Clinical approach to jaundice


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Clinical approach to jaundice

  2. 2. JAUNDICE  Yellowish discoloration of skin resulting from depostition of bilirubin.  Sign of liver disease or hemolytic disorder.  Imbalance between production and clearance of bilirubin.  Degree of elevation by physical examination.  Sclera- high affinity because of elastin content-3mg/dl  Normal day light, limitation.  Yellow-green.
  3. 3.  Yellowing of skin  Carotenoderma-yellow color imparted to the skin because of carotenes.  Carrots, green leafy vegetables, squash, peaches and oranges.  Palms, soles, forehead and nasolabial folds.  Spares the sclera.  Quinacrine-4-37% yellowish discoloration of skin, also sclera.
  4. 4. PRODUCTION AND METABOLISM OF BILIRUBIN.  Tetrapyrrole pigment  Break down product of heme-ferroprotoporphyrin IX  70-80% breakdown of hemoglobin from senescent red blood cells.  Prematurely destroyed erythroid cells in the bone marrow, myoglobin, cytochromes.  Reticuluendothelial cells of the spleen and liver.
  5. 5.  Bilirubin is insoluble  Reversible covalent binding to albumin.  Hepatocytes – glutathione superfamily.  Prevents efflux back into serum  Uridine diphosphate glucuronyl transferase.  Conjugated bilirubin from the ER to the canalicular membrane of bile duct by energy dependent mechanism involving MDR protein -2
  6. 6. MEASUREMENT OF SERUM BILIRUBIN  Van der Bergh reaction.  Bilirubin is exposed to diazotized sulfanilic acid  Dipyrrylmethene azopigments which absorbs light maximally at 540nm  Direct bilirubin.  Total BR after the addition of alcohol.  Normal-1mg/dl  0.3mg-DBR  DELTA FRACTION-albumin linked bilirubin fraction in pts with cholestasis and hepatobiliary disease.
  7. 7.  Because of the longer half life of albumin-12-14 days  Conjugated hyperbilirubinemia donot exhibit bilirubinuria because  Albumin bound BR not excreted in renal glomeruli  Serum BR also falls slowly.
  8. 8. MEASUREMENT OF URINE BILIRUBIN  Unconjuated bilirubin – not found in urine.  Conjugated bilirubin filtered by the glomerulus and reabsorbed by the prox tubules.  Urine dipstick test- ICTOTEST  False negative in prolonged cholestasis due to conjugated BR bound to albumin.
  9. 9. APPROACH TO THE PATIENT  HYPERBILIRUBINEMIA  Overproduction of BR  Impaired uptake , conjuagation or excretion of bilirubin.  Regurgitation of unconjugated or conjugated from damaged hepatocytes or bileducts.
  10. 10. HISTORY  Single most important part of the evaluation of the patient with unexplained jaundice  Duration of jaundice  Use or exposure to medication-OTC, physician prescribed  Complementary or alternative medicine-herbal or vitamin preparations or anabolic steroids  Parenteral exposures-transfusions, iv abuse  Tattoos, sexual activity and alcohol history.  Loss of weight or appetitite.  Bleeding diathesis.
  12. 12.  Recent travel history  Exposure of patients with jaundice  Occupational history-contact with rats  Place of origin-carriage of hepatitis  Exposure to contaminated foods or water.  Family history- hemolytic anemias, congenital hyperbilurbinemias and hepatitis  Travel history  Dyspepsia , fat intolerance or biliary colic  Accompanying symptoms- arthralgia, myalgias, rash, anorexia, weight loss, abdominal pain-choledocholithiasis and ascending cholangitis  Fever  Pruritis  Changes in color of urine and stools
  13. 13. PHYSICAL EXAMINATION  Assessment of patients nutritional status  Temporal and proximal muscle wasting- long standing disease like ca or cirrhosis  Scratch marks, purpura, fetor hepaticus  Stigmata of chronic liver disease –spider nevi,  palmar erythema,  gynecomastia,  caput medusa,  dupuytrens contractures,  parotid enlargement or testicular atrophy.- advanced alcoholic cirrhosis
  14. 14.  Enlarged left supraclavicular lymphnode  Periumblical nodule-sister mary josephs  Jvp-right heart failure  Right sides pleural effusion  Pedal edema, nails- clubbing and white nails.  Tremors or flaps, KF ring.  Abdominal examination-  Size and consistency of liver and spleen.  Enlarged left lobe of liver.
  15. 15.  Enlarged nodular liver-malignancy  Tender hepatomegaly-alcoholic, viral or parasites, amyloid, hepatic congestion.  MURPHYS sign-cholecystitis.  Palpable gall bladder and courvoiser law  Ascites with jaundice- cirrhosis or malignancy with peritoneal spread  Abdominal veins.
  16. 16. LABORATORY TESTS  Total and direct serum bilirubin  Aminotransferases  Alkaline phosphatases  Albumin  Low-chronic  Normal acute viral or choledocholithiasis.  Prothromin time-prolonged jaundice, malabsorption of vit k or significant hepatocellular dysfunction.  Failure to correct with parenteral administration of vit k-severe hepatocellular injury.
  17. 17. UNCONJUGATED HYPERBILURUBINEMIA  HEMOLYTIC DISORDERS  ACQUIRED OR INHERITED  Sickle cell anemia, heriditary spherocytosis or thalasemmia etc  SBR rarely exceed 5mg/dl  Higher levels when there is coexistent renal or hepatic dysfunction or crisis.  Pigmented calcium bilirubinate gallstones and choledocholithiasis  Acquired-HUS, PNH, malaria or babesiosis,  Ineffective erythropoiesis-cobalamin, folate deficiency or iron def.
  18. 18.  Problem with hepatic uptake and conjugation of BR  Rifampicin, probenicis, ribavirin  Genetic- impaired conjugated  Crigler najjar type I-rare  Neonated  SBR>20mg/dl  Neurological impairment-kernicterus  Death in infancy or childhood  Complete absence of UDPGT actitivy
  19. 19.  Type ii  Common, adulthood, SBR-6-25mg/dl  Reduced UDPGT activity  Induced by phenobarbital  Susceptible to kernicterus under stress or illness  GILBERT SYNDROME-1/3 UDPGT activity  Very common-3-12% of general population.  Mild unconjugated hyper bilirubinemia- less than 6mg/dl  Serum levels fluctuate and identified during periods of fasting.  Male predominance of 2-7:1
  20. 20. CONJUGATED HYPERBILIRUBINEMIA  DUBIN JOHHSON  ROTOR-hepatic storage of BR  Asymptomatic jaundice  Second generation of life  Multiple drug resistance protein 2  Altered excretion into bileducts  Benign.
  21. 21. HEPATOCELLULAR JAUNDICE  Viral hepatitis-IgM for hep A, Hep B surface antigen, core IgM antibody and Hepatitis C viral RNA.  Wilsons disease-ceruloplasmin, urinary copper, serum copper, hepatic copper  Auto immune hepatitis young and middle aged women of any age  ANA, SMA, LKM,  Alcoholic hepatitis- AST:ALT> 2, AST rarely exceed 300IU/L  Acute viral hepatitis and toxin related hepatitis aminotransferase >500U/L  Cirrhosis –normal or only slight elevation in aminotranferasses.
  22. 22. DRUG INDUCED HEPATOTOXICITY  Predictable drug reactions-dose dependent  and affect all pts who ingest a toxic dose of the drug.  Eg. Acetaminophen  Unpredictable or idiosyncratic approach-not dose dependent  Occurs in minority – eg isoniazid  Environmental toxins- vinyl chloride, herbal preparations, pyrrolizidine alkaloids, Jamaica bush tea, mushrooms.
  23. 23. CHOLESTATIC JAUNDICE  Intra hepatic or extrahepatic cholestasis  History, physical examination and lab test  USG-high degree of sensitivity and specificity  Inexpensive and non invasive  But not the site or cause of obstruction especially distal CBD due to overlying bowel gas.  False negative test- partial obstruction to the common bile ducts  Cirrhosis  Primary sclerosing cholangitis-scarring prevent intrahepatic radicals to dilate
  24. 24.  MRCP, ERCP  CT with MRCP- assessing head of pancreas and choledocholithiasis  ERCP- gold standard- side viewing endoscopy per orally into the duodenum  Catheter advanced.  Injection of dye allows visualization of CBD.  Removal of CBD stones, placement of stents.
  25. 25.  Fibrosing cholestatic hepatitis- in hepatis B and C  Alcohol hepatitis  Drugs- pure cholestasis- anabolic and contraceptive steroids  Cholestatic hepatitis-chlorpromazine, erythromycin, imipramine, tolbutamide, sulindac, cimetidine , TMP-SMX, ampicillin, dicloxacillin and clavulinic acid.  Chronic cholestasis- chlorpromazine and prochlorperazine
  26. 26.  Primary biliary cirrhosis  Autoimmune- middle aged women  Progressive destruction of interlobular bile ducts  Presence of antimitochondrial antibodies- 95%  Primary sclerosing cholangitis  Destruction and fibrosis of larger bile ducts  Intrahepatic and extrahepatic –95%  Multiple strictures of bile ducts with dilatations proximal to strictures.  75% inflammatory bowel disease.
  27. 27.  Vanishing bile duct syndrome and adult bile ductopenia Rare  Decreased number of bile ducts in liver biopsy  Chronic rejection after liver transplantation and  Graft versus host reaction after BMT  Sarcoidosis  drugs
  28. 28. FAMILIAL  Progressive intrahepatic cholestasis PFIC1-3 bile salt export pump, multidrug resistant protein  Benign recurrent cholestasis  Autosommal recessive  Manifests in childhood  Recurrent episodes of jaundice and pruritis  Self limited but can be debilitating.
  29. 29.  CHOLESTASIS OF PREGNANCY  Second or third trimester  Resolves after delivery  Cause is unknown  Inherited and cholestasis can be triggered by estrogen administration.
  30. 30.  TPN  Non hepatobiliary sepsis  Bening post operative cholestasis  Paraneoplastic conditions  Hodgkins lymphoma, medullary thyroid ca, renal cell ca, sarcoma, prostate and gi ca  STAUFFER’S syndrome- intrahepatic cholestasis with renal cell ca  ICU- sepsis, shock liver , TPN,  Jaundice with BMT- venoocclusive disease or GVHD
  31. 31.  Plasmodium falcifarum– combination of indirect BR from hemolysis and cholestatic and hepatocellular jaundice.  Poor outcomes in jaundice with encephalopathy and renal failure  Weils disease-severe presentation of leptospirosis-jaundice, with renal failure ass with headache and myalgias.
  32. 32. EXTRAHEPATIC CHOLESTATSIS  MALIGNANT- pancreatic, gall bladder , ampullary and cholangiocarcinoma  Similar to primary sclerosing cholangitis.  Ampullary ca highest surgical cure rates and present as painless jaundice  Hilar lymphadenopathy due to metastasis from other ca
  33. 33.  Extra hepatic cholestatis- benign  Choledocholithiasis  Mild upper right quadrant pain with only minimal elevation of enzymes to ascending cholangitis , jaundice, sepsis and shock.  Strictures.  Chronic pancreatitis- rarely strictures of distal CBD.  AIDS cholangiopathy- infection of bile duct epithelium with CMV or crytosporidia- cholangiographic appreance similar to PSC.  Elevated Serum alkaline phosphatase – mean 800IU/L  Mirizzi syndrome  Parasitic disease like ascariasis
  34. 34. TAKE HOME MESSAGE  Jaundice is a hallmark of liver disease  Through clinical examination and history becomes vital in all cases  Classified as pre hepatic, hepatocellular and cholestatis although overlaps do occur  Biochemical and radiological evaluation helps in making a diagnosis.  This is just a overview
  35. 35. THANK YOU.
  38. 38. TITLE AND CONTENT LAYOUT WITH LIST  Add your first bullet point here  Add your second bullet point here  Add your third bullet point here