Pancreas Flashcards
Why does a pancreas dissected out of a mouse have to be speedily placed into fluid which inactivates the enzymes?
The pancreas rapidly digests itself when removed.
What is the tail of the pancreas associated with, and what is the head of the pancreas associated with?
Tail = spleen Head = duodenum
What are the two divisions of the pancreas?
Exocrine (majority of pancreas) and endocrine (lighter staining)
What are the three parts of the exocrine pancreas?
Acinus
Intercalated duct - leads from acinus to striated duct
Striated duct - connects intercalated duct to intralobular duct
What is the function of the intercalated ducts of the exocrine pancreas?
To secrete bicarbonate which acts as a buffer to increase the pH so the enzymes in the duodenum can work.
What is the function of the exocrine pancreas?
To secrete bicarbonate, enzymes, zymogens, and this is controlled by CCK and secretin (which are stimulated by the parasympathetic vagus nerve).
Where is CCK secreted and what is its function in the exocrine pancreas?
Secreted by I cells in the duodenum in response to chyme. CCK helps digestion of fats, proteins and carbohydrates by acting on the cells of the acinus to stimulate secretion of digestive enzymes.
Where is secretin secreted, and what is its function in the exocrine pancreas?
Secreted by S cells in the duodenum. Secretin acts on the intercalated ductal cells to stimulate secretion of bicarbonate ions.
How does secretin cause the cells of the intercalated duct to secrete bicarbonate ions?
1) Secretin causes an increase in intracellular production of cAMP
2) The increase in cAMP activates K+ and Cl- channels to open
3) K+ diffuses down a concentration gradient out of the cell, which causes Cl- to diffuse out of the cell through CFTR down an electrical gradient
4) Carbon dioxide and water from carbonic acid in the cell which then dissociated to H+ and HCO3- ions
5) There is a concentration gradient fro Na+ into the cell, so the Na+/H+ exchanger pumps H+ out of the cell which causes HCO3- to accumulate inside the cell
6) The Cl-/HCO3- exchanger pumps HCO3- out of the cell and lets Cl- flow back in
Which organs are affected by cystic fibrosis?
Lungs, liver, pancreas, intestine
How does cystic fibrosis lead to the development of fibrotic scar tissue (fibrosis) in the pancreas, and why is this a problem?
The frameshift mutation in the CFTR gene leads to abnormal Na+ and Cl- transport across the membrane so that a thick sticky mucus is produced. This blocks the exocrine movement of digestive enzymes, and causes the enzymes to stay in the pancreas and rapidly begin to digest the pancreas itself. This is what causes fibrotic scar tissue to develop, and leaves the tissue non-functional.
What is the drug called that orally administers pancreatic enzymes (lipase, protease, amylase) in an enteric coating to aid digestion?
Pancreatin.
What are the five types of cells in the Islet of Langerhans, and what do they secrete?
1) Alpha cells - glucagon
2) Beta cells - insulin
3) Delta cells - somatostatin
4) Epsilon cells - ghrelin
5) Pancreatic polypeptide secreting cells - PP
Where in the Islet of Langerhans do you find alpha cells?
Around the periphery
Where in the Islet of Langerhans do you find beta cells?
In the middle, making up the majority of the islet
Where in the Islet of Langerhans do you find delta cells?
Sporadically throughout the islet
Where in the Islet of Langerhans do you find epsilon cells?
Sporadically on the periphery
Where does insulin go when it is released from beta cells?
It is pushed into the hepatic portal vein and goes to the liver, which is the prime target organ.
What are the two forms that insulin exists in?
1) Monomeric - active form, made up of an alpha chain and beta chain linked by disulphide bridges, easily transported through membranes but only a short half life (6 minutes)
2) Hexameric - storage form made up of six monomers around a central zinc atom linked by histidine bonds, long half life but slow diffusion rate
What are the three stages in insulin synthesis?
1) Preproinsulin formed, which is comprised of an alpha chain then connecting sequence then beta chain then signal peptide which targets polypeptide chain to rough endoplasmic reticulum.
2) Signal peptide cleaved to leave proinsulin. Proinsulin folds into a spiral and alpha and beta chain are linked by disulphide bridges.
3) Enteropeptidases in the Golgi body release the central C-peptide to leave insulin in its active form.
What level can be measured in the blood to detect how well someone’s body is synthesising insulin?
C-peptide
How is insulin secretion from a beta cell stimulated?
Glucose enters beta cell through Glut 2 channel. This allows ATP to be synthesised inside the cell.
ATP causes K+ channel to be blocked, so K+ does not leak out of cell and cell becomes depolarised.
Depolarisation activates the voltage-gated Ca2+ channels so Ca2+ diffuses into the cell.
Ca2+ influx stimulates constitutive secretion of the insulin granules.
What is the insulin receptor comprised of?
1) Two alpha subunits which are extracellular (sit on the cell membrane) and are bound together by disulphide bridges. They have the insulin binding site.
2) Two beta subunits which traverse the cell membrane and have tyrosine kinase domains.
What does insulin activating the insulin receptor lead to?
Phosphorylation of insulin receptor substrates (of which there are 4 types).
