• PNS input via vagus N.
  • postganglionic fibers release ACh
  • go to bv's, parenchymal cells
• SNS input from celiac and mesenteric ganglions
  • releases norepinephrine at smooth muscle cells of vasculature

• digestive enzymes
  • proteolytic (all secreted as zygomenes)
    • endopeptidases
    • exopeptidases
  • amylytic- amylase
  • lipolytic
    • lipase
    • procolipase

• HCO3 (second highest concentration of all the enzymes)
  • concentration in pancreatic juices increases with increasing flow rate
• Cl
  • concentration in pancreatic juices decreases with increasing flow rate
• Na (highest concentration of all the ions)
• K

1. H2O and CO2 form H2CO3
2. dissociates into H and HCO3
3. HCO3 goes into lumen via HCO3/Cl antiport
   1. Cl goes into lumen via CFTR channel (activated via cAMP) so it can function in the antiport with HCO3
4. basolateral side
   • H goes into blood in exchange for Na (Na/H antiport)
   • K go into blood via K channel
   • also a Na/K pump on basolateral side (Na out, K in)

CCK

secretin

• released from S cells in duodenum
• released in response to entry of acid in the duodenum
• stimulates bicarbonate and water secretion from the duct cells
• weakly stimulate enzyme secretion

FLASHBACK: VIP can also increase fluid secretion and act via cAMP

• released from I cells in duodenum
• in response to presence of fats and AA's in duodenum
• stimulates enzyme secretion from acinar cells
• weakly stimulate electrolyte, fluid secretion

FLASHBACK: gastrin can have the same effect but weaker, and act via increases in intracellular calcium.

• in response to chyme entering the duodenum
• ACh and VIP released from post ganglionic terminals
• results in increase in enzyme secretion from acinar cells (ACh responsibility) and slight increase in bicarbonate and water secretion from duct cels (VIP responsibility)

• inhibit vagal and secretin induced secretion
• inhibit pancreatic secretion by reducing blood flow

• basal phase
  • 10% of enzyme secretion
  • 1% of bicarb secretion
• cephalic- release of ACh and slight increase in VIP (weak increase in bicarb)
• gastric- stimulation of vagus N. releasing ACh and VIP continues and is augmented by gastrin
• intestinal- 70-80%
  • secretin released in response to acid (threshold: pH of 4.5 and maximal at pH of 3)
  • CCK released in response to protein and fat in duodenum
  • enterpancreatic reflex is initiated

• increase in trypsin and protease secretion
• presence of fats in lower intestines (believed to involve NPY)
• increase glucagon, somatostatin, pancreatic polypeptide

• inorganic substances
  • sodium
  • potassium
  • calcium
  • bicarbonate
  • chloride
• organic substances
  • bile acids (50% of it)
  • bile pigments
  • cholesterol
  • phospholipids
  • protein (IgA, albumin, glycoprotein)

• chenodeoxycholic acid and cholic acid

They are conjugated to Gly and Taurine (Gly outnumbers taurine 3:1).

bilirubin

biliverdin

1. heme, NADPH, O2 form biliverdin, CO2, NADP, ferric via heme oxygenase
2. biliverdin and NADPH form NADP and bilirubin via biliverdin reductase

1. free bile acids can diffuse into canalicular cells or via Na cotransport
2. free bile acids conjugated with Taurine or Glycine
3. diffuse into bile canaliculus

Note ther is also a Na/K pump

1. CO2 diffuses into canalicular cells
2. combines with water to form carbonic acid via CA
3. dissociate to form bicoarbonate and hydrogen
   1. hydrogen used in Na/H antiport (water will follow sodium into cell)
   2. HCO3 goes into the bile canaliculus

Na, Cl reabsorbed

HCO3 secreted

• bile salt dependent
  • not conrolled by nerves or hormones
  • bile salts taken up very efficiently from circulation
  • as we increase bile salts put in bile, we get a greater volume
    • clinical app.- choleretics increase bile, leading to reduction in cholesterol
• bile acid independent flow
  • electrolytic secretion from hepatic cells is modified as it goes the bile duct
    • increases in response to secretin
    • inhibited in response to somatostatin

1. bilirubin bound by albumin in the blood
2. uptaken by the liver, removing albumin
3. biliruben conjugated to 2 UDP glucoronate in ER to form bilirubin diglucoronate
4. bilirubin diglucoronate is deconjugated to form urobilinogen
5. 2 options
   1. urobilinogen further deconjugated to form stercobilinin (forms Brown stool)- 80%
   2. reabsorb via intestine and excrete in urine (20%)

• increased production (hemolytic jaundice)
• decrease liver uptake
• impaired conjugation (Gilberts, Criegler-Najar)
• blocked secretion of conjugated bilirubin (ex: gallstones, cholestasis)

• bile sent to the gallbladder during interdigestive period
  • clinical application- without gallbladder, we have slower emptying of the bile
• reabsorb sodium, chloride, water, and bicarbonate
• stimulated to contract by
  • release of ACh from vagus, which will also relax the sphincter of Oddi (during cephalic phase and gastric phase)
  • release of CCK from I cells in duodenum will cause contraction of the gallbladder, releasing bile (during intestinal phase)

cholesterol (majority seen in US)

pigment

• Process
  1. increases in cholesterol with decrease in bile acid production
  2. increase chance if gallbladder is made static (ex: female hormones decrease contractions)
  3. cholesterol crystalize
• Treatment
  • increase bile acid pool (choleretics) while decreasing cholesterol (soluble fiber)
• appearance
  • radioluscent on Xray
  • yellow-green color

• Process
  1. increases in unconjugated bilirubin due to infectino of biliary tree
  2. leads to precipitation with calcium, carbonate, phosphate, cholesterol
• appearance
  • radiopaque on Xray
  • brown stones
• treatment