GIS18 Control Of Biliary And Pancreatic Exocrine Secretions Flashcards
Pancreas secretion
Exocrine
- Enzymatic component
- secreted by **Acinar cells / Exocrine cells
- contains enzymes for digestion
- stored as **zymogen granules, released by exocytosis
- proteases secreted as inactive forms - Aqueous component (HCO3 / water):
- secreted by **Duct cells / **Epithelial cells of pancreatic ductules and ducts
- **largest supply of HCO3 in the duodenum (> biliary ductules and duodenal epithelial cells)
- neutralises acid chyme from stomach, **stops action of pepsin
- provide optimal pH (7-8) for the action of pancreatic enzymes
Endocrine (Endocrine cells / Islets of Langerhans)
- Insulin
- Glucagon
***Pancreatic enzymes
- Endopeptidases: **Trypsin, **Chymotrypsin, elastase
- protein —> peptide - Exopeptidases: ***Carboxypeptidase A, B (+ Aminopeptidase)
- splits off terminal amino acid from Carboxyl end of protein - Lipase
- TAG —> MG + 2 fatty acids
(- + Lipid esterase + Phospholipase A2) - Amylase
- polysaccharide —> glucose, maltose - Ribonuclease, Deoxyribonuclease
- nucleic acid —> free mononucleotides
Proteolytic digestion by pancreatic enzymes in intestine
Proteolytic enzymes:
- secreted as inactive precursors
- converted to active enzymes only when they reach the lumen of the small intestine
- Trypsinogen is converted to active Trypsin by membrane-bound ***Enterokinase
- Active Trypsin cleaves the other precursors of proteolytic enzymes (e.g. Chymotrypsin, Proelastase) —> make them active
Non-proteolytic enzymes (Amylase and Lipase):
- secreted as active forms by pancreas
Proenzyme and active enzyme (ALL converted by Trypsin)
Endopeptidase:
- Trypsinogen —> Trypsin
- Chymotrypsinogen —> Chymotrypsin
- Proelastase —> Elastase
Exopeptidase:
- Procarboxypeptidase A —> Carboxypeptidase A
- Procarboxypeptidase B —> Carboxypeptidase B
HCO3 secretion
- Primary secretion (intralobular ductal system)
- slightly ***hypertonic to plasma - Secondary secretion (extralobular ductal system)
- HCO3 secretion —> ↑ concentration of HCO3 (exchange with Cl-)
- H2O secretion —> dilution —> become ***isotonic to plasma
(vs Saliva: **Isotonic (NaCl + H2O secretion) —> **Hypotonic (NaCl reabsorption + KHCO3 secretion))
HCO3 secretion from pancreatic duct cell
Formation of HCO3:
- Inside cell: formation of HCO3 from CO2 and H2O by ***carbonic anhydrase
- From blood: transported into the cells by ***Na/HCO3 co-transporter (NBC-1)
—> **HCO3 transported into lumen via **Cl/HCO3 exchanger (apical membrane)
—> Cl recycled into lumen via Cl channel (CFTR cystic fibrosis transmembrane conductance regulator)
—> ***osmosis of H2O down osmotic gradient into lumen
Cystic fibrosis
- defect in CFTR —> cannot drive Cl- out into lumen —> no osmosis of water into lumen —> very viscous —> pancreatic insufficiency / pancreatitis
***Control of pancreatic secretion by small intestine
Hormonal control:
—> ***Secretin, CCK (paracrine) mostly secreted by duodenum and jejunum during Intestinal phase
Neural control:
—> **Vagal during Cephalic phase
—> **Vagovagal during Gastric phase
***Control of pancreatic secretion of HCO3
- Controlled by Intestinal phase (stimulus on small intestine)
↑ **Acid from stomach
—> ↑ stimulus to **S cells in duodenal lumen
—> ↑ **Secretin secretion
—> ↑ **HCO3 from pancreatic ***duct cells
—> ↑ HCO3 into small intestine
—> ↑ neutralisation of acidic chyme from stomach (-ve feedback to S cell)
—> enzymes in small intestine work best at neutral pH
Action of secretin on pancreatic duct cells
Secretin ↑ HCO3 secretion by:
—> ***↑ opening of CFTR (via ↑ cAMP)
—> ↑ outflow of Cl- (into lumen)
—> ↑ exchange of HCO3 into lumen (Cl- back into cells) via Cl/HCO3 exchanger on apical membrane
***Control of pancreatic enzyme secretion
- Controlled by Intestinal phase (stimulus on small intestine)
- Stimuli: fatty acids / amino acids
↑ intestinal **f.a. and a.a.
—> ↑ stimulus to **I cells in duodenal lumen
—> ↑ **CCK secretion by I cells in small intestine
—> ↑ plasma CCK
—> ↑ **enzyme secretion by pancreatic ***acinar cells
—> ↑ enzymes in small intestine
—> ↑ digestion of fats, proteins and carbohydrates
Action of CCK on pancreatic acinar cells
- Directly acting on ***CCK-1 receptor on acinar cells
- Indirectly activates **Vagovagal reflex from small intestine
—> activate pancreatic enteric neurones to release **neurotransmitter (VIP, GRP, ACh)
—> stimulate receptors on basolateral side
—> stimulate acinar cells to increase pancreatic enzymes secretion
—> enzyme washed into duodenum by ductular secretion
Biliary secretion
- secreted by liver cells
- concentrated and stored in gall bladder
- bile contains water, electrolytes, organic molecules including bile acids, cholesterol, phospholipids, bilirubin
- **Bile salts: synthesised from **cholesterol, for fat digestion
- **HCO3 in bile: secreted by bile duct **epithelial cells
- ***Cholesterol: extracted from blood, secreted by liver into bile, then excreted as faeces (cholesterol homeostasis in blood)
- ***Bilirubin / bile pigments: excretion, from RBC breakdown
Stages of biliary secretion
- First stage: **Hepatocytes secrete fluid rich in **Bile salts, ***Cholesterol and other organic components into canaliculi, then flows into bile ducts
- Second stage: **Ductal epithelial cells add watery, **HCO3 rich secretion to modify bile as it flows through the bile ducts
- Bile stored and concentrated in gall bladder between meals through ***absorption of H2O, Na, Cl and other electrolyte, but retaining and concentrating all organic molecules
- Gall bladder contracts and empties bile into duodenum in response to meal
Digestion of lipids
- Most ingested fat in form of TG, some in phospholipids and cholesterol
- mainly in small intestine by ***Pancreatic lipase
- Emulsification:
—> mechanical disruption into small droplets by contraction of stomach and small intestine
—> non-polar portions of phospholipid and bile salt associate with the non-polar portion interior of the lipid droplets
—> polar portions exposed at the water surface, repelling other lipid droplets
—> prevent re-aggregating back into larger droplets
—> allow digestion by water soluble pancreatic lipase at surface of lipid droplet (since fat are insoluble in water and lipase is in aqueous phase)
Formation of micelles:
**Bile salts + Fatty acids + Phospholipids + Monoglycerides
—> all cluster together with polar ends towards micelle’s surface and non-polar ends forming the core
—> cholesterol and fat-soluble vitamins inside core of micelles
—> **micelles ↑↑ solubility of lipid and fat-soluble vitamins in the intestine
—> facilitate their absorption
Fat absorption
- free molecules of fatty acids and MG diffuse into intestinal epithelial cells
- resynthesized into **TAG in **sER
- droplets of TAG secreted as ***chylomicrons which also contain cholesterol + fat-soluble vitamins
- chylomicron passed into ***lacteals
- lymph empties into systemic veins via ***thoracic duct
Enterohepatic circulation
- ~95 % bile salts reabsorbed into blood at the ***Ileum
- return via ***Hepatic portal vein to liver
- absorbed by hepatocytes and re-secreted into bile
- re-circulated several times in a single meal
- 5% lost in faeces replenished by synthesis in liver from cholesterol
- bile salts remain ionised —> unabsorbed to ensure full digestion before conjugation
***Control of biliary secretion
Bile salts secretion increased after absorption of bile salts in the blood from ileum
- Acid in duodenum
—> **Secretin secretion
—> stimulates **HCO3 secretion by bile duct (effect like in pancreatic duct) - Fatty acids in duodenum
—> **CCK secretion
—> stimulates 1. **Contraction of gall bladder and 2. ***Relaxation of sphincter of Oddi (this time not stimulate enzyme secretion)
—> increase bile flow to duodenum - ***Vagus nerve: stimulation of contraction of gall bladder
Bilirubin metabolism
Liver conjugates water-insoluble bilirubin (Free bilirubin)
—> water-soluble bilirubin-glucuronide (Conjugated bilirubin)
—> excreted into bile
—> Conjugated bilirubin —> ***Urobilinogen by bacteria in intestine
- reabsorbed and go to liver
—> Urobilinogen -(kidneys)-> Urobilinogen -(oxidation)-> ***Urobilin (excreted in urine) - unabsorbed
—> Urobilinogen —> Stercobilinogen -(oxidation)-> ***Stercobilin (excreted as faeces)
Summary of functions of biliary secretions
Digestive functions:
- Bile acids
- aid fat digestion and absorption
- promote absorption of fat soluble vitamin
- emulsification and formation of micelles - HCO3
- neutralises acidic chyme and provide optimal pH for enzyme action
Excretory functions:
- Bile pigments
- Excess cholesterol
- Drugs
Clinical relevance
- Chronic pancreatitis
—> pancreatic insufficiency leads to **fat indigestion —> **steatorrhoea - Cystic fibrosis
—> genetic disease, mutation in gene that encodes Cl channels
—> **impairs water and electrolyte transport
—> pancreatic ducts, acini and small airways clogged with **viscid mucus
—> imparted pancreatic exocrine function, ***fat digestion and absorption (carbohydrates and protein digestion can be compensated by other glands)
—> also respiratory problems - Gallstones
—> ***obstruction of common bile duct impairs fat digestion and absorption
—> also impairs absorption of fat soluble vitamins - Jaundice
—> increased bilirubin level in the blood, yellowish colouring of skin
