Functions of the Liver Flashcards
What is the main blood supply of the liver?
Portal Vein
What is the most abundant cell type in the liver?
Hepatocytes
What is the function of hepatic stellate cells?
Unknown role but they work in the production of collagen and it leads to fibrosis if there is hyperactivation
Describe the flow of blood for the hepatocytes.
Sinusoids bring in the blood and then it exits via the central vein to the hepatic vein to the vena cava
What is the hepatic triad?
Hepatic artery, portal vein and the bile duct
What is defined by the hepatic triad?
3 cellular zones of the liver
What are the Zone 1 cells?
They receive most of the blood supply and thus are affected last in cases of ischemia. However in cases of toxins, the Zone 1 cells will be affected first.
What are the Zone 3 cells?
They are the closest to the hepatic vein and most sensitive to ischemic injury.
What will happen to the zones in liver diseases?
Zone 2 and 3 cells can function as Zone 1 cells.
What form the origin point of the biliary system?
Hepatocytes
What is the canaliculus?
Apical membranes of adjacent hepatocytes forms a channel called canaliculus.
What is the function of the canaliculus?
These canaliculi drain bile from liver and transport to the biliary ductules.
What kinds of cells line the biliary ductules?
Cholangiocytes
What is special about the epithelium in the sinusoidal lumen?
Epithelium in the sinusoidal lumen is fenestrated to allow for the passage of plasma proteins as the liver is what synthesizes them
What is the role of hepatocytes in metabolism?
Hepatocytes participate in the metabolism of major nutrients – carbohydrates, lipids and proteins.
How is the liver important in glucose metabolism?
Liver plays an important role in gluconeogenesis – conversion of other sugars to glucose.
How is the liver important in glucose storage?
The liver stores excess glucose as glycogen and releases stored glucose in the bloodstream when needed.
What does impaired liver function cause in regards to carbohydrates?
Hyperglycemia after meals and hypoglycemia between meals
What is the function of the liver in regards to lipid metabolism?
The liver converts products of carbohydrate metabolism into lipids – synthesis of lipoproteins, cholesterol and phospholipids.
Hepatocytes also convert a significant portion of the cholesterol to bile acids.
What is the function of the liver in regards to protein synthesis?
The liver synthesizes all of the non-essential amino acids and all of the plasma proteins including albumin
What is the problem liver failure causes in regards to proteins?
It will lead to hypoalbuminemia – may lead to peripheral edema due to loss of plasma protein oncotic pressure and clotting disorders.
What is the function of the liver in regards to protein detoxification?
It converts ammonia into urea for excretion
What is the detoxification function of the liver?
It protects the body from toxic substances as it modifies them in “first pass metabolism” so little or none can enter systemic circulation
How does the liver achieve detoxification?
o Phase I reactions – oxidation, hydroxylation etc. – catalyzed by cytochrome P-450 enzymes.
o Phase II reactions – conjugate the substances with glucuronide, sulfate, amino acids or glutathione.
They are then secreted via urine or feces
What are the components of bile?
It is mostly made of bile acid with the rest being other constituents of which cholesterol and bilirubin are the most notable
What are the 2 primary bile acids secreted by hepatocytes?
Cholic Acid
Chenodeoxycholic Acid
What conjugates the bile acids in the hepatocytes?
Glycine and Taurine
What is the purpose of bile conjugation?
They are more water soluble and they can be actively absorbed in terminal ileum via apical Na+ -dependent bile salt transporter
What happens to deconjugated bile?
Deconjugated bile is usually a result of bacterial action and it will be excreted
What does secondary action of the bile acids by bacteria change them into?
o Ursodeoxycholic acid
o Deoxycholic acid
o Lithocholic acid
What is the function of 7α-hydroxylase and how is it regulated?
7α-hydroxylase acts to synthesize bile acids from cholesterol and it is regulated by feedback inhibition from bile. More bile coming back will down regulate the synthesis effect of the enzyme.
What happens to 7α-hydroxylase in people who constantly lose bile?
Under people who continually lose bile, the enzyme’s activity will be increased but the process is not very efficient so they will have lower than normal bile levels
What happens to bile synthesis with an ileal resection?
Synthesis is increased
What happens with feeding of bile acids?
Synthesis of bile will be decreased
What is enterohepatic circulation?
It is the process of recycling bile from the GI tract
How do cholangiocytes modify bile?
They have CFTR channels which will pump Cl- to be exchanged for HCO3-. This will pump HCO3- out of the cell and lead to bile being alkaline which serves to prevent the precipitation of the bile into gallstones
How do cholangiocytes control the concentration of bile?
Bile is diluted as secretin stimulates aquaporin water channels to pump water out.
What is the function of the gallbladder?
It serves to store bile and in here the bile becomes more concetrated
What is the major stimulus for bile secretion?
CCK
What is the effect of CCK?
o contraction of gallbladder
o relaxation of sphincter of Oddi.
What are gallstones?
They are precipitated bile constituents, usually cholesterol or Ca2+ bilirubinate (pigment) stones.
What is a risk factor for gallstones?
Prolonged periods of fasting
What are some possible side effects of gallstones if they block the ampulla of Vater??
It can lead to pancreatitis
How is bilirubin transported to the liver?
It binds to albumin to become more water soluble and then it enters the liver by hepatocytes via an OATP transporter.
How is bilirubin conjugated?
In hepatic microsomes, bilirubin is conjugated with glucoronic acid by enzyme UDP glucuronyl transferase.
Why do some newborns have jaundice?
The enzyme UDP glucuronyl transferase is synthesized slowly after birth
What happens to the bilirubin in the ileum and colon?
In terminal ileum and colon, it is deconjugated by bacterial enzymes – metabolized to urobilinogen. The remainder is converted to urobilin and stercobilin – excreted in feces.
What does an increase of unconjugated bilirubin in the plasma mean?
o Loss or absence of UGT
o Sudden oversupply of heme (e.g. in transfusion reactions)
What is jaundice?
Yellowness of skin, scleras and mucous membranes due to accumulation of free and conjugated bilirubin in the blood.
Jaundice becomes clinically manifest when total plasma bilirubin is >2 mg/dl (> 34 μM) = hyperbilirubinemia.
What are some causes of hyperbilirubinemia?
Excess production of bilirubin (e.g. hemolytic anemia)
Decreased uptake of bilirubin into hepatic cells
Disturbed intracellular protein binding and conjugation
Disturbed secretion of conjugated bilirubin into bile canaliculi
Intrahepatic and extrahepatic bile duct obstruction
Pre-surgery use of potent antibiotics (lack of bacteria)
Newborns (lack of UDP glucuronyl transferase).
What is the function of the urea cycle in the liver?
Converts NH3 to urea as NH3 is toxic to the CNS
What is hepatic encephalopathy?
Patients with chronic liver disease – may have a gradual decline of mental function – ammonia and other toxins not cleared by liver. This can lead to confusion and dementia that can be fatal.
What is liver cirrhosis?
An irreversible destruction of the functional anatomy of the liver that is often the result of alcohol. Portal hypertension is usually also present.
What is portal hypertension?
Caused by increased vascular resistance in the liver often due to cirrhosis which leads to increased blood pressure in the sinusoids reflects back to the portal vein
