Rao 5 - Pancreatic Secretions Flashcards

1
Q

What are the two general components of pancreatic secretions?
• What are their jobs?
• Cells that secrete these?

A

Ductal and Centriacinar cells secrete HCO3-. This neutralizes stomach acid and activates pancreatic enzymes.

Acinar cells secrete Proteins (enzymes) that degrade food.

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2
Q

T or F: the bulk of fluid volume in pancreatic secretions can be attributed to acinar cells.

A

False, most volume can be attributed to ductal and centraacinar cells.

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3
Q

What provides the sympathetic and parasympathetic innervation to pancreatic exocrine ducts?

A

Stimulation: Parasympathetic - Vagus n.

Inhibition: Sympathetic - celiac and superior mesenteric plexuses

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4
Q

T or F: like the salivary glands, the pancreas is not affected by hormonal stimulation

A

False, Secretin and CCK both are important in stimulating the pancreas

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5
Q

What transporters, pumps, and/or channels are found on the Basement membrane of Ductal and Centriacinar Cells?
• are these driven by primary or secondary active transport?

A
  1. NKATPase exports Na from the cells and Imports K (ouabain dependent)
    • This primary active transport drives the secondary active transport of all other enzymes
  2. Na/H+ Exchanger exports H into the cells and imports Na
    • Secondary active transport with gradient provided by NKATPase
  3. HCO3/Na Cotransporter moves both HCO3 and Na into cell from blood
    • Secondary active transport with gradient provided by NKATPase
  4. AQP1 - allows H2O to diffuse into the cell
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6
Q

What transporters, pumps, and/or channels are found on the Apical Side of Ductal and Centriacinar Cells?
• are these driven by primary or secondary active transport?

A
  1. CFTR HCO3/Cl Cotransporter - cAMP activated
  2. HCO3/Cl Exchanger - imports Cl into the cell and puts HCO3 into the lumen
  3. Cl Channel - allow Cl to flow back out of the cell so that the HCO3/Cl exchanger can continue to run
  4. AQP1 - allows passage of H2O to increase the volume of secretions
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7
Q

What ion can travel paracellularly between pancreatic ductal cells?

A

Na+ can travel between ductal cells in the pancreas.

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8
Q

What would happen if the chloride channel was knocked out from pancreatic ductal cells?

A

Cl Channel allows for recycling of Cl- into the ductal cell lumen so that it can flow back down its gradient through the HCO3/Cl channel so that HCO3 can get pumped out. A lack of Chloride would prevent HCO3 secretion from ductal cells.

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9
Q

What would happen if the Na/K ATPase was blocked in the pancreatic duct?

A

*All transport would be blocked because the secondary active transporters like Na/HCO3 cotransporter and N/H exchanger (Basal side) and Cl/HCO3 exchanger (apical side) would be inhibited.

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10
Q

T or F: like salivary secretions, the secretions of the pancreas are hypoosmolar.

A

False, secretions of the pancreas are ISOTONIC

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11
Q

How does the electrolyte composition of the pancreatic secretions different than the plasma?

A

The concentration of Na+ and K+ is the SAME as plasma, but HCO3- and Cl- levels are different

**Specifically HCO3- is higher than in the plasma and Cl- is lower

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12
Q

How does the composition of Pancreatic Secretions change at High and Low flow rates?
• How can this be explained?

A

**Remember this fluid is Isotonic at all flow rates with a constant composition of Na and K**

More HCO3- at HIGH flow rates because lots of NaCl is secreted by acinar cells which can be used to import Cl- and Export HCO3- into the lumen of the duct**

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13
Q

What are the steps in Enzymes Secretion from the acinar cells in the pancreas?

A
  1. Polysomes (ribosomes strung together by a single strand of mRNA) synthesize a protein
  2. Hydrophobic end of protein translocated to rER
  3. Vesicles bud off of the ER and go to to golgi, get processed and then are excreted from the golgi
  4. Enzymes are concentrated in cytoplasmic vacuoles to increase enzyme concentration
  5. Granules are released in cAMP => PKA dependent fashion
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14
Q

What is the only regulated step in enzyme secretion from Acinar Cells?
• What mediators trigger release?

A

cAMP-PKA dependent release of particles is the only regulated step in zymogen release

Regulators:
• Secretin
• Ach
• CCK

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15
Q

What is the cephalic phase of protein secretion?
• what mediated this effect?

A

In this phase ONLY pancreatic ENZYMES are released, very little bicabonate triggers this release.

Stimuli in the CNS (Smell, taste, chewing, swallowing, hypoglycemia) send excitatory signals down the parasympathetic pathways via the Vagal nerve leading to Ach secretion

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16
Q

Cephalic Phase of Pancreatic Secretion
• what happens?

A
17
Q

Gastric Phase of Pancreatic Secretion
• Stimulus?
• How is it mediated?

A

Stimulus=> Distention of the stomach

  • Mediated via a Vasovagal Reflex
  • Ach is again released with a similar outcome as the cephalic phase (Acinar cells predominantly stimulated)
18
Q

Which phase of pancreatic secretion leads to the most response from the meal?

A

Intestinal - this accounts for 70-80% of the total response to a meal

19
Q

What hormones are responsible for the intestinal phase of pancreatic secretion?
• What is the stimulus for each of these hormones?
• Cells/Part of intestine these are secreted from?

A

Hormones Responsible are:
H+ => S Cells of Duodenum => Secretin
• Phe, Trp, Met, Proteins, Fats => I Cells of Duodenum => CCK

20
Q

What effect does the pH of the duodenal secretions have on the pancreas?

A

pH lower than 4.5 will trigger release of Secretin that will lead to increased release of HCO3- (levels will increase until gastric pH reaches 3 and they max out)

21
Q

Explain what stimuli and mediators lead to increased panreatic secretions in the intestinal phase.

A

1. Acid Stimulates Secretin Release from S cells that acts directly on ductal cells with only a small effect on Acinar Cells

  1. Cholinergic Pathway Stimulates Acinar Cells
  2. I Cells sense Fat and Protein and Release CCK which trigger Vagal Reflex to stimulate the acinus
22
Q

T or F: like secretin, CCK acts directly on the pancreas to carry out its function.

A

False, CCK does NOT act directly on the pancreas, instead it acts on receptors that stimulate afferent fibers on the vagus n. that then sends an effent response via Ach to pancreatic acinar cells

23
Q

T or F: there is potentiation of CCK, Secretin, and Ach when acting on acinar cells.

A

False, there IS potentiation, but this is on DUCTAL cells not acinar cells

24
Q

What mediator acts as a feedback regulator of secretin release and potentiation by Ach and CCK?

A

Trypsin

25
Q

Why does the action of Ach, CCK, and Secretin have a potentiating effect on DUCTAL cells?

A

These all act through different receptors and pathyways so you can get potentiation

26
Q

What are 3 causes of pancreatic insufficiency?

A
  1. Pancreatitis
  2. Kwashiorkor
  3. Cystic Fibrosis
27
Q

How does pancreatitis lead to pancreatic insufficiency?

A
  • Decreased Volume and Bicarbonate
  • May impair digestion
28
Q

How pancreatitis lead to pancreatic insufficiency?

A
  • Malnutrition
  • Decreased Volume, Bicarbonate, Enzymes
  • Steatorrhea
29
Q

How does Cystic Fibrosis lead to pancreatic Insufficiency?

A
  • No Cl- conductance in apical membrane
  • Mucus Secretion
  • Decreased Volume, Bicarbonate, Enzymes
  • Steatorrhea