MALABSORPTION SYNDROME This occurs when the normal digestion and absorption of food is interrupted 1. Pathogenesis 2. Causes 3. Consequences 4. Clinical features 5. Investigations

Luminal digestion 1. Sufficient pancreatic enzymes (lipase, trypsin, chymotrypsin, amylase) 2. Conjugated bile acids from the liver

Mucosal digestion It requires: Small bowel brush border enzymes

Mucosal absorption It requires: 1. Adequate surface of normally functioning small bowel mucosa. 2. Normal intestinal lymphatics.

2.Causes of malabsorption Inadequate digestion: Postgastrectomy steatorrhea. Exocrine Pancreatic insufficiency. Reduced bile salt concentration in intestine: I.) Liver Disease II.) Cholestasis III.) Bacterial overgrowth IV.) Interruption of enterohepatic circulation of bile salt.

Inadequate absorptive surface: 1. Resection 2. Diseased intestine: Celiac disease Tropical sprue Crohn’s disease Disaccharide Deficiency Lymphoma TB

c. Lymphatic obstruction. e.g Lymphoma D. Decreased availability of ingested nutrients and cofactors for absorption. i) Vitamin B12 malabsorption: intrinsic factor deficiency e.g. gastrectomy, atrophic gastritis( antiparietal cell Ab). ii) Bacterial overgrowth –can bind B12.

3.Consequences of malabsorption 1. Fat malabsorption: steatorrhea (flow of fat, diarrhea of fat) It will result in weight loss because fat has the high caloric content. 2. Fat soluble vitamins malabsorption: (ADEK) A,D,E, and K.

3. Impaired protein absorption: protein malnutrition 4 3. Impaired protein absorption: protein malnutrition 4. Impaired carbohydrate absorption: clinically apparent carbohydrate malabsorption and diarrhea

5. Impaired absorption of iron, folate, and B12 5. Impaired absorption of iron, folate, and B12. This happen only small intetsinal mucosal disease and is not a feature of pancreatic insufficiency.

5. CLINICAL MANIFESTATIONS History: Diarrhea/steatorrhoea Weight loss Symptoms of anaemia Diarrhoea – bulky, floating, malodorous stool – difficult to flush. Weight loss – may be profound. Anaemia – B12, iron, folate malabsorption. Patient may complain of dizziness, dyspnoea and fatigue

Important part of history: 1. Ethanol abuse 2. Drugs 3 Important part of history: 1. Ethanol abuse 2. Drugs 3. Previous gastric or intestinal surgery 4. Positive family history (Celiac) 4. Pulmonary manifestations (cystic fibrosis) 5. Fever and weight loss (TB, lymphoma, Crohns disease of small bowel)

O/E: Normal. Pallor - muscle wasting Sign of vitamin deficiency glossitis – B deficiency ecchymoses parasthesia tetany

Clinical approach: 1. Identify nutritional deficiency: single, multiple or generalized 2. Document impaired digestion and or absorption 3. Identify underlying cause 4. Treat appropriately.

Investigations 1. Screening tests. 2. Specific diagnostic tests 3. Tests to identify the underlying cause.

Screening test)) Investigations: General: - CBC - Blood film - Ca. - B12, folate - Iron study - LFT, PT, PTT

6. 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

Sudan Black Test: This test has replaced fecal fat estimation It is much easier, done on single specimen of stool. It will be positive if abnormal amount of fat present in the stool.

Carbohydrate absorption test 1) Hydrogen breath test Hydrogen excretion ↑ in bacterial overgrowth small intestinal malabsorption

2. D-xylose test: An oral- labelled simple sugar that does not undergo any digestion Only need normal bowel mucosa to be absorbed and excreted in the urine. It is normal in pancreatic causes of malabsorption

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.

Tests to identify underlying cause: 1. Small bowel cause 2 Tests to identify underlying cause: 1. Small bowel cause 2. Pancreatic cause

A. Small bowel tests 1. D-xylose 2. Small bowel biopsy 3. Serological tests for celiac disease 4. Radiology: barium follow-through

B. Pancreatic functions 1. Direct: Secretin stimulation test: It stimulate the pancreas to release bicarbonate. After which duodenal fluid is collected and analyzed to quantify normal pancreatic secretory content (ie, enzymes, and bicarbonate).

2. Indirect: fecal fat estimation Sudan black 3 2. Indirect: fecal fat estimation Sudan black 3. Radiographic techniques: - Plain abdominal X-ray - U/S abdomen - ERCP - CT abdomen - MRI & MRCP - Endoscopic ultrasound

4. Fecal elastase measurement: It is the most sensitive and specific, especially in the early phases of pancreatic insufficiency. Values less than 200 mcg/g are suggestive of pancreatic insufficiency

Diseases causing malabsorption 1. Celiac disease 2. Exocrine pancreatic insufficiency 3. Disaccaharidase deficiency (lactase deficiency) 4. Tropical sprue 5. Small intestinal bacterial overgrowth. 6. Whipples disease. 7. Intestinal lymphangiectasia

Disaccharides malabsorption The terminal phase of digestion of ingested complex carbohydrate such as oligosaccharides and disaccharides including lactose occurs at the brush border membrane of intestinal absorptive cells where disacharideases enzymes are located.

Lactose malabsorption 1. Congenital lactase deficiency 2. Acquired: The most common cause of carbohydrate intolerance in adults. Low mucosal lactase levels are observed in over 90% of Asians

Pathogenesis Fermentation of unabsorbed lactose by intraluminal bacteria.

Clinical features & diagnosis History: Diarrhea Abdominal discomfort Flatulence following the ingestion of dairy products or other foods rich in lactose. 2. The diagnosis is confirmed by: lactose breath hydrogen test. oral lactose intolerance test.

Tropical Sprue Occurs among natives of, visitors to selected countries located in the tropics (major epidemics have been described in south Indian villages) Cause: Most probably infectious (no single causative pathogen has been identified) opi

Clinical features Non specific Diarrhea, steatorrhoea, weight loss, nausea, and anorexia. Anemia is common (megaloblastic or dimorphic)

Diagnosis & Treatment Mucosal biopsy of the small intestine reveals a nonspecific lesion of variable severity. Treatment: Antibiotic such as tetracycline and high-dose folic acid. Response is prompt. Treatment lasting 6 months- 1 year

Small intestinal bacterial overgrowth Under normal circumstances the proximal small intestinal lumen harbors less than 105 bacteria per milliliter of intestinal contents. Overgrowth of bacteria in the small intestine (there may be 108-1010/mL organisms) .

Pathogenesis 1. Bacteria deconjugate the bile salts 2. The bacteria produce toxins and proteolytic enzymes that damage the mucosa specially the brush border. 3. The bacteria bind and metabolize B12 preventing its absorption in the distal ileum.

Causes 1. Motility disorders Scleroderma, amyloidosis, vagotomy, diabetic visceral neuropathy. 2. Structural abnormalities Diverticula, strictures, afferent loop stasis, vascular. 3. Hypochlorhydria or achlorhydria 4. Hypogammablobulinemia or agammaglobulinemia •

Clinical features Watery diarrhoea and/or steatorrhoea Anaemia due to B12 deficiency

Diagnosis 1. Quantitative culture of the duodenal fluid is the diagnostic gold standard. 2. Breath tests utilizing lactulose, xylose, and Glucose 3. Serum vitamin B12 concentration is low, whilst folate levels are normal or elevated because the bacteria produce folic acid. 4. Response to antibiotics

Treatment Antibiotics are the treatment of choice. Amoxicillin–clavulanate alone or with metronidazole 2-week course of therapy (prolonged remission) Frequent intermittent courses of antibiotics when symptomatic may be required in some patients.

Whipple's disease A rare condition characterized by infiltration of small intestinal mucosa by 'foamy' macrophages The disease is a multisystem one and almost any organ can be affected, sometimes long before gastrointestinal involvement becomes apparent Middle-aged men are most commonly affected

Cause Infection with the Gram-positive bacillus Tropheryma whipplei

Clinical features The presentation depends on the pattern of organ involvement 1. GIT: Diarrhoea (75%), steatorrhoea, weight loss (90%), bloating, protein-losing enteropathy, ascites, hepatosplenomegaly (< 5%) 2. Mscloskeletal: Seronegative large joint arthropathy, sacroiliitis 3. Cardiovascular:Pericarditis, myocarditis, endocarditis, coronary arteritis .

4. Neurological: Apathy, fits, dementia, myoclonus, meningitis, cranial nerve lesions 5. Pulmonary: Chronic cough, pleurisy, pulmonary infiltrates 6. Hematological: Anaemia, lymphadenopathy 7. Other:Fever, pigmentation

Diagnosis Upper GI endoscopy and biopsy Villi are widened and flattened; densely packed macrophages occur in the lamina propria. which stain positive with periodic acid-Schiff (PAS) reagent These may obstruct lymphatic drainage, causing fat malabsorption

Treatment Antibiotics: 1. Intravenous ceftriaxone 2 gm, iv daily for 2 weeks 2. Followed by oral co-trimoxazole for at least 1 year. Symptoms usually resolve quickly Long-term follow-up is essential, as relapse occurs in up to one-third of patients.

Intestinal lymphangiectasia A. Primary: due to impaired lymphatic formation during development. B. Secondary: lymphatic obstruction 1. Infection such as TB or filariasis. 2. Neoplasm (lymphoma) 3. Retroperitoneal fibrosis. 4. Constrictive pericarditis

Consequences Rupture of the lymphatics result in: 1. leakage of lymph which is rich in fat, protein fat soluble vitamins and lymphocyte into the gut lumen. 2. Impaired transport of dietary lipids to the systemic circulation.

Clinical features 1. Weight loss, diarrhea, steatorrhea. 2. Edema, chylous ascites, and chylous pleural effusions Chyle: Milky-white fluid , rich in triglycerides

Investigations 1. Biochemical: Hypoalbuminemia Reduced serum immunoglobulin concentrations 2. Hematological: lymphocytopenia 3. Histological: Jejunal biopsies show greatly dilated lacteals. 4. Lymphangiography: may localize the site of lymphatic lymphatic obstruction or show leakage

Treatment 1. Low-fat diet with medium-chain triglyceride (transported in the portal blood) 2. A high protein diet. 3. Reduction of dietary long-chain triglycerides that stimulate lymph formation, increasing intralymphatic pressure and predisposing to lymphatic rupture and lymph leakage. 4. Treatment of the cause.

Short Bowel Syndrome The small intestine has sufficient reserve Resection of 50% is well-tolerated provided that the duodenum and proximal jejunum and the distal 100 cm of the ileum are not removed and are free of disease Extensive resection or disease of small intestine will result in maldigestion and malabsorption.

Consequences Depend on site and extent of resection Digestion and absorption are normally completed within the first 100 cm of jejunum, Extensive resection will cause maldigestion and malabsorption .

Pathogenesis 1. Reduction of the available absorptive surface. 2. Acid hypersecretion that induces intestinal mucosal damage and can inactivate pancreatic lipase ( postoperative hypergastrinemia) 3. Depletion of the bile salt pool. 4. Small intestinal bacterial overgrowth.

Clinical features Symptoms: Resection of 70–80% of the small intestine often produces catastrophic malabsorption with massive diarrhea and steatorrhea. Signs: Dehydration and signs of hypovolaemia are common Weight loss, loss of muscle bulk and malnutrition

Causes Small bowel resection due to: a. Acute mesenteric ischemia b. long-standing Crohn,s disease c. Radiation enterocolitis d. Malignant disease of the small bowel

Treatment 1. Parenteral nutrition initially. 2. Early initiation of continuous enteral feedings to minimize intestinal mucosal atrophy and maximize adaptive mucosal hyperplasia. 3. Proton pump inhibitor to control acid hypersecretion during the early period. 4. loperamide or codeine to decrease intestinal transit time and hence contact of nutrients with the intestinal mucosa

5. Transition to oral feedings, starting with multiple small meals while tapering parenteral nutrition is often feasible as intestinal adaptation progresses over time (morphological,length and diameter) 6. Small intestinal transplantation: In patients in whom adaptation is not adequate and long-term parenteral nutrition is not feasible.

Lymphoma (NHL) GIT may be involved: 1. As part of more generalised disease. 2. Primary gut lymphoma (rare) The small intestine being most commonly affected. Lymphomas occur with increased frequency in patients with: Coeliac disease, AIDS and other immunodeficiency states.

Age: most often in middle-aged men Site: usually focal with a predilection for the ileum Two variants of small intestinal lymphoma regularly cause malabsorption: 1. Immunoproliferative small intestinal disease-associated lymphoma (IPSID) 2. Enteropathy-associated T-cell lymphoma (EATL).

IPSID (Mediterranean lymphoma) Age: young adults ,native Middle-Eastern populations as well as in South Africa and Pakistan. Its cause is unknown It has been suggested that bacteria or other antigens cause excessive proliferation of lamina propria immunocompetent cells in people with poor hygiene

Clinical features 1. Early: Abdominal pain Diarrhea and steatorrhea Anorexia and weight loss. 2. Advanced: Edema, ascites Hepato-splenomegaly Palpable abdominal masses may become evident.

Investigations IPSID is associated with the production of an unusual IgA heavy chain protein, called α heavy chain, which is secreted by plasma cells 1. Immunoglobulin electrophoresis: It will reveal the presence of a paraprotein consisting of the Fc portion of IgA (heavy chain), devoid of light chains, as a broad band on protein electrophoresis

Histology 2. OGD and biopsy: In the early stages: Diffuse infiltration of the mucosa and submucosa with B lymphocytes and plasma cells. As the disease progresses the infiltrating cells develop histologically malignant characteristics and mesenteric nodes become involved

Treatment 1. Antibiotics: (long-term) Such as, tetracycline, ampicillin, and metronidazole Prolonged remissions can be obtained and even cure. 2. Chemotherapy : for those who fail to respond or who have aggressive disease.

Gut infection 1. Intestinal tuberculosis. 2. Giardiasis

Intestinal tuberculosis Usually results from human M. tuberculosis which is swallowed after coughing. The area most commonly affected is the ileocaecal region

Clinical features Abdominal pain can be acute or of several months' duration 2. Diarrhoea : less common 3. Low-grade fever is common

Diagnosis 1. Barium follow-through 2. Colonoscopy and terminal ileoscopy 3. Histological confirmation(caseation of granulomas is not always seen ) 4. Culture ( may take 6 weeks ) 5. PCR-based techniques on biopsy specimens.

Treatment Chemotherapy with four drugs (2 months) Isoniazid Rifampicin pyrazinamide ethambutol Continue isoniazid and rifampicin for 4 more months

Giardia lamblia The most common protozoal infestation Once cysts are ingested, the distinctive trophozoites are released in the upper small intestine The trophozoites attach to the intestinal epithelium and can produce significant enteritis with mucosal inflammation and architectural changes.

Clinical features 1.Asymptomatic: Approximately 50% of individuals infested with G lamblia have no symptoms (asymptomatic carriers) 2. Symptomatic: Diarrhea, flatulence, abdominal cramps, and epigastric pain and nausea and vomiting. 3. Some patients present with steatorrhea and weight loss.

Diagnosis 1. Stool examination: Concentrated, iodine-stained wet stool preparations Because cysts and trophozoites are present only intermittently in the stool, however, the sensitivity is only approximately 50%, even with examination of multiple specimens 2.Stool immunoassays (Molecular tests )including an ELISA with reported sensitivities and specificities approaching 100%.

3. Direct sampling of duodenal contents (e. g 3. Direct sampling of duodenal contents (e.g., duodenal aspiration or the “string test”), sensitivity can be improved to approximately 80% 4. OGD and duodenal biopsy: Identification of trophozoites with small intestinal biopsy specimens

Treatment Metronidazole, 250 mg orally three times a day for 5 days A single 2-g dose of tinidazole has been reported to be 90% effective