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Differential Diagnosis of Icterus/Jaundice
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Dr. Madhusudan. B. G., DD of Icterus 1
ByDr. Madhusudan. B. G
PG ScholarDept of ROGA NIDANA
GAMC, Bangalore
Guided byDr. Ananta. S. DesaiAsst. ProfessorDept of ROGA NIDANAGAMC, Bangalore
DD OF ICTERUS
Dr. Madhusudan. B. G., DD of Icterus 2
CONTENTS • MüÉqÉsÉÉ• Introduction• Bilirubin – PHYSIOLOGY• Bilirubin – PATHOLOGY• JAUNDICE – Types• LFT• Case studies• Differential Diagnosis• Treatment• Discussion• Conclusion
Dr. Madhusudan. B. G., DD of Icterus 3
MüÉqÉsÉÉ
MüÉqÉÇ ÌmɨÉÇ sÉÉÌiÉ uÉkÉïrÉÌiÉ CÌiÉ MüÉqÉsÉÉ |
MüÉqÉsÉÉ As a stage of mÉÉhQÒûAs a synonym of mÉÉhQÒûAs a type of mÉÉhQÒûAs a sɤÉhÉ in different diseases..
MüÉqÉsÉÉ can be seen as a disease and as a symptom.
Dr. Madhusudan. B. G., DD of Icterus 4
MüÉqÉsÉÉ• ÌmɨÉeÉ mÉÉhQÒû
• MüÉå¸zÉÉZÉÉÍ´ÉiÉ MüÉqÉsÉÉ – oÉWÒûÌmɨÉ
MüÉqÉsÉÉ
• xuÉiÉÇ§É MüÉqÉsÉÉ *** mÉUiÉÇ§É MüÉqÉsÉÉ
• ®mÉjÉ MüÉqÉsÉÉ zÉÉZÉÉÍ´ÉiÉ MüÉqÉsÉÉ
• MüÉqÉsÉÉ MÑüqpÉ MüÉqÉsÉÉ AsÉxÉMü /
sÉÉbÉUMü WûsÉÏqÉMü
• qɱeÉ rÉ¢ÑüiÉç ÌuÉMüÉUÉÈ
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 E L A S T I N .
• More appropriate to be considered as a symptom rather than a disease.
Dr. Madhusudan. B. G., DD of Icterus 6
BILIRUBIN METABOLISM-PREHEPATIC
@ the RES RBC Destruction
Globulin Heme+Globulin
Heme
Biliverdin
UNCONJUGATED BILIRUBINBilirubin+Albumin
UCB=UnConjugated BilirubinINDIRECT BILIRUBIN
Dr. Madhusudan. B. G., DD of Icterus 7
@ the RESRBC Destruction
Hb+Globulin
Heme
Biliverdin
Unconjugated Bilirubin
BILIRUBIN METABOLISM-HEPATICUCB
BilirubinAlbumin + +
Glucorunic Acid UDP-GT
CONJUGATED BILIRUBINDIRECT BILIRUBIN
Protein Y & Z
Dr. Madhusudan. B. G., DD of Icterus 8
UCB
CONJUGATED BILIRUBIN
BILIRUBIN METABOLISM-POST HEPATIC@ the RES
RBC Destruction
Hb+Globulin
Heme
Biliverdin
Unconjugated Bilirubin
EXCRETED TO INTESTINES
BACTERIAL ACTION
FecalUrobilinogen
Stercobilinogen
UrinaryUrobilinogen
ENTERO
-HEPATIC CIRCULATIO
N
Dr. Madhusudan. B. G., DD of Icterus 9
HEMOLYTIC OR PRE-HEPATIC JAUNDICE
@ the RES
HEME+GLOBULIN
HEME
BILIVERDIN
UNCONJUGATED BILIRUBIN
++++++++++
++++++++++
++++++++++
+++++++++++++++++++++++++++++++
UCB
UCBUCB
UCBUCB
UCB
UCB UCBUCBUCB
UCB
UCB
UCB UCBUCBUCB
UCB
UCBUCB
UCBUCB
UCB
UCBUCBUCB
UCBUCB
UCBUCBUCB
UCBUCBUCBUCB
UCBUCB
UCBUCBUCB
UCBUCB UCB
TO BLOOD
RBC DestructionRBC Destruction
RBC DestructionRBC Destruction
RBC DestructionRBC Destruction
RBC Destruction
RBC Destruction RBC Destruction
RBC DestructionRBC DestructionRBC Destruction
RBC Destruction RBC DestructionRBC Destruction
RBC Destruction
ANAEMIAJAUNDICE
SPLEENOMEGALY
Dr. Madhusudan. B. G., DD of Icterus 10
HEPATIC JAUNDICEUCB
Bilirubin+
Glucorunic AcidGlucorunyltransferase
CONJUGATED BILIRUBIN
Protein Y & Z
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
OROUTSIDE
ASCARIS
Dr. Madhusudan. B. G., DD of Icterus 12
WHAT CAUSES JAUNDICE..???
Excess production of Bilirubin
Impaired hepatic uptake of UCB
Impaired conjugation of Bilirubin
Decreased excretion of CB
Dr. Madhusudan. B. G., DD of Icterus 13
UNCONJUGATED
CONJUGATED
MIXED
RETENTION
REGURGITATION
PRE-HEPATIC
HEPATIC
POST-HEPATIC
TYPES OF JAUNDICE
Dr. Madhusudan. B. G., DD of Icterus 14
CONJ / UNCONJ HYPERBILIRUBINAEMIACO
NJU
GAT
ED
HEPATICPOST – HEPATIC
UN
CON
JUG
ATED
PRE – HEPATIC
HEPATIC
Dr. Madhusudan. B. G., DD of Icterus 15
LFT
Tests based on EXCRETORY Functions
• Bile salts• Bilirubin
• ALT• AST
• ALP• GGT
• Prothrombin Time• Albumin
Tests based on serum ENZYMES of Liver
Tests based on SYNTHETIC activity
Dr. Madhusudan. B. G., DD of Icterus 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 pathologyALT + CK Enzyme - Myopathies
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
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.
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
Dr. Madhusudan. B. G., DD of Icterus 20
gGT
• 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.
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…
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
Dr. Madhusudan. B. G., DD of Icterus 23
APPROACH TO A CASE OF JAUNDICE
• Detailed History• Associated complaints• Physical Examination• Laboratory Diagnosis• Radiological Investigations
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
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
A B C E
Dr. Madhusudan. B. G., DD of Icterus 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
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
27Dr. Madhusudan. B. G., DD of Icterus
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
Dr. Madhusudan. B. G., DD of Icterus 29
CASE STUDY – LIVER CANCER
• 3rd 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)
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
YELLOW FEVER
Dr. Madhusudan. B. G., DD of Icterus 31
ΔΔ
UÉåaÉqÉÉSÉæ mÉUϤÉåiÉ iÉiÉÉå AlÉliÉUqÉÉæwÉkÉqÉç |
iÉiÉÈ MüqÉï ÍpÉwÉMçü mɶÉÉiÉç ¥ÉÉlÉmÉÔuÉïÇ xÉqÉÉcÉUåiÉç ||
WûÉËUSìuÉhÉïÇ ÂÍkÉUÇ cÉ qÉÔ§ÉÇ ÌuÉlÉÉ mÉëqÉåWûxrÉ ÌWû mÉÔuÉïÃmÉæÈ |
DIAGNOSIS OF EXCLUSION
WHEN YOU HEAR HOOFBEATSLOOK FOR HORSES, NOT FOR ZEBRAS
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
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
Dr. Madhusudan. B. G., DD of Icterus 34
NEONATAL JAUNDICE
PHYSIOLOGICAL PATHOLOGICAL
STARTS @ After 4 days 1st or 2nd Day
BILIRUBIN < 20mg/dl > 20mg/dl
KERNICTERUS Rare Common
RESOLVES Early Late
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.
Dr. Madhusudan. B. G., DD of Icterus 36
ΔΔ - COLOUR
PALE YELLOWIn Hemolytic Jaundice, where Bilirubin doesn’t exceed 5mg/dl.
A symptom of UNCONJUGATED HYPERBILIRUBINAEMIA.
ORANGE YELLOWIn Hepatic and Mild to Moderate Cholestatic Jaundice.
YELLOW GREENIn COMPLETE Obstruction Jaundice/Chronic Jaundice
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
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
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…
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
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 |
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
Dr. Madhusudan. B. G., DD of Icterus 43
хвалаTHANK U