Pancreatic Exocrine Secretions

Question 1

Describe the pancreas

Answer 1

Pancreas: ~15cm long, leafy shape, tucked under the liver, near the gallbladder.
Lies across the body behind the stomach. The pancreatic lobules is composed of closely arranged acini (singular: acinus).
Pancreas = dual organ; has exocrine and endocrine portions

Question 2

What are the acini?

Answer 2

The acini are luminal structures which drain into a complex branching ductal system.
The pancreatic ductular system empties the secretions into the (proximal) duodenum via the pancreatic duct.

Question 3

Describe the complex branching ductal system of the acini

Answer 3

Acini start w intercalated ducts which drain into intralobular ducts. Both of these are lined w cuboidal epithelium
Intralobular → extralobular → Interlobular ducts → Pancreatic duct. These ducts are all lined w columnar epithelium.
The pancreatic duct enters the duodenum at the common bile duct where secretions are emptied.

Question 4

Describe the endocrine pancreas

Answer 4

Primary component is Islets of Langerhans: clusters of endocrine cells located throughout the pancreas, but most abundant in the tail – lots of blood vessels
Beta cells (70%) secrete insulin, taking glucose into cells
Alpha cells (20%) secrete glucagon which increases gluconeogenesis- increases blood glucose
Somatostatin: inhibits insulin and glucagon production, inhibits secretin, CCK, gastrin and motilin

Other cell types secrete VIP, and enterochromaffin cells secrete serotonin, motilin and substance P

Question 5

Label the anatomy of the pancreas

Answer 5

Question 6

Label this exocrine pancreas

Answer 6

Question 7

How are the acinar cells and zymogen granules related?

Answer 7

The acinar cells produce digestive enzymes which are stored inactivley in cytoplasmic zymogen granules. The granules are released by exocytosis.

Intercalated and intralobular ducts secrete Na and HCO3-to keep the stored enzymes inactive (pH >7.5).
Premature enzyme activation within acinar cells leads to acute pancreatitis

Question 8

What are the centroacinar cells and the basal lamina?

Answer 8

Centroacinar cells are aka intercalated ducts. they have nuclei in the centre, and make pancreatic juice more alkaline by secreting bicarbonate

The basal lamina = layer of extracellular matrix secreted by the epithelial cells; the epithelium sits on it.

Question 9

What are the pancreatic exocrine functions?

Answer 9

Secretes 1.5L of fluid/day (Na and HCO3- rich juice, albumin, globulin and digestive enzymes)

Acinar cells secrete digestive enzymes in inactive form (as zymogens) to prevent auto-digestion. Enzyme activation occurs in the duodenum

Question 10

Describe the anions and cations secreted by the pancreas

Answer 10

The anions secreted in the pancreatic juice:
HCO3-, Cl-, SO42-, HPO42-
The cations secreted in the pancreatic juice:
Na+, K+, Ca2+, Mg2+

Question 11

What are the alkaline secretions of the pancreas?

Answer 11

HCO3- rich juice from the pancreas/gallbladder neutralise gastric acid
Juice composition is modified as it travels thru the duct:
Epithelial cells actively exchange Cl- for HCO3- from the duct into the lumen/pancreatic juice
Na+/H+ exchanges H+ from the duct into the blood.
H+ neutralises HCO3- in the blood to form carbonic acid (H2CO3)
HCO3- also combines w C02 +H20 in the blood to form carbonic acid

Therefore HCO3- conc in pancreatic juice is directly proportional to conc of HCO3- produced in the blood

Question 12

What is the effect of secretin on the composition and volume of pancreatic juice?

Answer 12

Increased secretin means bicarbonate levels come up and then down as the body metabolises it. Cl- levels go down due to the high levels of bicarbonate secreted

Question 13

What are the major types of enzymes secreted by the pancreas?

Answer 13

Proteolytic enzymes (trypsin, chymotrypsin, carboxypeptidase)
Amylase (75% reaches small intestine)
Lipase (Pancreatic insufficiency → malabsorption of fats
Steatorrhoea)
Ribonuclease
Deoxyribonuclease

Question 14

Describe the Enterokinase enzyme

Answer 14

Enterokinase: found in the brush border of duodenum; secreted in response to CCK
Converts trypsinogen to trypsin. Trypsin activates other proenzymes and digests proteins so there is risk of autodigestion
Inhibitors of autodigestion:
Kazal inhibitor, enzyme Y. Intracellular pH of zymogen granule itself = acidic (keeps zymogens inactive)

Question 15

What suggests the bidirectional permeability to digestive enzymes?

Answer 15

Chymotrypsinogen and amylase cross the basolateral membrane of pancreas. This suggests bidirectional permeability of the basolateral membrane to digestive enzymes

Question 16

Pancreatic secretions are controlled by…

Answer 16

Neuroendocrine signals
Secretin and CCK: stimulate secretion of pancreatic fluid
Vagal (parasymp) stimulation: enhances secretion of enzymes and aqueous components of pancreatic juice
Symp stimulation: inhibits secretion

Question 17

Control of pancreatic secretions have 3 phases. What is the cephalic phase?

Answer 17

Cephalic phase: sight, taste, or smell of food stimulates the vagus nerve and muscarinic ACh receptors to release digestive enzymes via acinar cells.
To a lesser extent, it stimulates duct cells to secrete HCO3- and fluid.

Question 18

Control of pancreatic secretions have 3 phases. What is the gastric phase?

Answer 18

Gastric phase: food in the stomach stimulates pancreatic secretions, primarily from the acinar cells, via 2 routes.
First, stomach distension activates a vagovagal reflex, which also causes ACh release.

Second, peptides and aa stimulate G cells in the antrum to release gastrin→ release of enzyme-rich pancreatic juice.

Question 19

What happens to pancreatic secretions in the intestinal phase?

Answer 19

Intestinal phase: arrival of gastric acid in the duodenum stimulates S cells–>secretin–>HCO3 and fluid from duct cells.
Protein and lipid breakdown products have 2 effects:
they release CCK, which causes acinar cells to release digestive enzymes. 2nd, they initiate a vagovagal reflex that stimulates the acinar cells through M3 cholinergic receptors.

Question 20

Complete the table

Answer 20

Question 21

Describe the effects of secretin

Answer 21

Secretin from duodenum and jejunum induces pancreatic duct cells to secrete HCO3- -rich pancreatic juice
But, secretin ↓ enzyme content bc it’s a weak agonist of the acinar cells
Secretin also stimulates production of bile

Question 22

Describe the effects of CCK

Answer 22

CCK from duodenum and jejunum in response to fatty acids (aa, and peptides) stimulates pancreatic acinar cells.
These release enzyme-rich pancreatic juice.

CCK also contracts the gallbladder and relaxes the sphincter of Oddi (via VIP and NO) → releasing bile and some HCO3- into duodenum

CCK promotes effects of secretin, which is a weak agonist of acinar cells