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Physiology of Liver

The liver has many important functions in maintaining the physiological balance of the human body. The most important functions include:

Metabolic Functions

  • Carbohydrate metabolism

Liver performs many functions related to maintaining an appropriate glucose level, including the conversion of other simple sugars from the diet into glucose, the production of glycogen, and the conversion of some amino acids into glucose. The liver also uses some of the by-products of carbohydrate metabolism to form various chemical compounds necessary for other physiologic functions. It is critical for allanimals to maintain concentrations of glucose in blood within a narrow, normal range. Maintenance of normal bloodglucose levels over both short (hours) and long (days to weeks) periods of time is an important function of the liver.

Three important carbohydrate metabolic reactions carried out by the liver are:

Glycogenesis: The process of glycogen synthesis, in which glucose molecules are added to the chains of glycogen. This process is activated by insulin in response to high glucose levels in blood.

Glycogenolysis: The conversion of glycogen polymers to glucose monomers. The hormones glucagon and epinephrine stimulate glycogenolysis. This reaction is triggered by low blood glucose concentrations produced in the alpha cells of the islets of Langerhans.

Gluconeogenesis: The generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. It is one of the main mechanisms the body uses to keep blood glucose levels from dropping too low (hypoglycemia). This process occurs during periods of fasting, starvation, low carbohydrate diets, or intense exercise and is highly endergonic.

  •  Lipid metabolism

The liver is a major organ in the processing of dietary fat and the conversion of stored fat into products more readily used for energy. In particular, the triglycerides and fatty acids circulating in the blood after a meal can be hydrolyzed to glycerol and free fatty acids and used to produce metabolic energy (adenosine triphosphate [ATP]), or they can be released into the bloodstream as lipoproteins (lipids bound to proteins). The lipoproteins are carried by the blood to adipose cells for storage. Also, a large amount of the cholesterol used by the body is formed in the liver. The liver also synthesizes phospholipids and cholesterol, which are needed for the hepatic production of bile salts, steroid hormones, components of plasma membranes, and other special molecules.

  •  Protein metabolism

The liver’s role in protein metabolism is probably the most important of its metabolic functions. The liver functions to remove the nitrogen groups from amino acids, and also helps in the formation of urea (from the excess ammonia produced), various proteins (that circulate in the blood), and amino acids (for protein production). The plasma proteins, including albumins and globulins (excluding gamma-globulin), are synthesized by the liver. The liver also synthesizes several nonessential amino acids and serum enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase.

  •  Metabolism of bilirubin

Bilirubin, a by-product of the breakdown of hemoglobin (the oxygen-carrying substance in red blood cells), is produced when the body breaks down old red blood cells. It gives bile a greenish black color and produces the yellow tinge of jaundice. Aged red blood cells are taken up and destroyed by macrophages of the mononuclear phagocyte system, primarily in the spleen and liver. Within these cells hemoglobin is separated into its component parts—heme and globin. The globin component is further degraded into its constituent amino acids, which are recycled to form new protein. The heme moiety is converted to biliverdin by the enzymatic cleavage of iron. The iron attaches to transferrin in the plasma and can be stored in the liver or used by the bone marrow to make new red blood cells. The biliverdin is enzymatically converted to bilirubin in the macrophage of the mononuclear phagocytic system and then is released into the plasma. In the plasma, bilirubin binds to albumin and is known as unconjugated bilirubin, or free bilirubin, which is lipid soluble. Within hepatocytes, unconjugated bilirubin joins with glucuronic acid to form conjugated bilirubin, which is water soluble. When conjugated bilirubin reaches the distal ileum and colon, it is deconjugated by bacteria and converted to urobilinogen. Most of the urobilinogen is then excreted in the urine, and a small amount is eliminated in feces.

Secretory & Excretory Functions

  •  Bile secretion

The liver assists intestinal digestion by secreting 700 to 1200 ml of bile per day. Bile is an alkaline, bitter-tasting, yellowish green fluid that contains bile salts, cholesterol, bilirubin, electrolytes, and water. It is formed by hepatocytes and secreted into the canaliculi. Bile salts, which are conjugated bile acids, are required for the intestinal emulsification and absorption of fats. Having facilitated fat emulsification and absorption, most bile salts are actively absorbed in the terminal ileum and returned to the liver via the portal circulation for resecretion.

  • Excretion of bilirubin

Red blood cells last for about 120 days at which time they are destroyed by the spleen. Hemoglobin is broken down by the liver into bilirubin, and then excreted by the liver into the intestines with the bile, where it is eventually eliminated from the body.

Detoxification

The liver alters exogenous and endogenous chemicals (e.g., drugs), foreign molecules, and hormones to make them less toxic or less biologically active. This process, called metabolic detoxification, diminishes intestinal or renal tubular reabsorption of potentially toxic substances and facilitates their intestinal and renal excretion. In this way alcohol, barbiturates, amphetamines, steroids, and hormones (including estrogens, aldosterone, antidiuretic hormone, and testosterone) are metabolized or detoxified, preventing excessive accumulation and adverse effects. Although metabolic detoxification is usually protective, sometimes the products of metabolic detoxification become toxins. Those of alcohol metabolism, for example, are acetaldehyde and hydrogen. Excessive intake of alcohol over a prolonged period causes these end products to damage hepatocytes. Acetaldehyde damages cellular mitochondria, and the excess hydrogen promotes fat accumulation.

Storage of Minerals and Vitamins

The liver stores certain vitamins and minerals, including iron and copper, in times of excessive intake and releases them in times of need. The liver can store vitamins B12 and D for several months and vitamin A for several years. The liver also stores vitamins E and K. Iron is stored in the liver as ferritin, an iron-protein complex, and is released as needed for red blood cell production.

Vascular and Hematologic Functions

Because of its extensive vascular network, the liver can store a large volume of blood. The amount stored at any one time depends on pressure relationships in the arteries and veins. The liver can also release blood to maintain systemic circulatory volume in the event of hemorrhage. Kupffer cells in the sinusoids of the liver remove bacteria and foreign particles from the portal blood. Because the liver receives all of the venous blood from the gut and pancreas, the Kupffer cells play an important role in destroying intestinal bacteria and preventing infections. The liver also has hemostatic functions. It synthesizes prothrombin, fibrinogen, and clotting factors. Vitamin K, a fat-soluble vitamin, is essential for the synthesis of other clotting factors.