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Structure and Functions of the Liver Option H Paper 3 Structure and Functions of the Liver Assessment Statement H.4.1 Outline the circulation of blood through liver tissue, including the hepatic artery, hepatic portal vein, sinusoids and hepatic vein H.4.2 Explain the role of the liver in regulating levels of nutrients in the blood H.4.3 Outline the role of the liver in storage of nutrients, including carbohydrate, iron, vitamin A and vitamin D H.4.4 State that the liver synthesizes plasma proteins and cholesterol H.4.5 State the liver has a role in detoxification H.4.6 Describe the process of erythrocyte and haemoglobin breakdown in the liver, including phagocytosis, digestion of globin and bile pigment formation H.4.7 Explain the liver damage caused by excessive alcohol consumption Structure of the Liver The liver is the heaviest and the second largest organ in the body, after the skin. It is located under the diaphragm, on the right side of the body. The liver has excellent blood supply. The hepatic artery delivers blood from the heart, and the hepatic portal vein deliver blood from the organs. The hepatic vein takes away the blood from the liver to the heart. The liver is connected to the gall bladder, which is connected to the small intestine (duodenum) and the pancreatic duct, by the common hepatic duct. The common bile duct and the pancreatic duct enter the duodenum by a common duct called the hepatopancreatic ampulla (ampulla of Vater) The liver is made of several lobules. Each lobule consists of specialized epithelial cells called hepatic liver cells or hepatocytes. The cells are arranged in irregular branches, and irregular plates around the central hepatic vein. In between the lobules you find branches of the hepatic artery and hepatic portal vein and bile tubules. All of these together form the functional unit of the liver, called an acinus. Rather than capillaries, the liver has sinusoids. These are larger spaces lined by the epithelium. This is where the blood passes. The sinusoids differ from capillaries in three ways: 1. They have a dilated, irregular lumen. 2. Between the lining endothelial cell are spaces that facilitate exchange between the sinusoids and adjacent tissues. 3. The basement membrane-like material is not continuous but forms barrel, hooplike rings around the endothelial walls. Lining the sinusoids are also stellate reticulo endothelial cells, commonly called Kupffer Cells. They are phagocytes that destroy worn out white and red blood cells, bacteria and toxic substances. Draw a Diagram of the Liver and the Structure of the Acinus and Sinusoids Blood Supply, Bile and Functions of the Liver Blood Supply The liver receives blood from two sources, the hepatic artery and the hepatic portal vein. The blood in the artery carries oxygenated blood and the blood in the hepatic portal vein contains deoxygenated blood containing newly absorbed nutrients. This flow of blood is very important to the body. Both of the vessels carry blood to the sinusoids, where oxygen, most of the nutrients, and certain poisons are extracted by the hepatocytes. The Kupffer’s Cells phagocytize microbes and bits of foreign matter. Nutrients are stored to make new materials. Poisons are stored and detoxified (ex. alcohol). Products are manufactured by the hepatic cells Nutrients needed by the other cells in the body are secreted back into the blood. The blood then drains to the central vein and eventually to the hepatic vein. Bile and Bile Secretion The hepatic cells secrete about 1L of bile each day. Bile is a yellow, brownish or olive green liquid, with a pH of 7.6 – 8.6. Bile contains water, bile salts, bile pigments, inorganic salts and cholesterol. Bile is produced by the hepatocytes and travels via the bile canaliculi to the bile duct, which empties into the gall bladder. When the duct to the duodenum closes, the bile is pushed back and stored in the Gall Bladder. Bile salts are derivatives of cholesterol and sodium and potassium. The salts have a hydrophobic side, which will attach to a lipid and a hydrophilic side which will stick out and interact with the water. This emulsifies the fat, or makes into little fat droplets, making it easier to digest and absorb. Too little bile salts in the bile will raise the concentration of the cholesterol and may cause them to precipitate, forming gall stones. Bicarbonate (HCO3-) in the bile, helps neutralize the acid of the stomach as the food enters into the duodenum. The principle bile pigment is bilirubin. It is a product of the breakdown of red blood cells. When they break down, iron, globin and bilirubin, which is derived from the heme, are released. The yellow, brown bilirubin is released into the small intestine and is broken down. The action of bacteria breaks it down to urobilinogen, which give feces its normal brown color. Bile secretion is stimulated by both nervous and hormonal factors. When acid chyme come in contact with the wall of the duodenum, it will secrete a hormone CCK (cholecystokinin). CCK promotes the release of bile, by causing the wall of the gall bladder to contract, and a relaxing of the spincter of the ampulla of Vater. The bile will flow through the bile duct, joining the pancreatic juice before emptying into the duodenum. Functions of the Liver A regulating mechanism, which keeps the nutrient levels in the blood constant, is needed. This is where the liver comes in. The liver regulates the levels of nutrients in the blood. This is especially important, as large spikes in levels of some nutrients (i.e. glucose) can be harmful and in times of need, nutrients must be used. Since the liver receives all of the blood from the small intestine and other organs, it can store the excess or breakdown energy stores to be used. In the example of blood glucose, the liver, under the influence of insulin, will store the excess as glycogen. When blood glucose levels are low, the glucagons, stimulates the breakdown of glycogen to glucose in the blood. Proteins are broken down by proteases and the amino acids are used to build proteins, but also other amino acids can be made from existing ones in a process called transamination. Amino acids can also be used as an energy source after de-amination. This is done by the liver. The functions of the Liver are as follows: 1. Carbohydrate storage We have talked about this: see insulin and glucagon talk in homeostasis section. The liver maintains a healthy blood glucose level in blood. Generally it is constant at 90 mg glucose /100 mL blood. The liver converts all monosaccharides into glucose. Fructose and galactose are all converted. The surplus is stored as an insoluable polysaccharide, glycogen. The following steps are involved in glucose metabolism. Glycogenesis – for storing glucose. The liver can store up to 100 g of glycogen and muscles also store glycogen. Glycogenolysis – breaking down glycogen Phosphorylase is activated by hormones (glucagon, adrenalin, and nor adrenalin) o Since muscles lack some of the enzymes to convert glycogen directly to glucose, the muscles convert glycogen to pyruvate for respiration. We will learn more about this in Cellular Respiration. Gluconeogenesis – glucose from AA and glycerol in times of stress and hypoglycemia. Draw the diagram for the Summary of Carbohydrate Metabolism 2. Storage of Iron / Breakdown of Erythrocytes Iron is a very important component of haemoglobin, but is very hard to absorb from foods. After the erythrocytes (RBC) have been broken down, the iron is carefully stored. The breakdown is done by phagocytosis in the liver by the Kupffer Cells, spleen and bone marrow. The iron is packed and broken down into haem and globin. Haem is an iron containing group. The iron is stored in the liver, some goes to the bone marrow, for new RBC and the remainder of the group becomes biliverdin (a green bile pigment), which becomes bilirubin, which we talked about earlier. Globin is a protein and is broken down to its amino acids. These are then treated like other amino acids and can be used to make other proteins, or trans-aminated or de-aminated for energy. The iron will be used again to make new haemoglobin. It is stored in the liver in the form of ferritin, a complex of iron and B-globulin. Liver contains approx 1 mg of iron per dry gram 3. Storage of retinol and calciferol The Liver is capable of storing water soluble vitamins but main vitamins stored are the fat soluble ones – retinol (Vitamin A) and calciferol (Vit. D) Retinol (dairy and carrots) is part of a visual pigment and a deficiency can lead to night blindness. Calciferol (cod liver oil and dairy, or made by skin under UV light) helps in uptake of calcium – deficiency can lead to rickets as a child. 4. Protein Metabolism Without the role of the liver, death would occur in a few days. The liver deaminates (removes the amino group NH2) amino acids, so they can be used for ATP production or used as an energy source. It converts the resulting ammonia (NH3) to the less toxic urea. It is also involved in the production of plasma proteins. The most common type are proteins found in the blood. One is albumin, which transports a variety of molecules, calcium, amino acids and hormones. Other examples are alpha and beta globulin, prothrombin, and fibrinogen. The process of transamination is done by the liver. It is when one amine group is transferred to convert one amino acid to another. 5. Lipid Metabolism 6. The liver stores some triglycerides and breaks down fatty acids to acetyl coenzyme. The coenzyme is further broken down to ketones (called ketogenesis). It also synthesizes cholesterol to make bile salts. Removal of Drugs and Hormones The liver can detoxify or excrete into bile, drugs such as penicillin, erythromycin, and sulfonamides. It can alter or excrete thyroid hormones and steroids. Draw the diagram for the Summary of Metabolism in the Liver Liver Damage caused by alcohol consumption Those that drink alcohol often and in high volume can expect liver damage. The hepatic portal vein brings alcohol that has been absorbed in the small intestine to the liver. More alcohol, that is not removed, continues to flow through the body, and returns to the liver through the hepatic artery. The alcohol, as it flows through the sinusoids, passes by the hepatocytes that attempt to remove the alcohol. The tissue is bathed in alcohol, which damages the cell membranes, due to prolonged exposure. The three effects of the exposure to alcohol are: 1. Cirrhosis – scar tissue left when tissue is destroyed 2. Fat accumulation – damaged areas will build up fat in place of functioning tissue 3. Inflammation – sometimes referred to as alcoholic hepatitis. With ceasing the excessive amount of alcohol consumed, this damage is partially reversible, or can be fatal with prolonged, excessive use, due to the fact that the damage is too severe. Extension – Jaundice Jaundice is a yellowish coloration of the eyes, skin, and mucous membranes, due to a buildup of bilirubin. After bilirubin is formed from the breakdown of heme, it is transported to the liver, where it is processed and eventually excreted into bile. The three main categories of jaundice are: 1. Prehepatic jaundice Due to excess production of bilirubin. The liver cannot process it fast enough to avoid the buildup. In newborns, the liver functions poorly for the first week or so, and many babies experience mild jaundice, called neonatal jaundice. 2. Hepatic jaundice Due to dysfunction of the liver cells, such as congenital liver diseases, cirrhosis (liver tissue is replaced by scar tissue and fibrous nodules) and hepatitis. 3. Extrahepatic jaundice Due to an obstruction of the bile drainage. Causes gall stones and cancer if not treated. Surgery is needed.