Gastroenterology - Diseases of the small intestine Flashcards
What is the main function of the small intestine?
The main role of the small intestine is digestion and absorption of nutrients. Vitamin B12 and bile salts have specific receptors
What are the presenting symptoms of small bowel disease?
Presenting symptoms of small bowel disease include diarrhoea, steatorrhoea, abdominal pain or discomfort and anorexia causing weight loss. Small bowel disease may also be found after investigation for specific deficiencies such as vitamin B12. The two most common causes of small bowel disease in the western world are coeliac disease and Crohn’s disease. Investigation of suspected small bowel disease is initially with coeliac screen, small bowel barium follow or MRI and endoscopic small bowel biopsy.
What disorders of the small intestine are associated with malabsorption?
Coeliac disease Crohn's disease Dermatitis herpetiformis Tropical sprue Bacterial overgrowth Intestinal resection Whipple's disease Radiation enteritis Parasite infection - e.g. Giardia intestinalis
What is Coeliac disease?
This is an autoimmune condition characterised by an abnormal jejunal mucosa that improves when gluten (contained in wheat, rye and barley) is withdrawn from the diet, and relapses when gluten is reintroduced. About 1 in 100 individuals in European derived populations have coeliac disease, most of whom are undiagnosed.
What is the pathogenesis of coeliac disease?
There is a strong association between coeliac disease and HLA DQ2 and DQ8. The peptide alpha gliadin is the toxic portion of gluten. Gliadin is resistant to proteases in the small intestinal lumen and passes through a damaged (as a result of infection or possibly gliadin itself) epithelial barrier of the small intestine where it is deaminated by tissue transglutaminase so increasing its immunogenicity.
Gliadin then interacts with antigen presenting cells in the lamina propria via HLA DQ2 and HLA DQ8 and activates gluten sensitive T cells. The inflammatory cascade that follows and release of mediators contributes to the villous atrophy and crypt hyperplasia that are the typical histological features of coeliac disease. There is an increase in intraepithelial lymphocytes but the pathogenic role of these lymphocytes, compared with lamina propria lymphocytes is not known.
What are the clinical features of coeliac disease?
Presentation is at any age but there are two peaks in incidence; in infancy (after weaning on to gluten containing foods) and in adults in the fifth decade. There may be non specific symptoms of tiredness and malaise, or symptoms of small intestinal disease. Physical signs are usually few and non specific, and related to anaemia and nutritional deficiency. There is an increased incidence of atopy and autoimmune diseases.
Which individuals should be offered screening for coeliac disease?
Autoimmune diseases - type 1 DM - thyroid disease - autoimmune liver disease - Addison's disease IBS (symptoms may be similar to coeliac disease) Unexplained osteoporosis Those with a first degree relative Downs syndrome (20 fold increase) Turners syndrome Infertility and recurrent miscarriage
What investigations should be performed in patients with suspected coeliac disease?
1) Serum autoantibodies
2) Distal duodenal biopsy
3) FBC
4) Small bowel radiology or capsule endoscopy
5) Bone densitometry
What serum antibodies are present in coeliac disease?
IgA tissue transglutaminase antibodies have a very high sensitivity and specificity for coeliac disease. False negatives occur in IgA deficiency when IgG based tests should be used. IgA endomysial antibodies are less sensitive.
Serological testing is offered to patients with signs and symptoms or in conditions where there is an increased risk. Patients with positive serology, or if serology is negative but disease is strongly suspected, are referred for endoscopic biopsy.
What is required for a definitive diagnosis of coeliac disease?
Distal duodenal biopsy. Histological changes are of variable severity and show an increase in the number of intraepithelial lymphocytes, crypt hyperplasia with chronic inflammatory cells in the lamina propria and villous atrophy. The latter is seen in other conditions (e.g. tropical sprue, Whipple’s disease), but coeliac is the commonest cause of subtotal villous atrophy.
What important findings are seen on the blood count in coeliac disease?
A mild anaemia is present in 50% of cases. There is almost always folate deficiency, commonly iron deficiency and rarely vitamin B12 deficiency. Target cells, spherocytes and Howell-Jolly bodies are due to hyposplenism.
How often is small bowel radiography or capsule endoscopy performed in coeliac disease?
These are usually only performed when a complication is suspected such as lymphoma.
What other scan should be performed at diagnosis of coeliac disease?
Bone densitometry - increased risk of osteoporosis.
How is coeliac disease managed?
Treatment is with lifelong gluten free diet and correction of any vitamin deficiencies. Pneumococcal vaccine is given as coeliac disease is associated with hyposplenism. Symptoms and serologic testing (undetectable antibodies indicate a response) are used to monitor recovery and compliance with the diet. Re biopsy is reserved for patients who do not respond or in whom there is diagnostic uncertainty.
What complications are associated with coeliac disease?
There is an increased incidence of malignancy, particularly intestinal T cell lymphoma, small bowel and oesophageal cancer. The incidence may be reduced by a gluten free diet.
What is dermatitis herpetiformis?
This is an itchy, symmetrical eruption of vesicles and crusts over the extensor surfaces of the body with deposition of granular immunoglobulin (IgA) at the dermoepidermal junction of the skin, including areas not involved with the rash. Patients also have a gluten sensitive enteropathy, which is usually asymptomatic. The skin condition responds to dapsone, but both the gut and the skin will improve on a gluten free diet.
What is tropical sprue? How is it treated?
This is a progressive small intestinal disorder presenting with diarrhoea and steatorrhoea and megaloblastic anaemia. It occurs in residents or visitors to endemic areas in the tropics (Asia, the Carribean, Puerto Rico, parts of South America). The aetiology is unknown but likely to be infective.
Diagnosis is based on demonstrating evidence of malabsorption (particularly of fat and vitamin B12) together with a small bowel mucosal biopsy showing features similar, but not identical, to those in untreated coeliac disease. Infective causes of diarrhoea, particularly Giardia intestinalis, should be excluded. Treatment is with folic acid and tetracycline for 3-6 months and correction of nutritional deficiencies.
What is bacterial overgrowth?
Sometimes called “blind loop syndrome”, bacterial overgrowth occurs when there is stasis of intestinal contents as a result of abnormal motility - e.g. systemic sclerosis or hypogammaglobulinaemia or a structural abnormality - e.g. previous small bowel surgery or a diverticulum. The upper small intestine is almost sterile.
What are the clinical features of bacterial overgrowth?
The bacteria deconjugate bile salts causing diarrhoea and/or steatorrhoea and metabolise vitamin B12 which may result in deficiency.
How is bacterial overgrowth diagnosed?
A therapeutic trial of antibiotics is given when clinical suspicion is high. Otherwise, diagnosis is usually by a hydrogen breath test in which hydrogen is measured in exhaled air after oral lactulose. With bacterial overgrowth an early peak is seen in the breath hydrogen followed by a later colonic peak (normally present due to metabolism of lactulose by colonic bacteria).
Serum B12 concentrations are low; folate levels are normal or elevated. Immunoglobulin levels may exclude hypogammaglobulinaemia.
How is bacterial overgrowth managed?
The underlying cause should be corrected if possible. Otherwise, rotating courses of antibiotics - e.g. tetracycline and metronidazole are given.
How does intestinal resection cause malabsorption?
The effects of small intestinal resection depend on the extent and the area involved. Resection of the terminal ileum leads to malabsorption of:
- vitamin B12 leading to megaloblastic anaemia
- bile salts which overflow into the colon. This causes secretion of water and electrolytes and diarrhoea, and increased oxalate absorption which may result in renal oxalate stones
Ileal resection is usually performed as a treatment for Crohn’s disease. Parenteral administration of vitamin B12 and colestyramine or aluminium hydroxide for the diarrhoea are usually needed.
What is the short bowel syndrome?
More extensive resection leaving less than 1m of small bowel is followed by the short bowel syndrome. The majority of cases occur after resection for Crohn’s disease, mesenteric ischaemia, trauma, volvulus or surgical complications.
Clinical features include:
- large volume jejunostomy fluid loss
- if colon is preserved, diarrhoea and steatorrhoea
- dehydration and signs of hypovolaemia
- weight loss, loss of muscle bulk and malnutrition
How is short bowel syndrome treated?
Parenteral nutrition is the mainstay of treatment for patients in whom absorptive function has failed.
The ability of patients to cope without supplemental IV fluids or nutritions depends on:
- AMOUNT of resected bowel - most patients with <100cm of jejunum and no colon will require supplements
- LOCATION of resected bowel (jejunal resection is better tolerated than ileal)
- COLON intact which absorbs water and electrolytes
- HEALTH of residual tissue - i.e. there are fewer problems after resection following trauma than in patients with Crohns
What is Whipple’s disease?
This is a rare disease caused by the bacterium Tropheryma whipplei. Steatorrhoea, abdominal pain, lymphadenopathy, arthritis, cardiac (pericarditis, myocarditis, endocarditis) and neurological involvement occur. Small bowel biopsy shows periodic acid schiff (PAS) positive macrophages which on electron microscopy are seen to contain the causative bacteria. Treatment is with co-trimoxazole for 1 year after two weeks of IV ceftriaxone.
What is radiation enteritis? What are the clinical features?
Intestinal damage occurs in 10–15% of patients undergoing radiotherapy for abdominal or pelvic malignancy. The risk varies with total dose, dosing schedule and the use of concomitant chemotherapy.
Acutely, there is nausea, vomiting, cramping abdominal pain and diarrhoea. When the rectum and colon are involved, mucus, bleed- ing and tenesmus occur. The chronic phase develops after 5–10 yrs in some patients and may feature bleeding from telangiectasis, fis- tulae, adhesions, strictures or malabsorption.
How is radiation enteritis managed?
Acute phase: codeine, loperamide, corticosteroid enemas for proc- titis and antibiotics for bacterial overgrowth.
Nutritional supplements for malabsorption; colestyramine for bile salt malabsorption may be necessary.
Endoscopic laser or argon plasma coagulation therapy: may reduce bleeding from proctitis.
Surgery should be avoided, because the injured intestine is difficult to resect and anastomose, but it may be necessary for obstruction, perforation or fistula.
What is norovirus?
Norovirus (Norwalk agent) is the most common cause of infectious gastroenteritis in the UK and causes outbreaks in closed communities, such as hospital wards. Food handlers may also transmit norovirus. It is highly infectious via the faecal oral root and causes prominent vomiting and dirrahoea after an incubation period of 24-48 hours. Diagnosis is by electron microscopy or PCR of stool samples. Case isolation and rehydration is the main management.
What is the most common virus to cause diarrhoea in young children?
Rotavirus is the major cause of diarrhoeal illness in young children. Infection is endemic in developing countries. There are winter epidemics in developed countries, particularly hospitals. The virus infects enterocytes causing decreased surface absorption and loss of enzymes on the brush border.
The incubation period is 48 hours, and patients present with watery diarrhoea, vomiting, fever, and abdominal pain. The disease is self limiting but dehydration needs appropriate management. Effective vaccines have been developed.
What serotypes of adenovirus are associated with diarrhoeal illness?
40 and 41
What is gastroenteritis?
Gastroenteritis is acute diarrhoea with or without vomiting that is due to gastrointestinal infection with bacteria, viruses or protozoa. Gastroeneteritis can happen at home or whilst travelling abroad.
Not all cases of gastroenteritis are food poisoning as the pathogens are not always food or water borne - e.g. C.difficile as a complication of antibiotic therapy. Individuals at risk of infection include infants and young children, the elderly, travellers, the immunocompromised, and those with reduced gastric secretions (e.g. individuals using PPIs or with pernicious anaemia). Viral gastroenteritis is a common cause of diarrhoea and vomiting in young children.
What are the three mechanisms that bacteria can cause diarrhoea?
Bacteria cause diarrhoea by either:
- mucosal adherence (watery diarrhoea - e.g. Enteropathogenic E.coli, Enteroaggregative E.coli)
- mucosal invasion (bloody diarrhoea - e.g. Shigella, Campylobacter, Enteroinvasive E.coli)
- toxin production
Toxins can either be enterotoxic which causes fluid secretion without mucosal damage, or cytotoxic causing damage to the mucosa.
All three of these mechanisms produce either watery or bloody diarrhoea (called dysentery).
Does acute diarrhoea require investigation?
Most infectious causes of diarrhoea are self limiting. Routine stool examination for culture and microscopy for ova and parasites and stool testing for C.difficile toxin is not usually necessary other than in the following groups of patients:
- immunosuppressed patients with IBD (to distinguish a flare from infection)
- certain employees such as food handlers
- bloody diarrhoea
- persistant diarrhoea (>7 days, possible Giardia, Cryptosporidium)
- severe symptoms (fever, volume depletion) or recent antibiotic treatment or hospitalisation
How are patients with acute diarrhoea managed?
Management of patients with acute diarrhoea includes adequate hydration and antimotility agents such as loperamide (other than those with bloody diarrhoea or fever). Antibiotic therapy is not given in most cases since the illness is usually self limiting. Antibiotics are avoided in patients with suspected or proven enterohaemorrhagic E.coli infection as they may increase the risk of haemolytic uraemic syndrome. Empiric antibiotic therapy - e.g. ciprofloxacin and metronidazole - is given to patients with severe symptoms or bloody diarrhoea, pending the results of stool testing.
What agents typically cause acute food poisoning?
Staphylococcus aureus
Bacillus cereus
Clostridium perfringens
