University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

342

Pages:

4
Author:

Mariam A. A.

HORMONES AND ENZYMES OF THE PANCREAS Pancreas secretes: • CCK/Secretin • Bicarbonate secretion • Enzyme release via zymogen granules to digest food Pancreatic proteolytic enzymes • • • Trypsinogen requires enterokinase from SI brush boarder to become trypsin, which can then catalyse the formation of digestive enzymes Cathepsin B in the acinar cells can also activate trypsinogen, causing digestive pancreatic enzymes to be activated within the acini and cause cellular damage Trypsinogen autoactivates at pH 5 Pancreatitis • Acute, self-destructive disorder • Exocrine pancreas: Cathepsin B • Enzyme that belongs to a family of lysosomal cysteine proteases → plays important role in intracellular proteolysis • Upregulation is found in premalignant lesions and various pathological conditions Colocalisation theory • To activate trypsinogen, lysosomal enzymes and digestive enzyme zymogens must be brought together with an increase in cytosolic Ca caused by a stimulus. Hence, acinar autophagy is a normal process gone wrong • Phagopores wrongly digest zymogen granules → activates trypsinogen → acinar cell injury → pancreatitis Autophagy (self-digestion) in acinar cells • ZG: zymogen granule • PG: phagopore • AP: autophagosom • AM: amphisome • AL: autolysosome • ER: endoplasmic reticulum Autophagy and pancreatitis • Defective function of lysosomes → impaired autophagy → pancreatitis • Unknowns: o Do autophagosomes normally play a protective role and degrade activated pancreatic enzymes to prevent acute pancreatitis? Thus is the process faulty in acute pancreatitis? o Can stimulating (toxic) factors induce autophagy resulting in activation of trypsinogen to trypsin within the autolyosome? • Injecting mice with cerulein: o Mouse with autophagy gene developed pancreatic damage from pancreatitis o Mouse lacking gene for autophagy maintained a normal pancreas Clinical presentation • Chronic pancreatitis o Epigastric pain o Nausea o Vomiting o Reduced endocrine function of pancreas o Reduced exocrine function o Diabetes o Malabsorption Regulation of trypsin