Physiology Of The Liver And Gallbladder Flashcards
Zones of hepatocytes
Based on proximity to a portal triad
1) zone 1 = closest a portal triad
- receives blood first and is primarily affected by toxins
- also bile stasis affects this zone the most
2) zone 2 = middle ground
3) zone 3 = furthest from a portal triad
- receives blood last and is most likely to be damaged by ischemia and fat accumulation
Factors that influence bile secretion
- bile contains*
- salts/bilirubin/phospholipids and cholesterol
Factors that increase:
- CCK
- parasympathetic stimulation
Factors that decrease:
- any damage or resection of the ileum/ileal Cecal value
What are the highest ion concentrations in bile
Sodium = 145 mEq
Cl- = 100 mEq
Bicarbonate = 28 mEq
- this is actually pretty high
Calcium and potassium = 5 mEq
What controls bicarbonate secretion?
Secretin/glucagon and VIP
Causes increases in cystic fibrosis transmembrane conductance regulator and other chloride channel protein actions resulting in more chloride In the lumen that can be used to pump bicarbonate out into the lumen
note somatostatin inhibits this
What are the primary differences between liver and gallbladder bile?
Liver bile
- water is higher
- less bile products
- more sodium
- more chloride
- more bicarbonate
Gallbladder bile
- water is lower
- way more bile products
- less sodium
- more potassium and calcium
- less chloride and bicarbonate
gallbladder products = bile salts/bilirubin/FAs/cholesterol
How are primary and secondary bile acids produced?
- Both begin from cholesterol*
1) Liver then uses 7a-hydroxylase enzymes to convert to primary bile acids (cholic and chenodeoxycholic acid)
2) intestinal bacteria then converts primary bile acids to secondary bile acids (deoxycholic and lithocholic acids respectively from cholic and chenodeoxycholic acid)
How do bile acids get converted into bile salts
Deocycholic acid -> glycodeooxycholic and taurodeoxycholic acid
Lithocholic acid -> glycolithocholic acid and taurolithocholic acid
Both are done via conjugation in the liver
bile salts are more water soluble than bile acids
What is the enterohepatic recirculating of bile salts ?
1) bile salts are made and then move into the gallbladder via the bile duct
- secretin/glucagon/VIP controls movement of salts into gallbladder as well as ions and water in the bile salts*
2) relaxation of the sphincter of oddi allows gallbladder to secrete bile salts Into the duodenum via major duodenum papillae
- CCK causes relaxation and contraction of the gallbladder*
3) bile salts are then reabsorbed via the ileum and transported into the portal circulation via secondary sodium transport channels
4) portal circulation brings bile salts back to the liver
What are the 5 F’s of gallstones?
Fat
Fertile
Female
Forty
Fibrates
The steps of bilirubin pathway
1) starts from dead RBCs which release heme groups
2) heme gets natural deconstructed to unconjugated bilirubin (which is water insoluble)
3) unconjugated bilirubin is then combined with albumin in the blood stream to make complexes
4) the enzyme UDP-glucuronosyl-transferase in the liver takes the unconjugated bilirubin-albumin complex and converts it into conjugated bilirubin (which is water soluble)
5) conjugated bilirubin is then converted by gut bacteria into urobillogen which 80% is excreted in feces as stercobilin (why stool is brown)
6) the other 20% is sent back into the gut and 10% of 20% is converted into urobilin (yellow urine color) and excreted by kidneys, where as the other 90% is sent via enterohepatic circulation back to the liver.
Explaining jaundice
Jaundice is caused by elevated bilirubin either via an indirect or direct pathway
1) increased indirect bilirubin = excessive hemolysis or severe liver damage
2) increased direct bilirubin = excessive blockage of bile ducts
