Question 6

Outline the physiology of pancreatic secretion (80% of marks) and outline the pharmacology of octreotide (20% of marks).

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College Answer

An outline of exocrine function should have included the sources of secretions, secretions involved in the digestion of proteins, carbohydrates and fats, the roles of trypsin inhibitors and  bicarbonate secretion and the regulation of enzyme and bicarbonate secretion.” Knowledge of endocrine physiology was good whereas the depth of knowledge regarding exocrine function was generally shallow with many errors. Only some general facts around the pharmacology of octreotide were required to pass this section of the question. Responses revealed limited knowledge and contained many errors

Discussion

The physiology of pancreatic secretion is a tough chunk of endocrine lore to parse, to say nothing of the tasks of summarising "some general facts around the pharmacology of octreotide" in fifty words (as that's the most you can be expected to write in two minutes, which is what you have for a 20% SAQ fraction). What are "some general facts", anyway, i.e of the many possible facts which are general, and which would the examiners have valued more than others? Would it have been valuable to squander those two minutes describing its molecular weight, amino acid structure or receptor families?  In short, this SAQ asks more than can possibly be scribbled in the time provided, and it is rather surprising that 38% of the candidates scored a pass (one wonders which of their carpal bones they cracked). Still, let's have a go at a model answer:

Physiology of pancreatic secretion:

  • Exocrine:
    • Pancreatic acini and ducts produce 2500ml/day of ​​​alkaline fluid (pH 8.0)
    • 20-25% during cephalic phase, 10% during gastric, 60-80% during intestinal
    • Rich in enzymes (amylase, lipase, trypsin, elastase, nucleases) and proenzymes activated by duodenal pH
    • Digestive role includes breakdown of fat and protein molecules into small peptides and fatty acids (easier to absorb by diffusion and active transport)
    • Alkalinity and enzyme content increases in proportion to the rate of flow
    • Flow rate increased by cholecystokinin, vagovagal  reflex, secretin
    • Flow rate decreased by sympathetic stimulation, somatostatin, octreotide
  • Endocrine:
    • Islets of Langerhans produce insulin (β-cells), glucagon (α-cells), somatostatin (δ-cells) and secrete them into the portal circulation
    • Insulin is released in response to hyperglycaemia 
    • Glucagon is released in response to hypoglycaemia 
    • Both are also regulated by the autonomic nervous system
    • Each is involved in the control of blood glucose delivery by adjusting the rate of glycogenolysis in the liver and the rate of glucose uptake by insulin-sensitive cells.

Pharmacology of octreotide:

  • Somatostatin analogue , cyclic peptide with long half life (90 min), given as infusion
  • Inhibits endocrine and exocrine secretion (of the gastrointestinal tract, and more generally, eg. pituitary hormone release is also inhibited)
  • Decreased splanchnic blood flow and therefore portal pressure

References

Cade, Jennifer E., and James Hanison. "The pancreas." Anaesthesia & Intensive Care Medicine 18.10 (2017): 527-531.

Owyang, Chung, and John A. Williams. "Pancreatic secretion." Yamada's Textbook of Gastroenterology (2015): 450-473.

Susan, Bonner-Weir. "Endocrine pancreas." (2004): 675-680.

Lamberts, Steven WJ, et al. "Octreotide." New England Journal of Medicine 334.4 (1996): 246-254.