Session 6 Intestines and IBD

• Glucose enters mucosal cells via Na /glucose transporter: SGLT1
• Glucose leaves cell to ECF by facilitated diffusion via the Glucose transporter 2: GLUT2 transporter.
• Oral rehydration?

  • Uptake of Na + generates osmotic gradient.
  • Water follows.
  • Glucose uptake stimulates Na + uptake & generates its own osmotic gradient.
  • So, a mixture of glucose and salt will stimulate maximum water uptake - Oral rehydration salts/fluid
• Uptake of lipids

  1. Pancreatic lipase results in the production of monoglycerides and free fatty acids (FFAs) from triglycerides (TGs)

  2. This aggregate (with bile salts and phospholipids) to form micelles (suspension- non-polar)

  3. Micelle 'enters' the brush border and contents diffuse passively into the enterocytes

  4. The bile salts remain outside – join the enterohepatic circulation (EHC) from the distal ileum

  5. Inside enterocytes triglycerides (TGs) are reformed in the SER

  6. TGs aggregate to form chylomicrons which leave via exocytosis and into villi and then into the venous circulation
• Micelle


  Suspension of non-polar substances, also contains cholesterol and fat-soluble vitamins
• Potassium (K) is absorbed by passive diffusion via a concentration gradient set up by water absorption.
• Process of pumping out calcium requires Vitamin D stimulated by parathyroid hormone.
• • Vitamin C and ferric oxidoreductase in the brush border reduce Fe 3+ to Fe 2+
  • Fe 2+ is taken up via the DMT1 transporter.
• Stomach secretes gastroferrin - Solubises Fe
• • Chronic alcohol consumption can lead to poor uptake of vitamin B 1 (thiamine)
  • Lack of vitamin B 12 leads to macrocytic anaemia.
• Vitamin B12 absorbed with a co-factor only occurs in the terminal ileum - Intrinsic factor.
• Peristalsis - propulsion of luminal contents towards the anus.
• Segmentation - mixing and exposure to absorptive surfaces.
• Intestinal pacemakers?

  • Located at intervals along length of small intestine.
  • Frequency highest at stomach end - The ‘intestinal gradient’.
  • Causing intermittent contraction of smooth muscle along length - Dividing section into segments
• Two elements to large intestinal motility - Haustral shuttling and Mass movement
• Motility - mass movement - often triggered by eating - (gastro-colic reflex).
• Opioid drugs decrease mass movements.
• causes of bowel inflammation?

  • Infection – e.g. C Difficile, Campylobacter, Salmonella, E Coli.
  • Neoplasia – colorectal cancer.
  • Vascular – ischaemic colitis.
  • Inflammatory – e.g. Inflammatory bowel disease (Crohn’s & UC)
  • Trauma
  • Endocrine
  • Drugs – microscopic colitis from PPIs, NSAIDs
  • Metabolic
  • Degenerative
• Types of Colitis?

  • IBD - Ulcerative Colitis, Crohn’s Disease
  • Microscopic Colitis - Lymphocytic Colitis, Collagenous Colitis
  • Radiation Colitis - Develops 6 months to 5 years post regional radiotherapy.
  • Infectious Colitis - Viral, parasitic or bacterial infection, E Coli and Salmonella are common causes, C Difficile – often antibiotic induced
• Extra-intestinal Manifestations (EIMs) of IBD

  CLUECLUE

  In the limbs

  • C- Clubbing
  • L - Large joint arthritis
  • U - Ulcers (pyoderma gangrenosum)
  • E - Erythema nodosum
  • Outside the limbs
  • C - Cholangitis (primary sclerosing cholangitis)
  • L - Lower back arthritis
  • U - Ulcers (aphthous ulcers in mouth)
  • E - Eye signs e.g. acute uveitis
• Smoking is a risk factor for Crohn’s but protective in ulcerative colitis.
• Colonoscopy shows cobblestone appearance and skip lesions in crohn's disease.
• Pattern of disease in UC

  A) proctitis

  B) left-sided colitis

  C) pancolitis

  
• MRI Pelvis to assess known/ suspected peri-anal Crohn’s disease.
• Thumb printing - bowel wall inflammation.

  
• Lead-pipe colon = featureless colon due to loss of haustral folds in chronic UC.

  
• Backwash ileitis is a condition where the terminal ileum is inflamed due to the reflux of colonic material from the cecum. Seen in patients with UC.
• Can see p-ANCA autoantibodies in UC patients. (p-ANCA targets neutrophils - reduced immunity)
• Management of IBD?

  • Amino salicylates
  • Corticosteroids
  • Antibiotics
  • immunosuppressants
  • Biological Therapy
  • Surgery
  • Loperamide (with caution)
• Aminosalicylates or 5-ASA drugs e.g. Mesalazine/ Sulfasalazine?

  • act by activating a class of nuclear receptors involved in the control of inflammation, cell proliferation, apoptosis and metabolic function.
  • Side effects: Renal impairment; diarrhoea; hepatitis.
  • NOTE: Avoid in aspirin allergy
• Corticosteroids- e.g. Prednisolone, Budesonide?

  • Potent anti-inflammatories through transcription modulation of genes involved in inflammation.
  • Side effects: Significant so ideally not used long term - Weight gain, hypertension, glucose impairment, osteoporosis, adrenal suppression, mood disturbance.
• Antibiotics for IBD?

  • Treatment of septic complications and can reduce perianal fistula symptoms.
  • May have an immunomodulating effect.
  • Modest benefit in colonic CD - Metronidazole +/- Ciprofloxacin.
  • Some scanty evidence of possible benefit of rifaximin and clarithromycin.
• Immunosuppressants or DMARDs: Thiopurines-Azathioprine/Mercaptopurine/ Methotrexate?

  • Used as steroid-sparing agents to maintain remission.
  • Pre-Screening checks prior to IMM and or Biological Therapy -HIV, HBV, HCV, TB, Varicella and CXR (if TB result is positive), Vaccination History- live vaccines & childhood illnesses.
  • Side effects: Hepatoxic, Bone marrow toxicity
  • Require blood monitoring FBC, LFTs
• Biological therapies 1- Anti -TNF Therapy- Infliximab & Adalimumab?

  • Infliximab and Adalimumab are monoclonal antibodies targeting tumour necrosis factor α (TNF-α). They block the interaction of TNF α with its receptors by binding to the TNF.
  • Side effects: - Opportunistic infections, Anaphylaxis, Require blood monitoring FBC, U&Es, LFTs and CRP.
• Biological therapies- 2- Ustekinumab?

  • Blocks interleukin IL-12 and IL-23 which activate certain T-cells.
  • Side effects: Dizziness, sore throat, arthralgia, headaches, nausea, soreness around injection site.
• Biological therapies- 3 - Vedolizumab

  • binds to ɑ4β7 integrin, a mediator of GI inflammation - decreasing inflammation in the GI tract by blocking the entry of inflammation- stimulating lymphocytes.
  • Side effects: nasopharyngitis, upper respiratory tract infections, arthralgia, headache, fatigue, pyrexia.
• Biological therapies- 4 – JAK Inhibitors e.g. Tofacitinib, Upadacitinib

  • Limit the action of Janus kinase enzymes.
  • Side effects: Avoid grapefruit juice as it may enhance the therapeutic effect and increase risk of side effects.
• Surgery?

  UC - Colectomy or proctocolectomy.

  Crohn’s Disease - Colectomy, Segmental resection, Stricturoplasty, Perianal abscess or fistulae.
• Complications of IBD?

  • Primary sclerosing cholangitis (PSC) - bile duct in the liver gets inflamed. (UC)
  • Colorectal cancer
  • Strictures in CD
  • Fistulae in CD
• Colonoscopy for IBD after diagnosis?

  • Colonoscopy surveillance as per NICE Guideline - initially 8 years from diagnosis/symptom onset and then 1, 3 and 5 yearly as per BSG risk stratification. (UC&CD - colorectal cancer)
  • Colonoscopy at diagnosis in PSC and then annually thereafter.