Diagnostic Approach To Jaundice. By Dr. Mohamed M. Mohy Eldin Awad Professor of Internal Medicine Suez Canal University. Bilirubin Metabolism Bilirubin breakdown of mature RBCs in the RES. 15% of bilirubin comes from the catabolism of other haem-containing proteins, such as myoglobin.
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Dr. Mohamed M. Mohy Eldin Awad
Professor of Internal Medicine
Suez Canal University
1- Increased bilirubin load as in haemolysis.
2- Disturbance in the hepatic uptake & transport
of bilirubin within the hepatocytes
3- Defects in conjugation.
4- Defects in the excretion of conjugated
bilirubin across the canalicular cell
membrane or an obstruction of the large
Inability of the hepatocytes to take up bilirubin from the blood e.g. Gilbert & Crigler-Najjar syndromes.
By (for example) biliary calculi causes backup and reabsorption of conjugated bilirubin.
Blood levels of conjugated bilirubin increase.
1- Isolated elevation of s. bilirubin: when AST,
ALT & ALP levels are normal.
2- Hepatocellular jaundice: when the AST & ALT
levels are elevated out of proportion to the ALP
3- Cholestatic jaundice: when the ALP level is
elevated out of proportion to the AST & ALT
* Increase bil. production (e.g. haemolysis,
* Decrease hepatocellular uptake (e.g. rifampcin)
* Decrease conjugation (Gilbert S, Crig. Nagar S)
* Dubin-Junson syndrome
* Roter syndrome
Acute or subacute hepatocellular injury
Viral hepatitis, alcohol, drugs, ischemic hepatitis, Wilson's disease, acute fatty liver of pregnancy
Chronic hepatocellular Disease:
Viral hepatitis, alcoholic, autoimmune hepatitis, Wilson dis., Haemochromatosis, NASH, alpha 1 antitrypsin deficiency.
Hepatic disorders with prominent cholestasis.
* Diffuse infiltrative disorders (e.g. granulomat dise. as TB, sarcoidosis, lymphoma, drugs) Amyloidosis, malignancy.
* Inflammation of intrahepatic bile ductules (PBC), GVHD, Drugs (chloropromazine)
* Miscellaneous e.g. use of oestrogen & steroids, TPN, bact. Infection.
Choledocholithiasis, 1ry SC, AIDS, pancreatitis
Carcinoma gallbladder, periampullary carcinoma, cholangiocarcinoma, Cancer head of pancreas
Isolated elevation Unconjugated * Bil. production (e.g. haemolysis, resorption
of serum Bilirubin Hyperbilirubinaemia of haematoma)
* Hepatocellular uptake (e.g. rifampcin)
* conjugation (e.g. Gilbert S, Crig. Nagar S)
Conjugated * Dubin-Junson sundrome
Hyperbilirubinemia * Roter syndrom
Hepatocellular Acute or subacute Viral hepatitis, alcohol, drugs, ischemic hepatiti
Jaundice hepatocellular injury Wilsons disease, acute fatty liver of pregnancy
Chronic hepatocellu Viral hepatitis, alcoholic, autoimmune hepatitis
disease. Haemochromatosis, Wilson dis., NASH, alpha
1 antitrypsin deficiency.
Hepatic disorders * Diffuse infiltrative disorders (e.g. granulomat
with prominent dise. As TB, sarcoidosis, lymphoma, drugs)
cholestasis. Amyloidosis, malignancy.
* Inflammation of intrahepatic bile ductules
(PBC), GVHD, Drugs (chloropromazine)
* Miscellaneous e.g. use of oestrogen &
steroids, TPN, bact. Infection.
Obstruction of Benign Choledocholithiasis, 1ry SC, AIDS, pancreatitis
The bile duct
Malignant Carcinoma gallblader, periampullary carcinoma
cholangiocarcinoma, Cancer head of pancreas
-Stigmata of CLD J. is hepatocellular in origin.
-High fever, right upper abd. tenderness cholangitis & choledocholithiasis.
-Palpable abdominal mass Malignant obstructive J.
-Rt. upper abd. scar or palpable gallbladder Obst. J.
-Certain physical findings may suggest a particular liver disease:
*Kayser-Fleischer rings Wilson disease.
-Hard nodular liver 1ry or 2ry malignancy.
-Diffuse lymphadenopathy infectious mononucleosis or lymphoma.
*Serum Biochemical Tests:
-The normal serum bilirubin is <1.5mg/dl of which
<0.5% is conjugated.
-In haemolysis or genetic disorders e.g. Gilbert synd., there is unconjugated hyperbilirubinaemia (>90%).
-In hepatocellular j. >50% of bilirubin is conjugated.
-In obstructive j., the circulating bilirubin is mainly conj.
* The degree of elevation of s. bil., correlates poorly with clinical severity.
* Unconjugated bil is not excreted in the urine & thus in unconjugated hyperbilirubinaemia, bil. is absent in urine.
Enzymes raised in hepatocellular injury:
Aminotransferases include ALT (located in cytosol) & AST (located in mitochondria & cytosol).
ALT is found mainly in liver while AST is also found in other tissues such as skeletal & cardiac muscle.
ALT is more specific than AST in detecting liver dise.
AST & ALT are released following hepatocyte necrosis.
A marked raise in transaminases > 1000 U/L, is seen in AVH, ischaemic hepatitis & drug-induced liver disease.
In alcoholic liver disease, the enzyme levels are rarely
> 200-300 U/L, with AST:ALT ratio >2:1.
Alkaline Phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) & 5’-nucleotidase (5’NT).
ALP isoenzymes are also present in bone & placenta.
Increase in ALP, GGT & 5’NT hepatobiliary origin.
GGT levels are often disproportionately elevated in alcoholic liver disease.
Albumen is synthesized by liver & has a half-life of 15-20 days.
Decreased level of albumen are seen in advanced hepatic cirrhosis & signify severe hepatic dysfunction.
S. albumen usually remain normal in acute hepatitis; falling values in this setting imply an unusual sever course
Non-specific diffuse elevation is common in CLD.
There is a disproportionate elevation of IgG in autoimmune hepatitis, IgM in PBC & IgA in alcoholic liver disease.
INR/PT is a valuable index of the ability of liver to synthesize vit. K-dependent clotting factors.
An increasing INR/PT implies relatively severe hepatocellular dysfunction.
The INR/PT may be deranged in cholestasis as well, but this is due to the malabsorption of vit. K & is rapidly corrected by parenteral administration of vit K.
-Serological/replicative markers for specific diagnosis of acute or chronic viral hepatitis.
-Antimitochondrial antibody (AMA) for PBC; antinuclear factor (ANA), anti-smooth muscle antibody (ASMA) & anti-liver kidney microsome (LKM) antibody seen in autoimmune hepatitis; alpha-fetoprotien, which is raised in HCC & s. caeruloplasmin for Wilson disease.
Radiological imaging is important for the diagnosis of a focal liver mass or biliary disease. However, imaging plays little role in the evaluation of diffuse hepatocellular e.g. hepatitis
It is a valuable but operator-dependent investigation.
It has sensitivity of 55-91% & specificity of 82-95% for biliary obstruction.
Although US may not detect stones in the extrahepatic bile duct, which may be obscured by overlying gas, it reliably establishes the presence of a dilated bile ducts
Beside it can differentiate intrahepatic from extrahepatic cholestasis, US can also detect the associated abnormalities such as portal hypertension, focal lesions & fatty liver.
CT has a sensitivity of 63-96% & a specificity of 93-100% to detect biliary obstruction.
Non-calcified cholestrol gall stones can be easily missed on CT because they may be isodense with bile.
ERCP not only permits direct visualization of the biliary tree but also allows therapeutic intervention e.g. removal of CBD stones or biliary stenting. It is the gold standard test for the evaluation of extrahepatic biliary disease causing jaundice.
IN PTC, direct contrast visualization of the biliary tree is obtained via a percutaneous needle puncture of the liver. It is useful if there is high biliary obstruction e.g. a tumour at the bifurcation of the hepatic ducts.
It also permits therapeutic intervention such as stent insertion to bypass a ductal malignancy.
MRCP is superior to US & CT in detecting biliary obstruction. It has a sensitivity of 82-100% & a specificity of 92-98% to detect biliary obstruction.
It has relatively low risk, it is needed in only a minority of cases with hepatic dysfunction.
Major indications include chronic hepatitis, cirrhosis, unexplained liver enzyme abnormalities, hepatosplenomegaly of unknown aetiology, suspected infiltrative disorder, suspected granulomatous disease.
Relative contraindications include a tendency for clinical bleeding, INR>1.5 or PT >3 sec above the control, severe thrombocytopenia & marked ascites.
The risk of fatal haemorrhage in patients undergoing LB is 0.4% if they have a malignancy & 0.04% if they have non-malignant disease.