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H4 Functions of the liver H.4.1 Outline the circulation of blood through liver tissue, including the hepatic artery, hepatic portal vein, sinusoids and hepatic vein. There are two main blood vessels supplying the liver. The hepatic artery carrying oxygenated blood. The hepatic portal vein (carries deoxygenated blood from the gut to the liver). The content of this blood vessel is highly variable due to absorption of digestion products in the gut. The hepatic vein drains blood from the liver to the vena cava and the general circulation. The liver is divided into microscopic units called lobules. Each lobule is surrounded by branches of the hepatic artery and hepatic portal vein. Both these blood vessels connect to a small branch of the hepatic vein which runs centrally through the liver lobule. Each set of hepatic artery and hepatic portal vein is connected to the hepatic vein via a blood vessel called a sinusoid (has a highly fenestrated endothelial lining, which is very porous). Behind the sinusoid walls are the hepatocytes of the liver, cuboidal cells that carry out a wide range of homeostatic, detoxifying functions. Sinusoids differ in structure from capillaries: Irregular and wider lumen More porous walls (fenestrated, with a basement membrane that is not continuous) Close to hepatocytes The sinusoids drain into the hepatic vein H.4.2 Explain the role of the liver in regulating levels of nutrients in the blood. The nutrient content of blood is greatly affected by the frequency of feeding and the absorption of the products of digestion in the gut. If this entered the general circulation it could have a wide range of damaging effects. Therefore blood does NOT travel to the vena cava directly but rather passes via the hepatic portal vein for modification in the liver. In this way the blood is regulated before it can enter the general circulation. Glucose can affect the osmotic concentration of the blood and needs to be kept close to 90mg glucose per 100cm3 blood. Hypertonic blood due to sugar absorption in the gut could be damaging particularly to the brain and retina. Therefore rather than enter general circulation the blood sugar levels are regulated by the hepatocytes Salts (as above) can affect the osmotic concentration of the blood and are controlled for the same reason. Amino acids can also affect the osmotic concentration of blood. They cannot be stored like carbohydrate and therefore excess amino acids need to be regulated and detoxified. Vitamins & minerals: Although never required in great amounts, the regulation of these elements of the diet is crucial for enzyme function, skeletal development and vision along with a variety of other essential functions. H.4.3 Outline the role of the liver in the storage of nutrients, including carbohydrate, iron, vitamin A and vitamin D. Compound Stored Function Carbohydrate Storage of glucose as glycogen in hepatocytes Reduces hypertonicity after glucose absorption in gut Maintains blood sugar levels particularly for brain function Fat-soluble vitamin D is found in dairy products, cod liver oil and can be made in the skin in the presence of UV light. Rickets is a childhood disease caused by deficiency of vitamin D and sunlight associated with impaired absorption and metabolism of calcium and phosphorus A fat-soluble vitamin found in dairy products and carrots. Used to produce any of several fat-soluble vitamins essential for normal vision; prevents night blindness and/or inflammation or dryness of the eyes Iron is the inorganic prosthetic group found at the centre of the four haem group complexes of haemoglobin. Iron is stored as ferratin. Calciferol (Vitamin D) Retinol (Vitamin A) Iron H.4.4 State that the liver synthesizes plasma proteins and cholesterol. H.4.5 State that the liver has a role in detoxification. For example, the liver detoxifies alcohol and medicinal drugs such as paracetamol. H.4.6 Describe the process of erythrocyte and hemoglobin breakdown in the liver, including phagocytosis, digestion of globin and bile pigment formation. (a) Erythrocytes die after about 120 days and are broken down by the liver (b) The Kupffer cells (phagocytic cells found within the lumen of the sinusoid) engulf the erythrocytes. (c) Haemoglobin is broken down in the Kupffer cell to form haem and globin groups. (d) The protein globin group is hydrolysed by peptidases in the Kupffer cell to amino acids which are either used in protein synthesis or they are metabolised (transamination or deamination). (e) The haem group is broken down to remove the inorganic group, iron, which is then stored in the liver. Iron is sent to the major bones for the process of haemopoiesis (blood cell formation). (f) Bilirubin, the other by-product of haem breakdown, has no functional role and is modified by the hepatocytes before being secreted as part of Bile. H.4.7 Explain the liver damage caused by excessive alcohol consumption. Alcohol has a long history; it has been drunk for thousands of years as an alternative to bacteria-infected water. A little alcohol is known to have beneficial health effects. However, binge drinking, when a lot of alcohol is drunk quickly, is known to be harmful to the body. One unit of alcohol is measured as 10cm3. High speed drinking has a sedative effect, slowing down brain activity. Alcohol is broken down by the liver in a series of steps: Alcohol (ethanol) acetaldehyde (ethanal) by the enzyme alcohol dehydrogenase acetaldehyde (ethanal) acetic acid (ethanoic acid) by the enzyme acetaldehyde dehydrogenase This product will eventually be metabolised into carbon dioxide and water. Abuse of alcohol has harmful effects on the body: in particular, it can lead to cirrhosis of the liver. The liver becomes inflamed and hepatocytes are destroyed and replaced by fibrous or adipose connective tissue. Other effects on the body include obesity, gastritis, malnutrition, dementia and weakened heart muscles. The social effects of alcohol abuse are well-documented.