LIVER FUNCTION iii.

Phospholipids
ANATOMY:  Greatest source of cholesterol in the body comes
A. Characteristics of liver from what is produced by the liver, not from dietary
 Largest internal organ sources
 Biochemical role in  Approx. 70% of the daily production of cholesterol
 Metabolism (1.5 to 2.0g) is produced by the liver.
 Digestion
 Detoxification and elimination C. Detoxification
B. Gross Anatomy a) 1st pass (Drugs)
I. Vascular system i. Every substance that is absorbed in the GIT
 Hepatic artery (25%) must first pass through the liver
 Supplies oxygen rich blood b) Through this the liver can
 Portal vein (75%) i. Modify-eliminate
 Supplies nutrient rich blood ii. Inactivate compounds
 It may chemically modify the compound so it can be
*The 2 blood supplies eventually merge and flow into the eliminated
sinusoids which course between the individual  It may either bind the material reversibly so as to
hepatocytes. inactivate the compound.
*Flow of blood to the liver = 1500 mL/min
D. Storage
II. Excretory (Biliary System) *The liver is so important that if the liver becomes non
 Bile canaliculi functional, death will occur within 24 hours due to
 Right and left intrahepatic duct hypoglycemia.
 Common hepatic duct
 Cystic duct from the gall bladder THE REVIEW OF BILIRUBIN ANALYSIS:
 Common bile duct I. Conjugated Bilirubin
 Continues to the duodenum II. Unconjugated Bilirubin
III. Delta Bilirubin
C. Microscopic Anatomy a) Conjugated bilirubin covalently bound to albumin
 Lobules
 Functional unit of the liver
 Six sided with “central vein” and “portal triad”
Portal triad → hepatic artery, portal vein, bile duct
 2 major cell types:
1. Hepatocytes (80%)
- for metabolic functions
2. Kupffer cells (20) * B1 all with prefix
- macrophages
Liver Function alteration during Disease:
BIOCHEMICAL REACTIONS:  Jaundice (Icterus)
A. Excretory and Secretory  From the French word jaune which means “yellow”
a) Bilirubin  Yellow discoloration of skin, eyes, and mucous
i. End product of hemoglobin metabolism membrane most often resulting from the retention
ii. Major pigment of bile of bilirubin.
iii. RBC Destruction  3 classifications
B. Synthetic/Metabolism  PRE-HEPATIC
a) Protein A. Unconjugated hyperbilirubinemia
i. Almost all proteins are synthesized by the liver  Occurs when the problem causing the jaundice
EXCEPT for the immunoglobulins and adult occurs prior to liver metabolism.
hemoglobin  Due to excessive destruction or RBC
b) Carbohydrates  Acute and chronic hemolytic anemia
i. Metabolism of carbohydrates
ii. Glycogenesis
iii. Glycogenolysis
iv. Gluconeogenesis
c) Lipids
i. Cholesterol
ii. Triglycerides
  HEPATIC  Gall stones
A. Gilbert syndrome  Tumors
Bilirubin transport deficit
Characterized by impaired cellular uptake of
bilirubin
Diagnosed in young adults (20-30)
A. Cirrhosis
Affected individuals may have mild icterus and
 Scar tissue replaces liver tissue resulting to blockage of
show no symptoms
blood flow
 Caused by
 Chronic alcoholism
 Chronic hepatitis
B. Crigler-Najjar
Conjugation deficit B. Tumors
Can be divided into two types:  Primary (specific) or metastatic (spread)
 Type I  Benign (hepatocellular adenoma) or malignant
- Deficiency of enzyme (UDPGT) glucoronly (hepatocellular carcinoma)
transferase
- Total absence of B2 Production C. Reye’s Syndrome
 Type II  Disorder preceded by infections (viral) or drug (aspirin)
- Partial deficiency of (UDPGT) glucoronly related disease in children
transferase  Non- inflammatory encephalopathy and fatty liver
- Small amount of B2 is produced degeneration

Alcohol-related Disrders
a) Alcoholic Fatty Liver
b) Alcoholic Hepatitis
C. Dubin Johnson c) Alcoholic Cirrhosis
 Excretion Defecit
 Defective removal of B2 from the liver cell and EXCRETION FUNCTION TEST:
excretion to bile A. BILIRUBIN ANALYSIS
 Intense dark pigmentation of the liver due to the  1883 – Ehrlich – 1st person who introduced the
accumulation of lipofuchsin pigment reaction of bilirubin with diazotized sulfanilic acid
solution to form a colored complex azobilirubin
(Diazo Reaction)

 1913 – Van den Bergh – discovered that diazo reaction

D. Rotor syndrome
can be used in serum samples using an accelerator
Confused with dubin-johnson
(solubilizer)
No dark pigmented granules in liver biopsy
 1937 – Evelyn Malloy – 50% methanol as accelerator

 1938 – Jendrassic Grof – caffine-benzoate as

E. Physiologic jaundice of newborn
Deficiency in the glucoronyl transferase (UDPGT)
Leads to kernicterus accumulation of bilirubin in
the nuclei of the brain.
Treated with UV radiation
*Kernicterus often results in cell damage and death
in the newborn
*Ultraviolet radiation destroy the bilirubin as it
passes through the capillaries of the skin
accelerator
Method of analysis:
Measured using “diazotized sulfonilic acid”
Types of reaction
1.Direct Van Den Bergh (Measures B2)
i. B2 + Diazo reagent Azobilirubin
2.Indirect Van Den Bergh (measures total bilirubin)
a) B1 + Diazo reagent no reaction
b) B1 + Diazo reagent + accelerator azobilirubin

 POST HEPATIC
 Physical obstructions prevent flow of conjugated
bilirubin into bile canaliculi.
SPECIMEN CONSIDERATION:
 Specimen consideration
 Use serum
 Fasting sample
Lipemia causes false increase
 Avoid hemolysis
Hemolysis decreases the reaction of bilirubin with
the diazo reagent.
 Protect from light
Bilirubin levels may be reduced by 30 – 50 % per
hour when unprotected from light

B. UROBILINOGEN ANALYSIS (urine, feces)

 Colorless end product of bilirubin metabolism that is
oxidized by intestinal bacteria to pigment urobilin.
 Excreted either in stool/feces or urine or reabsorbed
in portal circulation and returned to liver.
 Reported in ehrlich units
 0.1 EU → normal
 > 0.1 EU → hepatitis, hemolytic disorder
 Biliary obstruction → clay colored stool

Method of Analysis:
 Ehrlich method (p-dimethylaminobenzaldehyde
reagent)
Enzyme Test for liver disease:
 AST
 ALT
 ALP
 GGT
 5’NT
 5 nucleotidase
 Marker for hepatobilliary diseases
 LDH

Test based on abnormalities in Serum Proteins:

 Serum Electrophoresis
 Albumin
 Alpha 1 globulin
 Alpha 2 globulin
 Beta globulin
 Gamma globulin

 Clotting Factor
 Prothrombin time
 Increased in liver disease
 Inadequate production of clotting factors
 Inadequate absorption of vitamin K in the
intestine