BY3BC1- Medical Biochemistry Lecture 3- Liver Function LO- - Basic structure and function of the liver - Conditions that can involve liver malfunction in particular jaundice. Liver disease - Fifth biggest killer in the UK and the only major cause of death that is increasing - Around 1 in 25 people in the UK have tested positive for abnormal liver function - Can be inherited, or viral, excessive alcohol use and obesity Liver ultrastructure - Liver gets 70% of blood from the portal vein and 30% from the hepatic artery fuel the livers dual blood supply - Portal vein does not drive into the heart itself, carries venous blood - By supplying the liver first so that substances ingested are processed by the liver first- detoxifies these substances - and the liver is the first organ that absorbs nutrients taken from the intestine. - Site of bile production Sinusoidal s pace Kupffer cell Nucleus Sinusoidal space Parenchymal cell 22 (hepatocyte) Biliary canaliculus Liver key functions (in exams good to state normal S&F to set essays) - Excretion of nitrogen makes urea - Protein biosynthesis: albumin (maintains osmotic pressure in the organs main function), clotting factors - Metabolism of many drugs
- Metabolism: main site of gluconeogenesis (generation of glucose from non-carbohydrate substrates e.g. lactic acid), makes very low-density lipoprotein - Formation of bile: - Phospholipids - Bile salts - Cholesterol - Bilirubin - a breakdown product of haem Jaundice - Abnormally high plasma concentration of bilirubin (yellow ish eyes goes yellow skin is pale) - >21umol/l - Most bilirubin is produced when haemoglobin is broke down into uncogitated bilirubin (binds to albumin in the blood for transport to the liver so if the liver is compromised the levels of bilirubin increase in the blood) - Prehepatic (condition not involved directly in the liver but liver is involved after) - Hepatocellular (damage of the liver itself) - Cholestatic Metabolism and transport of bilirubin Spleen Haemoglobin haem globin iron bilirubin albumin Bilirubin-albumin (unconjugated) urobilinogen Kidney Portal vein (entero-hepatic circulation) Liver Bilirubin diglucuronide Ā»(conjugated) Active transport of conjugate across the canaliculus bilirubin Urobilinogen in urine Bile duct b a bilirubin C + e urobilinogen urobilinogen r i urobilin a Large Intestine Bilirubin from haem is hydrophobic and must bound to albumin to travel to the liver. In the liver it becomes conjugated and is actively transported from the liver to the large intestine. Where it is broken down to urobilin which is responsible for the colour of your stool and its excreted. Excess blood cell breakdown leading to excess bilirubin, excess urobilinogen leads the intestine and is secreted in the urine which can act as a biomarker. Prehepatic jaundice - Markedly increases unconjugated bilirubin in blood due for example to haemolytic anaemia (and any condition that increase haemolysis) - No bilirubin in urine - Bound to albumin so not filtered by kidney (urobilinogen in the urine) - Detected with dipsticks impregnated with diazo reagent
- Urobilinogen in urine - Urobilinogen is water soluble