The Liver Flashcards
lecture 8 week 5
What is the blood supply to the liver
- the liver has a dual blood supply - 75% from the portal vein and 25% hepatic artery
- the portal vein drains nutrient rich blood from GI tract to the liver
- the hepatic artery receives oxygenated blood from the heart (aorta) and provides oxygen
- sinusoids (have oxygenated and nutrient rich blood) are lined with endothelial cells and Kupffer cell to remove any pathogens and cell debris
portal vein —> small portal venules —> sinusoids
hepatic artery —> arterioles —> sinusoids
blood from both then goes to central vein
What is the structure of the liver
- the liver makes up 2% of total body weight
- the liver is just beneath the diaphragm and above the stomach
-it is a critical organ with many functions: synthesis and secretion of bile, carbohydrate metabolism, fat metabolism, protein metabolism, secretes hormones, detoxification and storage of iron, vitamin A,D and B12 - there are four lobes in the liver the left and right liver separated by the falciform ligament and the caudate lobe and quadrate lobe with the gall bladder between
- the lobules are the structural and functional units of the liver, each is hexagonal and has a partial triad (portal vein, hepatic artery, bile duct) at the boundary
- there are six portal triads in a liver lobule
How is bile produced
bile is formed and secreted by hepatocytes, the liver produces between 600-1000 ml of bile each day
bile duct from different lobules form right and left hepatic duct which combines with cystic duct forming the bile duct
the bile duct transports bile to the duodenum
between meals, bile is continuously produced and sent to the gall bladder
the opening of the bile duct in the duodenum is guarded by the Sphincter of Oddi
the Sphincter of Oddi is closed when food is not taken and bile secreted is stored in the gall bladder
What does bile contain
- bile contains bile salts, phospholipids, bile pigments (bilirubin/biliverdin), cholesterol, lectin, mucus
- bile salt is amphipathic (hydrophobic and hydrophilic) so is important in fat emulsification. bile acid is conjugated to amino acids forming bile salts
- in emulsification fat has a micelle around it before being broken down into smaller fat droplets
How is bilirubin produced
- bilirubin is a major bile pigment that is formed when senescent red blood cells are broken down in the spleen
- it is carried to the liver in combination with plasmid albumin
- it is taken from the blood by hepatocytes and excreted as waste product in bile
excess bilirubin in the blood results in Jaundice from hepatic failure. In newborns its from excess lysis of red blood cells
bilirubin is formed from biliverdin, haemoglobin is broken down and converted to heme and then biliverdin
signs of Jaundice include yellow discoloration of the skin and sclera
How is plasma cholesterol maintained
cholesterol is needed for synthesis of bile acids and is mainly from the liver. Cholesterol can come from diet and too much causes gall stones. Cholesterol can narrow or block blood vessels if not regulated, if this is in the brain could lead to stroke
- cholesterol circulates in the blood in combination with lipoproteins LDL and HDL (LDL - bad - carries cholesterol to tissues, HDL - good - carries cholesterol to liver)
- HMG-CoA reductase controls the production of cholesterol
How is energy metabolism maintained
metabolic activity of the liver fuels the brain, the liver (and muscle) absorbs glucose from the blood and stores it as glycogen
high glucose: insulin and glycogensynthesis
low glucose: adrenaline/ glucagon, glycogenolysis and glucogenesis
What is glucogenesis
(production of glucose with carbohydrates)
Oxoloacetate —> Citrate —> alpha-Ketoglutarate —> Succinyl CoA —> Fumarate —> Oxoloacetate
PYRUVATE (alanine, cystine, serine, threonine, tryptophan) > ACETYL COA (tryptophan, leucine, isoleucine) = ACETOACETYL COA (phenylananine, leucine, lysine, tyrosine, tryptophase) into oxaloacetate
ALPHA- KETOGLUTARATE (argenine, glutamine, histidine, proline)
SUCCINYL COA (isoleucine, methionine, thereonine, valine)
FUMARATE (asparate, tyrosine, phenylananine)
Oxaloacetate —> phosphoenol-pyruvate —> glucose
- AMINO ACIDS first need to be deaminated in the liver before glucogenesis
What is detoxification
- deamination of amino acids in the liver results in the production of ammonia
- ammonia is a highly toxic strong base
- the liver converts ammonia to urea which is then excreted by the kidneys
Arginine —> Ornithine —> Citruline —> Arginosuccinate
Arginine + H20 = Ornithine + Urea
Ornithine + carbamyl phosphate —> citruline
What is the biotransformation of drugs/toxins
- the liver helps to get rid of xenobiotics (substances that are not usually present in the body eg. drugs/pesticides)
drugs in plasma —-> modified drugs —-> drugs conjugate —-> excretion
drug in plasma —> modified drug (phase 1: oxidation, reduction, hydrolysis)
modified drugs —> drug conjugate (phase 2: conjugation
Liver failure
- liver failure occurs when the liver is unable to perform its vital functions
- consequences of liver failure: Jaundice, Hypoglycemia, decline of bile production, rise in blood ammonia levels, decline in production of clotting factors, less able to carry out detoxification
- common causes of liver failure: cirrhosis (alcohol) - blood accumulates in portal vein as portal vein is obstructed - causes a leakage of fluid and swelling in abdomen
- treatment: carbohydrates intake to prevent protein breakdown to amino acids and a liver transplant
- ascites (swelling) from liver cirrhosis: hepatitis, paracetamol toxicity
What is paracetamol toxicity
therapeutic dose
- paracetamol conjugates with sulphate and glucuranide
- about 5% is oxidised into NAPQI (very toxic) by cytochrome P450
- NAPQI binds to gluthathione = cysteine and mercapturic acid conjugate excreted in urine
overdose
- sulphation and glucuronide pathway becomes saturated
- more paracetamol is oxidised into NAPQI
- glutathione (helps to detoxify NAPQI) becomes depleted
- NAPQI causes liver necrosis (death of liver cells)