Liver: Johnson

Question 1

Describe the constituents of bile and their functions.

Answer 1

Primary bile acids:
Cholic acid and chenodeoxycholic acid

Secondary bile acids (dehydroxylated by bacteria of gut):
Deoxycholic acid and lithocholic acid

Within bile ~50% of organics are bile acids-salts.
30% of organics are made up of phospholipids (mainly lecithin)
5% is cholesterol
Then you have bile pigments, such as bilirubin.

All these things come together to form micelles that encase otherwise insoluble nutrients.

Question 2

Understand the solubility of bile acids and salts and how it affects their reabsorption.

Answer 2

Acids are conjugated to bile salts (glycine and taurine) to make them soluble in water.

Bacteria in gut deconjugate the bile salt-acid combinations, making them less water soluble. They (50%) are then absorbed passively along the length of the small bowel. 45% are actively absorbed in the ileum. Remaining 5% lost in stool.

the more -OH groups a bile salt has, the more soluble it is

Question 3

Describe the enterohepatic circulation and its role in bile acid synthesis and secretion of bile.

Answer 3

::Enterohepatic circulation/role::
Bile acid-salt secreted by liver (secretin) stored in gallbladder, released from gallbladder (CCK + Ach)—> duodenum, and reabsorbed along entire length of small intestine passively (50%) and actively in ileum (45%)—> hepatic portal vein—> liver—> back to bile duct—> intestine.

::Synthesis::
The 5% of bile acids that are lost in stool are replaced by synthesis in the liver, based on how much is returned via enterohepatic circulation. More returned, less synthesized/secreted, and vice-versa.
7-hydroxylase is the enzyme involved in the rate-limiting step that converts cholesterol to bile acids.

::Secretion::

• On basolateral (capillary) membrane of hepatocyte, Na+/K+ATPase pumps Na+ out, creating gradient by which Na+ can travel down along (2ndary active transport) with bile acids to enter hepatocyte.
• Bile acids/salts (if reconjugated to taurine or glycine) then cross apical membrane (into bile caniliculus) via facilitated diffusion.
• Osmotic gradient created by bile acid/salt in bile canaliculus then pulls K+, Na+, Cl-, HCO3-, Ca2+, and H2O into lumen (“bile acid-dependent component”)

Question 4

Understand the processes involved in the excretion of bile pigments and its relationship to jaundice.

Answer 4

Reticuloendothelial system breaks hemoglobin down to bilirubin
–> binds to plasma albumin
–> bilirubin active uptake into liver
–> conjugated to glucuronic acid (now solublized)
–> bact. deconjugate bilirubin-glucuronide to urobilinogen
–> urobilinogen oxidized–> turns brown–> comes out your butt.
But(t), some urobilinogen is reabsorbed in intestines, is actively picked up by liver or kidney, and dumped back out into intestines or urine (as urobilin =>yellow color of urine).

::Jaundice::
When the liver is damaged (hepatitis, cirrhosis, etc.) bilirubin is not fully extracted from blood stream, accumulates, and jaundice (yellowing of skin/sclera) results.

Question 5

Explain the function of the gallbladder.

Answer 5

Absorbes NaCl and thus, pulling H2O with it, concentrates bile.
Solution is still isosmotic w/ plasma bc, although Na+ concentration increases greatly, most of it is bound to micelles.

Question 6

Describe the regulation of bile secretion from the liver and its expulsion from the gallbladder.

Answer 6

Constantly:
Secretin-dependent–> liver to secrete bile and bile duct to secrete Na, HCO3-, and H2O.
Bile acid-dependent- presence of bile in bile canaliculi pulls in H20 and electrolytes.

Food in duodenum: CCK/Ach–> GB to expel stored/concentrated bile. Relaxation of sphincter of Odi

Question 7

Explain how gallstones develop.

Answer 7

2 types:

Cholesterol stones- due to too much cholesterol and too little bile acid—> precipitation of cholesterol—> stones
Fat, Fertile, Forty y/o, Female

Pigment stones- bile saturated w/ unconjugated bilirubin (normally conjugated to glucuronide)
-Due to too much B-glucuronidase caused by bacterial damage to wall of GB.

Question 8

What would happen to your ability to digest fats in the absence of the gallbladder.
What about in the absence of enterohepatic circulation?

Answer 8

GB removal- no problem. Presence of gallbladder provides excessive surge of bile acid above physiological need.

No E.H.C.- PROBLEM. Not enough bile acids present to solubilize/absorb of fat–> steatorrhea.