The LiverTo get there, we need to1. 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

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

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

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.

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

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

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 liver2. Hepatic artery (review)

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, 20063. HISTOLOGY

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, 20064. CELL BIOLOGY

Kuppfer cellimmune function

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 “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 (from Colorado State University)

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.

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

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

“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

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