AUTO - B. IBD-COVERED Flashcards
Crohn’s disease
- can affect anywhere in GIT (mouth to anus)
- unknown cause ( changes in colonic bacteria?)
- we want patient kept in remission
- transmural (whole wall off GIT) inflammation
- dense infiltration of lymphocytes and macrophages
- fissuring ulceration
- submucosal fibrosis
symptoms of Crohn’s disease
- diarrhoea (nutrients not absorbed)
- pain
- narrowing of gut lumen leading to strictures and bowel obstruction (caused by fibrosis, may need removal of part of bowel where strictures are)
- abscess formation
- fistulisation to skin and internal organs
what are strictures
- scar tissue formation forms strictures
- caused by inflammation
- narrowing of lumen (lose of elasticity) and obstruction
- pain, cramping, bloating
- risk of rupture of GIT
what are fistulae
- inflam leads to ulcers
- ulcers develop into tunnels - fistulae
- can go between areas of GIT or between organs (to bladder) or to skin (anal fistula)
consequences of Crohn’s disease
- weight loss (large intestine, loss of water as diarrhoea)
- malabsorption
- macronutrient deficiencies
- micronutrient deficiencies (small intestine)
- fatigue (loss of electrolytes)
- proteins - energy malnutrition in 20-80% patients
Ulcerative colitis
- colon
- inflam only of mucosal layer
- infiltration of inflam cells into mucosa
- loss of goblet cells (mucus protects GIT wall to prevent ulcers)
- ulcerations
- loss of nutrients
Ulcerative colitis symptoms
- severe diarrhoea - changes in electrolytes and water
- blood loss as ulcers can eat at vessels in wall
- loss of peristaltic function - rigid colonic tube, stops contracting and therefore don’t get as much movement through colon, colon expands as more content goes in = megacolon
- toxic megacolon, perforation (rupture), sepsis
extra-intestinal inflammation (UC and Crohn’s)
- joints, eyes, skin, mouth, liver
- increased risk for colon cancer - esp UC
- no change in life expectancy
Treatment of IBD
drugs to reduce inflammatory response
- 5-aminosalicylate (Mesalazine)
- Corticosteroids (Prednisolone)
- immunosuppressants (Azathioprine and Methotrexate)
severe active Crohn’s - mAbs (Infliximab and Adalimumab)
Mesalazine
- inhibits leukotriene and prostanoid synthesis (LOX and COX pathways)
- scavenges free radicals
- decreases neutrophil chemotaxis (effects on PPAR-gamma receptor involved in changes in gene transcription therefore drug causes changes in neutrophils going to site of inflam)
- Sulfasalazine is metabolised to mesalazine
- Crohns? some effect in UC
Corticosteroids - Prednisolone
- induce remission
- anti-inflam immunosuppressive actions
- enemas (local effect) for distal/rectal inflammation eg - Predfoam
- Budesonide: poorly absorbed so far fewer side effects
Immunosuppressants (to start)
- Azathioprine (1st)
- inhibit purine synthesis and hence DNA
- reduce inflam cell proliferation
- azathioprine converted to 6-mercaptopurine which inhibits purine synthesis
Cyclosporin
- inhibits IL-2 induced gene expression
- used when there is resistance to drugs/steroid-sparing
what is TPMT activity
- 6-mercaptopurine metabolised by pathways incl thiopurine methyltransferase
Patients can have:
- low TPMT activity (use methotrexate?)
- no TPMT activity (use methotrexate): risk of drug-induced bone marrow toxicity
- high TPMT activity (maybe use methotrexate): risk of mercaptopurine resistance
TNF-alpha (Infliximab and Adalimumab)
- mAb for severe active Crohn’s
- neutralises inflam cytokine TNF-alpha in Crohn’s
- risk of TB
- Infliximab = infusion
- Adalimumab = injection
Nutrition with Crohn’s
- elemental (oral) feeds can induce remission
- used to reduce steroid use (ie - children)
- parenteral support may be required
- small bowel removal, shortened bowel:
reduced absorption
require nutritional support
