Secretions of the pancreas

Question 1

What is the pancreas?

Answer 1

An elongated gland located by the stomach.
It has exocrine and endocrine function.
Endocrine - secretions go all around the body.

Question 2

What is the exocrine function of the pancreas?

Answer 2

Secretes locally, goes into ducts on its own organ or neighbouring organs.
It secretes digestive enzymes and fluid rich in HCO3-.
The bicarbonate ions in the pancreatic fluid help to neutralise the acidity of the chyme coming from the stomach.
This prepares the chyme for entry into the small intestine.

Question 3

What is the structure of the pancreas?

Answer 3

Lobules have the acinar cells that produce the secretions.
Secretions drain into the intralobular duct, then interlobular duct, and then into the main duct.

Question 4

What is the ampulla of Vater?

Answer 4

The major pancreatic duct merges with the common bile duct to form a swelling in the duodenal wall called the ampulla of vater.
The muscular wall is thickened to form the sphincter of Oddi.

Question 5

What is the Sphincter of Oddi?

Answer 5

This regulates the secretions going into the duodenum.
It also prevents the contents of the duodenum going into the ducts.
This helps prevent reflux.

Question 6

What are the pancreatic acinus?

Answer 6

Within the lobules are the functional secretory units of the gland.
Each secretory unit is composed of an acinus and a small intercalated duct.

Question 7

What do acinar cells secrete?

Answer 7

Secrete zymogens (inactive enzyme precursors), digestive enzymes and an isotonic, plasma-like fluid that accompanies the secretory proteins.
They have vesicles which contain zymogen granules.

Question 8

What is the function of acinar cells?

Answer 8

Polarised/specialised for the production and export of large quantities of protein as predicted by the cellular architecture - RER, secretory granules, exocytosis at apical pole.

Question 9

What is the function of duct cells?

Answer 9

Have morphological heterogeneity along the ductal tree.
Predominantly specialised for the transport of electrolytes.

Question 10

What are the Centro acinar cells?

Answer 10

The first cells of the intercalated duct, so are located at the junction of the pancreatic acinar cells and duct cells.
Function is unknown.

Question 11

What is the function of goblet cells?

Answer 11

Produce mucus, important for lubrication, hydration, protection and immunological role.
They also produce HCO3-.

Question 12

What are the exocrine secretions of the pancreas?

Answer 12

Digestive enzymes
Alkaline juice

Question 13

What are the digestive enzymes?

Answer 13

CCK is responsible for them.
Digests all food types
Protease, lipases, nuclease, carbohydrase.

Question 14

What is alkaline juice?

Answer 14

Secretin is responsible for it.
Has numerous functions such as to neutralise acid and prevent ulcer formation.

Question 15

What is the rate of pancreatic secretion?

Answer 15

Pancreatic juice which is protein-rich is embedded within an alkaline fluid.
The rate is dependent on whether you’re in the fed or fasted state.
More food in the duodenum = more secretion.
The composition of the pancreatic fluid will alter the secretion.

Question 16

How does the pancreatic secretion rate change between the states?

Answer 16

Fasted/post-absorptive state - low level release of pancreatic enzymes.
Fed state /absorptive state - pancreatic secretion increases by 5 to 20x.

Question 17

What happens in the fasted state?

Answer 17

In an unstimulated (fasted) state acinar cells secrete low levels of digestive
proteins via a constitutive secretory pathway.

Question 18

How does the fasted state occur?

Answer 18

Stimulation is predominantly mediated through CCK receptors and the muscarinic acetylcholine receptors on the basolateral cell membrane.
These receptors signal through the PLC/Ca2+ signal-transduction pathway.
This leads to increased enzyme secretion from the acinar cell.

Question 19

What is the PLC signal-transduction pathway?

Answer 19

CCK and Ach binds to receptors, and triggers Gq, which activates PLC. PLC converts PIP2 to IP3 and DAG.
IP3 releases Ca2+ from the ER, which binds to calmodulin and activates PKC, whcih triggers secretion of vesicles of zymogens into the acinar cells.

Question 20

What does secretin do to acinar cells?

Answer 20

Secretin and VIP activate recepeots, which activate Gs.
The a-subunit binds to adenylyl cyclase, which converts ATP to cAMP, which increases PKA, which phosphorylates a protein to trigger secretion of zymogens.

Question 21

What does CCK do?

Answer 21

Arrival of chyme at the junction of the duodenum is detected by I cells, which stimulates the acinar cells via CCK to secrete pancreatic juices.
Chyme also squeezes the gall bladder to produce bile.

Question 22

How is CCK activated?

Answer 22

In response to a fatty meal, plasma CCK levels increase 5-10 fold quickly.
This is directly through a CCK-A receptor or indirectly through the parasympathetic nervous system.
CCK secretion is also stimulated by CCK-releasing factors.

Question 23

What are CCK-releasing factors?

Answer 23

e.g. LCRF - luminal CCK releasing factor - which are endogenously produced proteins secreted into the gut lumen, and which stimulate CCK.

Question 24

What does CCK do in the fasted state?

Answer 24

LCRFs are degraded by digestive enzymes so no CCK stimulation. During a meal, the digestive enzymes act on the chyme and LCRFs stimulate I-cells to release CCK and pancreatic secretion.

Question 25

What do goblet cells do?

Answer 25

Pancreatic duct cells secrete an HCO3- rich fluid that alkalinises and hydrates the protein-rich primary secretions of the acinar cell. This fluid is also important for enzymatic optimal pH, micelle formation and neutralising acid.

Question 26

How is HCO3- secreted?

Answer 26

HCO3- enters the pancreatic duct cell, then is pumped into the lumen against Cl- entry. Carbonic anhydrase is also used to produce HCO3- from OH- and H2O. Secretin activates Gs, leading to increased cAMP, which inserts the CFTR channel into the membrane, and pumps Cl- into lumen Produces high Cl- in the lumen so goes through the other channel so HCO3- leaves and goes into lumen.

Question 27

How is secretin involved in regulation?

Answer 27

Secretin triggers lots of Cl- into the lumen, so it is then pumped into the interstitial space, so that lots of HCO3- can enter the lumen. When something very acidic is eaten, secretin will trigger increased HCO3-.

Question 28

What does secretin do?

Answer 28

Activation of the secretin receptor on the duct cell stimulates adenylyl cyclase, which raises cAMP, and triggers PKA. This will trigger the CFTR Cl- channel and the Na/HCO3- cotransporter.

Question 29

How else is HCO3- secretion regulated?

Answer 29

Acetylcholine and the muscarinic receptors on the duct cells causes increased [Ca2+] and activation of the Ca2+ dependent protein kinases (PKC) in pancreatic duct cells.

Question 30

What is cystic fibrosis?

Answer 30

CTFR is not working, CFTR cannot get Cl- into the lumen so HCO3- cannot get into the lumen when Cl- leaves again. Less HCO3- present in duodenum - pH in duodenum will be low, and less mucous produced. Less mucous for movement of enzymes secretions for digestion.

Question 31

What is the cause of cystic fibrosis?

Answer 31

Mutant CTFR is prematurely degraded. This results in decreased secretion of HCO3- and water by the ducts. Results in a protein-rich primary secretion which thickens within the duct lumen and leads to ductal obstruction and pancreatic tissue destruction. The subsequent deficiency of pancreatic enzyme leads to maldigestion of nutrients - steatorrhea and diabetes.

Question 32

How does the different food affect secretion?

Answer 32

Proportion of secretions depends on food arrived. Acidic chyme entering the duodenum causes the enteroendocrine cells of the duodenal wall to release secretin, whereas fatty protein-rich chyme induces release of CCK.

Question 33

How do CCK and secretin differ?

Answer 33

CCK and secretin enter the bloodstream. When it reaches the pancreas, CCK induces the secretion of the enzyme-rich pancreatic juice. Secretin causes lots of secretion of HCO3- rich pancreatic juice.

Question 34

What is the cephalic phase of pancreatic secretion?

Answer 34

Stimulated by smell, taste, chewing and swallowing. Mediated by Ach through Vagus nerves on acinar cells, by CCK. 25% of pancreatic enzymes are produced.

Question 35

What is the gastric phase of pancreatic secretion?

Answer 35

Stimulated by proteins, gastric distention, gastrin. Activates CCK receptors on acinar cells. Mediated by Vaso-vagal reflex. 10-20% of pancreatic enzymes.

Question 36

What is the intestinal phase of pancreatic secretion?

Answer 36

Stimulated by acid in chyme and fatty acids. Mediated by secretin, CCK and Vaso-vagal reflex. 70-75% of pancreatic enzymes and fluid.

Question 37

What is somatostatin?

Answer 37

Somatostatin is present in D-cells in islets of Langerhans of the pancreas, in the S-14 form (14 amino acids). Somatostatin inhibits acid secretion by inhibiting release of CCK and secretin. Analogues of somatostatin are used clinically to inhibit pancreatic secretions.

Question 38

Why is autodigestion of the pancreas possible?

Answer 38

Pancreas produces enzymes which digests protein Lumen is made from proteins Has no protective mucous layer on top to prevent digestion.

Question 39

How is autodigestion of the pancreas prevented?

Answer 39

Enzyme inhibitors such as pancreatic trypsin inhibitor SPINK1 are co-packaged in the secretory granule. Zymogens becomes activated when they come into contact with the small bowel brush border enzyme enterokinase. This converts trypsinogen to trypsin which then initiates the conversion of all other zymogens to their active forms.

Question 40

What is acute pancreatitis?

Answer 40

Loss of protective mechanisms in the pancreas. Abdominal pain, nausea and vomiting. X3 amount of amylase and lipase in the serum, as not in the GI tract. Can be seen on a CT scan.

Question 41

What is acute pancreatitis produced by?

Answer 41

Premature activation of trypsin within pancreatic acinar cells - hyperstimulation inhibits acinar secretion. Intra-pancreatic inflammation by activation of inflammatory and endothelial cells. Extra-pancreatic inflammation including sepsis and multi-organ failure.

Question 42

What are the causes of acute pancreatitis?

Answer 42

Caused by autodigestion, trypsin is produced prematurely. Duct can be blocked, or the sphincter has a problem, enzymes are not released into duodenum so activate themselves.

Question 43

What is the treatment for acute pancreatitis?

Answer 43

Regulate diet, IV fluids for hydration, acute - ERCP is done. Gives the pancreas a break.

Question 44

What is chronic pancreatitis?

Answer 44

Inflammation of the pancreas that does not heal or improve - worsens over time and leads to permanent damage. Enzymes are prematurely activated.

Question 45

What are the causes of chronic pancreatitis?

Answer 45

Chronic alcohol abuse. Can also be hereditary - cystic fibrosis, leading to pancreatitis, hypercalcemia, hyperlipidaemia.

Question 46

What is the treatment for chronic pancreatitis?

Answer 46

IV hydration and nutritional support, can be supplemented by synthetic pancreatic enzymes if the pancreas does not secrete enough on its own. Diet low in fat and is small, frequent portions.

Question 47

How can chronic pancreatitis worsen?

Answer 47

Can lead to calcification of the fibrotic pancreas, the tissue hardens from deposits of insoluble calcium salt. When the tissue is destroyed it can lead to diabetes.