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800_Tavill_Anatomy-Physiology-Liver.pdf

800_Tavill_Anatomy-Physiology-Liver.pdf

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August 2012

Anatomy and Physiology of the Liver
Structure-function relationships
Anthony S. Tavill M.D.

Liver cell population
• Hepatocytes- 90% of mass and 76% of cells • Non-parenchymal cells - Endothelial cells- 60% - Kupffer cells- 30% - Stellate (Ito) cells- 10% We will concentrate on structurefunction relationships in hepatocytes

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August 2012

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August 2012 Liver with Reidel lobe. Wanless I.In portal HTN total splanchnic venous flow increased but majority shunted away from liver by collaterals 3 . therefore hepatic artery thrombosis has greater impact .R. 2012 Message 1-Structure-function relationships • The liver receives a dual blood supply that determines its segmental anatomy . remainder hepatic arterial). a prominent caudal extension of the right lobe.Cirrhotic liver and post-transplant liver more dependent on hepatic artery. but O2 mostly from HA .Total blood flow 1500 ml/min (> 2/3 portal venous.

2012 4 . 2012 Measurements of the portal vein and its main branches.) Wanless I.R. in centimeters.August 2012 • Schematic representation of segments of liver according to vascular anatomy (nomenclature of Couinaud revised Strasberg) Wanless I. (Reproduced from Gilfillan with permission from American Medical Association.R.

August 2012 Factors that Increase Portal Venous Blood Flow Message 2: Structure-function relationships • The liver receives a dual blood supply • The liver is a multitask organ • But some tasks more affected by disease than others • That is. some liver tests more sensitive than others depending on type and location of liver injury 5 .

But never exclusively one vs.Reflects in hepatocellular vs. cholestatic dysfunction .August 2012 Normal Hepatic Function Message 3: Structure-function relationships • The liver receives dual blood supply • The liver is a multitask organ • The liver cell is bipolar . other 6 .

August 2012 Ultrastructure of hepatocyte Flow Patterns in the Liver Lobule 7 .

showing several small ducts. 2012 Message 4: Structure-function relationships • • • • The liver receives dual blood supply The liver is a multitask organ The liver cell is bipolar The liver acinus has zonal functions but each cell is totipotent 8 . (H&E) Wanless I. a portal vein. and occasional lymphocytes.R. two arteries.August 2012 Normal portal tract from a human liver.

119:11. Rec. It is to be noted that the cells in Zone 1 nearest these nutrients. Anat. et al.) Wanless I. 2012 Functional Unit of Liver Parenchyma It consists of the parenchyma centered around the terminal branches of the hepatic artery and portal vein. 1954 9 . Reproduced from with permission from Elsevier. as conceived by Rappaport and modified by Matsumoto and Kawakami. while the cells of Zone 2 are less favored and those of Zone 3 near the terminal hepatic venules are least favorably situated..R.August 2012 Acinar structure of the hepatic microcirculation. Redrawn after Rappaport AM.

2012 10 . 2012 Wanless I. Wanless I.R.R.August 2012 Blood supply of one simple liver acinus and the zonal arrangement of cells.

August 2012 Normal Hepatic Function: Glucose Regulation Glucose-alanine cycle Liver Blood Glucose Muscle Glucose Glucose Pyruvate -NH2 Alanine Urea Pyruvate Alanine Alanine -NH2 Amino Acids 11 .

August 2012 Normal Hepatic Function: Excretion (secretion) Steps in Hepatic Excretion of Bilirubin 12 .

Soluble Compounds (non polar) Conjugated Products (highly polar) Step 1 Modification • • • • • Hydroxylation Sulfoxidation Dealkylation Reduction Oxidative ̶ Dehalogenation ̶ Deamination Weakly Polar Derivatives Step 2 Conjugation With • Uronic acids • Sugars • Sulfate • Glutathione • Taurine • Glycine 13 .August 2012 Specificity of Steps in Hepatic Excretory Function Hepatic Biotransformation of Lipidsoluble Compounds Lipid .

August 2012 Average Composition of Biliary Lipids Percent by Weight Bile Salts 72% Molar Ratios 15 3 1 Cholesterol 4% Phospholipids 24% Structure of Mixed Micelles in Bile 14 .

August 2012 Bile lipids: Triangular coordinates (Admirand and Small.1968) Lithogenic bile composition 50 40 30 20 10 60 0 10 20 30 40 50 60 90 80 70 60 50 40 Metastable zone Unsaturated zone = Effects of CDCA and UDCA Saturated zone 0 100 Bile salts (%) 15 .

August 2012 Primary Bile Acids Synthesized in Liver Glycochenodeoxycholic Glycocholic Chenodeoxycholic + Glycine Cholic Acid + Taurine Taurochenodeoxycholic Taurocholic Bile Salt Kinetics in Man (5-7 Day Steady-state Studies) 16 .

August 2012 Hepatic Removal of LipidSoluble Compounds Normal Hepatic Function: Detoxification 17 .

August 2012 Liver Clears Ammonia by Synthesis of Urea and Glutamine Normal Hepatic Function: Synthesis 18 .

Semin. Dis.August 2012 Pathway of secretory proteins in hepatocyte Tavill. 1985 Electrophoretic Separation of Liver secreted Plasma Proteins 19 .Liv.

g. glycogen.August 2012 Dietary Intake Protein= 90 g Hepatic Synthesis 12 g/day Extravascular Albumin Pool 180 g Intravascular Digestion Albumin and Pool Absorption 120 g 11 g/day 1 g/ day Enzyme Secretion: Cell Turnover Amino Acid Pool Catabolism Relationship between dietary protein and GI protein turnover (Tavill 1971) Urine N Output Fecal Output = 80 g protein =10 g Normal Hepatic Function: Storage • Note: Storage may occur to excess e. iron. copper 20 .

August 2012 21 .

August 2012 Message 5: Structure-function relationships • • • • The liver receives a dual blood supply The liver is a multitask organ The liver cell is bipolar The liver acinus has zonal functions but each cell is totipotent • Functions of the liver are coordinated within hepatocyte structure and among other organs 22 .

341:1986 Iron Metabolism: Normal Monocyte-Macrophage System Circulating Red Blood Cells Muscle.4g RBCs Storage iron Other Andrews NC. Other Parenchymal Cells Tf GI T R A C T Functional Iron Storage Iron Transport Iron Erythroid Marrow Hepatocytes 23 .August 2012 Iron Transport and Storage Transport Transferrin . N Engl J Med 1999.two iron atoms Intracellular storage Ferritin .thousands of iron atoms Total body iron .

2007 24 . 12) HO OH Chua et al.August 2012 Cholesterol  Bile Acids Nucleus Bio-transformations Cholesterol (3) HO COOH Chenodeoxycholic Acid (3.. 7. 7) Multiple Hydroxylations HO OH OH COOH Cholic Acid (3.

August 2012 Enterohepatic Circulation of Bile Pigments Effects of Hepato-Biliary Disease on Prothrombin Time 25 .

August 2012 Hepatic Removal of LipidSoluble Compounds CH2 CH2 H C () CH3 CH Pathway of bilrubin synthesis from heme Tavill 1975 CH3 CH N H-C () N Fe () C CH2 CH2 COOH CO Fe CH2 CH H O N C H N H C COOH CH2 CH2 H N ( ) C-H N HAEM (Ferroprotoporphyrin IX) CH3 CH2 CH2 COOH CH3 Haem oxygenase COOH CH2 CH2 CH3 H N C N H O CH3 CH3 CH3 CH2 CH Biliverdin IX () Biliverdin reductose COOH CH2 CH2 H N H C H N H COOH CH2 CH2 CH3 H C N H O CH3 CH2 CH H C CH3 CH3 CH2 CH Bilirubin IX () O N H UDP glucuronyl transferase COOH O OH HO CH3 A O N H CH2 CH H C OH CH3 B N H O C CH2 CH2 H C H O O C CH2 CH2 C N H O HOOC O HO HO CH3 H C N H O CH3 D OH CH2 CH Bilirubin IX () diglucuronide 26 .

Bilirubin IX () diglucuronide Kupffer Cells Lining the Hepatic Sinusoid 27 . Bilirubin IX () B.August 2012 Bilirubin conjugation to diglucuronide COOH CH2 CH3 A O N H COOH O OH HO OH CH2 CH3 A O N H CH H C CH3 B N H H C H CH2 CH2 CH2 CH2 C N H O C OO C HO CH3 H C O CH H C CH3 B N H H C H CH2 CH2 COOH CH2 CH2 C N H HOOC O HO OH CH2 CH3 D N H O CH CH3 H C CH3 D N H O CH2 CH A.

August 2012 Gallbladder Filling Concentration of Bile in the Gallbladder 28 .

August 2012 Gallbladder Emptying 29 .

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