Structure and function of liver Flashcards
What is the blood supply to the liver?
75% from the portal vein and 25% from the hepatic artery.
What is a lobule?
Hexagonal functional unit of the liver divided by connective tissue.
What lies at the angle of each lobule?
Portal tract/triad - contains branch of hepatic artery, hepatic portal vein and bile duct.
Into what structures does the blood from the hepatic artery and portal vein run in to?
Sinusoids - run between plates of cells to central venule and then into hepatic vein i.e. away from the portal triad
Where does bile flow within the liver?
From hepatocytes to canaliculi to the bile ducts i.e. towards the portal triad.
How are the plates of hepatocytes arranged in the liver?
So that each cell has access to blood supply on one side and bile on the other. Sinusoid-facing side has fenestrated endothelium.
What lies between the endothelial cells and hepatocytes?
Space of Disse
What is the most important liver cell type?
Hepatocyte - 60% of cells, carry out most of metabolic functions.
What are Kupffer cells?
Macrophages, located within sinusoidal lining. Protect liver and phagocytose old erythrocytes.
What are pit cells?
Liver-specific NK cells.
What are hepatic stellate cells?
Primary site of vit. A storage. Also control turnover of connective tissue, synthesise collagen, regulate contractility of sinusoids.
What are the functions of the liver?
Synthesis - CHO, lipids, protein and bile Waste management - detox of xenobiotics, removal of internal waste eg bilirubin Storage - glycogen, vit A
What is the composition of bile?
Water, bicarb, bile salts, cholesterol and phopholipids.
What is the synthesis pathway for conjugated bile acids?
Either:
Cholesterol -> primary bile acids eg cholic acid -> (via gut bacteria) -> secondary bile acids eg deoxycholic acid -> conjugated with glycine/taurine
Cholesterol -> primary bile acids eg cholic acid -> conjugated with glycine/taurine
What percentage of bile salts are recirculated?
95%
What is the function of Cholestyramine?
Binds bile acids in the gut. Prevents the recirculation of bile. Increases bile acid synthesis. Decreases blood cholesterol.
What effect does an increased intake of dietary fibre have on cholesterol?
Decreases blood cholesterol.
What causes the formation of cholesterol gallstones.
Bile contains free cholesterol as well as bile salts. If more cholesterol enters the bile than can be solubised by bile salts precipitation of cholesterol occurs.
What are phase 1 reactions?
Oxidation, hydroxylation, hydrolysis and reduction.
What are phase 2 reactions?
Conjugation, sulphation and glucuronidation.
What properties do liver metabolites have?
Usually pharmacologically inactive and more hydrophilic.
What enzymes mainly perform phase 1 reactions?
Cytochrome P450 (CYP) enzymes. Large family of haem proteins. Found in SER.
What reactants are required for phase 1 reactions aside from the main?
NADPH -> NADP+
O2 -> H2O
What is an inducible enzyme?
One that is present in minute quantities but dramatically increases if a substrate is present. CYP enzymes are inducible by certain drugs eg carbamazapine
What is conjugation?
Addition of glucuronyl, sulphate, methyl, acetyl and gycyl groups.
Apart from the liver, where else do conjugation reactions occur?
Lung and kidney
When might detoxification reactions be a problem?
When drugs are given orally - first past metabolism.
What is the first step in the ethanol metabolism pathway and where does it occur?
Ethanol -> acetaldehyde
Via alcohol dehydrogenase and NAD -> NADH
Occurs in the cytosol.
What is the second stage of alcohol metabolism?
Acetaldehyde -> acetate
Via acetaldehyde dehydrogenase and NAD -> NADH
Occurs in the mitochondria
What is the lifespan of a red blood cell?
120 days
How are RBCs disposed of?
Phagocytosed mainly by Kupffer cells in liver, also in spleen and bone marrow.
The globin part of haemoglobin is degraded. What happens to haem?
Heam -> biliverdin. Looses Fe3+ and CO. Also via O2 -> H2O and NADPH -> NADP+
Biliverdin -> bilirubin via NADPH -> NADP+
What happens to bilirubin following haem metabolism?
Transported to liver hepatocytes attached to albumin.
What happens to bilirubin in the liver?
Conjugation (glucaronic acid) and secretion into canaliculi. Active process requires ATP.
What happens to bilirubin in the gut?
Further metabolised by bacteria to urobilinogen. Urobilinogen can be converted to urobilin (urine) and stercobilin (faeces).
What is prehepatic jaundice?
Too much haem overloads the system (eg haemolytic anaemia) - liver can’t manage to conjugate it all
Unconjugated bilirubin levels rise.
Prehepatic as problem occurs before liver is involved.
What is intrahepatic jaundice?
Problems with the conjugation process if liver is inflamed/damaged – again increase in unconjugated bilirubin.
What is posthepatic jaundice?
Problem lies with secretion e.g. gallstones then raised levels of conjugated bilirubin as this leaks back into the blood if the alternative route is blocked.
What is Gilbert’s syndrome?
Affects 2-7% of population – maybe 10 people in this room. Harmless inherited disorder – not enough of the conjugating enzyme present. Usually asymptomatic, picked up in routine checks. Mild jaundice can result if stressed/ill. Major risk is too much medical investigation!
