Hepatic & Biliary Functions

Question 1

Hepato Portal Circulation

Answer 1

Majority of liver supplied by portal v.

Liver strategically located to receive not only absorbed nutreints but also potentially harmful absorbed molecs such as drugs & bac toxins.

“first pass metabolsim”

Recieves blood from all GI organs

Question 2

Detox

Answer 2

First pass metabolism- the blood supply to liver & hepatocyte metabolic activity, some substances not make it into systemic circulation.

Pharm admin of drugs orally not always effective

Phase 1= P450 ox,red, hydrolysis

*usually generates toxic intermid, like free radicals

Phase 2= conjugation, inactivates toxic metabolite

Excreted in bile!

Question 3

Bile Formation

Answer 3

Isoosmotic with plasma

Cnalicular bile & ductal secretion of bicarb & H2O

Canalicular bile secreted by hepatocytes & consists of:

• dep on transport of bile acids *most*
• bile-acid indep

Ductal secretion produced by cholangiocytes lining ductules & bicarb rich fluid.

Canalicular bile & ductul secretion mix to form bile

*the rate of total bile flow dep on sum of hepatic & ductul secretion

Rate of canalicular bile incresaes linearly w/ rate of bile acid secretion

Question 4

Bile Components

Answer 4

Bile Acids- emulsify lipids, incrase SA for lipase action

• primary= cholic & chendeoxycholic
• syn in hepatocytes (7a hydroxylase)
• main route of cholesterol metabolism
• secondary= deoxycholic & lithocholic
• syn by bac
• conjugated & free

Cholesterol & phospholipids- cholesterol & lecithin solubilizing f

Pigment & other organics- bilirubin, other drugs, toxins

water & electrolytes- All major secreted isotonically, HCO3- secretion by ducts

Question 5

Bile Formation, cellular

Bile Acid Dependent Flow

Answer 5

Na/K ATPase basolateral mem

• gradient for Na dep uptake of bile salts across sinusoidal (basolateral) mem
• after conjugation, secreted into canalicular lumen
• variety of active transporters

Na & H2O follow passage of bile salts into biliary canaliculus by diffusion across tight junction b/t hepatocytes & through hepatocytes.

Question 6

Bile Formation, Cellular

Bile acid indep flow

Answer 6

H2O flow due to accumulation of other osmotically active solutes such as bicarb which exit cell through similar mec as in ducts.

Question 7

Enterohepatic Circulation

Answer 7

95% secreted bile acids & salts returned to liver

Mech of absorption: passive diffusion Na+ dep

Carrier mediated absorption in terminal ileum- most important

Deconjugation to primary bile acids before absorbed passively/actively

Conversion of primary bile acids to secondary with absorption of deoxycholic acid

*recycles 7x/day

* bile flow dep on bile salts return to liver

*lithocholic acid cytotoxic & sulfated. Sulfated form not absorbed & excreted.

Question 8

Ductular Secretion

Answer 8

Bicarb & H2O dilute canalicular bile

Bile becomes alkaline & reduces Ca precipitation

Cl- ions secreted via CFTR & exchanged for HCO3-

Secretion increased during ingestion & digestion, secretin & VIP increase HCO3- & stimulate H2O aquaporins into apical mem of cholangiocyte.

Bile flow increast postprandial while bile acids needed in lipid digestion

Secretion I by somatostatin

Question 9

Concentration of Bile Acids in Gall Bladder

Answer 9

Max volume gallbladder can hold 30-60 mL

Bile acids not transported become so concnetrated b/c left behind during isotonic reabsorption of NaCl & NaHCO3 & H2O by leaky gallbladder epithelium

Question 10

Concentrations in Bile

Answer 10

Gallbladder stores bile & isosmotically removes salts & H2O.

Results that gallbladder [] key remaining solutes in bile: fluid bile salts, bilirubin, cholesterol & lecithin.

Bile isotonic bc:

Cl- [] falls dramatically & bicarb falls

Na+ changes slightly

K+/Ca2+ increases

Bile acids incorporated into mixed micelles & single micelle actsa as 1 osmotically active particle.

Duodenum: dilute hepatic bile & [] gallbladder bile

Question 11

Digestion & Absorption of Lipids

Answer 11

dietary fat mainly triglycerides & some cholesterol & fat soluble vitamins

Fat emulsified by mech action of somach (low pH, mix, churn)

Bile contains bile acids

Act to solubilize fat & promote hydrolysis of triglycerides in duodenum by lipase

At enterocyte luminal mem, lipid contents of micelles absorbed while bile salts remain in lumen (brush border absorption)

Inside the cell, monoglycerides & FA re-esterified to triglycerides

Tri & other fat molecs (cholesterol) incorporated into chylomicrons to transport by lymph (lacteal)

Question 12

Micelle Formation

Answer 12

BA, phospholipids, fat vitamins & prod of fat digestion cluster together w/ hydrophilic ends on outside to form aggregations= mixed micelles.

Trapped in center are hydrophobic monoglycerids, FA, cholesterol

Question 13

Surface Hydrolysis

Answer 13

Lipase & Co lipase yeild short & medium chain FA that can enter enterocyte by free diffusion through lipid bilayer of PM

Micellses increase rate @ which molecs like FA can diffuse

Co secreted

Adhere to brush border

pH= 7

Question 14

Brush Border Uptake

Answer 14

Lipids reconstititued in smooth ER & linked to apoproteins syn in RER

All components are assembled into chylomicrons in Golgi apparatus, secreted across basolateral side of cell.

When micelles hit the unstirred layer, allows FA, cholesterol etc. to quickly be absorbed.

Question 15

Summary

Answer 15

Question 16

Steatorrhea

Answer 16

Early warning sign of CF

Pale, malodorous stool

Question 17

Bile Release Fasting

Answer 17

During Fasting, sphincter of Oddi contracted & bile flow in common bile duct redirected into gall bladder

Question 18

Bile Relase Fed

Answer 18

Cephalic phase of response to a meal, gall bladder displays mild rhythmic contraction mediated by pulsatile Ach release from ENS cholinergic motor neurons.

Entry of chyme into duodenum, CCK release, powerful contraction of gall bladder smooth m.

CCK mediates relax of sphincter of Oddi

Relaxed sphincter, bile & pancreatic juice enter duodenum

During intestinal phase, secretin relased stimulates pancreas & cholangiocytes to secrete HCO3- & prepare pH for pancreatic anz action

Question 19

Neural Reflex Pathway

Answer 19

CCK stimulus from FA , acts on CCK A R on gallbaldder to cause smooth m. contraction

CCK binds CCK A on ENS sensory n. endings. Stimulates ENS inhibitory NO & VIP to relax sphincter of Oddi.

Ejection of concentrated bolus of mixed bile into duodenal lumen w/ pancreatic juice where mixed micells aid lipid uptake.

Question 20

CCK

Answer 20

CCK regulates 4 components= duodenal cluster unit (sphincter of Oddi, pancreas, proximal duodenum)