The Liver

1450 cm 3 of blood flows through the liver every minute. Wide range of functions; 1)Amino acids to glucose cm 3 of blood flows through the liver every minute 2)Metabolism of fat. 3) Synthesis of Triglycerides. 4) Synthesis & regulation of cholesterol. 5) Deamination/ transamination/ urea formation 6) Production of bile. 7) Detoxification

A – Liver B – Hepatic vein C – Hepatic artery D – Portal vein E – Bile duct F – Stomach G – Cystic duct H – Gall bladder

Blood enters the liver through two vessels: 1)Hepatic artery 2)Portal vein 3x the blood enters via the Portal vein. The blood here comes from the small intestine it is rich is dissolved nutrients. The blood here is deoxygenated and at low pressure compared to the hepatic artery

Small intestine Liver Stomach Pancreas AORTA VENA CAVA

Histology of the liver…… 2mm Liver Lobule. Central vein HP vein Hepatic artery Bile duct

Histology of the liver…… There are 10,000 lobules one adult liver Blood flows up thru. HPV & hepatic art. HPV HA Blood then flows thru. into Central vein thru. SINUSOIDS Lobules are made of Cells called HEPATOCYTES Blood then flows to hepatic vein & out

2mm Histology of the liver…… Bile ducts Special cells produce bile, which flows thru. BILE CANALICULI. Special cells (KUPFFER) are macrophages that eat bacteria that come in blood From the HPV

CBH metabolism in the liver…… Liver stores glycogen and Hepatocytes respond to insulin & glucagon GLUCOSE GLYCOGEN GLUCAGON & ADRENALINE INSULIN GLYCOGEN 25% LIVER 75% MUSCLES

High blood Glucose level βcells in the Islets of Langerhans secrete INSULIN INSULIN Glycogen formed Blood glucose drops This occurs in HEPATOCYTES

Low blood glucose level αcells in the Islets of Langerhans secrete GLUCAGON GLUCAGON & ADRENALINE Glycogen This occurs in HEPATOCYTES High blood glucose level

CBH metabolism in the liver…… ……GLUCONEOGENESIS Gluconeogenesis – literally ‘making new glucose’ 3 biological molecules can be broken down to form glucose; AMINO ACIDS, LACTATE & LIPIDS. 3 biological molecules are initially broken down to form triose sugars (3C), which are then metabolised into glucose. There are 3 biochemical pathways, each of which are only used when glucose concentrations are low.

CBH metabolism in the liver…… ……GLUCONEOGENESIS Excess amino acids Glucose DEAMINATION Amino Grp (-NH 2 ) removed Urea formed Pyruvate Triose phosphate

CBH metabolism in the liver…… ……GLUCONEOGENESIS Excess lipids Glucose HYDROLYSIS Fatty Acids Triose phosphate Glycerol

CBH metabolism in the liver…… ……GLUCONEOGENESIS Lactate Glucose Triose phosphate Pyruvate What is Lactate? By product of anaerobic respiration, very common in large muscles.

Lipid metabolism in the liver…… Gluconeogenesis only occurs when blood glucose levels are low. When glucose levels are high, lipids are produced. So excess glucose forms lipids, lipids are needed for; Energy store in adipose cells Used in respiration to produce ATP Cell structures (membranes) Formation of steriods, which then form hormones

Lipids as an energy source…… Lipids are used as energy sources even when blood glucose levels are high. Often fatty acids are used as a preferred energy source, this is particularly true of cardiac muscle. Triglycerides are broken down into glycerol and fatty acids (hepatocytes),the fatty acids are broken down into acetyl coenzyme A, this is then fed into the Krebs Cycle, producing ATP.

Glycerol 3 fatty acids TRIGLYCERIDE Glycerol Glucose Triose phosphate 1 2 Acetyl Coenzyme A ATP KREBS CYCLE Lipids as an energy source……

Synthesising triglycerides…… Once lipids are synthesised, they are converted to TRIGLYCERIDES and then stored in adipose tissue. But, lipids are insoluble in water, meaning they are difficult to transport. They are converted to LIPOPROTEINS as low density lipoproteins (LDLs) For each fat that needs transporting, there is specific lipoprotein that does the job – the all have different densities.

Synthesising & regulating cholesterol…… The liver makes cholesterol. Cholesterols functions are: 1) Cell membrane stability. 2) Cell membrane fluidity. 3) Membrane barrier to hydrophilic substances. 4) Synthesis of steroid hormones (oest/test) 5) Deposited under skin, making it waterproof. 6) Involved in Vit D synthesis. 7) Involved in synthesis of bile salts.

Synthesising & regulating cholesterol…… Meat, eggs and other diary products have high cholesterol. less When you eat lots of these foods, your liver synthesises less cholesterol. This is called dietary cholesterol. High levels of dietary cholesterol stops…… Acetyl Coenzyme A CHOLESTEROL..Enzymes So high levels of DIETARY CHOLESTEROL does not always lead to high BLOOD CHOLESTEROL

Synthesising & regulating cholesterol…… Alternatively, if your diet contains high levels of SATURATED FATS… …synthesis of cholesterol increases. No C-C double bonds, e.g. all C-H bonds Lots of evidence to suggest that genetics Has a role to play

Transporting cholesterol…… Cholesterol is a lipid, therefore not water soluble. It is also transported in LIPOPROTEINS. It is transported as either……. High Density Lipoproteins HDLs These are good for you. Protecting you from LDLs May also remove LDLs Low Density Lipoproteins LDLs These are not good for you. They deposit cholesterol on walls of arteries (AKA plaques)

Protein metabolism…… Convert one amino acid to another - AKA TRANSAMINATION. Removing excess amino acids - AKA DEAMINATION. Production of urea – linked to DEAMINATION. Production of 3 blood proteins – FIBRINIGEN/ALBUMIN/GOBULINS

TRANSAMINATION - converting one amino acid to another. If our dietary intake of amino acids does not match the bodies requirements, then the liver has the ability to add/remove elements from R groups inorder to make new amino acids. There are a group of amino acids that the body can not do this with, they are called ESSENTIAL AMINO ACIDS.

DEAMINATION – removing excess amino acids. If our dietary intake of amino acids exceeds the bodies requirements, then the excess needs to be removed. Deamination removes the AMINE GRP (-NH 2 ), with the rest of the molecule being converted to CBH or fat. The AMINE GRP (NH 2 ) is converted to AMMONIA (NH 3 ) – this is very soluble and toxic, so is not around for long! It is then combined with CO 2 using ATP to produce UREA (CO(NH 2 ) 2 this occurs in the ornithine cycle.

The ORNITHINE CYCLE. Deamination NH 3 CO 2 ATP UREA CO(NH 2 ) 2

SYNTHESIS of PLASMA PROTEINS……… There are 3 important proteins in blood; Fibrinogen Globulin Albumin Each of these proteins are globular and are produced in the liver. Hwrk: Read and make notes on GLOBULIN & ALBUMIN (pg 24).

SYNTHESIS of PLASMA PROTEINS……… Damage to blood vessels leads to the collagen fibres being exposed, this stimulates platelets. Prothrombin Thrombin Fibrinogen Fibrin Thrombin – an enzyme, which catalyses the removal of AA from fribrinogen, to allow it to polymerase and form FIBRIN. Fibrin is an insoluble protein that forms long fibres, they tangle up trapping rbcs and leading to a clot.

Production of BILE……… 2mm Bile ducts Special cells produce bile, which flows thru. BILE CANALICULI. 1000cm 3 of bile is produced each day Cholesterol made in the Liver is needed to prd. bile Bile to gall bladder

Production of BILE……… BILE is composed of water & BILE SALTS. BILE SALTS emulsify fats, then LIPASE can act on the larger surface area. BILE SALTS also contain cholesterol – if there is too much cholesterol or not enough water, gall stones can form. They can block bile duct and interfere with lipase digestion.

BILE & dead RBCs……… RBCs only live for about 120 days, then they are broken down in the spleen. (below the heart, lower than the diaphragm). HAEMOGLOBIN is broken down in the LIVER into HAEM & GLOBIN. GLOBIN is broken down into its constituent AA, these are then recycled. HAEM is broken down into iron and the greenish yellow product called BILIRUBIN – this is excreted into bile.

DETOXIFICATION Many drugs/dangerous substances are broken down in the smooth endoplasmic reticulum of hepatocytes. Metabolising alcohol Alcoholic drinks contain ethanol (C 2 H 5 OH) It is lipid soluble, so moves thru. cells very easily. Alcohol dehydrogenase catalyses the breakdown of ethanol to ethanal. Aldehyde dehydrogenase then catalyses the breakdown of ethanal to ethanoate Ethanoate can then enter the Krebs cycle to produce ATP.

ETHANOLETHANALETHANOATE The KREBS CYCLE ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE Oxidised NAD Reduced NAD Reduced NAD Oxidised NAD DETOXIFICATION of ALCOHOL If you drink too much, reduced NAD builds up and levels of oxidised NAD become low. These means fatty acids build and a condition called ‘fatty liver’ develops.

DETOXIFICATION of ALCOHOL Drinking too much leads to Low levels of oxidised NAD, failure to metabolise fatty acids and ‘fatty liver’ develops. Destruction of hepatocytes, leads to replacement with inferior hepatocytes. Reduced blood supply to the lobules This is called CIRRHOSIS The liver can not function properly, e.g. NH 3 builds up and can Lead to coma and death in extreme cases