Exam #5: Liver & Gallbladder Flashcards
Describe the directional flow of blood through the liver.
- Grossly, deoxygenated blood flows from the GI organs to the liver via the portal vein, which is located in the “corner” of each liver lobule–at the portal triad
- Oxygenated blood flows from the aorta/ hepatic artery to the portal triad
- From the portal vein/ hepatic artery in the corner of the lobule, blood flows to the central vein in the middle of the liver lobule
- Central vein dumps into hepatic veins, which ultimately return blood to the heart via the SVC
Describe the directional flow of bile.
Bile is produced by liver hepatocytes & moves in the OPPOSITE direction of blood i.e. away from the central vein to the bile duct in the corner of the liver lobule, part of the portal triad
How do hepatocytes “handle” chemical compounds i.e. what are the four key steps in hepatocyte biotransformation of compounds?
1) Uptake
2) Transport
3) Biotransformation
4) Secretion
Describe the uptake process of hepatocyte biotransformation.
Uptake occurs across the basolateral membrane of the hepatocyte via two general mechanisms:
1) Free diffusion
2) Transporters
How are compounds transported through the cell to the site of biotransformation?
Compounds taken up by liver hepatocytes bind proteins & are carried to the site of chemical modification.
*****Note, these proteins serve an important function: prevention of damage to the liver by harmful compounds
How are substances transported back into the blood for excretion by the kidneys or into the bile for fecal elimination, after biotransformation has occurred?
Water-soluble
- After biotransformation, compounds are transported back into the blood if they’re water soluble–>kidney–>excreted in urine
Lipid-soluble
-If the compound is still lipophillic–>bile–>feces
*These processes are mediated by a number of different transporters with a differential expression
What is Phase I biotransformation? What is the end result of Phase I biostranformation?
*****Remember that the end goal of biotransformation is to make a substance more hydrophilic
Phase I= step taken to make the molecular more polar by exposing a functional group (better substrate for phase II). Specific reactions that occur include:
- Oxidation
- Reduction
- Hydrolysis
**Note that not all molecules undergo Phase I
What is Phase II biotransformation? What is the end result of Phase I biostranformation?
*****Remember that the end goal of biotransformation is to make a substance more hydrophilic
Phase II= conjugation of a large bulky molecule to the functional group exposed in phase I. Specific reactions include:
- Glucuronidation
- Sulfation
- Acetylation
How are bile salts synthesized?
Remember that hepatocytes produce bile that moves from the central vein to the bile duct in the portal traid. The steps involved in this process include:
1) Cholesterol is transformed into the bile acids
2) The main bile acid is “cholic acid”
3) Bile acids undergo Phase I & II biotransformation, to produce the more hydrophilic bile salt
Where is bile produced? Where is bile stored? Where is bile secreted? What happens to secreted bile salts?
- Bile produced & secreted by the liver
- 1/2 of the bile produced is secreted into the gallbladder & concentrated
- 1/2 is secreted directly into the duodenum
*****95% of the secreted bile is recycled via the portal vein carrying bile back to the liver from the intestines
What are the key stimuli that promote the secretion of bile into the duodenum?
There are two key stimuli regulating the secretion of bile:
1) Fat in the duodenum= CCK release
2) Vagal stimulation in response to sight, taste, smell, & intestinal distention cause ACh release
- **BOTH CCK & ACh lead to:
- Gallbaldder contraction & secretion of bile into the bile duct
- Relaxation of the sphincter of Oddi for release into the duodenum
What key stimulus inhibits the secretion of bile into the duodenum?
Somatostatin
What is enterochepatic circulation? Outline the pathway of enterohepatic circulation.
The is the circulation the recycles bile acids i.e.:
1) Bile from the liver & gallbladder travels to the duodenum via the bile duct
2) Bile is reabsorbed into the portal vein from the distal ileum & carried back to the liver for recycling
What is portal hypertension?
This is a sign of liver dysfunction; there is high blood pressure in the portal venous system
Describe the pathophysiology of portal hypertension.
- Portal HTN is high blood pressure in the portal vein i.e. the vein that carries blood to the liver from the GI tract
- This high blood pressure is caused by impedance of blood flow
