H4: Functions of the Liver

The Liver The largest gland in the body The second largest organ (after the skin) About 1.5 kg in mass Located just below the diaphragm and over the upper portion of the stomach

Circulation of Blood and from the Liver The liver receives blood from 2 major blood vessels and blood leaves the liver by 1 blood vessel The HEPATIC ARTERY is a branch of the aorta It carries oxygenated blood (from the heart) to the liver tissues.

The HEPATIC PORTAL VEIN brings deoxygenated blood from the digestive tract to the liver This blood is rich in absorbed nutrients from the villi of the small intestine. The hepatic artery and hepatic portal vein carry blood into the “capillaries” of the liver, called the sinusoids.

All sinusoids are then drained by a central vein which is a branch of the HEPATIC VEIN, which is the sole blood vessel that takes blood away from the liver and delivers it to the vena cavas so it may return to the heart.

HEPATIC PORTAL VEIN The blood delivered to the liver via the hepatic portal vein is unique (in comparison to the type of blood that is usually delivered to an organ) because: It is low pressure, deoxygenated blood because it has already been through a capillary bed. It has a high quantity of nutrients (particularly glucose) – though this is based on the types of food and the timing of digestion and absorption

Sinusoids: The Capillaries of the Liver A major function of the liver is to remove some things from the blood and to add others to it. This is done by hepatocytes (liver cells) O2-rich blood from the hepatic artery, and (sometimes) nutrient-rich blood from the hepatic portal vein, both flow into the sinusoids of the liver.

Sinusoids Sinusoids are where the exchange of materials occur between blood and hepatocytes.

Kupffer Cells: cells that line the sinusoids. They ingest foreign particles and are involved in the breakdown of old erythrocytes (rbc) The hepatocytes produce bile. Bile will move in the opposite direction of the blood, towards the bile ducts.

Sinusoids vs Capillary Beds Sinusoids differ from a typical capillary bed in the following ways: Sinusoids have larger lumens Sinusoids have Kupffer cells that breakdown rbc for recycling Sinusoids are lined by endothelial cells with gaps between them. These gaps allow large molecules (like proteins) to be exchanged between hepatocytes and the bloodstream Hepatocytes are in direct contact with blood components making all exchanges with the bloodstream more efficient

Regulating Nutrients in the Blood Each type of solute dissolved in blood plasma has a normal homeostatic range. Concentrations below or above this range creates physiological problems in the body. The liver helps regulate the levels of nutrients in the blood and maintain homeostatic ranges.

Ex: after a meal, blood glucose will be converted into glycogen by the hepatocytes. When blood glucose levels are low, the hormone glucagon tells the hepatocyte to release the glycogen so it may be converted back into glucose.

Detoxification The liver is the main organ for detoxification. Pesticides, medicines, food additives, alcohol, and other toxins are removed from the blood stream and broken down in the hepatocytes of the liver. The liver does not extract all excess glucose, toxins etc in a single trip through the sinusoids, The chemicals within the blood will be acted on by hepatocytes multiple times as blood continuously makes circuits through the liver.

Alcohol & the Liver After drinking alcohol, each time blood passes through the liver, hepatocytes attempt to remove the alcohol from the bloodstream. The breakdown of alcohol produces free radicals and other reactive molecules that damage proteins, lipids and DNA.

Alcohol and the Liver The liver breaks down alcohol in the following way: Alcohol  acetaldehyde  acetic acid  carbon dioxide

Alcohol & the Liver Long term alcohol abuse seems to interfere with normal liver metabolism of proteins, fats and carbohydrates Long term alcohol abuse can result in: cirrhosis, fat accumulation, inflammation

Cirrhosis The scar tissue left when areas of hepatocytes, blood vessels and ducts have been destroyed by exposure to alcohol. Areas of the liver, showing cirrhosis no longer function

Fat Acummulation “Fatty liver” Damaged areas of the liver will build fat in place of normal liver tissue thus decreasing function.

Inflammation This is swelling of damaged liver tissue due to alcohol exposure Sometimes referred to as alcoholic hepatitis

Hepatitis Inflammation of the liver Often leads to jaundice, lack of appetite, and general discomfort Most cases are cause by a hepatitis virus; can also be caused by the ingestion of toxins (such as alcohol)

Hepatitis A Acute infectious disease of the liver, caused by a hepatitis A virus. Transmission: oral-fecal route from contaminated water or infected individual. Greater risk of contracting virus in a developing country (because of inadequate water treatment) Symptoms: fever, nausea, fatigue, loss of appetite, jaundice

Hepatitis B Caused by hepatitis B virus Sexually transmitted diseased (transmitted in body fluids: semen, blood, vaginal secretions) Symptoms: liver inflammation, jaundice, vomitting, death in rare cases, chronic cases may result in cirrohosis

Hepatitis C Caused by the hepatitis C virus Transmission: blood (transfusions, unsterilized lab equipment) Symptoms: asymptomatic (no symptoms) however, if it becomes chronic, cirrhosis, liver cancer, and liver failure may result.

Liver Storage As mentioned, carbohydrates are stored in the liver in the form of glycogen. The liver also stores iron, vitamin A, and vitamin D

Iron Hemoglobin is an important component of rbc and it contains iron Iron is present in food, however it is hard for the body to absorb. After red blood cells are broken down, their iron is stored in the liver until it can be used again.

Vitamins The main vitamins stored in the liver are fat soluble vitamins A and D VITAMIN A: found in dairy products; associated with good vision VITAMIN D: often found as an additive in dairy products made by the skin in the presence of UV light Important in the uptake of calcium

Synthesis of Plasma Proteins Plasma Proteins: (blood proteins) ALBUMIN – regulates osmotic pressure of fluids in the body FIBRINOGEN – involved in forming blood clots. GLOBULINS – antibodies (defend the body from foreign invaders)

Synthesis of Cholesterol Some cholesterol is ingested and some is made by the liver Used to produce bile Used to make cell membranes Used to make lipid based hormones

Recycling of Erythrocytes Erythocytes have a life span of about 120 days They do not have a nucleus so, they are destroyed (do not undergo mitosis – remember, new rbc come from bone marrow) When rbc get to 120 days, their cell membranes become weak and eventually ruptures This usually occurs in the spleen

Spleen Fist sized organ that regulates and stores red blood cells.

The spleen removes old rbc from circulation When a rbc ruptures, it released millions of hemoglobin molecules that now will circulate in the blood stream and eventually pass through the liver. As these molecules make their way through the liver, they are absorbed by the Kupffer cells via phagocytosis Hemoglobin is broken down into heme group (the iron and non amino acid component) and globin (the amino acid component)

Hemoglobin

HEME Contains the iron component The iron is stored in the liver before being transported back to the bone marrow to be reused in new erythrocytes The remainder of the heme group become biliverdin (a green bile pigment), which is then converted into bilirubin (a yellow pigment) that is secreted into the small intestine via bile duct with bile. Bilirubin turns to stercobilin in the colon an is what gives feces its characteristic colour reddish brown colour

Bilirubin Gives the reddish brown colour to feces Gives the yellow colour to urine When the liver isn’t functioning properly, high amounts will circulate in the blood and give your skin the yellowish appearance known as jaundice.

GLOBIN Broken down into amino acids These amino acids can then be reused to make other proteins They can also be broken down for energy