liver physiology

week 3 ctb

functions of the liver

1. energy metabolism and substrate interconversion

2. cholesterol processing

3. production of bile

4. excretion of bilirubin

5. drug metabolism and detoxification

6. synthesis of plasma proteins

7. storage of vitamins and minerals

8. immune functions

histological organisation of the liver

2 major fluid inputs:

1. oxygenated blood from the arterial system via the hepatic artery

2. deoxygenated blood from the intestine via the hepatic portal vein

2 major fluid outputs:

1. deoxygenated blood to the venous system via hepatic veins

2. bile to the small intestine via bile ducts

• these are linked by central veins running through liver lobules containing hepatocytes

histological organisation of the liver

organisation of liver

zone I periportal hepatocytes:

• most oxygenated 

• cells specialise in oxidative metabolism, gluconeogenesis. urea synthesis

zone II pericentral hepatocutes:

• least oxygenated

• cells specialise in drug metabolism, glycolysis, lipogenesis

• differential of oxygen content from HIGH on the outside to LOW in the centre

histological organisation of liver cont.

• liver lobules contain plates of hepatocytes, lying in a cage of reticuloendothelial cells

• plates separated by vascular spaces called sinusoids

• blood from sinusoids converges on the central vein

• in turn, central veins coverge on the hepatic vein

liver cell type diagram

liver cell types

• hepatocytes 

• endothelial cells

• Kupffer cells

• stellate cells

• cholangiocytes

hepatocytes

• major parenchymal (functional) cells of liver

• responsible for metabolic and secretary roles

• cuboidal in shape and contain abundant mitochondria, ribosomes and ER

endothelial cells

• flattened and specialised

• structural role lining the sinusoids

• small in volume, form a large surface area

• fenestrations for filtering fluid

Kupffer cells

• tissue macrophages (capable of phagocytosis)

• located in hepatic sinusoids

• attached to the endothelial cell lining

stellate cells (lipocytes)

• located in perisinusoidal space (space of Disse)

• long protusions that wrap around the sinusoids and may act as APCs

• contain lipid droplets and store lipid soluble vitamins

cholangiocytes

• epithelial cells lining bile ducts of liver and hepatobiliary system

• vary in shape from cuboidal in small interlobular bile ducts to columnar in the larger bile ducts

• contribute to bile production through secretion of bicarb

energy metabolism

• carb metabolism

  • liver stores energy in the form of glycogen, performing glycogenesis in fed state and glycogenolysis in fasting state

  • all gluconeogenesis takes place in liver → produces new glucose from glyceral, lactate from anaerobic glycosis and AAs

• lipid metabolism

  • liver carries out beta oxidation of fatty acids and triglyceride synthesis

  • in fasting state, liver performs ketogenesis, producing ketone bodies from acetyl-CoA and releasing them into the circulation

• protein metabolism

  • liver carries out transamination and deamination of AAs, producing urea for excretion via urea cycle

energy storage diagram

energy utilsation diagram

cholesterol

• lipid molecule that has many important functions

  • plasma membranes

  • components of bile salts

  • precursor for steroid hormones

  • myelin

• 15% of cholesterol comes from diet

• 85% cholesterol is synthesised within body (mostly in liver)

• transported in blood plasma in complexes called lipoproteins (synthesised mainly by liver)

cholesterol processing diagram

cholesterol processing

multiple key roles in cholesterol processing:

• synthesises cholesterol from acetyl-CoA

• synthesises lipoproteins, which transport cholesterol in blood plasma

• distributes cholesterol via circulation to body cells, for synthesis of key products (steroid hormones)

• utilises cholesterol for synthesis of bile salts

• extracts excess cholesterol from blood plasma

• exports excess cholesterol in bile for excretion in faeces

bile

• complex aqueous solution produced by liver

• released into SI to aid digestion of lipids

• intially made by hepatocytes and then modified in bile duct system (involves both absorption and further secretion by epithelial cells)

• its production and release into duodenum after a meal are stimulated by intestinal hormones secretin and CCK

• bile salts act as a surfactant, emulsifying dietary lipid droplets in intestine by reducing surface tension at the lipid/water interface

bile composition

1. bile salts (steroid bile acids conjugated with taurine or glycine)

2. lecithin (amphiphilic phospholipids)

3. cholesterol

4. bile pigments (bilirubin)

5. HCO₃^- and other salts

6. trace metals

bile production

• hepatocytes secrete

  • bile salts

  • lecithin

  • cholesterol

  • bile pigments

• cholangiocytes secrete:

  • bicarb

  • water

• components of bile are secreted into bile canaliculus and drain into bile duct

bile secretion

• liver produces and secretes 1L of bile a day, stimulated by hormone secretin

• bile is stored and concentrated in the gall bladder, which contracts when stimulated by CCK

• then enters duodenum via common bile duct

excretion of bilirubin

• bile pigments are excretory products being disposed of by the liver via the intestine

• main bile pigments is bilirubin, formed from the breakdown of haem in the spleen and bone marrow

• hepatocytes conjugate bilirubin with glucuronic acid to form a polar, water-soluble molecule

• secreted in bile

biosynthetic functions of the liver

liver synthesises many proteins that are released into blood plasma:

carriage proteins (binding proteins)

• albumin

• transferrin (iron transport)

• sex hormone binding globulin (SHBG)

• thyroid binding globulin (TBG)

factors involved in haemostasis/fibrinolysis

• coagulation (fibrinogen)

• fibrinolysis (plasminogen)

pro hormones, apolipoproteins, immunoglobulins

liver function tests

• allows clinical assessment of liver in a cheap, safe and non-invasive manner

• decrease in blood component produced by liver (albumin) can indicate impaired liver function

• increase in a substance normally cleared from blood by liver (bilirubin) can also indicate impaired liver function

• increase in blood plasma conc of enzymes normally found in liver (transaminases) could indicate a loss of structural integrity of liver cells