Pancreas & liver physio Flashcards
functional division of pancreas (2)
- exocrine pancreas
- endocrine pancreas
what does the exocrine pancreas secrete (3)
- Enzyme secretion (acinus)
- Electrolyte secretion (duct)
- Mucin (goblet)
acinar cells + ductal cells form a gland together
what does the endocrine pancreas secrete
- Insulin
- Glucagon
- (Somatostatin)
- Pancreatic polypeptide
**ALL FROM ISLETS OF LANGERHANS
what regulates enzyme secretion by acinar cells
- hormone CCK (cholecystokinin) increases production of enzymes
what regulates ductal fluid secretion by ductal cells
- hormone SECRETIN
why is ductal fluid produced by ductal cells alkaline
- ductal cell contains carbonic anhydrase -> convert CO2 to H2CO3 -> produce HCO3- which is excreted out of cell
- HCO3- is exchanged for Cl- at the lumen site
- H+ produced from H2CO3 dissociation is pushed into blood with exchange for Na+
- alkaline solution favours enzymatic activity of small intestines
how does pancreas protect itself from its enzymatic secretions (4)
- packaging protease as PRECURSOR FORMS (zymogens) -> protease inactivated, cannot digest pancreas
- presence of PROTEASE INHIBITORS (eg trypsin inhibitor) -> protect pancreas from unlikely case that protease is activated
- protease are COMPARTMENTALISED away from main cells, cannot do damage
- protein exist in LOW pH environment -> will denature if activated
how are pancreatic enzymes activated
- enterokinase present in luminal walls of intestine -> cleaves trypsinogen in pancreatic juice to trypsin
- active trypsin continues on to cleave remaining zymogens in pancreatic juice (chymotrypsinogen, proelastase, procarboxypeptidase A, procarboxypeptidase B)
pancreatic enzymes that are secreted in ACTIVE form & function
Pancreatic α-amylase
– Hydrolyzes glycogen, starch, complex carbohydrate
(except cellulose) into disaccharides
Pancreatic lipases
– Water-insoluble esters require bile salts to work
– Water-soluble esters do not require bile salts
Nucleases
what is pancreatic secretion stimulated by (2)
Neural
- vagus nerve
Hormonal
- secretin -> ductal cell secrete water, electrolytes & HCO3- rich secretion
- CCK -> acinar cell produce enzyme rich secretion
what stimulates secretin release
- gastric acid stimulus (acid from stomach entering duodenum)
- sensed by pH sensors in DUODENUM -> presence of H+ leads to secretin production in S cells of duodenum -> boost HCO3- secretion from ductal cells
what stimulates CCK secretion
- LCFA (long chain fatty acid), amino acid, gastric acid stimulus -> stimulate I cells in duodenum to secrete CCK
- CCK causes increase secretion of enzyme rich pancreatic fluid + increase hepatic secretion of bile salts -> pancreatic fluid & bile released into duodenum
how does vagus nerve stimulate secretin & CCK release (2)
CEPHALIC & GASTRIC PHASE (30%)
cephalic phase
- sight/smell/taste of food
gastric phase
- presence of food in stomach
cephalic + gastric phase -> CNS effect -> vagus nerve act on M3 receptors on acinus & ductal cells (ACh neurotransmitter) -> release secretin & CCK
INTESTINAL PHASE (70%)
- protein + lipid breakdown -> stimulate vagovagal reflex -> stimulates primarily ACINAR cells
**hormonal control of secretin & CCK secretion also falls under INTESTINAL PHASE (ie intestinal phase = vagus + hormones; cephalic & gastric = only vagus)
how is pancreatic secretion regulated according to amount of food in stomach
- by CCK-RP (releasing peptide) and monitor peptide -> similar function, both binds to I cells in duodenum to increase CCK production
- CCK-RP & monitor peptides are broken down by TRYPSIN
too much food in stomach
- all available trypsin are used to digest food -> CCK-RP & monitor peptide not broken down -> binds to receptor on I cells -> stimulate more CCK secretion & enzyme secretion
stomach empty
- many free trypsin -> digest CCK-RP & monitor peptide -> no longer binds to receptor -> I cells do not secrete CCK
functions of CCK (4)
- contraction of gallbladder (push bile out)
- acinar secretion in pancreas
- reduce rate of stomach emptying
- relax sphincter of Oddi (allow bile to flow out when gallbladder contracts)
how is pancreatic function lost
- loss of exocrine pancreas cells -> loss of digestive enzymes & malabsorption -> steatorrhea (fat in faeces)
- loss of endocrine pancreas cells -> loss of islet cells > diabetes
how to assess pancreatic function
Indirect
- stool fat -> indicates absorption
- stool elastase, chymotrypsin -> reflects pancreatic secretion
Direct
- inject secretin and obtain the amount of secretion from secretin injected
what are hepatocytes
Epithelial cells one cell thick separating two fluid compartments
– canalicular lumen (bile)
– sinusoids (blood)
Presence of hepatocyte polarity
– Apical membrane faces the canalicular lumen
– Basolateral membrane faces perisinusoidal space (space of Disse)
do bile canniculi and sinusoids flow in the same direction?
- NO. countercurrent flow
what do liver lobules (hexagons) contain
- a central vein that drains into
a BRANCH of HEPATIC VEIN -> eventually drain into IVC - periphery contains portal triad (hepatic artery + bile duct + portal vein) -> formed from BRANCHES of PORTAL VEIN -> sends blood to sinusoids
how does hepatocyte carry out its excretory function
- sinusoid endothelial contains large gaps -> products from blood (even albumin) can diffuse into hepatocyte
- products are metabolised and drained into bile canaliculus -> released via bile duct
basal daily bile secretion & its contents
500-600mL
- majority bile acids
- bile pigments (bilirubin)
- lecithin & phospholipids; cholesterol; proteins; electrolytes
describe bilirubin transport within hepatocyte
- ALB(albumin):UCB(unconj. bili) from sinusoid diffuse into space of disse -> UCB moves into hepatocyte easily (UCB is non polar)
- UCB converted eventually to bilirubin diglucuronide (water soluble) -> discharged to bile canaculi by MRP2 (multidrug resistance associated protein 2)
how is bile release regulated
CCK
- gallbladder contraction -> push bile into common bile duct
- sphincter of Oddi relaxation -> release bile from common bile duct into duodenum
types of bile acids
pri bile acids
- cholic & chenodeoxycholic acids
sec bile acids
- deoxycholic & lithocholic acids
- formed from pri bile acid by bacteria in gut
bile salt
- sec bile acids conjugated to glycine or taurine
characteristics of conjugated bile acids (bile salt)
- bound to glycine, taurine
- more amphiphatic -> easier to form micelles (aid fat absorption), reabsorb poorly thus stay longer in gut
- resistant to hydrolysis by pancreatic enzymes -> stable in gut lumen
how are bile salts excreted by hepatocytes
- bile salt enter hepatocyte from sinusoids
- excreted into bile canaliculus via BSEP (bile salt export pump); ACTIVE TRANSPORT (similar to bilirubin)
function of bile acids
- Promote bile flow
- Solubilise cholesterol, phospholipids in GB
- Enhance dietary lipid digestion and absorption by mixed micelle formation (detergent function)
where and why are bile acids reabsorbed
- 80-90% of bile salts absorbed in terminal ileum by active Na dependent process
- bile acid synthesis is energy intensive
effects of loss of bile salts
- bile salts are limited (energy intensive production) -> need to recycle by reabsorption at terminal ileum
- loss of bile salts -> diminished fat digestion -> fat malabsorption -> loss of calorie & vitamins ADEK (fat soluble) deficiency
