Normal absorption requires?
Normal absorption nRequires integrated gut response: nMotility: physical disruption nIntraluminal digestion: lumen and brush border nAbsorption through enterocytes nTransport via blood or lymphatic system
Carbohydrates split into?
nComplex carbohydrates (polysaccharides =starch) split by salivary and pancreatic amylase & maltase into disaccharides.
Lactose and sucrose split into?
nSucrase splits sucrose to glucose and fructose nLactase splits lactose to glucose and galactose
Disaccharides split where? And into what?
nDisaccharides split at brush border enterocyte into monosaccharides :
Monosaccharide are absorbed by the?
Monosaccharides absorbed through enterocyte into portal vein
Discuss fat absorption.
nTriglycerides (TG) are split by pancreatic lipase to fatty acids (FA) and glycerol. nLong chain (FA) are solubilized by bile salts to form water soluble structure = micelles, which pass via enterocyte to lymphatics. Bile salts are reabsorbed in the terminal ileum (enterohepatic circulation). nTG containing medium chain (FA) can be absorbed without bile salts via enterocyte into portal vein
Discuss absorption through the gi Tract
Splitting and absorption of proteins?
nSplit by pancreatic enzymes such as trypsin or chymotrypsin, which are activated in the gut lumen, into oligopeptides, dipeptides and amino acids nAmino acids (AA) are absorbed through enterocyte into portal vein as single AA or dipeptides
nB12 – intrinsic factor from parietal cells in stomach helps absorption in terminal ilium nWater soluble = B, C – follow flux of water from gut lumen through mucosa nFat soluble = A, D, E, K – follow pathway for fat
Symptoms of b12 deficiency?
nDiarrhoea and pain on eating dairy products : lactose nPeripheral neuropathy: B12
Conditions throughout the gi tract?
Symptoms of malabsorption?
Specific to underlying cause or problem
Nutritional deficiencies : eg iron (breathless), Vit B12 (neurological) calcium (tetany), Vit K (bruising)
Crohn’s disease or pancreatic disease = abdominal pain
Past history eg radiation, surgery, travel
Examination for malabsorption?
Specific to underlying problem
Nutritional deficiencies : eg iron (stomatitis), Vit B12 (neurological), calcium, Vit D (osteomalacia) K (bruising), albumin (oedema)
eg Crohn’s disease (perianal features), abdominal mass
Liver disease: jaundice
Investigation for malabsorption?
Full blood count, MCV, folate, Vit B12, ferritin, clotting time
Tissue transglutaminase antibody (TTG-ab)
ESR, CRP, Immunoglobulins
Endoscopy with biopsy
Barium follow through
U/S, ERCP, Abdominal CT
Faecal fat collection
Lactose breath test for lactase deficiency
Glucose breath tests for bacterial overgrowth
Schilling test for B12 or whole body B12 absorption studies
Bile salt malabsorption test (SeCHAT)
Small bowel permeability studies
Pancreatic exocrine function tests
Is the pancrease a peritoneal or retroperitoneal organ?
Retroperitoneal organ –exocrine (98%) and endocrine
Pancrease stores and release what?
Exocrine : pancreatic acinar cells produce and store for release :
Lipase, amylase, colipase, phospholipase, proteases (trypsinogen and chymotrypsinogen)
Regulatory factors: cephalic, gastric (vagal) and intestinal phases ie neuronal and hormonal control
Secretin: released when acid in duodenum – stimulates bicarbonate rich pancreatic secretion
Cholecystokinin: released in response to intraluminal food particularly fat - may cause release of enzymes
Investigatations for excess pancreatic production?
Overt fat malabsorption (steatorrhoea) doesn’t occur until 85-90% of function lost. Large reserve means tests based on enzymes or breakdown products are insensitive
Serum biochemistry – serum lipase, amylase, trypsin (not useful due to large reserve)
Fat estimation = increases (not popular with biochemists) collect over 3 days after 100g /day fat in diet. Normal excretion <6g/day (17 mmol)
Chymotrypsin = decreases (only useful in severe disease)
Elastase = decreases (not degraded in the SB – decreased levels in mod to severe failure)
Oral pancreatic function tests:
Fluorescein dilaurate test: (Pancreolauryl test)
Relies on pancreatic enzymes to release a soluble compound (marker) which can be absorbed and measured in the urine.
2 collections – test and control capsule (latter to correct for small bowel problems)
Prone to error if there are small bowel problems or poor urine collection
Less sensitive and specific if only moderate failure.
Oral pancreatic function tests:
Fluorescein dilaurate test: (Pancreolauryl test)
First 24 hour collection (test capsule):
Oral fluorescein dilaurate given (insoluble and not absorbed unless esterase present)
Digested by pancreatic esterase
Releases fluorescein (soluble) which is absorbed and excreted in the urine and measured
Second 24 hour collection (control capsule) to correct for small bowel causes of malabsorption
Fluorescein alone given (readily absorbed)
Quantity from test capsule as % of control = T/K ratio
Significant if <20%
Measure the amount of 14CO2 in expired air after:
Labelled fatty acid (oleic acid)
Labelled triglyceride (triolein)
Impaired triglyceride absorption with normal fatty acid absorption indicates pancreatic disease
Duodenal sampling after intubation
All rely on passing an NG tube
Rely on analysis of duodenal aspirate following pancreatic stimulation by some means
Original (Lundh) – specified meal given
Now use intravenous – secretin or cholecystokinin to stimulate the pancreas.
Aspirate is assessed for bicarbonate (secretin) or enzyme activity
Only helpful in moderate to severe failure
Invasive and time consuming
Serum markers – no good
faecal fat (not popular + not specific)
Faecal elastase +chymotrypsin (mod/severe disease)*
Urine collections – Pancreolauryl* reasonable
Breath tests – specialised centres
Direct intubation – specialised centres
Those used in clinical practice*.
In addition, simply use response to pancreatic enzyme supplements
Imaging excess pancreatic function?
Plain abdominal x-ray – calcification (chronic pancreatitis – particularly alcohol)
Ultrasound – calcification, tumours, cysts
Spiral CT – as with ultrasound but more detailed
Endoscopic Retrograde Cholangio Pancreatography ERCP – duct system (allows intervention)
Magnetic Resonance Cholangio Pancreatography MRCP – non invasive and gives detail of pancreatic and bile duct system as well as of pancreas and liver
Endoscopic ultrasound – Defines small lesions in pancreas and allows biopsy – also good for small stones in bile duct
Treatment for excess pancreatic excression?
Correct underlying abnormality:
Coeliac : avoid gluten
Pancreatic disease : replace enzymes
Crohn’s disease : treat inflammation
Ensure adequate nutrition and replacement
Diseases that cause malabsorption?
Pathology of chronic pancreatis?
Gland becomes fibrotic and exocrine and endocrine function fails:
Alcohol the most common cause in UK
Trypsinogen and inhibitory protein defect
Pathogenesis: possibly due to inappropriate activation of enzymes within the pancreas eg unopposed trypsin activity
Signs of chronic pancreatitis?
Early disease = asymptomatic (may or may not have past history of recurrent bouts of acute abdo pain and pancreatitis)
Acute on chronic pancreatitis may still occur with its complications of pseudocysts etc
Later on in the course pain is severe and persistent with associated weight loss – may mimic cancer of pancreas
Serum amylase – unhelpful
Faecal – elastase and chymotrypsin (low)
Pancreolauryl test (<20%)
Abdo xray – calcification
US – small gland and calcification
CT – atrophy, calcification and duct dilation
ERCP – as for CT
Trial of pancreatic enzyme supplements eg creon
Glucose tolerance test for diabetes
Exocrine failure leads to
Steatorrhoea (pale, offensive bulky stool which floats and is difficult to flush away)
very occasionally evidence of Vit ADEK malabsorption
weight loss due protease deficiency
Very occasionally jaundice due to narrowing of common bile duct through distorted pancreas
Endocrine failure – diabetes – polyuria, polydypsia, and weight loss
Chronic pancreatitis treatment?
Pain control – analgesia (opiates, NSAIDS, tricyclic antidepressants, coeliac axis nerve blocks and surgery) – 60% become pain free with time (6-10 years)
Exocrine failure and malnutrition:
low fat, high calorie diet with vitamin supps
pancreatic enzymes supplements at meal times with acid suppression therapy
Medium chain triglycerides to decrease steatorrhoea
Endocrine - insulin
Complications of chronic pancreatitis?
Pseudocysts – drain surgically or endoscopically
Coeliac disease pathology?
Gluten sensitive enteropathy
Subtotal villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis
Prevalence in UK 1/100-1/300
Associated with other autoimmune disease eg thyroid, diabetes
Presentation varies – can be asymptomatic, or IBS like, or Fe deficiency etc
Diagnosed on TTG-ab
Gold standard : duodenal Bx on normal diet
Treatment : gluten free diet (wheat, rye and barley)
Any site in the luminal gut – classically TI (occasional B12 deficiency)
Malabsorption usually only a problem if there is extensive small bowel involvement or after extensive surgery
Treatment: steroids, immunuosuppressive agents eg azathioprine, and biologics eg anti TNF
Causes of chronic pancreatitis?
Acute or chronic infection in developing world
Severe diarrhoea and folate deficiency occur
Antibiotics and folate supplements
Uncommon, middle aged- men
Multisystem disease eg pleurisy, CNS, arthritis, gut
Treatm with antibiotics
Usually presents a number of years later
Bowel may be strictured
Secondary bacterial overgrowth
Seen in any situation where the small bowel is anatomically abnormal eg Crohn’s, previous surgery, radiation damage, scleroderma, diverticulosis
Treat with antibiotics eg tetracycline orally
Surgical resection (short gut syndrome)
Usually have 3-5m of small bowel
Problems arise if more than a half removed
Severe if <1m left (particulary if lost colon)
May need Total Parenteral Nutrition (TPN)
Common causes of short gut –
Acute vascular events e.g. ischaemia resulting in infarction