Jaundice

By
Prof. Hydi Ahmed
Professor of Clinical and Chemical Pathology
Consultant of Clinical Pathology
 Hepatobiliary disorders
Learning objectives:
1. Explain the physiologic functions of the liver
2. Classify the three types of jaundice and their causes
3. Identify the enzymes most commonly used in assessment of hepatobiliary
diseases
4. Discussion of students by cases in a report discussion in skill lab session
Liver functions:
1. Synthesis of carbohydrate, lipids and wide range of proteins
2. Exchanging substance with plasma
3. Formation of bile
4. Detoxication of many drugs and carcinogens
Bilirubin:
Plasma contains two different forms of bilirubin: Unconjugated bilirubin and Conjugated bilirubin
The sum of the two forms is the total bilirubin
Bilirubin metabolism:
Bilirubin is formed from breakdown of RBCs with liberation of hemoglobin. It is conjugated with glucuronic
acid by hepatocytes, making it water soluble. Conjugated bilirubin is secreted into the bile and passes out
into gut. Some is taken up again by the liver(enterohepatic circulation) and the rest is converted to
urobilinogen by gut bacteria. Urobilinogen is reabsorbed and excreted by the kidney or converted to
stercobilinogen, which color faeces brown.
 Jaundice
Clinical jaundice (icterus):is caused by plasma levels of bilirubin exceeding
1 mg/dL , and it presents as a yellow pigmentation of skin, sclera and
mucosa. The colour of the sclera is the best indicator, but it must be
examined in good white light. Jaundice becomes apparent when total
bilirubin exceeds 3mg/dL.
Types:
I. Pre-hepatic Jaundice (Increased unconjugated bilirubin):
Occurs in:
1. All forms of hemolytic of anemia.
2. Ineffective erythropoiesis (pernicious anemia)
3. Hemolytic disease of newborn
4. Bleeding into the tissues( sport injuries)
 Jaundice
II. Hepatocellular Jaundice: occurs in
1. Impaired hepatic uptake (increased unconjugated bilirubin) occurs in:
a. Gilbert’s syndrome
b. Hepatitis
c. Cirrhosis
2. Impaired conjugation(increased unconjugated bilirubin) occurs in:
a. Newborn especially premature infants
b. Generalized hepatocellular damage (Viral hepatitis, cirrhosis)
c. Crigler-Najjar and Gilbert’s syndromes
d. Novobiocin intake
3. Impaired secretion of conjugated bilirubin(increased conjugated bilirubin)occurs in:
a. Dubin Johnson and Rotor syndromes
b. Generalized hepatocellular damage
 Jaundice
III. Cholestatic Jaundice: Either intrahepatic(medical) or extrahepatic (Surgical),
there is conjugated hyperbilirubinemia and bilirubinuria.
a. Intrahepatic cholestasis occurs in :
• Acute hepatocellular damage(infectious hepatitis, cirrhosis, intrahepatic carcinoma)
• Drugs(methyl testosterone, phenothiazines)
• Primary biliary cirrhosis
b. Post-hepatic cholestasis occurs in:
• Gall stones
• Carcinoma of head of pancreas or biliary tree
Post-hepatic jaundice
Normally, conjugated bilirubin passes from the liver to the gallbladder where it
is stored and then released into the duodenum following a fatty meal.
In the terminal ileum, intestinal flora convert it first to urobilinogen (some of
which is reabsorbed and excreted in the urine) and then to stercobilinogen, which
is excreted in the faeces (giving them their brown colour).
In post-hepatic jaundice, the passage of conjugated bilirubin through the
biliary tree is blocked, and it leaks into the circulation instead. It is soluble and
excreted in the urine, making it dark. However, the faeces are deprived of their
stercobilinogen and are pale.
These are key symptoms in the history. There is no problem with the synthesis of
any of the bile products in post-hepatic obstructive jaundice, only its release into
the duodenum. Obstruction also results in cholestasis. Therefore, bile salts, along
with conjugated bilirubin, escape into the circulation, and this causes itching
(pruritus), another important symptom.
 Further investigations for jaundice:
Investigations other than liver function tests, a full blood count, serum bilirubin
levels, virology screening and urine analysis that can be performed are:
▪ Ultrasound
▪ Liver biopsy
▪ Endoscopic ultrasound (EUS)
▪ Endoscopic retrograde cholangio-pancreatography (ERCP)
▪ Magnetic resonance cholangio-pancreatography (MRCP).
N.B Lack of bile salts and, therefore , lack of fat absorption, causes the slow clotting
time associated with jaundice. Vitamin K (a clotting factor) is a fat-soluble vitamin
which requires fat for absorption from the gut. In jaundice: decreased fat
absorption=low vitamin K concentrations=slow clotting
 Liver Function Tests

Tests For Serum Enzyme Tests for

Manufacture and Assays Metabolic
Excretion of Bile functions

Immunologic Ancillary
Tests Diagnostic Tests
 Liver Function Tests
Tests for Metabolic functions

Tests For Manufacture and

Serum Enzyme Assays 1. Amino acid and protein metabolism:
1. Transaminases: i) Serum proteins
Excretion of Bile
i) SGOT(AST) ii) Immunoglobulins
.Serum bilirubin ii) SGPT(ALT) iii) Clotting factors
-In faeces 2. Alkaline Phosphatase
iv) Serum ammonia
3. Gamma Glutamyl Transpeptidase
-In urine v) Aminoaciduria
4. Other enzymes:
.Urobilinogen i) 5 Nucleotidase 2. Lipid and lipoprotein metabolism
.Bile salts ii) Lactic dehydrogenase 3. Carbohydrate metabolism
Blood glucose and GTT

Immunologic tests
1. Non specific immunologic reactions:
i) Smooth muscle antibody Ancillary Diagnostic tests:
ii) Mitochondrial antibody 1. Ultrasound examination
iii) Antinuclear antibody
2. Antibodies to specific etiologic 2. Liver biopsy
agents:
i. Antibodies to Hepatitis B
Type of jaundice Signs
Pre-hepatic • Increased concentrations of unconjugated bilirubin
(no bilirubin in the urine because it is insoluble
Hepatic (congenital and • Increased clotting time
hepatocellular) • Increased ALT and AST
• Hepatocellular damage

Post-hepatic (obstructive • Dark urine (with bilirubin, not urobilinogen)

or cholestatic) • γ-GT and ALP increase (canalicular enzymes raised
due to damage to the biliary tree)
• Pale stools
• Itching
 Normal liver function tests
Test Normal range
Total bilirubin 0.2 - 1 mg/dL

Direct bilirubin 0.0 - 0.2 mg/dL

Total protein 6.5 - 8.5 g/dL

Albumin 3.8 - 5.4 g/dL

ALP 3 - 13 KAU (35 - 129 U/L)

GGT Up to 50 U/L

AST Up to 37 U/L

ALT Up to 41 U/L
 Expected laboratory results in various types of jaundice
Lab. test Hemolytic Acute hepatocellular Chronic hepatocellular Obstructive
Jaundice Jaundice

Total Bilirubin N or

Conjugated Bilirubin N or

Unconjugated Bilirubin

Albumin N N N

Globulin N N N

ALT N

AST N or N or

ALP N N or N or

GGT N N or N or

5 nucleotidase N N or N or

Prothrombin Time(PT) N N Prolonged Prolonged

Effect of vitamin K on PT No effect No effect No effect Correct PT
 Case
60 years old Male patient, he is alcoholic. He is admitted with
hematemesis, his investingation shows: T Bil 1.5 mg, Direct 0.8
His liver enzymes are normal, TP= 6.4, Albumin 2.5,Prothrombin time is
prolonged?
What is the most likely cause of these results?
A. Hepatitis
B. Hemolytic anemia
C. Cancer head of pancreas
D. Chronic liver disease
 Plasma protein abnormalities in liver diseases
1. Albumin: Impaired synthesis in chronic hepatocellular damage leading to
decrease in plasma albumin in later stages(Low albumin with high globulin
reflects chronic liver disease)
2. Prothrombin time: prolonged later in hepatic disease may be due to:
-Failure of Vit K absorption due to cholestasis
-Failure of synthesis of coagulation factors
3. Alpha fetoprotein: is increased in 50-95% of patients with hepatocellular
carcinoma
4. Gamma Globulins: are increased (polyclonal) in cirrhosis
IgA is increased in cirrhosis
IgM is increased in primary biliary cirrhosis
IgG is increased in chronic active hepatitis
 Plasma enzymes in liver disease
1. ALT and AST are the standard tests of hepatocellular damage,ALT is more
specific than AST
2. Alkaline phosphatase(ALP) and gamma glutamyl transferase: GGT is more
liver specific and more sensitive. GGT is increased in alcohol abuse.
3. In hemolytic jaundice: AST and ALT are normal, Lactate dehydrogenase (LDH)
may be increased and normal Alkaline phosphatase
4. In hepatocellular jaundice: AST and ALT are often increased to more than 6
times the upper reference value while alkaline phosphatase is less than twice
normal, marked increase with more obstruction.
5. In cholestatic jaundice: ALT and AST are slightly increased whereas alkaline
phosphatase activity is more than twice the upper reference range
GGT and 5’ nucleotidase(5’NT) are increased.
 Other miscellaneous tests in liver disease
1. Plasma urea show significant decrease late in hepatic disease
2. Hypoglycemia may occur due to impaired gluconeogenesis or glycogen
breakdown
3. Lipogram lipids is increased in cholestatic jaundice
4. Immunological tests
5. Urine analysis Normally bilirubin is absent in urine and urobilinogen is trace
In hemolysis, urobilinogen in urine is increased due to increased bilirubin
exceretion in bile
 Effects of cirrhosis
1. Portal hypertension
2. Hypo-proteinemia
3. Failure of normal inactivation of estrogen by the liver lead to testicular
atrophy and gyn-ecomastia
4. Hepatocellular carcinoma
5. Liver cell failure: Cholemia is the usual end result
Laboratory finding in liver cirrhosis
1. Decreased Albumin
2. Increased immunoglobulins
3. Decreased cholesterol
4. Prolonged prothrombin time
5. In biliary cirrhosis: serum ALP is the earliest abnormal result
Bilirubin, AST and ALT are only slightly elevated.
 Laboratory findings in liver failure
1. Increased bilirubin mainly unconjugated
2. ALP, AST, ALT will be elevated early in the disease. They return to normal levels
as the condition improves or the liver cell injury becomes massive.
3. Elevated GGT
4. Low levels of Albumin
5. Low level of cholesterol
6. Prolongation of prothrombin time which parallels the degree of liver failure
Laboratory finding in liver carcinoma
No single laboratory test is useful for early detection,diagnosis and monitoring
of cancer. So markers with high clinical specificity must be coupled with markers
with clinical sensitivity.
1. Marked elevation of Alpha fetoprotein
2. Enzymes:
a. Alkaline phosphatase
Total ALP is increased in liver metastasis and in cancer patients with extensive
bone metastasis
b. GGT
It is elevated in the majority of cases of hepatocellular carcinoma and in liver
metastasis.
 Serologic test results in stages of HBV infection
Test Acute Window Complete Chronic Chronic Post-
phase recovery Hepatitis active vaccination
Hepatitis
HBsAg Positive Negative Negative Positive Positive Negative

HBc IgM Positive Positive Negative Negative Negative Negative

HBc IgG Negative Positive Positive Positive Positive Negative

HBsAb Negative Negative Positive Negative Negative Positive

HBeAg Positive Negative Negative Negative Positive Negative

N.B. Window phase (Serological gAap): is the period between the disappearance of HBsAg and the appearance of HBsAb.