JAUNDICE
Vineela Nekkanti V Pharm.D
Contents of the topic
Definition
Classification
Signs and symptoms
Diagnosis
Pathophysiology
Prevention
Treatment
Definition :
Jaundice, as in the French jaune, refers to the yellow discoloration of the skin.
Also known as Icterus
Jaundice is a liver disease characterized by elevated levels of bilirubin in the blood termed as hyperbilirubinaemia.
Normal range of serum bilirubin concentration is 0.3-1.3mg/dl
Jaundice occurs when bilirubin levels exceeds 2mg/dl
Introduction to Bilirubin :
Bilirubin is a orange-yellow pigment formed
in the liver by the breakdown of
hemoglobin and excreted in bile.
Two types of bilirubin :
Conjugated and Unconjugated bilirubin
Sources of Bilirubin :
• Catabolism of heme of hemoglobin (80-
85%)
• Non-hemoglobin heme containing
pigments such as myoglobin, catalase
and cytochromes
Conjugated Bilirubin
Unconjugated Bilirubin
Water soluble Water Insoluble
It reacts quickly to produce azobilirubin
It reacts slowly to produce azobilirubin
It produces azobilirubin only in the presence of
dye
It produces azobilirubin in the absence of dye
Known by Direct bilirubin Known by Indirect bilirubin
Metabolism of Bilirubin
Types of Jaundice
Prehepatic Jaundice
Intrahepatic jaundice
Post hepatic Jaundice
Type of Jaundice
Pre-Hepatic
Intra-hepatic
Post-Hepatic
Other Name Hemolytic jaundice
Hepatocellular Jaundice
Obstructive/Regurgitation
Jaundice
Cause Increased hemolysis of erythrocytes
Dysfunction of liver due to damage to
parenchymal cells
Obstruction of bile duct –
prevents the passage of bile into intestine
Examples Malaria, sickle cell anemia, incompatible
blood transfusion
Viral infection(hepati
tis), poisons and
toxins(chloroform, carbon
tetrachloride, phosphorus),
cirrhosis
Gallstones, cancer of
pancreas, gall bladder and
bile duct
Type of Jaundice
Pre-Hepatic
Intra-hepatic
Post-Hepatic
Biochemical characteristics
serum unconjugated bilirubin
serum conjugated and unconjugated bilirubin, SGPT and SGOT
Serum conjugated bilirubin and ALP
Clinical manifestations
Dark brown color stools
Nausea and anorexia
Nausea; GI pain and clay colored feces
Stercobilinogen content
Increased Absent Absent
Urobilinogen content
Increased Increased Increased
Etiology/Causes
Common Drugs Associated With Hyperbilirubinemia
HEPATOCELLULAR CAUSES
• Acetominophen• Alcohol• Amiodarone• Azulfidine• Carbenicillin• Clindamycin• Colchicine• Cyclophosphamide• Diltiazem• Ketoconazole• Methyldopa
• Niacin• Nifedipine• NSAIDs• Propylthiouracil• Pyridium• Pyrazinamide• Quinidine • Rifampicin• Salicylates• Verapamil
Common Drugs Associated With Hyperbilirubinemia
CHOLESTATIC CAUSES Amitriptyline
Androgenic steroids (B) Atenolol Augmentin Azathioprine Bactrim (D) Benzodiazeprines Captopril Carbamazole Chlordiazepoxide (D)) Clofibrate Coumadin Cyclosporine Danazol (B) Dapsone Disopyramide Erythromycin Estrogens (B) Ethambutol Floxuridine
5-Flucytosine Fluoroquinolones Griseofulvin Haloperidol (D) Labetolol Nicotinic acid NSAIDs Penicillins Phenobarbital Phenothiazines (D) Phenytoin Tamoxifen Tegretol Thiabendazole (D) Thiazides Thiouracil Tolbutamide (D) Tricyclics (D) Verapamil Zidovudine
1. Increased bilirubin production
2. Reduced bilirubin uptake by hepatic cells
3. Disrupted intracellular conjugation
4. Disrupted secretion of bilirubin into bile canaliculi
5. Intra/extra-hepatic bile duct obstruction
Lead to increases in free (unconj.) bilirubin
Result in rise in conj. bilirubin levels
Etiopathogenesis
1. INCREASED BILIRUBIN PRODUCTION(unconj. Hyperbilirubinemia) Hemolysis
Increased destruction of RBCs eg sickle cell anemia, thalassemia
Drastic increase in the amount of bilirubin produced Unconj. bilirubin levels rise due to liver’s inability to
catch up to the increased rate of RBC destruction Prolonged hemolysis may lead to precipitation of
bilirubin salts in the gall bladder and biliary network - result in formation of gallstones and conditions such as cholecystitis and biliary obstruction
Other Degradation of Hb originating from areas of tissue
infarctions and hematomas Ineffective erythropoiesis
2. DECREASED HEPATIC UPTAKE(unconj. Hyperbilirubinemia)
Several drugs have been reported to inhibit bilirubin uptake by the liver
e.g. novobiocin, flavopiridol
Bile
MRP2
B + GST
CB
Plasma Hepatic cell
Alb B
Alb :GSTB
sER
B + UDPGA UGT1A1
Neonatal jaundice occurs in 50% of newborns fetal bilirubin is eliminated by mother’s liver causes:
hepatic mechanisms are not fully developed resulting in decreased ability to conjugate bilirubin rate of bilirubin production is increased due to shorter lifespan of RBCs
Acquired disorders
hepatitis, cirrhosis impaired liver function
3) DISRUPTED INTRACELLULAR CONJUGATION (unconj. Hyperbilirubinemia)
Crigler-Najjar Syndrome, Type I (CN-I)
recessive allele; mutation-induced loss of conjugating ability in the critical enzyme glucuronosyltransferase CN-II greatly reduced but detectable glucuronosyltransferase activity due to mutation (predominantly recessive); enzymatic activity can be induced by drugs
Gilbert’s Syndrome glucuronosyl transferase activity
reduced to 10-30% of normal; also accompanied by defective bilirubin uptake mechanism
4) DISRUPTED SECRETION OF BILIRUBIN INTO BILE CANALICULI
(conj. Hyperbilirubinemia)
Dubin–Johnson Syndrome
mild conj. hyperbilirubinemia, but can increase with
concurrent illness, pregnancy, and use of oral contraceptives;
otherwise asymptomatic
Inability of hepatocytes to secrete CB after it has formed
Due to mutation in the MRP2 gene (autosomal recessive trait)
Rotor Syndrome
Autosomal recessive condition characterized by increased
total bilirubin levels due to a rise in CB
Caused by a defect in transport of bilirubin into bile
5) Intra/extra-hepatic bile duct obstruction
Intra-hepaticObstruction of bile canaliculi, bile ductules or hepatic
ducts
Extra-hepaticObstruction of cystic duct or common bile duct
Cholecystitis
Obstruction causes backup and reabsorption of CB which
results in increased blood levels of CB
Signs and
Symptoms Skin and sclerae - yellow
Stool - light colour, clay
coloured
Dark urine
Pain in abdomen
Itching
Trouble with sleeping
Fatigue
Swelling
Ascites
Mental confusion
Coma
Bleeding
Diagnosis
Medical history and examination
Urine test
Liver function and blood tests
Imaging tests
Liver biopsy
Medical history and physical examination
Patient interview for- abdominal pain, itchy skin or weight loss- malaria or hepatitis A- change of colour in your urine and stools- history of prolonged alcohol misuse- Flu like symptoms- Medications- Occupation
Physical examination :- Yellowish discoloration of eye and skin- Swelling of legs, ankle and feet- Hepatomegaly
Urine test :
- to measure levels of a substance called urobilinogen
- more than normal urobilinogen levels : Pre and Intra
hepatic
jaundice
- Less than normal urobilinogen level : Post hepatic
jaundice
Liver function and blood tests :Damage to liver releases liver enzymes like SGPT,
SGOT and ALP and proteins, this indicates
- Hepatitis
- Alcoholic liver disease
- cirrhosis
Imaging tests
- CT Scan
- MRI Scan
- Ultrasound Scan
- Endoscopic retrograde
cholangiopancreatography (ERCP)
Used to check for abnormalities inside the liver or
bile duct systems.
Liver biopsy
Used to diagnosis Cirrhosis and liver cancer.
Jaundice treatment
The treatment given to someone with jaundice will depend on what type they have, how serious it is and what caused it.
It may include tackling an underlying condition such as malaria and bothersome symptoms, such as itching.
For genetic conditions that don't get better, like sickle cell anaemia, a blood transfusion may be given to replenish red blood cells in the body.
If the bile duct system is blocked, an operation may be needed to unblock it. During these procedures measures may be taken to help prevent further problems, such as removal of the gallbladder.
If the liver is found to be seriously damaged, a transplant may be an option
Treatment & Therapeutic
Considerations
PHOTOTHERAPY
Through absorption of the wavelengths at the blue end of
the spectrum (blue, green and white light), bilirubin is
converted into water-soluble photoisomers. This
transformation enhances the molecule’s excretion into
bile without conjugation.
PHENOBARBITAL
This drug is not approved by FDA for use in neither
adult nor pediatric hyperbilirubinemia patients, due to
possibility of significant systemic side-effects.
Exact pathway is not known, but it is believed to act as
an inducing agent on UDP-glucuronosyl transferase,
thereby improving conjugation of bilirubin and its
excretion.
ALBUMIN
A 25% infusion can be used in treating
hyperbilirubinemia (esp. due to hemolytic disease).
It is used in conjunction with exchange transfusion to
bind bilirubin, enhancing its removal.
CLOFIBRATE (ATROMID-S)
This drug has been shown to reduce bilirubin levels
via an unknown mechanism.
Clofibrate is also associated with increased risk of
developing cholelithiasis, cholecystitis, as well as
functional liver abnormalities, which can worsen
hyperbilirubinemia.
PERCUTANEOUS TRANSHEPATIC
CHOLANGIOGRAPHY
Allows extraction of stones and thus removal of the
source of obstruction when present.
Prevention of Jaundice :
• Limit alcohol intake to not more than two drinks
a day for men or one drink a day for women.
• Avoid exposure to industrial chemicals.
• Do not use illegal drugs.
• Do not share needles or nasal snorting
equipment.
• Vaccination : Hepatitis A and Hepatitis B
• Maintain healthy body weight.