Gastrointestinal Anatomy and Physiology Underpinning Pathology and Therapeutics 3 Flashcards
How does the GI function depend on motility to maintain flow (4)
- Functional compartments are typically separated by sphincters
- Motility facilitates mixing to promote digestion/absorption
- Nerve-muscle activity is required for the voiding of waste or the expulsion of irritants.
- DISORDER: IBS and IBDs (CD & UC) both involve Motility disorder & Malabsorption
How is movement in the gut achieved (3)
- Coordinated movements of the gut are required to mix and propel chyme.
- Complex patterns of contraction and relaxation are generated by nerves & smooth muscles:
- Basic propulsive movement is peristalsis – waves of contraction - e.g. oesophagus
How is movement achieved in the GI sphincter (2)
- Relaxation of a sphincter enables bolus transit to next compartment - eg Lower oesophageal sphincter (LOS)
- allowing entry to the stomach (fundus).
How is movement achieved in the small intestine (2)
- Small intestine (SI) also undergoes segmentation – sections of small bowel contract to mix chyme.
- SI undergoes ~11 contractions per minute; which promotes availability for absorption.
How is movement achieved in the large intestine (3)
- Large intestine (LI) undergoes mass movement that fills rectum; rectal distention stimulates the defecation reflex –
- this involves involuntary relaxing of internal anal sphincter & peristalsis
- if voluntary control of the external anal sphincter permits; Assistance by abdominal straining (Valsalva) risks haemorrhoid injury and CV stress.
What are the GI movement muscles (3)
- Circular - common throughout
- Longitudinal - common throughout
- Oblique: - Unique to stomach-churning, vigorous mixing liquefies meal
what are the consequences of irregular gut motility (4)
- A homeostatic system exists for controlling gut motility.
- Decreased motility can result in constipation: Failure to shift faecal bolus can result in the hardening of stool through increased fluid extraction, making it harder/injurious to pass.
- An increased motility (through response to stress or infection) will promote diarrhoea; accompanied by malabsorption from insufficient time to absorb nutrients & water.
- Nutrient loss & watery stools leads to dehydration and electrolyte imbalance (potassium loss) particularly serious in infants, the frail and elderly.
What is the definition of intestinal motility disorder (2)
- Inability to coordinate muscular activity
- GI Spasms or Paralysis
What are the signs/symptoms of intestinal motility disorder (7)
- Abdominal distension (abdomen isabnormally swollen outward)
- Recurrent obstruction
- Severe abdominal colicky pain
- Severe constipation
- faecal incontinence (diarrhoea)
- Gastroesophageal reflux disease (GORD)
- Intractable, recurrent vomiting
What are the consequences of intestinal motility disorder (acute & chronic) (2)
- Acute: The colon may become massively dilated; if not decompressed, the patient risks perforation, peritonitis, and death.
- Chronic: Nutritional disorder; Debilitation.
What are worst prognosis of intestinal motility disorder (3)
- Acute intestinal pseudo-obstruction (Ogilvie syndrome; colonic)
- Chronic intestinal pseudo-obstruction
- Hirschsprung’s disease (congenital aganglionic megacolon)
What are the defining criteria of acute intestinal pseudo-obstruction (3)
- the absence of barium radiographic evidence of obstruction
- therefore, assigned to neuromuscular cause
- one hypothesis = high SNS low PsNS activities
What is Hirschsprung’s disease (congenital aganglionic megacolon)
Nerves of myenteric (Auerbach plexus) and submucosal (Meissner plexus) fail to develop from migrating neural crest
What are the better prognosis of intestinal motility disorder (3)
- Irritable bowel syndrome (IBS), “spastic colon”; with constipation or diarrhoea or alternating (IBS-C, IBS-D, IBS-A)
- Fecal incontinence
- Constipation
What is the epidemiology (association) of intestinal motility disorders (7)
- Worldwide, 30-45% of all GI conditions can be termed intestinal motility disorders.
- Broadly affects any age group, but specific for the type of intestinal motility disorder:
- IBS occurs more frequently in people aged 20-40 years
- Intestinal pseudo-obstruction may occur in either newborns or elderly patients.
- Most patients are female
- female-to-male ratio of 2.8:1.
- Primary intestinal motility disorders are most common in white persons and are usually thought to be related to diet.
How are intestinal motility disorders prevented (8)
- A healthy lifestyle (diet and activity) is preventative of intestinal motility disorders.
- Mild physical exercise may be useful for symptom relief in patients with irritable bowel syndrome or constipation.
- Diets rich in fibre, especially insoluble fibres may prevent constipation and impaction, its more severe complication.
- Diets rich in fibre are also helpful in weight control, preventing diseases related to obesity (eg, cardiovascular and endocrine).
- Avoid drugs that interfere with gastrointestinal motility: Laxatives, diuretics, benzodiazepines
- anticholinergic drugs should only be administered if benefits are clear, and only for a limited time.
- Patients older than 50 years should be scheduled forcolonoscopy, even if not symptomatic.
- Patient history of abdominal surgery or radiotherapy of the abdomen or pelvis should be monitored for bowel habit disorders.
What are the pharmacological drug categories used in the management of intestinal motility disorders (constipation/diarrhoea) (4)
- Cholinergic agonists (direct cholinergic actions)
- Prokinetic agents (Parasympathomimetics: cholinergic & serotonergic)
- Opioid antagonists
- Antidiarrheals and Antibiotics
What agents are used for the treatment of gut motility disorders (5)
- Neostigmine (indirect cholinergic agonist)
- Bethanechol (M-R cholinergic agonist; esterase resistant)
- Cisapride (Serotonergic agonist promoting cholinergic GI release; indirect parasympathomimetic ) Risks arrhythmia WITHDRAWN
- Metoclopramide (DA-R antagonist; M-R & 5HT4R agonist) & Domperidone
- Loperamide (opioid R-antagonist; brand name imodium; to treat diarrhoea; a side effect of constipation)
What is nausea and vomiting (emesis) (4)
- Nausea is the feeling that one might readily vomit
- (synonyms: gag; heave; retch; regurgitate, others)
- N & V can also be a response to pain or stress; conditioned (smell or taste) and other repulsive sensory or psychological stimuli.
- Two brain nuclei in the medulla integrate stimuli/drive emesis
What are the causes suggesting alternative N&V mechanisms (11)
- Food poisoning: GI infections (viral or bacterial)
- Intoxication – alcohol
- Medicinal drug-induced (anti-cancer); SSRI; NSAID
- Renal failure (uraemia)
- Motion sickness (discordant visual & vestibular sensation)
- Vestibular disorder (Meniere’s disease)
- Migraine
- Pregnancy
- Peptic ulceration; Gallstones
- Myocardial infarction, MI
- Head trauma
What is the emetic reflex (5)
- Involuntary control of abdominal muscles
- Squeeze stomach/duodenum
- Relax oesophagus
- Food moves upwards (reflux - “flow in opposite direction”)
- Adaptive defence against food poisoning
What is the physiology of vomiting - Neurological basis (3)
- Neuromuscular reflex to void stomach (and duodenum)
- “Vomiting Centre” of CNS = Reticular formation of medulla oblongata
- Predominantly M, 5HT3 & DA2 Rs (also H1)
What is the drugs/toxins causing N&V pharmacological intervention (4)
- Visceral afferents - 5HT3-R
- Chemoreceptor trigger zone - D2 + 5HT3 + Opoid
- Vomiting centre
- Abdominal muscle/stomach/pharynx
What is the motion/balance causing N&V pharmacological intervention (5)
- labyrinth
- vestibular nuclei - H1 + M-R
- Chemoreceptor trigger zone - D2 + 5HT3 + Opioid
- Vomiting centre
- Abdominal muscle/stomach/pharynx
What is the cortical sensations causing N&V pharmacological intervention (3)
- Medulla
- Vomiting centre
- Abdominal muscle/stomach/pharynx
What is the irritation to the stomach/pharynx causing N&V pharmacological interventions (4)
- Visceral afferents - 5HT3-R
- Nucleus Tractus Solitarius (NTS) - H1 + M-R
- Vomiting centre
- Abdominal muscle/stomach/pharynx
How is the chemoreceptor trigger zone stimulated in Chemically–induced nausea (4)
- in the medulla but outside BBB, permeable to circulating substances, toxins eg chemotherapy: cisplatin/digitalis)
- stimulate vomiting centre via 2 kinds of R:
- DA 2 - Haloperidol (Haldol) & Domperidone (Motilium); suppository formulations useful if too sick to swallow
- 5HT 3 - Ondansetron; 5HT3 R antagonist Anti-emetic
How is the vomiting centre (Vestibular nucleus) stimulated in motion sickness (3)
- via 2 kinds of R:
- M Rs Anti-muscarinic hyoscine (UK) / scopolamine (US)
- Histamine 1 Rs Promethazine
How is the vomiting centre - Higher centres stimulated (2)
- Afferents of cortical sensations: pain, foul smell, repulsive sight (blood)
- even memory stimulates vomiting centre
How is the vomiting centre - Sensory Vagal afferents from gut stimulated (2)
- includes Uvula; oesophagus, stomach
- stimulate vomiting centre.
What are anti-emetic therapeutics (5)
- Histamine H1 receptor antagonists - eg Promethazine; Older drugs include appreciable anti-muscarinic action, which is the basis of their anti-emetic action.
- Anti-muscarinic agents - eg Hyoscine; Antiemetic; also reduce gastrointestinal motility; other muscarinic effects limit use.
- Dopamine receptor antagonists - eg Domperidone (anti-emetic also prokinetic); some have unwanted Parkinsonism; Also metoclopramide (5HT3-R antagonist); Acts in CrTZone
- 5HT-R antagonists - eg Ondansetron (also metoclopramide); Particularly effective against anti-cancer drugs that may elicit 5HT in the gut
- OTHERS - Steroids (Dexamethasone); Cannabinoid antagonists (Nabilone, via CrTZone)
