Physiology - Unit 3 - L3 - Pancreatic Juices

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  1. Function of pancreas
    • exocrine: 90%. enzymes and neutralization. 1.5L/d
    • endocrine: 10%.
  2. Structure/function of exocrine pancreas
    • acinar cells -> synthesizing and secreting digestive enzymes, low volume
    • centroacinar cells -> add volume, similar to plasma
    • duct cells -> large volume of alkaline juice; HCO3-; neutralize gastric content to pH 7; discourage ulcers
  3. Unlike saliva, the secretion of pancreas is regulated by
    • both neurocrine and endocrine, which allows it to regulate under a wider range of
    • conditions.
    • In pancreas, receptors are species specific, and mostly G-protein coupled.
  4. The pH sensing mechanism is located within ______ that are stimulated to releases _____ when the luminal pH drops below ___.
    • the S-cells of the intestine
    • secretin
    • 4.5
  5. Structural Compartmentalization of pancreas
    • - resembles salivon
    • - secretes aqueous and organic component
  6. acinar cells
    • – secrete organic component
    • - contains digestive enzymes - amylase, protease, lipase
    • - low volume fluid - similar to plasma
  7. duct cells
    • – secrete high volume aqueous alkaline juice
    • - neutralizes gastric juice
    • - provides optimal pH
    • - discourages ulcers
  8. Endocrine hormones regulate pancreas
    • "full status"
    • CCK (cholecystokinin)
    • secretin
  9. CCK
    - released from
    - releasing signals
    - receptor
    - second messengers
    • - intestinal I-cells
    • - nutrients - fatty acids and amino acids
    • - CCK-A (CCK-1) receptor; highly specific for CCK; low affinity to gastrin
    • - IP3 and Ca2+
  10. Secretin
    - released by
    - releasing signals
    - second messenger
    • S-cells of upper small intestine
    • gastric acid in duodenum
    • cAMP
  11. Neural Regulation of pancreas
    • ACh: most important; M3; IP3/Ca
    • VIP: less important postganglionic peptide
    • GRP: less important postganglionic peptide
    • sympathetic: celiac and superior mesenteric plexus; indirectly inhibit secretion via reducing blood flow, not receptors.
  12. Direct Regulation of Enzymatic Component (historical textbook; rodent model):
    agonist binds directly to basolateral receptor on acinar or duct cells
  13. Direct Regulation of Enzymatic Component (historical textbook; rodent model):
    Acinar cells
    • 1) CCK (endo)
    • - CCK-A (CCK-1) receptor
    • - IP3/Ca2+
    • 2) Gastrin (endo)
    • - competes with CCK; lower affinity (50%)
    • 3) ACh (neural)
    • - M3
    • - IP3/Ca2+
    • - additive to CCK
    • - inhibited by vagotomy and atropine

    Enzymes
  14. Direct Regulation of Enzymatic Component (historical textbook; rodent model):
    Duct cells
    • Secretin (endo; key mediator)
    • - cAMP
    • - potentiates CCK and ACh

    Alkaline juice
  15. Indirect Regulation of Acinar Cell in Humans – new model
    • - low expression of acinar CCK-1 receptors and very low affinity
    • - CCK still important but indirect
    • - neural CCK-1 receptors -> vago-vagal pathway  (intestine -> brain -> vagus) ->ACh -> pancreas -> M3 receptor
    • - high M3 density
    • - most potent enzyme releaser
  16. Enzymatic Component
    - Enzyme secretion initiated on _______
    - ___ determines type of enzymes synthesized
    - Control of action:
    • food intake; no secretion when sleeping or fasting; protective
    • Diet
    • active at duodenal pH
  17. __ Enzyme Families (over __ enzymes):
    • 5
    • 20
    • 1) Pancreatic Amylases
    • 2) Pancreatic Proteases - largest family
    • 3) Pancreatic Lipases
    • 4) Ribonucleases – degrade nucleic acids
    • 5) Pancreatic associated protein - bacteriostatic; increase when damaged
  18. 1) Pancreatic Amylases
    - substrate
    - vs. salivary amylase
    - releasing signal

    2) Pancreatic Proteases
    - substrate
    - release as ____
    - representative:

    3) Pancreatic Lipases
    - synthesized and secreted ______
    - substrate
    • – starches
    • - 94% identical
    • - high carbohydrate diet increases gene expression for amylases
    • - released in active form

    • – proteins
    • - inactive zymogens
    • - trypsin
    • -- most aggressive enzyme
    • -- trypsiogen - major proenzyme; only activated in duodenum
    • -- inhibitor in acinar cells prevents premature activation and autodigestion

    • - in active form
    • - lipids
  19. Aqueous Component
    rate of synthesis and secretion
    • - 1.5L/d isotonic
    • - low during fasting or interdigestive states
    • - stomach empties (acid) into duodenum, increase 5-20 fold
    • - highest rate of synthesis and secretion of any organ
  20. Finger print of pancreatic juice
    Image Upload
  21. The Aqueous Component
    - Resting State
    - volume ____
    - [Na+] ____
    - [K+] ____
    - [HCO3-] ________
    - [Cl-] _________
    - relationship among major ions concentration
    - pH _____
    - osmolarity
    • low
    • similar to plasma - all rates
    • similar to plasma - all rates
    • higher than plasma and increases with rate
    • lower than plasma and decreases with rate
    • [Na+] >[Cl-]>[HCO3-]>[K+]
    • slightly alkaline and increases with
    • secretory rate
    • isotonic at all rates
  22. The Aqueous Component
    - Simulated State
    - volume ____
    - [Na+] ____
    - [K+] ____
    - [HCO3-] ________
    - [Cl-] _________
    - relationship among major ions concentration
    - pH _____
    - osmolarity
    • high
    • similar to plasma
    • similar to plasma
    • much higher than plasma
    • much lower than plasma
    • [Na+] > [HCO3-] >> [Cl-] > [K+]
    • alkaline (8.1)
    • isotonic
    • food->duodenum->S cells->secretin->ductal cells
  23. HCO3 secretion

    - Basolateral absorption sources:

    - Apical secretion into duct lumen:
    • 1) enters from blood as CO2 -> carbonic anhydrase
    • 2) absorption from blood - cotransport with Na+ (NBC-1; 2HCO3:1Na; in response to the alkaline tide)

    • - against electrochemical gradient
    • - Cl/HCO3 exchanger (key)
    • - several other apical chan
    • -- CFTR: primary; only in duct cells
  24. HCO3 secretion - H+
    • 1) Na/H exchanger (NHE-1)
    • 2) H-ATPase- some species- neutralizes alkaline tide; acid tide; neutralized by HCO3
  25. Cl- secretion
    - primary driving force for ______

    - basolateral membrane: ______

    - apical membrane key: _______
    -- resting state - ______
    -- stimulated state
    --- pathway: ______
    volume

    Na/K/2Cl – absorption

    • Cystic Fibrosis Transmembrane Regulator (CFTR)
    • channels closed
    • secretin -> basolateral receptor -> cAMP -> PKA -> chan phosphorylated and open
  26. How does Cl- secretion helps increasing the lumenal volume?
    • - anion increases negativity of duct lumen
    • - paracellular Na+ transport
    • - water follows via paracellular and transcellular (aquaporins)
  27. Disorders of Pancreatic Secretion - Cystic Fibrosis – may develop before birth
    - Cause:
    • only becomes significant when <10% is normal
    • - mutation of gene that encodes for CFTR
    • - defective CFTR degraded by endoplasmic reticulum
    • - reduces number of channels
  28. Symptoms of Cystic Fibrosis:
    1) secretion
    2) function
    • - thickened pancreatic, respiratory, GI secretions
    • - mucous obstructed ducts
    • - cells and glands destroyed

    • - low levels digestive enzymes secreted
    • - malnutrition
    • - reduced driving force in acinar cells
    • - steatorrhea - inactivated lipases; fat in stool; early sign of pancreatic deficiency

    - can test CCK and secretin for examining pancreatic functions
  29. Treatment for CF
    • - oral enzymes
    • - ingest medium chain fatty acids
  30. Animal models for CF
    • rat: unsatisfactory
    • piglet: same symptom as human
Author:
Anonymous
ID:
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Card Set:
Physiology - Unit 3 - L3 - Pancreatic Juices
Updated:
2016-02-08 06:55:17
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physiology GI pancreas
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Description:
Physiology - Unit 3 - L3 - Pancreatic Juices
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