MLAB 2401: Clinical ChemistryKeri Brophy-Martinez

Liver Anatomy and Physiology

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

Liver

From Aorta

From GI tract

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

Bilirubin Metabolism

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

Storage

• Glycogen• Vitamins• Iron• Blood

Immunologic

• Phagocytosis of bacteria• IgA secretion

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 .