Secretion in the Pancreas and Small Intestine

Question 1

What is the overall function of the pancreas?

Answer 1

Important in digestion of nutrients, fat, proteins with huge reserve capacity resection (95%)
Providing the appropriate environment for enzymatic digestion in the small bowel
important in regulating the fed and fasted states (insulin and glucagon)

Question 2

What does the pancreas bicarb rich fluid do?

Answer 2

The bicarb rich fluid is used by the pancreas to neutralise stomach acid (exocrine function)

Question 3

How is the pancreas connected to the small intestine?

Answer 3

Via a series of ducts such as the intra/interlobular ducts and then the main ducts

Question 4

What is the Ampulla of Vater?

Answer 4

The point at which the pancreatic duct merges with the common bile duct

(contents of gall bladder, liver and pancreas all go via the main pancreatic duct into the small intestine

Question 5

What is the function of the pancreatic acinar cells?

Answer 5

are specialized/polarised for the production and export of large quantities of zymogens

Secretes isotonic NaCl rich fluid to hydrate the dense protein rich material

Question 6

What is the function of the goblet cells?

Answer 6

Goblet cells produce mucus important for 1. Lubrication 2. Hydration, 3. Mechanical protection of surface epithelial cells. 4. Immunologic role -binding of pathogens and interacting with immune-competent cells ultimately preventing pancreatic infections

Question 7

What is the function of the centroacinar cells?

Answer 7

are the very first cells of the intercalated duct and thus are located at the junction of the pancreatic acinar cells and duct cells, function questioned

Question 8

What are the triggers for the protein secretion from the pancreatic acinar cell?

Answer 8

Ach and CCk both ultimately activate PKC and release of calcium leading to zymogen release.

VIP and secretin activate adenyl cyclase leading to cAMP production and PKA activation.

Question 9

What is the function of the pancreatic duct cell

Answer 9

Secrete HCO3- rich fluid which hydrates and alkinizes the protein rich secretions of the acinar cell. (neutralise the acid)

Question 10

How does the pancreatic duct cell carry of the chloride bicarbonate exchange?

Answer 10

1. cl- and HCO3 exchanger brings Cl- into the pancreatic duct cell and HCO3- enters the duct lumen
2. CFTR allows the diffusion of Cl- ions to leave the duct cell and return back to the duct lumen (chloride recycling)
3. This process is triggered by ACh and secretin as they stimulate the PKC pathway.

Question 11

What are S cells?

Answer 11

Found in the small bowel and secrete secretin when they recognise the acidic chyme to neutralise it.

Question 12

What happens when CFTR is lost?

Answer 12

You wont get chloride recycling and therefore be unable to neutralise the acidic chyme from the stomach. You would also be unable to hydrate the thick proteinous fluid secreted by the acinar cells.
This would lead to thickening protein secretion and could lead to ductal obstruction or even pancreatic cell death (cystic fibrosis)

Question 13

composition and function of pancreatic secretion

Answer 13

product of acinar, duct and goblet cells results in secretion of a pancreatic juice which is protein-rich embedded within an alkaline fluid.
the pancreas exhibits the highest rates of protein synthesis and secretion
Product is over 20 proteins which are mostly zymogens (inactive proproteins) which get activated when needed.

Question 14

Why is the rate of pancreatic secretion dependent on being in the fed/fasted state?

Answer 14

Tightly interlinked with biliary/gastric secretions
Fasted state - post absorptive so low level release of pancreatic enzymes
Fed state - increased secretion

Question 15

How are pancreatic secretions inhibited?

Answer 15

Somatostatin produced by D cells in the islets of Langerhans.
Inhibit the release of CCK and secretin as well as glucagon and insulin

Question 16

What are the different phases of pancreatic secretion?

Answer 16

Cephalic phase
Gastric phase
Intestinal phase

Question 17

What is the cephalic phase of pancreatic secretion?

Answer 17

Sight, taste, and smell of food. • Accounts for 25% Mediated by the stimulation of Ach receptors on the acinar cell and to a lesser extent duct cells. No involvement of CCK or secretin.

Question 18

What is the gastric phase of pancreatic secretion?

Answer 18

Accounts for 10-20%

1. release of hormones (gastrin) stimulated by amino acids in the G cells of the antrum. This signals through the CCk receptor on acinar cells
2. stimulation of neural pathways, gastric distention stimulates low levels of pancreatic secretion through a vagovagal gastropancreatic reflex

Question 19

What is the intestinal phase of pancreatic secretion?

Answer 19

Accounts for 50-80%
chyme entering the proximal small intestine stimulates a pancreatic secretion by 3 main mechanisms:
1. Gastric acid stimulates duodenal S cells to release secretin, which stimulates duct cells to secrete HC03 and fluid. 2. Lipids (monoglycerides/FFA) predominantly stimulate duodenal I cells to release CCK, which stimulates acinar cells to release digestive enzymes. 3. Lipids also activate a vagovagal enteropancreatic reflex that predominantly stimulates acinar cells.

Pattern of pancreatic enzymatic secretion is going to depend on the relative composition of the chyme (eg. High carb vs fats!)

Question 20

How does the pancreas prevent autodigestion?

Answer 20

By preventing enzyme activity in the pancreas as the enzymes are produced in the inactive form initially.
Eg. Trypsinogen (inactive zymogen) when converted to trypsin will activate all the other zymogen enzymes.. Therefore we only want trypsinogen to become activate in the small intestine.

Question 21

How is trypsinogen activate in the small intestine?

Answer 21

Enterokinase on the boarder of the small intestine cleaves trypsinogen into trypsin which activates the rest of the zymogen enzymes

Question 22

What is SPINK1?

Answer 22

A pancreatic trypsin inhibitor

Question 23

How is autodigestion prevented?

Answer 23

1. Zymogens produced in inactive form
2. secretory vesicles are impermeable preventing automatic release
3. enzyme inhibitors (SPINK1)
4. Low pH and ionic conditions in secretory pathway limiting enzyme activity.

Question 24

what are the causes of acute pancreatitis?

Answer 24

GET SMASHED
Gallstones, Ethanol, Trauma
Steroids, Mumps, Autoimmune, Scorpion sting, Hypercalcaemia, ERCP, Drugs

Question 25

how is acute Pancreatitis diagnoses?

Answer 25

characteristic abdominal pain.
serum amylase and/or lipase at the upper limit of normal.
characteristic findings of acute pancreatitis on CT scan

Question 26

How can we treat pancreatitis?

Answer 26

Rest
remain hydrated
pain relief 
ultrasound scan
ERCP

Question 27

What are the main phases of the pathophysiology of acute pancreatitis?

Answer 27

Phase 1 - premature activation of trypsin within acinar cells.

1. disruption of calcium signalling
2. cleavage of trypsinogen to trypsin at the wrong time
3. decreased activity of the intracellular pancreatic trypsin inhibitor SPINK1

Phase 2 - intra pancreatic inflammation

Phase 3 - extra pancreatic inflammation including systemic sepsis and multi-organ failure

Question 28

What is chronic pancreatitis?

Answer 28

inflammation of the pancreas that does not heal or improve.

most common cause of chronic pancreatitis is chronic alcohol abuse

Question 29

What are the main causes of chronic pancreatitis?

Answer 29

chronic alcohol abuse
hereditary disorders
cystic fibrosis
hypercalcemia
hyperlipidemia

Question 30

How can you treat chronic pancreatitis?

Answer 30

hospitalisation for pain management, IV hydration and nutritional support

Question 31

What is the role of CCK in pancreatic stimulation?

Answer 31

CCK from duodenal I cells stimulates the pancreatic acinar cells to increase protein secretion.
CCK levels increase in response to a fatty meal plasma.
CCK secretion is also stimulated by CCK-releasing factors (LCRF) which are proteins secreted into the gut lumen.
The fasting state, LCRFs are degraded by digesting enzymes so no CCK stimulation ocurs

Question 32

What is the sphincter of Oddi?

Answer 32

regulate the flow of bile and pancreatic juices as well as to prevent the reflux of duodenal contents into the pancreatobiliary system.

Question 33

What stimulates the pancreatic acinar cells?

Answer 33

Stimulation mainly mediated through CCK receptors and muscarinic ACh receptors on the basolateral cell membrane.

Question 34

What is the pancreatic duct cell HCO3 fluid secretion important for?

Answer 34

alkinizes and hydrates the protein rich secretion of acinar cell,

Important for enzymatic optional pH and micelle formation and neutralising acid.i

Question 35

What would an analogue of somatostatin be used for clinically?

Answer 35

Used to inhibit pancreatic secretions.

Question 36

What causes low levels of pancreatic acinar cell secretions in an unstimulated state?

Answer 36

Constitutive secretory pathway.

Question 37

What is the most important humoral regulator of duct cell secretion?

Answer 37

Secretin (from S cells)

Question 38

What Stimulates Duct cell release?

Answer 38

Secretin binds to its receptor on the duct cell stimulating adenyl cyclase to raise cAMP levels and trigger PKA.
This leads to the stimulation of the apical CFTR Cl channel and basolateral Na/HCO3 cotransporter.

Question 39

What is Cystic Fibrosis?

Answer 39

Common genetic disease caused by a mutation in the CF gene resulting in an altered functioning CFTR protein.

Question 40

What happens to the CFTR protein in Cystic fibrosis?

Answer 40

CFTR is prematurley degraded and thus the apical transport process of HCO3/Cl ions is interupted.
This leads to a thicker protein secretion since it is not hydrated leading to ductal obstruction.

Question 41

How does gastric acid in the intestinal phase of pancreatic secretion cause pancreatic secretion?

Answer 41

Gastric acid stimulates duodenal S cells to release secretin. This stimulates duct cells to secrete HCO3 and fluid.

Question 42

How do lipids in the intestinal phase of pancreatic secretion cause pancreatic secretion?

Answer 42

Lipids (monoglycerides/FFA) predominantly stimulate duodenal I cells to release CCK, which stimulates acinar cells to release digestive enzymes.

And vagovagal enteropancreatic reflux stimulating acinar cells.

Question 43

How do ACh and CCK lead to increased acinar cell secretion?

Answer 43

Receptors signal through the phospholipase C and protein Kinase C pathway signal transduction which leads to increased Ca ions causing enzyme secretion from the cell