Differential Diagnosis of Icterus/Jaundice

Differential Diagnosis of Icterus/Jaundice

1. By Dr. Madhusudan . B. G PG Scholar Dept of ROGA NIDANA GAMC, Bangalore Guided by Dr. Ananta . S. Desai Asst. Professor Dept of ROGA NIDANA GAMC, Bangalore DD OF ICTERUS 1 Dr. Madhusudan. B. G., DD of Icterus

2. CONTENTS 2 Dr. Madhusudan. B. G., DD of Icterus MüÉqÉsÉÉ Introduction Bilirubin – PHYSIOLOGY Bilirubin – PATHOLOGY JAUNDICE – Types LFT Case studies Differential Diagnosis Treatment Discussion Conclusion

3. MüÉqÉsÉÉ MüÉqÉÇ ÌmɨÉÇ sÉÉÌiÉ uÉkÉïrÉÌiÉ CÌiÉ MüÉqÉsÉÉ | MüÉqÉsÉÉ As a stage of mÉÉhQÒû As a synonym of mÉÉhQÒû As a type of mÉÉhQÒû As a sɤÉhÉ in different diseases.. MüÉqÉsÉÉ can be seen as a disease and a s a symptom. 3 Dr. Madhusudan. B. G., DD of Icterus

4. MüÉqÉsÉÉ ÌmɨÉeÉ mÉÉhQÒû MüÉå¸zÉÉZÉÉÍ´ÉiÉ MüÉqÉsÉÉ – oÉWÒûÌmÉ¨É MüÉqÉsÉÉ xuÉiÉÇ§É MüÉqÉsÉÉ *** mÉUiÉÇ§É MüÉqÉsÉÉ Â®mÉjÉ MüÉqÉsÉÉ zÉÉZÉÉÍ´ÉiÉ MüÉqÉsÉÉ MüÉqÉsÉÉ MÑüqpÉ MüÉqÉsÉÉ AsÉxÉMü / sÉÉbÉUMü WûsÉÏqÉMü qɱeÉ rÉ¢ÑüiÉç ÌuÉMüÉUÉÈ 4 Dr. Madhusudan. B. G., DD of Icterus

5. ICTERUS Yellowish pigmentation of Sclera, Skin and Mucous membranes. This condition is also termed as JAUNDICE. French word jaune meaning yellow . Yellow discolouration will be because of accumulation of Bile Pigments in the Sclera, Mucous membranes, Skin, Nails. Bile pigments have affinity to tissues containing ELASTIN . More appropriate to be considered as a symptom rather than a disease. 5 Dr. Madhusudan. B. G., DD of Icterus

6. BILIRUBIN METABOLISM-PREHEPATIC @ the RES RBC Destruction Globulin Heme+Globulin Heme Biliverdin UNCONJUGATED BILIRUBIN Bilirubin+Albumin UCB = UnConjugated Bilirubin INDIRECT BILIRUBIN 6 Dr. Madhusudan. B. G., DD of Icterus

7. @ the RES RBC Destruction Hb+Globulin Heme Biliverdin Unconjugated Bilirubin BILIRUBIN METABOLISM-HEPATIC UCB Bilirubin Albumin + + Glucorunic Acid UDP-GT CONJUGATED BILIRUBIN DIRECT BILIRUBIN 7 Dr. Madhusudan. B. G., DD of Icterus Protein Y & Z

8. UCB CONJUGATED BILIRUBIN BILIRUBIN METABOLISM-POST HEPATIC @ the RES RBC Destruction Hb+Globulin Heme Biliverdin Unconjugated Bilirubin EXCRETED TO INTESTINES BACTERIAL ACTION Fecal Urobilinogen Stercobilinogen Urinary Urobilinogen ENTERO-HEPATIC CIRCULATION 8 Dr. Madhusudan. B. G., DD of Icterus

9. HEMOLYTIC OR PRE-HEPATIC JAUNDICE @ the RES HEME+GLOBULIN HEME BILIVERDIN UNCONJUGATED BILIRUBIN ++++++++++ ++++++++++ ++++++++++ +++++++++++++++++++++++++++++++ UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB UCB TO BLOOD RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction RBC Destruction 9 Dr. Madhusudan. B. G., DD of Icterus ANAEMIA JAUNDICE SPLEENOMEGALY

10. HEPATIC JAUNDICE UCB Bilirubin + Glucorunic Acid Glucorunyl transferase CONJUGATED BILIRUBIN Protein Y & Z 10 Dr. Madhusudan. B. G., DD of Icterus

11. OBSTRUCTIVE JAUNDICE INTRA-HEPATIC CHOLESTASIS EXTRA-HEPATIC CHOLESTASIS @ COMMON HEPATIC DUCT @ COMMON BILE DUCT @ AMPULLA OF VATER OBSTRUCION WITHIN THE LIVER OR OUTSIDE 11 Dr. Madhusudan. B. G., DD of Icterus ASCARIS

12. WHAT CAUSES JAUNDICE..??? Excess production of Bilirubin Impaired hepatic uptake of UCB Impaired conjugation of Bilirubin Decreased excretion of CB 12 Dr. Madhusudan. B. G., DD of Icterus

13. TYPES OF JAUNDICE 13 Dr. Madhusudan. B. G., DD of Icterus

14. CONJ / UNCONJ HYPERBILIRUBINAEMIA 14 Dr. Madhusudan. B. G., DD of Icterus

15. LFT Tests based on EXCRETORY Functions Bile salts Bilirubin ALT AST ALP GGT Prothrombin Time Albumin 15 Dr. Madhusudan. B. G., DD of Icterus Tests based on serum ENZYMES of Liver Tests based on SYNTHETIC activity

16. ALT=ALAT=SGPT Alanine Transaminase = Alanine Aminotransaminase = Serum Glutamic Pyruvic Transaminase ALT – Viral Hepatitis, Liver damage, Bile duct pathology, Diabetes, CCF, IM, Myopathies, NSAIDs, Antibiotics, Anti- convulsants , Anti-psychotics. ALT+ ALP – Bile duct pathology ALT + CK Enzyme - Myopathies 16 Dr. Madhusudan. B. G., DD of Icterus

17. AST=ASAT=SGOT Aspartate Transaminase = Aspartate Aminotransaminase = Serum Glutamic Oxaloacetic Transaminase Found in Liver, Heart, Skeletal muscle, Kidneys, Brain , Pancreas, Lungs, WBCs and RBCs. AST – MI, Hepatitis, Ac. Pancreatitis, Ac. Hemolytic Anaemia , ARF, Trauma, Musculoskeletal diseases, Burns. ALT is more specific indicator of Liver inflammation than AST 17 Dr. Madhusudan. B. G., DD of Icterus

18. ALP – ALKALINE PHOSPHATASE Present in most tissues, richest being in Bone osteoblasts, Bile canaliculi , S I Epithelium, PCT of Kidneys, Placenta, Lactating breasts. Adults – mainly derived from Liver. In Infancy, Childhood, Rickets, Paget’s disease, Fractures, Bone cancers – mainly derived from Bones. ALP – Post Menopausal women on HRT, Pernicious Anaemia , Aplastic Anaemia , CML, Cretinism, Wilson’s disease. 18 Dr. Madhusudan. B. G., DD of Icterus

19. ALP – ALKALINE PHOSPHATASE ALP – Primary Hypothyroidism, Hyperthyroidism, Hodgkin’s Lymphoma, Polycythemia Vera, IM, DM, CCF, Amyloidosis. Ca – Liver, Breast, Colon, Lung, Pancreas. Almost all Liver disorders – such as – Hepatitis, Cholecystitis , Cholangitis, Cholestasis, Tumours , Cirrhosis, etc. LOOK FOR GGT & 5’- NUCLEOTIDASE 19 Dr. Madhusudan. B. G., DD of Icterus

20. g GT γ- glutamyl transferase Present in cell membranes of many tissues – Liver, Bile duct, Gall bladder, Kidneys, Pancreas, Spleen, Heart, Brain, Seminal vesicles. Isolated or disappropriate elevation – ALD GGT – Diseases of Liver, Biliary tract, Pancreas and also in MI. GGT has better sensitivity than ALP in biliary tract diseases. 20 Dr. Madhusudan. B. G., DD of Icterus

21. SERUM ALBUMIN Produced in Liver Half of the serum proteins Oncotic pressure, Carrier protein in – Chronic Liver diseases – Cirrhosis, Renal disorders, Burns, Pregnancy. in – Severe or chronic Dehydration, high protein diet. IMP. IN CHRONIC CONDITIONS… 21 Dr. Madhusudan. B. G., DD of Icterus

22. PROTHROMBIN TIME Except factor VIII all others are synthesized in the Liver by hepatocytes Factors II, VII, IX, X are Vit -K dependant Vit -K – Fat soluble vitamin Prognostic tool 22 Dr. Madhusudan. B. G., DD of Icterus

23. APPROACH TO A CASE OF JAUNDICE Detailed History Associated complaints Physical Examination Laboratory Diagnosis Radiological Investigations 23 Dr. Madhusudan. B. G., DD of Icterus

24. CASE STUDY - HEPATITIS History- Travel, Contact, Sex, Rx, Alcohol,… Symptomatology- Fever, fatigue, pain abd ,… Examination- Sick look, Tender liver, icetrus ,.. Laboratory Investigations- Mixed, AST, ALT Recovery / Relapse Chronic Hepatitis- B,C,D Complications- B,C,D Viral Toxic Drugs Auto-immune 24 Dr. Madhusudan. B. G., DD of Icterus

25. DD – VIRAL HEPATITIS HAV – IgM anti-HAV HBV – ACUTE – HBsAg , IgM anti- HBc CHRONIC – IgG anti- HBc , HBeAg HCV – anti-HCV, HCV RNA HDV – anti-HDV , HDV RNA HEV – IgM / IgG anti-HEV 25 Dr. Madhusudan. B. G., DD of Icterus A B C E

26. CASE STUDY - ALD 2 billion alcoholics, 76.3 million diseased. 30% Indian adults are alcoholics. Risk factors Fatty liver Alcoholic Hepatitis Cirrhosis MADDREY’S Discriminant Function DF=[4.6X(PT-Control)]+Bilirubin 26 Dr. Madhusudan. B. G., DD of Icterus

27. CASE STUDY - CIRRHOSIS Causes- Alcohol, Fatty Liver, Ch.Hepatitis -B,C, Wilson’s Dis, PBC, Auto-immune Hepatitis Symptomatology- Chronic Jandice , Weight loss, Abd pain, Abd distension, Intense nausea Signs- Jaundice, Ascites, Palmar erythema, Spider angioma , Spleenomegaly , Tremor Diagnosis- BIOPSY, Alb , Bil , PTT, Globulins 27 Dr. Madhusudan. B. G., DD of Icterus

28. CASE STUDY – OBSTRUCTIVE JAUNDICE History- Gall stones, Pain abd , Weight loss Causes- Impacted Gall stones, Worms, Growth in the Biliary tract or Head of Pancreas Symptomatology- Pain abd , Intolerable itching, Weight loss, pale stools Signs- Greenish yellow sclera, mucous, skin, Diagnosis- CB, ALP, GGT. USG, ERCP 28 Dr. Madhusudan. B. G., DD of Icterus

29. CASE STUDY – LIVER CANCER 3 rd leading cause of death Risk factors- Hep -B,C, Cirrhosis, Obesity, Aflatoxins , Tumors of abdomen and pelvis Symptomatology- Weight loss, Pain abdomen, Abd mass, Vomiting, Fever, Fatigue Diagnosis- USG, CT, α - feto protien (AFP) 29 Dr. Madhusudan. B. G., DD of Icterus

30. CASE STUDY - LEPTOSPIROSIS Weil’s Syndrome, Black jaundice Spirochete – Leptospira Commonest ZOONOTIC disease. Mild febrile illness to MULTIPLE ORGAN FAILURE Diagnosis-Culture, MAT, IgM ELISA 30 Dr. Madhusudan. B. G., DD of Icterus YELLOW FEVER

31. ΔΔ UÉåaÉqÉÉSÉæ mÉUϤÉåiÉ iÉiÉÉå A lÉliÉUqÉÉæwÉkÉqÉç | iÉiÉÈ MüqÉï ÍpÉwÉMçü mɶÉÉiÉç ¥ ÉÉlÉmÉÔuÉïÇ xÉqÉÉcÉUåiÉç || WûÉËUSìuÉhÉïÇ ÂÍkÉUÇ cÉ qÉÔ§ÉÇ ÌuÉlÉÉ mÉëqÉåWûxrÉ ÌWû mÉÔuÉïÃmÉæÈ | DIAGNOSIS OF EXCLUSION WHEN YOU HEAR HOOFBEATS LOOK FOR HORSES, NOT FOR ZEBRAS 31 Dr. Madhusudan. B. G., DD of Icterus

32. ΔΔ - AGE NEONATES – Pathological / Physiological CHILDREN – Viral Hepatitis, Drugs, Wilson’s, Thalassemia, Sickle Cell disease ADULTHOOD – Viral Hepatitis, ALD, Cirrhosis, Drugs, OLD – Cirrhosis, Primary or Secondary tumours , Biliary tree atresia PREGNANCY – Obstetric Hepatosis , Acute fatty liver of Pregnancy 32 Dr. Madhusudan. B. G., DD of Icterus

33. NEONATAL JAUNDICE Commonest requiring medical intervention Clinically detectable when bilirubin is above 5mg/dl Why does it occur..??? Breast milk Jaundice Breastfeeding Jaundice 33 Dr. Madhusudan. B. G., DD of Icterus

34. NEONATAL JAUNDICE PHYSIOLOGICAL PATHOLOGICAL STARTS @ After 4 days 1 st or 2 nd Day BILIRUBIN < 20mg/dl > 20mg/dl KERNICTERUS Rare Common RESOLVES Early Late 34 Dr. Madhusudan. B. G., DD of Icterus

35. ΔΔ - SEVERITY MILD – Hemolytic, Gilbert’s Syndrome, Rotor Syndrome. MODERATE – Drugs, Chemotherapy, Hepatitis, Benign or Malignancy. SEVERE – Neonatal, CBD Obstruction, Severe Hepatic Failure, CNS, DJS, Choledocholithiasis . Jaundice in Cirrhosis might be Mild, Moderate and Severe based on the extent and features. 35 Dr. Madhusudan. B. G., DD of Icterus

36. ΔΔ - COLOUR PALE YELLOW In Hemolytic Jaundice, where Bilirubin doesn’t exceed 5mg/dl. A symptom of UNCONJUGATED HYPERBILIRUBINAEMIA. ORANGE YELLOW In Hepatic and Mild to Moderate Cholestatic Jaundice. YELLOW GREEN In COMPLETE Obstruction Jaundice/Chronic Jaundice 36 Dr. Madhusudan. B. G., DD of Icterus

37. ΔΔ – LABORATORY INVESTIGATIONS SBR, Normal ALT, AST, ALP. SBR, Tranaminases , Normal or mild ALP. SBR, ALP, Normal or mild Transaminases. S. Albumin abnormalities 37 Dr. Madhusudan. B. G., DD of Icterus

38. ΔΔ – ICTERUS VERY LIMITED CAROTENAEMIA – Yellowish discoloration of skin, especially on the palms and soles, but not of the mucous membranes . SCLERA SPARED QUINACRINE OVERDOSE EXCESSIVE EXPOSURE TO PHENOLS 38 Dr. Madhusudan. B. G., DD of Icterus

39. PRINCIPLES OF TREATMENT Treat the ÌlÉSÉlÉÉjÉïMüU UÉåaÉ | ÌiÉ£ü UxÉ SìurÉÉÈ , qÉëÑSÒ ÌuÉUåcÉlÉ , MüTüWûUhÉ | Where to treat and where not to.. In Pre-hepatic and Post-hepatic Jaundice, TREAT THE CAUSE Post-hepatic / Obstructive = SURGICAL JAUNDICE Hepatic – ÌmÉ¨É UåcÉMüÉÈ , ÌiÉ£ü mÉëkÉÉlÉ SìurÉÉÈ , Hepatoprotectives … 39 Dr. Madhusudan. B. G., DD of Icterus

40. DISCUSSION MEDICAL ERROR / MISDIAGNOSIS HUMAN ERROR 15,00,000/8,00,000/4,00,000/5,30,000 1,80,000 die of medical error. Affects 1 in every 10 patients. mÉUϤrÉMüÉËUhÉÉå ÌWû MÑüzÉsÉÉ pÉuÉÎliÉ 40 Dr. Madhusudan. B. G., DD of Icterus

41. CONCLUSION Consequences, Dependency, Func reserve… UÉåaÉqÉÉSÉæ mÉUϤÉåiÉ iÉiÉÉå AlÉliÉUÇ AÉæwÉkÉqÉç | iÉiÉÈ MüqÉï ÍpÉwÉMçü mɶÉÉiÉç ¥ ÉÉlÉmÉÔuÉïÇ xÉqÉÉcÉUåiÉç || Proper Diagnosis – Proper treatment Improper preparations, Improper dosages end up in hepatotoxicity xÉÉkrÉ AxÉkrÉiÉÉ ÌlÉSÉlÉ mÉËUuÉeÉïlÉ , xÉqmÉëÉÎmiÉ ÌuÉbÉOûlÉ , urÉÉÍkÉ mÉëirÉlÉÏMü ÍcÉÌMüixÉÉ | 41 Dr. Madhusudan. B. G., DD of Icterus

42. SOME INTERESTING FACTS Bilirubin on the higher note is beneficial as it has potent anti-oxidant effects and so person has reduced risk of Cardio vascular diseases. Napoleon-I had Gilbert’s Syndrome In ancient Greece it was thought that jaundice could be cured if the patient gazes at a yellow bird as the disease would transmigrate from patient to bird. Napoleon army while conquering Egypt had suffered from Leptospirosis 42 Dr. Madhusudan. B. G., DD of Icterus

43. хвала THANK U 43 Dr. Madhusudan. B. G., DD of Icterus