Lower GI tract Flashcards
what is the anatomy of the large intestine?
what are the arteries and veins of lower GI tract?
what does the inferior mesenteric artery supply?
left side of the colon
what area is under parasympathetic control?
- Ascending colon and most transverse colon in innervated by vagus nerve
- More distal innervated by pelvic nerves
what area is under sympathetic control?
lower thoracic and upper lumbar spinal cord
what is the external anal sphincter controlled by?
somatic motor fibres in pudendal nerves (S1,S2,S3)
afferent sensory neurons detect pressure- send signals for emptying of rectum
what does the enteric nervous system do?
pace maker in the bowel
what disease is caused by lack enteric nervous system?
Hirschsprung’s disease
no enteric intramural ganglia
where is the myenteric plexus ganglia located?
concentrated below taenia coli
what are lower GI disorders split into?
inflammatory
infective
structural
functional
neoplastic
other
what inflammatory lower GI disorders are there?
inflammatory bowel disease (IBD)
microscopic colitis
what are the infective lower GI disorders?
C.Diff
E. Coli
what are the structural lower GI disorders?
diverticular disease
hemorrhoids
fissures
what are the functional lower GI disorders?
irritable bowel syndrome
what are the neoplastic lower GI disorders?
colonic polyps and colon cancer
what are the other lower GI disorders?
neurological
metabolic
vascular
what are the subsets of inflammatory bowel disease?
Ulcerative colitis (UC) and Crohn’s disease (CD)
what are the concepts of ulcerative colitis?
- Inflammatory disorder limited to the colonic mucosa
- Superficial layer
- Continuous
- Always involves the rectum
- M = F
- NO granulomas
what are the types of ulcerative colitis?
what are the features of chron’s disease?
- Can affect any part of the gastrointestinal tract
- Patchy chronic transmural granulomatous inflammation
- Tendency to form fistula or strictures
- F>M (1.5:1)
- Hallmark = ulceration
what is a fistula?
penetration from deep inflammation between 2 different walls
what is a stricture?
narrowing of lumen due to inflammation and oedema
form fibrous tissue that does not open up again
what are the types of crohn’s disease?
what are the symptoms of UC and Crohns?
depends on site of inflamation
-
Colitis
- Bleeding
- Mucus
- Urgency
- Diarrhoea
-
Perianal (crohn’s disease only)
- Anal pain
- Leakage
- Difficulty passing stool
-
Small bowel disease (crohn’s disease only)
- Abdominal pain
- Weight loss
- Tiredness/lethargy
- Diarrhoea
- Abdominal mass
what are some extra-intestinal manifestations of IBD?
-
Arthritis
- Axial – Ankylosing Spondylitis
- Peripheral
-
Skin
- Erythema nodosum
- Pyoderma gangrenosum
-
Eyes
- Anterior uveitis
- Episcleritis/Iritis
-
Liver
- Primary Sclerosing Cholangitis (PSC)
- Autoimmune hepatitis
what is the aetiology of IBD?
combination of impaired mucosal immune response to the gut microbiota in a genetically susceptible host
imbalance between pathological and healthy microbiota
what is the genetic susceptibility to IBD?
NOD2
HLA
ATG
IL23R
what is the immune response causing IBD?
Anti-saccharomyces cervisiae (ASCA)- Crohn’s
pANCA-UC
what other environmental factors may contribute to the formation of IBD?
luminal microbes
(mycobacterium paratuberculosi)
what affect does diet have on IDB?
unhealthy food= change microbiota causing dysbiosis (unhealthy microbiota)
what is the effect of appendectomy on IBD?
protection from UC but can develop Crohn’s disease
(appendix is a store of microbiota)
what is the effect of smoking on IBD
protective against UC
makes Crohn’s worse
what is the effect of hygiene on IBD
high hygiene can develop IBD
what is dysbiosis?
development of poor and unbalanced bacterial communities in gut lumen
pathologies= autoimmunity,allergy, metabolic disorders
what is the management for IBD?
- Induce clinical remission
- Maintain clinical remission
- Improve patient quality of life
- Heal mucosa
- Decrease hospitalisation/ surgery & overall cost
- Minimise disease and therapy related complications
what drugs can be used to treat IBD?
- Steroids
- 5 ASA
- Immune suppressants
- Azathioprine
- Methotreaxate
- Biologic therapy
- Others –diet, FMT, antibiotics, probiotics, novel agents
what are the modes of delivery of steroids?
IV, orally, rectal enemas
how do steroids work in IBD?
-
Diffuse and bind in nucleus to Glucocorticoid Responsive Elements (GRE).
- GRE interact with specific DNA sequences
- Increase anti-inflammatory gene products
- Block pro-inflammatory genes `
what is the use of steroids in IBD?
short term
as a bridge to other therapy/interventions
in acutely unwell patients
what are the side effects of steroids?
what is the effect of 5 ASA?
- Inhibition of pro-inflammatory cytokines (IL-1 and TNF-a )
- Inhibition of the lipo-oxygenase pathway i.e. prostaglandin and leukotrienes
- Scavenging of free radicals
- Inhibition of NF-kB/ TLR via PPAR-gamma induction (peroxisome proliferator activated receptor-gamma)
- Some immunosuppressive activity – inhibiting T cell proliferation, activation and differentiation
- Impairs neutrophil chemotaxis and activation
what is the mode of delivery of 5 ASA?
orally or rectally
what are the side effects of 5 ASA?
- Intolerance
- Diarrhoea
- Renal impairment
- Headache
- Malaise
- Pancreatitis
- Pneumonitis
how does azathioprine work?
- 6-TG (the active metabolite) interferes with adenine and guanine ribonucleotide production.
- Results in reduced number of B and T lymphocytes, immunoglobulins and interleukins.
- Another pathway potentially results in apoptosis of T cells
what needs to be checked before giving asathioprine?
- Thiopurine Methyltransferase (TPMT) (low in patients on this medication)
- Hep B/C
- HIV
- Chicken pox
- Vaccinations
- TB
- Frequent bloods on starting
- Maintenance bloods
how does methotrexate work?
- Interferes with DNA synthesis & cell reproduction
- Increased adenosine levels (anti-inflammatory)
- Increased apoptosis of peripheral T cells
what happens when taking methotrexate?
- Takes 3 months to work
- Need history re liver abnormalities
- Monitor LFTs, FBC
- Advise NO pregnancy
- Folic acid supplements (reduces side effects)
- WEEKLY DOSE
what are the side effects of methotrexate?
- Rash
- Nausea, mucositis, Diarrohea
- Bone marrow suppression
- Hypersensitivity pneumonitis
- ↑’ed liver enzymes
- Hepatic fibrosis/cirrhosis
- Known abortifacient
- No documented ↑ed risk of lymphoma or skin cancer
what are the types of biologics that can be used?
- Anti-TNFα – infliximab, adalimumab
- Anti- α4β7 Vedolizumab
- Anti-IL12/IL23 Ustekinumab
what are the effects of TNF alpha?
how is infliximab delivered?
IV
in hospital-less frequent
induction 0,2,6 weeks
maintenance 8 weekly
how is adalimumab delivered?
S/C
160/80/40mg Every other week
at home -more frequent
how is golimumab delivered?
S/C
what are the side effects of biologics?
- Opportunistic infections
- Infusion or site reactions
- Infusion reactions
- Neutropenia
- Infections
- Demyelinating disease
- Heart failure (HF)
- Cutaneous reactions, including psoriasis
- Malignancy
- Induction of autoimmunity
how is IBD managed?
combination therapy
- AZA/ 6MP and aTNF act synergistically
- Combination is superior in inducing and maintaining response and remission
- Reduces the rate of antibody formation
other mediations
- Cilosporin
- Vedolizumab (anti-integrin)
- Ustekinemab (anti IL12/23)
what are other consideration treatments in IBD?
- Dietary therapy
- Liquid therapy diet
- Increased use in children
- As effective as steroids
- Use in small bowel Crohns disease
- Weeks
- Antibiotics
- No hard evidence
- Good for sepsis
- Faecal Microbiota Transplantation (FMT)
- Lots research into the role of the microbiome
- Novel agents
