Pancreas

Question 1

Describe the embryology of the pancreas.

Answer 1

The pancreas develops as a ventral bud (part of the hepatobiliary bud) and the dorsal bud. During development, the duodenum will rotate to form a C shape, the ventral bud will swing around and both buds fuse.
-Ventral bud duct becomes main pancreatic duct

Question 2

What are the five parts of the pancreas?

Answer 2

Uncinate process (hook-like), head, neck, body and tail

Question 3

Where is the pancreas positioned? What are its posterior relations?

Answer 3

Within the C of the duodenum tp hilum of spleen
Posterior to the pancreas is the inferior vena cava, the abdominal aorta and the left kidney.

Lies mainly on posterior abdominal wall extending from
C-shaped duodenum to
hilum of spleen

Question 4

Describe the blood vessels around the pancreas.

Answer 4

The coeliac trunk is just superior to the pancreas

The superior mesenteric arteries arise from in between the uncinate process and the body of the pancreas.

Question 5

What are the main endocrine products of the pancreas?

Answer 5

Glucagon, Insulin, Somatostatin, Pancreatic Polypeptide

Insulin: anabolic hormone, promotes glucose transport into cells and storage as glycogen, reduces blood glucose, promotes protein synthesis and lipogenesis

Glucagon: Increases gluconeogenesis and glycogenolysis (increases blood glucose)

Somatostatin: “Endocrine cyanide” tends to supress the release of other hormones.

Question 6

what are the 2 functions of the liver?

Answer 6

Endocrine - 2% of gland
Islets of Langerhans
Secretes hormones into blood - Insulin & Glucagon (also Somatostatin and Pancreatic Polypeptide)
Regulation of blood glucose, metabolism & growth effects - (Endocrine course)
Exocrine - 98% of gland.
Secretes (Pancreatic Juice) into duodenum via pancreatic duct/common bile duct.
Digestive function

Question 7

what is endocrine and exocrine ?

Answer 7

Endocrine: Secretion into the blood stream to have effect on distant target organ (Autocrine/Paracrine) - Ductless Glands
Exocrine: Secretion into a duct to have direct local effect

Question 8

Why is somatostatin described as endocrine cyanide?

Answer 8

It inhibits most other endocrine processes

Question 9

Describe the development of the endocrine and exocrine parts of the pancreas from ductal budding.

Answer 9

Eeverything develops from the ducts system.
The endocrine and exocrine parts of the pancreas develop from the ductal budding but the endocrine components lose their connection with the duct whereas the exocrine parts retain their connection.

Yellow: exocrine, Acini
Pink: endocrine, ilets of the pancreas

Question 10

Where are most of the endocrine cells of the pancreas found?

Answer 10

Tail of the pancreas

Question 11

what is the pancreatic cell differentiation differences between exocrine and endocrine>

Answer 11

Exocrine:
Ducts
Acini are grape-like clusters of secretory units
Acinar cells secrete pro-enzymes into ducts

Endocrine:
Derived from the branching duct system
Lose contact with ducts – become islets
Differentiate into α- and β-cells secreting into blood
Tail > head

Question 12

What percentage of the islets of Langerhans are a) alpha cells, b) beta cells and c) delta cells and what do each of them release?

Answer 12

Alpha cells - 15-20%
-secrete glucagon

Beta cells - 60-70%
-secrete insulin

Delta cells - 5-10%
-secrete somatostatin

Question 13

How does the staining of the islets of Langerhans differ from the rest of the pancreas?

Answer 13

Islets of Langerhans stain lighter than the other cells

Question 14

what are the 2 components of the pancreatic juice?

Answer 14

TWO components of pancreatic juice and therefore the release is differently controlled and comes from different cell types:

• low vol, viscous,enzyme-rich Acinar cells (blind ended tubule)
• high vol, watery, HCO3-rich. Duct and Centroacinar cells

Question 15

What is the role of the bicarbonate produced by the duct cells?

Answer 15

Bicarbonate neutralises the acid chyme and hence protects the mucosa
Bicarbonate also raises the pH to optimum range for pancreatic enzymes.

• Duct & centroacinar cells
• Juice = RICH in bicarbonate ~ 120 mM (mmol/L) - (plasma ~25 mM). pH 7.5-8.0
• Neutralises acid chyme from the stomach
• prevents damage to duodenal mucosa
• Raises pH to optimum range for panreatic enzymes to work
• Washes low volume enzyme secretion out of pancreas into duodenum

Question 16

How does bicarbonate secretion change with duodenal pH?

Answer 16

As duodenal pH decreases, bicarbonate secretion increases to a maximum at around pH 3.

Question 17

Why does bicarbonate secretion stop at pH 5 (i.e. when it is still acidic)?

Answer 17

Neutralisation of the acid chyme is also affected by the bicarbonate in bile and the Brunner’s glands secreting alkaline fluid

Bile also contains bicarbonate and helps neutralise the acid chyme (liver functions lecture).
Brunners glands secrete alkaline fluid (Small intestine lecture).

Question 18

What is the mechanism of pancreatic bicarbonate secretion

Answer 18

1. CO2 diffuses into the duct cell from the blood and reacts with water in the presence of carbonic anhydrase
2. Carbonic acid is produced which dissociates to produce H+ and HCO3- (this is put into the pancreatic juice)
3. Na+ moves down gradient via paracellular (“tight” junctions) into the duct lumen, H20 also follows
4. CFTR channel becomes activated and Cl- from the duct cell moves out into the duct lumen, and this creates a concentration gradient
5. Cl/HCO3 exchange at lumen so HCO3- out into the lumen and cl- into the duct cell
   6.Na/H exchange at basolateral membrane into bloodstream, H+ out into the blood and Na+ into the duct cell
6. Na+ gradient into cell from blood maintained by Na/K exchange pump, Na+ out of the cell and K+ into the duct cell.
   7.Uses ATP - Primary active transport
7. Leak channel for Potassium which allows K returns to blood via K- channel
8. Cl returns to lumen via Cl-channel, this is dependant on the electrochemical gradient.
   The cl- is important for cystic fibrosis.

Exchange driven by electrochemical gradients
High ec (blood) Na compared to ic (duct cell)
High Cl in lumen compared to ic (duct cell)

Question 19

What is the role of CFTR in this mechanism of bicarbonate secretion?

Answer 19

CFTR allows the outwards movement of chloride ions so the gradient can be used to pump out bicarbonate ions. A defective CFTR doesn’t allow chloride ions out so you get thick secretions.

Question 20

what happens in the stomach and the pancreas?

Answer 20

Same reaction in gastric parietal cells (acid)
and pancreatic duct cells (alkaline)

In stomach, H+ goes into gastric juice, HCO3- into blood. Gastric venous blood is alkaline
In pancreas, HCO3- secreted into juice and H+ into blood. Pancreatic venous blood is acidic

Question 21

what does the duodenum secrete?

Answer 21

Duodenal mucosa secretes an enzyme - Enterokinase (enteropeptidase) - that converts trypsinogen to trypsin.
Trypsin then converts all the other proteolytic and some lipolytic enzymes (note lipase secreted in active form but requires colipase, which is secreted as precursor)

Question 22

What does Orlistat do?

Answer 22

Pancreatic lipase inhibitor - reduced digestion and absorption of fats leading to steatorrhoea

Increased faecal fat – occurs when pancreatic lipase secretion significantly reduced
Eg cystic fibrosis, chronic pancreatitis, Orlistat – a weight loss agent which inhibits pancreatic lipase and hence intestinal fat absorption

Question 23

What is the main nerve controlling pancreatic secretion?

Answer 23

VAGUS NERVE
Cholinergic
communicates information from gut to brain

Question 24

Describe the phases of secretion ?

Answer 24

Initial cephalic phase
Reflex response to sight/smell/taste of food
Enzyme-rich component only. Low volume - “mobilises” enzymes

Gastric phase
Stimulation of pancreatic secretion originating from food arriving in the stomach
Same mechanisms involved as for cephalic phase

Intestinal phase (= 70-80% of pancreatic secretion)
Hormonally mediated when gastric chyme enters duodenum.  
BOTH components of pancreatic juice stimulated (enzymes + HCO3 - juice flows into duodenum)

Question 25

how are the 2 components of the pancreatic juice controlled?

Answer 25

The two components of pancreatic juice are separately controlled
Bicarbonate secretion is controlled by release of a hormone - Secretin (cAMP)
Enzyme secretion is controlled by vagal reflex and by a hormone - Cholecystokinin (CCK) (Ca2+/PLC)

Question 26

what stimulates bile secretion

Answer 26

Cholecystokinin also stimulates bile secretion

Question 27

how can you switch off CCK?

Answer 27

Cephalic phase ends when meal eaten

Absorption of fats and peptides removes local luminal stimulus for CCK release from mucosa

Question 28

Describe what the findings were for CCK and secretin?

Answer 28

CCK alone - no effect on bicarbonate secretion
Secretin alone- increases bicarbonate secretion, has no effect on enzyme secretion from acinar cells
CCK + secretin - CCK amplifies the effect of secretin on bicarbonate secretion
Vagus nerve has similar effect to CCK

Question 29

what happens during a meal

Answer 29

Food mixed, digested in stomach, pH 2
Chyme squirted into duodenum
H+ ions in duodenum stimulate release of secretin, stimulating release of pancreatic juice (plus bile and Brunner’s gland secretions) to raise pH to neutral/alkaline.
Peptides + fat in duodenum cause sharp rise in CCK, vagal nerve, stimulating pancreatic enzyme release, peaks by 30 mins, continues until stomach empty.
CCK potentiates effects of secretin on aqueous component (necessary because most of duodenum not at low pH).

Question 30

Describe the exocrine functions of the pancreas?

Answer 30

Acinar cells release these pro-enzymes at the terminal ends of the pancreatic duct.

• Protease zymogen
• Trypsinogen
• Procolipase
• pancreatic amylase
• lipase

Trypsinogen becomes active to form trypsin. This is stimulated by duodenal brush border enzyme: enterokinase, therefore when trypsinogen moves from the pancreas to the duodenum, it will then be converted to its active form, preventing breakdown of the pancreas.

Trypsin catalyses the conversion of protease zymogens to become active protease and procolipase to become colipase. It also autocatalysis the conversion of trypsinogen to trypsin, so amplifying the effect.
tHEREFORE accelerates the whole digestion.
The acinar cells from the pancreas also releases trypsin inhibitor.

Amylase converts polysaccharides to disaccharides
Protease and trypsin convertes proteins to shorter peptides, brush border enzymes then covert it to individual amino acids

Liver releases bile, and it is stored into the gall bladder, which is then released into the ampulla of vater and then into the duodenum.
Bile emulsifies fat and then turn them into fatty droplets, helping to liberate triglycerides. Pancreatic lipase and colipase work together to convert triglycerides into monoglycerides and fatty acids, which is then absorbed.

Question 31

what leads to acute pancreatitis?

Answer 31

Blockage of pancreatic duct may overload protection and result in auto-digestion.
This is because the blockage leads to a build of the trypsinogen and the trypsin inhibitor doesn’t work so you get auto-digestion and therefore acute pancreatitis.

Question 32

How is bicarbonate secretion controlled?

Answer 32

• presence of acid chyme in the proximal duodenum, this very low pH stimulates secretin secretion from S cells.
• Secretin travels in blood to pancreas via the long root so it goes to the liver then the heart,
• secretin binds to receptors on the basolateral duct cells.
• This increases cAMP which is a 2nd messenger
• this activates chloride channels in apical membrane
• leads to chloride efflux
• this produces a concentration gradient, which allows secondary active transport, which allows increases activity of anion exchange
• bicarbonate efflux into lumen of pancreatic duct
• fluid moves out into the duodenum, and goes through the ampulla of vater, out of the sphincter of Oddi.

Question 33

Describe the hormonal control of enzyme secretion?

Answer 33

• stimulated by fats and peptides in duodenum
• these are detected by the duondenal wall, I cells
• the I cells release CCK, and travels in the bloodstream to other places and to the pancreas
• CCK binds to CCK-1 receptors on the basolateral acini cells in the pancreas
• this activates of the PLC and converts to IP3, which increases cytosolic ca2+.
• thsi is the amplification signal
• this triggers the exocytosis of the granules of the zymogen, trypsin inhibitor and active enzymes e.g. amylase
• these get secreted into the duct
• move from the smaller duct into the larger duct, out into the duodenum
• zymogen then converted active form by enterokinase.

Central input
-vagus nerve releases acetylcholine, these bind to acinar cells, these are muscarinic receptors, when activated they also trigger an increase in cytosolic calcium which then causes release of zymogen inhibitor, enzyme granules.

Hormonal regulation via CCK
Central regulation via vagus nerve.

Question 34

what are the phases of pancreatic secretion

Answer 34

Phase:
Cephalic - head
Gastric - gut
Intestinal - stomach

Stimulus:
Sight, smell and taste of food
Mechanoreceptors for Distension of stomach
Acid and nutrient detection in duodenum (acid chyme)

Key mediator:
Vagus nerve
Vagus nerve
Hormones

Proportion of acinar cell secretion:
20%
10%
70%

Activated cells:
Acinar cells
acinar cells
acinar cells and duct cells

Question 35

Describe the negative feedback in pancreatic secretion

Answer 35

Hormones released in the intestinal phase, neutralises the food in the stomach and therefore allows the digestion of the food and the secretion is cut off.