800_tavill_anatomy-physiology-liver.pdf

7/27/2019 800_Tavill_Anatomy-Physiology-Liver.pdf

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Anatomy and Physiology of

the Liver

Anatomy and Physiology of

the Liver

Structure-function relationships

Anthony S. Tavi ll M.D.

Liver cell populationLiver 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 structure-

function relationships in hepatocytes


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Liver with Reidel lobe, a prominent caudal extension of the right lobe.

Wanless I.R. 2012

Message 1-Structure-function

relationships

Message 1-Structure-function

relationships

The liver receives a dual blood supply

that determines its segmental anatomy

- Total blood f low 1500 ml/min (> 2/3 portal

venous, remainder hepatic arterial), but O2

mostly from HA

- Cirrhotic liver and post-transplant liver more

dependent on hepatic artery, therefore hepaticartery thrombosis has greater impact

- In portal HTN total splanchnic venous flow

increased but major ity shunted away from l iver

by collaterals


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Wanless I.R. 2012

Schematic representation of segments of liver according to

vascular anatomy (nomenclature of Couinaud revised Strasberg)

Wanless I.R. 2012

Measurements of the portal vein and its main branches, in centimeters.(Reproduced from Gil fillan w ith permission f rom American Medical Association.)


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Factors that Increase Portal

Venous Blood Flow

Factors that Increase Portal

Venous Blood Flow

Message 2: Structure-function

relationships


relationships


The liver is a mult itask organ

But some tasks more affected by d isease than

others

That is, some liver tests more sensitive than

others depending on type and location of l iver

injury


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Normal Hepatic FunctionNormal Hepatic Function


relationships


relationships

The liver receives dual blood supply


The liver cell is bipolar

- Reflects in hepatocellular vs. cholestatic

dysfunction

- But never exclusively one vs. other


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Ultrastructure of hepatocyteUltrastructure of hepatocyte

Flow Patterns in the Liver LobuleFlow Patterns in the Liver Lobule


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Wanless I.R. 2012

Normal portal tract from a human liver, showing several small ducts, two

arteries, a portal vein, and occasional lymphocyt es. (H&E)


relationships


relationships

The liver receives dual blood supply



The liver acinus has zonal functions but

each cell is totipotent


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Reproduced from with permission from Elsevier.)

Wanless I.R. 2012

Acinar structure of the hepatic microcirculation, as conceived by

Rappaport and modified by Matsumoto and Kawakami.

Functional Unit of Liver ParenchymaFunctional Unit of Liver Parenchyma

It consist s of the parenchyma centered around the terminal branches of the hepatic artery and port al

vein. It is to b e noted that the cells in Zone 1 nearest these nutrients, while the cells of Zone 2 are

less favored and thos e of Zone 3 near the terminal hepatic venules are least favorably situated.

Redrawn after Rappaport AM, et al.Anat. Rec., 119:11, 1954


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Wanless I.R. 2012

Blood supp ly of one simple liver acinus and the zonal arrangement of cells.

Wanless I.R. 2012


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Normal Hepatic Funct ion:

Glucose Regulation


Glucose Regulation

Liver Blood MuscleGlucose

Glucose Glucose

PyruvatePyruvate

Alanine

Alanine

Alanine

Amino Acids

-NH2

-NH2

Urea

Glucose-alanine cycleGlucose-alanine cycle


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Excretion (secretion)


Excretion (secretion)

Steps in Hepatic Excretionof Bilirubin

Steps in Hepatic Excretionof Bilirubin


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Specifici ty of Steps in Hepatic

Excretory Function

Specifici ty of Steps in Hepatic

Excretory Function

Hepatic Biotransformation of Lipid-soluble CompoundsHepatic Biotransformation of Lipid-soluble Compounds

Lipid - Soluble

Compounds

(non polar)

Conjugated

Products

(highly polar)

Weakly Polar

Derivatives

Step 1

Modification

Step 2

Conjugation Hydroxylation

Sulfoxidation Dealkylation

Reduction

Oxidative

Dehalogenation

Deamination

With

Uronic acids Sugars

Sulfate

Glutathione

Taurine

Glycine


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Average Composition of Biliary

Lipids

Average Composition of Biliary

LipidsPercent by Weight Molar Ratios

Phospholipids

24%

Cholesterol

4%

Bile Salts

72%

1

3

15

Structure of Mixed Micelles in BileStructure of Mixed Micelles in Bile


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Lithogenic bilecomposition

Bile salts (%)

100 90 80 70 6060

60

50

40

30

20

10

0

50

40

30

20

10

0

50 40

Saturated

zone

Metastable zone

Unsaturated zone

= Effects of CDCA

and UDCA

Bile lipids: Triangular coordinates(Admirand and Small,1968)

Bile lipids: Triangular coordinates(Admirand and Small,1968)


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Primary Bile Acids

Synthesized in Liver

Primary Bile Acids

Synthesized in Liver

Chenodeoxycholic

Cholic Acid

+ GlycineGlycochenodeoxycholic

Glycocholic

Taurochenodeoxycholic

Taurocholic+ Taurine

Bile Salt Kinetics in Man(5-7 Day Steady-state Studies)Bile Salt Kinetics in Man(5-7 Day Steady-state Studies)


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Hepatic Removal of Lipid-

Soluble Compounds


Soluble Compounds

Normal Hepatic Function: DetoxificationNormal Hepatic Function: Detoxification


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Liver Clears Ammonia by Synthesis

of Urea and Glutamine

Liver Clears Ammonia by Synthesis

of Urea and Glutamine

Normal Hepatic Function:Synthesis

Normal Hepatic Function:Synthesis


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Pathway of secretory proteins in hepatocyte

Tavill . Semin.Liv. Dis. 1985

Pathway of secretory proteins in hepatocyte

Tavill . Semin.Liv. Dis. 1985

Electrophoretic Separation of

Liver secreted Plasma Proteins

Electrophoretic Separation of

Liver secreted Plasma Proteins


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Dietary Intake

Protein= 90 g

Hepatic

Synthesis

12 g/day

Extravascular

Albumin Pool

180 g

Intra-

vascular

Albumin

Pool

120 g

Enzyme

Secretion: Cell

Turnover

Amino Acid

Pool

Fecal Output

=10 g

Catabolism

11 g/day1 g/

day

Urine N Output

= 80 g protein

Digestion

and

Absorpt ion

Relationship

between dietary

protein and GI

protein turnover

(Tavill 1971)

Normal Hepatic Function: StorageNormal Hepatic Function: Storage

Note: Storage may occur to excess e.g. glycogen,

iron, copper


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relationships


relationships




The liver acinus has zonal functions but

each cell is totipotent

Functions of the liver are coordinated

within hepatocyte structure and amongother organs


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Iron Transport and Storage

TransportTransferrin - two iron atoms

Intracellular storageFerritin - thousands of iron atoms

Total body iron - 4gStorage iron Other

RBCs

Andrews NC, N Engl J Med 1999; 341:1986

Iron Metabolism: NormalIron Metabolism: Normal

Circulating Red

Blood Cells

Monocyte-Macrophage

SystemMuscle, Other

Parenchymal Cells

Erythroid

Marrow Hepatocytes

Functional Iron

Storage Iron

Transport Iron

GI

T

R

A

C

T

Tf


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Cholesterol Bile AcidsNucleus Bio-transformations

Cholesterol Bile AcidsNucleus Bio-transformations

Multiple

Hydroxylations

Cholesterol (3)

Chenodeoxycholic

Acid (3, 7)

Cholic Acid

(3, 7, 12)HO OH

OHOHHO

HO

COOH

COOH

Chua et al., 2007


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Enterohepatic Circulation of

Bile Pigments

Enterohepatic Circulation of

Bile Pigments

Effects of Hepato-Biliary Diseaseon Prothrombin Time

Effects of Hepato-Biliary Diseaseon Prothrombin Time


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Soluble Compounds


Soluble Compounds

COOH

HAEM

(Ferroprotoporphyrin IX)

CH2 CH2

CH3CH3 CH CHH

C

N N

()

Fe

COOHCOOH

CH3CH3 CH2 CH2

CH2 CH2

H-C () () C-HN N

()C

H

CO

Fe

Haem oxygenase

COOH

CH2 CH2CH2 CH2 CH3 CH3 CH

CH2CH

CH2CH3CH3

O N

H

CH

C

H

CN

H

N N

HO

Biliverdin IX ()

Biliverdin reductose

COOHCOOH

CH2 CH2CH2 CH2 CH3 CH3 CH

CH2CH

CH2CH3CH3

O N

H

H

CH

C

H

CN

H

N

HN

H O

Bilirubin IX ()

UDP glucuronyl transferase

H

C

CH2

CH2 CH3 CH3 CH

CH2CH

CH2CH3CH3

O N

H

H

CH

C

H

CN

H

N

HN

HO

Bilirubin IX ()diglucuronide

H

A B

C

CH2

CH2

O

COOH

O

OH

OHHO

O O O O

HOOH

HO

HOOC

C D

Pathway of bilrubin

synthesis from hemeTavill 1975


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Bilirubin conjugation to diglucuronideBilirubin conjugation to diglucuronide

A.

Bilirubin IX ()

COOH

CH2

CH2 CH3 CH3 CH

CH2CH

CH2

CH3CH3

O N

H

H

C

N

HN

HNH

O

C C

O

COOH

O

OH

OHHO

O O O

HOOH

HO

HOOC

B.

Bilirubin IX ()diglucuronide

A

COOH

CH2

CH2

H

CH

B CH

CD

CH2 CH3 CH3 CH

CH2CH

CH2

CH3CH3

O N

H

H

C

NH

N

HN

HO

AH

CH

B C HC

D

CH2

O

CH2

CH2

Kupffer Cells Lining the HepaticSinusoid

Kupffer Cells Lining the HepaticSinusoid


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Gallbladder FillingGallbladder Filling

Concentration of Bile in the GallbladderConcentration of Bile in the Gallbladder


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Gallbladder EmptyingGallbladder Emptying

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