Mammalian Physiology- Liver

Generalistic organ thus made of a homologous tissue out of hepatocytes.

Blood supply involves three vessels- 2 taking blood to the liver, and 1 taking blood away

• Hepatic artery- blood from the aorta to the liver, oxygen rich
• Hepatic portal vein- blood from small intestine to liver, nutrient rich
• Hepatic vein- blood from liver to heart, nutrient and oxygen deficient

Liver made up of three lobes. Each lobe is made up of hepatic lobules. Cells in lobules are arranged in rows, to create channels for blood flow (sinusoids) and bile flow (bile canaliculi)

Glucose converted to glycogen for storage

When blood glucose levels fall, alpha cells in islets of langahans in pancreas secret a hormone called glucagon. This binds to the glycoprotein receptors in the plasma membranes of hepatocytes. Results in glycogenolysis.

Interconversion of other substances

The liver can convert other substances, i.e. fats/amino acids, to glucose. This is gluconeogenisis. This is also triggered by the release of glucagon. Starts with amino acids, which are firstly deaminated. The carbohydrate part of the molecule is then converted to pyruvate.

Lactate can be converted into pyruvate also. This is done anaerobically.

Most tissues use fatty acids as respiratory substrate. Triglyceride molecules split into glycerol and fatty acidsin the hepatocytes. Fatty acids are converted to acetyl CoA (krebs cycle). Excess acetyl CoA is converted to acetoacetate.

Synthesis of triglycerides

Stored in adipose tissue. Triglycerides combine with proteins to form lipoproteins. Most are transported as LDL's. Centre filled with hydrophillic lipids while outside is a polar shell

Synthesis/regulation of cholesterol

Liver makes cholesterol. Cholesterol is a component of cell membranes (for stability/fluidity/impermeability). It is deposited in the skin

When cholesterol is absorbed from the small intestine, the liver thus decreases its rate of synthesis. This is due to the cholesterol reducing the activity of an enzyme. Large quantities of saturated fats increase cholesterol synthesis. Cholesterol transported around the blood as lipoproteins- LDL's and HDL's.

Transamination: conversion of one amino acid into another. Some can only be obtained from our diet- essential amino acids.

Deamination and formation of urea

• Deamination involves the removal of the nitrogen containing part of a protein
• The nitrogen conytaining part is ammonia, which is highly toxic and highly soluble. Using ATP the ammonia is combined with CO2 to form urea- Ornithine cycle
• The urea is released from hepatocytes into the blood and excreted from the kidneys

• Fibrinogen and prothrombin are important in blood clotting. When a vessel is damaged collagen fibres are exposed. This activates platelets which results in the conversion of prothrombin into its active form, thrombin.
• Thrombin catalyses the conversion of fibrinogen into its active form of fibrin.
• Fibrin is insoluble and forms a mesh of fibres in which platelets and RBC's get trapped. It also stops the entry of pathogens
• Globulin is a term for globular proteins in the blood plasma. Some of those are antibodies (not made by liver)
• Albumin is the most abundant plasma protein. It prevents too much water from leaving the blood.

Formed from water and soluble molecules which pass through holes in the capillary wall. The rate at which this happens depends on the relative hydrostatic pressure and the solute potential gradient.

The difference in hydrostatic pressure pushes water out of the capillary.

The presence of albumin in the blood results in the solute potential of blood is lower than the tissue fluid. This gradient makes water move from the tissue fluid into the blood, while the hydrostatic pressure makes it move the other way.

At the arterial end the hydrostatic gradient is larger than the solute gradient, thus fluid flows out of the blood. Vice versa at venous end

If albumin was not present then hydrostatic pressure would outweigh the solute potential. Water would accumulate in the tissue fluid --> oedema (kwashiorker's)

• Most of the cholesterol formed in the liver is used to make bile. Bile is made in the lobules, by the hepatocytes and secreted into the bile canaliculi. Bile also contains bile salts and water.
• Cholesterol interacts with bile salts, forming water soluble molecules. However, sometimes this precipitates out to form gallstones. Gallstones remain in the bladder or get trapped in the bile duct (interfering with fat digestion).

Metabolism of ethanol

• Ethanol is small and lipid soluble. Toxic
• Enzyme responcible for its breakdown to ethanal is alcohol dehydrogenase
• Enzyme responcible for breakdown of ethanal to ethanoate is aldehyde dehydrogenase. This carbohydrate can then be used in the krebs cycle
• Breakdown of ethanol produced reduced NAD. Reaction requiring oxidised NAD can not take place, such as the breakdown of fatty acids.
• Fatty acids accumulate in the liver, altering the structure and reducing hepatocyte efficiency --> fatty liver
• Fatty liver can then lead to cirrhosis. Liver cells now die and are replaced by fibrous tissue. The structure of the lobules is lost

The liver can also breakdown hormones and drugs. Elimination of the products of detoxification is done via the liver. Here they are converted to water soluble molecules and then transported to the bladder.