Malabsorption / Maldigestion - Lecture 154

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Malabsorption / Maldigestion - Lecture 154
1. Explain secretory function of pancreas
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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
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Bicarbonate (HCO3) 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)
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2. Principles of proteolytic enzyme activation
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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:
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trypsin, chymotrypsin, elastase cleave peptides bonds within the interior of
polypeptide chains
Exopeptidases:
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carboxypeptidase removes amino acids from the carboxyl end
aminopeptidases removes amino acids from the amino end
- 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
3. Explain clinical problems encountered in exocrine pancreatic
insufficiency and principles of treatment
Pancreas not working:
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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
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
o
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Maldigestion:
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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
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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)
4. Pancreatic neoplasia (rare)
1. Pancreatic acinar atrophy - most common
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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
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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)
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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:
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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:
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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
Treatment for EPI:
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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 - 1-3 weeks
supplement fat soluble vitamins and B12
o weekly injection for 6-8 weeks
o may need lifelong
Malabsorption:
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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:
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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:
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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:
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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:
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IBD
severe small intestine bacterial overgrowth (SIBO)
lymphangiectasia
GI lymphoma
Dry feline infectious peritonitis (FIP)
Clinical signs:
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weight loss
diarrhoea (mild to severe)
coprophagia (sometimes)
Treatment:
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Depends on pathology, disease
o steroids, drugs, bile acids for hepatic disease
Hyperthyroidism
o tablets
o surgery
o radioactive iodine
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