Tests of intestinal function
Carbohydrate absorption
- Polysaccharides such as starch are hydrolysed to form disaccharides by SALIVARY and PANCREATIC α-AMYLASES
- The disaccharides such as maltose, sucrose and lactose are hydrolysed to their constitutive monosaccharides by α and β-glucosidases located on the brush border of enterocytes, particularly in duodenum
- Monosaccharides are actively absorbed in the duodenum and proximal jejunum
Protein absorption
- Dietary protein is broken down by gastric pepsin and in the dueodenum by TRYPSIN and other proteolytic enxymes secreted in the pancreatic juice
- Pancreatic trypsinogen in converted to active trypsin by ENTEROKINASE located on the brush border
- The products of digestion are small peptides and amino acids
- May peptides are further hydrolysed by peptidases on the brush border
- Amino acids are actively absorbed by the small intestine. Small peptides are absorbed by an active transport that is independent of that of amino acids and mostly are hydrolysed intracellularly
Lipid absorption
- Triglycerides are the main form of dietary fat and are esters of glycerol with three usually different fatty acids
- Primary bile salts are synthesised in the liver from cholesterol, conjugated to GLYCINE or TAURINE and enter the intestinal lumen in the bile
- In the alkaline duodenal fluid their sodium salts act as detergents, emulsifying and facilitating fat digestion
- Most of the bile salts are actively reabsorbed in the distal ileum, although some enter the colon where they are converted by bacteria into secondary bile salts, some of which are absorbed
- Triglycerides are emulsified by bile salts within the duodenum
- They are then hydrolysed by PANCREATIC LIPASE – with the end products being monoglycerides, diglycerides and free fatty acids
- COLIPASE is a peptide conenzyme secreted by the pancreas which is essential for lipase activity
- Monoglycerides and free fatty acids aggregate with bile salts to form micelles. These also contain cholesterol, phospholipids as well as fat soluble vitamins (A, D, E and K)
- Within the enterocytes, the triglycerides are resynthesised from monoglycerides and free fatty acids, the cholesterol is re-esterified
- Triglycerides, cholesterol esters, phospholipids together with fat soluble vitamins, combine with apoplipoproteins produced within the enterocytes to form chylomicrons. These are suspended in water and can be passed into the lymphatic circulation
- Some short chain and medium chain free fatty acids pass directly through the intestinal cells into the portal bloodstream
Vitamin Absorption
- Vitamin B12 can only be absorbed when it is in complex with INTRINSIC factor, a glycoprotein secreted by the parietal cells of the stomach
- This complex is resistant to proteolytic digestion and binds to specific receptor in the distal ileum from which it is absorbed
- Most of the other water soluble vitamins (C and the other B vitamins) are absorbed in the upper small intestine via specific transport mechanism
Malabsorption
- Generalised malabsorption may result from either intestinal or pancreatic disease
- In intestinal malabsorption, fat digestion is generally normal, but absorption of the products of digestion is impaired
- In pancreatic malabsorption, the absorptive capacity is normal but there is a deficiency of digestive enzymes
- It is usually associated with steatorrhoea
- Mechanisms of malabsorption
·       Reduction of absorptive areas or generalised impairment of transport mechanisms
o      Celiac disease
o      Tropical sprue
o      Extensive surgical resection resulting in short gut syndrome
o      Crohn’s or Whipples which result in inflammation of the intestinal wall
·       Increased rate of transit though the small intestine
o      After gastrectomy (generally not severe)
o      Carcinoid syndrome – rare condition associated with excessive production of 5-HT by tumours of the argentaffin cells usually of the small intestine or their metastases (e.g. in the liver)
·       Impaired digestive enzyme activity
o      Failure of digestive enzyme secretion
§        Chronic pancreatitis
§        CF
o      Inactivation of pancreatic enzymes by acid
§        The increased intestinal pH of Zollinger-Ellison syndrome may inactivate pancreatic lipase and cause precipitation of bile salts within the lumen, so resulting in malabsorption
- Altered intestinal flora may cause malabsorption of vitamin B12 and fat. This can occur due to the following condition;
- ‘Blind loop’ syndrome which is caused by bacterial proliferation due to impaired intestinal motility and stagnation of the intestinal contents. It may occur as a result of small intestinal diverticula or due to surgery
- Some bacteria may cause malabsorption be deconjugating bile salts
- Bacteria can use up the Vitamin B12 and folate (causing megalolastic anaemia)
- Some bacteria may cause malabsorption be deconjugating bile salts
- Biliary obstruction causes malabsorption of fats by preventing the secretion of bile salts into the intestinal lumen
- Local diseases or surgery of the small intestine may cause selective malabsorption of substances absorbed primarily at those sites e.g. diseases involving the terminal ileum e.g. Crohns or TB may impair the absorption of Vit B12
- Intrinsic factor deficiency (either due to damage to the gastric parietal cells in pernicious anaemia or gastrectomy or malignant infiltration of the stomach) can cause Vit B12 malabsorption
- ‘Blind loop’ syndrome which is caused by bacterial proliferation due to impaired intestinal motility and stagnation of the intestinal contents. It may occur as a result of small intestinal diverticula or due to surgery
- Disaccharide deficiency may occur in more generalised disorders of the intestinal wall because the enzymes are located on the brush border of the enterocytes. One example is lactose deficiency which may be acquired, associated with prematurity or congenital
Faecal fat estimation test
- After digestion, dietary fat is normally completely absorbed in the small intestine, and generally only a very small amount is excreted in the faeces but this is derived from enterocytes
- With malabsorption of fat, the excretion in the faeces is increased
- The problem is that bowel transit is variable as is rectal emptying as accurately times faecal collections are required
- This can be aided by giving a non-absorbable coloured marker such as carmine orally, when it starts to appear in the faeces, one starts to collect, a second dose of marker can be given 72-120 hours later and the collection is terminated when this appears
- A daily fat excretion of more than 5g per day indicates steatorrhoea
Schilling test
- Assesses the absorption of vitamin B12 (which is absorbed in the teminal ileum)
- The test involves giving Vit B12 with and without intrinsic factor and measuring subsequent urinary excretion
- Intrinsic factor corrects for the malabsorption of vit B12 in pernicious anaemia but not in terminal ileal disease
14C-Glycocholate Test
- Test for bacterial overgrowth
- 14C-labelled glycocholate is given orally, in the presence of bacterial overgrowth, extensive deconjugation of the 14C glycine occurs
- The labelled glycine is rapidly absorbed and metabolised to 14C- carbon dioxide which is detected in the breath
Hydrogen breath test
- Tests for carbohydrate malabsorption
- Hydrogen is not produced by mammalian cells, its presence in expired air is due to bacterial fermentation of unabsorbed carbohydrate
- Patients are given an oral solution of lactose
- In lactase deficiency, unabsorbed lactose is digested by colonic bacteria resulting in an elevated hydrogen content in expired air
- Bacterial overgrowth can do the same but the two condition can be distinguished by using oral glucose instead of lactose
Pancreolauryl test
- Tests pancreatic exocrine function
- It depends on the hydrolysis fluorescein dilaurate by cholesterol ester hydrolase, an enzyme normally present in pancreatic juice.
- Fluorescein is water soluble. It is absorbed by the intestine, conjugated in the liver, and excreted in the urine where it’s fluorescence can be measured.
- Abnormal results may occur if there is renal glomerular dysfunction, liver disease of malabsorption
- The effects of these are assessed by repeating the test with unconjugated fluorescein
Coeliac Disease
- Antibodies to gliadin, reticulin and endomysium are present in the serum in active disease
- Detection of antoendomysial antibodies can be used as a screening test
- Serum total IgA can be measured but false negatives occur in IgA deficiency (10% of patients)
Tests for pancreatic function
- Plasma enzymes can be measured;
- Amylase
- Lipase
- Trypsin – may be used to screen of CF in the first 6 weeks of life (levels may fall after this time as pancreatic insuffiency develops
- Duodenal enzymes
- The measurement of pancreatic enzymes and bicarbonate concentration in duodenal aspirates before and after stimulation with cholecystokinin can be done. Very invasive and rarely performed
Intestinal permeability
- Give an oral mixture of L-rhamnose and lactulose and measure their urinary excretions
- The normal lactulose/rhamnose excretion ratio is <0.06
- It is increased in untreated Coeliac disease and in active Crohn disease when the intestinal permeability to lactulose is increased but the absorption of rhamnose is decreased