1. MALABSORPTION Dr. WM Simmonds Internal Medicine (Gastroenterology) 15 August 2011

2. Aims Define malabsorption and discuss various causes. Briefly discuss celiac disease. Discuss chronic pancreatitis.

3. Malabsorption A state arising from abnormality in absorption of single or multiple nutrients across the gastrointestinal (GI) tract. Abnormalities in 3 necessary processes Intraluminal MALDIGESTION – Bile or pancreatic enzyme deficiency whereby fat and protein malabsorption results. Mucosal MALABSORPTION – Small bowel resection or small bowel epithelial damage causing a diminished absorptive surface area and brush border enzyme activity. Post-mucosal lymphatic system obstruction – Prevents uptake and transport of nutrients

4. Malabsorption Syndrome Pallor/Anaemia Night blindness (Vit A) Osteoporosis with pathological fractures Muscle wasting Muscle weakness Tetany (Low Calcium) Hypopigmentation/ Pellagra(Niacin) Ascites (Low Albumin) Dehydration (Diarrhoea) Ecchymoses (Vit K factor deficiency) Steatorrhoea Increased fecal fat Oedema (Low Albumin) Peripheral neuropathy (B12 def) Glossitis, stomatitis Apthous ulcers (Iron & B Vitamin deficiency) Pathological Weight loss

5. Causes of Malabsorption Due to infective agents – Intestinal tuberculosis – HIV related malabsorption – Tropical sprue – Parasites e.g. Giardia lamblia. Due to structural defects – Inflammatory bowel diseases - Crohn's Disease – Fistulae, diverticulae and strictures, – Infiltrative conditions - amyloidosis amyloidosis – Short bowel syndrome Due to mucosal abnormality – Celiac disease – Cows' milk intolerance – Soya milk intolerance – Fructose malabsorption Due to enzyme deficiencies – Lactase deficiency – Sucrose intolerance – Intestinal disaccharidase deficiency – Intestinal enteropeptidase deficiency Due to digestive failure – Pancreatic insufficiencies: Cystic fibrosis Chronic pancreatitis Pancreas carcinoma Zollinger-Ellison syndrome – Bile salt malabsorption Terminal ileal disease Obstructive jaundice Liver cirrhosis Bacterial overgrowth Primary bile acid diarrhea

6. Celiac disease Gluten-sensitive enteropathy More common in caucasian populations (1:300 in European countries) Rare in black populations HLA DQ2 and DQ8 Can present at any age Classically - fatigue, weight loss and anaemia in a young to middle aged female.

7. Celiac disease

8. Associated with: Diabetes Mellitus type 1 Thyroid disease Addison's disease Diagnosis Anti-endomysial antibodies Anti-tTG (tissue Transglutaminase) Small bowel mucosal biopsy

9. Celiac disease Treatment – Strict Gluten free diet. Dietary advice. – Supplementation (FeSo4, Vitamins) – Exclude other related autoimmune conditions. – Follow up using clinical parameters as well as antibodies.

10. Chronic Pancreatitis

11. Chronic Pancreatitis Definition Permanent and irreversible damage to the pancreas Histological or radiological evidence of chronic inflammation and fibrosis Destruction of exocrine (acinar cell) and endocrine (islets of Langerhans) pancreatic tissue

12. Chronic pancreatitis Etiology (TIGAR-O) Toxic/Metabolic – Alcohol – Smoking – Hypercalcaemia – Hyperlipidaemia Idiopathic – Early onset – Late onset – Tropical Genetic – Autosomal dominant Hereditary pancreatitis (PRSS1 mutations) – Autosomal recessive or modifier genes CFTR mutations SPINK1 mutations Others Alcohol and Gallstones most common causes in developed countries (70%) Autoimmune -Autoimmune pancreatitis -IgG4 related systemic disease Recurrent Post Necrotic Chronic alcoholism Diabetes Mellitus Radiotherapy Obstructive Benign pancreatic duct obstruction Gallstones Stricture Pancreas divisum Malignant stricture Ampullary of duodenal carcinoma Pancreatic adenocarcinoma

13. Gallstones

14. Chronic pancreatitis Pathophysiology (Alcohol) Direct toxins and toxin metabolite s Oxidative stress Necrosis with Fibrosis Intraductal plugging and obstruction Alcohol Cytokine release stimulate stellate cells to form collagen (fibrosis) and increase cell - mediated inflammation Chronic Pancreatitis

15. Jaster, Molecular Cancer. 2004 3:26 doi:10.1186/1476-4598-3-2

16. Chronic Pancreatitis Clinical features

17. Abdominal pain

18. Chronic Pancreatitis Clinical features Abdominal pain Diabetes Mellitus

19. Chronic Pancreatitis Clinical features Abdominal pain Steatorrhoea Diabetes Mellitus

20. Chronic Pancreatitis Clinical features Abdominal pain Steatorrhoea Diabetes Mellitus Other: - Constitutional symptoms, malaise etc - Weight loss due to malabsorption - Pain associated with meals with high protein and fat content

21. Chronic Pancreatitis Abdominal pain Most common clinical problem Decreases appetite and limits food consumption - weight loss and malnutrition Dramatic reduction in quality of life Character: – Epigastric, often with radiation to the back. – Boring, deep, and penetrating and is often – Associated with nausea and vomiting. – Relieved by sitting forward or leaning forward, the knee-chest position – Worsens after a meal and often is nocturnal. Possible causes: – Acute inflammation/noxious stimuli – Increased intra-pancreatic pressure and ischaemia – Neuropathic (Alterations in nociceptive nerves) – Other

22. Chronic pancreatitis Steatorrhoea Exocrine insufficiency. Passage of bulky, floating, foul-smelling stools or may even note the passage of frank oil droplets. Occurs when pancreatic lipase secretion is reduced to less than 10% of the maximum output. A feature of far-advanced chronic pancreatitis or complete blockage of the pancreatic duct.

23. Chronic Pancreatitis Diabetes Mellitus Endocrine insufficiency Half of patients with chronic pancreatitis who develop diabetes will require insulin. Insulin-producing beta cells and glucagon-producing alpha cells are injured. Increased risk of prolonged and severe hypoglycemia with over vigorous insulin treatment due to the lack of a compensatory release of glucagon.

24. Chronic pancreatitis Diagnosis(1) Clinical features (Abdominal pain, Steatorrhoea, Diabetes Mellitus) Test of pancreatic function – Direct Tests Direct hormonal stimulation tests are believed to be the most sensitive function test for chronic pancreatitis. Bicarbonate estimation after Secretin administration. (ERCP) – invasive, not routinely done. – Indirect Tests Serum Trypsinogen Pancreatic Enzymes in Stool eg chymotrypsin or elastase Fecal Fat Excretion/Steatocrit

25. Chronic pancreatitis Diagnosis(2) Tests of pancreatic structure – Abdominal xray with pancreas calcifications – CT Scan/MRI – Ultrasound (Conventional/EUS) – ERCP/MRCP Other – IgG4, ESR, RF, Calcium, Triglyceride levels

30. Chronic pancreatitis Treatment No curative therapy available Treatment of the cause Stop smoking. Stop alcohol. Abdominal pain Analgesics (Paracetamol, NSAIDs, Opiates) Decrease intra-pancreatic pressure by oral pancreatic enzyme supplementation (eg. Creon) Surgery (Endoscopic or Open surgery) Steatorrhoea Dietary fat restriction (<20g/day) Pancreatic enzyme supplementation (eg. Pancrelipase - Creon TM ) PPI to increase duodenal pH for optimal pancreatic enzyme activity Diabetes Mellitus Carbohydrate restriction Insulin therapy (NB. Be wary of risk of hypoglycaemia) Other Supplemenation of fat soluble vitamins (A, D, E, K)

31. Chronic pancreatitis Complications Pseudocysts Bleeding Obstruction Pancreatic Fistulae – Follows seudocyst – External (surgery) – Internal (Ascites, pleural effusion) Malignancy – Risk highest with hereditary pancreatitis and smoking – Pancreatic adenocarcinoma – CA19-9 Dysmotility – Gastroparesis and antroduodenal dysmotility perigastric inflammation hormonal changes associated with chronic pancreatitis (e.g. CCK) side effect of narcotic analgesics.

32. Thank you.