The Liver

The Challenge: In 20 minutes, can we at least start to find out what the liver has to do with cholesterol levels in our body?
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 cellsare they perhaps the most intelligent entities on the planet? (CELL BIOLOGY)
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

Liver Brainstorm
Largest solid-mass organ of the body Perhaps least understood, both popularly and scientifically? Brainstorm: 30 seconds and three adjectives or phrases (good to do in previous class or on-line) Liver Brainstormtake 30 seconds to write what comes outtop of your head Adjective/phrase 1: Adjective/phrase 2:

Adjective/phrase 3:

Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

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
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

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

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.
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

What does the liver do?

Multi-function, blood-processing factory
Temporary nutrient storage (glucoseglycogen) Remove toxins from blood Remove old/damaged RBCs Regulate nutrient or metabolite levels in bloodkeep constant supply of sugars, fats, amino acids, nucleotides (including cholesterol) Secrete bile via bile ducts and gall bladder into small intestines.

Needs blood supply laden with stuff to process

2. PHYSIOLOGY
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

Dual blood supply to liver: 1. Hepatic portal system (review)

Main drainage of blood from gutwhy to liver? Why does liver need another blood supply? What does this blood NOT have that liver (and any organ) needs?
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

Dual blood supply to liver 2. Hepatic artery (review)

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
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

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. Sinusoidsspecial liver capillaries where blood mixes and liver cells actby-products leave as bile in caniliculi which merge to form bile ducts Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006 3. HISTOLOGY

Hepatocytes at work
Metabolic map of liverPDF link 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
Kuppfer cell immune function

4. CELL BIOLOGY

Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

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

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 recycledoften 2 or 3 times during the digestion of a single meal

Great bile page with enterohepatic recirculation animation (from Colorado State University)

Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

Cholesterolone example of liver processing

Our body needs cholesterol for
Cell membranes Vitamin D Hormonesprogesterone 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 goodor even healthy?

Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

Cholesterol in the liver: Wheres it from? Wheres 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

Good and bad cholesterol

Two ways cholesterol is packed
LDLlow density lipo-proteins (bad) HDLhigh 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

Cholesterol processing in liver and relation to cardio-vascular disease and arterial plaques

Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006

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

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