liver physiology and function

• liver anatomy

  two lobes: left and right - separated by falciform ligament

  liver can be subdivided into 9 functional segments - this is based on vascular supply and biliary drainage
• the liver receives how much of cardiac output?

  about 20%
• what are the two routes blood goes into the liver?

  1. Splanchnic blood (nutrient-rich and deoxygenated) from the gut via the portal vein to regulate nutrient levels/detoxification)
  2. Oxygenated blood via the hepatic artery (comes from the lungs) - used to sustain liver cells (hepatocytes)
• the liver is composed of smaller structures called what?

  lobules
• lobules...

  each surrounded by branches of the hepatic artery and portal vein
• the portal triad includes what?

  hepatic artery, portal vein and bile ductule
• vessels drain into capillary-like structures called?

  sinusoids
• sinusoids drain into a central vein → deoxygenated blood → hepatic vein
• sinusoids

  • are specialised capillaries - that have similar function
  • but they have increased permeability allowing larger molecules to cross (e.g. proteins) as they have pores - this is vital for liver function
• how do sinusoids have increased permeability?

  They have an incomplete basement membrane/surrounding diaphragm. The endothelial layer also contains large intracellular gaps. Together this permits passage of larger molecules.
• name the cells of the liver.

  Sinusoidal endothelial cells

  Kupffer cells

  Stellate cells

  Hepatocytes

  Chlolangiocytes
• what are sinusoidal endothelial cells?

  they line the sinusoidal blood vessels - less tight junctions
• what are kupffer cells?

  they're macrophages of the liver, reside in the lumen of sinusoids - they are exposed to immunogens from the gut
• what are stellate cells?

  found in peri-sinusoidal space, quiescent (inactive) and activated in response to damage
• what are hepatocytes?

  Large cuboid cells, extremely metabolically active have a lot of mitochondria. Contains large numbers of organelles (especially smooth ER), and binucleate. They are the main cells of the liver (90% of the cell mass).
• what are cholangiocytes?

  the epithelial cells lining the bile ducts
• which organelle is found in the liver quite a lot?

  lysosomes
• name some functions of the liver

  1. Metabolises nutrients from food to produce energy when needed
  2. Prevents shortages of nutrients by storing vitamins, minerals and sugars
  3. Removes potentially toxic byproducts of certain medications
  4. Produces most proteins needed by the body
  5. Product bile
• nutrient processing;

  absorbed nutrients are transported to the liver for metabolism from the GI tract.

  the liver then:

  • converts them into forms that can be stored or used
  • mediates their transport to tissues
• name of nutrients stored within the liver include:


  glycogen, fat, iron and vitamin A
• protein metabolism;

  The body cannot store amino acids so need to be broken down and excrete excess proteins. Amino acid breakdown releases a potentially toxic amine group. The liver removes the amine group via deamination and converting it into urea. The liver also synthesises non-essential amino acids = called transamination.
• how is urea excreted?

  by the kidneys
• carbohydrate metabolism;

  Excess glucose is stored as glycogen. If blood glucose drops, the liver breaks down glycogen into glucose and exports it.

  If hepatic glycogen reserves become exhausted, the liver synthesises glucose from other sources (e.g. fats). These metabolic processes are coordinated by pancreatic hormones - insulin and glucagon.
• fat metabolism;

  liver synthesises phospholipids and cholesterol and converts excess carbohydrates and proteins into fats.
• what is VLDL?

  very low density lipoprotein - these allow lipids (triglycerides) made in the liver to be transported to rest of the body
• Cholesterol is exported to cells by different types of lipoproteins (HDL or LDL)

  • LDL transports cholesterol to cells
  • HDL transports excess cholesterol from cells back to the liver
  • LDL is ‘bad’ as it raises blood cholesterol levels
  • HDL is “good” as it lowers cholesterol levels
• surplus cholesterol is converted by the liver into bile salts and excreted
• what are statins?

  HMG-CoA reductase inhibitors - lowers LDL
• how is vitamin A stored in the liver?

  Vitamin A (retinol) is absorbed from the gut. It is carried around the blood in a complex with TTR and is stored in stellate cells.

  In some immune cells (esp. dendritic cells) retinol is converted to retinoic acid

  • very metabolically active
  • delivered to cells that need it
  • then metabolised by the liver again
• detoxification occurs in two steps;

  1. Phase I: Toxins (fat-soluble) are processed by oxidation, reduction and hydrolysis reactions

  • mediated by enzymes: cytochrome P450 group
  • produce free radicals → neutralised by antioxidants

  1. Phase II: Toxin (or metabolite from Phase I) is conjugated to another compound (e.g. cysteine)

  • the compound is even less harmful
  • water-soluble → so can be excreted (urine)
• what are plasma proteins?

  proteins in the blood plasma
• examples of plasma proteins produced in the liver...

  albumin, globulins, and fibrinogens. they are made by hepatocytes via ER and Golgi apparatus.
• what does albumin do?

  regulates the osmotic pressure of the blood. it's unable to escape capillaries as they are too large
• globulins: transport and antibodies

  A) lipids

  B) copper

  C) iron

  D) immunoglobulins

  
• major types of plasma proteins

  A) osmotic

  B) antibodies

  C) transport

  D) clotting

  
• biliary system;

  • Gall bladder
  • Storage of bile
  • Release to duodenum
  • Absorption of water (mucosa)
  • Concentrates bile
  • Dilates and contracts
  • Pressure control
  • Responds to cholecystokinin
  • Cholecystokinin (CCK) - hormone
  • Released from the duodenum
• production of bile;

  Bile released into the GI tract is stimulated by food in the small intestine (chyme). Bile is alkaline and bile salts neutralise the chyme coming from the stomach as enzymes in the intestine like alkaline conditions. Bile salts are produced in the liver, secreted by hepatocytes and stored in the gall bladder.
• what do cholangiocytes do to bile?

  modify the bile volume and composition
• what is the purpose of secretion of bile salts into the small intestine?

  Emulsify fats - emulsification increases the surface area allowing the increase in action of lipases
• Bile salts are reabsorbed by the gut and metabolise them to detoxify them and so re up-taken by the liver - recycling of the bile salts and bile acids = metabolically efficient.