6 Pancreas

Question 1

Q: How does the pancreas develop?

Answer 1

A: from 2 buds at the foregut and midgut junction-> dorsal bud and ventral bud which is a part of the hepatobiliary bud

Duodenum rotates to form a C shape – ventral bud swings round to lie adjacent to the dorsal bud – both buds fuse

Ventral bud duct becomes main pancreatic duct

Question 2

Q: How is the pancreas subdivided? Where are islets most abundant?

Answer 2

A: R head, neck, body, tail and uncinate= below L

Islet tissue most abundant in tail

Question 3

Q: Where does the pancreas lie? In relation to duodenum?

Answer 3

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

Pancreatic juice reaches duodenum via main (and accessory) pancreatic ducts

Question 4

Q: What are the main posterior relations to the pancreas? (3) What supplies blood to it? (2)

Answer 4

A: IVC, abdominal aorta and left kidney

Close relations with (and supply from) coeliac and superior mesenteric arteries

Question 5

Q: How do you define Endocrine vs Exocrine secretion? Type of effect?

Answer 5

A: 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 6

Q: What are the main endocrine secretions of the pancreas and their actions? (3)

Answer 6

A: 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 suppress lots of cells in terms of their hormone release and regulate locally insulin and glucagon release

Question 7

Q: What are the 2 functional parts of the pancreas? Percentage of gland? Structure? Secretes? Type of function? (3,1) Pancreatic disease? eg?

Answer 7

A: Endocrine - 2% of gland

• Islets of Langerhans
• Secretes hormones into blood - Insulin and Glucagon (also Somatostatin and Pancreatic Polypeptide)
• Regulation of blood glucose, metabolism and growth effects

Exocrine - 98% of gland.

• Acinar cells secrete pro-enzymes into ducts
• Secretes (Pancreatic Juice) into duodenum via pancreatic duct/common bile duct.
• Digestive function

Pancreatic disease may involve BOTH exocrine and endocrine effects- eg cystic fibrosis

Question 8

Q: Describe early pancreatic development. (2)

Answer 8

A: begin as 2 structure types-> become endo and exo tissue

exocrine:
Ducts
Acini are grape-like clusters of secretory units

Endocrine:
Derived from the branching duct system
Lose contact with ducts (thick vines) – become islets
Differentiate into alpha- and beta-cells secreting into blood

Tail > head

Question 9

Q: What is the composition of islets of langerhans? (3) Percentage of islet tissue? Secrete? Islets are highly? ensures?

Answer 9

A: alpha-cells (A) form about 15-20% of islet tissue and secrete glucagon

beta-cells (B) form about 60-70% of islet tissue and secrete insulin

delta-cells (D) form about 5-10% of islet tissue and secrete somatostatin

The islets are highly vascular, ensuring that all endocrine cells have close access to a site for secretion

Question 10

Q: What’s the structure of an acinar? (3) Shape? What is it?

Answer 10

A: hair pin= blind ended tubules where acinar cells form blind end

• sticks are duct cells
• connection to curve are centroacinar cells (predominantly act like duct cells)
• curve has acinar cells (contains packaged enzymes at apical end pointing into the hair pin that will be released)

functional unit of exocrine pancreas

Question 11

Q: What are the 2 components of pancreatic juice?

Answer 11

A: -low vol, viscous, enzyme-rich = Acinar cells (ENZYME SECRETION)

-high vol, watery, HCO3-rich = Duct and Centroacinar cells (BICARBONATE SECRETION)

Question 12

Q: What produces the bicarbonate component of pancreatic juice. Main component? compared to plasma? pH? Role? (4)

Answer 12

A: Duct and 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 13

Q: What’s the effect of duodenal pH on bicarbonate secretion rate? Draw graph.

Answer 13

A: duodenal pH (X)- decreasing from 5 to 2
bicarbonate secr rate (Y)- 0 to 2

exponential and levels at 3 rate

Duodenal pH <3 = not much more increase in bicarbonate secretion
Duodenal pH < 5 = significant linear increase in pancreatic bicarbonate secretion

lower pH = more bicarbonate = released

stops bicarbonate secretion when pH is still acidic (5)

Question 14

Q: Why does bicarbonate secretion stop when pH is still acidic? (2)

Answer 14

A: Bile also contains bicarbonate and helps neutralise the acid chyme

Brunners glands (in duod) secrete alkaline fluid

Question 15

Q: What are the steps of pancreatic HCO3 secretion? (8)

Answer 15

A: HCO3- production

1. CO2 enters duct cell from blood and via carbonic anhydrase -> carbonic acid -> dissociates into H+ and HCO3-
2. Na+ moves down gradient via paracellular (“tight” junctions) from blood/interstitium to lumen of duct
3. H2O follows

HCO3- secretion

4. Cl- leaves cell via apical membrane via CFTR into lumen
5. Cl/HCO3 exchange between duct cell and lumen where HCO3- exits cell and Cl enters (Cl is coming down concentration/electrochemical gradient)
6. Na/H exchange at basolateral membrane where H exits blood and Na enters cell (Na is coming down concentration/electrochemical gradient)

Na+ management

7. Na gradient into cell from blood maintained by Na/K exchange pump where K is pumped into cell and Na out into blood => uses ATP: primary active transport (basolateral membrane)
8. K returns to blood via K-channel down gradient

Question 16

Q: How does CF relate to bicarbonate secretion? Result? Another disease?

Answer 16

A: Cl channel which allows Cl return to lumen via Cl-channel = CFTR (CF transmembrane regulator)

doesn’t function

get less watery excretion

• > become thick and can block pancreatic duct
• > may overload protection and result in auto-digestion (= acute pancreatitis)

Question 17

Q: Name 3 enzymes produced by acinar cells. What are they put into? In what form? Why? What aids this? When does this form change? Name an exception.

Answer 17

A: Enzymes for digestion of fat (lipases), protein (proteases) and carbohydrates (amylase) are synthesised and stored in zymogen granules
Zymogens = pro-enzymes = inactive pro-enzymes

protects acini and ducts from auto-digestion

trypsin inhibitor to prevent trypsin activation (would usually cause cascade of enzyme activation)

Enzymes become activated ONLY in duodenum

(note lipase secreted in active form but requires colipase, which is secreted as precursor)

Question 18

Q: Name a key brush border enzyme which plays a role in the activation of enzymes. Where is it? meaning? What does it allow? What aids this?

Answer 18

A: enterkinase: causes trypsinogen to become trypsin

wall of duodenum (secreted by duodenal mucosa)-> should only get trypsin in duodenum

trypsin can also convert trypsinogen

Question 19

Q: What can trypsin do in terms of other enzymes?

Answer 19

A: converts all the other proteolytic and some lipolytic enzymes

Question 20

Q: How can pancreatic secretions adapt?

Answer 20

A: pancreatic secretions adapt to diet e.g. high protein, low carbs, increases proportion of proteases, decreases proportion of amylases

Question 21

Q: What differentiates pancreatic enzymes and salivary/gastric enzymes?

Answer 21

A: Pancreatic enzymes (+ bile) are essential for normal digestion of a meal. Lack of these can lead to malnutrition even if the dietary input is OK. (unlike salivary, gastric enzymes)

Question 22

Q: Name a drug that inhibits pancreatic lipases. What side effects might you expect? What else can cause this side effect? (2)

Answer 22

A: Orlistat= anti obesity

Increased faecal fat – occurs when pancreatic lipase secretion significantly reduced (by 1/3 by above drug)-> less fat absorption

cystic fibrosis, chronic pancreatitis

Question 23

Q: Which tends to inhibit and which tends to excite-

autonomic NS: sympa or para?

Answer 23

A: sympa inhibit

pare excite

Question 24

Q: What is the vagus nerve? Communicates? NT?

Answer 24

A: parasympathetic stimulation

info from gut to brain and back

cholinergic- ACh

Question 25

Q: How is secretion controlled in the 3 phases of digestion?

Answer 25

A: Initial cephalic phase

• produces enzyme-rich component only
• Low volume - “mobilises” enzymes

Gastric phase
-Same mechanisms involved as for cephalic phase
= both can involve vagal nerve signalling that can cause a little mobilisation of enzymes

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 26

Q: How is the secretion of the 2 components of pancreatic juice controlled? (1,2)

Answer 26

A: The two components of pancreatic juice are separately controlled

Bicarbonate secretion is controlled by release of a hormone - Secretin (cAMP)= proportional

Enzyme secretion is controlled by vagal reflex and by a hormone - Cholecystokinin(CCK)

Question 27

Q: Aside from enzymes, what does CCK stimulate?

Answer 27

A: bile secretion (Cholecystokinin(CCK))

binds to receptors on smooth muscle of gall bladder -> stimulates squeeze bile into duodenum

Question 28

Q: Explain the method of bicarbonate secretion control? (pancreatic juice)

Answer 28

A: 1. get acidic chyme in duodenum

2. causes secretin release into blood via enterendocrine cells in duodenal wall (sensitive to pH)
3. causes cAMP release in pancreatic duct= increases secretion of pancreatic juice= increase HCO3 release
4. pH in duodenum lumen increases and switches off secretin secretion

Question 29

Q: How is enzyme secretion controlled? (pancreatic juice) 2 signals.

Answer 29

A: 1. food enters duodenum containing peptides and fat
2. enterendocrine cells in duodenal wall detect and release CCK/Cholecystokinin

2. alternative= vagus nerve via ACh
3. CCK binds to acinus cell receptors and causes intracellular Ca2+ cascade and activates phospholipase C/PLC= an intracellular messenger in cells
4. zymogen granules to fuse with membrane and release enzymes into tubules-> secreted

Question 30

Q: What switches off the CCK? (2)

Answer 30

A: Cephalic phase ends when meal eaten

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

Question 31

Q: How does CCK affect bicarbonate secretion alone? Secretin alone? Together? Why? Secretin on acinar activity?

Answer 31

A: CCK alone - no effect on bicarbonate secretion

small increase (some effect)

CCK can markedly increase bicarbonate secretion that has been stimulated by secretin = synergistic

WHY- you need to sense a pH change for secretin release, but won’t necessarily want large portion of duodenum to get a low pH as it could cause damage

Secretin NO EFFECT on enzyme secretion from acinar cells (CCK does it all without help from secretin)

Question 32

Q: Summarise what happens during a meal. (5-3,1,3,4,1)

Answer 32

A: 1. Food mixed, digested in stomach, pH 2

2. Chyme enters duodenum
3. 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.
4. Peptides + fat in duodenum cause sharp rise in CCK, vagal nerve, stimulating pancreatic enzyme release, peaks by 30 mins, continues until stomach empty.
5. CCK potentiates effects of secretin on aqueous component (necessary because most of duodenum not at low pH)