Liver Function Flashcards
Why is cholesterol important?
Synthesis of cell membranes and contributes to the fluidity of membranes (lipid rafts)
Precursor for the synthesis of several molecules including vitamin D, cortisol, aldosterone, progesterone, estrogen, testosterone, bile salts
Cholesterol synthesis
Cholesterol is synthesized de novo and obtained from dietary sources
Liver is a major site of cholesterol biosynthesis
Synthesized from Acetyl Co-A
Multi-step pathway to form cholesterol from Acetyl Co-A that can be divided into 3 major steps.
Cholesterol synthesis. Steps 2/3
Squalene is synthesized from isopentenyl pyrophosphate
Cyclization of squalene to form lanosterol
Lanosterol goes through several steps to eventually form cholesterol.
Cholesterol transport in the body
Lipophilic molecule and does not dissolve well in aqueous environment
Packaged with phospholipids and apolipoproteins to form a series of different lipoproteins
Lipoproteins contain a lipid core (contain cholesterol esters and triglyercides) and a hydrophilic outer surface containing phospholipids, free cholesterol and apolipoproteins
Main cholesterol carrying lipoproteins are low density and high density lipoproteins (LDL and HDLs)
Liver cholesterol metabolism
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke
Elevated levels of circulating LDL associated with the development of atherosclerosis
Inhibitors of cholesterol synthesis used to treat atherosclerosis
Statins inhibit HMG CoA Reductase in the cholesterol synthesis pathway
SYNTHESIS: Bile salts
Liver receives blood from the gastrointestinal tract via the hepatic portal vein and oxygenated blood from the heart via the hepatic artery.
Blood returns to the system circulation via the hepatic vein into the vena cava.
Liver continuously produces bile into the bile duct that goes to the GI tract or gall bladder
Bile Production
Hepatocytes secrete hepatic bile into the bile canaliculi
Hepatic bile also contains bile salts, bile pigments, cholesterol and lecithin (a phospholipid)
Epithelial cells that line the bile ducts secrete a bicarbonate rich fluid that increase the volume of the bile
Liver produces 600 – 1000 ml bile per day discharged into the duodenum or stored in gall bladder
Chemical nature of bile acids
Primary Bile acids (e.g. cholic acid) are synthesized from cholesterol and released into the intestine upon hormone stimulation
Secondary bile acids (e.g. deoxycholic acid) are formed in the intestine by the action of bacteria flora.
Bile Acid Conjugation
Primary or secondary bile acids are conjugated to amino acids (e.g. glycine) to generate water soluble bile salts.
Example cholic acid with glycine forms glycocholate
Sometimes called bile salts
Bile salts – hydrophobic and hydrophilic regions that aggregate to form micelles at a critical concentration
Important for the emulsification of fats
Enterohepatic circulation
The majority of bile salts are re-absorbed in the ileum (last segment of small intestine)
Approx. 95% bile salts that enter intestine are recycled back to the liver via the portal vein.
Uptake of bile salts from the portal blood into hepatocytes occurs via an active transport pathways.
Recycling from the GI tract to the liver is known as the enterohepatic circulation5% are lost in faeces (but liver makes new bile from cholesterol to replace the lost bile)
During digestion – Bile can be recycled several times via the enterohepatic circulation
Sphincter of oddi
Sphincter of oddi is a ring of smooth muscle found where the common bile enters the small intestine
Cholecystokinin (CCK)
Peptide hormone
Produced by the small intestine
Stimulus for release = amino acid, fatty acids in the intestine
Gall bladder
Sphincter of oddi closed -> bile is diverted to the gall bladder
Stores bile not required immediately for digestion of meals
Concentrates the bile by removal of salts and water
Can increase concentration of bile salts up to 20 fold
Excretory role of bile
Bile pigments are breakdown product of heme portion of haemoglobin from erythrocytes broken down in the liver and spleen
Bile contains approx 0.2 % bile pigments
Responsible for characteristic colour of bile (greenish yellow)
Major pigment is bilirubin found in bile and secreted into duodenum
SYNTHESIS: Plasma proteins
Liver secretes large numbers of proteins
Albumin: plasma protein, transport lipids and steroid hormones
Globulins: approx 40% total plasma proteins; a- and b-globulins also transport lipids and steriod hormones
Clotting factors: most are produced by liver e.g. fibrinogen and prothromin
