MALABSORPTION SYNDROME The term maldigestion refers to defective hydrolysis of nutrients, whereas malabsorption refers to impaired mucosal absorption.

MALABSORPTION SYNDROMEMALABSORPTION SYNDROME

• The term maldigestion refers to defective hydrolysis of nutrients, whereas malabsorption refers to impaired mucosal absorption.

• The major part of digestion occurs in the duodenum and most proximal jejunum.

• The complete process of absorption consists of a luminal phase, in which various nutrients are hydrolyzed and solubilized; a mucosal phase, in which further processing takes place at the brush border of the epithelial cell with subsequent transfer into the cell; and a transport phase, in which nutrients are moved from the epithelium to the portal venous or lymphatic circulation.

LUMINAL PHASE

• pancreatic enzymes, particularly lipase, colipase, and trypsin;

• gastric digestive enzymes

Mucosal Phase

• Extensive mucosal loss (resection or infarction)• Diffuse mucosal disease (celiac sprue;

Crohn's disease; irradiation; infection; infiltrations; drugs: alcohol, colchicine, neomycin, iron salts)

• Brush border hydrolase deficiency (lactase deficiency)

• Transport defects (vitamin B12 and folate uptake)

TRANSPORT PHASE

• After absorption, nutrients leave the cells through venous or lymphatic channels. Consequently, malabsorption may occur after mesenteric venous obstruction, lymphangiectasia, or lymphatic obstruction from malignancy or infiltrative processes (such as Whipple's disease.)

Fat malabsorption.Fat malabsorption. The confirmation of the presence The confirmation of the presence of steatorrhoea is only occasionally necessary. of steatorrhoea is only occasionally necessary. Three-Three-day faecal fat analysisday faecal fat analysis, , breath tests and serum β breath tests and serum β carotenecarotene are now rarely performed. In the rare cases are now rarely performed. In the rare cases when it is really necessary to confirm steatorrhoea, when it is really necessary to confirm steatorrhoea, Sudan III staining Sudan III staining of a faecal sample can be used. of a faecal sample can be used.

Lactose tolerance test.Lactose tolerance test. This involves the oral This involves the oral ingestion of 50 g of lactose and the measurement of ingestion of 50 g of lactose and the measurement of blood glucose. The test is of little use in adults as blood glucose. The test is of little use in adults as lactose intolerance is not a clinical problem since these lactose intolerance is not a clinical problem since these patients avoid milk by choice. patients avoid milk by choice.

These are required only in These are required only in complicatedcomplicated cases. cases.Tests of absorptionTests of absorption

Other tests Other tests Hydrogen breath testHydrogen breath test.. This is frequently This is frequently

used as a screening test to detect bacterial used as a screening test to detect bacterial overgrowth. Oral lactulose or glucose is overgrowth. Oral lactulose or glucose is metabolized by bacteria with the metabolized by bacteria with the production of hydrogen. production of hydrogen.

An early rise in the breath hydrogen will An early rise in the breath hydrogen will indicate bacterial breakdown in the small indicate bacterial breakdown in the small intestine. intestine.

Rapid transitRapid transit of the lactulose to the large intestine of the lactulose to the large intestine will also produce a rise in breath hydrogen. As will also produce a rise in breath hydrogen. As bacteria are present in the oral cavity, the mouth bacteria are present in the oral cavity, the mouth should be rinsed out with an antiseptic mouthwash should be rinsed out with an antiseptic mouthwash prior to the test being performed. prior to the test being performed.

This test is simpleThis test is simple to perform and it does not to perform and it does not involve radioisotopes. However, interpretation is involve radioisotopes. However, interpretation is often difficult with a low sensitivity and specificity. often difficult with a low sensitivity and specificity.

14C-glycocholic acid breath test. This was performed to look for bacterial overgrowth. Bacteria deconjugate the bile salts, releasing [14C]-glycine, which is metabolized and appears in the breath as 14CO2. It has largely been replaced by the hydrogen breath test.

Direct intubation. Aspiration of intestinal juices is another method by which bacterial contamination can be detected, but is seldom used. Bacterial counts are performed on aerobic and anaerobic cultures. Chromatography of bile salts can also be performed on the aspirate to detect evidence of deconjugation by bacteria.

Pancreatic tests. these are used in the differential diagnosis of steatorrhoea.

Other blood tests. Serum immunoglobulins are measured to exclude immune deficiencies. Gut peptides (e.g. vasoactive intestinal peptide - VIP) are measured in high-volume secretory diarrhoea, and chromogranins A and B are raised in endocrine tumours.

MALABSORPTIONIn many small bowel diseases, malabsorption of specific substances occurs, but these deficiencies

do not dominate the clinical picture.

An example is Crohn's disease, in which malabsorption of vitamin B12 can be

demonstrated, but this is not usually a problem and diarrhoea and general ill-health are the

major features.

Disorders of the small intestine Disorders of the small intestine causing malabsorption causing malabsorption

Coeliac disease

Dermatitis herpetiformis

Tropical sprue

Bacterial overgrowth

Intestinal resection

Whipple's disease

Radiation enteritis

Parasite infestation (e.g. Giardia intestinalis)

Coeliac diseaseCoeliac disease (gluten-sensitive (gluten-sensitive enteropathy)enteropathy)

Coeliac disease is a condition in which there is an inflammation of the jejunal mucosa that

improves when the patient is treated with a gluten-free diet and relapses when gluten is

reintroduced. Gluten is contained in the cereals wheat, rye and barley..

It is closely related to dermatitis herpetiformis, a skin disorder that has an associated gluten-

sensitive enteropathy (see below).

Incidence Coeliac disease is common in Northern Europe and

epidemiological studies have shown a prevalence of 1 in 100 to 1 in 6500 in different temperate

countries. It occurs throughout the world, but is rare in the black African.

There is an increased incidence of coeliac disease within families but the exact mode of inheritance is

unknown; 10-15% of first-degree relatives will have the condition, although it may be asymptomatic.

DQ2 (DQA*0501, DQB1*0201) and DQ8 (DQA1*0301, DQB1*0302) are associated with

coeliac disease. Over 90% of patients will have DQ2, compared with 20-30% of the general population.

Non-HLA regions linked to coeliac disease are chromosome 5q31-33, possibly 11q, and others are

being identified. However, the fact that not all patients have these haplotypes, and that as many as

30% of identical twins are discordant for the condition, suggests an additional factor, e.g.

environmental.

Aetiology

Gluten is a high - molecular - weight, heterogeneous compound that can be fractionated to produce α-, β-,

γ- and ω-gliadin peptides. α-Gliadin is the main damaging peptide to the small intestinal mucosa

although the other smaller peptides are also 'toxic'.

T cells play a central role in the aetiopathogenesis and react with the enzyme tissue transglutaminase

(the main antigen of the endomysial antibody).

PathologyPathology The mucosa of the proximal small bowel is

predominantly affected, the mucosal damage decreasing in severity towards the ileum as the

gluten is digested into smaller 'non-toxic' fragments.

There is an absence of villi, making the mucosal surface flat. Histological examination shows crypt

hyperplasia with chronic inflammatory cells in the lamina propria and villous atrophy (Marsh type III).

Clinical features Clinical features Coeliac diseaseCoeliac disease can present at any age. In infancy it appears can present at any age. In infancy it appears

after weaning on to gluten-containing foods. The peak after weaning on to gluten-containing foods. The peak incidence in adults is in the fifth decade, with a female incidence in adults is in the fifth decade, with a female preponderance. preponderance.

The symptomsThe symptoms are very variable and often non-specific with are very variable and often non-specific with tiredness and malaise often associated with an anaemia. tiredness and malaise often associated with an anaemia. Many patients are asymptomatic (silent) and picked up on Many patients are asymptomatic (silent) and picked up on incidental findings, e.g. a raised MCV. incidental findings, e.g. a raised MCV.

Common GI symptomsCommon GI symptoms include diarrhoea or steatorrhoea, include diarrhoea or steatorrhoea, abdominal discomfort, bloating or pain and weight loss. abdominal discomfort, bloating or pain and weight loss.

Mouth ulcers andMouth ulcers and angular stomatitis are frequent and can angular stomatitis are frequent and can be intermittent. Infertility and neuropsychiatric symptoms be intermittent. Infertility and neuropsychiatric symptoms of anxiety and depression occur. Osteoporosis is common of anxiety and depression occur. Osteoporosis is common and occurs even in patients on long-term gluten-free diets. and occurs even in patients on long-term gluten-free diets.

Rare complicationsRare complications include tetany, osteomalacia, or gross include tetany, osteomalacia, or gross malnutrition with peripheral oedema. Neurological malnutrition with peripheral oedema. Neurological symptoms such as paraesthesia, ataxia (due to cerebellar symptoms such as paraesthesia, ataxia (due to cerebellar calcification), muscle weakness or a polyneuropathy occur; calcification), muscle weakness or a polyneuropathy occur; the prognosis for these symptoms is variable. the prognosis for these symptoms is variable.

There is an increasedThere is an increased incidence of atopy and incidence of atopy and autoimmune disease, including thyroid disease, autoimmune disease, including thyroid disease, insulin-dependent diabetes, primary biliary cirrhosis insulin-dependent diabetes, primary biliary cirrhosis and Sjögren's syndrome. and Sjögren's syndrome.

Other associatedOther associated diseases include inflammatory diseases include inflammatory bowel disease, chronic liver disease, fibrosing bowel disease, chronic liver disease, fibrosing allergic alveolitis and epilepsy. IgA deficiency is allergic alveolitis and epilepsy. IgA deficiency is more common than in the general population.more common than in the general population.

Physical signs arePhysical signs are usually few and non-specific and usually few and non-specific and are related to anaemia and malnutrition.are related to anaemia and malnutrition.

InvestigationsInvestigationsEndomysial (EMA) and tissue transglutaminase (tTG) Endomysial (EMA) and tissue transglutaminase (tTG)

antibodies (IgA).antibodies (IgA).

These antibodies have a high sensitivity and specificity for the diagnosis of untreated coeliac disease and can also be used as screening tests.

They are the investigation of first choice. An immunofluorescent test for endomysial antibodies (EMA) can be performed on umbilical cord tissue or monkey oesophagus and the antigen for EMA is tissue transglutaminase.

Anti-tissue transglutaminase antibodies are measured using an ELISA. In the presence of a typical clinical picture and the presence of these antibodies, a confirmatory small bowel biopsy may not always be required although most doctors prefer to have one performed.

Anti-reticulin antibodies (ARA)Anti-reticulin antibodies (ARA) are also very sensitive but not so specific, as they are seen in other gastrointestinal conditions (e.g. Crohn's disease). Anti-gliadin antibodies (AGA) are less sensitive and are not used.

Duodenal/jejunal biopsy.Duodenal/jejunal biopsy. The mucosal appearance of a small bowel biopsy specimen is diagnostic and regarded as the 'gold standard' although errors occur, particularly with poorly orientated specimens. Other causes of a flat mucosa in adults are rare and are shown in.

At endoscopy, the duodenal folds look effaced and a dye can be sprayed on to the duodenal mucosa to accentuate the smoothness of the mucosa (positive dye test) before the biopsy is taken.

Haematology.Haematology. A mild or moderate anaemia is present in 50% of cases. Folate deficiency is almost invariably present in coeliac disease, giving rise in most instances to a high MCV. B12 deficiency is rare but iron deficiency due to malabsorption of iron and increased loss of desquamated cells is common.

A blood film may therefore show microcytes and macrocytes as well as hypersegmented polymorphonuclear leucocytes and Howell-Jolly bodies due to splenic atrophy found in most patients.

Absorption testsAbsorption tests are often abnormal but are seldom performed.

Radiology.Radiology. A small bowel follow-through may show dilatation of the small bowel with a change in fold pattern. Folds become thicker and in the severer forms total effacement is seen. Radiology is now mainly used when a complication, e.g. lymphoma, is suspected.

Wireless capsule endoscopyWireless capsule endoscopy. is used to look for gut abnormalities when a complication is suspected.

Bone densitometry.Bone densitometry. (DXA) should be performed on all patients because of the risk of osteoporosis.

BiochemistryBiochemistry. In the severely ill patient, biochemical abnormalities, e.g. hypoalbuminaemia, low calcium and high phosphate (osteomalacia) are seen.

Treatment and management Treatment and management Treatment with a gluten-free diet usually

produces a rapid clinical and morphological improvement.

Replacement haematinics, e.g. iron, folic acid, calcium, are given initially to replace body stores.

The usual cause for failure to respond to the diet is poor compliance. Dietary adherence can be monitored by serial tests for EMA and tTG. If clinical progress is suboptimal then a repeat intestinal biopsy should be taken.

If the diagnosis is equivocal a gluten challenge, i.e. reintroduction of gluten with evidence of jejunal morphological change, confirms the diagnosis, but is only performed if the diagnosis is equivocal.

A transient glutenA transient gluten intolerance can occur in early childhood.

Despite advice, manyDespite advice, many patients do not keep to a patients do not keep to a strict diet but nevertheless maintain good health. strict diet but nevertheless maintain good health. The long-term effects of this low gluten intake The long-term effects of this low gluten intake are uncertain but osteoporosis is seen even in the are uncertain but osteoporosis is seen even in the treated case.treated case.

Patients shouldPatients should have pneumococcal have pneumococcal vaccinations (because of splenic atrophy) once vaccinations (because of splenic atrophy) once every 5 years every 5 years

Complications Complications A few patientsA few patients do not improve on a strict diet do not improve on a strict diet

(unresponsive 'coeliac disease'). Often no cause for (unresponsive 'coeliac disease'). Often no cause for this is found, but intestinal lymphoma, ulcerative this is found, but intestinal lymphoma, ulcerative jejunitis or carcinoma are sometimes responsible. The jejunitis or carcinoma are sometimes responsible. The incidence of enteropathy-associated T-cell lymphoma incidence of enteropathy-associated T-cell lymphoma (EATCL) is increased in coeliac disease. (EATCL) is increased in coeliac disease.

Ulcerative jejunitisUlcerative jejunitis may present with fever, may present with fever, abdominal pain, perforation and bleeding. abdominal pain, perforation and bleeding.

Diagnosis for theseDiagnosis for these conditions is with barium studies but conditions is with barium studies but laparotomy with full-thickness biopsies is often required. laparotomy with full-thickness biopsies is often required.

Steroids and immunosuppressiveSteroids and immunosuppressive agents, e.g. agents, e.g. azathioprine, are used. azathioprine, are used.

Carcinoma of the smallCarcinoma of the small bowel and oesophagus as well as bowel and oesophagus as well as extragastrointestinal cancers are also seen. Malignancy extragastrointestinal cancers are also seen. Malignancy seems to be unrelated to the duration of the disease but the seems to be unrelated to the duration of the disease but the incidence is reduced by a gluten-free diet. incidence is reduced by a gluten-free diet.

Dermatitis herpetiformis Dermatitis herpetiformis This is an uncommonThis is an uncommon blistering subepidermal eruption blistering subepidermal eruption

of the skin associated with a gluten-sensitive enteropathy. of the skin associated with a gluten-sensitive enteropathy.

Rarely there mayRarely there may be gross malabsorption, but usually be gross malabsorption, but usually the jejunal morphological abnormalities are not as severe the jejunal morphological abnormalities are not as severe as in coeliac disease. as in coeliac disease.

The inheritanceThe inheritance and immunological abnormalities are and immunological abnormalities are the same as for coeliac disease. The skin condition the same as for coeliac disease. The skin condition responds to dapsone but both the gut and the skin will responds to dapsone but both the gut and the skin will improve on a gluten-free diet. improve on a gluten-free diet.

Tropical sprue Tropical sprue This is a conditionThis is a condition presenting with presenting with

malabsorption that occurs in residents or malabsorption that occurs in residents or visitors to a tropical area where the disease is visitors to a tropical area where the disease is endemic. endemic.

Malabsorption of a mildMalabsorption of a mild degree, sometimes degree, sometimes following an enteric infection, is quite following an enteric infection, is quite common and is usually asymptomatic. This is common and is usually asymptomatic. This is sometimes called tropical malabsorption. sometimes called tropical malabsorption.

The term tropicalThe term tropical sprue is reserved for severe sprue is reserved for severe malabsorption (of two or more substances) that is malabsorption (of two or more substances) that is usually accompanied by diarrhoea and usually accompanied by diarrhoea and malnutrition. Tropical sprue is endemic in most of malnutrition. Tropical sprue is endemic in most of Asia, some Caribbean islands, Puerto Rico and Asia, some Caribbean islands, Puerto Rico and parts of South America. parts of South America.

Epidemics occurEpidemics occur,, lasting up to 2 years, and in lasting up to 2 years, and in some areas repeated epidemics occur at varying some areas repeated epidemics occur at varying intervals of up to 10 years. intervals of up to 10 years.

AetiologyAetiologyThe aetiologyThe aetiology is unknown, but is likely to be is unknown, but is likely to be infective because the disease occurs in infective because the disease occurs in epidemics and patients improve on antibiotics.epidemics and patients improve on antibiotics.

A number of agentsA number of agents have been suggested but have been suggested but none has been shown to be unequivocally none has been shown to be unequivocally responsible. Different agents could be involved responsible. Different agents could be involved in different parts of the world.in different parts of the world.

Clinical featuresClinical features These vary in intensityThese vary in intensity and consist of diarrhoea, anorexia, and consist of diarrhoea, anorexia,

abdominal distension and weight loss. The onset is sometimes abdominal distension and weight loss. The onset is sometimes acute and occurs either a few days or many years after being in acute and occurs either a few days or many years after being in the tropics. Epidemics can break out in villages, affecting the tropics. Epidemics can break out in villages, affecting thousands of people at the same time. The onset can also be thousands of people at the same time. The onset can also be insidious, with chronic diarrhoea and evidence of nutritional insidious, with chronic diarrhoea and evidence of nutritional deficiency.deficiency.

The clinical featuresThe clinical features of tropical sprue vary in different parts of of tropical sprue vary in different parts of the world, particularly as different criteria are used for diagnosis. the world, particularly as different criteria are used for diagnosis.

Diagnosis Diagnosis Acute infective causesAcute infective causes of diarrhoea must be excluded , of diarrhoea must be excluded , particularly Giardia, which can produce a syndrome very particularly Giardia, which can produce a syndrome very similar to tropical sprue. similar to tropical sprue.

Malabsorption shouldMalabsorption should be demonstrated, particularly of fat be demonstrated, particularly of fat and B12. and B12.

The jejunal mucosaThe jejunal mucosa is abnormal, showing some villous is abnormal, showing some villous atrophy (partial villous atrophy). In most cases the lesion is atrophy (partial villous atrophy). In most cases the lesion is less severe than that found in coeliac disease, although it less severe than that found in coeliac disease, although it affects the whole small bowel. Mild changes can be seen in affects the whole small bowel. Mild changes can be seen in asymptomatic individuals in the tropics, so jejunal mucosal asymptomatic individuals in the tropics, so jejunal mucosal changes must be interpreted carefully. changes must be interpreted carefully.

Treatment and prognosis Treatment and prognosis Many patients improveMany patients improve when they leave the sprue area and when they leave the sprue area and take folic acid (5 mg daily). Most patients also require an take folic acid (5 mg daily). Most patients also require an antibiotic (usually tetracycline 1 g daily) to ensure a complete antibiotic (usually tetracycline 1 g daily) to ensure a complete recovery; it may be necessary to give this for up to 6 months. recovery; it may be necessary to give this for up to 6 months.

The severely ill patientThe severely ill patient requires resuscitation with fluids and requires resuscitation with fluids and electrolytes for dehydration; any nutritional deficiencies should electrolytes for dehydration; any nutritional deficiencies should be corrected. Vitamin B12 (1000 μg) is also given to all acute be corrected. Vitamin B12 (1000 μg) is also given to all acute cases. cases.

The prognosis isThe prognosis is excellent. Mortality is usually associated with excellent. Mortality is usually associated with water and electrolyte depletion, particularly in epidemics. water and electrolyte depletion, particularly in epidemics.

Bacterial overgrowth Bacterial overgrowth The gut containsThe gut contains many resident bacteria with many resident bacteria with

anaerobic bacteria, e.g. Bacteroides, bifidobacteria, anaerobic bacteria, e.g. Bacteroides, bifidobacteria, being 100-1000 times more abundant than aerobic being 100-1000 times more abundant than aerobic (facultative anaerobes), e.g. Escherichia, (facultative anaerobes), e.g. Escherichia, Enterobacter, Enterococcus. Enterobacter, Enterococcus.

This gut microflora hasThis gut microflora has major functions including major functions including metabolic, e.g. fermentation of non-digestible metabolic, e.g. fermentation of non-digestible dietary residues into short chain fatty acids as an dietary residues into short chain fatty acids as an energy source in the colon. Bacteria also initiate energy source in the colon. Bacteria also initiate vitamin K production. vitamin K production.

They control epithelialThey control epithelial cell proliferation and are cell proliferation and are involved in the development and maintenance of the involved in the development and maintenance of the immune system. They protect the gut mucosa from immune system. They protect the gut mucosa from colonization by pathogenic bacteria.colonization by pathogenic bacteria.

The upper part The upper part of the small intestine is almost sterile, of the small intestine is almost sterile, containing only a few organisms derived fromthe mouth. containing only a few organisms derived fromthe mouth. Gastric acid kills most organisms and intestinal motility Gastric acid kills most organisms and intestinal motility keeps the jejunum empty. The normal terminal ileum keeps the jejunum empty. The normal terminal ileum contains faecal-type organisms, mainly Escherichia coli contains faecal-type organisms, mainly Escherichia coli and anaerobes and the colon has abundant bacteria.and anaerobes and the colon has abundant bacteria.

Bacterial overgrowthBacterial overgrowth is normally only found associated with a is normally only found associated with a structural abnormality of the small intestine, although it can structural abnormality of the small intestine, although it can occur occasionally in the elderly without such abnormality. E. occur occasionally in the elderly without such abnormality. E. coli and/or Bacteroides, both in concentrations greater than coli and/or Bacteroides, both in concentrations greater than 106/mL are found as part of a mixed flora.106/mL are found as part of a mixed flora.

These bacteria areThese bacteria are capable of deconjugating and capable of deconjugating and dehydroxylating bile salts, so that unconjugated and dehydroxylating bile salts, so that unconjugated and dehydroxylated bile salts can be detected in aspirates by dehydroxylated bile salts can be detected in aspirates by chromatography. The clinical features are chiefly diarrhoea and chromatography. The clinical features are chiefly diarrhoea and steatorrhoea. Steatorrhoea occurs as a result of conjugated bile steatorrhoea. Steatorrhoea occurs as a result of conjugated bile salt deficiency. salt deficiency.

The bacteria are able to metabolize vitamin B12 and interfere with its binding to intrinsic factor, thereby leading to B12 deficiency. Conversely some bacteria produce folic acid giving a high serum folate.

Bacterial overgrowth has only minimal effects on other substances absorbed from the small intestine. The vitamin B12 deficiency is not so severe as to produce a neurological deficit. Confirmation of bacterial overgrowth is with the hydrogen breath test ; aspiration studies are not routinely performed.

Treatment Treatment If possible, the underlyingIf possible, the underlying lesion should be lesion should be corrected (e.g. a stricture should be resected). corrected (e.g. a stricture should be resected). With multiple diverticula, grossly dilated With multiple diverticula, grossly dilated bowel, or in Crohn's disease, this may not be bowel, or in Crohn's disease, this may not be possible and rotating courses of antibiotics possible and rotating courses of antibiotics are necessary, such as metronidazole, a are necessary, such as metronidazole, a tetracycline, or ciprofloxacin. tetracycline, or ciprofloxacin.

Intestinal resection Intestinal resection Intestinal resectionIntestinal resection is usually well tolerated, but is usually well tolerated, but massive resection is followed by the short-bowel massive resection is followed by the short-bowel syndrome. syndrome.

The effects of resectionThe effects of resection depend on the extent and depend on the extent and the areas involved. Because the gut is long, a 30-the areas involved. Because the gut is long, a 30-50% resection can usually be tolerated without 50% resection can usually be tolerated without undue problems. Residual jejunum shows less undue problems. Residual jejunum shows less capacity for structural and functional adaptation capacity for structural and functional adaptation than residual ileum. than residual ileum.

Ileal resection Ileal resection The ileum has specificThe ileum has specific receptors for the absorption receptors for the absorption of bile salts and vitamin B12, so that relatively of bile salts and vitamin B12, so that relatively small resections will lead to malabsorption of these small resections will lead to malabsorption of these substances. Removal of the ileocaecal valve substances. Removal of the ileocaecal valve increases the incidence of diarrhoea. increases the incidence of diarrhoea.

The following occurThe following occur in ileal resection: in ileal resection: Bile salts Bile salts and fatty acids enter the colon and cause and fatty acids enter the colon and cause malabsorption of water and electrolytes leading to malabsorption of water and electrolytes leading to diarrhoea . diarrhoea .

Increased bile saltIncreased bile salt synthesis can synthesis can compensate for loss of approximately one-compensate for loss of approximately one-third of the bile salts in the faeces. third of the bile salts in the faeces.

Greater loss thanGreater loss than this results in decreased this results in decreased micellar formation and steatorrhoea, and micellar formation and steatorrhoea, and lithogenic bile and gallstone formation. lithogenic bile and gallstone formation.

Increased oxalateIncreased oxalate absorption is caused by the absorption is caused by the presence of bile salts in the colon. This gives rise to presence of bile salts in the colon. This gives rise to renal oxalate stones. renal oxalate stones.

There is a low serumThere is a low serum B12 and macrocytosis. B12 and macrocytosis.

Glucagon-like peptideGlucagon-like peptide 2 (GLP-2) is low following 2 (GLP-2) is low following ileal resection. GLP-2 is a specific growth hormone ileal resection. GLP-2 is a specific growth hormone for the enterocyte and this deficiency may explain for the enterocyte and this deficiency may explain the lack of adaptation with an ileal resection. the lack of adaptation with an ileal resection.

Investigations includeInvestigations include a small bowel follow- a small bowel follow-through, measurement of B12, bile salts and through, measurement of B12, bile salts and occasionally fat absorption. A hydrogen breath occasionally fat absorption. A hydrogen breath test will show rapid transit . test will show rapid transit .

Many patients requireMany patients require B12 replacement and B12 replacement and some need a low-fat diet if there is steatorrhoea. some need a low-fat diet if there is steatorrhoea.

If diarrhoea is a problem,If diarrhoea is a problem, colestyramine, colestyramine, which binds bile salts, often helps. which binds bile salts, often helps.

Jejunal resection Jejunal resection The ileum can take over the jejunal The ileum can take over the jejunal

absorptive function. Jejunal resection may absorptive function. Jejunal resection may lead to gastric hypersecretion with high lead to gastric hypersecretion with high gastrin levels; the exact mechanism of this is gastrin levels; the exact mechanism of this is unclear. unclear.

Structural and functional intestinal Structural and functional intestinal adaptation take place over the course of a adaptation take place over the course of a year, with an increase in the absorption per year, with an increase in the absorption per unit length of bowel. unit length of bowel.

Shortened small intestine ending at a Shortened small intestine ending at a terminal stoma terminal stoma

The major problemThe major problem is of sodium and fluid is of sodium and fluid depletion and the majority of patients with 100 depletion and the majority of patients with 100 cm or less of jejunum remaining will require cm or less of jejunum remaining will require parenteral supplements of fluid and electrolytes, parenteral supplements of fluid and electrolytes, often with nutrients. Sodium losses can be often with nutrients. Sodium losses can be minimized by increasing salt intake, restricting minimized by increasing salt intake, restricting clear fluids between meals and administering clear fluids between meals and administering oral glucose-electrolyte mixture with a sodium oral glucose-electrolyte mixture with a sodium concentration > 90 mmol/L. concentration > 90 mmol/L.

Jejunal transit timeJejunal transit time can be increased and stomal can be increased and stomal effluent loss of fluids and electrolytes reduced by effluent loss of fluids and electrolytes reduced by treatment with the somatostatin analogue treatment with the somatostatin analogue octreotide, and to a much lesser extent, with octreotide, and to a much lesser extent, with loperamide, codeine phosphate or co-phenotrope. loperamide, codeine phosphate or co-phenotrope.

There is no benefitThere is no benefit of a low-fat diet, but fat of a low-fat diet, but fat assimilation can be increased on treatment with assimilation can be increased on treatment with colestyramine and synthetic bile acids. colestyramine and synthetic bile acids.

Shortened small intestine in continuity Shortened small intestine in continuity with colon with colon

Only a small proportionOnly a small proportion of these patients require of these patients require parenteral supplementation of fluid, electrolytes and parenteral supplementation of fluid, electrolytes and nutrients because of the absorptive capacity of the nutrients because of the absorptive capacity of the colon for fluid and electrolytes. colon for fluid and electrolytes.

Unabsorbed fat resultsUnabsorbed fat results in impairment of colonic in impairment of colonic fluid and electrolyte absorption so patients should be fluid and electrolyte absorption so patients should be on a low-fat diet. A high carbohydrate intake is on a low-fat diet. A high carbohydrate intake is advised as unabsorbed carbohydrate is metabolized advised as unabsorbed carbohydrate is metabolized anaerobically to short-chain fatty acids (SCFAs). anaerobically to short-chain fatty acids (SCFAs).

Whipple's disease Whipple's disease This is a rare disease usually affecting males. It This is a rare disease usually affecting males. It

presents with steatorrhoea and abdominal pain along presents with steatorrhoea and abdominal pain along with systemic symptoms of fever and weight loss. with systemic symptoms of fever and weight loss. Peripheral lymphadenopathy, arthritis and Peripheral lymphadenopathy, arthritis and involvement of the heart, lung and brain may occur. involvement of the heart, lung and brain may occur.

Histologically, in the small bowel, the villi are stunted Histologically, in the small bowel, the villi are stunted and contain diagnostic periodic acid-Schiff (PAS)-and contain diagnostic periodic acid-Schiff (PAS)-positive macrophages. On electron microscopy, bacilli positive macrophages. On electron microscopy, bacilli can be seen 'within' the macrophages. can be seen 'within' the macrophages.

The organism wasThe organism was identified by the polymerase identified by the polymerase chain reaction and can be cultured; it is classified chain reaction and can be cultured; it is classified as an actinobacterium and has been given the as an actinobacterium and has been given the name Tropheryma whippeii. name Tropheryma whippeii.

A dramatic improvementA dramatic improvement occurs with occurs with antibiotic therapy, which should include an antibiotic therapy, which should include an antibiotic that crosses the blood-brain barrier antibiotic that crosses the blood-brain barrier (e.g. co-trimoxazole) for 6 months. (e.g. co-trimoxazole) for 6 months.

Radiation enteritis Radiation enteritis Radiation of more thanRadiation of more than 40 Gy will damage the 40 Gy will damage the

intestine. The ileum and rectum are the areas most intestine. The ileum and rectum are the areas most often involved, as pelvic irradiation is frequently often involved, as pelvic irradiation is frequently used for gynaecological and urinary tract used for gynaecological and urinary tract malignancies. malignancies.

There may be nauseaThere may be nausea, vomiting, diarrhoea and , vomiting, diarrhoea and abdominal pain at the time of the irradiation. These abdominal pain at the time of the irradiation. These symptoms usually improve within 6 weeks after symptoms usually improve within 6 weeks after completion of therapy. completion of therapy.

Chronic radiationChronic radiation enteritis is diagnosed if enteritis is diagnosed if symptoms persist for 3 months or more. The symptoms persist for 3 months or more. The prevalence is more than 15%. Many patients prevalence is more than 15%. Many patients suffer from an increased bowel frequency. suffer from an increased bowel frequency.

Radiation producesRadiation produces muscle fibre atrophy, muscle fibre atrophy, ulcerative changes due to ischaemia, and ulcerative changes due to ischaemia, and obstruction due to strictures produced by obstruction due to strictures produced by radiation-induced fibrosis. radiation-induced fibrosis.

Abdominal painAbdominal pain is the main symptom due to the is the main symptom due to the obstruction, which is usually partial but eventually obstruction, which is usually partial but eventually may be complete. Malabsorption due to mucosal may be complete. Malabsorption due to mucosal damage as well as bacterial overgrowth in dilated damage as well as bacterial overgrowth in dilated segments can occur. segments can occur.

Treatment is symptomaticTreatment is symptomatic, although often , although often unsuccessful in chronic enteritis. Surgery should be unsuccessful in chronic enteritis. Surgery should be avoided if at all possible, being reserved for life-avoided if at all possible, being reserved for life-threatening situations such as complete obstruction or threatening situations such as complete obstruction or occasionally perforation. occasionally perforation.

Radiation damageRadiation damage to the rectum produces a radiation to the rectum produces a radiation

proctitis with diarrhoea, with or without blood and proctitis with diarrhoea, with or without blood and

tenesmus. Local steroids sometimes help initially. tenesmus. Local steroids sometimes help initially.

The telangiectasiaThe telangiectasia that form and cause persistent that form and cause persistent

bleeding can be treated with argon plasma coagulation bleeding can be treated with argon plasma coagulation

or by placing a formalin-soaked swab in the rectum or by placing a formalin-soaked swab in the rectum

(for 2 min), both of which heal the lesions. (for 2 min), both of which heal the lesions.

Parasite infestation Parasite infestation Giardia intestinalisGiardia intestinalis not only produces diarrhoea but not only produces diarrhoea but

can produce malabsorption with steatorrhoea. Minor can produce malabsorption with steatorrhoea. Minor changes are seen in the jejunal mucosa and the changes are seen in the jejunal mucosa and the organism can be found in the jejunal fluid or mucosa. organism can be found in the jejunal fluid or mucosa.

Cryptosporidiosis canCryptosporidiosis can also produce malabsorption. also produce malabsorption.

Patients with HIV infectionPatients with HIV infection are particularly prone are particularly prone to parasitic infestation.to parasitic infestation.