Maldigestion and Malabsorption DR.RAHIMI The only clinical situations in which absorption is increased are hemochromatosis and Wilson's disease, in which absorption of iron and copper, respectively, are increased. Disorders of absorption must be included in the differential diagnosis of diarrhea The demonstration of the effect of prolonged (>24 h) fasting on stool output can be very effective in suggesting that a dietary nutrient is responsible for the individual's diarrhea. The presence of a significant osmotic gap suggests the presence in stool water of a substance (or substances) other than Na/K anions that is presumably responsible for the patient's diarrhe. MALABSORPTION SYNDROME PATHOPHYSIOLOGICAL (MECHANISM): - Is divided into: A) Intraluminal stage Impaired hydrolysis and solubilization of nutrients B) Intestinal stage C) Lymphatic transport A) Intraluminal stage 1) Impaired fat absorption: i) Pancreatic lipase is necessary for triglyceride hydrolysis in duodenum. Pancreatic enzyme deficiency leads to fat malabsorption. ii) Inactivation of pancreatic lipase by low gastric luminal pH – fat malabsorption. iii) Interruption of enterohepatic circulation of bile salt – impaired micelle formation – fat malabsorption. Absorption of fat soluble vitamins may be impaired as well. 2) Impaired carbohydrate absorption: Most diseases that causes carbohydrate malabsorption do so by affecting intestinal stage. But amylase catalyse hydrolysis of starch to oligosaccharides. 3) Impaired protein absorption: Hydrolysis of polypeptides occurs mainly in small intestine by action of pancreatic enzyme trypsin, chymotrypsin. Deficiency of pancreatic proteases – impaired protein absorption. Diseases like: Chronic pancreatitis Cystic fibrosis Ca. pancreatic resection - Protein malnutrition B) Intestinal stage 1) Abnormalities of small intestinal mucosa. Lactase deficiency e.g. Congenital or acquired Result – malabsorption of lactose. Acquired:- i) Celiac disease ii) Crohn’s disease iii) Infective enteritis 2) Impaired epithelial cell transport: Many diseases cause loss of intestinal surface area - malabsorption of many nutrients. e.g. i) Celiac disease ii) Tropical spure iii) Extensive surgical resection iv) Drugs C) Lymphatic transport: Lymphatic obstruction – fat malabsorption e.g. i) Intestinal lymphangiectasia iii) Tuberculous enteritis iv) Intestinal lymphoma D) Decreased availability of ingested nutrients and cofactors for absorption. i) Vitamin B12 malabsorption if intrinsic factor is deficient. e.g. gastrectomy, antiparietal cell Ab. ii) Bacterial overgrowth –can bind B12. iii) Patient infected with fist tapeworm – B12 deficiency. Tests for steatorrhea Quantitative test 72hr stool fat collection – gold standard >7gm/day – pathologic up to 14 g per day (secondary fat malabsorption) could be used as the upper limit of normal in patients with diarrhea Qualitative tests Sudan lll stain Detect clinically significant steatorrhea in >90% of cases Although it cannot be used to exclude steatorrhea; its sole advantage is its ease of performance. Acid steatocrit – a gravimetric assay NIRA (near infra reflectance analysis) Equally accurate with 72hr stool fat test Investigations: Specific: Tests of fat absorption: Quantitative fecal fat Patient should be on daily diet containing 80-100 grams of fat. Fecal fat estimated on 72 H collection. 6 grams or more of fat/day is abnormal. May be due to: - Pancreatic - Small intestinal - Hepatobiliary disease 14C-Triolein Test: Is triglyceride which is hydrolysed by pancreatic lipase. absorption of metabolism ↑ 14CO2 lung Tests for pancreatic function: 1) Bentiromide test: Chymotrypsin PABA + pepside PABA absorbed and conjugated in liver urine excretion 2) Schilling test 3) Pancreatic stimulation test Secretin stimulation – 4) Radiographic techniques: - Plain abdominal X-ray - U/S abdomen - ERCP - CT abdomen Schilling test The Schilling test can be used clinically to distinguish between gastric and ileal causes of vitamin B12 deficiency. Alternative approaches to diagnosing pernicious anemia are to document atrophic gastritis by endoscopy and biopsy, to confirm achlorhydria by acid secretion analysis and increased serum gastrin levels, and to look for antibodies in the serum directed against parietal cells or intrinsic factor. Schilling test results are normal in patients with dietary vitamin B12 deficiency, in protein-bound (foodbound) vitamin B12 malabsorption, and sometimes in congenital transcobalamin II deficiency. False-positive results on the Schilling test can result from renal dysfunction or inadequate urine collection Schilling test To determine the cause of cobalamine(B12) malabsorbtio Helps to asses the integrity of gastric, pancreatic and ileal functions. Abnormal cobalamine absorbtion in: pernicious anemia, ch. Pancreatitis, Achlorohydria, Bacterial overgrowth, ileal dysfunction The test : Administering 58Co-labeled cobalamine p.o. Cobalamine 1mg i.m. 1hr after ingestion to saturate hepatic binding sites Collecting urine for 24 hr (dependant on normal renal & bladder function) Abnormal - <10% excretion in 24 hrs Schilling Test 1. Ingestion of labeled Vit B12 and Non- labeled IM Vit B12 2. Urine labeled Vit B12 <8%/24 hr= malabsorption Intrinsic factor (Corrects) Pancreatic enzymes Antibiotic therapy Ileal disease or resection IF def (PA) Panc exoc def Bact overgrowth Carbohydrate absorption test 1) Hydrogen breath test Hydrogen excretion ↑ in bacterial overgrowth small intestinal malabsorption Carbohydrate absorption test 2) D-xylose test 5-carbon sugar excreted unchanged in urine 25 grams given Urine collected for 5 hours Normally 25% is excreted In patients with fat malabsorption, this test differentiates pancreatic from small intestinal malabsorpton. D-xylose is normal in pancreatic disease Serum level of D-xylose at 1-2 hours after ingestion can be measured. Test for bacterial overgrowth: Intestinal aspiration and culture 2) Breath test 3) C-D xylose breath test 1) Glucose Hydrogen most widely used breath test in clinical practice With bacterial overgrowth, : the glucose is cleaved by bacteria into carbon dioxide and hydrogen. rise of 20 parts per million (ppm) above the baseline is regarded as diagnostic of SIBO. Fasting breath hydrogen levels of more than 20 ppm also are considered positive. High baseline hydrogen levels also are common in untreated celiac disease and normalize after gluten withdrawal for as-yet-unknown reasons.[ Patients must avoid smoking and ingestion of nonfermentable carbohydrates, such as pasta and bread, the night before the test, because these factors can raise baseline breath hydrogen values. Exercise can induce hyperventilation, thereby reducing baseline breath hydrogen values, and should be avoided for two hours before the test. sensitivity of 62% and specificity of 83%. Very rapid intestinal transit can lead to a false-positive test result, because glucose can reach the colon before it can be absorbed. Lactulose Hydrogen Lactulose is a disaccharide that is not absorbed in the small intestine but is metabolized by bacteria in the proximal colon, producing a late peak in exhaled hydrogen. In the presence of bacterial overgrowth, an early hydrogen peak is observed. Results of this test may be difficult to interpret with either slow or fast intestinal transit, and sensitivity and specificity have been disappointing sensitivity and specificity rates of 68% and 44%, respectively. Sensitivity of the test may be increased by the addition of scintigraphy to correct for abnormalities of intestinal transit, but the lactulose hydrogen breath test cannot be recommended for routine clinical use. Xylose The 14C-xylose and 13C-xylose breath tests measure labeled carbon dioxide that is produced by breakdown of labeled substrates by bacteria. The isotope may be radioactive (14C) or stable (13C); the stable isotope has been used in children. d-Xylose is the most widely used substrate and is a good substrate for breath testing for SIBO because it is absorbed completely in the small intestine, is metabolized minimally, and is catabolized by Gram-negative bacteria. The 14C-d-xylose breath test appears to perform better than the glucose or lactulose hydrogen breath test The 14C-d-xylose breath test result is considered positive when the “cumulated dose at four hours exceeds 4.5% of the administered radioactivity.” Disturbances in intestinal transit particularly affect the performance of this test, and accuracy may be improved by the addition of a transit marker (such as barium or diatrizoate meglumine–diatrizoate sodium [Gastrografin]) and radiologic imaging Radiography of small intestine: barium contrast (small-bowel series or study)– to see - Blind loop - Strictures and fistulas (as in Crohn's disease) - J. diverticular A normal barium contrast study does not exclude the possibility of small-intestinal disease. 2) CT enteroclysis and magnetic resonance (MR) enteroclysis 1) 2) Intestinal mucosal biopsy: indications ; A small-intestinal mucosal biopsy is essential in the evaluation of a patient with documented steatorrhea or chronic diarrhea (lasting >3 weeks) Diffuse or focal abnormalities of the small intestine defined on a small-intestinal series Disease that Can Be Diagnosed by Small-Intestinal Mucosal Biopsies Lesions Diffuse, Specific Whipple's disease Agammaglobulinemia Abetalipoproteinemia Patchy, Specific Intestinal lymphoma Intestinal lymphangiectasia Eosinophilic gastroenteritis Amyloidosis Crohn's disease Infection by one or more microorganisms (see text) Mastocytosis Pathologic Findings Lamina propria contains macrophages containing PAS+ material No plasma cells; either normal or absent villi ("flat mucosa") Normal villi; epithelial cells vacuolated with fat postprandially Malignant cells in lamina propria and submucosa Dilated lymphatics; clubbed villi Eosinophil infiltration of lamina propria and mucosa Amyloid deposits Noncaseating granulomas Specific organisms Mast cell infiltration of lamina propria Lesions Diffuse, Nonspecific Celiac disease Tropical sprue Bacterial overgrowth Pathologic Findings Short or absent villi; mononuclear infiltrate; epithelial cell damage; hypertrophy of crypts Similar to celiac disease Patchy damage to villi; lymphocyte infiltration Folate deficiency Short villi; decreased mitosis in crypts; megalocytosis Vitamin B12 deficiency Similar to folate deficiency Radiation enteritis Similar to folate deficiency Zollinger-Ellison syndrome Mucosal ulceration and erosion from acid Protein-calorie malnutrition Villous atrophy; secondary bacterial overgrowth Drug-induced enteritis Variable histology Results of Diagnostic Studies in Different Causes of Steatorrhea D-Xylose Test Schilling Test Duodenal Mucosal Biopsy Normal Chronic pancreatitis Normal 50% abnormal; if abnormal, normal with pancreatic enzymes Bacterial overgrowth syndrome Normal or only modestly abnormal Often abnormal; if abnormal, normal after antibiotics Usually normal Ileal disease Celiac disease Normal Decreased Abnormal Normal Intestinal lymphangiectasia Normal Normal Normal Abnormal: probably "flat" Abnormal: "dilated lymphatics" Malabsorption due to bacteral over growth of small bowel Normal small intestine is bacterial sterile due to: Acid Int. peristalsis (major) Immunoglobulin Cause of bacterial growth. e.g. Small intestinal diverticuli Blind loop Strictures DM/ Scleroderma Pathophysiology 1) Bacterial over growth: Metabolize bile salt resulting in deconjugation of bile salt Bile Salt Impaired intraluminal micelle formation Malabsorption of fat. Intestinal mucosa is damaged by Bacterial invasion Toxin Metabolic products Damage villi may cause total villous atrophy. 2) Clinically: Steatorrhea Anaemia B12 def. Reversed of symptom after antibiotic treatment. Diagnosis: Breath test Cxylose test Culture of aspiration (definitive) Treatment: Antibiotic Tetracyclin Ciproflexacin Metronidazole Amoxil Short Bowel Syndrome Three different situations in adults demand intestinal resections: (1) mesenteric vascular disease, including atherosclerosis, thrombotic phenomena, and vasculitides (2) primary mucosal and submucosal disease, e.g., Crohn's disease (3) operations without preexisting small intestinal disease, such as trauma. Sequella of bowel resection Adaptation of remaining bowel:last for up to 6–12 months. Enteral nutrition with calorie administration must be maintained, especially in the early postoperative period The presence of the colon (or a major portion) is associated with substantially less diarrhea and lower likelihood of intestinal failure as a result of fermentation of nonabsorbed carbohydrates to SCFAs. Increase in oxalate absorption in the colon Cholestyramine, an anion-binding resin, and calcium have proved useful in reducing the hyperoxaluria. Gastric hypersecretion ( due to reduced hormonal inhibition of acid secretion or increased gastrin levels due to reduced smallintestinal catabolism of circulating gastrin) proton pump inhibitors can help in reducing the diarrhea and steatorrhea but only for the first six months. Absence of the ileocecal valve decrease in intestinal transit time and bacterial overgrowth from the colon. Whipple's Disease Etiology:gram-positive bacillus, T. whipplei Clinical Presentation:diarrhea, steatorrhea, abdominal pain, weight loss, migratory large-joint arthropathy, and fever as well as ophthalmologic and CNS symptoms (dementia,..). The steatorrhea in these patients is generally believed secondary to both small-intestinal mucosal injury and lymphatic obstruction secondary to the increased number of PAS-positive macrophages in the lamina propria of the small intestine. Diagnosis:tissue biopsies from the small intestine and/or other organs . PAS-positive macrophages containing the characteristic small (0.25—1–2 mm) bacilli is suggestive of this diagnosis. Treatment:trimethoprim/sulfamethoxazole for approximately 1 year. Protein-Losing Enteropathy Normally, about 10% of total protein catabolism occurs via the gastrointestinal tract. Increased protein loss into the gastrointestinal in more than 65 different diseases with mucosal ulceration or nonulcerated mucosa or lymphatic dysfunction Peripheral edema and low serum albumin and globulin levels in the absence of renal and hepatic disease. Treatment: treat the underlying disease process .