Next Lesson - Distal Gastrointestinal Tract Pathology
Core
Coeliac disease is an autoimmune inflammatory condition of the bowel that arises from an immunological response to the gliadin fragment of gluten (gluten is a protein found in wheat, barley and rye, and gliadin is one part of it). This reaction to gluten causes the small bowel to be chronically inflamed, resulting in atrophy of the villi (the tiny finger-like projections that absorb nutrients) within the intestine and therefore reduced absorption of other nutrients. There is often a genetic link, so a thorough family history is important when diagnosing coeliac disease.
Symptoms include abdominal pain, bloating, excessive flatulence, diarrhoea, and weight loss. Some people have few bowel symptoms and present instead with prolonged tiredness, severe or persistent mouth ulcers, or a low iron, vitamin B12 or folate level.
To investigate coeliac disease, the patient must still be eating gluten (in more than one meal every day for at least 6 weeks before testing), because the tests are only accurate on a gluten-containing diet. The first blood tests are total IgA (immunoglobulin A, a class of antibody) and IgA anti-TTG antibodies (antibodies against tissue transglutaminase, an enzyme in the gut lining). Endomysial antibodies (antibodies against the endomysium, the connective tissue around muscle fibres) are tested if the anti-TTG result is only weakly positive. In adults, a positive blood test is followed by an endoscopy and duodenal biopsy (a tissue sample from the duodenum) to confirm the diagnosis. In children, a specialist decides which further tests are needed.
The treatment of this condition is to completely exclude gluten from the diet. This sounds simple, but gluten is present in any food made from wheat, barley or rye. That includes all foods made with traditional flour, such as bread, pasta, cereals, beer and sauces.
Image - Atrophic villi of Coeliac disease, note the blunted ends of the villi
Creative commons source by Samir [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Crohn’s Disease is a type of Inflammatory Bowel Disease (IBD) that can affect anywhere in the gastrointestinal (GI) tract but most commonly occurs at the terminal ileum. It most often starts in adolescence and early adulthood, but it can start at any age. Smoking is a risk factor.
Patients typically present with diarrhoea: an increased frequency of watery stools that usually do not contain blood. They also often have weight loss, right lower quadrant pain and/or perianal (around the anus) inflammation. They may also have associated conditions such as arthritis. If the disease affects the terminal ileum (the last part of the small bowel, and the most commonly affected region), the patient may also have anaemia. This is because this region is responsible for the absorption of vitamin B12, which is required for the creation of red blood cells.
Investigations may include blood tests (full blood count [FBC] and C-reactive protein [CRP]), faecal calprotectin (a marker of inflammation in the stool), colonoscopy (a camera test of the large bowel) and small bowel imaging with MRI, CT or ultrasound. Barium studies (X-rays taken after the patient has swallowed or been given a contrast liquid containing barium) have largely been replaced by these.
On colonoscopy, the visible (gross) features that may be seen are skip lesions (areas of normal bowel between two affected areas), mucosal oedema, deep ulcers, a cobblestone appearance (raised, swollen mucosa between ulcers, like cobbles on a road) and narrowing of the bowel. Transmural inflammation (inflammation through the full thickness of the bowel wall) and fistulae (abnormal channels between the bowel and the bladder, vagina or skin) are shown better by imaging such as MRI or CT. If a tissue sample (biopsy) is taken, microscopy may show granulomas: collections of epithelioid macrophages (immune cells that look like epithelial cells). Granulomas are found in only about half of patients with Crohn’s disease.
Surgical resection (removal of part of the bowel) does not cure Crohn’s disease for most patients, because the disease often comes back after surgery. Surgical intervention may still be needed to manage a stricture (a narrowing of the bowel) or fistula formation, or if medicines are not working.
Flare-ups are usually treated first with a steroid such as prednisolone. Immunomodulators (drugs that reduce the activity of the immune system) such as azathioprine or mercaptopurine are not used alone to induce remission. They are added to a steroid if flare-ups are frequent, and are used to maintain remission. Aminosalicylates (anti-inflammatory drugs such as mesalazine) have a more limited role in Crohn’s disease: they are only considered for a first or single flare-up if steroids cannot be used, and they are not offered for severe flare-ups.
Image - Granuloma of Crohn’s disease
Creative commons source by Nephron [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Ulcerative colitis (UC) is another type of inflammatory bowel disease that begins in the rectum and can spread continuously to involve the entire colon. Similarly to Crohn’s Disease, it is also seen in relatively young adults, but smoking appears to be a protective factor against developing UC, and the risk is higher in ex-smokers, especially soon after stopping. Smoking is still harmful, so patients who smoke should be encouraged to stop.
Presenting symptoms often include increased frequency of stools with blood and mucus, abdominal pain and weight loss, typically without any perianal inflammation. Patients may have associated extraintestinal complications (problems outside the bowel) such as scleritis (inflammation of the white of the eye) or arthritis.
Investigations include blood tests (FBC and CRP), faecal calprotectin, colonoscopy and CT/MRI. Contrast studies such as barium enema are now rarely used and are avoided in severe disease due to perforation risk.
On colonoscopy, the inflammation is continuous from the rectum. The mucosa (lining) looks red (erythema), with loss of the normal vascular pattern and friability (it bleeds easily on contact). In more severe disease there are erosions (shallow breaks in the surface), ulceration and spontaneous bleeding. Pseudopolyps (post-inflammatory polyps, islands of mucosa left standing after the surrounding lining has been damaged) can also be seen. In acute severe disease, a limited examination (flexible sigmoidoscopy, which views only the rectum and lower colon) is done with care because of the perforation risk. Microscopy of a tissue sample will show inflammation of the lamina propria (the connective tissue layer under the lining of the bowel), crypt distortion (the glands in the lining lose their regular shape) with or without crypt abscesses (collections of white blood cells in the crypts) and fewer goblet cells (the mucus-producing cells).
UC can be cured with surgical resection but if surgery is contraindicated or medical management is preferred by the patient, aminosalicylates and oral steroids can be used.
Complications of UC include bowel perforation and toxic megacolon (a dangerously widened colon with severe inflammation).
Image - Crypt distortion of ulcerative colitis
Creative commons source by User:KGH [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Inflammatory Bowel Disease Comparison
Table - Comparison of the different types of inflammatory bowel disease
Image - Pattern of disease in Crohn’s disease vs ulcerative colitis
Creative commons source by RicHard-59 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Irritable bowel syndrome (IBS) is a clinical diagnosis, made using symptom-based criteria with targeted tests to exclude red flag pathology (features that suggest a more serious cause, such as cancer or inflammatory bowel disease). The exact cause of IBS is unknown. It is probably multifactorial (several factors act together, such as gut sensitivity, infection, food and psychological factors). Stress can be one trigger for symptoms, along with food, infection and some drugs. It is more common in women than men and often seen in the 20-40 year old age group.
Patients typically present with abdominal pain, bloating, excessive flatulence, alternating diarrhoea and constipation, and rectal urgency (a sudden need to open the bowels). There is no blood in the stools. The symptoms can be similar to coeliac disease, IBD and malignancy (cancer) of the GI tract, so a few blood tests are done to help exclude them: a full blood count, an inflammatory marker (CRP, or ESR or plasma viscosity) and coeliac antibodies.
The diagnosis itself is made from the symptoms. The person needs abdominal pain or discomfort that is relieved by opening the bowels, or linked to a change in how often they go or in the form of the stool. They also need at least 2 of these 4 features: altered stool passage (straining, urgency or incomplete emptying), bloating, symptoms made worse by eating, and passing mucus. Assessment for IBS is considered when symptoms have lasted at least 6 months. Colonoscopy and barium enema are not needed to confirm IBS if the criteria are met. Red flag features need referral for further investigation.
Treatment is symptom management. The first step is advice on diet, lifestyle and physical activity (self-help). An antispasmodic (a drug that relieves gut cramps) can be taken as required. Laxatives can be used for constipation, but lactulose should be avoided. Loperamide (a drug that slows the gut and reduces diarrhoea) is the first choice for diarrhoea. A low-dose tricyclic antidepressant (a type of antidepressant) is second-line if these have not helped. Psychological therapies such as cognitive behavioural therapy (CBT) or hypnotherapy are considered if symptoms do not respond to medicines after 12 months.
A hernia is a protrusion of visceral contents (such as bowel or fat) beyond the confines of the cavity in which it is supposed to reside. Most commonly, these are abdominal hernias, where abdominal organs protrude outside the abdominal wall.
Hernias usually occur in areas of weakness such as the inguinal canal, femoral canal, umbilicus (navel) and at sites of previous incisions.
A hernia can be reducible, irreducible (incarcerated) or strangulated, and these present differently:
A reducible hernia presents with a lump/swelling that is not causing pain. It can be pushed back in, or it only bulges out when the patient is straining or laughing.
An irreducible hernia cannot be pushed back in. It is also called an incarcerated hernia: the contents are stuck, but the blood supply is still intact. It may be painful, and nausea and vomiting can occur. An incarcerated hernia can become strangulated. Strangulation is where the blood supply to the contents that have protruded through the wall has been reduced or cut off. It usually causes severe pain. A strangulated hernia is a surgical emergency, because that portion of bowel will become necrotic (the tissue dies) without a blood supply.
Diagram - Common sites of hernias
Creative commons source by BruceBlaus [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
- About 75% of abdominal wall hernias are inguinal.
- More common in men than women and can descend into the scrotum.
- Most commonly occur via the indirect route (lateral to the inferior epigastric vessels, the blood vessels that run up the inside of the abdominal wall). The hernia passes through the deep ring (the entrance to the inguinal canal), follows the path of the canal and exits via the superficial ring (the exit of the canal).
- Less commonly occur via the direct route (medial to the inferior epigastric vessels). The hernia pushes through Hesselbach’s triangle, which is bordered by rectus abdominis, the inguinal ligament and the inferior epigastric vessels.
Image - A CT scan of an incarcerated inguinal hernia
Creative commons source by James Heilman, MD [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
- Uncommon.
- More common in women than men.
- High risk of strangulation.
- Occurs in the femoral canal (the space medial to the femoral vein), inferiorly to the inguinal ligament.
Children
- Bulge at the site of the umbilicus in infants.
- Not usually painful.
- Low risk of strangulation.
- Most close on their own, usually by the age of 5.
Adults
An adult umbilical hernia is fat or bowel protruding through a weakness at the umbilicus. Obesity, pregnancy and ascites (fluid in the abdominal cavity) can contribute. Unlike many childhood umbilical hernias, an adult defect is unlikely to close spontaneously. Contents can become trapped (incarcerated) or lose their blood supply (strangulated). These complications can sometimes happen in adults. A painful, hard or enlarging lump needs assessment. Severe persistent abdominal pain, vomiting, skin colour change or inability to pass stool or wind requires emergency help. See the NHS guidance on umbilical hernias.
- Bulge through the linea alba (the midline strip of fibrous tissue between the two rectus abdominis muscles), usually in the region of the umbilicus.
- More common in women than men.
- Can become incarcerated or strangulated, as for adult umbilical hernias (see above).
Incisional/Epigastric/Spigelian
- Incisional: through a weakness at the site of a previous surgical incision. This is a common surgical problem.
- Epigastric: through the linea alba between the xiphoid process (the lower tip of the sternum) and the umbilicus. These are rare.
- Spigelian: a rare hernia through the Spigelian fascia, the layer lateral to the rectus abdominis muscle.
Diverticular disease is an umbrella term for diverticulosis that causes symptoms and for diverticulitis. Diverticulosis without symptoms is common and needs no specific treatment.
Diverticulosis refers to a condition where outpouchings (diverticula) of mucosa (the lining) and submucosa (the layer beneath it) herniate through the muscularis layers (the muscle layers) of the colon. Diverticula are most common in the sigmoid colon (the S-shaped part of the colon just above the rectum). Diverticulosis is usually asymptomatic (about 80 to 85% of people with diverticula have no symptoms) and is often an incidental finding (found by chance) on colonoscopy or imaging. The cause of diverticulosis is raised intraluminal pressure, thought to often be due to chronic constipation and a low fibre diet. NICE advises a healthy, balanced diet with whole grains, fruit and vegetables, and increasing fibre gradually with enough fluid. Bulk-forming laxatives (which add bulk to the stool) can be considered for constipation. Exercise, weight loss and stopping smoking may reduce the risk of acute diverticulitis and symptomatic disease. There is no need to avoid seeds, nuts, popcorn or fruit skins.
Diverticulitis is the inflammation +/- perforation of the diverticula. This occurs in a minority of patients with diverticulosis (the lifetime risk is about 4%). It is thought to occur when faeces blocks the opening of the diverticulum, or when a tiny perforation (microperforation) forms at its tip. This leads to bacteria invading the wall of the diverticulum, causing inflammation. If there is a large amount of inflammation, the diverticulum may perforate. Patients with diverticulitis typically present with abdominal pain (often lower left segment - sigmoid), fever, abdominal distension, and constipation. If the bowel has perforated, they may also have signs of peritonitis (inflammation of the lining of the abdominal cavity), such as abdominal rigidity, guarding and rebound tenderness (pain when pressure on the abdomen is released). Haematochezia (fresh red blood from the rectum) is a different problem: diverticular bleeding is usually abrupt and painless.
In suspected complicated diverticulitis, investigations in hospital include blood tests (FBC, urea and electrolytes, and CRP). If inflammatory markers are raised, a contrast CT scan is offered within 24 hours of admission to confirm the diagnosis and plan management. Colonoscopy is avoided in the acute setting due to perforation risk, but a planned colonoscopy or CT colonography (a CT scan of the colon) may be arranged after recovery in selected patients, to exclude other diagnoses such as inflammatory bowel disease or colorectal cancer.
If there are no signs of perforation, uncomplicated diverticulitis in a patient who is systemically well (not showing signs of whole-body illness) is treated with simple analgesia (painkillers such as paracetamol), and a no-antibiotic strategy can be considered. Antibiotics are offered if the patient is systemically unwell, immunosuppressed (has a weakened immune system) or has significant comorbidity (other long-term conditions). The first-choice oral antibiotic is co-amoxiclav. NICE found no evidence to support bowel rest (clear fluids only), although some experts advise clear fluids or a low residue diet (a diet that leaves little undigested material in the bowel) while symptoms settle. If an abscess is suspected, patients need intravenous antibiotics and a contrast CT scan. An abscess larger than 3 cm may need percutaneous drainage (a needle or tube placed through the skin) or surgery. If there is a perforation with generalised peritonitis, surgical intervention is needed: either laparoscopic lavage (washing out the abdominal cavity with keyhole surgery) or resectional surgery (removing the diseased bowel).
Diagram - Diverticular disease in the colon
Creative commons source by Lfreeman04 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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