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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 large number of lobules Each lobule contains many vertical rows of liver cells (hepatocytes) arranged radially around a central blood vessel called the 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 Lobule Central vein of lobule (to hepatic vein) Plates of liver cells (hepatocytes) Sinusoid Canaliculus Branch of hepatic portal vein Branch of hepatic artery Bile duct Network of canaliculi between liver 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

blood flow molecules enter liver cells blood flows into central vein bile from liver cells flow of bile 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 hepatic portal vein Liver cells; Hepatocytes Sinusoid Phagocytic Kupffer cell Central vein of lobule (to hepatic vein) Branch of hepatic artery 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 lining cells Basement membrane

Rows of liver cells (hepatocytes) Sinusoids Central Vein

Carbohydrate Metabolism 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 concentrations in 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 glucose when blood sugar levels fall glucagon and adrenaline Glycogenesis; the conversion of 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 which non-essential amino acids are synthesised

Protein Metabolism The fate of surplus amino acids within the 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 ATP

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 produce water-soluble lipoproteins for transport to other 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