understanding and clinical approach to a case of jaundice

1. JAUNDICE ( ICTERUS )
2015
DR A.A.MOKHTAR
Professor of Internal Medicine
Mansoura University

2. Definition :
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3. Definition :
 Jaundice is yellow discoloration of
the skin , mucus membranes and
sclera of the eyes due to increase in
the level of circulating bilirubin.
 Other causes of yellow skin ?????
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 Carotenemia.
 Xanthomatosis.
 Myxoedema.
 Drugs e,g Atebrine , Miracil D ( yellow skin )
Pecric acid yellow skin & mucus membrane ( more
around the limbus ).

4. Clinical aspects :
 Normal Serum Bilirubin (SB) is 0.3 to 1.0 mg%
 Jaundice is increased levels of SB > 1.0 mg%
 It becomes clinically evident at 2.0 -3.0 mg / dl.
 Factors affecting the depth of jaundice :
1. Serum bilirubin level.
2. Elastic fibers have more affinity ( sclera).
3. Protein content of the tissue or body fluid
( exudates seems more icteric than transudates ).
4. With edema and dark skin – Jaundice is masked
Where to detect :
In fair skin...most noticeable on the face , trunk , and
sclera.
In dark skin on the hard palate , sublingual mucosa , and
sclera.
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5. Physiologic
cycle of
Bilirubin :
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6. Bilirubin is the metabolic end
product of Haeme metabolism
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• RBC life span in blood stream is 90-120 days
• Old RBCs are phagocytosed and/or lysed
• Lysis occurs extravascularly in the RE system
subsequent to RBC phagocytosis
• Intravascular Hemolysis of young RBC
• This is due to hemolytic diseases of RBC

7. Pathway for RBC Scavanging
Liver, Spleen &
Bone marrow
Hemoglobin
Globin
Amino acids
Amino acid pool
Heme Bilirubin
Fe2+
Excreted
Phagocytosis & Lysis
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Processed through the liver

8.  Bilirubin in the RES ( production) :
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300 mg daily in the RES

9. Bilirubin in the Liver Cell
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• Hepatocyte (HC) uptake of UCB
• Alb+UCB dissociates and UCB enters HC
• By passive diffusion into HC – Ligandin bound
• Insoluble UCB is to be made soluble in HC
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• Conjugation in ER of Hepatocyte (HC)
• Formation of mono and di glucuronides
• ( bilirubin monoglucoronide & bilirubin diglucoronide ).
• UDP (uridine diphospho Glucuronosyl transferase is energy depend.
• Insoluble UCB made water soluble for excretion
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• Excretion in into biliary canaliculi
• Rate limiting step in metabolism
• CB 50% is not protein bound – no loss of albumin
• Remaining 50%  bilirubin – Irreversibly bound

12. Bilirubin in blood
Properties Unconjugated Conjugated
Normal serum fraction 90% 10%
Water solubility (polarity) 0 (non polar) + (polar)
Affinity to lipids (Kernicterus) +++ 
Renal excretion Nil +
Vanden Berg Reaction Indirect Direct
Temporary Albumin Binding +++ 0
Irreversible Delta Bilirubin 0 ++
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In late stages of cholestasis or hepatocellular J bilirubin is not detected in urine due to 3rd
type of bilirubin which is conjugated bilirubin covalently bound to albumen so not appear
in urine.

13. Bilirubin in the Intestine
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3. From gut, UBG but not CB enters EHC
Kidney excretes absorbed UBG In biliary obst. UBG absent in urine
2. Conversion of CB into uro & stercobilinogen by bacterial B-
glucourinidases in terminal ilium & colon
Urobilinogen excreted in stool
( stercobilinogen )
Part of the UBG enters EHC
1. CB is excreted from hepatocytes into Duodenum
CB 10% diffuses in to blood CB excreted is not reabsorbed
Unless hydrolysed by bacteria in the terminal ilium & colon

14. Bilirubin handling in Kidney
Conjugated
Bilirubin
Unconjugated
Bilirubin
Urobilinogen
in urine
• Bound (20 days)
• Bilirubin in urine
is conjugated
• Not filtered
or secreted
• Nil in urine
• Normally traces
• ↑ in hemolysis
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15. Bilirubin Metabolism - Summary
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16. Jaundice – Classification
 Normal Serum Bilirubin (SB) is 0.3 to 1.0 mg%
 Over production of Bilirubin (Hemolytic)
 From hemolysis of RBC
 Lysis of RBC precursors – Ineffective erythropoesis
 Impaired hepatic function (Hepatitic)
 Hepatocellular dysfunction in handling bilirubin
 Uptake, Metabolism and Excretion of bilirubin
 Obstruction to bile flow (Obstructive)
 Intrahepatic cholestasis
 Extrahepatic Obstruction (Surgical Jaundice)
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22. How to clinically evaluate the patient ?
What tests will help us in D.D ?
What imaging modalities will be useful ?
How to monitor the progress ?
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Algorithmic approach for Jaundice
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23. HISTORY TAKING
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24. History taking :
Personal History
Age
Childhood……..Hemolytic J.
……..Infective H (A)
Middle age……………..G.stones.
Old age……………………Malignancy.
Occupation :
Contact with rats………weil`s disease
Medical personnel.……Hcv, HBV
Habits ……….Alcoholism & parentral drug addiction.
Locality Egyptian HCV
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25.  Nausea , vomiting , flu like symptoms
then fever subsides and jaundice appears
……….Viral hepatitis.
 Gradual , following long history of fat
dyspepsia and associated with relatively
fair general condition ……Calcular
cholestatic jaundice …………..with fever and
rigors…….Cholangitis due to stone or bile
stricture,
 Rapid progressive with failure of health
and weight loss ………….suggest
malignancy.
Complaint :
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26. Qnset
Acute ( infective & Drug ).
Rapid Calcular & malignancy.
Chronic Cirrhosis.
Associated with :
Surgery …..any surg ??? Halthane T. ? Hepatitis.
….. Surg for malig???? Liver mets.
… Biliary surgery ?? Missed stone
?? Stricture.
Present History :
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27. Regressive ……viral hepatitis.
Intermittent …….calcular or hemolytic.
Progressive……….Malignancy or cirrhosis,
Duration:
Short Viral hepatitis.
Chronic Cirrhosis.
Course :
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28. Associated with Fever - pain – stool colour –
urine colour :
Fever preceeds J. then disappear with J ?? V,hepatitis
persists with J ????Weil`s disease ,
Brucellosis , Malaria , filaria , Amoebic
hepatitis,
Fever with J …….Hemolytic crisis.
Fever after J…….. 2ry infection on top of calc obst J
Associated with :
Pain Biliary ???????
Dull aching in the Rt Hpoch……?????? Hepatitis.
Bone aches???? Mets , hemolytic crisis , ?? osteomalacia
Pruritus……..due to bile salts in obstructive jaundice , ??
Hepatocellular J
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29. Stool : Pale , clay with steatorrhoea……..Obstructive J.
Dark coloured……………………Haemolytic J.
Urine Pale ( acholuric J.) in hemolytic J as the indirect
bilirubin is non filtrable
Associated with drug intake :.
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Drugs causing Cholestasis.
Hepatotoxic drugs.

30. Drugs causing Cholestasis
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 Anabolic steroids (testosterone, norethandrolone)
 Antithyroid agents (methimazole)
 Azathioprine (Immunosuppressive drug)
 Chlorpromazine HCI (Largactil)
 Clofibrate, Erythromycin estolate
 Oral contraceptives (containing estrogens)
 Oral hypoglycemics (especially chlorpropamide)

31. Hepato toxic drugs
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Conventional Drugs Natural Substances
Acetaminophen, Alpha-methyldopa Vitamins, Hypervitaminosis A
Amiodarone, Dantrolene, Diclofenac Niacin, Cocaine, Mushrooms
Disulfiram, Fluconazole, Glipizide Aflatoxins, Herbal remedies
Glyburide, Isoniazid, Ketaconazole Senecio, crotaliaria,
Labetalol, Lovastatin, Nitrofurantoin Pennyroyal oil, Chapparral,
Thiouracil, Troglitazone, Trazadone Germander, Senna, Herbal mix.
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32. Causes of recurrent J.
Obstructive multiple gall stones ,
ampullary carcinoma,
pseudopancreatic cyst regressing with tt
Hemolytic J.
Liver cirrhosis complicated with sepsis or drugs
Congenitaln hyperbilirubinemia.
Family History :
of similar conditions , hemolytic A, splenectomy ,
cholecystectomy ,,etc
Past History :
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33. PHYSICAL EXAMINATION
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Cachexia ? malignancy
•Colour of jaundice : Lemon yellow , orange
yellow , olive green.
Anaemia hemolysis , cancer or cirrhosis
• Cutaneous manifestations :
• Skin pig & shin ulceration ??? Haem A
• Pigmentation & Clubbing ??? 1ry biliary cirrhosis.
• Scratch marks , Xanthomas in eye lids & palmar creases Chronic cholestasis.
• Malignant nodules & multiple venous thrombosis….cancer head of pancreas.
• Cutaneous features of chronic liver insufficiency in hepatocellular J
• Bruising denotes coagulpathy eiter with hepatocellular or cholestatic J.
• Oedema .
• ASTIGMATA OF CHRONIC LIVER DISEASE.
General Examination:

35. I- Portal Hypertension : collaterals , venous hum , ascites.
2 – Organomegaly :
Jaundice with hepatomegaly
Huge liver Hard liver ……1ry HCC.
Firm …………..Extra hepatic cholestasis.with
palpable GB ( Cancer head of pancreas )
Impalpable GB Calcular Jaundice.
Mild Hepatomegaly :
Intrahepatic cholestasis except in 1ry BC there is also
splenomegaly.
Acute hepatitis.
ABDOMINAL EXAMINATION :
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36. Huge Liver :
Secondaries ……….metastasis in both liver & spleen.
1ry HCC on top of cirrhosis,
Primary biliary cirrhosis,
Moderately ++ liver :
Hepatitis group 20% of viral hepatitis is associated
with splenomegaly.
Hemolytic jaundice.
Jaundice with Hepato-splenomegaly :
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37. Jaudice + Splenomegaly + Lymphadenopathy
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• Young……..Acute
• Old………Chronic
• Tender sternum + huge spleen
+ severe pallor ( CML )
• Mild splenomeg , mild pallor,
non tender sternum ( CLL)
Symmetrical
LN
LEUKAEMIAS
• Soft , Rubbery in young ….HL
• Firm to hard in elder …NHL
Asymmetrical
LN
Lymphomas

38. Palpable GB…… ? Cancer pancreas.
Palpable other masses e.g: cancer stomach , colon ,
rectum,….etc.
3- Other palpable Abdominal masses
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39. INVESTIGATIONS
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40. First Step
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Estimate Serum Bilirubin
Is it less than 1 mg % - Normal
Is it more than 1 mg % - Elevated
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41. Second Step : If SB > 1.0 mg
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Is it unconjugated bilirubin ?
Haemolytic Jaundice
Is it Conjugated Bilirubin ? (> 20%)
Hepatocellular jaundice
Obstructive jaundice
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42. ↑ in Unconjugated Bilirubin
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Hemolytic Jaundice - Uncommon
1. Hemolytic Disorders + Anemia
Inherited – Sphero, SS, G6PD, PK
Acquired – MAHA, PNH
2. Ineffective Erythropoesis –B12, Fe, F
3. Drugs – Rifampicin, Probenecid
4. Inherited –Crigler Najjar, Gilberts
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43. Third Step : If CSB is increased
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Do - AST and ALT (SGOT and SGPT)
Elevated AST and ALT
Hepatocellular jaundice
AKP, 5N, GGT will be normal
Do - Alkaline Phosphatase and GGT
AKP, GGT ↑↑ in Obstructive Jaundice
AST and ALT will be normal
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44. Fourth Step : Hepatocellular
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Hepatocellular – Features and D.D
Conjugated SB is increased
AST and ALT are increased
AKP, 5NS, GGT are normal
Hepititis – A,B,C,D,E, CMV,EBV
Toxic Hepatitis – Drugs, Alcohol
Malignancy – Primary Ca
Cirrhosis – ALD, NAFLD
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45. What imaging we need
 Ultrasonography – 98% Sp, 90% Sen.
 For GB stones USG better than CT
 For duct stones –only 40% seen in USG
 PTC – Extrahepatic obstr. – drainage
 ERCP – Distal biliary obstruction Dx.Rx.
 MRCP – Most useful for duct stones
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46. Acute Cholecystitis
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GB wall is thickened and striated.
Courtesy of Udo Schmiedl, M.D.
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47. Retrograde Cholangiogram - ERCP
Bile leak from the cystic duct after cholecystectomy
Courtesy of Michael Kimmey, M.D.

48. Primary Sclerosing Cholangitis
Normal Extra hepatic BD
Narrowed abnormal
intra-heptic bile ducts.

49. Conclusions
 Jaundice and liver injury are very common
 Careful history and physical examination are a must
 Acute hepatocellular diseases with jaundice
 Chronic hepatocellular jaundice (CLD)
 Cholestasis and obstructive jaundice
 LFT – SB, CB, – AST. ALT, AKP, 5’NS, GGT, Alb, PT
 Ultasonography, MRCP, ERCP, PTC
 Laparoscopy and liver biopsy
 Treatment as per the cause