Liver

Functional Unit of Liver

• Liver Lobule - hexagonal shaped, perform all 500 functions

Hepatocytes

• liver cells

• prominent nuclei, golgi, lysosomes, mitochondria, glycogen granules and fat droplets

• microvilli for faster exchange of material

• GLYCOGENESIS takes place here

• produce bile salts from cholesterol

• contain peroxisomes (catalase) detoxify toxic substances

Lobules are supplied with blood from

• hepatic artery - this is oxygenated blood

• hepatic portal vein - blood coming from the small intestine

• central vein - hepatic vein - which takes the blood back to the heart, found at the center of each lobule)

Sinusoids

• join the hepatic vein to hepatic artery and hepatic portal vein

• sinusoids alternate w bile canaliculi - carry bile from hepatocytes to bile duct - gall bladder

• bile canaliculi and sinusoids run countercurrent to each other - and DONT MIX

• blood channels rather then blood vessles

• thin lining of endothelial cells

Kupffer Cells

• attached to the wall of sinusoid

• phagocytic - engulf bacteria

• remove old blood cells and send products to hepatocytes

Macrophages

• wander around in the liver

• identify and remove pathogens via phagocytosis

Portal Triad

• branch of hepatic artery

• branch of hepatic portal vein

• branch of bile duct

Brief Overview of Functions perfomed by the liver

• Carbohydrate metabolism

  • Glycogenesis

  • Glycogenolysis

  • Gluconeogenesis

  • Cori Cycle - Break down lactin acid - glucose

  • Carbohydrates to fats

• Protein Metabolism

  • deamination

  • detoxification

  • Transamination

  • Synthesis of Plasma Proteins

  • Breakdown of RBC

• Fat Metabolism

  • Cholesterol breakdown/synthesis

  • Gluconeogenesis

  • Bile Production

• Vitamin, mineral storage - detoxification - hormone breakdown

Glycogenesis

• Decreases blood sugar (creation of glycogen from glucose)

• stimulated by hormone INSULIN

• hepatic portal vein carries the sugars to liver - only vessel which has v variable sugar content

• maintain 70mg-100mg/100ml of blood

Glycogenolysis

• Increase of blood glucose level (breakdown of glycogen into glucose)

• Stimulated by Glucagon

• prevent blood lvl going below 60mg/100ml

• adrenaline/noradrenaline released by adrenal medulla and ends of sympathetic neurons respectively can also stimulate this effect

Gluconeogenesis

• making glucose from NON-CARBOHYDRATE SOURCES - amino acids, fats and glycerol

• low blood gluc levels stimulate release of adrenocortiocotrophic releasing factor (CRF) stimulates ACTH → release of cortisol

• cortisol - release of amino acids, glycerol and fatty acid from tissue to blood

• increase rate of synthesis of enzymes in liver which convert these into glucose

• fatty acids → acetyl coA → used directly in krebs

Cori Cycle

• muscles only breakdown glycogen → glucose → pyruvate which is used to produce atp during aerobic or anaerobic resp

• lactic acid produced during aerobic resp. is turned into glucose in the liver - then glycogen

Conversion of Carb to Fat

• carbs which cannot be used or turned into glycogen are converted to adipose tissue

• stored beneath the skin

Demination

• removal of NH2 group from amino acid - turned into ammonia Nh3

• this leaves an acid which can be used in Kreb’s to produce energy

Detoxification

• involves the conversion of NH3 to urea via the ORNITHINE CYCLE

• take place in mitochondria and cytosol

1. Co2 + Nh3 —ATP→ carbamoyl phosphate

2. Carbamoyl Phosphate + ornithine → citrulline + h20

3. Citrulline + Nh3 → Fumarate + H20 + Arginine

4. Arginine + H20 → Urea + Ornithine

--overall ; 2 NH3 are used, 1CO2 and 1 H20 and 1 urea are made

Transamination

• synthesis of non-essential amino acids through the transfer of an amino group from an amino acid onto an organic/keto acid

• produces NON-ESSENTIAL amino acid

• essential must be obtained through DIET

Plasma Protein Production

1. Albumin

   1. creates osmotic pressure which opposes the hydrostatic pressure created in vessels - allows for absorption of tissue fluid BALANCE OF FLUID

   2. transport molecules - calcium, bile, salts and steroid hormones

2. A and B Globulins

   1. transport insulin, thyroxine, cholesterol, vitamins and lipid

3. Clotting Factors

   1. Factor VIII, prothrombin, fibrinogen

Breakdown of rbc and haemoglobin

• phagocytic macrophages breakdown rbc after 120 days

• haemoglobin is taken by macrophages to liver

• Globin - protein broken down into its amino acids to be re-used

• Haem - iron is removed, remaining part is converted to biliverdin —> bilirubin (component of bile

• Iron can either combine w a plasma protein in blood to form TRANSFERRIN - then taken to bone marrow to make more hemoglobin

• or taken up by hepatocytes and stores as ferritin

Liver of Fetus

• rbc production

• however this is then taken over by bone marrow

Breakdown/Synthesis of Cholesterol

• cholesterol is removed from blood and broken down and also synthesized

• Thyroxine stimulates cholesterol formation and excretion in bile

• needed for synthesis of hormones and membranes

• risk of formation of blood clot - narrow arteries

Types of Cholesterol

• High-Density Lipoproteins

  • pick up dietary cholesterol and transport it to membrane

  • make bile

  • good cholesterol

• Low-Density and Very Low Density Lipoproteins

  • these are ‘bad’ cause blood clotting due to depositing on the side of arteries

Gluconeogenesis - Fat metabolism

• break down fats into fatty acid n glycerol

• glycerol → glucose in gluconeogenesis

• beta oxidation of fatty acid → acetyl → acetyl coa → krebs

Contents of Bile

• water

• cholesterol

• bile salts - emulsify - made from cholesterol

• bile pigment - no function (bilirubin and biliverdin) simply product of broken down rbc

• inorganic salts

Bile Production

• bile is produced by hepatocytes and secreted into bile canaliculi → bile duct and then stored and conc in gall bladder

• released into duodenum due to presence of Cholecystokinin (CCK)

• bile emulsifies fats into smaller fat droplets → increases surface area on which lipase can act

Other functions of liver

• vitamin and mineral storage - A,D,E,K

• detoxification → removing toxic substances, alc and nicotine, eg catalase breaks down H2o2 into H2 and O2

• hormone breakdown