Jaundice-approach,DD,management,other investigation.pptx

Jaundice all about

1. APPROACH TO JAUNDICE

2. JAUNDICE Yellowish discoloration of body tissues resulting from the deposition of bilirubin Sclera -High elastin -3mg/dL 2nd Site - Under the tongue Skin → Yellow → Long standing - Green ( Biliverdin)

3. JAundcie - scleral Under tongue biliverdin

4. Differential Diagnosis for yellowing Carotenoderma Most commonly due to - Ingestion of excessive amount of vegetables - Carrots , leafy vegetables Commonly associated with Diabetes Hypothyroidism Anorexia Nervosa Drug induced Quinacrine Sunitinib Sorafenib Phenol exposure

5. Carotenoderma Pigment concentrated on Palms Soles Forehead Nasolabial folds Sclerae Spared

6. Bilirubin Prematurely destroyed erythroid cells Myogolobin Cytochromes 80-85 % Breakdown of Senescent RBC Reticuloendothelial Cells Biliverdin CO Iron

7. Biliverdin Bilirubin Biliverdin Reductase Insoluble in Water Bind to Albumin for transport Carrier Mediated Membrane transport to Hepatocytes

8. Unconjugated Bilirubin Glutathione -S - Transferase Superfamily Reduce Efflux back Endoplasmic Reticulum Conjugation to Glucouronic acid Uridine Diphosphate glucouronosyl transferase Bilirubin Monoglucouronide Bilirubin Diglucouronide Bile Canaliculi Sinusoid MRP 2 MRP 3 OATP1B1 / OATP1B3

9. Conjugated Bilirubin Small Intestine Distal Ileum /Colon Unconjugated bilirubin Urobilinogen / Urobilins 80-90 % Excreted in Fecus 10-20 % Enterohepatic cycling Not absorbed due to Hydrophilicity Large molecular size Bacterial Beta-Glucuronidase Normal Gut Bacteria

10. Serum Bilirubin Direct = Conjugated Indirect = Unconjugated Diazotized sulfanilic acid → Stable compound absorbs maximally @ 540nm Accelerator - Alcohol

11. New Techniques 1) In Normal Persons /Gilbert Syndrome = almost 100% of Serum Bilirubin is Unconjugated : <3 % is Monoconjugated 2)Hepatobiliary disease = Monoconjugated predominance 3)Direct fraction also includes Delta Fraction D elta fraction = delta Bilirubin = Biliprotein Conjugated Bilirubin which covalently Bound to albumin Important fraction in people with Hepatobiliary disorders / Cholestasis This explains - Absence of Bilirubinuria and Serum bilirubin falls slowly

12. Urine Bilirubin Unconjugated = Bound to albumin = Not excreted in Urine Delta Bilirubin = Bound to albumin = Not excreted in Urine → Conjugated → Filtered in Glomerulus → Majority absorbed at PCT Presence of Bilirubinuria = Elevated Conjugated fraction = Hepatobiliary disease False Negative

13. Kumar and clark 34.8 49-1 table harrison

14. Unconjugated Hyperbilirubinemia Hemolytic disorders Inherited Spherocytes Sickle cell anemia Thalasemia Pyruvate Kinase Deficiency G-6-PD deficiency Aquired Microangiopathic Hemolytic anaemia Paroxysmal nocturnal hemoglobinuria Spur cell anaemia Immune Hemolysis Parasitic Infections

15. Crigler Najjar Type 1 Exceptionally rare Bilirubin > 20 mg/dL Neurological deficit Death at infancy / Childhood Absence of UDPGT Activity Type 2 Live into adulthood Bilirubin ~ 6-25 mg/dL <10% of Enzyme is active due to mutation UDPGT activity can induced by Phenobarbital Susceptible under illness

16. Gilbert Syndrome Impaired conjugation due to reduced Bilirubin UDPGT activity (10~35 %) Bilirubin ~ 6 mg/dL Intermittent Jaundice Incidence is 3-7 % Male : Female = 1.5-7

17. Conjugated Hyperbilirubinemia Patient presents with asymptomatic jaundice Rotor Syndrome Dubin johnson Syndrome

18. History Exposure to chemicals/ medications/Alternative medicines Any transfusions/ IV drug intake/ ABuse Alcohol COnsumption Arthralgia / Myalgia preceding the jaundice →Drug induced / Viral Hepatitis Sudden onset of Right upper quadrant pain with Chills → CHoledocolithiasis ? Ascending cholangitis

19. Physical Examination Proximal muscle wasting → Long standing disease Look for stigmata of Chronic Liver disease

20. Abdominal Examination Any dilated Veins Visible Organomegaly Abdominal distension Liver - Size and consistency → Look below xiphoid for enlarged Left lobe Ascites +/- Splenomegaly Murphy's sign

21. Laboratory Tests Total and DIrect bilirubin Fraction SGOT,SGPT,ALP (49-1) Albumin levels → if low = Chronic Disease Prothrombin time → Vit K deficiency due to prolonged jaundice / Malabsorption If the PT not corrected with Vitamin K supplementation → Hepatocellular Injury

22. Wilson - Young Patients Alcoholic -> Pattern of AST:ALT >2:1 Viral / Toxin → Enzyme > 500 u/L ALT > AST Acute hepatocellular disease 25 x Normal Value may be seen Hepatocellular / Cholestatic disease < 8 x Normal Value

23. ACUTE VIRAL HEPATITIS Hepatitis A IgM Antibody Assay Hepatitis B Surface Antigen (HbSAg) Anti- HbC IgM Assay Hepatitis C Viral RNA test Hepatitis E IgM Antibody Assay Done depending on the circumstances Not Use full in Acute Hep C Takes 6 weeks to Positive EBV CMV Hep D WILSONS Ceruloplasmin Level Autoimmune Hepatitis ANA Anti - SMooth muscle Antibody

24. Drug Induced Predictable Acetaminophen Unpredictable Idiosyncratic reaction Environmental toxins Vinyl Chloride Kava Amanita phalloides Jamaica bush tea

25. Cholestatic Conditions Intrahepatic Extra -hepatic USG Absence of biliary dilatation Presence of biliary dilatation CT MRCP -INITIAL DIAGNOSTIC TEST ERCP -GOLD STD -CHOLEDOCOLITHIASIS PTC EUS-Has comparable sensitivity to MRCP and can take Biopsy

26. Intrahepatic Hepatitis B Hepatitis C Hepatitis A & E Alcoholic Hepatitis EBV CMV Anabolic Contraceptives Chlorpromazine Tolbutamide Primary biliary cholangitis Progressive destruction of interlobular bile ducts Anti-mitochondrial Ab Primary sclerosing cholangitis Fibrosis of larger bile duct Segmental sclerosis MRCP 75 % have inflammatory bowel disease TPN Malignancy Paraneoplastic stauffer syndrome - RCC Hodgkin,Medullary Carcinoma Thyroid Infection Sepsis Plasmodium falciparum Weil's disease - Jaundice + Renal failure + fever Other Ischemic hepatitis Heart failure - Congestion

27. Intrahepatic Familial forms Progressive familial intrahepatic cholestasis type 1-3 Benign recurrent cholestasis type 1&2 Benign recurrent cholestasis type 1&2 Episodic attacks of pruritus Cholestasis Jaundice - debilitating Serum bile acids = elevated GGT =Normal Doesn’t lead to chronic Liver disease Progressive familial intrahepatic cholestasis type 1-3 Begin at childhood Lead to CLD Progressive cholestasis Serum bile acids = Elevated Type 3 —> GGT = elevated

28. Extrahepatic Choledocolithiasis Mild right upper quadrant discomfort Cholangitis with jaundice Sepsis Circulatory collapse IgG4 associated cholangitis Responds to corticosteroids Chronic pancreatitis AIDS cholangiopathy Infection of epithelium with CMV / Cryptosporidium No jaundice Elevated ALP

29. Thank you