Lower GI tract disorders Flashcards
What arteries supply the large intestine/colon?
branches of superior and inferior mesenteric arteries
What are the layers of the colon wall?
- mucosa: epithelium, lamina propria, muscularis mucosae
- submucosa: glands here produce mucin (lubricates bowel)
- muscularis: circular adn longitudinal muscle
- serosa: connective tissue and nerve supply
What is the nerve supply to the colon?
- parasympathetic: ascending and most of transverse colon innervated by vagus nerve–> more distally innervated by pelvic nerves
- sympathetic: lower thoracic and upper lumbar spinal cord
- external anal sphincter controlled by somatic (voluntary) motor fibres in the pudendal nerves
How can we divide lower GI tract disorders into 6 categories?
- inflammatory: IBD, miscrosopic colitis (normal looking mucosa in colonoscopy, but histological abnormalities)
- infective: C diff, E coli etc…
- structural: diverticular disease, haemorrhoids, fissures
- functional: irritable bowel syndrome (normal investigations, but significant symptoms)
- neoplastic: colonic polyps + colon cancer
- other: neurological, metabolic + vascular
What is inflammatory bowel disease?
- lifelong chronic disease, often affecting young people
- comprises ulcerative colitis and Crohn’s disease
- takes major toll on patients and healthcare
What is ulcerative colitis?
- inflammation limited to colonic mucosa- mainly superficial layer
- continuous inflammation
- always involves rectum
- M=F incidence
- no granulomas
What is Crohn’s disease?
- can affect any part of GI tract
- patchy in nature e.g. part of colon, part of small bowel
- deeper inflammation- doesn’t just affect mucosa–> transmural
- granulomatous inflammation
- tendency to form fistulas (communication btwn diff. walls of bowel) and strictures (narrowing of lumen due to fibrous tissue)
- F>M (1.5: 1)
What is proctitis?
UC that only involves rectum
What is proctosigmoiditis?
UC that involves sigmoid colon and rectum
What is distal colitis?
UC that extends up through descending colon
What is extensive colitis?
UC that extends through to the transverse colon
What is pancolitis?
UC that involves the whole of the colon and rectum
What symptoms are associated with colitis?
- bleeding
- mucus
- urgency (hallmark of lower rectal disorder)
- diarrhoea
What symptoms are associated with perianal Crohns disease?
- anal pain (Crohns- pain bc deeper ulcers)
- leakage
- difficulty passing stool
What symptoms are associated with small bowel Crohns disease?
- abdominal pain
- weight loss (bc less absorption)
- tiredness/lethargy (bc less absorption of vitamins)
- diarrhoea
- abdominal masses
What extra-intestinal manifestations can present in IBD?
- arthritis: axial ankylosing spondylitis, peripheral
- skin problems: erythema nodosum, pyoderma gangrenosum
- eyes: anterior uveitis, episcleritis/iritis
- liver: primary sclerosing cholangitis (PSC)- mainly associated w/UC, autoimmune hepatitis
due to autoimmune nature
What is the aetiology of IBD?
- combination of impaired mucosal immune response to the gut microbiota + a genetically susceptible host
- imbalance between healthy microbiota and pathological microbiota
- immune system reacts inappropriately to imbalance and induces inflammation
What autoantibody is associated with UC?
pANCA
What genes are associated with IBD?
- NOD2- crohns
- HLA
- ATG
- IL23R
What environmental factors are thought to impact IBD?
- poor diet–> altered microbiota (dysbiosis- unhealthy gut microbiota)
- hygiene- limited exposure to microorganisms in childhood
- physical activity- less=bad
- stress
- appendectomy- protective for UC, bad for CD
- smoking/nicotine- bad for CD (affects permeability of mucosa), but protective for UC
What are the main goals of management for IBD?
- induce clinical remission
- maintain clinical remission
- improve patient quality of life
- heal mucosa
- dec. hospitalisation/surgery + overall cost
- minimise disease+ therapy related complications
What drugs are used to manage IBD?
- steroids: IV, orally or rectal enemas, acute therapy (ineffective long-term)- steroids bind to glucocorticoid responsive elements (GRE) to block pro-inflammatory genes
- 5 ASA: orally or rectally- inhibits pro-inflammatory cytokines (IL-1 and TNF-a), inhibits lipo-oxygenase pathway and scavenge free radicals, also immunosuppressive
- immunosuppressants e.g. azathioprine, methotreaxate
- biologics, which target TNF- one of main drivers of immune reaction
What are the significant side effects of using steroids long-term?
- psychiatric
- neurologic
- endocrine
- opthalmic
- developmental
- cardiovascular
- skin/soft tissue
- MSK
What are the side effects of 5 ASA?
- intolerance
- diarrhoea
- renal impairment
- headache
- malaise
- pancreatitis
- pneumonitis
How does azathioprine act as an immunomodulator?
- precursor of 6-MP, which can lead to enzymes XO, TPMT and HPRT (which leads to 6-TGN, which interferes w/ adenine and guanine ribonucleotide production)
- results in fewer B+T lymphocytes, immunoglobulins and interleukins
- suppresses immune system and immune reaction, reducing inflammation
What are the side effects of azathioprine and what do you need to check?
- infection
- pancreatitis
- bone marrow suppression
- malignancy/lymphoma
need to check:
- TPMT (bc if low, then all 6-MP will lead to 6-TGN–> lots of side effects- so you reduce dose of AZA)
- hep B/C (can be reactivated)
- HIV
- chicken pox
- vaccinations
- TB
- frequent bloods
How does methotrexate work?
mechanism unclear but:
- interferes w/ DNA synthesis+cell reproduction
- inc. adenosine levels (anti-inflammatory)
- inc. apoptosis of peripheral T-cells
- takes 3 months to work
What biologics are anti-TNF alpha?
infliximab and adalimumab
What are the side effects of biologics?
- opportunistic infections
- infusion or site reactions
- neutropenia
- infections
- demyelinating disease
- heart failure
- cutaneous reactions, inc. psoriasis
- malignancy
- induction of autoimmunity
What is combination therapy in IBD and what is its advantage?
- AZA/6MP and anti-TNF act synergistically
- combination therapy= superior bc induces and maintains resposne and remission
- reduceds rate of antibody formation
What other considerations are there apart from drugs in IBD management?
- diet: liquid therapy diet- inc. use in children- as effective as steroids
- antibiotics- no hard evidence but good for sepsis
- faceal microbiota transplantation (FMT): lots of research into role of microbiome
- novel agents
