Lower GI tract disorders

Question 1

What arteries supply the large intestine/colon?

Answer 1

branches of superior and inferior mesenteric arteries

Question 2

What are the layers of the colon wall?

Answer 2

1. mucosa: epithelium, lamina propria, muscularis mucosae
2. submucosa: glands here produce mucin (lubricates bowel)
3. muscularis: circular adn longitudinal muscle
4. serosa: connective tissue and nerve supply

Question 3

What is the nerve supply to the colon?

Answer 3

• 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

Question 4

How can we divide lower GI tract disorders into 6 categories?

Answer 4

1. inflammatory: IBD, miscrosopic colitis (normal looking mucosa in colonoscopy, but histological abnormalities)
2. infective: C diff, E coli etc…
3. structural: diverticular disease, haemorrhoids, fissures
4. functional: irritable bowel syndrome (normal investigations, but significant symptoms)
5. neoplastic: colonic polyps + colon cancer
6. other: neurological, metabolic + vascular

Question 5

What is inflammatory bowel disease?

Answer 5

• lifelong chronic disease, often affecting young people
• comprises ulcerative colitis and Crohn’s disease
• takes major toll on patients and healthcare

Question 6

What is ulcerative colitis?

Answer 6

• inflammation limited to colonic mucosa- mainly superficial layer
• continuous inflammation
• always involves rectum
• M=F incidence
• no granulomas

Question 7

What is Crohn’s disease?

Answer 7

• 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)

Question 8

What is proctitis?

Answer 8

UC that only involves rectum

Question 9

What is proctosigmoiditis?

Answer 9

UC that involves sigmoid colon and rectum

Question 10

What is distal colitis?

Answer 10

UC that extends up through descending colon

Question 11

What is extensive colitis?

Answer 11

UC that extends through to the transverse colon

Question 12

What is pancolitis?

Answer 12

UC that involves the whole of the colon and rectum

Question 13

What symptoms are associated with colitis?

Answer 13

• bleeding
• mucus
• urgency (hallmark of lower rectal disorder)
• diarrhoea

Question 14

What symptoms are associated with perianal Crohns disease?

Answer 14

• anal pain (Crohns- pain bc deeper ulcers)
• leakage
• difficulty passing stool

Question 15

What symptoms are associated with small bowel Crohns disease?

Answer 15

• abdominal pain
• weight loss (bc less absorption)
• tiredness/lethargy (bc less absorption of vitamins)
• diarrhoea
• abdominal masses

Question 16

What extra-intestinal manifestations can present in IBD?

Answer 16

• 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

Question 17

What is the aetiology of IBD?

Answer 17

• 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

Question 18

What autoantibody is associated with UC?

Answer 18

pANCA

Question 19

What genes are associated with IBD?

Answer 19

• NOD2- crohns
• HLA
• ATG
• IL23R

Question 20

What environmental factors are thought to impact IBD?

Answer 20

• 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

Question 21

What are the main goals of management for IBD?

Answer 21

• induce clinical remission
• maintain clinical remission
• improve patient quality of life
• heal mucosa
• dec. hospitalisation/surgery + overall cost
• minimise disease+ therapy related complications

Question 22

What drugs are used to manage IBD?

Answer 22

• 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

Question 23

What are the significant side effects of using steroids long-term?

Answer 23

• psychiatric
• neurologic
• endocrine
• opthalmic
• developmental
• cardiovascular
• skin/soft tissue
• MSK

Question 24

What are the side effects of 5 ASA?

Answer 24

• intolerance
• diarrhoea
• renal impairment
• headache
• malaise
• pancreatitis
• pneumonitis

Question 25

How does azathioprine act as an immunomodulator?

Answer 25

* 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

Question 26

What are the side effects of azathioprine and what do you need to check?

Answer 26

* 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

Question 27

How does methotrexate work?

Answer 27

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

Question 28

What biologics are anti-TNF alpha?

Answer 28

infliximab and adalimumab

Question 29

What are the side effects of biologics?

Answer 29

* opportunistic infections * infusion or site reactions * neutropenia * infections * demyelinating disease * heart failure * cutaneous reactions, inc. psoriasis * malignancy * induction of autoimmunity

Question 30

What is combination therapy in IBD and what is its advantage?

Answer 30

* AZA/6MP and anti-TNF act synergistically * combination therapy= superior bc induces and maintains resposne and remission * reduceds rate of antibody formation

Question 31

What other considerations are there apart from drugs in IBD management?

Answer 31

* 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