LIVER FUNCTION

I. Anatomy
II. Biochemical Functions
III. Liver Function Alterations During Disease
IV. Excretory Function Test (Bilirubin)
V. Enzyme Test in Liver Disease
VI. Measurement of Hepatic Synthetic Ability
VII. Test Measuring Nitrogen Metabolism
Chapter Outline
I. Anatomy
A. Characteristics of Liver
B. Gross Anatomy
C. Microscopic Anatomy
Liver Function
I. Anatomy
A. Characteristics of Liver
i. Largest internal organ
ii. Biochemical role in:
 Synthesis
 Metabolism
 Digestion
 Detoxification
Liver Function
I. Anatomy
B. Gross Anatomy
1. Vascular System
(Two Blood Supplies)
i. Hepatic Artery (25%)
 supplies oxygen
rich blood
ii. Portal vein (75%)
 supplies nutrient
rich blood
Liver Function
I. Anatomy
B. Gross Anatomy
1. Vascular System (Blood Supply)
 Blood flows into the Sinusoids which course
between hepatocytes.
Liver Function
I. Anatomy
B. Gross Anatomy
2. Excretory (Biliary) System
 Excretory products of the cell drain to
Intrahepatic ducts then to Bile canaliculi
 1. Intrahepatic ducts  2. R & L Hepatic ducts 
3. common hepatic duct + Cystic duct 
4. Common bile duct  Doudenum
Liver Function
I. Anatomy
C. Microscopic Anatomy
 Lobules
 Functional units
 Six sided with central vein and portal triads
(hepatic artery, portal vein and a bile duct)
 Major Cells types
 Hepatocytes
 Kupffer Cells
Chapter Outline
II. Biochemical Functions
A. Excretory and Secretory
B. Synthetic
C. Detoxification
Liver Function
II. Biochemical Functions
A. Excretory and Secretory
A. Eliminate heme waste products
1. Hemoglobin is broken down:
i. Globin
ii. Iron
iii. Heme
2. Heme is converted to
Bilirubin and bound by albumin
(B1) then transported to the liver.
Liver Function
II. Biochemical Functions
A. Excretory and Secretory
A. Eliminate heme waste products
3. In the liver B1 is released from albumin and
picked up by ligandin
4. Ligandin carries B1 to the smooth ER for
conjugation forming B2
5. B2 is secreted from the hepatocyte to the
intestine, which bacteria metabolized to
urobilinogen.
6. Urobilinogen is oxidized to Stercobilin, recycled
through the liver, filtered in the kidneys .
Chapter Outline
II. Biochemical Functions
B. Synthetic
i. Synthesis and metabolism of Carbohydrates
ii. Fat Metabolisms
iii. Plasma protein production
Liver Function
II. Biochemical Functions
B. Synthetic
i. Synthesis and metabolism of Carbohydrates
1

 Metabolism of glucose to lactate or pyruvate

Glycolysis
for production of energy
 Formation of glucose-6-phosphate from non
Gluconeogenesis
carbohydrate source
 Breakdown of glycogen to glucose for use as
Glycogenolysis
energy
Glycogenesis  Conversion of glucose to glycogen for storage
Liver Function
II. Biochemical Functions
B. Synthetic
ii. Fat metabolism
 Synthesis of bile salts and lipids
 Metabolism of Lipids by LPP
iii. Plasma protein Production
 albumin, α & β globulins, Coagulation proteins
C. Detoxification
i. Detoxification “First pass”
 foreign materials (drugs and poisons)
 metabolic products (bilirubin and ammonia)
Chapter Outline
III. Liver Function Alterations During Disease
A. Jaundice
B. Cirrhosis
C. Tumors
D. Reyes Syndrome
E. Drug and Alcohol-Related Disorders
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Yellow discoloration of skin, eyes and mucous
membranes (overt jaundice with 3 mg/dL)
 Classification:
1. Pre-hepatic
2. Hepatic
3. Post-hepatic
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
1. Pre-hepatic (Unconjugated hyperbilirubinemia)
 Excessive destruction of RBC
 Acute and chronic hemolytic anemia
i. Hemolytic Disease of the Newborn
ii. Hemolytic Transfusion Reaction
iii. Malaria
 ↑ Total Bilirubin (↑ B1, Normal B2)
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
2. Hepatic
i. Gilbert Syndrome (Conjugation Deficit)
 Unconjugated hyperbilirubinemia due to
defective conjugation system
 Reduced expression of UGT1A1 (20-30% of
normal values)
 ↑ Total Bilirubin (↑ B1, Normal B2)
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
2. Hepatic
ii. Crigler-Najjar Syndrome (Conjugation Deficit)
 Molecular defect of gene
 Type 1 – complete absence of conjugation
 Type 2 – severe deficiency of UDP-GT
 ↑ Total Bilirubin (↑ B1, ↓ B2)
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
2. Hepatic
iii. Dubin Johnson (Excretion Deficit)
 Deficiency of the canalicular MDR2/cMOAT
 Defective removal of B2 from the liver
cell and the excretion to bile
 ↑ Total Bilirubin (Normal B1, ↑ B2)
 Hyperbilirunemia, Bilirubinuria
 Presence of Delta Bilirubin
 Dark-stained granules on a liver biopsy
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
iv. Rotor Syndrome(Transport Deficit)
 Confused with Dubin-Johnson
 ↑ Total Bilirubin (Normal B1, ↑ B2)
 No dark pigmented granules in liver biopsy
v. Physiologic Jaundice (Conjugation Deficit)
 Deficiency in the glucoronyl transferase
 ↑ Total Bilirubin (↑ B1, Normal B2)
 Leads to Kernicterus
Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
 Classification:
3. Post-Hepatic Jaundice
 Biliary obstructive disease
 ↑ Total Bilirubin (Normal B1, ↑ B2)
 Physical obstructions which prevent flow of
conjugated bilirubin into bile caniculi.
i. Gall stones
ii. Tumors
 Liver Function
III. Liver Function Alterations During Disease
A. Jaundice (Icterus)
Total Bilirubin B1 B2
HDN, HTR ↑ ↑ N
Gilberts Syndrome ↑ ↑ N
Crigler-Najjar Syndrome ↑ ↑ ↓
Dubin Johnson ↑ N ↑
Rotor ↑ N ↑
Gall Stones, Tumors ↑ N ↑
Liver Function
III. Liver Function Alterations During Disease
B. Cirrhosis
 Scar tissue replaces liver tissue resulting to
blockage of blood flow
 Chronic alcoholism and Chronic hepatitis C
C. Tumor - Primary/Metastatic and Benign/Malignant
D. Reyes Syndrome
 Disorders preceded by infectious (viral) or drug
(aspirin) related disease in children.
 Noninflammatory encephalopathy and fatty liver
degeneration
Liver Function
III. Liver Function Alterations During Disease
E. Alcohol Related Disorder
i. Alcoholic Fatty Liver
ii. Alcoholic Hepatitis
iii. Alcoholic Cirrhosis
 ↑ AST, ALT, GGT, ALP, Bili.
 ↓ Albumin,↑ PT
F. Drug Related Disorder
 Acetaminophen

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Chapter Outline
IV. Excretory Function Test (Bilirubin)
A. Review of Bilirubin Analysis
B. Methods of Analysis
C. Specimen Collection and Storage
Liver Function
IV. Excretory Function Test (Bilirubin)
A. Review of Bilirubin Analysis
1. Unconjugated Bilirubin (Indirect Bilirubin or B1)
 Non-polar and water insoluble
 Found in plasma bound to albumin
 Reacts with Diazo reagent with an accelerator
2. Conjugated Bilirubin (Direct Bilirubin or B2)
 Polar and Water soluble
 Found in plasma in a free state
 Reacts with Diazo reagent directly
3. Delta Bilirubin
 Conjugated bilirubin bound to albumin
Liver Function
IV. Excretory Function Test (Bilirubin)
B. Methods of Analysis
1. Measured using Diazotized Sulfanilic Acid
2. Types of reaction:
a. Direct Van den Bergh
B2 + Diazo reagent  Azobilirubin
Measures the Conjugated Bilirubin
b. Indirect Van den Bergh
B1 + Diazo reagent  No reaction
B1 + Accelerator + Diazo reagent  Azobilirubin
Measures the Total Bilirubin
 Liver Function
IV. Measurement of Bilirubin

METHODS OF ANALYSIS
Malloy-Evelyn Jendrassik-Grof
Accelerator 50% Methanol Caffeine-Benzoate
Stopper None Ascorbic Acid
pH Acidic (1.2) Basic (Alkaline Tartrate)
End Color Red-Purple (560 nm) Blue (600 nm)

B1 = Total Bilirubin – B2
Liver Function
IV. Excretory Function Test (Bilirubin)
C. Specimen Collection and Storage
1. Use serum
 For Malloy-Evelyn
2. Fasting sample
 Lipemia - False ↑
3. Avoid hemolysis
 Hemolysis - False ↓
4. Protect from Light
 ↓ by 30-50% / hour
Chapter Outline
V. Enzyme Test in Liver Disease
A. Aspartate Aminotransferase (AST)
B. Alanine Aminotransferase (ALT)
C. Alkaline Phosphatase (ALP)
D. Gamma glutamyl transferase (GGT)
E. 5’-Nucleotidase (5NT)
F. Lactate Dehydrogenase (LD)
Liver Function
VI. Measurement of Hepatic Synthetic Ability
A. Albumin
B. α1-globulins
C. γ-globulins
D. Clotting Factors
 Liver Function (Serum Proteins)
Method Target
Kjeldahl Nitrogen content
Refractometry Refractive index
Biuret Chelate (violet): Cu2+ and peptide bonds
Dye Binding Spectral shift in the absorbance maximum
Method Principle
Proteins separated based on
Electrophoresis
electric charge densities
Liver Function
VI. Measurement of Hepatic Synthetic Ability
A. Albumin
 ↓ in chronic liver disease
B. α1-globulins
 ↓ in α1 –antitrypsin deficiency
C. γ –globulin
 ↑ in acute and chronic liver disease
 IgG & IgM – chronic active hepatitis
 IgM – primary biliary cirrhosis
 IgA – alcoholic cirrhosis
Liver Function
VI. Measurement of Hepatic Synthetic Ability
D. Clotting Factors
 Prothrombin Time (PT)
 ↑ PT in Liver disease
i. Inadequate production
of clotting factors
(I, II, V, VII, IX and X)
ii. Inadequate absorption
of Vitamin K in intestine
Liver Function
VII. Test measuring Nitrogen Metabolism (Ammonia)
1

 By product of amino acid deamination.

 Converted to urea in the liver for excretion
1

1. Hepatic failure and hepatic coma

2. Reye’s syndrome
3. Inherited deficiencies of urea cycle
Enzymatic Method Principle
GLDH
NH4+ + 2-oxoglutarate + NADPH + H+
↓ in absorbance is
GLDH Glutamate + NADP+ + H2O
measured at 340 nm