Jaundice: Diagnostic

Approach & Problem

Zelalem M.
Definition:
Jaundice or icterus,
Yellowish discoloration:
♦skin, mucous membranes, sclera.
♦excess plasma Bilirubin
Normal range : 5-17 m mol/l
Clinically obvious : 50 m mol/l

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 Classification
Classical: 1.Hemolytic
2.Hepatocellular
3.Obstructive
Bilirubin: 1.Conjugated
2.Unconjugated
1.Cholestatice (Obstructive): Intrahepatic
Extrahepatic
2.Noncholestatic
1.Medical
2.Surgical
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 No satisfactory classification
Soundest Approach:-

► Bilirubin Metabolism

► The stages that may be disturbed by

disease

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 Bilirubin Metabolism
NL Serum [ ] - <1mg/dl
< 5% - Conjugated

1. Formation:- R-E System

-Breakdown of Heme in Hgb.(80%):
-Heme oxygenase
-Biliverdine reductase
2. Transport:- Blood

-Bound to albumin
-Keeps it in vascular space
3.Uptake:- Hepatocytes : Sinusoidal membrane

-Facilitated diffusion( passive)

-[ ] Gradient ► bilateral

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4.Storage:-
♦Binding to GSTs:- ↓es efflux
- ↑ing Net uptake
5.Conjugation:-
♦Enzyme-catalyzed glucuronidation
♦Water soluble by B-UGT-1
♦B-Diglucuronide
6.Excretion:- Hepatocytes: Canalicular membrane
♦Into Bile
♦Against [ ] gradient (active)
♦cMOAT

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7.Degradiation : GIT:-
98% Conjugated
Lipid membrane of small intestinal epithm.
Most cant be reabsorbed
In Colon:-
Reduction → Urobilinogens
Most excreted in feaces
Enterohepatic circulation
 2% of unconjugated
urobilinogens

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I. R-E-S: Production
↓
II. BLOOD: Transport
↓
III. LIVER CELLS : Uptake & Conjugation
↓
IV. LIVER CELLS : Excretion into bile
↓
V. BILE DUCTS : Excretion into intestine
↓
INTESTINE
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Depending on the stages it may be disturbed:-
I. Excessive production (hemolytic jaundice):-
A. Inherited hemolytic anemia's
B.Acquired hemolytic anemia's
1.Hemolytic anemia's
2.Sepsis
3.Hemolysins
4.Absorption of sequestered blood
5.Burns
6.Mismatched or massive blood
transfusions
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II. Impaired transport to liver:-
-Gilbert’s syndrome( some forms)
III. Impaired hepatic conjugation:-
A. Inborn errors
1.Crigler- Najar syndrome
2.Gilbert syndrome
B. Immaturity of enzymes
1.Physiologic jaundice of newborn
2.Jaundice of prematurity

Unconjugated Hyperbilirubinemia
Retention Jaundice
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IV. Impaired excretion(hepatocellular jaundice)
A. Acquired liver diseases
1.Hepatitis
2.Cirrhocis
3.Neoplasms,etc
B.Intrahepatic cholestasis
1.Drug induced
2.Disease related
3.Idiopatic
C.Dubin-Jonson & Rotor syndrome
 Regurgitation jaundice
.  Direct & Indirect Bilirubinemia

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V. Bile duct obstruction(obstructive
jaundi)
A. Extra hepatic:-
1.Stone
2.Neoplasms
3.Stricture
4.Atresia,ect
B. Intrahepatic

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 Approach to the jaundiced pt.
With Hx ,P/E & LFT ≈ 85% ► Accurate Dx
History:
 Rapidity of onset & course of jaundice
 Color of urine & stools
 Wight loss
 Abdominal pain
 Digestive symptoms
 Malaise
 Anorexia
 Occupation
 Travel
 Jaundice in family or contact
 Exposure to hepatotoxines
 Alcohol consumption
 Ingestion of drugs
 Transfusions
 Injections
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 Previous operations 15
Physical exam:-

Nutritional status
Scleral icterus
Virchoff's nodes
The abdominal exam should focus on :-

Size and consistency of liver

Whether the spleen is enlarged
Whether there is Ascites
Grossly enlarged nodular liver/abdominal mass---
malignancy
Bruit heard over the liver ---- hepatoma
Large, tender liver with rounded edge --- viral/alcoholic
hepatitis
Murphy's sign --- A. cholecystitis
Courvoisier's gall bladder--- malignant obstruction
Blood on DRE---malignancy
Stigmas of CLD
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Screening ( Initial ) Lab. Testes:-
Non invasive
Efficacy of Rx. & Progression of Disease
Clue about OBSTRUCTIVE or HEPATOCELLULAR
 Next modality of investigation !
Liver Function Tests (LFT):-
1.Hepatocyte injury : Aminotransferases ,AST ,ALT
2.Biosynthetic capacity : Albumin , PT
3.Altered Immunoregulation : Specific Auto Abs.
.Acute or Chronic inflmn : Serology( hepatitis), Serum Img
4.Metabolizing & Excreting capacity: Bilirubin
Reserve Capacity:
-Max. daily Excn. ≈ 55mg/kg  >10x Avg daily Production
 Can remove >2x nl daily B. load ► No Hyperbilirubinemia
 Severity
Fractionation :

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 Imaging
Modality of choice of investigation if:-
1.Hitory
2.Physical Examination &
3.Innitial Lab studies , suggest :
Obstruction of the Biliary Tree : Intrahepatic
Extrahepatic
US
CT
ERCP
PTC
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Ultrasound:
1st line
Dilatation , S – 85-96%
GB stone – Extreme, CBD – 60% maybe
missed
Cause of obstruction;
Anatomic level of Dilatation:-
1. Intra & Extahepatic ducts → distal CBD
Distal obstruction :- CBD stone
- Ca. head of
pancreas
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 2.Proximal ,esp. intrahepatic ducts,
Proximal obstruction :-
- Hilar cholangioca. (Klatskin
tumor)
- Mirizzi syndrome
- Metastatic LAP
3.Dilated CBD only:-
-Previous surgery
-Fluctuating Jaundice  CBD stone
-Co-existing cirrhosis
4. No biliary dilatation
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Computed Tomography (CT):
Site & Nature ( cause ) of obstruction
Asses Resectability

C/Fs + US &/or CT → No obstruction ,

 A logical stopping point
C/Fs. + US / CT → Biliary obstruction
 Direct visualization Biliary
Tree
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Endoscopic Retrograde Cholangiography (ERCP)
Dx. Obstruction , 99% s & s
Site & Nature (Cause) , 90% of pts.
Distal Biliary Obstruction:
- CBD stone
- Ampulary or Duodenal lesions in Panc. Ca.
- Post cholecystectomy jaundice
-PSC
Therapeutic interventions:
-Removal of stones
-Sphincterectomy
-Stenting : palliative or temporary
-Dilatation of strictures
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-Placement of biliary drainage 25
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Percutaneous Transhepatic
Cholangiography(PTC)
Proximal obstruction
►Proximal extent
►Drainage of intrahepatic ducts
Ascites , coagulopathy

MRCP & other studies

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Criterion ERCP PTC
Success rate 80-90% 80-90%
Mortality 0.20% 0.20%
Conditions for
use skilled personnel skilled personnel

distal lesion proximal lesion

ascites or abnormal
coagulopathy anatomy

failed PTC failed ERCP

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 If ERCP/PTC  -V Study
Endpoint in work-up of obstruction in
jaundiced pt.

Liver Biopsy
Cholestasis :  Hepatocellular
 Obstructive
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 References:-
1. N Assy et al,Diagnostic approach to patients with
Cholestasis jaundice,WJG,1999 June;5(3):252-62
2. A Blakeborough et al Investigation & Management of
Obstructive Jaundice,Surgery,2003; 105-112
3. R.C.G. Russell The gallbladder ,bile ducts& Pancreas
,Bailey & Love’s;
4. Josef E et al ;Manifestations of GI Disease; Schwartz
Principles of Surgery; 7th edn. 1999; 1067-1073

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