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The Mammalian Liver

The liver is the largest gland in the body and the second largest organ after the skin

The liver is situated under the diaphragm on the right side of the abdominal cavity

Numerous metabolic reactions occur within the liver and it is an important organ of homeostasis

Blood Supply

The liver receives blood from two sources

The hepatic artery delivers oxygenated blood to the

liver

The hepatic portal vein delivers blood, rich in digested food molecules,

from the small intestine

Blood leaves the liver along the hepatic vein and

enters the vena cava

The Mammalian Liver

The liver is composed of a largenumber of lobules

Each lobule contains many vertical rows of liver cells (hepatocytes) arranged radially

around a central blood vessel calledthe central vein

Branches of the hepatic artery and hepatic portal vein supply blood to the capillaries

(sinusoids) of each lobule

Running between the lobules in the opposite direction to the blood, are fine ducts

(canaliculi), carrying bile from the liver cells towards the main bile duct

The Liver LobuleCentral vein of lobule

(to hepatic vein)

Plates of livercells (hepatocytes)

SinusoidCanaliculus

Branch of hepatic portal vein

Branch of hepatic artery

Bileduct

Network of canaliculi betweenliver cells

An enlarged portion of the liver lobule

provides further detail

Blood flows from branches of the hepatic portal vein and

hepatic artery along sinusoids (dilated capillaries) between

the liver cells

bloodflow

molecules enterliver cells

blood flowsinto central vein

bile from liver cells

flow ofbile

Part of Liver Lobule

Hepatocytes bear numerous microvilli at their surfaces in contact with the sinusoids, thereby increasing the surface area for facilitating the exchange of materials; numerous mitochondria within the cytoplasm reflects their high demand for ATP to provide for the numerous endergonic reactions

Branch of hepaticportal vein

Liver cells;Hepatocytes Sinusoid

PhagocyticKupffer cell

Central vein of lobule (to hepatic vein)

Branch of hepaticartery

Branch to bile duct Bile canaliculus

Fine channels, called canaliculi, collect bile from the liver cells and carry it towards the bile duct

Sinusoids Sinusoids are dilated capillaries in which the lining epithelial cells and basement membrane are discontinuous

Sinusoids have larger diameters than other capillaries with distinct gaps in their lining

The structure of the sinusoidal capillaries allows for the ready exchange of materials (including macromolecules) between

the blood and the liver cells

Epithelial liningcells

Basementmembrane

Rows of liver cells(hepatocytes)

Sinusoids

Central Vein

CarbohydrateMetabolism

Protein Metabolism

Lipid Metabolism

Haemoglobin and Hormone breakdown

and Detoxification

Storage of Vitamins and

Minerals

Bile Production

Carbohydrate Metabolism

The liver’s major role in the metabolism of carbohydrates is that of glucose homeostasis

Under the influence of the hormones insulin and glucagon (secreted by the Islets of Langerhans of the pancreas) and adrenaline from the adrenal

glands, blood glucose concentrations are regulated and adjusted to meet the metabolic

demands of the tissues

The digestion of polysaccharides and disaccharides in the gut yields the

monosaccharides glucose, fructose and galactose; these sugars are transported to

the liver along the hepatic portal vein

Carbohydrate Metabolism

In the liver, most of the fructose and galactose molecules are converted to glucose; the liver plays a significant role in the control

of blood glucose concentrationsin three major ways:

• Glycogenesis; activation of the liver enzymes that convert glucose into glycogen for storage

• Glycogenolysis; activation of the liver enzymes that convert glycogen into glucose when blood glucose levels fall

• Gluconeogenesis; activation of the liver enzymes that convert non-carbohydrates into glucose in response to low blood glucose concentrations

Glycogenolysis; the conversion

of stored glycogen into glucosewhen blood sugar levels fall

glucagon and adrenaline

Glycogenesis; the conversionof glucose into glycogen when

blood sugar levels rise

insulin

Gluconeogenesis is the conversion of non-carbohydrates, such as amino acids

and glycerol, into glucose by the liver

When the demand for glucose depletes the glycogen

stores, non-carbohydrate sources are converted by the

liver into glucose

Protein Metabolism

During digestion, proteins are hydrolysed into their constituent amino acids and transported to

the liver along the hepatic portal vein

Unlike glucose, excess amino acids cannot be stored in the liver; excess dietary amino acids undergo deamination and are also converted

into glucose and triglycerides

Transamination reactions occur in the liver; this involves the conversion of one amino acid

into another and is the process by whichnon-essential amino acids are synthesised

Protein Metabolism

The fate of surplus amino acids withinthe liver cells involves:

• Deamination; the removal of the amino group from an amino acid, producing ammonia and a keto acid; the toxic ammonia is converted into urea, which is transported to the kidneys for excretion; the keto acid may enter the respiratory pathway to yield ATP or, may be used for the synthesis of glucose and fatty acids

• Gluconeogenesis; liver cells can convert amino acids into carbohydrate

• Lipogenesis; liver cells can convert amino acids into fats

Surplus amino acids cannot be stored and undergo deamination in the liver

The amino group of the amino acid, together

with a hydrogen atom, is removed to form ammonia and a keto acid

The highly toxic ammonia enters the ornithine cycle and is converted into urea

The keto acid either enters the respiratory

pathway and generates ATP, or it is converted into carbohydrates or

fats

The less toxic urea is excreted by the kidneys

deamination

conversion to urea in the

ornithine cycle

Excretion by the kidneys

respired

converted to carbohydrates

or fats

ATPATP

Transamination involves the transfer of an amino group from a donor amino acid to a recipient keto acid; the donor amino acid becomes a keto acid and the recipient

keto acid becomes an amino acid

All non-essential amino acids may be synthesised by transamination

Lipid Metabolism

The lipids are a diverse group of molecules and include cholesterol,

triglycerides and phospholipids

The liver synthesises, modifies, releases and eliminates lipids, playing a major role in

their homeostatic regulation

Surplus cholesterol and phospholipids are eliminated in the bile; the liver manufactures bile, which is stored in the gall bladder and

secreted into the duodenum of the gut

Lipid Metabolism

The roles of the liver in lipid metabolism include:

• Lipogenesis; the synthesis of triglycerides from glucose when glycogen stores are depleted; the resulting triglycerides can be stored or utilised in the production of cholesterol and phospholipids

• The synthesis of cholesterol and phospholipids

• The modification of cholesterol and triglycerides (combined with liver proteins) to producewater-soluble lipoproteins for transport toother body tissues

• The elimination of surplus cholesterol and phospholipids in the bile

Liver cells synthesise triglycerides from glucose or amino acids (lipogenesis)

when glycogen stores are full

The liver synthesises most of the cholesterol and

phospholipid found in the body and regulates their

concentrations in the blood

The resulting triglycerides can be stored or used to synthesise other lipids, such as cholesterol

and phospholipids

Excess cholesterol and phospholipid is removed in the bile and delivered to the

gut for elimination

The synthesis, release and elimination of cholesterol

and phospholipids is regulated by the liver

Surplus cholesterol and phospholipid is eliminated in the bile

Cholesterol and triglycerides are combined

with liver proteins to render them soluble for transport in the blood (lipoproteins)

‘Good’ and ‘Bad’ Cholesterol

Low density lipoproteins (LDLs) are loosely termed ‘bad cholesterol’ since excess LDLs remain in the

bloodstream and deposit cholesterol in and around the muscle fibres in arteries (forming fatty plaques); this

may lead to atherosclerosis (narrowing of the arteries)

LDLs attach to specific receptors on the surfaces of cells and are taken into the cells by

endocytosis where the cholesterol is released

When a cell’s cholesterol needs are met, the production of LDL receptors is shut down, and the

receptors already present are gradually removed; the lack of receptors raises plasma LDL levels, making it more likely that plaques will develop in the arteries

Fatty deposits begin to build up in the artery wall

Fatty deposits (plaques) build up in large quantities; calcium deposits harden the arteries;

blockage is extreme and blood flow is seriously affected

High density lipoproteins (HDLs) are associated with a decreased risk of atherosclerosis

HDLs remove excess cholesterol from body cells and transport it to the liver for elimination; accumulation of cholesterol in the blood is

prevented and the risk of fatty plaque formation in the arteries is reduced

‘Good’ and ‘Bad’ Cholesterol