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4-Dig

Guidelines

Teaching 17 Sep 2009 Wythenshawe Hospital

Gut Brain Axis

  • Peter Paine (Hope)
  • Narcotic Bowel Syndrome (NBS)
  • Opioid induced hyperalgesia (OIH) eg allodynia
  • Treatment for chronic pain
    • Nortriptyline eg 50->150 on (better than Amitriptyline)
    • SSRI: Duloxetine, Venlafaxine
    • Clonidine (Sympatholytic)
    • Lorazepam
    • Hyoscine
    • Cathartics: polyethylene glycol
    • CBT
    • Alvimopan (SR naloxone)
    • [Pregabalin > Gabapentin]
  • early involvement of pain team
  • psychiatrist guided opioid withdrawal
  • Bloating: FODMAPs; consider probiotics
  • colonoscopy: 1:1000 perforation

Appetite and satiety

  • John McLaughlin (Hope)
  • enteroendocrine cells -> vagus -> brain: hypothalamus
  • hypothalamus: also effects of leptin, ghrelin, insulin, ...
  • enteroendocrine cells <- {chemical | microbial | physical} stimuli
  • stomach: leptin, ghrelin, orexin
  • upper small intestine: CCK, amandramide
  • ileum + colon: GLP-1/-2, PYY
  • eg: CCK: icrs satiety and delays gastric emptying
  • CCK: only stimulated by fatty acids > C12 (ie only those that need bile acids for uptake; and solid at body temperature, compared to C11 or below [eg dairy products, coconut])
  • nutrient-sensing receptors: bitter/sweet, fatty acid receptors (GPR40, GPR41, ...)
  • C12 (compared to C10) icrs satiety and experimentally dcrs tolerance to water load (b/o delayed gastric emptying): therefore: "fatty starter"!
  • hyperphagia:
    • usu hedonistic + obesogenic environment;
    • rarely leptin deficiency, MC4R mutations, Prader-Willi syndrome, hypothal tu
    • bulimia
  • anorexia: ..., alcohol abuse, ..., disinterest/depression
    • palliative Tx: corticosteroids, megestrol, in development: s.c. Ghrelin analogues (i.e. "orexogenic")
  • Nutrition: macronutrients, micronutrients, weight
  • bariatric surgery: 'ileal brake': nutrients usu don't get there, but if they do, then icrd secretion of GLP-1, PYY, which stop transit, stop eating

Diabetic Gastroenteropathy (DGE)

  • Piyara Begum (Res Fellow, Hope)
  • DGE
    • oesophageal dysmotility
    • diabetic gastroparesis
    • small intestinal dysfx
    • colonic abnlties
  • Diabetic autonomic neuropathy (DAN)
    • 20-40% (50-60% if >25y duration)
    • Argyll-Robertson pupil
  • vagotomy: gastroparesis
  • Corneal Confocal Microscopy: CCM (small C-fibres): dcrd nerve fibre density, dcrd nerve branch density, dcrd nerve fibre length = reproducible
  • COMPASS=Composite Autonomic Symptoms Scale
  • CASS = score from autonomic fx tests
  • mechanisms of DAN
    • axonal damage
    • microvascular damage
    • autoimmune neuropathy; ...
  • gastric interstitial pacemaker cells of Cajal (ICC)
  • Syndromes
    • Dysphagia: NB: treat candida (trush, odynophagia, ...)
    • N&V: NB: treat H pylori if present
      • often on endoscopy: food residue (but NB: 30-50% diabetics have delayed gastric emptying, not necessarily with symptoms!)
      • delayed/rapid emptying (see Camilleri'07NEJM:356)
      • no trial evidence for Tx: small, frequent, liquid meals; rarely: post-pyloric feed
      • Metoclopramide, Domperidone, Erythromycin (but tachyphylaxis); +- pregabalin, 5HT3; no benefit from botox into sphincter
      • in development: Motilin, Ghrelin receptor agonists

Obesity

  • Dr John New (Hope)
  • OSA:
    • Epworth Sleepiness Scale
    • prevalence: ~50% if BMI>40;
    • mort x2.7
  • Diet vs Exercise: 1kg fat = 7500kcal
    • =13 hamburgers
    • =50 pints
    • =130km run (if 70kg), =90km run (if 100kg)
  • Orlistat/Sibutramine:
    • unlikely to succeeed if no wt loss in 4 wks
    • helps dieting (cf nicotine replacement)
  • Orlistat
    • best dietetic result (in that trial): -5kg in 12mth
    • combined with Orlistat: -10kg in 12mths
    • XENDOS trial: dcr obesity->dcrd DM; NB: lose 2kg (-5.7kg vs -3.6kg) dcrs DM incidence by 1/3!!
    • 6.2% wt loss->-0.5% HbA1c; 5-10% wt loss->-0.95% HbA1c; >10% wt loss->-1.53% HbA1c
  • Sibutramine:
    • icrs BP by 2mm, need to see GP q2wks initially
    • amphetamine derived: ie pt feels well
    • STORM trial
    • 600kcal deficit diet->-10% wt in 6/12
    • Salford: max 800kcal + multivit diet, daily wt, then 1200kcal and icr until wt maintained
  • best medical success: ~20%
  • bariatric surgery:
    • £7-9k
    • NICE:
      • first line if BMI>50
      • also after other interventions for BMI>40, or BMI>35 + complications
      • usu 18y+ age
    • wt loss and mortality
      • bypass: -35% wt [but maybe 70% fat mass!], mort 1:200
      • band: -20%, mort 1:2000
      • may need cor. angio and PCI beforehand
    • stomach volume: 800ml->50ml
    • "physical [as opposed to cognitive] behavioural therapy"
    • SE:
      • steatorrhoea with fat
      • dumping with CHO
      • saggy skin
    • SOS=Swedish Obesity Study NEJM'07: mort at 15yr: 12% vs 9%, dcrs DM, Htn,

NAFLD

  • Dr Das (Stepping Hill)
  • prevalence ~1/3 #?
  • 80-90% benign outcome
  • decompensated cirrhosis from NAFLD: poor survival:
    • similar to those with decompensated ALD and continued to drink: ~5% at 2yr 
    • whereas ALD and stopped drinking: ~60% at 2yr
  • AST>2xULN: SMR=1.78, ALT>2xULN: SMR=1.51
  • NAFLD: icrd use of FFA as myocyte energy -> effects on heart, etc; therefore a/w CHD
  • "fast food hepatotoxicity": effect of high energy density food