Gastroenterology

Large Bowel Disease

Irritable Bowel syndrome

About

  • IBS typically decreases with age
  • Functional as there are no real demonstrable pathological findings
  • However that is not to say that the illness is "imaginary" .

Aetiology

  • Test have shown some degree of visceral hypersensitivity.
  • IBS may be regarded as part of a functional gastrointestinal disorder - a dysregulation of "brain-gut function"

Clinical Findings

  • Patients do suffer and deserve empathy and consideration and an attempt at symptoms control.
  • IBS also is an expensive illness as it causes sickness and work absence.
  • It is seen more commonly in women
  • There is increased anxiety and depression scores in sufferers
  • Abdominal pain is usually variable but tends to be relieved by defecation
  • Incomplete evacuation is a typical complaint
  • The passing of mucus per rectum, Abdominal bloating
  • Nausea alone or vomiting alone
  • Patients may complain of heartburn as a symptom of their IBS - indeed there may be extracolonic symptoms and even extra-GI tract features such as atypical chest pain, globus hystericus

Diagnosis - as there are no histological or laboratory tests the diagnosis depends upon symptoms

  • Rome II 1999 Diagnostic criteria - These criteria state that, in the preceding 12 months there should be at least 12 weeks (consecutive) of abdominal discomfort or pain that has two of three of the following features
    • relieved with defecation; and/or
    • onset associated with a change in frequency of stool; and/or
    • onset associated with a change in form (appearance) of stool.
  • The following symptoms cumulatively support the diagnosis of IBS:
    • abnormal stool frequency ('abnormal' may be defined as > 3/day and < 3/week)
    • abnormal stool form (lumpy/hard or loose/watery stool)
    • abnormal stool passage (straining, urgency, or feeling of incomplete evacuation)
    • passage of mucus
    • bloating or feeling of abdominal distension

May be divided by clinical history into different types

  • Diarrhoea predominant
  • Constipation predominant
  • A mixture of both with patients flitting between types at different times

Important to consider alternative diagnoses

  • Red flag symptoms suggesting further investigations such as colonoscopy for polyps, malignancy and diverticular disease or abdominal CT or small bowel investigations and screening for coeliac disease etc
  • Anaemia, Fever, Weight loss
  • Rectal bleeding
  • Nocturnal GI symptoms
  • Family history of GI cancer/Inflammatory bowel disease/Coeliac
  • New onset age > 50

Investigations

  • NO specific biochemical and structural abnormalities that explain symptoms and this is part of the definition of IBS.
  • Normal FBC, ESR, CRP, Anti endomysial ab, TFT's, LFT's, U&E
  • If suspicions of colorectal disease - colonoscopy and stool culture.
  • Sigmoidoscopy and air insufflation may recreate some of the symptoms.
  • If suspicions of Upper GI disease - OGD + duodenal biopsies

Management

  • Reassurance is important and consideration of psychosocial and other factors
  • High fibre diet can be helpful
  • Antispasmodics such as Mebeverine can be useful
  • Psychology - Biofeedback and antidepressants and other therapies have been used with mixed results  

Inflammatory bowel disease

Summary

Feature Ulcerative Colitis Crohn's disease
Prevalence 1 in 1000 1 in 1500
Immune response Th2 dominant Th1 dominant
Smoking Less common More common
Genetic influence Both Stronger
Disease extent Colorectal disease, diffuse distribution, thin wall, strictures very rarely Mouth to anus, skip lesions, strictures common and thickened wall
Clinical Colorectal symptoms Small bowel disease, Fat/Vitamin malabsorption
Toxic megacolon No Yes
Recurrence after surgery No Yes
Antibodies to Saccharomyces cerevisae absent present
pANCA positive 75% 11%
Pathology Red mucosa and pseudopolyps, minimal fibrosis Transmural rosethorn ulcers, Cobble stoning, skip lesions, Marked fibrosis, Perianal disease
Histology Inflamed mucosa,Goblet cell depletion, Crypt abscess Transmural inflammation, Granulomas, Marked lymphoid reaction, serositis

Crohn's disease

Introduction

  • A chronic relapsing inflammatory granulomatous disease
  • Can affect any part of the Gut from mouth to anus.

Aetiology

  • Smoking is a risk factor
  • Familial types - polymorphisms in NOD2/CARD15 gene on chromosome 16 correlate ileal disease
  • Exposure to antigens

Pathology

  • The inflammation is oedematous with granulomatous transmural inflammation and cobble stoning
  • Skip lesions are seen i.e. 2 affected areas with unaffected bowel between, mucosal fissures
  • Crypt abscesses, Submucosal fibrosis, Noncaseating granulomas
  • Deep ulceration and fistula formation may be seen. Fistulas - bladder, uterus, vagina, rectal

Disease

  • Terminal ileum, Ileum, Ileocaecal valve 40%
  • Small and large intestine 30%
  • Colonic disease alone
  • Perianal disease < 10%

Clinical

  • Crampy abdominal pain - inflammation, fibrosis, partial obstruction
  • Fever, malaise, Weight loss, anorexia, Steatorrhoea, Mouth ulcers
  • Bloody or non bloody diarrhoea - Crohn's colitis
  • Perianal lesions - skin tags and fistula formation, abscesses
  • Right iliac fossa mass and tenderness may mimic appendicitis

Non GI manifestations

  • Finger clubbing and anaemia
  • Eye - Uveitis, Episcleritis
  • Kidney stones
  • Arthropathy, Sacroiliitis , Ankylosing spondylitis
  • Erythema nodosum, pyoderma gangrenosum
  • Amyloidosis
  • Pericholangitis and Primary sclerosing cholangitis seen but moreso with Ulcerative colitis
  • Risk of colonic malignancy with long term Crohn's colitis

Investigations

  • Anaemia , B12 folate Ferritin
  • Elevated WCC and platelets
  • Raised ESR and CRP correlates with disease activity
  • LFT's, Bone profile
  • Stool for ova, cysts and parasites
  • AXR - look for obstruction
  • Small bowel follow through - string sign of Kantor, deep rose thorn ulcers, cobblestone mucosa.
  • CT with contrast has a high sensitivity for disease
  • Small bowel histology usually not needed where diagnosis clear but one can do a technetium labelled white cell scan to pick up areas of disease activity
  • Where the diagnosis is in doubt laparotomy and resection and biopsy may be needed
  • MRI - best for perianal disease
  • OGD/Colonoscopy for biopsies
  • +ve antibody to Saccharomyces cerevisiae in 60% but are quite specific

Differential

  • Tuberculosis
  • Yersinia

Management

  • Low residue diet, antidiarrhoeals as required, antispasmodics, B12 and calcium supplements may be needed
  • Mesalazine or Sulfasalazine (5 ASA) are useful in Crohn's colitis in inducing remission. Given orally or rectally
  • Localised proctitis can be treated with Mesalazine enemas/Steroid enemas.
  • Oral prednisolone 40 mg or IV hydrocortisone for acute flare ups
  • Azathioprine/6 Mercaptopurine may be used in those who fail to settle with 5-ASA. Side effects are Bone marrow suppression and pancreatitis. Need to closely monitor FBC
  • Methotrexate - used in those with active Crohn's disease resistant to steroids
  • Metronidazole - Useful in perianal Crohn's disease. Has antibacterial and immunosuppressive actions
  • Infliximab : Anti TNF monoclonal antibody given as infusion for Crohn's disease which fails to respond to steroids. Useful for those with fistulas. Infusions given every 8 weeks.
  • Budesonide for ileocaecal Crohn's disease
  • Surgery - bowel resection or strictureplasty or management of abscesses or fistulas

Colorectal disease

Ulcerative colitis

Introduction

  • Affects only the colon with some systemic manifestations
  • Increasing Incidence 10-20/100,000 and Prevalence 50-100/100,000

Aetiology

  • Response to an environmental trigger
  • Ulcerative colitis is commoner than Crohn's disease
  • Smokers seem to be protective

Clinical

  • Patients present with low volume diarrhoea often bloody due to bowel inflammation.
  • Disease is confined to the colon and rectum
  • Patients may complain of diarrhoea often 10-20/day and urgency
  • Flare up can be provoked by infection, stress, NSAIDs, antibiotics Presenting features
  • Weight loss, Malabsorption, Malaise, Tenesmus
  • Anaemia, Abdominal pain
  • Small Bowel Obstruction
  • Bloody diarrhoea from proctosigmoiditis
  • Toxic Megacolon
  • Extraarticular manifestations
    • Chronic active hepatitis
    • Pericholangitis
    • Sclerosing cholangitis
    • Cholangiocarcinoma
    • Colorectal cancer
    • Ankylosing spondylitis
    • Uveitis

Pathology

  • Confined to Colon and almost always rectum (proctitis)
  • Pan colitis develops in 30% over 10 years and lesions usually continuous
  • Goblet cell depletion and Shortening and pseudopolyps
  • Granulomas absent
  • Chronic inflammation in lamina propria and superficial mucosal layers
  • Mucosal islands between severely ulcerated mucosa
  • Malignancy risk
  • Backwash ileitis - inflamed distal ileum

Define Severe colitis* a good exam questions

  • Stool frequency > 6/day
  • Temp > 38 C
  • Pulse > 90 bpm
  • ESR > 30 mm/hr
  • Hb < 10.5 g/dl Investigations
  • FBC - anaemia, Ferritin

Investigations

  • Anaemia , B12 folate ferritin
  • Elevated WCC and platelets
  • Raised ESR and CRP correlates with disease activity
  • LFT's, Bone profile
  • Stool for ova, cysts and parasites
  • AXR - look for obstruction
  • Colonoscopy and biopsies
  • Positive pANCA

Management

  • Difficult to diagnose the initial episode from infective causes but prolonged history over 10 days or other factors may help.
  • 5-Aminosalicylic acid : Mesalazine or Sulfasalazine are useful in UC or Crohn's colitis in inducing remission. Given orally, rectally. Maintain remission - Oral Mesalazine or balsalazide. Sulfasalazine best for those with associated arthropathy
  • Localised proctitis - Mesalazine enemas/Steroid enemas. Oral prednisolone 40 mg is an alternative
  • Azathioprine/6 Mercaptopurine : Both CD and UC who fail to settle with 5-ASA. Side effects are Bone marrow suppression and pancreatitis. Need to closely monitor FBC
  • Ciclosporin - severe acute UC who fail to settle with IV steroids
  • Surgery may still be needed with ongoing disease. Usually a pan proctocolectomy removing colon and rectum with a pouch procedure. The operation is curative. However the main problem is defaecation 6-8 times a day as pouch capacity is low. Some may develop a pouchitis
  • Severe colitis - see definition above. There is abdominal pain and the patient is toxic. AXR shows dilated bowel, thumb printing and mucosal oedema and if bowel diameter > 6 cms there is a high risk of perforation. Joint care from both gastroenterology and surgeons. Transfuse > 10 g/dl. IV methylprednisolone. Nutritional support, Antibiotics, VTE prophylaxis. Consider IV Ciclosporin or Infliximab if no response to high dose steroids after 3-5 days reduces need for surgery. Laparotomy and urgent colectomy if fails to settle

Indeterminate Colitis

Introduction

  • Inflammatory bowel disease affecting colon
  • Has features of both UC and CD

Aetiology

  • See UC and CD

Clinical

  • Symptoms of colonic disease

Pathology

  • Diffuse colonic disease

Investigations

  • Colonoscopy and biopsies
  • pANCA and Antibodies to Saccharomyces cerevisae conflict with other findings

Management

  • As Inflammatory bowel disease Colitis

Microscopic colitis

Introduction

  • Collagenous colitis
  • Lymphocytic colitis

Aetiology

  • Lymphocytic associated with autoimmune disease

Clinical

  • Watery diarrhoea, not bloody
  • No weight loss
  • Usually older females

Investigations

  • Anaemia, Raised CRP, low potassium in severe cases
  • Colonoscopy normal. Biopsies taken
  • Investigate other causes of chronic diarrhoea

Biopsies

  • Collagenous - dense subepithelial collagen layer
  • Lymphocytic - increased lymphocytes

Management

  • Symptomatic e.g. loperamide
  • Avoiding NSAIDs
  • Cholestyramine has been used
  • Steroids e.g. budesonide can be used
  • Methotrexate in severe disease
  • Colectomy or ileostomy in severe refractory cases

Colorectal malignancy

Colorectal cancer

Introduction

  • Common cause of cancer in older patients

Risk factors

  • Sporadic 70%
  • Familial 10-30%
  • Hereditary non polyposis col 2-3%
  • Familial adenomatous polyposis < 1%
  • Hamartomatous < 0.1%
  • Ulcerative colitis > 10 years
  • Crohn's colitis over many years
  • Additional risk factors
  • High meat low fibre diet

Aetiology

  • Acquired genetic defects
  • Activation of tumour promoting genes / oncogenes K-ras, c-myc
  • Loss of suppression of tumour suppressor genes p53, MCC, DCC
  • Adenoma eventually becomes carcinoma

Clinical

  • Rectal bleeding
  • Left sided lesions with Iron deficiency anaemia or a mass
  • Altered bowel habit - diarrhoea
  • Right sided lesions - Intestinal obstruction, altered bowel habit
  • Tumour spreads to lymphatic locally and then on to liver and beyond

Investigations

  • FBC, Microcytic anaemia, Low Ferritin - Iron deficiency anaemia
  • Ba enema may show a lesion
  • Colonoscopy enables visualisation, marking and biopsy
  • FOBs are only used as screening tools in certain trials

Management

  • Preventative surgery in FAP : Colectomy and ileorectal anastomoses the life expectancy of FAP has risen from 35 to 65 years old
  • Tumour resection and reanastomasos
  • Chemotherapy for Dukes 3 : 5 fluorouracil and leucovorin
  • Radical surgical excision is not contraindicated with peritoneal or hepatic metastases as it may help with palliation.
  • Colostomy is performed for tumours which cannot be resected and it may allow palliative high dose radiotherapy to the tumour
  • Radiotherapy is useful for palliation of pain and rectal bleeding

Dukes classification

  • Dukes A: Tumour confined to bowel wall (80% 5 yr survival)
  • Dukes B: Tumour extending through bowel wall (50% 5 yr survival)
  • Dukes C1 lymph node involvement but not up to vascular ligation point (40% 5 yr survival)
  • Dukes C2 lymph node involvement but up to the vascular ligation point (12% 5 yr survival)
  • Dukes D : Distant metastases

Hereditary non polyposis coli (HNPC)

Introduction

  • Autosomal dominant with incomplete penetrance.
  • Accounts for 2-4% of Colorectal cancers
  • There are at least 2 generations affected
  • At least one individual is a first degree relative of one of the affected and One case diagnosed age < 50

Aetiology

  • At the molecular biology level there is a defect in DNA mismatch repair genes (MMR).
  • 95% of cases due to defects in hMLH1 and hMSH2.

Clinical

  • Develop tumours more on the right side.
  • There are associated malignancies of the ovary, uterus and stomach.

Investigations

  • Colonoscopy - There are less than 100 adenomas in the proximal colon.

Management

  • Screen with colonoscopy every 2 years
  • Treat as for colorectal cancer

Familial adenomatous polyposis (FAP)

Introduction

  • Accounts for 0.5-1% of Colorectal cancer

Aetiology

  • Gene is on chromosome 5q band 21 or 22.
  • Autosomal dominant defect.
  • There is loss of one of two Adenomatous polyposis coli (APC) genes.
  • Hypertrophy of the retinal pigment layer. At the molecular biology level the APC genes act as caretakers or a "gatekeeper" gene.

Investigations

  • Colonoscopy - development of 100-1000's of colorectal adenomas in teenage years.

Management

  • Untreated patients develop bowel cancer by the age of 40.
  • Requires Panproctocolectomy + ileoanal pouch