H 4 Functions of the liver Ms. TRS

H 4.1 Circulation in the Liver Blood is supplied to the liver through the hepatic portal vein and hepatic artery The hepatic artery supplies oxygenated blood from the heart The hepatic portal vein supplies deoxygenated blood from the stomach or intestines – contains nutrients The hepatic vein drains blood from the liver and carries it back to the heart. Several short veins originate within the lobes of the liver as small branches, which unite to form the hepatic veins. These lead directly to the inferior vena cava, draining blood from the liver.

Circulation in the Liver Bile caniculus Sinusoid Tube connecting to bile duct

H 4. 2 The role of liver in regulating levels of nutrients in blood Nutrient levels fluctuate in the bloodstream – based on what? Excessively high nutrient levels could damage organs, especially the brain. The liver regulates blood nutrient levels before blood reaches the rest of the body. Glucose and salts affect osmotic concentration of blood ( increased water in blood/hypertonic/harmful to brain cells). Excess amino acids and vitamins can be harmful

Storage of nutrients Levels of nutrients in the body need to be controlled, otherwise they can rise to levels which can become harmful excess glucose causes osmotic stress excess iron can cause iron deposits in tissues excess Vitamin D (calciferol) can cause elevated calcium levels, anorexia, nausea and kidney failure excess Vitamin A (retinol) can be fatal 30 – 90 g of polar bear liver contains enough Vitamin A to kill a human if eaten in one meal

H 4.3 Role of liver in storage of nutrients The hepatocytes of the liver control levels of iron, Vitamin A and Vitamin D by: Absorbing and storing each nutrient when it is in excess Releasing the nutrient into the blood stream when levels start to drop Synthesis of important chemicals important for cell membranes, bile and steroid synthesis Some cholesterol is absorbed from food The majority of the body’s cholesterol is synthesised by the liver and used in bile

Synthesis of important chemicals continued hepatocytes produce 90% of plasma proteins The main plasma proteins are: albumin – maintains osmotic pressure and carries molecules of low solubility fibrinogen – involved in clotting globulins – have a wide variety functions including the transport of iron and sex hormones, preventing oxidation and immune responses Hepatocytes produce albumin, fibrinogen and most globulins except immunoglobulins

H 4. 5 Role of liver in detoxification Responsible for the removal of many substances toxic to the body. Examples: Ethanol Food preservatives Pesticides/herbicides

H 4. 6 Erythrocyte and hemoglobin breakdown Senescent erythrocytes are removed by phagocytic cells in the spleen, liver and bone marrow, or… … they may rupture, releasing haemoglobin into the plasma Haemoglobin is removed from the plasma by phagocytic cells in the walls of the sinusoids, called Kupffer cells

Globins Amino acids Iron Haemoglobin Haem groups Bile pigments (protein part) Amino acids In the Kupffer cells… Iron (sent to bone marrow via blood& recycled) Haemoglobin Haem groups (prosthetic group) passed to hepatocytes Haem group Bile pigments (formed from porphyrin ring) Porphyrin ring

A healthy liver and liver with cirrhosis

H 4. 7Alcohol and Liver Damage The hepatic portal vein brings alcohol to the liver from the stomach. Alcohol is readily absorbed from the gastrointestinal tract; however, alcohol cannot be stored and therefore, the body must oxidize it to get rid of it. Alcohol can only be oxidized in the liver, where enzymes are found to initiate the process. Any alcohol not removed from the blood immediately will recirculate into the sinusoids again via the hepatic artery. Thus, alcohol can have a MAGNIFIED effect on liver tissue

Prolonged abuse of alcohol can lead to following types of liver damage: The liver is a very tough and resilient organ, capable of regenerating itself. Despite this resilience, prolonged alcohol misuse over many years can damage the liver. Each time the liver filters alcohol, some of the liver cells die. The liver can regenerate new cells. But after heavy drinking, for many years, the liver will lose its ability to regenerate new cells, causing serious damage Cirrhosis – scar tissue left from hepatocytes, blood vessels, and ducts being destroyed by alcohol. Fat accumulation – damaged areas often build up with fat deposits. Inflammation – swelling of the liver

3 Functions of the Liver Metabolic regulation Hematological regulation Bile production

Storage Functions of the Liver carbohydrates – stored as glycogen in the liver & muscle. If glucose levels drop too far below 90 mg/dl, glycogen is broken down and glucose is released into the bloodstream. iron – large quantities of free iron are toxic, so the liver stores excess iron as ferritin.

Storage Functions of the Liver fat soluble vitamins – Vitamins A, D, E, and K are stored in the liver. These reserves are called on when the diet contains inadequate amounts of these vitamins.

Recycling RBCs

Metabolism of Alcohol 1st liver enzyme--Alcohol Dehydrogenase (ADH)-----> Acetaldehyde 2nd liver enzyme--Acetaldehyde Dehydrogenase----> Acetic Acid Acetic Acid oxidized by body organs----> CO2 + H2O

Stages in alcoholic liver disease Alcoholic fatty liver disease: It is the first stage of alcoholic liver disease. Heavy consumption of alcohol, even for only a few days, can lead to a build-up of fatty acids in the liver. Fatty liver disease rarely causes any symptoms but it is an important warning sign that the current drinking level is harmful to the health. Fatty liver disease is reversible. After stopping drinking alcohol for two weeks, the liver should return to normal.

Stages in alcoholic liver disease Alcoholic hepatitis: It is the second more serious stage of alcoholic liver disease. Extended alcohol misuse over many years can cause the tissues of the liver to become inflamed. This is known as alcoholic hepatitis. In some rare cases, alcoholic hepatitis can occur after drinking a large amount of alcohol in a short period of time (binge drinking). Alcoholic hepatitis is usually reversible by stopping alcohol consumption for several months or years.

Stages in alcoholic liver disease Cirrhosis: It is the final stage of alcoholic liver disease. Cirrhosis occurs when prolonged inflammation of the liver has caused scarring of the liver and subsequent loss of function. Loss of liver function can result in death. The damage caused by cirrhosis is not reversible. In mild to moderate cases, stopping drinking alcohol immediately can prevent further damage. Gradual recovery of the liver function can be achieved. In more severe cases, a liver transplant may be required.