LIVER FUNCTION

CLINICAL CHEMISTRY II

presented by: Jannica Dominique Claros, RMT

FACULTY- LPU-ST. CABRINI SCHOOL OF HEALTH
SCIENCES
 Topic Outline:
• ANATOMY OF THE LIVER
• PHYSIOLOGY OF THE LIVER
• FUNCTIONS OF THE LIVER
A. Excretory function
B. Metabolic Function
C. Detoxification
D. Storage
• DISORDERS OF THE LIVER
A. Pre hepatic
B. Hepatic
C. Post hepatic
• LIVER FUNCTION TESTS
• HEPATITIS
A. TYPES
B. DETECTION
C. SEROLOGIC TIMELINE
D. INTERVENTION
 THE LIVER

- major organ affecting all body systems

- responsible for many key bodily processes
- sole organ of the body with regenerative
properties
ANATOMY OF THE LIVER

Gross Anatomy:
Weight: 1.2-1.5 kg
Location: Beneath the diaphragm (attached)
Parts: Left lobe and Right lobe
Microscopic anatomy:
Kupffer Hepatocytes
Bile duct Bile canal cells
Lobules - basic funtional unit

Two major cell types within the liver:

1. Hepatocytes (80%)
2. Kupffer cells (20%)

Two major blood source:

1. Hepatic Artery
2. Portal Vein
OTHER COMPONENTS OF THE LOBULE

• Hepatic sinusoid - merged portion of the hepatic arter

and portal vein
• Central canal
• Bile canaliculi
BIOCHEMICAL FUNCTIONS OF THE LIVER

1. Excretion
-wastes are drained to the bile duct (and some on urine)
- in the urine, bilirubin is the principle pigment

2. Metabolism
- the liver can metabolize energy souces in three ways
1. energy can be used by the liver for itself
2. the liver can circulate energy through out the body
3. Formation of storage forms
BIOCHEMICAL FUNCTIONS OF THE LIVER

3. Synthesis
- synthesis of cholesterol
- sythesis of other proteins (except
immunoglobulins and Hemoglobin A)

4. Drug detoxification/metabolism
First pass mechanism
LIVER FUNCTION ALTERATIONS AND
DISEASE

Jaundice - yellowish discoloration of the

skin, eyes, mucuous membranes due to
retention of bilirubin
Overt Jaundice : a subtle form of jaundice
where discoloration is not easily observed
by the naked eye
Bilirubin level: 1.0-1.5
TYPES OF JAUNDICE

1. Pre-hepatic
2. Hepatic
3. Post-hepatic
 TYPES OF HYPERBILIRUBINEMIA

1. UNCONJUGATED HYPERBILIRUBINEMIA
A. Gilbert Syndrome
-benign autosomal defect in chromosome 2 at the
UGT1A1 gene
-decrease in UDGPT levels

B. Crigler Najjar Syndrome

Type 1: complete absence of conjugation
Type 2: sever deficiency of the enzyme

C. Physiologic Jaundice of the Newborn

-deficiency of glucoronyl transferases
- rapid buildup of unconjugated bilirubin, leading to
kernicterus
2. CONJUGATED HYPERBILIRUBINEMIAS

A. Dubin Johnson syndrome

-deficiency of the MDR2/cMOAT gene
-conjugation happens but cannot proceed to the bile duct
-conjugated bilirubin circulates freely bound to albumin
(delta bilirubin)

B. Rotor Syndrome
-reduction in ligandin activity
- no threat posed to afflicted individual but must be
diagnosed correctly
OTHER DISEASES/DISORDERS OF
THE LIVER
• Cirrhosis
- scar tissue replaces normal tissues, causes
blockage of blood flow
- seen in patients with chronic alcoholism,
hepatitis, obstruction, hepatotoxic drug intake

• Tumors
• Reye's syndrome - group of disorders caused by
an infectious, toxic metabolic or drug agent
• Drug and alcohol related causes
- theliver is the main target of adverse reactions
because it is in control of drug metabolism

Ethanol - most important/relative hepatotoxic drug

-metabolized by liver's alcohol dehydrogenase and
acetaldehyde dehydrogenase
CHANGES IN BILIRUBIN CONCENTRATIO WIT RELATION TO JAUNDICE
JAUNDICE TYPE TOTALBILIRUBIN B1/UNCONJUGATED B2/CONJUGATED

Pre-hepatic Increased Increased Normal

Hepatic
Gilbert's Increased Increased Normal
Crigler Najjar Increased Increased Decreased
Dubin Johnson Increased Normal Increased
Rotor syndrome Increased Normal Increased
Newborns Increased Increased Normal
Post hepatic Increased Increased Increased
CONSEQUENCES OF CHRONIC
ALCOHOLISM
• Alcoholic fatty liver
- mildest, slight increase in transferases
• Alcoholic hepatitis
- comes aong with renal involvement
• Alcoholic cirrhosis
-most severe stage, decreased albumin and
prothrombin time
LIVER FUNCTION TESTS
1. Bilirubin analyis
- principle relies on the diazotization of bilirubin
- conjugated bilirubin acts without the help of an
accelerator, nonconjugated bilirubin rlies on
accelerator during reaction
- Presence of delta bilirubin

Specimen collection:
• Serum as sample of choice
• Non hemolyzed and lipemic samples
• Protected from light
Methods for bilirubin analysis:
1. Evelyn Malloy
-sulfanilic acid reacts wiith central methylene carbon of
bilirubin to split it into two molecules of azobilirubin
-azobilirubin: red-purple product with max absorbance at
560 nm
Accelerator: methanol

2. Jendrassik Grof
- diazotization in sulfanilic acid annd sodium nitrite
-accelerator: caffeine benzoate
-reaction is terminated by ascorbic acid
-product is measured at 600 nm
2. Testing for Fecal Urobilinogen
- testing with alkaline ferrous hydroxide followed by
p-dimethylaminobenzaldehyde (Ehrlich's reagent)

3. Urine Urobilinogen
-same principle as fecal urobilinogen testing
-uses ascorbic acid to maintain urobilinogen in
reduced state
-must performed only by using two-hour urine
sample
4. Enzyme testing
-differentiates between functional and mechanical
liver injury
- aminotransferases, phosphatases, LD
-enzyme levels can fall when disease already
progressed into chronic stage
TESTS OF HEPATIC SYNTHETIC ABILITY
1. Production of serum proteins
2. Decreased albumin
3. Decreased alpha globulins
4. Increased gamma globulins
5. Increased prothrombin time due to
inadequate vitamin K absorption
TEST FOR METABOLISM CAPABILITY

Conversion of Plasma Ammonia

-decreased absorbance of ammonia at 340 nm
- sample must be placed immediately on ice, no
torniquet used to avoid metabolizing
compounds and forming ammonia
- collect in EDTA, lithium heparin, potassium
oxalate
- ammonia is falsely increased in presence of
elevated GGT
HEPATITIS

- inflammation of liver tissue

- can be infectious or non infectious
- common symptoms: jaundice, dark urine,
fatigue, nausea and vomiting, abdominal
pain
VIRAL HEPATITIS TYPES

1. Hepatits A
- other names: short incubation/infectious
hepatitis
- belongs in Picornaviridae
- fecal-oral route
-serologic markers: HAV IgG and HAV IgM
- Testing methods: ELISA, Reverse
transcriptase-PCR
Hepatitis B

- also known as serum hepatitis/incubation

hepatitis
- belongs in family Hepadnaviridae
- prevalent in individuals 25-45 years of age
- detected on all bodily fluids
- transmission: sexual, parenteral, perinatal
- health care workers at risk
- have several serologic markers
 SEROLOGIC MARKERS FOR HEPATITIS B
1. HBsAg
- first detectable marker, appears before symptoms
arise
- appears 3-5 weeks after infection
- routinely tested on blood units

2. HbeAg (envelope antigen)

- signifies severe course of infection and active
viral replication
- concentration is directly proportional to infection
severity
3. HB core antigen and Anti-HBc
- signifies acute infection
- HB core antigen is only present in
hepatocytes, can be deteted only by liver
biopsy
Sample ELISA kit for detection of Hepatitis B markers
 ACUTE HBV CHRONIC CLEARED VACCINATION
HBV HBV
HBsAg + + - -
HBeAg + +/- - -
HBcAb IgM + - - -
HBcAb IgG + + + -
Anti HBe - +/- +/- -
Anti HBs - - + +
HBV DNA High to Low Low to High
Hepatitis C

- also known as non A non B hepatitis

- belongs in family Flaviviridae
- parenteral route
- leading cause of need for liver transplants
- testing methods: kits, ELISA, RNA-PCR
-treatment: ribavirin, pegylated interferon
Hepatitis D
- satellite virus, needs HBV for replication
- markers: HDV Antigen and HBV markers
- treatment: a-Interferon

Hepatitis E
- waterborne hepatitis
- only member of the Hepevirus
- short term: 21-42 days
- can spread through zoonosis
- fatal in pregnant women
END OF LECTURE. Thank you