1. The Liver To get there, we need to 1.Get it situated (ANATOMY) 2.Get it a blood supply with all the “stuff” in the blood that it needs to do its work (PHYSIOLOGY or organ-level function) 3.See the micro-structure of the liver (HISTOLOGY) 4.Marvel at the wonder of hepatocytes, or liver cells— are they perhaps the most ‘intelligent” entities on the planet? (CELL BIOLOGY) Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

2. Locate your liver Upper right quadrant deep to inferior ribs Dome of liver abuts aganst inferior diaphragm surface Left/right lobes Gall bladder is thin muscular sac on inferior surface where bile collects (1 above) 1. ANATOMY

3. Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 Measuring liver span by percussion: variation in liver span Variation in liver span according to the vertical plane of examination. Since there is variability in where clinicians determine the mid-clavicular line to be, the inevitable consequence is that liver span may also vary even if multiple observers are perfectly accurate in measuring it. Percuss your liver Easiest organ to percuss Dense tissue gives rock-solid sound/feel on percussion Mid-clavicular line moving inferiorly from mid-chest to lower right quadrant

4. Gross Anatomy The liver is divided) into four lobes: the right (the largest lobe), left, quadrate and caudate lobes. Supplied with blood via the protal vein and hepatic artery. Blood carried away by the hepatic vein. It is connected to the diaphragm and abdomainal walls by five ligaments. Gall Bladder – Muscular bag for the storage, concentration, acidification and delivery of bile to small intestine The liver is the only human organ that has the remarkable property of self-regeneration. If a part of the liver is removed, the remaining parts can grow back to its original size and shape.

5. Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 What does the liver do? Temporary nutrient storage (glucose- glycogen) Remove toxins from blood Remove old/damaged RBC’s Regulate nutrient or metabolite levels in blood—keep constant supply of sugars, fats, amino acids, nucleotides (including cholesterol) Secrete bile via bile ducts and gall bladder into small intestines. 2. PHYSIOLOGY Multi-function, blood-processing “factory” Needs blood supply laden with “stuff” to process

6. Storage of Nutrients Hepatocytes absorb and store excess nutrients in the blood – Glucose (glycogen) – Iron – Retinol (Vitamin A) – Calciferol (Vitamin D) Nutrients released when levels are too low

7. Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 Primary branch from celiac artery which is one of the three main visceral branches of aorta (review from circulation) Brings oxygen-rich blood Within liver lobules, blood mixes: –Nutrient-rich, toxin-laden, oxygen-poor blood from gut via hepatic portal vein –Oxygen-rich blood from hepatic portal artery Dual blood supply to liver 2. Hepatic artery (review)

8. Where do the two blood supplies mix? Triads: Branches of three vessels: hepatic portal vein, hepatic artery, along with bile drainage ductiles all run together to infiltrate all parts of liver. Sinusoids—special liver capillaries where blood mixes and liver cells act…by-products leave as bile in caniliculi which merge to form bile ducts Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 3. HISTOLOGY

9. Hepatocytes at work Metabolic map of liver Hepatocytes are incredible chemical transformation factories Just deep to epithelial lining of sinusoids Able to convert from one type of organic substrate (sugar, protein, fat, nucleotide) to another Produce bile Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 4. CELL BIOLOGY Kuppfer cell immune function

10. What is bile? Bile composed of water, ions, bile acids, organic molecules (including cholesterol, phospholipids, bilirubin) Gallstones are mostly cholesterol Acids and salts emulsify fats for absorption across wall of small intestines into lacteal lymph capillaries (review) Contains waste products from RBC breakdown and other metabolic processing (color of feces from bilirubin in bile)(review) Ions buffer chyme from stomach (review) Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

11. Bile processing and recycling Hepatocytes initially secrete bile into canaliculi, carried to gall bladder via hepatic ducts Gall bladder stores bile until needed in gut when secreted out cystic duct to common bile duct to duodenum 95% of the bile produced by the liver is “recycled”…often 2 or 3 times during the digestion of a single meal Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 Great bile page with entero- hepatic recirculation animation Great bile page with entero- hepatic recirculation animation (from Colorado State University)

12. Synthesis of Cholesterol Produced by hepatocytes Some used for bile production Some trasnsported for use in the rest of the body – Synthesis and repair of cell membranes or stored in the liver. – Precursor by testis, ovaries or the adrenal gland to make steroid hormones. progestins glucocortoids androgens estrogens mineralocortoids – It is also a precursor to vitamin D.

13. Cholesterol—one example of liver processing Our body needs cholesterol for – Cell membranes – Vitamin D – Hormones—progesterone and testosterone – Myelin (neuron axonal “wrapping”) – Component of bile salts 85% of cholesterol in our blood is “endogenous” or manufactured by our own cells (mostly liver) 15% comes from the food we eat So, is zero-cholesterol good…or even healthy? Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

14. Cholesterol in the liver: Where’s it from? Where’s it go? Liver constantly manufactures cholesterol using acetyl-CoA as substrate Some cholesterol to gut via bile for emulsification of dietary fats Some cholesterol to blood for cell membranes, myelin, hormones, vitamins Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

15. “Good” and “bad” cholesterol Two ways cholesterol is “packed” – LDL—low density lipo-proteins (“bad”) – HDL—high density lipo-proteins (“good”) LDL is component of arterial plaques that can lead to “blocked arteries” HDL can help to clear LDL from arterial walls “Packing” of cholesterol and interactions with other dietary and liver-produced fats maybe more important than cholesterol levels alone Trans and saturated fats (especially artificially hydrogenated fats) may be most culpable element of diet in raising LDL levels Mono-unsaturated fats (such as olive oil, canola oil) along with dietary fiber raise HDL levels Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

16. Cholesterol processing in liver and relation to cardio- vascular disease and arterial plaques Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

17. Other liver cell functions Red blood cell decomposition and recycling of components Toxin neutralization Conversion of “substrates:” altering amino acids, amino acids to sugars, sugars to amino acids, etc….to insure adequate supply of necessary “molecules of life.” Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

18. Summary ANATOMY: Locate liver by percussing upper right quadrant of abdomen PHYSIOLOGY: Liver is blood processing organ with dual blood supply. HISTOLOGY: Blood mixes in sinusoids where hepatocytes “do their magic” CELL BIOLOGY: Multiple functions for hepatocytes. Manufacture cholesterol for use and recycling in digestion (via bile) and delivery to cells of body via circulatory system (via central vein of liver lobules). – Cholesterol is necessary for many normal metabolic processes – High levels of LDL cholesterol may contribute to plaque formation in arteries – HDL cholesterol may help to break down plaques Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006