gastric secretions II

what is the structure of the pancreas?

• bile duct

• duodenum

• blood vessel

• pancreatic duct

• endocrine - islets of langerhans cells secrete hormones into blood vessels

• exocrine - acinar cells secrete digestive enzymes into the pancreatic duct

what is the functional unit of the exocrine pancreas?

• duct cells secrete aqueous NaHCO3- rich secretions (~75%)

• granules accumulate during fasting

• acinar cells secrete enzymes and NaCl rich secretions (~25%)

what is pancreatic exocrine secretion compose of?

• 1-1.5 L per day

• isotonic or slightly hypertonic and alkaline (pH ~8.0)

functions:

• digestion - lipase, amylase and proteolytic enzymes important for nutrient digestion

• pH buffering - high levels of HCO3- neutralise HCl emptying from stomach

what do proteolytic enzymes require

• activation!

  • zymogens = inactive enzymes, released from the acinar cells by exocytosis - activated in the upper cell intestine

what is the aqueous component of pancreatic secretion?

• generated from columnar epithelial cells that line the ducts

  • resting - spontaneous secretion

  • stimulated by secretin (interlobular duct)

what does the aqueous component of pancreatic secretion look like in the unstimulated state?

• occurs in the lobules, plasma like in nature

• low levels of aqueous secretion

• don’t get modification in the interlobular duct

what does the aqueous component of pancreatic secretion look like in the stimulated state?

• occurs in the interlobular duct, stimulated by secretin

• high levels of aqueous secretion that are high in HCO3- and low in Cl-

• CFTR could drive HCO3- and Cl- exchange

  • CFTR has conductance to both Cl- and HCO3-

• predominant pathway for HCO3- in the stimulated state

• unclear whether less Cl- secreted and or what is in 1ry secretion is diluted

what are the differences between salivary and pancreatic secretion?

describe pancreatic disease in cystic fibrosis.

• pancreatic acinar cells secrete large quantities of enzymes

  • Cl- and HCO3- are normally secreted into the ductal lumen via CFTR. this provides a driving force for the fluid movement necessary to maintain solubility of ductal enzymes

• in cystic fibrosis:

  • impaired CFTR function results in low volumes of more acidic fluid, leading to enzyme precipitation

  • the resultant obstruction of ducts in CF causes:

    • pancreatic insufficiency

    • reduced efficiency of nutrient digestion

    • progressive pancreatic damage

how is pancreatic secretion controlled?

• nerves - parasympathetic

• hormones:

  • cholecystokinin (CCK)

  • secretin

  • gastrin - from stomach

• 3 phases of pancreatic secretion:

  • cephalic - 20%

  • gastric - 10%

  • intestinal - 70%

what is the cephalic phase?

• sight, smell, taste, chewing → vagal stimulation → secretion of Ach at vagal nerve endings → acinar duct cell secretion → enzymes → HCO-3

what is the gastric phase?

• gastric dimension → vago-vagal reflex → secretion of Ach at vagal nerve endings → - acinar & duct cell secretion → enzymes & HCO3- → gastrin release from g cells (via gastric nerves)

• peptides in antral lumen → gastrin release from g cells → acinar cell secretion → enzymes & HCO3-

what is responsible for the intestinal phase of pancreatic secretion?

• hormones

  • increase H+ (pH <3.5) - cause secretin release

  • fat & protein digestion products cause CCK release

what is the pH-stat function of secretin?

secretin controls duodenal pH by:

• increase pancreatic HCO3- secretion

• decrease gastric emptying

• decrease gastric acid secretion

what are the functions of the liver?

• carbohydrate metabolism

• protein metabolism

• lipid metabolism

• iron storage

• detoxification

• synthesis and secretion of bile

what does the liver lobule contain?

• central vein

• liver cells

• bile canaliniculi

• portal vein, hepatic duct, bile duct

what are the characteristics of bile?

• cholesterol

• bile salts & bile acids

• water & electrolytes

• bile pigments (bilirubin)

  • 0.6-1L per day

  • isotonic & alkaline

  • yellow-green in colour

what is the production of bile?

• bile acids are derivatives of cholesterol

• bile acids are synthesised by hepatocytes or extracted from the blood by an active process

• bile acids are conjugated in hepatocytes to form bile salts which are actively secreted into the bile canaliculi

• Cl-, HCO3-, Na+, H2O are then added to the hepatic bile as it moves along the bile duct

how is bile circulated?

• production = 0.3-0.5g/day + pool of 3g

• excretion = 0.3 - 0.5g/day

what are the cellular mechanisms involved in bile secretion?

two component:

• bile acid-dependent

  • Na+/BA transporter

  • 95% BA recycled

• bile acid-independent

  • BA conjugated

  • secreted with Na+ & H2O

  • in duct Na+, HCO3-, H2O

how is hepatic bile along the bile duct modified?

• similar mechanisms to pancreatic secretions

• volume is not to the same extent as the pancreas

what is the role of the gallbladder?

• stores up to 50% of hepatic bile during the inter digestive phase

• concentrates hepatic bile by absorbing Cl-, HCO3-, Na+ and H2O

• bile salts in gallbladder are concentrated up to 20-fold

• presence of chyme in the duodenum stimulates the release of CCK which causes contraction of the gall bladder

how is bile modified in the gallbladder?

• large and long lateral channels creates local high osmotic pressure

• concentrated bile → ‘critical micellar concentration’

how is bile secretion regulated?

• PNS stimulates blood flow & therefore BA recycling

• fatty acid & amino acids in chyme entering the duodenum stimulate secretion of CCK into the blood

• acidic chyme entering duodenum stimulates secretion of secretin into the blood

• CCK causes contraction of gallbladder

• secretin enhances flow of bile rich in HCO3- from liver

what is the role of bile in fat digestion & absorption?

1. Digestion

   • emulsification of fat - increases efficiency of lipase action

   • activation of pancreatic lipase, cholesterol esterase

2. Absorptive

   • micelle formation - a micellar solution differs from an emulsion in that:

     • a far soluble compounds are in solution

     • much smaller particles (greater stability)

   • micelles are essential for uptake of fat-soluble compounds, BUT are not absorbed into the epithelial cell at the same time as the fat

how is fat emulsified?

• in the stomach, ingested fat form large fat globules

• as the fat globules enter the duodenum, they are coated with bile salts

• fatty droplets are pulled off the large fat globules and a stable emulsion is created

how are mixed micelles formed?

why are micelles important to fat absorption?

• made in liver

• are formed of around 20-40 bile salt molecules and lechitin

• they absorb fat-soluble vitamins, cholesterol, fatty acids and monglycerides

• hydrophilic shell allows the micelle to cross the unstirred water layer to the epithelial surface

explain intestinal absorption of fat absorption.

• unstirred H2O layer

• ~80g/day absorbed by jejunal enterocytes

• resynthesised to triglycerides

• packaged into chylomicrons

• bile acids (from micelles) are actively absorbed in terminal ileum

what is the excretory role of bile?

what is obstructive jaundice?