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The Liver

The Liver. 1450 cm 3 of blood flows through the liver every minute. 1450 cm 3 of blood flows through the liver every minute. 1)Amino acids to glucose. Wide range of functions;. 7) Detoxification. 2)Metabolism of fat. 6) Production of bile. 3) Synthesis of Triglycerides.

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The Liver

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  1. The Liver

  2. 1450 cm3 of blood flows through the liver every minute. 1450 cm3 of blood flows through the liver every minute 1)Amino acids to glucose. Wide range of functions; 7) Detoxification 2)Metabolism of fat. 6) Production of bile. 3) Synthesis of Triglycerides. 5) Deamination/ transamination/ urea formation 4) Synthesis & regulation of cholesterol.

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

  4. Blood enters the • liver through two • vessels: • Hepatic artery • 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

  5. VENA CAVA Stomach Liver Pancreas Small intestine AORTA

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

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

  8. 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 2mm

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

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

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

  12. 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.

  13. CBH metabolism in the liver…… ……GLUCONEOGENESIS Amino Grp (-NH2) removed Urea formed Excess amino acids DEAMINATION Glucose Pyruvate Triose phosphate

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

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

  16. 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; Formation of steriods, which then form hormones Cell structures (membranes) Energy store in adipose cells Used in respiration to produce ATP

  17. 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.

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

  19. 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.

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

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

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

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

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

  25. 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.

  26. DEAMINATION– removing excessamino acids. If our dietary intake of amino acids exceeds the bodies requirements, then the excess needs to be removed. Deamination removes the AMINE GRP (-NH2), with the rest of the molecule being converted to CBH or fat. The AMINE GRP (NH2) is converted to AMMONIA (NH3) – this is very soluble and toxic, so is not around for long! It is then combined with CO2 using ATP to produce UREA (CO(NH2)2 this occurs in the ornithine cycle.

  27. The ORNITHINE CYCLE. Deamination ATP NH3 CO2 ATP UREA CO(NH2)2

  28. 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).

  29. SYNTHESIS of PLASMA PROTEINS……… Prothrombin Damage to blood vessels leads to the collagen fibres being exposed, this stimulates platelets. Fibrinogen Thrombin 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.

  30. Production of BILE……… Bile ducts Special cells produce bile, which flows thru. BILE CANALICULI. 1000cm3 of bile is produced each day Bile to gall bladder Cholesterol made in the Liver is needed to prd. bile 2mm

  31. 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.

  32. 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.

  33. DETOXIFICATION Many drugs/dangerous substances are broken down in the smooth endoplasmic reticulum of hepatocytes. • Metabolising alcohol • Alcoholic drinks contain ethanol (C2H5OH) • 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.

  34. DETOXIFICATION of ALCOHOL ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE ETHANOL ETHANAL ETHANOATE Oxidised NAD Reduced NAD Oxidised NAD Reduced NAD The KREBS CYCLE 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.

  35. 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. NH3 builds up and can Lead to coma and death in extreme cases

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