1. The Liver, Gall Bladder and Pancreas 6.1 (cont.) Option D.2 & D.4

2. Circulation in the Liver The liver is the largest gland in the body and it performs over 500 different vital functions! Because of this, it has a unique input of blood from two separate sources. The hepatic artery delivers oxygen-rich blood from the heart to the liver The hepatic portal vein delivers nutrient-rich blood from the gut (intestines) to the liver Blood enters the liver through the hepatic artery and hepatic portal vein and flows into star-shaped structures (lobulues) made up of sinusoids. Sinusoids are wide blood vessels (capillaries) surrounded by a single layer of hepatocytes (liver cells) that filter and detoxify the blood. Kupfer cells line the sinusoids to break down “old”/ damaged erythrocytes (red blood cells). After passing through the sinusoids of the liver, “clean” blood passes into the hepatic vein (which carries “clean,” deoxygenated blood back to the heart)

3. Sinusoids and Blood Flow in the Liver Lobules (star-shaped structures) in the liver each have a centralized hepatic vein into which filtered blood drains from the sinuosoids. Blood from the hepatic artery (heart) and hepatic portal vein (intestines) drains into each sinusoid (wide blood vessel made up of a single layer of hepatocytes) to be filtered before it drains into the hepatic vein to be taken to the heart.

4. Liver Functions The liver performs over 500 different vital functions for the body! 1.Synthesis of Plasma Proteins a. Proteins found in the blood plasma (liquid component of the blood) b. Albumin (regulates osmotic pressure), Fibrinogen (blood clotting protein), Cholesterol (for cell membrane s and bile production) 2.Detoxification a. Removal of a toxic substance from an organism b. Toxic substances removed/ detoxified by the liver in humans: alcohol, food preservatives, drugs, poisons, metabolic waste products (Ex: urea – from the deamination (breakdown) of excess amino acids, as they cannot be stored in the body)

5. Detoxification, Alcohol and the Liver 1. The products of alcohol metabolism (by liver) may be toxic to cells 2. Healthy liver cells exposed to toxins are replaced by fibrous scar tissue, reducing the liver’s ability to: a. Metabolize carbohydrates, proteins and fats b. Produce bile/ remove toxins from body c. Transport materials (blocks blood flow to and from liver) 3. Over time, this leads to nutritional deprivation and increased susceptibility to illness Long-term alcohol abuse: 1. Inflammation (alcoholic hepatitis): damaged liver tissue swells 2. Fat accumulation: Fat replaces normal liver tissue (blocks blood flow – tissues die = necrosis) 3. Cirrhosis: scar tissue (collagen) in areas of liver destroyed by prolonged alcohol exposure

6. 3. Breakdown of Erythrocytes (red blood cells) and Hemoglobin a. Erythrocytes “live” ~120 days, and then they rupture b. Kupfer cells (phagocytic cells in the liver) engulf ruptured red blood cells and their “pieces” (in the sinusoids) and break down their hemoglobin molecules into heme and globin. c. Peptidases (hydrolytic enzymes that break peptide bonds) break down globin into individual amino acids -Amino acids are used in the body to synthesize new proteins or they are deaminated (broken down) by the liver (urea) – amino acids are NEVER stored! d. Heme groups are broken down into iron and bilirubin -Iron is stored as ferritin in the liver OR transported to the bone marrow to be used in the production of new red blood cells -Bilirubin is used as a bile pigment (bile is used by the body to emulsify fats), or it is simply released into the alimentary canal to be egested

7. 4. Bile production Bile (made of bile salts, water, cholesterol, and bilirubin) is made in the liver (hepatocytes) and stored in the gall bladder Bile is released from the gallbladder into the duodenum to help emulsify fats (lipids) Lipids = hydrophobic (form large fat droplets in body = fat globules) Lipase (enzyme digesting fats) is water soluble – can only bind to lipids at water/ fat interface (surface of fat globule) making digestion very slow! Bile (produced by liver – bile salts and bilirubin pigment; stored by gall bladder) has both hydrophobic and hydrophilic portions; Hydrophobic portions attach to lipid and hydrophilic portions interact with water – not allowing fat globules to form (lipids attaching to each other); this is emulsification and allows faster lipid digestion by lipases (increased surface area for lipases to “attack”)

8. 5. Regulating levels of nutrients in the blood and storing nutrients (carbohydrates, iron, vitamin A and vitamin D). -The hepatic portal vein passes ALL absorbed nutrients from the intestine to the liver BEFORE they enter the general circulation -The liver sequesters (stores) essential vitamins, minerals and molecules so they are available to the body at ALL times (to maintain homeostasis) regardless of the diet -An excess or a shortage of nutrients in the blood can cause damage to tissues/ organs -Carbohydrates (glucose) are stored as glycogen in hepatocytes (liver cells) – controlled by insulin/ glucagon (from the pancreas) -Iron (from red blood cell breakdown) is stored as ferritin -Vitamin A (retinol) is stored for cone cells in the eye (rhodopsin) – deficiencies cause “night blindness” -Vitamin D (calciferol) is stored for skeletal development (helps with calcium uptake – deficiencies cause rickets

9. The Pancreas and Digestion The pancreas secretes digestive enzymes into the duodenum Pancreatic juice is slightly alkaline (pH ~8) and contains the enzymes: – Amylase (starchmaltose) – Lipase (triglycerides glycerol + fatty acids) – Trypsin(ogen) (polypeptidesamino acids) Note: Trypsin is initially synthesized and secreted as an “inactive precursor” called trypsinogen. It is activated into trypsin by enterokinase in the small intestine. This prevents auto-digestion of pancreatic cells (just like pepsin in the stomach!)

10. The Pancreas and Blood Sugar Cells require glucose for cellular respiration (which they are always carrying out – so the effect of cells is to constantly lower blood glucose levels) When you eat, carbohydrates in your food are digested into simple sugars (glucose) and absorbed into the bloodstream by villi in the small intestine (increasing blood glucose levels) The pancreas and the liver work to maintain balanced blood glucose levels in the body (even though these levels are constantly fluctuating throughout every day)

11. Cells in the Pancreas Monitor and Control Blood Glucose Levels

12. Blood Glucose and Diabetes Diabetes is the reduced ability of the body to control blood glucose levels through insulin (hyperglycemia)