H 4 FUNCTIONS OF THE LIVER H4.1 Outline the circulation of the blood through liver tissue including the hepatic artery, hepatic portal vein, sinusoids, and hepatic vein - The liver is composed of sesame seed-sized structural and functional units called liver lobules

Each lobule is a six-sided structure consisting of plates of liver cells (hepatocytes) organized like bricks around a garden wall The hepatocyte plates radiate outward from the central vein running within the longitudinal axis of the lobule

Blood from the hepatic portal vein and the hepatic artery trickles through the sinusoids and empties into the central vein From the central vein, blood eventually enters the hepatic veins, which drain the liver, and empty into the inferior vena cava Inside the sinusoids are star-shaped hepatic macrophages called Kupffer cells which remove debris such as bacteria and worn-out blood cells from the blood as it flows past

Sinusoids are different from capillaries in 3 ways: they have dilated, large, irregular lumens   between the endothelial cells which line them, are spaces (spaces of Disse) that facilitate exchange between the sinusoids and adjacent tissues the basement membrane-like material is not continuous but forms barrel hooplike rings around the endothelial walls

Liver lobule a=central vein, b=hepatocytes (liver cells in "slabs"), c= sinusoid, d=arteriole(from hepatic artery), e=lymphatic vessel, f= venule from portal vein

H4.2 Explain the role of the liver in regulating levels of nutrients in the blood Because the hepatic portal vein carries blood from the stomach and intestine directly to the liver, the liver is in a position to chemically modify the substances absorbed in the GI tract before they reach the rest of the body The liver metabolizes alcohol and other drugs and removes toxins, pesticides, carcinogens, and other poisons, converting them to less toxic forms The regulation of nutrients in the blood by the liver is important because the rate at which nutrients are used is not always constant and the supply of nutrients depends on how recently a meal was ingested

The liver is also involved with the regulation of blood-glucose levels by removing excess glucose from the blood which can be damaging, and storing it as the polysaccharide glycogen When blood glucose levels decrease, the liver secretes glucose into the blood through the breakdown of stored glycogen in the liver (glycogenolysis); this process is stimulated by release of glucagon from the pancreas When glycogen stores are exhausted, the liver converts amino acids and glycerol to glucose (gluconeogenesis)

The liver also produces most of the proteins found in blood plasma Plasma protein concentration must be kept within normal limits to maintain osmotic balance between the blood and interstitial tissue If it is too low, fluid accumulates in the tissues (edema); this often occurs as the result of cirrhosis of the liver

The liver also forms nonessential amino acids (one that can be made by the body and is not required in the diet) and converts the ammonia resulting from their deamination to urea, a less toxic secretory product The liver packages fatty acids into forms that can be stored or transported The liver also stores certain vitamins, i.e. vitamin A, D, and B12

H4.3 Outline the role of the liver in the storage of nutrients including carbohydrate, iron, retinol (Vitamin A), and calciferol (Vitamin D) The liver converts all monosaccharides into glucose and stores any surplus as glycogen, an insoluble polysaccharide

The following processes are involved in glucose metabolism: Glycogenesis: for storing glucose insulin Glucose ↔ glucose-6-phosphate ↔ glucose-1-phosphate ↔ glycogen (phosphorylation) (condensation)   The liver can store up to 100 grams of glycogen The muscles can also store glycogen

Glycogenolysis: for breaking down glycogen and mobilizing glucose The process occurs in the liver when the blood glucose level falls below 60 mg/cm3   phosphorylase Glycogen ↔ glucose-1-phosphate ↔ glucose-6-phosphate ↔ glucose (stored) (free) The enzyme phosphorylase is activated by the pancreatic hormone glucagon, adrenalin from the adrenal medulla, and noradrenalin from the nerve endings of sympathetic neurons

Gluconeogenesis: glucose can be produced from amino acids and glycerol in times of hypoglycemia   Iron is stored, mostly in the liver, as ferritin (iron bound to protein) or hemosiderin (another protein-iron complex) These complexes result from the breakdown of old or damaged erythrocytes with the iron component being separated from the hemoglobin portion of the broken down erythrocyte

Retinol (Vitamin A) is stored in the liver (90%) and can supply the body’s needs for a year It is found in deep-yellow and deep-green leafy vegetables in the form of carotene and as vitamin A in fish liver oils, egg yolk, liver, fortified foods such as margarine and milk It is required for the synthesis of photoreceptor pigments, skin integrity, and normal tooth and bone development; it also has anticancer and antiatherosclosis effects Deficiency can lead to night blindness

Calciferol (Vitamin D) is concentrated in the liver and to a lesser extent in the skin, kidneys, spleen, and other tissues   It is important in the regulation of blood calcium levels by working with PTH; Vit. D facilitates calcium absorption and PTH stimulates calcium ion release from bones Deficiency leads to rickets in children and osteomalacia in adults Major food sources are cod liver oil, egg yolk and fortified milk

H4.4 State that the liver synthesizes plasma proteins and cholesterol Since the liver plays an important role in amino acid metabolism, it stands to reason that it is involved in the production of plasma proteins Plasma proteins are an important constituent of blood plasma Most plasma proteins are produced by the liver except for blood-borne hormones and gamma globulins (antibodies)

Albumin makes up 60% of plasma protein and acts as a carrier to shuttle certain molecules through the circulation, is an important blood buffer, and is the major blood protein contributing to the plasma osmotic pressure which helps keep water in the bloodstream Other plasma proteins produced by the liver include fibrinogen and prothrombin which are important in blood clotting, and alpha and beta globulins which act as transport proteins binding to lipids, metal ions, and fat-soluble vitamins

85% of cholesterol is made from acetyl CoA* by the liver * a sulfur-containing co-enzyme derived from pantothenic acid (a B vitamin) Cholesterol serves as the structural basis of bile salts, steroid hormones, and vitamin D, and is the major component of plasma membranes It is lost from the body when it is catabolized and secreted in bile salts, which are eventually excreted in feces

H 4.5 State that the liver has a role in detoxification. The hepatic portal vein carries blood from the stomach and intestine directly to the liver The liver, then, must chemically modify most substances before they reach the rest of the body For example, liver enzymes break down alcohol into fatty acids Long term alcohol use leads to a fatty liver and the liver’s fat-storing cells produce collagen which leads to the formation of scar tissue (cirrhosis)

The liver also removes toxins, pesticides, carcinogens, and other poisons which could include drugs, converting them to less toxic forms For example, the liver converts ammonia produced by intestinal bacteria into urea, which can be safely carried by the blood at higher concentrations and eventually excreted by the kidneys; ammonia is also produced by the deamination of proteins as they are broken down to produce energy

Another example is steroid hormones which are converted into less active and more water-soluble forms by the liver and can be included in bile and eliminated from the body in feces or excreted in the urine

H 4.6 Describe the process of erythrocyte and hemoglobin breakdown in the liver including phagocytosis, digestion of globin, and bile pigment formation Red blood cells are unable to synthesize proteins, to grow, or to divide They become “old” as they lose their flexibility and become increasingly rigid and fragile, with their hemoglobin beginning to degenerate Red blood cells have a life span of 120 days after which they become trapped, and fragment in smaller circulatory channels, particularly those of the spleen

Dying erythrocytes are engulfed and destroyed by macrophages of the liver (Kupffer cells), spleen, and bone marrow The heme of the hemoglobin is split off from the globin The iron core is bound to protein as ferritin or hemosiderin and stored in the liver for reuse The rest of the heme group is degraded to bilirubin, a yellow pigment which is released to the blood and gets picked up by liver cells which secrete it in bile; it leaves the body in feces as a brown pigment The protein (globin) part of hemoglobin is broken down to amino acids which are then released into the circulation

H 4.7 Explain the liver damage caused by excessive alcohol consumption. There are 3 kinds of alcohol-induced liver disease fatty liver Marked by the build up of fat cells in the liver There are no symptoms, but the liver may become enlarged and lead to discomfort in the upper abdomen The condition improves after drinking has stopped

2. alcoholic hepatitis inflammation of the liver due to excessive alcohol consumption in a mild form, may last for years causing progressive liver damage; may be reversible if drinking is stopped in the severe form, the disease may appear suddenly after binge drinking and can quickly lead to life-threatening complications

3. alcoholic cirrhosis the most serious type of alcohol-induced liver damage normal liver tissue is replaced by scar tissue and this damage is not reversible it is a life-threatening disease that may stabilize if drinking is stopped

Serious complications from alcohol-induced liver damage include: accumulation of fluid in the abdomen (ascites)

bleeding from veins in the esophagus (esophageal varices)

enlarged spleen