Functions of the Liver Flashcards
Differentiate the blood high in nutrients vs the blood high in oxygen running feeding the liver
75% of blood is high in nutrients- comes from portal vein
25% of blood is high in O2- comes from the hepatic artery
What makes up the hepatic triad?
Branches of the hepatic artery, portal vein, and bile duct
Differentiate the functions of the cells in zone 1 of the hepatic triad from zone 3 of the hepatic triad.
Zone 1: periportal cells are closest to the triad and therefore have the largest supply of O2 and nutrients, and are most active in detoxification
Zone 3: pericentral cells- closest to the hepatic vein- are the most active in bile synthesis
Zone 2: transition between zones 1 and 3
Contrast the directionality of blood flow and bile flow in the liver
Blood travels from the periphery towards the central vein, while bile flows from the center towards the periphery
Describe the glucose buffer function of the liver
The liver stores excess glucose as glycogen and releases stored glucose in the bloodstream when needed
Where does protein metabolism take place?
The liver- the liver synthesizes non-essential amino acids, albumin, clotting factors, and converts ammonia to urea
Briefly describe the two steps of detoxification in the liver
1) Oxidation/hydroxylation etc by cytochrome P450
2) Conjugate the substances with glucuronide, sulfate, amino acids and glutathione
How is waste from the liver excreted?
Feces (via bile) for larger molecules or protein bound molecules
Kidneys for small water soluble catabolites
What are the two main bile acids?
Hepatocytes synthesize Cholic acid and chenodeoxycholic acid
How are secondary bile acids produced?
Colonic bacterial enzymes act on the primary acids to produce secondary acids (Ursodeoxycholic acid, deoxycholic acid, and lithocholic acid)
What are bile salts?
Conjugated bile acids - acids conjugated to either glycine or taurine.
Conjugation of bile acids makes them more water soluble and therefore better at emulsifying fat
What is the scaffold of bile acids?
Cholesterol
How are conjugated bile acids in the ileum reabsorbed?
Na+ dependent manner: ASBT symporter
How are bile acids in the colon reabsorbed?
They are deconjugated and then reabsorbed passively
What is the role of cholangiocytes?
Cholangiocytes line the biliary ductules and can modify bile the same way the the ductal cells of glandular tissue modifies the secretions
Why is it important that HCO3- is secreted into the bile (in exchange for Cl-)?
HCO3- makes bile slightly alkaline, which protects against gallstone formation
Where is bile diluted?
Bile is diluted in the biliary ductules– where the cholangiocytes modify the bile
What happens to bile in the gallbladder?
It is concentrated
What is the major stimulus for bile secretion and what happens?
CCK is the major stimulus
- The gallbladder contracts
- The sphincter of Oddi relaxes
Describe the neural reflex that leads to contraction of the gallbladder.
CCK is released in response to nutrients in the duodenum. CCK travels through the blood and stimulates the dorsal vagal complex, which relays the signal through vagal efferents to release ACh at the gallbladder. The vagus also synapses at the sphincter of Oddi where VIP and NO are released and causes relaxation of sphincter.
What are the two different types of gallstones?
Precipitated cholesterol
Precipitated Ca2+ bilirubinate
What normally prevents cholesterol precipitation?
Anti-nucleating proteins
Where is heme degraded?
The reticuloendothelial system (RES) –> meaning macrophages.
What are the first two breakdown products of hemoglobin?
Hemoglobin –> biliverdin (green) –> bilirubin (yellow)
Why is bilirubin bound to albumin?
Conjugation to albumin makes bilirubin soluble such that it can enter the bloodstream and be taken to the liver for further processing in the liver.
Unbound bilirubin is insoluble at neutral pH
What is the OATP transporter?
The OATP transported takes up bilirubin-albumin into the hepatocytes
Why is bilirubin conjugated with glucuronic acid by UDP glucuronyl transferase?
Conjugated bilirubin is soluble again and can be excreted in urine or secreted in bile.
Why are many newborns jaundiced?
UDP glucuronyl transferase is slow to be synthesized after birth - therefore bilirubin is not conjugated to glucuronic acid and cannot be excreted
In what forms is hemoglobin excreted in feces?
urobilin and sterocobilin
What causes jaundice?
Accumulation of bilirubin
WHy is bacteria necessary for the excretion of bilirubin?
In the terminal ileum and colon, bilirubin is deconjugated by bacterial enzymes.
It is metabolized to urobilinogin
Why is ammonia produced in the first place, even though it is toxic to the CNS?
Protein catabolism produces urea
How is ammonia excreted?
Ammonia is converted into ammonium in the colon by colonic bacteria and excreted in the stool
