addition to the classic GI effects that occur later in the course of disease (diarrhea, abdominal pain, weight loss). Diagnosis: To diagnose Whipple Disease we use PAS-positive staining after small bowel biopsy. Key histopathological features are PAS-positive foamy macrophages in the lamina propria and villous atrophy. Because the neurologic effects of Whipple Disease can be disabling, be sure to use PCR tests for T. whipplei DNA in the CSF. Treatment: Antibiotics (ceftriaxone or penicillin, then trimethoprim/sulfamethoxazole); it is fatal without treatment. Be aware that relapses are common.