Malabsorption / Maldigestion - Lecture 154

Malabsorption / Maldigestion - Lecture 154

1. Explain secretory function of pancreas

• Produce enzymes for the digestion of all major types of food
• Proteins:
• Typsin: peptides into polypeptides (measure this to determine function of pancreas)
• Chymotrypsin - proteins into polypeptides 
• Caboxypolypeptidase - peptides into amino acids
• Carbohydrates:
• Amylase: hydrolyses starches - glycogen to diasaccharides
• Fat:
• Pancreatic lipase: neutralise fat into fatty acids and monoglycerides
• Cholestorol enterase: hydrolyses cholesterol esters
• Phospholipase: splits fatty acids from phospholipids

• 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
• Vitamin A - retina needs - eyesight
• Vitamin D - for calcium metabolism
• Vitamin E - important for protection from toxins (especially liver)
• Vitamin K - for clotting factors to be activated
• Assistance with absorption of cobalamin (vitamin B12)

2. Principles of proteolytic enzyme activation

• lower activation energy
• influenced by 
• temperature
• pH
• concentration of cofactors and coenzymes
• concentration of enzyme and substrates
• 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

- 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: 

• Protein maldigestion
• carb maldigestion
• fat maldigestion
• impaired assimilation of fat soluble vitamins
• 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
• absent in EPI
• thus, increased uptake by bacteria in gut
• creates environment for bacteria to grow
• chyme lies undigested in upper GIT
• provides growth media for bacteria
• leads to bacterial overgrowth (SIBO - small intestine bacterial overgrowth)
• sometimes treated with antibiotics

Maldigestion:

• Exocrine Pancreatic Insufficiency  (EPI) - most common (esp dogs)
• Secondary enzyme deficiency
• 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)
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: 
• Stage 1 - subclinical
• inflammation - T-lymphocyte infiltration
• partial acinar atrophy
• 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
• grey or yellow
• maldigested carbs ---> increase in water content
• 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)
• small amount of trypsin leaks into blood stream
• species specific assay - can measure decrease in trypsin
• Faeces microscope - can see fat/starch

Treatment for EPI: 

• Avoid high fat diets. Give:
• normal to moderate restricted fat
• high caloric density
• highly digestible
• low fibre
• Avoid high fibre
• impairs pancreatic enzyme activity
• 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 
• weekly injection for 6-8 weeks
• 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
• EPI
• loss of bile salts due to ileal or liver disease

Mucosal Phase: 

• Brush border enzyme deficiency
• congenital - trehalase (cats)
• acquired - lactose deficiency
• brush border protein transport deficiency
• congenital - intrinsic factor deficiency
• acquired - diffuse small intestine disease
• enterocyte defects
• IBD

Transport phase: 

• lymphatic obstruction
• primary - lymphangiectasia
• secondary - obstruction due to neoplasia, infection
• vascular compromise
• vasculitis - infection, immune mediated
• 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
• steroids, drugs, bile acids for hepatic disease
• Hyperthyroidism
• tablets
• surgery
• radioactive iodine