Lower GI Disorders Flashcards
Which artery supplies the proximal colon?
Superior mesenteric artery
Which artery supplies the distal colon?
Inferior mesenteric artery
Which venous vessels drain the colon?
Inferior and superior mesenteric veins draining into the portal vein
What structures reside within the submucosal space?
Submucosal glands and Meissner’s plexus
Which molecule is secreted by the submucosal glands, lubricating the mucosal surface?
Mucin
Between which two layers does the myenteric plexus reside?
Intermediate between the circular and longitudinal muscles within the muscularis layer
Where are the myenteric plexus ganglia located in relation to the taenia coli?
Concentrated deep to the taenia coli
Which nerve provides the parasympathetic supply to the ascending and proximal transverse colon?
Vagus nerve
Which nerves provides parasympathetic supply to the distal transverse and descending colon?
Pelvic nerves
What is the sympathetic supply of the colon?
Pre-ganglionic fibres arise from the thoracolumbar spinal cord
Which nerve controls the external anal sphincter?
Pudenal nerves
What are the nerve roots of the pudenal nerves?
S1-S3
What is Hirschprung;s disease?
Characterised by a congenial absence of myenteric and Meissner’s ganglion.
• Peristalsis is impaired due to unstimulated muscular contractions within the muscularis layer.
• Obstruction Constipation.
• There is an absence of propulsive peristalsis and mass contraction in the aganglionic segment.
What are the inflammatory causes of lower GI tract disorders?
IBD and microscopic colitis
What are the infective causes of lower GI tract disorders?
C. difficile
E. coli
What are the structural causes of lower GI tract disorders?
Diverticular disease
Haemorrhoids
Fissures
What are the functional causes of lower GI tract diosrders?
IBS
What are the neoplastic causes of lower GI tract disorders?
Colonic polyps
Colon cancer
What are the two causes of IBD?
Ulcerative colitis
Crohn’s disease
What is ulcerative colitis?
Inflammatory disorder characterised by diffuse inflammation of colonic superficial mucosa.
No granulomas
Extends continuously and proximally from the rectum
Which GI organ is always concerned with ulcerative colitis?
Rectum
What is proctitis?
Inflammation of the rectum
What is pancolitis?
Inflammation of the entire colon
What term describes ulcerative colitis of the rectum and sigmoid colon?
Proctosigmoiditis
What is distal colitis?
Diffuse continuous inflammation from the rectum to the ascending colon
What are the symptoms concerned with ulcerative colitis?
Patients present with severe and frequent rectal bleeding, diarrhoea, and blood in stool (detected on digital rectal examination)
What is Crohn’s disease?
Characterised by transmural inflammation of the gastrointestinal tract, predominantly in the terminal ileum and perianal locations
Skip lesions
inflammation can penetrate through the serosa, giving rise to perforations and fistulae
Inflammatory infiltrate initially begins around intestinal crypts, developing into ulcerations of the superficial mucosa.
• Inflammation progresses to involve non-caseating granulomas (all layers of the intestinal wall and the mesentery are affected).
• Granulomatous inflammation is characteristic of CD.
• Strictures are narrowing of the bowel due to inflammation.
N.B: Involvement of the terminal ileum will disrupt bile acid absorption Steatorrhea and fat-soluble vitamin deficiency.
Which areas of the GI tract does Crohn’s disease predominantly affect?
Terminal ileum and perianal locations
What are the characteristic features of Crohn’s disease?
Skip lesions Fistulae Transmural inflammation Strictures Non-caseating granulomas
What is a fistula?
Inflammation can penetrate through the serosa giving rise to perforation and fistulae
What type of granulomas form in Crohn’s disease?
Non-caseating granulomas
What is a stricture?
Narrowing of the bowel due to inflammation
What are the side effects concerned with Crohn’s disease of the terminal ileum?
Disrupts bile reabsorption, manifesting as steatorrhea
Which gender is most likely to be affected by Crohn’s disease?
Females (1.5:1)
What are the symptoms of Crohn’s disease?
- Abdominal pain (Right lower quadrant and peri-umbilical regions common – ileitis).
- Prolonged diarrhoea
- Perianal lesions (skin tags, fistulae, abscesses, scarring or sinuses)
- Bowel obstruction – strictures Manifests as bloating, vomiting and constipation.
- Fever
- Abdominal tenderness
What are the symptoms concerned with colitis?
- Bleeding
- Mucus
- Urgency- hallmark of lower-rectal disorder due to sensory changes. Urgency occurs when the arrival faeces in the rectum causes strong contractions and precipitate anal relaxation.
- Diarrhoea
What is urgency?
occurs when the arrival of faeces in rectum results in strong contractions and precipitate anal relaxation
What are the symptoms of perianal inflammation?
- Anal pain
- Leakage
- Crohn’s disease is fistulating and associated with deep ulcerations.
What are the symptoms associated with small bowel disease?
- Abdominal pain
- Weight loss (Inadequate absorption Anaemic).
- Tiredness/lethargy
- Diarrhoea
- Abdominal mass
What extra-intestinal manifestations are linked with IBD?
Arthritis
• Axial- Ankylosing spondylitis
• Peripheral
Skin
• Erythema nodosum
• Pyoderma gangrenosum
Eyes
• Anterior uveitis
• Episcleritis/iritis
Liver
• Primary sclerosing cholangitis (PSC) – Inflammation and scarring of the bile ducts.
• Autoimmune hepatitis
Which genes lead to a genetic predisposition of IBD?
NOD2
HLA
ATG
IL23-R
Which specific auto-antibodies are concerned with Crohn’s disease?
ASCA
Which specific auto-antibodies are associated with ulcerative colitis?
pANCA
Which bacteria has a possible relationship with IBD?
Mycobacterium paratuberculosis
What is dysbiosis?
: In Crohn’s disease there is dysbiosis, as the gut microbiota is disrupted – lipopolysaccharides enter into systemic circulation.
• Loss of peripheral tolerance.
What are the three management strategies for the treatment of IBD?
- Induce clinical remission
- Maintain clinical remission Decrease hospitalisation/surgery & overall cost.
- Improve quality of life.
What is the first line of treatment for IBD?
Short-acting steroids (as a bridge to other interventions + used in acute unwell patients).
How do steroids work in IBD?
Diffuse into the nucleus, and bind onto glucocorticoid responsive elements (GRE)
GRE interacts with specific DNA sequences
Increase expression anti-inflammatory gene products
Block pro-infammatory genes
Which immunmodulators are used in the treatment of IBD?
Azathioprine
Methotrexate and folic acid
What is the mechanism of immunomodulators?
Immunomodulators help induce remission in active CD, downregulating DNA & RNA synthesis (causing cell proliferation to arrest).
What is the mechanism of action of Azathioprine?
6-TGN interferes with adenine and guanine ribonucleotide production, inhibiting DNA synthesis within B- and T-lymphocytes (apoptosis of WBCs)
Decreased Ig and IL production
Which ribonucleotides are affected by 6-TGN in azathioprine?
Adenine and guanine
What type of drug is azathioprine?
Prodrug (That is activated into TGNs)
What is the active metabolite of azathioprine?
6-TGN
Which enzyme inactivates TGNs?
Thiopurine methyltransferase (TPMT)
What is the risk in individuals with reduced activity of TPMT?
Thus, individuals with reduced activity of TMPT are exposed to higher levels of thioguanine – high risk of toxicity (including myelosuppression).
-Reduce dose in those with low TPMT.
What are the side effects associated with azathioprine?
- Bone marrow suppression
- Lymphoma
- Pancreatitis
- Infection
- Nodular regenerative hyperplasia/hepatotoxicity
- GI-disturbances
- Allergic reaction: Fever, rash, arthralgias, myalgias, fatigue.
What is the mechanism of action of methotrexate?
Interferes with DNA synthesis and reproduction
- Increased adenosine levels (anti-inflammatory)
- Increased apoptosis of peripheral T cells
What are the side effects associated with methotrexate?
• Rash • Nausea, mucositis, diarrhoea • Bone marrow suppression • Hypersensitivity pneumonitis • Increased liver enzymes • Hepatic fibrosis/cirrhosis • Abortifacient N.B: There is no documented increased risk of lymphoma or skin cancer.
What is the mechanism of 5 ASA?
• Inhibition of lipo-oxygenase pathway (Prostaglandin and leukotrienes).
• Inhibition of pro-inflammatory cytokines (IL-1 and TNF-alpha).
• Scavenging of free radicals
• Inhibition of NF-kB/TLR via PPAR-gamma induction (peroxisome proliferator activated receptor-gamma).
N.B: Expresses immunosuppressive activity through inhibiting T-cell proliferation and differentiation. In addition to impairing neutrophil chemotaxis and activation.
Which pro-inflammatory cytokines are inhibited by 5 ASA?
IL-1 and TNF-alpha
Which pathway is inhibited by 5 ASA?
• Inhibition of lipo-oxygenase pathway (Prostaglandin and leukotrienes).
How is 5 ASA delivered?
Mode of delivery: Orally & Rectal
What are the side effects with using 5 ASA?
- Diarrhoea
- Renal impairment
- Headache
- Malaise
- Pancreatitis
- Pneumonitis
- Intolerance
How do biologics work?
Anti TNF-alpha
Infliximab and adalimumab
What is infliximab?
A biologic - anti-TNF alpha
How is Infliximab administered?
IV infliximab 8 weekly maintenance, induction 0,2,6 weeks, in hospital – less frequent.
What is the effect of TNF-alpha on macrophages?
Increased release of pro-inflammatory cytokines and chemokines
What is the effect of TNF-alpha on the endothelium?
Increased expression of adhesion molecules (increased cell infiltration)
What is the effect of TNF-alpha on fibroblasts?
Increased acute phase response and metalloproteinase synthesis
Decreased collagen production (Tissue remodelling)
Increased CRP in serum
What is the effect of TNF-alpha on the epithelium?
Increased ion transport
Increased permeability
This compromises barrier function
What are the side effects with using biologics in IBD?
vSide effects: • Opportunistic infections • Infusion or site reactions • Infusion reactions • Neutropenia • Infections • Demyelinating disease • Heart failure (HF) • Cutaneous reactions, including psoriasis • Malignancy • Induction of autoimmunity
Which two drugs are used as a combination therapy in the treatment of IBD?
AZA/6MP and an anti-TNFA work synergistically, thus combination therapy improves patient outcomes and recovery.
• Reduces the rate of antibody formation.
