1. The Liver

2. Outline the circulation of blood through liver tissue, including the hepatic artery, hepatic portal vein, sinusoids and hepatic vein. Explain the role of the liver in regulating levels of nutrients in the blood. Outline the role of the liver in the storage of nutrients, including carbohydrate, iron, vitamin A and vitamin D State that the liver synthesizes plasma proteins and cholesterol State that the liver has a role in detoxification. Describe the process of erythrocyte and hemoglobin breakdown in the liver, including phagocytosis, digestion of globin and bile pigment formation. Explain the liver damage caused by excessive alcohol consumption.

3. Blood enters the liver and flows into the sinusoids ( capillaries of the liver ) from two main blood vessels: –Hepatic artery – a branch of the aorta that carries oxygenated blood to the liver –Hepatic portal vein – brings in blood from the capillaries of the small intestines (blood filled with nutrients); this blood flow is at low pressure and deoxygenated since it has already flowed through an organs capillary bed (small intestines); the nutrients in the blood can vary greatly depending upon what you ate and the time of day (esp. glucose)

4. Blood leaves the liver from one vein: –Hepatic vein – deoxygenated, low pressure blood; does not contain a wide variety of nutrients since they have been “dropped off” in the liver for storage; this blood returns to heart and lungs to be reoxygenated

6. *Note: A portal type of blood vessel is one is which blood travels through two capillary beds before return to the heart/lungs. There are only 3 locations where we have portal veins: 1.Hepatic portal vein to liver from small intestines 2.Portal blood vessels in parts of kidneys 3.Portal blood vessel extending from hypothalamus to pituitary gland

7. The function of the liver is to add or remove things from the blood; the transfer of products to/from blood is done by hepatocytes (liver cells) as O 2 rich and/or nutrient-rich blood flows into sinusoids of the liver Sinusoids - the capillary beds of the liver and they are where the exchanges take place

9. Other features of the liver we need to know include: –Sinusoids are lined by a single layer of endothelial cells w/ gaps between them which a) allow large molecules (proteins) to be exchanged between hepatocytes and bloodstream and b) allow direct contact between blood and liver cells for maximum efficiency –Sinusoids contain Kupffer (koop-fer) cells that breakdown older red blood cells (~120 days old) *Note: molecules w/in the blood will be acted on by hepatocytes multiple times as blood circulates through liver

10. Regulating Nutrients in the Blood Solutes (dissolved molecules in blood) vary in concentration depending on what you ate or when you last ate, but there is always a normal homeostatic range for each type of solute Your liver will add or remove solutes from your blood depending on chemical signals (i.e., hormones) it receives Note: We will cover this more in depth when we discuss how the liver and pancreas cooperate with one another to regulate your blood glucose level

11. Storage of Nutrients NutrientRelevant Information GlycogenPolysaccharide; converted back to glucose when blood glucose levels get low after signal from pancreas IronIron is removed and stored following breakdown of erythrocytes (red blood cells) and hemoglobin molecules Vitamin AAssociated with good vision, one of the first signs of deficiency is “night blindness”; also responsible for good skin/hair Vitamin DAids in the uptake of calcium which is essential for blood clotting and normal bone and tooth formation

12. Molecules Synthesized in the Liver Plasma proteins –Albumin – most common; helps regulate osmotic pressure of fluids in the body b/c it transports a variety of molecules including calcium, amino acids and some hormones –Fibrinogen – soluble form of blood clotting protein which is converted to fibrin when clot is needed –Globulins – widely diverse group of blood proteins Cholesterol –Most cholesterol used to make bile salts –some carried in bloodstream and used in cell membranes

13. Detoxification by the Liver The liver regulates all molecules moving through your bloodstream and can store and breakdown harmful molecules when in limited amounts The liver has the ability to “heal” if the negative results are limited/short-lived The liver detoxifies items such as ethanol (from alcohol), food preservatives (added to food to avoid spoiling), pesticides and herbicides, caffeine and excessive hormones

14. Excessive Alcohol Consumption It has been shown that frequency and volume of alcohol consumed are both positively correlated with liver damage Alcohol in the bloodstream often requires multiple passes through the liver sinusoids as the hepatocytes work to remove the alcohol, alcohol has a magnified effect on liver tissue as compared to other tissues

15. Long-term alcohol abuse can result in: a. Cirrhosis – scar tissue left when areas of hepatocytes, blood vessels and ducts have been destroyed by exposure to alcohol (these areas can no longer function) b. Fat accumulation – damaged areas of the liver will often build up fat in place of normal tissue c. Inflammation – the swelling of damaged liver tissue due to alcohol exposure

17. Breakdown of Erythrocytes Erythrocytes are replaced after ~120 days by bone marrow (they cannot undergo mitosis b/c they do not have a nucleus) As red blood cells age their cell membranes weaken and eventually rupture resulting in millions of hemoglobin molecules in blood

18. The circulating hemoglobin are ingested by Kupffer cells which are a type of leucocyte (white blood cell) Ingestion is by phagocytosis since hemoglobin is a large protein molecule consisting of 4 globin molecules each with a center heme group (heme is a group of atoms surrounding an iron molecule) The Kupffer cells recycle the components: a) globin molecules are broken down into amino acids and released into bloodstream b) some iron atoms are stored in liver and some sent to bone marrow to make new erythrocytes c) remainder of molecule is bilirubin (bile pigment) and is absorbed by hepatocytes to make bile