D3 - Liver functions

Function liver & what is it responsible for

regulate the chemical composition of blood

* storage and release of key nutrients (glycogen, cholesterol and triglycerides e.g.)
* detoxification of potentially harmful ingested substances (e.g. amino acids, medication, alcohol)
* produces plasma proteins that function to maintain sustainable osmotic conditions within the bloodstream
* Breakdown of rbc and production of bile salts

Arteries & vein

* hepatic artery → receives oxygenated blood
* portal vein → receives nutrient rich blood
* hepatic vein → deoxygenated blood

What is the liver composed of?

Hepatic lobules

* surrounded by branches of hepatic artery and the portal vein
* These vessels drain into capillary-like structures called sinusoids, which exchange materials directly with the hepatocytes
* The sinusoids drain into a central vein, which feeds deoxygenated blood into the hepatic vein
* Hepatocytes also produce bile, which is transported by vessels called canaliculi to bile ducts, which surround the lobule

Sinusoids

Type of small blood vessel

* increased permeability, allowing larger molecules (e.g. plasma proteins) to enter and leave the bloodstream.

Why are sinusoids permeable?

For liver function

How are sinusoids more permeable?

* The surrounding diaphragm (basement membrane) is incomplete or discontinuous in sinusoids (but not in capillaries)
* The endothelial layer contains large intercellular gaps and fewer tight junctions (allowing for the passage of larger molecules)

Regulating levels of nutrients in bloodstream

* Nutrients absorbed by the small intestine are transported by hepatic portal vein to the liver for metabolism


* The liver converts these nutrients into forms that can be stored or used and mediates their transport to various tissues
* Nutrients stored within liver include glycogen, iron, vitamin A and vitamin D.

Carbohydrate metabolism

* excess glucose in the bloodstream is taken up by the liver and stored as glycogen
* when blood glucose levels drop, the liver breaks down glycogen into glucose and exports it to body tissues
* When hepatic glycogen reserves become exhausted, the liver synthesizes glucose from other sources (e.g. fats)
* These metabolic processes are coordinated by the pancreatic hormones – insulin and glucagon

protein metabolism

* Cannot store amino acids, meaning they must be broken down when in excess
* Amino acid breakdown releases an amine group (NH2) which cannot be used by the body and is potentially toxic
* The liver is responsible for the removal of the amine group (deamination) and its conversion into a harmless product
* The amine group is converted into urea by the liver, which is excreted within urine by the kidneys
* The liver can also synthesize non-essential amino acids from surplus stock (via transamination)

Fat metabolism

* liver is the major site for converting excess carbohydrates and proteins into fatty acids and triglycerides
* also responsible for synthesis of large quantities of phospholipids and cholesterol
* these compounds are then stored by the liver or exported to cells by different types of lipoproteins.
* Low density lipoprotein (LDL) transports cholesterol to cells, for use in the cell membrane and in steroid synthesis
* High density lipoprotein (HDL) transports excess cholesterol from cells back to the liver (for storage conversion)
* LDL is considered ‘bad’ as it raises blood cholesterol levels, while HDL lowers cholesterol levels and is therefore ‘good’

liver and how it acts on drugs and toxins

The liver acts on drugs and toxins that have entered the bloodstream 

* Many of these toxic compounds are fat soluble, making them difficult for the body to excrete
* These compounds are converted into less harmful and more soluble forms, which are then excreted from the body

Two phases of detoxification of compounds (phase one)

1. Toxins are converted into less harmful chemicals by oxidation, reduction and hydrolysis reactions
* These reactions are mediated by a group of enzymes known as the cytochrome P450 enzyme group
* These conversions produce damaging free radicals, which are neutralised by antioxidants within the liver

Two phases of detoxification of compounds (phase two)

1. The converted chemical is then attached to another substance (e.g. cysteine) via a conjugation reaction
* This renders the compound even less harmful and also functions to make it water soluble
* The water soluble compounds can now be excreted from the body within urine by the kidneys

Plasma proteins + where they are produced

 proteins present in the blood plasma and are produced by the liver (except for immunoglobulins)

* The proteins are produced by the rough ER in hepatocytes and exported into the blood via the Golgi complex

Different types of plasma proteins

* albumins
* globulins
* fibrinogens

Albumins (types of plasma proteins)

regulate the osmotic pressure of the blood (and hence moderate the osmotic pressure of body fluids)

Globulins (types of plasma proteins)

Participate in the immune system and also act as transport proteins

Fibrinogen (types of plasma proteins)

involved in the clotting process

Erythrocyte recycling

In humans, red blood cells possess minimal organelles and no nucleus in order to carry more haemoglobin

* Consequently, red blood cells have a short lifespan (\~120 days) and must be constantly replaced

The liver is responsible for the break down of red blood cells and recycling of its components

* These components are used to make either new red blood cells or other important compounds (e.g. bile)

Cells that break down red blood cells

Kupffer cells

Breakdown of RBCs

Kupffer cells are specialised phagocytes within the liver which engulf red blood cells and break them down

* Kupffer cells break down haemoglobin into globin and iron-containing heme groups
* Globin is digested by peptidases to produce amino acids (which are either recycled or metabolised by the liver)
* Heme groups are broken down into iron and bilirubin (bile pigment)

Breakdown of released iron from breaking down rbcs

The released iron must be complexed within a protein in order to avoid oxidation to a ferric state

* iron can be stored by the liver within a protein shell of ferritin
* iron can be transported to the bone marrow (where new haemoglobin is produced) within the protein transferrin

Jaundice

Condition caused by an excess of bile pigment - bilirubin

Bilirubin

* Produced as part of the natural breakdown of haemoglobin by the liver
* Normally, the liver conjugates this bilirubin to other chemicals and then secretes it in bile
* When there is an excess of bilirubin, it may leak out into surrounding tissue fluids

What causes jaundice?

may be caused by any condition which impairs the natural breakdown of red blood cells, including:

* Liver disease – impaired removal of bilirubin by the liver may cause levels to build within the body
* Obstruction of the gall bladder – preventing the secretion of bile will cause bilirubin levels to accumulate
* Damage to red blood cells – increased destruction of erythrocytes (e.g. anemia) will cause bilirubin levels to rise

Consequence of jaundice

The main consequence of jaundice is a yellowish discoloration of the skin and whites of the eyes (sclera)

* Other common symptoms include itchiness, paler than usual stools and darkened urine