Unit VI- Pancreatic and Biliary Secretion Flashcards Preview

MS 1 Unit VI Physiology > Unit VI- Pancreatic and Biliary Secretion > Flashcards

Flashcards in Unit VI- Pancreatic and Biliary Secretion Deck (39)
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1
Q

Digestive Enzymes

A

Salivary- Amylase, Lingual lipase

Gastric- pepsin

Pancreatic- amylase, trypsin, chymotrypsin, carboxypeptidase, elastase, lipase-colpase, phospholipase A2, cholesterol esterase- nonspecfic lipase (1 L digestive juices/day)

Intestinal- enterokinase, disaccharidases (maltase, sucrase, lactase, trehalase, isomaltase), peptidases (aminooligopeptidase, dipeptidase)

2
Q

Proteases

A
  • digest proteins
  • Trypsinogen
  • chymotrypsinogen
  • procarboxypeptidase A and B
  • zymogens have no enzymatic activity until activated in the gut
3
Q

Lipases

A
  • digest fats
  • lipase
  • phospholipase
4
Q

Amylases

A

-digest carbohydrates

5
Q

Nucleases

A
  • digest nucleic acid
  • ribonuclease
  • deoxyribonuclease
6
Q

Pancreatitis

A

-the pancreas becomes inflamed and the digestive enzymes are activated before they reach the intestine causing damage to the pancreas

7
Q

Pancreas

A
  • most important digestive gland
  • 1 L of fluid secreted per day
  • Exocrine secretions(into ducts thence to the lumen) : aqueous juice high in HCO2- from centro-acinar and duct cells; enzyme juice from acinar cells and centro-acinar cells into the intercalary ducts which merge into the secretory ducts- then the secretion flow through the ducts of Wirsung and Santorini and are delivered into the duodenum

-endocrine secretions (into blood) from islets of langerhands regulate blood sugar and metabolism; glucagon secreted by alpha cells, insulin secreted by beta cells, somatostatin secreted by delta cells

8
Q

Pancreatic Aqueous Secretion

A
  • bicarbonate neutralizes acid from stomach and allows pancreatic enzymes to function at their optimal neutral pH
  • pepsin is inactivated at neutral pH, and thus cannot attack the duodenal mucosa
  • neutralization of pH prevents damage to duodenal and intestinal mucosa by gastric acid
  • aqueous secretion also serves to dilute the enzyme juice
  • aqueous secretion originates in the centro-acinar cells and epithelial cells of intercalary ducts
9
Q

Organization of the Exocrine Pancreas

A
  • fundamental secretory unit is composed of an acinus and an intercalated duct
  • intercalacted ducts merge to form intralobular ducts which in turn merge to form interlobular ducts and then the main pancreatic duct
  • the acinar cell is specialized for protein secretion
  • large condensing vacuoles are gradually reduced in size and form mature zymogen
10
Q

Synthesis and Secretion of Enzymes

A
  • originates in pancreatic acinar cells
  • formed on ribosomes accumulate in rough surfaced cisternae
  • smooth surfaced vesicles containing enzymes bud off, coalesce to form zymogen granules that usually contain pro-enzymes
  • mature zymogen granules fuse with apical membrane and contents are discharged into lumen of acinus during secretion
11
Q

Pancreatic Acinar Cells Showing Potentiation of Enzyme secretion by secretin and CCK

A
  • vagal stimulation is via ACh
  • CCK, ACh, and gastrin increase intracellular calcium
  • secretin and VIP increase cAMP via G coupled receptor which activates Gs, which adenylate cyclase which activates cAMP
  • ACh- binds muscarinic receptor Gq coupled increase PLC make PIP2 and DAG
  • secretin and CCK act synergistically- their effect when both are present is greater than the sum of their effects when either is acting alone
  • VIP is a neurotransmitter in the gut normally not important in pancreatic secretion, but it becomes important in certain pancreatic tumors known as vipomas, which result in a watery diarrhea
  • note that secretin and CCK potentiate each others actions both on pancreatic enzyme secretion
12
Q

VIP

A
  • vasoactive intestinal peptide
  • neurotransmitter in the gut normally not important in pancreatic secretion but it becomes important in certain pancreatic tumors which result in watery diarrhea
13
Q

Secretion of Chloride by the Acinar Cells

A
  • the Na-K pump creates the inwardly directly Na+ gradient across the basolateral membrane
  • the Na/K/Cl cotransporter produces the net Cl- uptake, driven by the Na+ gradient, which is generated by the Na-K pump
  • rise in intracellular K+ that results from the activity of the pump and cotransporter is shunted by basolateral K_channels that provide an exit pathway for K+ (CCK and cholinergic neurotransmitter ACh stimulators of Cl- secretion-probably through phosphorylation of basolateral and apical ion channels)
  • intracellular Cl- establishes the electrochemical gradient that drives Cl- secretion into the acinar lumen through apical membrane Cl- channels
  • the movement of Cl- into the lumen makes the transepithelial voltage more lumen negative, driving Na into the lumen via tight junctions
14
Q

Na and HCO3- secretion by pancreatic duct cells

A
  • diffusion of CO2 from the blood across the basolateral membrane into the duct cell
  • hydrated by carbonic anhydrase to carbonic acid which dissociates to form H+ and HCO3-
  • proton moves across basolateral membrane by Na+/H+ exchanger or an electrogenic proton pump
  • bicarbonate accumulates in duct cell and exits across apical membrane via Cl-/HCO3- exchanger
  • chloride channel is CFTR which is activated by secretin using cAMP, which stimulates PKA
  • there is also a Ca2+ activated K channel
  • CCK uses Ca2+ as second messenger to potentiate action of secretin
  • K+ leaves the cell to to prime the Na+/K+ pump increasing the rate of secretion by the duct cell
  • this generates negative transmembrane PD- driving force to move Na+ and K+ ions into the lumen via cation selective paracellular pathway
15
Q

Features of Aqueous Secretion

A
  • venous blood is acidified during secretion by an electrogenic proton pump and by Na+/H+ exchange in the basolateral membrane; tends to negate “akaline tide”
  • in the intestinal phase both secretin and cholecystokinin (CCK) stimulate aqueous secretion by pancreatic duct cells
16
Q

Secretin

A

-using cAMP as its second messenger, activates the CFTR Cl- channel thereby replenishing lumenal Cl- needed for Cl-/HCO3- exchange

17
Q

Cholecytokinin

A
  • CCK
  • acts via PLC to increase the intracellular concentration of Ca++ this potentiates the action of secretin by priming the Na+/K+ ATPase
  • apical k+ channel is activated by Ca++
  • increased K+ efflux primes the Na+/K+ -ATPase
18
Q

Composition of pancreatic juice and flow rate

A
  • secreted fluid is high in HCO3- as seen at fast rates of secretion
  • HCO3- exchanges with Cl- in ducts when rate of secretion is low
  • Na+ and K+ concentration remain constant at different flow rates
  • -the exchange hypothesis accounts for the increase in bicarbonate with increase secretory rate
19
Q

Cystic Fibrosis

A
  • when CFTR channel is defective pancreatic secretions are thick and viscous, thus clogging the pancreatic ducts and interfering with digestion
  • pulmonary mucous is also thick with viscous, causing dyspnea (labored breathing) and premature death
  • aqueous secretion is needed to dilute the pancreatic enzyme secretion and reduce its viscosity
20
Q

Regulation of Pancreatic Secretion

A
  • pancreatic secretion is in 3 stages. The first 2 are low in volume and high in enzyme content
  • cephalic phase: vagal stimulation has greater effect on enzyme secretion from acini than on ductal aqueous secretion
  • gastric phase:-distension of body of stomach induces pancreatic enzyme secretion by vago-vagal reflex
  • antral distension release gastrin which stimulates acinar cells to secrete enzymes (and the oxyntic parietal cells to secrete HCl)
  • intestinal phase: secretion and cholecystokinin (CCK) released into the blood from intestinal cells in response to products of digestion
21
Q

Secretin

A
  • 27 amino acid peptide hormonne released into blood by S cells in duodenal mucosa in response to acid entering the intestine
  • natures antacid because it inhibits gastric acid secretion and release of gastrin
  • but stimulates gastric chief cells to secrete pepsinogen
  • elicits aqueous secretion by pancreatic duct cells with secondary effect on acinar cells
  • secretion is high in volume, high in HCO3 and low in enzyme content
22
Q

Cholecystokinin

A
  • 33 amino acid peptide released into blood from I cells in duodenal mucosa in response to fatty acids or amino acids entering the duodenum
  • elicits enzyme secretion by acinar cells and also potentiates aqueous secretion during intestinal phase
  • also causes gallbladder contraction and relaxes sphincter of Oddi to release bile from gallbladder into duodenum
  • also slows gastric emptying
  • pancreatic enzyme secretion is high in enzyme content, low in volume
23
Q

Composition of Bile

A
  • a yellow green alkaline solution containing bile salts, bile pigments, cholesterol, neutral fats, phospholipids and electrolytes
  • bile salts are cholesterol derivatives that emulsify fat, facilitate fat and cholesterol absorption, help solubilize cholesterol
  • enterohepatic circulation recycles bile salts
  • the chief bile pigment is bilirubin, a waste product of heme
24
Q

Biosynthesis of Bile Salts

A

-the rate limiting step in bile acid formation is the addition of the hydroxyl group at position 7 by cholesterol 7 alpha-hydroxylase. Expression of this enzyme is reduced by bile acid and increased by cholesterol

25
Q

Bile acids

A
  • steroid hormones, made by liver and activating a nuclear hormone receptor to regulate expression of cholesterol 7 alpha-hydroylase
  • production must be carefully balanced since at high levels they have carcinogenic properties
  • liver conjugates primary and secondary bile acids with glycine or taurine to their respective bile salts
  • the resulting bile salt is named for the bile acid and the conjugating amino acid
26
Q

Choleretic

A

-an agent that stimulates the liver liver to increase output of bile

27
Q

Bile acid sequestrants

A

-bind bile acids and prevent reabsorption from the gut and can be used to lower cholesterol

28
Q

Bile salts

A
  • amphipathic, they contain both a hydrophobic end (steroid nucleus) and a hydrophilic end. All contain the same hydrophobic end, but the hydrophilic ends differ
  • they emulsify and solubilize fats and steroids (cholesterol)
  • water solubility is conferred by the presence of -OH groups and ionized groups
  • non conjugated bile salts have a pK of 7
  • conjugated with glycine (75%) or taurine (25%) in the liver.
  • glycine conjugates have pK of 3.7; taurine conjugated have a pK of 1.5
  • therefore at pH 7 virtually all conjugated bile salts are anionic- they are very water soluble
29
Q

Bile is secreted into Canaliculi

A
  • bile is produced and secreted continuously by hepatocytes of the liver
  • secreted into bile canaliculi which empty into bile ducts
30
Q

Bilary Function

A
  • Bile ducts -> hepatic ducts -> common bile duct -> duodenum
  • cystic duct -> gall bladder
  • when sphincter of Oddi is open bile is free to flow into the duodenum. When closed it is diverted into the galbladder
  • stored and concentrated in gall bladder
  • CCK contracts the gall bladder and relaxes the Sphincter of Oddi
  • necessary for digestion and absorption of lipids as well as elimination of cholesterol and bile pigments
  • composed of bile acids (-50%), phospholipids (25%), cholesterol (4%), bile pigment (2%) inorganic ions and IgA
31
Q

Daily Bile Salt Turnover

A
  • bile salts serve to emulsify fats and cholesterol in the intestine
  • bile salt balance
  • total bile salt pool: 3-4g
  • daily secretion by liver: 12-25 g
  • bile salts are reabsorbed and secreted twice during a meal and several times daily via the enterohepatic circulation
  • daily loss in feces and replaced by synthesis in liver -0.5g
  • hepatic production of bile acids is the major route of cholesterol and steroid hormone breakdown
  • body makes 800 mg of cholesterol every day and 50% of that used to make bile salts
32
Q

Bilary Secretion

A
  • bile captured from the intestine flows to the liver through the portal vein
  • then it is absorbed by the hepatocytes
  • finally it is secreted into the canaliculus
  • bile returns to the liver bound to albumin
  • it is taken up by the liver by specific transporters: sodium taurocholate cotransporting polypeptide (CTCP) and organic anion transporting polypeptide (OATP)
33
Q

Bile Acid Secretion

A
  • bile acid-independent secretion of watery HCo3- rich fluid by cholangiocytes of the ducts and ductules similar to pancreatic aqueous secretion- stimulated by secretin
  • bile acid-dependent secretion by hepatic parenchymal cells
  • stimulated to secrete by bile acids returning to lover in portal blood
  • synthesis of bile acids is inhibited by bile acids returning to liver via portal blood (feedback inhibition)
34
Q

Enterohepatic Circulation of Bile Acids and Salts

A
  • most bile acid are reabsorbed as conjuated bile salts in the terminal ileum through an Na+-coupled cotransporter (ASBT)
  • bacteria deconjugate a small amount of bile salts to unconjugated bile acids which are passively absorbed by nonionic diffusion
  • bacteria also dehydroxylate primary bile acids to secondary bile acids
  • some are captured and returned to liver others are excreted in the feces
  • bile salt malabsorption caused by terminal ileum resection can cause chronic diarrhea
  • bile acid sequestrants is often an effective treatment
35
Q

BA Concentration in gallbladder

A
  • bile pigments, bile salts, cholesterol, lecithin and fatty acids are concentrated in the gallbladder
  • results from active transport of Na+, Cl- and HCO3- out of lateral membranes of gallbladder epithelial cells and continued micellar formation
  • isotonic fluid reabsorbed by the gallbladder epithelium
  • the apical step is parallel Na-H exchange and Cl-HCO3 exchange
  • because Na-H exchange is faster net secretion of acid into lumen occurs
  • basolateral step of NaCL absorption is mediated by the NaK pump and Cl channels
  • K channels provide a route for basolateral K+ recycling
  • water follows passively through the tight junctions and through the basolateral membrane
36
Q

Release of Bile from Gallbladder

A
  • Neural-vagus
  • Hormonal-CCK
  • relaxes sphincter of Oddi and contracts the gallbladder
  • the gallbladder like the stomach responds to cephalic stimuli, such as highly emotional situations
37
Q

Approximate composition of human bile in liver and gallbladder

A
  • isosmotic to plasma but the total number of ions exceeds 300 mOsmolar, due to formation of micells consisting of bile salts, lecithin and cholesterol
  • Gallbladder bile are 10C
38
Q

Bile Micelles

A

-serve as solvents for hydrophonic waste products to be removed from the body and hydrophobic components of the diet to be captured from the intestine

39
Q

Formation of gallstones

A

1) supersaturation of cholesterol- in liver
2) nucleation and precipitation- seeding of cholesterol crysals or microstones- probably in gallbladder
3) growth of microstones to form macrostones

15% lecithin
80% bile salts
5% cholesterol