Malabsorption syndromes

Malabsorption syndromes

1. Candidate:- Dr. Rohit Mehtani RMO Medicine M.Y. Hospital MALABSORPTION SYNDROMES Guide:- Dr. Amit Agrawal Assistant Professor Dept. of Medicine M.Y. Hospital

2. Madigestion – impaired breakdown of nutrients to absorbable products Malabsorption – defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements. Most malabsorption syndromes are associated with steatorrhoea – increase in stool fat excretion of >6% of dietary fat intake. Malabsorption syndromes must be included in the differentials of diarrhoea . Symptomatology

3. Diarrhoea – Decrease in stool consistency, an increase in stool volume, an increase in number of bowel movements, or any combination of these three changes. Q uantitative increase in stool water or weight > 200-225 mL or gram per 24 hour, when a western type diet is consumed. Individuals consuming high fibre diet may normally have a stool weight upto 400 g/24h . Secretory diarrhoea – D ue to small and/or large intestinal fluid and electrolyte secretion. Does not respond to prolonged fasting. Osmotic diarrhoea – D ue to diminished absorption of one or more dietary nutrients. Responds to prolonged fasting.

4. HISTORY – Diarrohoea – duration, consistency, frequency, stool characteristics, volume, association with diet, etc. Bloating, Abdominal pain Weight loss Weakness, bone pains Unexplained skin changes M outh ulcers Previous abdominal surgery – partial/total gastrectomy , small bowel resection, pancreas resection History of chronic pacreatitis Medications, Alcohol intake, history of radiotherapy Recurrent peptic ulcer disease Diabetes, CLD Family history – celiac disease, crohn’s disease, cystic fibrosis, lactase deficiency Risk factors like HIV infection CLINICAL EVALUATION

5. Signs & symptoms

6. CBC & ESR S. Proteins, S. Albumin Electrolytes & RFT Calcium PT-INR Alkaline Phosphatase Cholesterol Screening Investigations

7. Take careful history including drug intake, travelling and special foods, drinks or sweets Consider family history. Notice hints for malabsorption from physical examination. Look at stool for volume, appearance, admixtures of mucus, blood, parasites. Draw blood for screening laboratory examination to find additional hints. Diagnostic Algorithm

8. If the case warrants further exploration go on with -

9. Specific : Tests of fat absorption : Quantitative fecal fat estimation 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 . 14 C -Triolein Test – it is a triglyceride which is hydrolysed by pancreatic lipase. Absorption and metabolism of 14 C – triolein leads to increased excretion of 14 CO 2 by lungs. Sudan III test – qualitative test which detects clinically significant steatorrhea in >90% cases NIRA (Near Infra Reflectance Assay) – equally accurate with 72 hours fecal fat estimation Allows simultaneous measurement of fecal fat, nitrogen, carbohydrate

10. SCHILLING TEST Patient is given oral dose of radiolabelled vitamin b-12 One hour later, the patient is given i.m injection of unlabelled vitamin B-12 Patients urine is collected for a period of 24 hours Normally atleast 10% of the excreted Vitamin B-12 in urine is radiolabelled

11. Carbohydrate absorption test D -xylose test – it is a pentose which is excreted unchanged in urine. 25 g D-xylose is given and urine is collected for 5 hours. <4.5 g excretion reflects the presence of duodenal/ jejunal mucosal disease. It may also be abnormal in blind loop syndrome and false positive in patients with large fluid collections in third space, impaired renal functions, patients on ASA, indomethacin, neomycin. In patients with fat malabsorption , this test differentiates pancreatic from small intestinal malabsorpton . D-xylose is normal in pancreatic disease.

12. H2 breath test Baseline levels of hydrogen in breath are measured. Patient is given pure lactose (20 to 25 grams) and then hydrogen levels in breath are measured every 15, 30 or 60 minutes for 2-3 hours. If the level of hydrogen rises above 20ppm above the preceeding value within the test period, the test is positive. Lactose Tolerance test 50 gram lactose given p.o Blood glucose is measured at 0, 60 and 120 minutes Blood glucose <20 mg/l along with development of symptoms is characteristic of lactose intolerance Tests for bacterial overgrowth Q uantitative bacterial count from aspirated small bowel <10 5 /ml – jejunum >10 5 /ml – ileum Enteral Protein loss is measured by measuring clearance of alpha-1 antitrypsin Pancreatic insufficiency is tested by administering a meal of hormonal secretagogues and then analysing d uodenal fluid.

13. Radiographic Evaluation – Barium swallow and follow-through – to see Blind loop, Stricture or J. diverticula. Normal Celiac Sprue Jejunal Diverticulosis Crohn’s Disease

14. Primary indications are – evaluation of a patient with documented or suspected steatorrhea or chronic diarrhoea . Diffuse or focal abnormalities of small intestine defined on a small intestinal series. Lesions on small bowel biopsy may be – Diffuse, specific Patchy, specific Diffuse, nonspecific Identification of micro-organisms Intestinal Biopsy

15. Normal small bowel mucosa Celiac Sprue Treated Celiac Sprue Intestinal lymphangiectasia Whipple’s Disease Intestinal Lymphoma

16. INADEQUATE DIGESTION Deficiency or inactivation of pancreatic lipase Exocrine pancreatic insufficiency – chronic pancreatitis, pancreatic carcinoma, cystic fibrosis, congenital or acquired pancreatic insufficiency Gastrinoma – acid inactivation of lipase Drugs – orlistat IMPAIRED MICELLE FORMATION Liver disease Bacterial overgrowth in small intestine – anatomic stasis (blind loop/fistula/stricture) or functional stasis (diabetes/scleroderma/intestinal pseudo- ostruction ) Interrupted enterohepatic circulation of bile salts – ileal resection, crohn’s disease Drugs – Neomycin, cholestyramine , calcium carbonate Impaired mucosal absorption Intestinal resection or bypass Inflammation, infiltration or infection – crohn’s disease, amyloidosis, scleroderma, lymphoma, eosinophilic enteritis, mastocytosis , tropical sprue , celiac sprue , collagenous sprue , whipple’s disease, radiation enteritis, folate and b12 deficiency, giardiasis, graft versus host disease Genetic disorders – disaccharidase deficiency, agammaglobulinemia , abetalipoproteinemia , cystinuria , hartnup disease CLASSIFICATION OF MALABSORPTION SYNDROMES

17. IMPAIRED NUTRIENT DELIVERY TO AND/OR FROM INTESTINE Lymphatic disorders – lymphoma, lymphangiectasia Circulatory disorders – CHF, constrictive pericarditis, vasculitis, mesentric artery atherosclerosis ENDOCRINE AND METABOLIC DISORDERS – Diabetes, hyperthyroidism, hypoparathyroidism , adrenal insufficiency, carcinoid syndrome. CLASSIFICATION OF MALABSORPTION SYNDROMES

18. Enterohepatic Circulation of Bile acids

19. Process Pathophysiologic Defect Disease Example Synthesis Decreased Hepatic Function Cirrhosis Biliary Secretion Altered canalicular function Primary biliary Cirrhosis Maintainence of Conjugated Bile acids Bacterial overgrowth Jejunal diverticulosis Reabsorption Abnormal ileal function Crohn’s Disease Defects in Enterohepatic Circulation Of Bile acids

20. Ileal dysfunction results in decrease in bile acid reabsorption and increase in bile acid delivery to the large intestine which results in diarrhoea with or without steatorrhea . In patients with limited ileal disease often have diarrhoea due to active chloride secretion in the colon because of bile acids, also known as choleretic enteropathy .

21. Dietary fat is composed exclusively of long chain triglycerides. Assimilation of dietary lipids has three phases – Intraluminal or digestive phase Mucosal or absorptive phase Delivery or postabsorptive phase LIPID DIGESTION

22. Defects in Lipid Digestion

23. Carbohydrates in diet are present in the form of starch, disaccharide and glucose. They are absorbed only in small intestine and only in the form of monosaccharides . Lactose malabsorption is the only clinically important disorder and is due to lactase deficiency. It may be primary or secondary – Primary Lactase deficiency – genetically determined decrease or absence of lactase is noted. Secondary Lactase deficiency – seen in small intestinal mucosal disease with abnormalities in both structure and function of brush border enzymes and transport processes. Ex:- Celiac disease. CARBOHYDRATE DIGESTION

24. Mostly individuals with primary lactase deficiency are asymptomatic. Few develop symptoms of lactose intolerance, like diarrhoea , abdominal pain, cramps or flatus.

25. Protein is present in diet as polypeptides and is hydrolysed to dipeptides, tripeptides and amino acids before absorption. Proteolysis occurs both in stomach and small intestine, mediated by pepsinogen and trypsinogen . Protein digestion disorders are relatively rare. Three rare genetic disorders are :- Enterokinase deficiency – due to absence of brush border enzyme that converts trypsinogen to trypsin and is associated with diarrhoea , growth retardation and hypoproteinemia Hartnup Syndrome – defect in neutral amino acid transport, characterised by pellagra like rash and neuropsychiatric manifestations Cystinuria – defectin dibasic amino acid transport, associated with renal calculi and chronic pancreatitis. Protein Digestion

26. Celiac sprue is a common cause of malabsorption occurring at ages ranging from the first year of life through the eighth decade. Etiology : is not known, but three factors can contribute: 1. environmental. 2. immunologic. 3. genetic factors. 29

27. 1. Environmental factor: - There is association of the disease with gliadin , a component of gluten that is present in wheat. 2. Immunologic factor: - Serum antibodies are detected such as anti- gliadin . 3. Genetic factor: Almost all patients express the HLA-DQ2 allele Diagnosis – made by abnormal small intestinal biopsy. 30

28. Normal small intestinal mucosa is seen at the left, and mucosa involved by celiac sprue at the right Show blunting and flattening of villi with increased lymphocytes and plasma cells in the lamina propria in celiac disease 31

29. Tropical Sprue Caused by infectious agents including Giardia lamblia , Yersinia enterocolitica , Clostridum difficile . 32