Liver and Gallbladder Flashcards
What are the two metabolic functions of the liver?
Energy metabolism
Detox
What are the two excretory functions of the liver?
Lipid soluble waste products
What are the three major functions of the liver?
- Metabolic
- Excretory functions
- Storage and transport
What percent of blood going into the liver is from the portal vein?
70%
What is the “first pass effect”?
Concept that the first organ that a drug passes is the liver
What are at the apices of the hepatic lobule? (and what are its three contents)
Portal spaces (portal vein, hepatic artery, and bile duct)
What is the blood flow from through hepatocytes? Bile?
From the edges (branches of the portal vein), to the central vein
Bile is opposite
What type of cells are hepatocytes?
Polarized epithelial cell that interface with blood and bile
What are Kupffer cells?
Macrophages in the sinusoidal lumen that are exposed to portal blood
What is the significance of the endothelial cells in the liver?
Large pores between the cells and minimal basement membrane
this serves as a filter
What are the stellate cells of the liver?
Cells that fill the gaps in the BM of hepatic endothelial cells, and function to regulate the flow of blood
What are the four processes that occur in the liver?
- Uptake
- Transport intracellularly
- Biotransformation
- Secretion
Why is there specific intracellular transport in hepatocytes? What regulates this?
Chemical may be damaging to cells. Thus specific
Specific binding proteins regulate this
What is the goal of the biotransformation in the liver?
Make something more water soluble
Where do hepatocytes secrete chemicals?
Across the apical or basolateral membrane
What is the space between hepatocytes and the endothelium?
Space of Disse
How is intracellular movements effected?
binding proteins
What is phase I of biotransformation? (3 rxns)
Oxidation
Reduction
Hyrolysis
Do all chemical undergo phase I and II of biotransformation?
No, can go only to phase II or whatever
What is phase II of biotransformation? (3 conjugations)
Glucuronidation
Sulfation
Acetylation
What is the function of the oxidative transformations that the liver undergoes?
Make it more water soluble, and make the chemical more amenable to phase II transformations
What is the function of glucuronidation?
UDP-glucose added
What are the two places that biotransformed molecules goes?
Bile cannuliculus
Blood
What is the transporter for bile salts from the hepatocyte?
BSEP (bile salt export pump)
What is the transporter for bulky, organic cations, (e.g. xenobiotics, cytotoxins, anti CA drugs etc) from the hepatocyte?
MDR1 (multidrug resistance associated protein)
What is the transported for glucuronate, glutathione, and sulfate, from the hepatocyte?
MRP2 (multi-specific resistance associated protein)
What is the transported for phosphatidylcholine, from the hepatocyte?
MDR3 (multidrug resistance associated protein)
What are the two major components of bile?
Bile acids and salts
How much bile does the liver secrete? Where does this go?
900 ml
- Half to the gallbladder
- Half to the duodenum
Bile acids are synthesized from what precursor molecule?
Cholesterol
What happens to bile acids?
Biotransformed to a bile salt (water soluble) and secreted into the duodenum
What is the primary human bile acid?
Cholic acid
What are secondary bile acids?
Bile salts that are modified by intestinal bacteria
What is primary bile acid?
Secreted from the liver, untransformed by the gut microbiota
The liver secretes 12-36 g/day, but synthesizes only 600 mg. How can this be?
There is reuptake of bile salts/acids in the intestines (Enterohepatic circulation)
Where are bile salts absorbed in the intestines?
Ileum
What is the function of somatostatin on the gallbladder? Ach?
Ach increased contraction
Somatostatin inhibits
What is the MOA behind hepatic encephalopathy?
Toxins increase in [c] in the plasma, eventually crossing the BBB
What is the function of somatostatin on the the sphincter of Oddi? Ach?
Ach induces relaxation
Somatostatin inhibits relaxation
Obstruction of the pancreatic duct leads to what symptoms (besides pancreatitis symptoms)?
Pale stools d/t increased fat content
What are the cells that regulate the flow of blood constituents between the fenestrae and across the Space of Disse to the hepatocytes?
Stellate cells
Which phase of biotransformation includes oxidative, reductive and hydrolytic reactions?
Phase I
What is the final result of phase I biotransformation by the liver?
the exposure of a functional group on the parent compound. This can render the compound a substrate for Phase II biotransformation
What is the enterohepatic circulation?
The recycling of bile salts from the ileum back into the digestive system
What are the two main promoters of bile secretion? What inhibits these?
CCK and ACh
Inhibitor = somatostatin
What is the cause of hemolytic jaundice?
simply caused by excessive breakdown of red blood cells
What is obstructive jaundice?
Extrahepatic obstructive jaundice (EOJ) is caused by an obstruction, such as in the bile duct, which impedes bilirubin excretion outside the liver
What is intrahepatic jaundice?
caused by an obstruction in the liver, such as impaired hepatocyte function or blocked bile canaliculi
What causes alcoholic cirrhosis?
Accumulation of acetaldehyde (breakdown product of EtOH)
What is biliary cirrhosis?
Anything that chronically impedes the passage of bile through the bile duct, leading to fibrotic changes in the liver
What are the two types of cholelithiasis?
Cholesterol or pigmented
What causes cholesterol gallstones?
Overproduction of cholesterol, or impaired production of bile salts
Where are pigmented stones from?
Pigmented stones are derived from calcium bilirubinate or other pigmented polymers
What is the term for imparied bile flow?
Cholestasis
