Liver

Objective

 To understand
 The function of the liver
 The classification of jaundice
 The laboratory assessment of liver disease
 Biochemical features of liver disease
Function of the liver
Function Description
Carbohydrate metabolism Glycogen synthesis and breakdown
gluconeogenesis
Protein metabolism Deamination of amino acids
Urea synthesis
Synthesis of plasma protein (non
immunoglobulins)
Fat metabolism Uptake and Synthesis of lipoproteins
Bilirubin conjugation and excretion
Metabolism of hormones Polypeptide hormones
25-hydroxylation of vitamin D
Storage Glycogen
Vitamins
Iron
Kuppfer cells Contribute to activities of the
reticuloendothelial system
Metabolism and excretion of drugs and
toxin
Hydrogen ion homeostasis Decrease in uresgenesis and increased
glutamine synthesis in acidosis
Bilirubin metabolism
Liver function test
 “Measurements of blood components that simply
provide a lead to the existence, the extend and the type
of liver damage”
 Will provide results for
 Bilirubin
 Aminotransferases (AST and ALT)
 Akaline phosphatases (ALP)
 Gamma-glutamyl transpeptidase (γGT)
 Lactate dihydrogenase (LDH)
 Albumin
 Protrombin time
Other liver function tests

 serological tests (to demonstrate antibodies)

and
 DNA tests for hepatitis and other viruses;
 Tests for antimitochondrial and smooth muscle
antibodies, transthyretin (prealbumin), protein
electrophoresis, bile acids, alpha-fetoprotein,
and a constellation of other enzymes.
 that help differentiate necrotic (characterized by death of
tissues) versus obstructive liver disease.
Patterns of Abnormal

 Elevations in ALT & AST only: suggests cellular

injury
 Highest levels seen with hepatitis, hepatic ischemia
and drug/toxin-induced necrosis
 Elevations in ALP& Bilirubin: suggests
cholestasis or obstruction
 ALP differentiates hepatobiliary disease from bone
disease
 Mixed pattern: ALT, AST, ALP & Bilirubin:
probably the most common scenario
Patterns of Abnormal

 GGT elevated in biliary obstruction and in

chronic alcoholism
 LDH serves as a nonspecific marker of cellular
injury
 Urobilinogen
 Increase – hemolytic diseases, hepatitis
 Decreases – Complete biliary obstruction
Urobilinogen

INCREASED DECREASED

 Hemolytic disease  Complete biliary

 Hepatitis obstruction
Alteration of liver
Jaundice

 Jaundice is a Yellow discoloration of the skin,

eyes and mucous membranes due to
deposition of bilirubin
 Onset when Plasma bilirubin >50μmol/L
 Classified as
 Pre-hepatic
 Hepatic
 Post hepatic
Classification of jaundice
Pre-hepatic (Haemolytic) •Haemolysis
> When the liver is presented with •Inneffective erythropiosis
bilirubin in an amount that exceeds the Gilbert syndrome
conjugating mechanism

Hepatic (Hepatocellular damage) •Diffuse hepatocellular damage-

> When the causal abnormality is in the hepatitis,toxin
liver •Intra-hepatic cholestasis
•Dubin-Johnson syndrome

Post-hepatic (Cholestatic) •Gallstones

> When there is obstruction to the biliary •Carcinoma of the head of the pancrease
system
Classifications of Jaundice

 Prehepatic
 Abnormality is outside the liver
 Liver function is normal
 Cause: too much bilirubin presented to liver
 Result
▪ Increase in unconjugated bilirubin, urine and fecal
urobilinogen, serum iron
 Examples: acute /chronic hemolytic anemias
Classifications of Jaundice
 Hepatic
 Intrinsic liver disease or defect
▪ Conjugation failure
▪ Neonatal physiological jaundice
 UDPG-transferase activity is deficient or suppressed
▪ Crigler-Najjar syndrome
 Defective UDPG-transferase
▪ Bilirubin transport disturbances
▪ Gilbert’s disease
 Pre-conjugation failure
▪ Dublin-Johnson disease
 Post-conjugation failure
 Result: Increase in unconjugated bilirubin
Classifications of Jaundice
 Posthepatic
 Abnormality is outside the liver
 Liver function is normal
 Biliary obstruction due to gallstones, tumors, edema
 Stool turns clay-colored due to lack of bile
 Results:
▪ Increased: Conjugated bilirubin, urinary bilirubin, ALP,
GGT
▪ Decreased: Urine and fecal urobilinogen
Laboratory differential diagnosis of
jaundice
Haemolytic Cholestatic Hepatocellular

•Billurubin<75μmol/L •Billirubin may be •AST, ALT

•No bilirubin in urine •Bilirubin in urine •Bilirubin later

•Reticulocytes •Alkaline phosphatase, •Bilirubin in urine

usually>3x upper limit of
•Haemoglobin reference range •Alkaline phosphatase
later
•Haptaglobulin •AST, ALT,LDH usually
modestly
•LDH may
Liver disease

 Acute
 Poisoning
 Infection
 Inadequate perfusion
 Chronic liver disease
 Alcoholic fatty liver
 Chronic active hepatitis
 Primary biliary chirrhosis
Biochemical features of liver
disease
Cirrhosis
 Scar tissue replaces normal healthy liver tissue
 As time moves forward, function deteriorates and signs
appear
 Fatigue, nausea, weight loss, jaundice, etc
 Common causes
 Chronic alcoholism
 Hepatitis
 Results:
 Increased: unconjugated and conjugated bilirubin, ALP,
GGT,AST, ALT
 Decreased: cholesterol, albumin
Tumors

 Two types
 Primary: cancer in liver cells
 Metastatic: tumors in other parts of the body
spread to liver
▪ 90-95% of cases
 Can be benign or malignant
Reye Syndrome

• Group of disorders caused by infectious,

metabolic, toxic or drug-induced disease
found mostly in children
• Often preceded by viral syndrome
• Related to aspirin consumption during the
viral syndrome
• Symptoms
– Profuse vomiting
– Neurological impairment
Drug and Alcohol Disorders

 Accounts for 1/3 to ½ of acute liver failure

since the liver plays a major role in drug
metabolim
 Drugs cause an immune mediated injury to
the hepatocytes, resulting in disease
 Ethanol is the most significant
 Several stages of classification based on
disease severity
Hepatitis

 Inflammation of the liver

 Viral, bacterial, radiation, drugs, chemicals
and others can cause inflammation
 Viral infections account for the majority of
cases in the clinical lab
 Includes subtypes A, B,C, D, and E
 Clinical Symptoms
 Jaundice, dark urine, fatigue, nausea, abdominal
pain
Common form of viral hepatitis
Liver Assessment
Specimen Collection and Storage

 Serum preferred
 Fasting sample preferred
 Lipemia increases bilirubin concentrations
 No hemolysis
 Hemolysis decreases the reaction of bilirubin with
the diazo reagent
 Light sensitive
 Bilirubin levels decrease by 30-50% per hour.
Methods of Bilirubin Analysis

 Jendrassik-Grof
 Measures Total and Conjugated bilirubin
 Principle
▪ Bilirubin pigments in serum or react with a diazo reagent
which results in the production of azobilirubin( a purple
product). Cafeine sodium benzoate accerlerates the
coupling of bilirubin with the diazo reagent. Ascorbic
acid stops the reaction. This product is measured
spectrophotometrically
Jendrassik-Grof

 Advantages
 Not affected by pH changes
 Maintains optical sensitivity at low bilirubin
concentrations
 Insensitive to high protein concentrations
Reference ranges
Reference ranges

 Aspartate transaminase (AST)

 10-60 IU/L
 Alkaline phosphatase (ALP)
 30-10 IU/L
 γ- Glutamyl transferase (GGT)
 5-55 IU/L
Homework

 Find Reference range for

 Urobilirogen
 LDH
 Albumin
 Define Icterus and kernicterus
 Significance of anti-mitochondrial antibody
test and Alpha-fetoprotein test