PBL 50 Flashcards
Chronic inflammatory bowel disease is an umbrella term for which diseases?
- Crohn’s disease
2. UC
What are the theories for IBD aetiology?
Probably a classical auto-immune disease with a genetic predisposition, and then sensitising & triggering elements but there are other theories:
- Toxic response to luminal contents: specific microbial pathogen, abnormal luminal constituents, or increased absorption of luminal macromolecules
- Enhanced immune response to normal constituents
- Autoimmune response: to epithelial cell or mucous glycoprotein, molecular mimicry or to immune cells.
What are typical symptoms of IBD?
- Pain
- General malaise
- Fever
- Swelling
- Cramping
- Recurring or bloody diarrhoea
- Weight loss
- Extreme tiredness
- Stools w/blood, mucus & pus
What are different complications of IBD?
- arthritis
- iritis
- erythema nodosum
- pyoderma gangrenosum
- sclerosing cholangitis
- aphthous stomatitis
- gall & renal stones
- colorectal cancer risk
What are the different drugs used in treating IBD?
- Aminosalicylates (5-ASAs)
- Corticosteroids
- Immunosuppressants
- Biologics
What are other treatments for IBD that modulate immune system and/or response to intestinal microbiota?
- Helminth therapy
- Fecal microbiota transplantation
- Bacterial cocktails
- Small-molecule approaches
Give examples of 5-ASAs and how they treat IBD
- Sulphasalazine
- Mesalazine
- They dampen the inflammatory process
Give examples of corticosteroids used to treat IBD and, in short, how they do this
- Prednisolone
- Prednisone
- Hydrocortisone
- Block substances that trigger inflammation
Give examples of immunosuppressants used to treat IBD and, in short, how they do so
- Azathioprine
- Methotrexate
- Suppress the immune system
Give examples of biologics used to treat IBD and, in short, how they do so
- Infliximab - anti-TNFa monoclonal antibody
2. Adalimumab - anti-TNFa monoclonal antibody
Which mutations are associated with a genetic disposition to Crohn’s disease?
- NOD2
2. IL-23 receptor
What is NOD2 and how does this mutation lead to Crohn’s?
- NOD2 is a pattern recognition receptor expressed in Paneth cells of the gut, so a mutation of NOD2 affects production of anti-microbial peptides.
- NOD2 is also expressed in innate immune cells, macrophages or DCs. So, once stimulated with a microbe, depending on the NOD2 phenotype, this may affect production by these innate immune cells of downstream cytokines, one of them being IL23
How does mutation of IL-23R lead to Crohn’s?
IL-23 is produced by innate cells following the activation via PRRs. IL-23 acts on the IL23R which is expressed by innate cells such as the Th17 cell, so mutation in the IL23R will hinder the activity of innate cells
What are risk factors for Crohn’s?
- FHx
- Smoking: increases the risk in genetic susceptible people and also risk of disease relapse & need for surgical resection
- Infectious gastroenteritis: risk increases 4fold
- Appendicectomy
- Drugs: NSAIDs increase the risk of relapse or exacerbation, but absolute risk is low.
- Microvascular infarction - Oral contraceptive pill (procoagulant)
- Triggers appears to be infective agents - Mycobacteria, measles virus
Signs and symptoms of Crohn’s
- Persistent diarrhoea – including nocturnal diarrhoea with possible blood or mucus in stool
- Abdominal pain or discomfort
- Bleeding
- Weight loss
- Fistulae
- Perianal disease
- Faltering growth or delayed puberty
- Non-specific symptoms: fever, malaise, anorexia, fatigue.
Crohn’s can affect any part of the intestinal tract, but which part is most commonly affected?
The small intestine
Presentation of Crohn’s depends on the disease location, explain the difference in presentation depending on which part of the GI tract is affected: COLON, UPPER GI/SI, PERIANAL.
- Colon - bloody diarrhoea
- Upper GI/SI - Severe abdominal pain, vomiting, weight loss, small intestinal obstruction due to strictures
- Perianal - ulcers, fissures, perianal abscess, fistula
What is the main principle for surgery of Crohn’s?
Preserve bowel length to avoid short bowel syndrome and intestinal failure
Complications of Crohn’s?
- Malabsorption - Short loop/bowel syndrome due to repeated resection
- Fistula formation
- Anal lesions (60%) - Fissures, fistula
- Perforation, haemorrhage, toxic dilatation not as frequent as ulcerative colitis
- Increased risk of malignancy of small intestine but less frequent than ulcerative colitis
How is Crohn’s diagnosed?
- On examination there may be abdominal tenderness or mass, for example in RLQ. Perianal pain or tenderness, anal or perianal skin tags, fissure, fistula, or abscess. Signs of malnutrition or malabsorption. Abnormalities of the joints, eyes, liver and skin.
- Routine bloods for anaemia, infection, thyroid, kidney and liver function
- CRP indicates inflammation and active disease
- Faecal calprotectin (released by the intestines when inflamed) is a useful screening test (> 90% sensitive and specific to IBD in adults)
- Endoscopy (OGD and colonoscopy) with biopsy is diagnostic
- Imaging with ultrasound, CT and MRI can be used to look for complications such as fistulas, abscesses and strictures.
How is Crohn’s treated?
Inducing remission:
• First line: Steroids (e.g. oral prednisolone or IV hydrocortisone)
If steroids alone don’t work, consider adding immunosuppressant medication under specialist guidance: • Azathioprine • Mercaptopurine • Methotrexate • Infliximab • Adalimumab
Maintaining remission: • Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well. First line: • Azathioprine • Mercaptopurine
Alternatives:
• Methotrexate
• Infliximab
• Adalimumab
Surgery
• When the disease only affects the distal ileum it is possible to surgically resect this area and prevent further flares of the disease. Crohns typically involves the entire GI tract
• Surgery can also be used to treat strictures and fistulas secondary to Crohns disease.
Explain the pathophysiology of UC
- Inappropriate immune response to an unknown environmental stimulus in the colon
- Unknown cause - Infection, diet, environmental factors, primary immunological defects, abnormalities in mucin, genetic disorders, psychomotor disorder
Explain the progression of UC
- Always begins in rectum
- Can remain limited to rectum (ulcerative proctitis)
- Extends proximally to a variable length, or involve the entire large intestine (pancolitis) in a continuous manner
- Changes always most severe distally
- Primarily affects mucosa, but in severe disease, deeper layers can be involved - Fulminant colitis (toxic megacolon)
Explain the risk factors for UC
- FHx: risk is greatest in first-degree relatives
- No appendectomy: appendicectomy before adulthood is thought to be protective against development of UC. Appendicectomy may be protective, delay onset, producing a milder form
- Not smoking: smoking appears to be preventive - Could be linked to increased glycoprotein synthesis maintaining protective mucosal barrier
- NSAIDs known to reactivate CIBD, especially UC, and in some patients, implicated in initiating UC
Signs and symptoms of UC
- Pr blood
- Frequency and urgency of defecation
- Cramping abdominal pain
- Fever
Diagnosis for UC
- Serum blood count: for anaemia, infection, thyroid, kidney and liver function
- CRP indicates inflammation and active disease
- Faecal calprotectin (released by the intestines when inflamed) is a useful screening test (> 90% sensitive and specific to IBD in adults)
- Endoscopy (OGD and colonoscopy) with biopsy is diagnostic
- Imaging with ultrasound, CT and MRI can be used to look for complications such as fistulas, abscesses and strictures.
Explain the treatment for UC
Inducing Remission
Mild to moderate disease:
• First line: aminosalicylate (e.g. mesalazine oral or rectal)
• Second line: corticosteroids (e.g. prednisolone)
Severe disease:
• First line: IV corticosteroids (e.g. hydrocortisone)
• Second line: IV ciclosporin
Maintaining Remission
• Aminosalicylate (e.g. mesalazine oral or rectal)
• Azathioprine
• Mercaptopurine
Surgery
• Ulcerative colitis typically only affects the colon and rectum. Therefore, removing the colon and rectum (panproctocolectomy) will remove the disease. The patient is then left with either a permanent ileostomy or something called an ileo-anal anastomosis (J-pouch). This is where the ileum is folded back in itself and fashioned into a larger pouch that functions a bit like a rectum. This “J-pouch” which is then attached to the anus and collects stools prior to the person passing the motion.
Crohn’s vs UC: NESTTS vs CLOSEUP
Crohn’s - think crow’s nests
N - No blood or mucus (less common)
E – Entire GI tract
S – “Skip lesions” on endoscopy
T – Terminal ileum most affected and Transmural (full thickness) inflammation
S – Smoking is a risk factor (don’t set the nest on fire)
Crohn’s is also associated with weight loss, strictures and fistulas.
Ulcerative Colitis (remember U – C – CLOSEUP) C – Continuous inflammation L – Limited to colon and rectum O – Only superficial mucosa affected S – Smoking is protective E – Excrete blood and mucus U – Use aminosalicylates P – Primary Sclerosing Cholangitis
Are granulomas more commonly found in UC or Crohn’s?
Crohns
