Structure and function of the liver Flashcards
where is the liver and what is its structure
lies on RHS of upper abdomen and protected by lower ribs
has two lobes
covered in capsule of connective tissue
what is the function of the common bile duct
transports bile synthesised in the liver to the duodenum
what does the common bile duct merge with
the pancreatic duct to form a common passageway known as the ampulla of vater
what regulates secretions into the duodenum
sphincter of oddi
what happens to the all bladder during meals
stimulated to contract and forcing stored bile down the common bile duct
how much blood supply does the liver receive from the heart
25% of resting cardiac output
what are the two main inputs of blood supply to the liver and where does it stem from
portal vein (75%) - from small intestine, stomach, pancreas, spleen hepatic artery (25%) - oxygenated blood
what is the output of blood from the liver
hepatic vein - into inferior vena cava
describe the structure of the lobules in the liver
hexagonal with a portal tract at each angle - contains 3 vessels (HPV, HA, bile duct)
blood from the hepatic artery and HPV flow in sinusoids
what is the flow of bile in the liver
from the cells in the liver down bile cannliculi to the bile ducts ie in the opposite direction to the blood flow
where is the space of disse
between the hepatocytes and the endothelial cells
what fills the space of disse
stellate cells and collagen fibres
what are the 5 types of cells in the liver
hepatocytes
endothelial cells
kupffer cells
pit cells (liver associated lymphocytes)
hepatic stellate cells (Ito cells or lipocytes)
what are the most common cells in the liver
hepatocytes (60%)
carry out most metabolic functions
what is the structure of endothelial cells in the liver
lining cells of the sinusoids
contain fenestrations so do not form a barrier against small molecules
what are kupffer cells
located within sinusoidal lining - macrophages
phagocytose bacteria, old erythrocytes, protect liver from gut derived bacteria
what are pit cells in the liver (liver associated lymphocytes)
NK cells - help protect against tumours or viruses
what are and what is the role of hepatic stellate cells (Ito cells or lipocytes)
lipid filled cells
primary site of vit A storage
control turnover of connective tissue, synthesise collagen and regulate contractility of sinusoids
what are the two main functions of the liver
“the factory” - raw materials, making new stuff, recycling, storage
carb, lipid and protein metabolism, bile formation
waste management
detoxification of xenobiotics
removal of waste such as degradation of bilirubin
what 8 modules can be stored in the liver
glucose as glycogen
vit A,D,K, B12, iron, copper
what are the 3 metabolic functions of the liver
raining blood glucose levels
nitrogen metabolism
lipid metabolism
what blood components are synthesised in the liver
albumin, clotting factors, lipoproteins
what is bile made from
made up of water, bicarbonate, bile salts, cholesterol, phospholipids
describe the formation of bile
formed in the hepatocytes from cholesterol. hydroxylation and then conjugation with glycine or taurine
describe the recirculation of bile
reabsorbed into the portal vein from the intestine
describe how cholestryamine lowers blood cholesterol
binds to bile acids in the gut and prevents recirculation and therefore more cholesterol used to form bile acids
what are gall stones
more cholesterol enters the bile than can be solubilised by bile slats which causes precipitation - these stones get stuck in the common bile duct
what diseases are caused by gall stones
biliary colic and acute cholecystitis
what are xenobiotics and give examples
toxic or of no nutritional value
drugs - both pharma and recreational
food additives or toxins in food
what waste products are broken down by the liver
hormones eg insulin, GH and oestrogen
bilirubin - breakdown of erythrocytes
urea - removal of NH4 ions mainly from metabolism of protein
describe of a xenobiotic compound becomes a secondary metabolite
phase one reactions (hydroxylation, hydrolysis, redox) - primary metabolite
phase two reactions (conjugation, sulphonation, glucuronidation) - secondary metabolite
what is the difference between phase 1 and phase two products
phase 1 - catabolic and often yield more reactive substances
phase 2 - produce inactive compounds with decreased lipid solubility to aid excretion
what dictates phase 1 metabolism
CYP P450 enzymes
where are CYP enzymes found
smooth ER
can drugs affect CYP enzymes
enzymes are inducible baby drugs such as alcohol and carbamazepine
what is phase 1 reactions catalysed by
molecular oxygen as donor of O atom, and requires NADPH as cofactor
what in summary are phase two reactions
range of addition reactions mainly in the liver but also in other tissues such as lungs and kidneys
what is a prodrug
inactive compound which is metabolised to produce the therapeutically active form in the body
why do you use prodrugs
improve absorption of the drug in the gut
allow alternative routes of administration
why are some women less affected by tamoxifen
they lack CYP2D6 depending on ethnic group and therefore less potent metabolite produced
describe why taking too much paracetamol is bad
normally a phase two 2 pathway
when you take too much there is too little glutathione which allows free NAPQI to react with cell membranes
hepatic necrosis results and leads to liver failure
describe the stages of bilirubin metabolism
first phase mainly by kupffer cells - haem broken down after 120 days to biliverdin which is greenish, then to bilirubin which is yellow/orange
what is bilirubin attached to during transportation
albumin to liver hepatocytes
what happens to bilirubin the the liver
conjugation (mainly glucuronic) and secretion into biliary canlicula (requires ATP)
what happens to bilirubin in the gut
further metabolism by bacteria in the gut to urobilinogen which is then converted to urobilin (excreted in the urine) and stercobilin (excreted in faeces)
what is preheaptic jaundice
too much haem maybe from haemolytic anaemia such as in sickle cell and liver can’t conjugate it all
what is gilberts syndrome
harmless inherited disorder but not enough conjugating enzyme present - mild jaundice from illness
what problems occur if problems with secretion of bile
gall stones - raised levels of conjugated bilirubin as leaks back into blood
