D.

3 Liver Functions
 “
The chemical composition of the blood
is regulated by the liver
Understandings

● The liver intercepts blood from the gut to regulate nutrient levels
● Some nutrients in excess can be stored in the liver
● Surplus cholesterol is converted into bile salts
● The liver removes toxins from the blood and detoxifies them
● Endoplasmic reticulum and Golgi apparatus in hepatocytes produce
plasma proteins
● Components of red blood cells are recycled by the liver
● The breakdown of erythrocytes starts with phagocytosis of red blood
cells by Kupffer cells
● Iron is carried to the bone marrow to produce haemoglobin in new red
blood cells
Applications

■ Dual blood supply to the liver and differences

between sinusoids and capillaries
■ Causes and consequences of jaundice
Liver blood flow

The liver is a lobed organ located below the diaphragm that

functions to regulate the chemical composition of blood
■ It receives oxygenated blood via the hepatic artery, which is used
to sustain liver cells (hepatocytes)
■ It also receives nutrient rich blood from the gut via the portal vein
■ Deoxygenated blood is transported from the liver via the hepatic
vein
Hepatic circulation
Liver blood flow

The liver functions to process the nutrients absorbed from the gut and
hence regulates the body’s metabolic processes
■ It is responsible for the storage and controlled release of key nutrients
(e.g. glycogen, cholesterol, triglycerides)
■ It is responsible for the detoxification of potentially harmful ingested
substances (e.g. amino acids, medications, alcohol)
■ It produces plasma proteins that function to maintain sustainable
osmotic conditions within the bloodstream
■ It is responsible for the breakdown of red blood cells and the production
of bile salts
Liver structure: Hepatic Lobules

The liver is composed of smaller histological structures called lobules, which are
roughly hexagonal in shape
■ Each lobule is surrounded by branches of the hepatic artery (provide oxygen) and
the portal vein (provide nutrients)
■ 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
Liver Structure: Sinusoids

Sinusoids are a type of small blood vessel found in the liver that perform a similar
function to capillaries (material exchange)
■ Sinusoids have increased permeability, allowing larger molecules (e.g. plasma
proteins) to enter and leave the bloodstream

The increased permeability of sinusoids is important for liver function and is due to a
number of structural features:
■ 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)
Sinusoids vs Capillaries
Nutrient metabolism

The liver plays an important role in regulating the levels of

nutrients in the bloodstream
■ Nutrients absorbed by the small intestine are transported by the
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 the liver include glycogen, iron, vitamin
A and vitamin D
Carbohydrate Metabolism

■ Excess glucose in the bloodstream (e.g. after meals) 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
synthesises glucose from other sources (e.g. fats)
■ These metabolic processes are coordinated by the pancreatic
hormones – insulin and glucagon
Protein Metabolism

■ The body can’t 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 synthesise non-essential amino acids from
surplus stock (via transamination)
Lipid Metabolism

■ The liver is the major site for converting excess carbohydrates and proteins into
fatty acids and triglycerides
■ It is also responsible for the 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 or conversion)
■ LDL is considered ‘bad’ as it raises blood cholesterol levels, while HDL lowers
cholesterol levels and is therefore ‘good’
■ Surplus cholesterol is converted by the liver into bile salts, which can be
eliminated from the body
Lipid Metabolism
Detoxification

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
Detoxification: chemical pathways

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 neutralized by
antioxidants within the liver
2. The converted chemical is then attached to another substance (ex. 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

Plasma proteins are 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
Plasma Proteins

There are a number of different types of plasma proteins, each

serving different specific functions:
■ Albumins regulate the osmotic pressure of the blood (and
hence moderate the osmotic pressure of body fluids)
■ Globulins participate in the immune system (ex.
immunoglobulins) and also act as transport proteins
■ Fibrinogens are involved in the clotting process (soluble
fibrinogen can form an insoluble fibrin clot)
■ Low levels of other plasma proteins have various functions (e.g.
α-1-antitrypsin neutralizes digestive trypsin)
RBC Recycling

In humans, red blood cells possess minimal organelles and no

nucleus in order to carry more hemoglobin
■ 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 (ex. bile)
RBC Recycling

Kupffer cells are specialized phagocytes within the liver which engulf red blood cells
and break them down
■ Kupffer cells break down hemoglobin into globin and iron-containing heme groups
■ Globin is digested by peptidases to produce amino acids (which are either recycled
or metabolized by the liver)
■ Heme groups are broken down into iron and bilirubin (bile pigment)

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 hemoglobin is produced)
within the protein transferrin
Erythrocyte and Hemoglobin Recycling
Jaundice

Jaundice is a condition caused by an excess of bile pigment –

bilirubin – within the body
■ Bilirubin is produced as part of the natural breakdown of
hemoglobin 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
Causes of Jaundice

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 (ex. anemia) will
cause bilirubin levels to rise
Jaundice

Signs and Symptoms

■ Yellowish discoloration of the skin and whites of the eyes
(sclera)
■ Itchiness
■ Paler than usual stools
■ Darkened urine

Jaundice may be resolved by treating the underlying cause for the

build up of bilirubin within the body