Lower GI Tract Flashcards
Describe the basic anatomy of the Lower GI tract?
Appendix Caecum Ascending Colon Transverse Colon Descending Colon Sigmoid Colon Rectum Anus Small bowel
What is the parasympathetic supply to the lower GI tract?
Ascending colon and most of transverse colon innervated by vagus nerve
More distal innervated by pelvic nerves
What is the sympathetic innervation of the GI tract?
lower thoracic and upper lumbar spinal cord
What is the purpose of the illiocaecal valve?
Gives access to the terminal illeum
What provides the blood supply to the lower GI tract? (Arterial)
Small bowel - SMA
Colon - branches of SMA and IMA (mainly left side)
What provides the blood supply to the lower GI tract? (Venous)
SMV
IMV
Both join the portal vein and eventually the inferior vena cava
What are the 4 layers of the gut?
Mucosa: Epithelium, Lamina propia and muscularis mucosae
Submucosa
Muscularis: Circular and Lpongituidinal
Serosa: Nerve supply
What are the nerve plexuses in the gut?
Myenteric plexus
Submucosal plexus
What is the main features of the mucosa?
Glands that produce mucin that lubricates the bowel making the passing of faeces easier
What is the nerve supply to the external anal sphincter?
somatic motor fibres in the pudendal nerves
What is the function of the afferent sensory neurons?
Detect pressure
Send signals to empty
Where is the myenteric plexus gangila?
Concentrated below the teniae coli?
What are the inflammatory bowel disorders?
Inflammatory bowel disease
Micrscopic colitis (normal looking mucosa, but histological abnormalities on biopsy)
What are some infective bowel disorders?
C Diff
Ecoli
What are some structural bowel disorders?
Diverticular disease
Haemorrhoids
Fissures
What are some functional bowel disorders?
Irritable bowel syndrome
What are some neoplastic bowel disorder?
Colonic polyps
Colon cancer
What are some other causes of bowel disorders?
Neurological
Metabolic
Vascular
How many people in Europe and America are affected by IBD?
1.5 million people in America and 2.2 million in Europe
Particularly high in the northern hemisphere
But more recently studies in Asia and the Middle East have shown increasing incidence world wide
Who does IBD often affect?
Often young people
Lifelong chronic disease
What is the toll of IBD?
Burden of therapy for patients Hospitalisation Surgery Health-related quality of life Economic productivity Social functioning
What does IBD comprise?
Ulcerative Colitis
Crohn’s disease
What are the features of Ulcerative Colitis?
Inflammatory disorder limited to the colonic mucosa Superficial Continuous Always involves the rectum Only large bowel M = F NO granulomas
What are the features of Crohn’s disease?
Can affect any part of the gastrointestinal tract
Patchy chronic transmural granulomatous inflammation
Tendency to form fistula or strictures
Affects deeper structures
Small and Large bowel
F>M (1.5:1)
What is UC involving only the rectum?
Proctitis
What is UC involving the rectum and sigmoid?
Proctosigmoiditis
What is UC involving the rectum, sigmoid and descending?
Distal colitis
What is UC involving the rectum, sigmoid, descending and transverse?
Extensive Colitis
What is UC involving the whole large bowel?
Pancolitis
What are the symptoms of Colitis?
Bleeding
Mucus
Urgency
Diarrhoea
What are the perianal symptoms of perianal disease? (Crohn’s)
Anal pain
Leakage
Difficulty passing stool
What are the symptoms of small bowel disease?
Abdominal pain Weight loss Tiredness/lethargy (Caused by reduces absorption) Diarrhoea Abdominal mass
What are the 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 causes IBD?
In genetically susceptible patients
They respond inappropriately to git microbiota
Imbalance between healthy and pathological microbiota
Causing inflammation
What are the three factors of IBD aetiology?
Luminal microbes (environmental factors)
Genetic susceptibility
Immune respnse
Using GWAs, which genes were found to be involved with IBD?
NOD2
HLA
ATG
Il23R
30+ genes now known
What are the environmental factors?
Poor diet results to alteration of the microbiota
What is dysbiosis?
Unhealthy gut microbiota
Who are less likely to have IBD?
Physically active
Those who have and appendectomies do not get UC
What worsens crohn’s disease?
Smoking
Diagnosed earlier
Worsens symptoms
Oddly protective of UC
What are the main management goals with IBD?
Induce clinical remission
Maintain clinical remission
Improve patient quality of life
What are the other management goals?
Heal mucosa
Decrease hospitalisation/ surgery & overall cost
Minimise disease and therapy related complications
What treatments are used for IBD?
Steroids
5 ASA
Immune suppressants
Azathioprine
Methotreaxate
Biologic therapy
Others –diet, FMT, antibiotics, probiotics, novel agents
How do steroids work?
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
Used short term and to induce healing in hospital settings
Significant side effects long term
Can be delivered IV, Orally or Rectally
How does 5 Amino-Salycylic-Acids work?
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 (perioxisome proliferator activated receptor-gamma)
Some immunosuppresive activity – inhibiting T cell proliferation, activation and differentiation
Impairs neutrophil chemotaxis and activation
Orally or rectal
What are the sides effects of 5 ASA?
Intolerance
Diarrhoea
Renal impairment
Headache
Malaise
Pancreatitis
Pneumonitis
What immunomodulator is used in IBD?
Azathioprine
How does Azathroprine work?
6-TG interferes with adenine and guanine ribonucleotide production.
Results in reduced number of B and T lymphocytes, immunoglobulins and interleukins.
Reduces inflammation via suppressing immune system
Another pathway potentially results in apoptosis of T cells
What are the side effects of Azathioprine?
Allergic reaction Infection Pancreatitis Bone marrow surpression GI gisturbances Hepatotoxicity
What is checked before giving immunosurpressants?
Thiopurine Methyltransferase (TPMT) Hep B/C HIV Chicken pox Vaccinations TB Frequent bloods on starting Maintenance bloods
How does methotrexate work?
Mechanism not clear
Interferes with DNA synthesis & cell reproduction
Increased adenosine levels (anti-inflammatory)
Increased apoptosis of peripheral T cells
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 biologic drugs are used?
Anti-TNFα – infliximab, adalimumab
Anti- α4β7 Vedolizumab
Anti-IL12/IL23 Ustekinumab
More and more on the way
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
Give examples of how biologics are used in hospital?
IV infliximab
in hospital – less frequent
Induction 0,2,6 weeks
Maintenance 8 weekly
s/c adalimumab (humira)
160/80/ 40mg EOW
At home – more frequent
s/c Golimumab
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
What combination therapy is used in IBD?
AZA/ 6MP and aTNF act synergistically
Combination is superior in inducing and maintaining response and remission
Reduces the rate of antibody formation
What other considerations can be made when managing 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
