PATHOPHYSIOLOGY OF JAUNDICE AND ITS TYPES.pptx

PATHOPHYSIOLOGY OF JAUNDICE

1. Pathophysiology of Jaundice DR.PRIYANKA VERMA MBBS, MD PHYSIOLOGY 1

2. FATE OF RBC AND HAEMOGLOBIN Senile RBCs (after 120 days)  ↓ se NADPH activity  cell membrane  more fragile. The destruction of red cells occurs mostly in the capillaries of spleen [ graveyard of RBCs]. The haemoglobin released after the haemolysis of red cells is taken up by the tissue macrophages . 2

3. The tissue macrophage system ( Reticuloendothelial System) includes the following phagocytic cells: In the bone marrow these cells form part of the lining of the blood sinuses (littoral cells ) In the liver they lie at intervals along the vascular capillaries (Kupffer cells ) In the spleen they are found in the pulp. In the lymph nodes they line the lymphatic path 3

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5. 5 Fixed tissue macrophages Known by different names in different sites Liver Kupffer cells Lung Alveolar macrophages Skin Langerhans cells Connective tissue Histiocytes CNS Microglia Bone Osteoclasts Spleen/Bone marrow/Lymph nodes Reticular or Dendritic cells

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7. 7 After destruction of RBC - Hb is released. It splits into haem and globin. Globin is broken into amino acids within the RES cells and will be utilized later for the synthesis of body proteins. FATE OF RBC AND HAEMOGLOBIN

8. Next iron is released into plasma  transported by transferrin to the storage sites  utilized by the body for the synthesis of new haemoglobin . 8

9. 9 The porphyrin ring of haem gets converted into biliverdin and a molecule of carbon monoxide is released . Biliverdin gets reduced to form bilirubin , which is released into the plasma.

10. 10 This unconjugated bilirubin soluble in lipid solvents is carried by the plasma in combination with albumin . Hence it is not excreted into urine by the kidney .

11. 11 A small percentage of RBC may breakdown in the circulation. The Hb released combine with heptoglobin in the plasma and is picked up by the liver where heme is converted into iron and biliverdin . Biliverdin latter gets converted into bilirubin .

12. 12 Enterohepatic Circulation of Bilirubin In the liver , bilirubin undergoes conjugation with glucuronic acid and forms bilirubin mono- and di glucuronide . These compounds are soluble in water and pass into the duodenum in the bile digestion.

13. 13 In the intestine (colon), by bacterial degradation bilirubin is converted into a colourless com-pound called stercobilinogen ( urobilinogen ).

14. 14 About 20% of urobilinogen is absorbed into the portal blood and reaches liver. A part of this urobilinogen enters general circulation and is filtered by the kidney into the urine.

15. 15 Urobilinogen gets oxidized to urobilin after exposure to sunlight and provides the color to the urine. The rest of urobilinogen is resecreted into the bile and participates in enterohepatic recirculation .

16. 16 Stercobilinogen will be excreted into the feces. It may get oxidized into stercobilin . The brown color of the feces is due to stercobilin and stercobilinogen .

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18. State of bilirubin in the body. BILIRUBIN The normal serum bilirubin level ranges from 0.3 to 1.0 mg/ dL . The total serum bilirubin includes conjugated as well as unconjugated bilirubin . 18

19. JAUNDICE Yellow discoloration of the skin, conjunctiva and mucous membrane caused by the presence of excess accumulation of bilirubin in plasma and tissue fluids is called jaundice. The word Jaundice -a French word ' Jaune ' which means yellow. 19

20. JAUNDICE Normal bilirubin levels: 0.3 to 1.0 mg/ dL . When the bilirubin level exceeds 2 mg/100 mL , then clinical jaundice develops. 20

21. Yellow coloration of the conjunctiva (white of the eye) is the confirmative indication for the jaundice . 21

22. Types of Jaundice 22 These are Hemolytic jaundice, Hepatocellular or hepatic jaundice Obstructive jaundice.

23. Hemolytic Jaundice (Prehepatic Jaundice) Excessive red blood cell destruction  excess bilirubin formation. Liver function is normal. Liver tries to increase excretion of bilirubin , but cannot cope up with the increased production of bilirubin. 23

24. 24 As a result, unconjugated bilirubin level in the plasma increases and causes jaundice. There is also increased formation of urobilinogen .

25. Excess haemolysis is seen in a ) Splenomegaly b ) Erythroblastosis fetalis c ) Haemolysis due to mismatched transfusion d ) Hb abnormality e ) Drug toxicity 25

26. 2. Hepatocellular or Hepatic Jaundice This jaundice develops due to damage to the liver cells. In this case liver function is affected. 26

27. 2. Hepatocellular or Hepatic Jaundice As a result, conjugated bilirubin is not excreted. Hence there is an increase in both conjugated and unconjugated plasma bilirubin levels. 27

28. Liver damage is seen in: Infective hepatitis (mostly viral), Drug toxicity, Carcinoma of liver, Cirrhosis of liver 28

29. 3.Obstructive Jaundice (Post Hepatic Jaundice ) This develops due to obstruction to the bile flow at any level of biliary system (obstruction may be inside or outside the liver). 29

30. Due to obstruction, bile cannot enter small intestine , Bile salts and bile pigments enter circulation and later excreted into urine . There is an increase in the conjugated plasma bilirubin level . 30

31. This type of jaundice is seen in : Obstruction of bile ducts by gallstones, Carcinoma of pancreas which grows into the bile ducts and blocks them . 31

32. VAN DEN BERGH REACTION Vanden Bergh reagent is a mixture of equal volumes of sulfanilic acid and sodium nitrate . The principle of the reaction is that sulfanilic acid of the above mixture reacts with bilirubin to form purple - coloured azobilirubin. 32

33. Direct reaction: Van den Bergh reagent reacts with conjugated bilirubin and gives a purple color immediately within 30 seconds. This is referred to as a direct positive Van den Bergh reaction . 33

34. Indirect reaction: Alcohol or methanol is added to unconjugated bilirubin, which then gives the Van den Li Bergh reaction positive and is referred to as indirect positive . 34

35. Difference Between Three Types of Jaundice 35

36. FEATURES HEMOLYTIC [PREHEPATIC] HEPATIC [HEPATOCELLULAR] OBSTRUCTIVE [POSTHEPATIC] Cause Due to excess destruction of RBCs Due to a decline in function of the liver as in hepatitis and drug toxicity Due to obstruction of bile ducts by gallstones or carcinoma of pancreas. Serum bilirubin Increase in unconjugated bilirubin levels Increase in both forms of bilirubin but mainly conjugated form Increase in the levels of conjugated bilirubin. 36

37. FEATURES HEMOLYTIC [PREHEPATIC] HEPATIC [HEPATOCELLULAR] OBSTRUCTIVE [POSTHEPATIC] Urine bilirubin and bile salts No bilirubin or bile salts in urine Bilirubin and bile salts are present in urine. Conjugated bilirubin is water soluble and excreted into urine Bilirubin and bile salts are present in urine. Conjugated bilirubin is excreted into urine. Urine urobilinogen Urobilinogen in urine is more Urobilinogen is present in urine but is less compared to normal as less stercobilinogen is formed No urobilinogen in urine, if obstruction is complete 37

38. FEATURES HEMOLYTIC [PREHEPATIC] HEPATIC [HEPATOCELLULAR] OBSTRUCTIVE [POSTHEPATIC] Vit K deficiency No deficiency No deficiency Deficiency develops due to lack of bile salts Stool color and fecal stercobilinogen Stools yellow or dark brown in color due to increased stercobilinogen Pale stools due to decreased stercobilinogen in stools Fatty, bulky and clay-colored stools as stercobilinogen is absent Van den Bergh test Van den Bergh indirect positive due to unconjugated bilirubin Van den Bergh direct and indirect positive Van den Bergh direct positive due to the presence of conjugated bilirubin 38

39. FEATURES HEMOLYTIC [PREHEPATIC] HEPATIC [HEPATOCELLULAR] OBSTRUCTIVE [POSTHEPATIC] Alkaline Phosphate Normal serum alkaline phosphatase Increase in serum alkaline phosphatase Marked increase in serum alkaline phosphatase due to complete obstruction of bile ducts Fecal Fat Normal Increased Increased Plasma A/G Ratio Normal Decreased due to ↓ sed levels of albumin Normal Blood Picture Anemia , reticulocytosis Normal Normal 39

40. Deficiency of Glucuronyl Transferase Jaundice may develop due to deficiency of glucuronyl transferase as in ( i ) Crigler - Najjar syndrome and ( ii) Gilbert syndrome . 40

41. Clinical Features of Jaundice Common symptoms of jaundice  include : A yellow tinge to the skin and the whites of the eyes, normally starting at the head and spreading down the body Pale stools Dark urine Itchiness 41

42. Clinical Features of Jaundice Accompanying symptoms of jaundice resulting from low bilirubin levels include : Fatigue Abdominal pain Weight loss Vomiting Fever 42

43. Investigations In many cases, the likely underlying cause can be  elicited from the history , with the investigations simply confirming suspicions. Laboratory Tests Liver function tests  (LFTs), Coagulation studies  (PT can be used as a marker of liver synthesis function) 43

44. Investigations Laboratory Tests CBC  ( anaemia , raised MCV, and thrombocytopenia all seen in liver disease ). Imaging: USG Abdomen. Magnetic Resonance Cholangiopancreatography  ( MRCP )  44

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46. Table – LFT serum markers. * as an estimate, if the AST:ALT ratio >2 , this is likely alcoholic liver disease , if AST:ALT is around 1 , then likely viral hepatitis as the cause 46

47. Management Rest : Prolonged bed rest is not usually needed but patients feel better with restricted activities. Nutrition: A high calorie diet should be given. It is usually given in the morning because many patients experience nausea in the evening . If there is persistent vomiting, intravenous fluids must be given. Usually excessive fatty foods are not tolerated well and are hence avoided . Oral glucose 47

48. Management Drugs : There are no specific drugs useful for viral hepatitis . All hepatotoxic drugs as well as alcohol must be withdrawn . Antihistamines for itching 48

49. Jaundice of Newborn (Physiological Jaundice ) In the newborn, the plasma bilirubin level will be more than 1 mg/100 mL. It continues to rise during the first week and then declines. If the level exceeds 5 mg%, jaundice is always present. But rarely it exceeds 12 mg%. 49

50. Jaundice of Newborn (Physiological Jaundice ) This is physiological jaundice. This is attributed to : 1 . Excessive hemolysis 2 . May be due to immaturity of the hepatic conjugating enzyme system ( glucuronyl transferase ) 50

51. Treatment Phototherapy : Exposure of the skin to light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin . Hence this is indicated in hemolytic jaundice in newborn . Phototherapy is of value in treating infants with jaundice irrespective of its cause . 51

52. Acholuric jaundice: Hemolytic jaundice is also called acholuric jaundice. The unconjugated bilirubin is bound to protein and is not excreted into urine hence the name. Icterus gravis neonatorum: It is a severe form of hemolytic jaundice that develops in the new born due to Rh incompatibility. Bilirubin levels may reach 25 mg/ dL . 52

53. Types of Jaundice a . Haemolytic (pre-hepatic) - ↑ Uncongjugated bilirubin levels . b . Hepatic-Liver function affected- ↑ In both conjugated and unconjugated bilirubin. c . Obstructive (post-hepatic) - ↑ In conjugated bilirubin. (due to obstruction) 53

54. Q. An young man visited hospital with severe yellow coloration of the conjunctiva and mucous membrane with fever and loss of appetite for the last one week. Lab tests indicated-Serum bilirubin 5 mg/100 ml. Stool-Fatty and bulky stools Urine- Positive for bilirubin, bile salts Urobilinogen absent Vandenberg test - Direct positive Haemogram - Normal Liver function tests - Normal What is the clinical condition. Why fat content is more in the stools. 54

55. Obstructive jaundice Fatty, bulky and clay coloured stools as stercobilinogen is absent. 55

56. THANK YOU 56