Question 8

College Answer

This question was best answered by using a classification system, or systematic approach to gastric emptying. Receptive relaxation (triggered by movement of food through the pharynx and oesophagus), vagally mediated relaxation of fundus and upper body of stomach, the  pyloric pump (being intense peristalsis in lower body of the stomach that results in stomach  emptying) and the pyloric sphincter(a circular muscle that allows water and fluids to easily pass through but restricts solids until it is mixed in chime to almost fluid consistency). Candidates were also expected to mention regulatory factors e.g. food volume through  myenteric reflexes / gastrin stimulatory motor effects and enhanced pyloric pump, acidity  and osmolality of chyme in duodenum, presence of breakdown products of protein and fat through enteric nervous system, sympathetic and parasympathetic nervous systems and hormones such as cholecystokinin, secretin and gastric inhibitory peptide.

Erythromycin is a commonly used prokinetic and some knowledge of effects was expected (e.g. the fact that it 
stimulates motilin receptors on GI smooth muscle and promote onset, frequency and duration of migrating motor complex, from stomach and spreading caudally thus increasing gastric emptying).

Discussion

Gastric emptying:

• Fasting state:
  • Migrating motor complexes sweep the stomach at regular intervals
  • These are slow peristaltic waves that originate in the fundus
  • Their role is to keep the stomach empty of secretions and food debris
  • They are interrupted by eating
• Fed state: 
  • Receptive relaxation: shortly following swallowing, the proximal stomach relaxes by a vagally mediated reflex
  • Tonic contraction:  the body of the stomach contracts, propelling food slowly towards the antrum
  • "Lag" phase with solid food: 
    • The antrum contracts forcefully against a tightly closed pylorus
    • This triturate the food until it is well mixed with gastric secretions and its particles are less than 1-2mm in size
    • During this phase, there is minimal passage of food into the duodenum
    • Depending on the food, this takes 30-90 minutes
  • Linear emptying phase with solid food: 
    • small food particles are pushed through the pyloric sphincter at a stable linear rate
    • Time to empty half of the meal = 30 minutes for relatively nutrient-poor solids, 60-120 minutes for especially fatty solids
  • Exponential emptying with liquids:
    • Liquids have no lag phase and begin emptying rapidly and immediately
    • Emptying rate is exponential and determined by the antral-duodenal pressure gradient, which is usually 5mmHg but which can increase to over 40 mmHg with peristalsis
    • 15-20 minutes is the half-time of non-nutritive fluids, eg. water

Regulation of gastric emptying:

• Factors that affect gastric emptying:
  • Position (fastest when upright or right lateral)
  • Consistency of the food (solids empty slower)
  • The volume of liquid (larger volume empties faster)
  • Gastric pH (acidic pH decreases the rate of emptying)
  • Tonicity of contents (decreases gastric emptying)
  • Lipid content (fatty meals slow gastric emptying)
  • Caloric content (high-calorie meals slow gastric emptying)
• Hormonal influences on gastric emptying:

  Hormones which:
  Enhance gastric empyting	Slow gastric emptying
  Ghrelin Motilin	Cholecystokinin Secretin Gastric inhibitory polypeptide Glucagon Glucagon-like peptides 1 and 2

Erythomycin:

• A prokinetic antibiotic used to promote gastrointestinal motility in critically ill patients

• Acts as a motilin receptor agonist and motilin release enhancer

• Increases the automaticity of enteric nervous system motor function

  Doses of 250mg (as low as 40mg) are effective, whereas the antimicrobial dose is 1g

  Main side effect is QT prolongation

Minami, Howard, and Richard W. Mccallum. "The physiology and pathophysiology of gastric emptying in humans." Gastroenterology 86.6 (1984): 1592-1610.

Hellström, Per M., Per Grybäck, and Hans Jacobsson. "The physiology of gastric emptying." Best Practice & Research Clinical Anaesthesiology 20.3 (2006): 397-407.

Mittal, Ravinder K., and Raj K. Goyal. "Sphincter mechanisms at the lower end of the esophagus." GI Motility online (2006).

Goyal, Raj K., Yanmei Guo, and Hiroshi Mashimo. "Advances in the physiology of gastric emptying." Neurogastroenterology & Motility 31.4 (2019): e13546.