Malabsorption / Maldigestion - Lecture 154
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1 Malabsorption / Maldigestion - Lecture Explain secretory function of pancreas Produce enzymes for the digestion of all major types of food o Proteins: Typsin: peptides into polypeptides (measure this to determine function of pancreas) Chymotrypsin - proteins into polypeptides Caboxypolypeptidase - peptides into amino acids o Carbohydrates: Amylase: hydrolyses starches - glycogen to diasaccharides o Fat: Pancreatic lipase: neutralise fat into fatty acids and monoglycerides Cholestorol enterase: hydrolyses cholesterol esters Phospholipase: splits fatty acids from phospholipids Bicarbonate (HCO 3 ) and water are secreted by epithelial cells of ductules Bicarbonate neutralises the HCl coming from stomach This provides a suitable environment for pancreatic enzymes to work in duodenum Assimilation of fat soluble vitamins o Vitamin A - retina needs - eyesight o Vitamin D - for calcium metabolism o Vitamin E - important for protection from toxins (especially liver) o Vitamin K - for clotting factors to be activated Assistance with absorption of cobalamin (vitamin B12)
2 2. Principles of proteolytic enzyme activation lower activation energy influenced by o temperature o ph o concentration of cofactors and coenzymes o concentration of enzyme and substrates o simulators/inhibitors proteolytic - enzymes that break down proteins Endopeptidases: trypsin, chymotrypsin, elastase cleave peptides bonds within the interior of polypeptide chains Exopeptidases: carboxypeptidase removes amino acids from the carboxyl end aminopeptidases removes amino acids from the amino end
3 - Free amino acids absorbed by cotransport sodium into epithelial cells then secreted into capillary - di/tri peptides may enter epithelial cells but are then digested further into amino acids Phases of absorption: - Luminal phase - Mucosal phase - Transport phase
4 3. Explain clinical problems encountered in exocrine pancreatic insufficiency and principles of treatment Pancreas not working: Protein maldigestion carb maldigestion fat maldigestion impaired assimilation of fat soluble vitamins o lack of Vitamin K very bad as animals develop bleeds impaired absorption of cobalamin (B12) - needed for cell turnover
5 o intrinsic factor synthesised by pancreas is essential to permit absorption from gut o absent in EPI o thus, increased uptake by bacteria in gut creates environment for bacteria to grow o chyme lies undigested in upper GIT o provides growth media for bacteria o leads to bacterial overgrowth (SIBO - small intestine bacterial overgrowth) o sometimes treated with antibiotics Maldigestion: Exocrine Pancreatic Insufficiency (EPI) - most common (esp dogs) Secondary enzyme deficiency o luminal conditions not optimal for enzyme function Deficiency of bile acid Loss of brush border enzymes EPI - Exocrine Pancreatic Insufficiency insufficient production of pancreatic enzymes insufficient bicarbonate to neutralise HCl large reserve capacity normally need loss of 90% before clinical signs of maldigestion Causes: 1. Pancreatic acinar atrophy - most common 2. Chronic inflammation of pancreas (pancreatitis) 3. Pancreatic hypoplasia (uncommon)
6 4. Pancreatic neoplasia (rare) 1. Pancreatic acinar atrophy - most common Selective destruction of digestive enzyme producing acinar cells endocrine function usually unaffected progressive due to autoimmune disease 2 stages: o Stage 1 - subclinical inflammation - T-lymphocyte infiltration partial acinar atrophy o Stage 2 - clinical sever endstage atrophy Common in many breeds of dogs - many times in German shepherds rough coated collies, English setters, chows. Under reported in rotweilers, labs, weimaraners 2. Chronic inflammation of pancreas (pancreatitis) most common in cats progressive destruction of both exocrine and endocrine pancreas with fibrosis can develop signs of EPI and diabetes mellitus develops in some dogs - middle age to older, small-medium sized Clinical signs of EPI: Weight loss despite normal or increased appetite Increase in faecal volume abnormal faeces o grey or yellow o maldigested carbs ---> increase in water content o maldigested fats ---> make it look greasy flatulence (extra bacteria) coprophagia sometimes (animal eats faeces) Diagnosis of EPI: some clinical signs, but can occur with small bowel disease specific blood test for trypsin (TLI) o small amount of trypsin leaks into blood stream o species specific assay - can measure decrease in trypsin Faeces microscope - can see fat/starch
7 Treatment for EPI: Avoid high fat diets. Give: o normal to moderate restricted fat o high caloric density o highly digestible o low fibre Avoid high fibre o impairs pancreatic enzyme activity o soluble fibre can absorb enzymes small meals - 2 or more per day Due to pancreatitis: benefit from low fat diets Pancreatic enzyme replacement - lifelong antimicrobial therapy weeks supplement fat soluble vitamins and B12 o weekly injection for 6-8 weeks o may need lifelong Malabsorption: nutrients digested normally, but absorption impaired can be due to structural disease of small intestine (most common) can be due to metabolic disease making absorption more difficult Luminal Phase: involves digestion dysmotility - hyperthyroidism pancreatic enzyme deficiency or inactivation due to gastric acid hypersecretion Fat maldigestion o EPI o loss of bile salts due to ileal or liver disease Mucosal Phase: Brush border enzyme deficiency o congenital - trehalase (cats) o acquired - lactose deficiency brush border protein transport deficiency o congenital - intrinsic factor deficiency o acquired - diffuse small intestine disease enterocyte defects o IBD Transport phase:
8 lymphatic obstruction o primary - lymphangiectasia o secondary - obstruction due to neoplasia, infection vascular compromise o vasculitis - infection, immune mediated o portal hypertension - hepatopathy, right-sided heart failure Diseases: IBD severe small intestine bacterial overgrowth (SIBO) lymphangiectasia GI lymphoma Dry feline infectious peritonitis (FIP) Clinical signs: weight loss diarrhoea (mild to severe) coprophagia (sometimes) Treatment: Depends on pathology, disease o steroids, drugs, bile acids for hepatic disease Hyperthyroidism o tablets o surgery o radioactive iodine
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