Differential Diagnosis of Icterus/Jaundice

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


CONTENTS • MüÉqÉsÉÉ• Introduction• Bilirubin – PHYSIOLOGY• Bilirubin – PATHOLOGY• JAUNDICE – Types• LFT• Case studies• Differential Diagnosis• Treatment• Discussion• Conclusion


MüÉqÉsÉÉ

MüÉqÉÇ ÌmÉ¨ÉÇ sÉÉÌiÉ uÉkÉïrÉÌiÉ CÌiÉ MüÉqÉsÉÉ |

MüÉqÉsÉÉ As a stage of mÉÉhQÒûAs a synonym of mÉÉhQÒûAs a type of mÉÉhQÒûAs a sÉ¤ÉhÉ in different diseases..

MüÉqÉsÉÉ can be seen as a disease and as a symptom.


MüÉqÉsÉÉ• ÌmÉ¨ÉeÉ 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

• qÉ±eÉ rÉ¢ÑüiÉç ÌuÉMüÉUÉÈ


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.


BILIRUBIN METABOLISM-PREHEPATIC

@ the RES RBC Destruction

Globulin Heme+Globulin

Heme

Biliverdin

UNCONJUGATED BILIRUBINBilirubin+Albumin

UCB=UnConjugated BilirubinINDIRECT BILIRUBIN


@ the RESRBC Destruction

Hb+Globulin

Heme

Biliverdin

Unconjugated Bilirubin

BILIRUBIN METABOLISM-HEPATICUCB

BilirubinAlbumin + +

Glucorunic Acid UDP-GT

CONJUGATED BILIRUBINDIRECT BILIRUBIN

Protein Y & Z


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


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 Destruction

RBC Destruction RBC Destruction

RBC DestructionRBC DestructionRBC Destruction

RBC Destruction RBC DestructionRBC Destruction

RBC Destruction

ANAEMIAJAUNDICE

SPLEENOMEGALY


HEPATIC JAUNDICEUCB

Bilirubin+

Glucorunic AcidGlucorunyltransferase

CONJUGATED BILIRUBIN

Protein Y & Z


OBSTRUCTIVE JAUNDICE

INTRA-HEPATIC CHOLESTASIS

EXTRA-HEPATIC CHOLESTASIS

@ COMMON HEPATIC DUCT

@ COMMON BILE DUCT

@ AMPULLA OF VATER

OBSTRUCION WITHIN THE LIVER

OROUTSIDE

ASCARIS


WHAT CAUSES JAUNDICE..???

Excess production of Bilirubin

Impaired hepatic uptake of UCB

Impaired conjugation of Bilirubin

Decreased excretion of CB


UNCONJUGATED

CONJUGATED

MIXED

RETENTION

REGURGITATION

PRE-HEPATIC

HEPATIC

POST-HEPATIC

TYPES OF JAUNDICE


CONJ / UNCONJ HYPERBILIRUBINAEMIACO

NJU

GAT

ED

HEPATICPOST – HEPATIC

UN

CON

JUG

ATED

PRE – HEPATIC

HEPATIC


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


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


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


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.


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


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.


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…


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


APPROACH TO A CASE OF JAUNDICE

• Detailed History• Associated complaints• Physical Examination• Laboratory Diagnosis• Radiological Investigations


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


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


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


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


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)


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


ΔΔ

UÉåaÉqÉÉSÉæ mÉUÏ¤ÉåiÉ iÉiÉÉå AlÉliÉUqÉÉæwÉkÉqÉç |

iÉiÉÈ MüqÉï ÍpÉwÉMçü mÉ¶ÉÉiÉç ¥ÉÉlÉmÉÔuÉïÇ xÉqÉÉcÉUåiÉç ||

WûÉËUSìuÉhÉïÇ ÂÍkÉUÇ cÉ qÉÔ§ÉÇ ÌuÉlÉÉ mÉëqÉåWûxrÉ ÌWû mÉÔuÉïÃmÉæÈ |

DIAGNOSIS OF EXCLUSION

WHEN YOU HEAR HOOFBEATSLOOK FOR HORSES, NOT FOR ZEBRAS


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


NEONATAL JAUNDICE

• Commonest requiring medical intervention

• Clinically detectable when bilirubin is above 5mg/dl

• Why does it occur..???• Breast milk Jaundice• Breastfeeding Jaundice


NEONATAL JAUNDICE

PHYSIOLOGICAL PATHOLOGICAL

STARTS @ After 4 days 1st or 2nd Day

BILIRUBIN < 20mg/dl > 20mg/dl

KERNICTERUS Rare Common

RESOLVES Early Late


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.


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


ΔΔ – LABORATORY INVESTIGATIONS

• SBR, Normal ALT, AST, ALP.

• SBR, Tranaminases, Normal or mild ALP.

• SBR, ALP, Normal or mild Transaminases.

• S. Albumin abnormalities


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


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…


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.• mÉUÏ¤rÉMüÉËUhÉÉå ÌWû

MÑüzÉsÉÉ pÉuÉÎliÉ


CONCLUSION

• Consequences, Dependency, Func reserve…• UÉåaÉqÉÉSÉæ mÉUÏ¤ÉåiÉ iÉiÉÉå AlÉliÉUÇ

AÉæwÉkÉqÉç |iÉiÉÈ MüqÉï ÍpÉwÉMçü mÉ¶ÉÉiÉç

¥ÉÉlÉmÉÔuÉïÇ xÉqÉÉcÉUåiÉç ||• Proper Diagnosis – Proper treatment• Improper preparations, Improper dosages end up in

hepatotoxicity• xÉÉkrÉ AxÉkrÉiÉÉ • ÌlÉSÉlÉ mÉËUuÉeÉïlÉ, xÉqmÉëÉÎmiÉ

ÌuÉbÉOûlÉ, urÉÉÍkÉ mÉëirÉlÉÏMü ÍcÉÌMüixÉÉ |


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


хвалаTHANK U

Health & Medicine

Differential Diagnosis of Icterus/Jaundice