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Where is the Liver?
• Upper right quadrant, beneath the diaphragm
• Largest internal organ• Weighs ~ 1500 grams
Anatomy of the Liver
• Consists of 2 lobes divided by falciform ligament
• There is no known difference between the lobes
Microscopic Anatomy of the Liver
• Lobules make up the liver– 6-sided structure– Central vein with portal
triads at each corner– Triad contains a hepatic
artery, portal vein and bile duct surrounded by connective tissue
– Function in metabolic and excretory actions
Microscopic Anatomy of Liver
• Cell types – Hepatocytes
• 70% of volume of liver• Regenerative• Perform major functions
of liver
– Kupffer cells• Macrophages acting as
phagocytes
Biochemical Function of the Liver
• Excretion/Secretion• Synthesis• Detoxification• Storage• Immunologic
Excretory System
• Excretion of bile acids, cholesterol, bilirubin
• Begins at the bile canaliculi, enters hepatic ducts, then to common hepatic & bile duct
Excretion/Secretion
• Liver processes and excretes– Bile• Water, electrolytes, phospholipids, bile salts or acids,
bile pigments, cholesterol , heme waste products, and other substances from blood• 3L produced/day• 1L excreted/day• Functions
• Bile acids needed for fat absorption• Mechanism to remove cholesterol and waste
• Bilirubin is the principal pigment in bile
Metabolism of Bilirubin
• Around 126 days, RBCs are phagocytized and hgb released
• Hgb broken down into:– Heme• Converted to bilirubin
– Globin • Broken into amino acids and recycled
– Iron• Bound by transferrin and returned to iron stores in the
liver or bone marrow
Metabolism of Bilirubin• Bilirubin
– Bound by albumin and taken to liver (unconjugated or indirect bilirubin)• Water insoluble• Can not be removed from body
• Once at the liver, unconjugated bilirubin flows into sinusoidal tissue and albumin releases it
• Ligandin, picks up the unconjugated bilirubin and presents it to glucuronic acid
• In the liver it becomes conjugated with the help of UDP-glucuronyl transferase– Water soluble– Combines with gallbladder secretions and expelled into intestines
Metabolism of Bilirubin
• Intestinal bacteria degrade conjugated bilirubin to form urobilinogen– 80% of urobilinogen formed is oxidized to stercobilin and
excreted in feces, giving stool the brown color– 20% of urobilinogen formed• Absorbed by extrahepatic circulation to be recycled
through liver and re-excreted• Enters systemic circulation to be filtered by kidney and
excreted in urine
Synthesis
• Synthesize many biological compounds– Carbohydrates• Metabolism important
– Uses glucose for its own cellular energy– Circulates glucose to peripheral tissue– Stores glucose as glycogen
• Major player in maintaining stable glucose concentration due to glycogenesis, glycogenolysis and gluconeogenesis
Synthesis
– Lipids• Liver gathers free fatty acids from diet and breaks them
down to Acetyl- CoA to form triglycerides, phospholipids or cholesterol• Converts insoluble lipids to soluble forms• 70% of cholesterol produced by the liver
– Proteins• Almost all proteins made in the liver• Exceptions are immunoglobulins and hgb
Detoxification
• Liver serves as a gatekeeper between the circulation and absorbed substances– First pass: every substance absorbed in GI tract passes
through liver• Detoxification includes drugs and poisons, and metabolic
products like ammonia, alcohol, and bilirubin• 3 mechanisms– Binds material reversibly to inactivate– Chemically modify compound for excretion– Drug metabolizer for detox of drugs and poisons
References
• Biofortified. (2012). Retrieved from http://www.biofortified.org/2010/03/glowing-phagocytosis/
• Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins.
• http://www.livercancer.com/liver_anatomy.html• Sunheimer, R., & Graves, L. (2010). Clinical Laboratory
Chemistry. Upper Saddle River: Pearson .
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