Jaundice PDF

Jaundice Dr L. S KATHTHIRIARACHCHI MD (Hon) Dip Med Physiology, Cert Med Edu, PhD - Neurophysiology Objectives Define jaundice Classification of jaundice Causes of jaundice Treatment for jaundice Prevention  Bilirubin Bilirubin is a greenish yellow pigment excret...

Jaundice Dr L. S KATHTHIRIARACHCHI MD (Hon) Dip Med Physiology, Cert Med Edu, PhD - Neurophysiology Objectives Define jaundice Classification of jaundice Causes of jaundice Treatment for jaundice Prevention  Bilirubin Bilirubin is a greenish yellow pigment excreted in bile, urine and feces. It is the end product of heme degradation derived from breakdown of aged erythrocytes by reticulo-endothelial system of the spleen, liver and bone marrow.  The Reticuloendothelial System (RES) The Reticuloendothelial System (RES) is a group of specialized cells found in various tissues throughout the body. primarily responsible for engulfing and breaking down foreign substances such as bacteria, viruses, and cellular debris. Essentially, they act as the body's clean-up crew. Key functions of the RES: Phagocytosis: The process of engulfing and digesting foreign particles. Immune response: Interacts with the immune system to help fight off infections. Removal of old or damaged cells: Cleans up cellular debris. Iron recycling: Reclaims iron from broken-down red blood cells.  The Reticuloendothelial System (RES) Components of the RES: The RES is made up of different types of cells, including:  Macrophages: These are the main players in phagocytosis. They are found in various tissues like the liver, lungs, spleen, and lymph nodes.  Kupffer cells: Macrophages specifically found in the liver.  Microglia: Macrophages found in the brain.  Dendritic cells: These cells also play a role in immune response. Types of bilirubin Indirect bilirubin Direct bilirubin Total bilirubin Unconjugated conjugated Total conjugated + unconjugated Lipid soluble Water soluble Jaundice Clinical sign Yellowish discoloration of skin, scleras and mucous membranes due to accumulation of unconjugated or conjugated bilirubin in blood Usually detectable when the total plasma bilirubin is greater than 2mg/dL (34 µmol/L) Clinical sign: An objective finding that can be observed or measured by a healthcare professional. «i!q p !^diu Important 4 terms 1. Hyperbilirubinemia Bilirubin is produced following breakdown of RBC Daily production – 0.2 to 0.3 mg/dl. Highly toxic  should be excreted from the body If bilirubin level exceed the normal level (1 – 2mg/dl)  = Hyperbilirubinemia But jaundice to be visualized the level of bilirubin should ≥ 2.0 mg/dl Therefore, hyperbilirubinemia does not cause jaundice always. (from 1 to 2 mg/dl is hyperbilirubinemia but not jaundice)  2. Jaundice Yellowish discoloration of the skin, sclera, mucus membranes due to hyperbilirubinemia. Total plasma bilirubin is greater than 2mg/dL (34 µmol/L)  3. Icterus – Yellowish discoloration of the sclera due to hyperbilirubinemia. Icterus can be appreciated before jaundice of the other parts of the body. Yellow discoloration of the sclera due to other reasons is not jaundice.  4. Cholestasis Impaired bile outflow. The 3 main contents of bile is bilirubin, bile acids or bile salts and cholesterol. In cholestasis not only bilirubin but other contents of bile will also come into the blood stream. Classification of jaundice 1) Pre-hepatic jaundice 2) Hepatic jaundice 3) Post-hepatic jaundice  1. Pre-hepatic jaundice (unconjugated hyper- bilirubinaemia)  Results from high unconjugated bilirubin in serum due to excess haemolysis  Haemolysis occurs due to: Physiological jaundice of new born Hemolytic disease of the newborn Structurally abnormal RBCs - Hemoglobinopathies (abnormal hemoglobin): Sickle cell anemia, Thalassemia - Red Blood Cell Membrane Defects : Hereditary spherocytosis, Hereditary elliptocytosis - Enzyme Deficiencies: Glucose-6-phosphate dehydrogenase (G6PD) deficiency  Clinical features Unconjugated bilirubin is absent in urine. Darker color stool due to excessive stercobilin formation. Physiological jaundice of newborn HbF  HbA in the first few days of life Excessive breakdown of Fetal Haemoglobin  unconjugated hyper- bilirubinaemia Reduce conjugation of the unconjugated/indirect bilirubin – due to immaturity of the liver:  immature Ligandin Y & Z receptor in the hepatocyte – impaired uptake of Unconjugated Bilirubin (UB) Reduce conjugation of UB ( glucuronyl transferase enzyme is not active) Life span of a RBC in an adult is 120 days. Life span of a RBC in newborn is 90 days. Hemolytic disease of the newborn cont… Rh negative mother and Rh positive fetus Feto-maternal hemorrhage during delivery  fetal RBC can cross towards the maternal circulation Mother will produce Rh factor antibodies In subsequent pregnancies, Rh factor antibodies crosses towards the fetal circulation Rh factor antibodies + fetal RBC  Ag – Ab complex  agglutination hemolysis of fetal RBC  Anaemia Oxygen delivery to tissues will reduce  fetal heart tries to compensate by increasing force of contraction & HR  Fetal cardiac failure Hemolytic disease of the newborn cont… Haemolysis increase unconjugated bilirubin  jaundice Immature blood brain barrier (BBB) bilirubin crosses the BBB  Bilirubin encephalopathy  permanent brain damage In the fetus RBC are produced in the liver and the spleen Anaemia  increase production of RBC  Hepatosplenomegaly Hepatomegaly  decrease albumin synthesis in the liver  reduce colloid oncotic pressure  Odema  Hydrops Fetalis In most serious cases  Intra Uterine Death (IUD) Kernicterus Kernicterus occurs in baby’s as immature blood brain barrier allow bilirubin to cross it and enter the brain. Occurs when serum bilirubin level > 25mg/dl. As a result bilirubin deposits in the basal ganglia and brain stem nuclei. Permanent neurological damage occur including, hearing impairment, movement disorders, intellectual disabilities etc. Unconjugated hyper- bilirubinemia Occurs in inherited diseases like Glibert Syndrome Benign, Genetic condition  Mutation in UGT gene  Causes mild decrease in activity of Glucoronyltransferase Unconjugated bilirubin ---> Glucoronyltransferase  ( combines Glucuronic acid with uncongugated bilirubin)  Conjugated bilirubin (water soluble) + Recurrent episodes of jaundice Unconjugated bilirubinaemia Treatment – No treatment required Unconjugated hyper- bilirubinemia Crigler-Najjar Syndrome Absent of Glucoronyltransferase Unconjugated bilirubinaemia Conjugated hyper- bilirubinemia Dubin Syndrome Unexcretable conjugated bilirubin  conjugated bilirubin accumulate in the liver  Dark colour liver appearance Rotor Syndrome Mildly unexcretable conjugated bilirubin  Intra Hepatic Jaundice Conjugated & unconjugated bilirubin are present in blood in high concentration. Due to; Impaired uptake of bilirubin into hepatic cells. impaired conjugation. Disturbed active secretion of bilirubin into bile canaliculi (intra hepatic bile duct obstruction).  Occurs in Damage to liver cells e.g; Viral hepatitis, Alcohol, toxins, Cirrhosis, Malaria Dubin johnson syndrome Clinical features pale clay colour stool- due to deficiency of stercobilin. dark brown urine - due to filtration of excess conjugated bilirubin Post Hepatic Jaundice obstruction of bile flow in biliary tract distal to bile canaliculi (extra hepatic bile duct obstruction). Occurs in  Biliary stenosis  Gall stones  Carcinoma in the head of the pancreas The conjugated bilirubin formed cant pass into small intestine therefore it returns back into blood. Clinical features Dark brown urine- conjugated bilirubin Urine is free from urobilinogen. Stools are clay (mud) color due to absence of stercobilin.  Direct Indirect uro- Sterco- Bilirubin uria (conjugated) (unconjugated) bilinogen bilinogen Pre-hepatic Intra- hepatic post- hepatic Treatment for jaundice in adults Jaundice treatment targets the cause rather than the jaundice symptoms. Anemia-Iron supplements Hepatitis-antiviral or steroid medications. Biliary obstruction-surgical removal of the obstruction. CA pancreas- chemotherapy Treatment for jaundice in infants PHOTOTHERAPY Exposure of skin to white light isomerization of Bilirubin to water soluble Lumirubin which is excreted in Bile without conjugation or with urine. Exchange transfusion In severe jaundice blood is removed and replaced with plasma or donor blood. Prevention In neonates-Breastfeeding Feeding will make baby pass more stools. Milk gives liver the energy it needs to process the bilirubin.  Summery How Bilirubin is formed RES: location, functions, cells of RES Define jaundice Classification of jaundice Causes of jaundice: Pre-hepatic, Hepatic & Post-hepatic Treatment for jaundice in adults and in infants Prevention Q&A Thank you