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| CONTINUING MEDICAL EDUCATION |
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| Year : 1997 | Volume
: 63
| Issue : 5 | Page : 288-295 |
Approach To jaundice (CME)
A Riyaz
Correspondence Address:
A Riyaz
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 20944358 
How to cite this article:
Riyaz A. Approach To jaundice (CME). Indian J Dermatol Venereol Leprol 1997;63:288-95 |
Jaundice can be defined as a condition characterized by yellowish discoloration of sclera, skin and mucous membranes, due to increased circulating bilirubin of more than 2-2.5mg%.[1] It can result from a variety of disorders ranging from benign conditions like physiologic jaundice of newborn and Gilbert's syndrome, to life-threatening conditions like fulminant hepatitis and hepatocellular carcinoma.
The term 'icterus' refers to a bird called golden oriole or Icterus, which has got long beautiful yellowish feathers.[2]
| Etiology of jaundice | |  |
Depending on pathophysiology, there are 3 types of jaundice. (a) Hemolytic (prehepatic)(b) Hepatocellular and,(c) Cholestatic
| Hemolytic jaundice | | |
This is caused by hemolytic anemia or by a familial disturbance of bilirubin metabolism like Gilbert syndrome.
| Hepatocellular jaundice | | |
The major cause of hepatocellular jaundice is viral hepatitis. The past two decades have witnessed an amazing explosion in the knowledge of viral hepatitis. Hepatitis virus A, B, C, D and E are well characterized agents with unequivocal disease associations. The latest additions to the list of hepatotropic viruses are F and GB/G virus. [3,4] Hepatitis C virus (HCV) is the most common cause of post transfusion hepatitis in the world today. It is associated with several dermatological conditions. [5,6]
Exotic viruses like ebola, marburg and lassa fever viruses and mumps, measles, rubella, coxsackie and infectious mononucleosis viruses can also produce jaundice.
Bacterial hepatitis can occur due to typhoid, Brucellosis More Details and disseminated tuberculosis. Spirochaetes (leptospira) and protozoans (plasmodium, toxoplasma and schistosoma) are other causative organisms.
Drugs are notorious to produce hepatocellular jaundice. [7,8] The common ones are dapsone, sulfonamides, tetracyclines, erythromycin, augmentin, cloxacillin, ketoconazole and all antituberculosis drugs except streptomycin. NSAIDS like ibuprofen, naproxen, sulindac and aspirin, retinoids especially etretinate, methotrexate, and paracetamol are other known hepatotoxic drugs.
Other rare causes of hepatocellular jaundice are aflatoxin, poisonous mushrooms (Amanita phalloides), and metabolic diseases like Wilson's disease, alpha-antitrypsin deficiency and cystic fibrosis.
| Cholestatic jaundice | | |
Gallstones, carcinoma of head of pancreas, cholangiosarcoma and choledochal cyst are causes of extrahepatic cholestasis. Intrahepatic cholestasis is mainly caused by virus A hepatitis, primary biliary cirrhosis and drugs like azathioprine, nitrofurantoin and erythromycin.
[TAG:2]Evaluation of a patient with jaundice [9,10][/TAG:2]
In the majority of patients the cause of jaundice can be usually diagnosed by a careful clinical history and a meticulous physical examination, supplemented by relevant laboratory tests.[7]
| History | | |
Fever: Fever without chills is seen in viral hepatitis and drug induced hepatitis. However, if the patient has high fever with chills, bacterial infections should be considered like cholangitis, liver abscess and leptospirosis, in addition to malarial hepatitis.
Pain: Right hypochondrial pain and fever suggest cholangitis, cholecystitis and liver abscess. The tenderness can be extreme in liver abscess.
Anorexia and fatigue: These are early signs of hepatitis. They are due to the production of cachexin or tumour necrosis factor alpha. This is a catabolic cytokine produced by macrophages and T-cells, in response to infections or neoplasms. Chronic hypoglycemia may also lead to anorexia and fatigue in glycogen storage disease, and hereditary fructose intolerance in children.
Jaundice: If in a jaundiced patient, the urine is of normal colour, he most probably has haemolytic jaundice. If the urine is high colored, it could be either hepatocellular or cholestatic jaundice. Normal stool in such a patient indicates hepatocellular jaundice and pale stool cholestatic jaundice.
Pruritus: It develops in cholestatic jaundice eg: virus A hepatitis, carcinoma pancreas, gall stones etc. It is due to bile salts getting deposited in the skin and irritating the itch receptors. However the latest theory of pruritus of cholestasis is that it is due to increased opiodergic tone, and hence I.V. naloxone or oral nalmofen may be very useful in relieving the pruritus.[8]
Upper GI bleed: is suggestive of ruptured oesophageal varices due to portal hypertension.
Risk factors of viral hepatitis: These include contact with jaundiced patients (Hep. A and E); injection with unsterile needles, dental extraction, blood tests, tuberculin testing, and blood transfusion.
Drug history: especially antituberculosis antileprosy and antipsychotic drugs may give a clue about the cause of jaundice.
Family history: History of any sibling death due to jaundice or neuropsychiatric illness in the family (Wilson's disease), may help in arriving at an aetologic diagnosis of jaundice.
| Clinical features | | |
Pallor is seen in hemolytic anemia and cirrhosis. The colour of the eyes gives a clue to the type of jaundice. Lemon-yellow colour denotes hemolytic jaundice whereas orange colour is a feature of hepatocellular jaundice and greenish-yellow of cholestatic jaundice. Fetor hepaticus and flapping tremor indicate hepatocellular failure.
The presence of subconjunctival hemorrhage suggests Weil's disease. KF rings and sunflower cataract are features of Wilson's disease. Signs of vitamin A deficiency like xerosis and Bitot spots are seen in prolonged cholestatic jaundice. Chorioretinitis is a feature of TORCH infections.
Nail changes like clubbing, leuconychia, Terry's nails (proximal 80% opaque and distal 20% normal) and Muehrcke's lines (Parallel white lines) are seen in cirrhosis. Blue lunulae are characteristic of Wilson's disease. Polished nails are seen in cholestatic jaundice. Hepatitis C is associated with essential mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus.[5] It has been suggested that patients with chronic lichen planus should be screened for HCV induced chronic active hepatitis. Just as alcohol and estrogens can precipitate PCT, the HCV can decrease the activity of uroporphyrinogen decarboxylase in the liver.[8]
The skin changes described in cirrhosis are acne, spider nevi, palmar erythema (Dawson palms) and telangiectasia. Xanthomas and scratch marks are seen in cholestatic jaundice.
Ecchymoses are seen in hepatocellular failure and diffuse pigmentation in Wilson's disease.
| Work up of a patient with jaundice | | |
| I. Urine tests | | |
1) Foam test: When normal urine is shaken vigorously in a test tube, we get a white unstable froath or foam. If the patient has hepatocellular or cholestatic jaundice, we get stable yellow froath; the stability is due to bile salts and the yellow color due to bilirubin. The bubbles will remain intact for a long time. This is a very simple test which can be performed in the consultation room itself, when one suspects hepatitis.
2) Bile pigment (Bilirubin)
Bilirubinuria is the earliest abnormality in hepatitis. It is present even when the serum bilirubin is normal. Hence bilirubinuria in a febrile patient is diagnostic of hepatitis. It is demonstrated by the modified Fouchet's test (Harrison's spot test). Late in the course of the disease, when deltabilirubin is formed, the test becomes negative, eventhough the patient continues to be icteric.
3) Urobilinogen
Urobilinogen appears in the urine in the late preicteric phase of hepatitis, after bilirubinuria. At the height of the jaundice, the hepatocytes cannot excrete bilirubin into the bile and hence urobilinogen disappears from the urine.'Its reappearance in the urine indicates that the patient is recovering. Urobilinogen is demonstrated using the Ehrlich's aldehyde test.
| Significance of urobilinogenuria and bilirubinuria | | |
- 1) Hemolytic jaundice- urobilinogen (UBG) positive; bile pigment (BP) negative
- 2) Hepatocellular jaundice- UBG positive; BP positive
- 3) Cholestatic jaundice- UBG negative; BP positive
Normal excretion of UBGis 1-4 mg/24hr. It is decreased in cholestatic jaundice, diarrhoea, and prolonged antibiotic therapy, which destroys the bacteria that convert bilirubin to UBG. It is increased in hemolytic jaundice and constipation.
| II. Hematological tests in jaundice | | |
Leucopenia is seen in viral hepatitis. In Weil's disease and cholangitis, there is leucocytosis with a striking neutrophilia and very high ESR. ESR is only minimally increased in viral hepatitis.
Peripheral smear examination may show large atypical lymphocytes (virocytes) in viral hepatitis. In chronic liver disease, spur cells or burr cells may be seen and in cholestatic jaundice target cells. If hemolytic jaundice is suspected, peripheral smear for evidence of hemolysis, reticulocyte count, fragility test, Coomb's test etc are indicated.
| III. Liver function tests | | |
1) Serum bilirubin
This confirms jaundice, indicates its depth and is used to know the progress. If the conjugated fraction is more than 50% of the total patient has conjugated hyperbilirubinemia; if the unconjugated fraction is more than 90%, the patient has unconjugated hyperbilirubinemia.
2) Transaminases
The two enzymes which are sensitive indicators of parenchymal cell integrity are : a) aspartate aminotransferase (AST or SGOT) b) alanine aminotransferase (ALT or SGPT). SGOT is a mitochondrial enzyme present not only in liver, but also in the heart, skeletal muscle and kidney. Hence, whenever these are acutely destroyed, serum SGOT will be increased. The SGPT is a cytosolic enzyme seen mainly in hepatocytes. Hence an increased SGPT is more specific for liver disease than SGOT. SGOT is more specific for chronic liver disease and SGPT for acute liver disease. In acute hepatitis, the transaminases are 10 times above normal. In cholestatic jaundice, they are about 5 times above normal. Very high levels may be seen in drug-induced hepatitis, especially paracetamol.
In chronic hepatitis, the levels are around 5 times above normal. A mild, long-standing elevation of SGOT may be observed in the presymptomatic phase of Wilson's disease. Fluctuating levels of transminases may be seen in hepatitis C infection (Yo-Yo phenomenon). A sudden fall in the transaminases in a sick jaundiced patient is indicative of a bad prognosis, as it is seen in acute fulminant hepatitis. An unexpectedly elevated aminotransferase may be seen in obesity, diabetes mellitus, hepatic drug reaction, alpha1 anti-trypsin deficiency and hepatitis C infection.
In anicteric hepatitis and inapparent hepatitis, the only biochemical abnormality may be an elevated SGOT or SGPT, which may be useful in epidemiological screening studies.
| 3. Alkaline phosphatase (AP) | | |
| Normal levels | | |
Three to 13 King-Armstrong units/l00ml or upto 100 IU/litre.
In cholestatic jaundice, AP is raised 3 times more above normal and in hepatitis less than 3 times. Hence it is a sensitive indicator of cholestasis but not of hepatitis.
Cholestasis induces the secretion of alkaline phosphatase, which enters the plasma directly. The levels are higher in extrahepatic cholestasis (eg. biliary atresia) than in intrahepatic cholestasis (eg. virus A hepatitis).
The extrahepatic sources of AP are bone, intestine and placenta. Hence in children, serum AP may be upto 25 KAUs due to bone growth. It is also increased in rickets, osteomalacia and secondary deposits in bone.
| GGT (Gamma Glutamyl transpeptidase) | | |
This is the most sensitive test for the presence of hepatobiliary disease. It is always elevated in established, or even in incipient, liver disease. It is increased equally in both hepatocellular jaundice and cholestatic jaun- dice. An elevated S.GGT helps to confirm that a raised serum alkaline phosphatase is of hepato-biliary origin.
| Proteins | | |
The hepatocytes manufacture a number of proteins which are released into the plasma. These include albumin, fibrinogen, alpha-antitrypsin, haptoglobin, ceruloplasmin, transferrin and prothrombin. Hence reduced levels of these reflect a decline in the synthetic capacity of the liver. Of these, ceruloplasmin, fibrinogen, alpha, antitrypsin and haptoglobin are acute phase reactants. Their serum levels may be raised when the patient has 'acute hepatitis or chronic hepatitis.
The normal serum albumin is about 3.5 to 5gm%. The normal liver produces about l0gm albumin daily, whereas a cirrhotic liver can produce only about 4gm. In liver disease, the fall in serum albumin concentration is slow, as the half-life of albumin is about 22 days. Thus a patient with fulminant hepatitis may die with a virtually normal serum albumin value, while a patient with a decompensated cirrhosis will have a low serum albumin.
The gamma globulin level is increased in cirrhosis due to increased production by plasma cells in the bone marrow and liver.
A low serum albumin is seen in many non hepatic disorders like nephrotic syndrome, PEM and protein losing enteropathy. Nevertheless, hypoalbuminemia is an excellent indicator of the severity of chronic liver disease.
| IV. Prothrombin time | | |
The liver synthesizes all the clotting factors, and requires vitamin K to activate factors II, VII, IX and X. Reduced plasma concentration of coagulation factors occurs in liver damage, which is easily recognized by prolongation of prothrombin time, which depends on factors I, II, V, VII and X.
These factors are reduced in severe liver damage and in cholestasis, which reduces vitamin K absorption. Thus a prolonged prothrombin time may be seen in hepatocellular jaundice and in cholestatic jaundice. If the prothrombin time becomes normal after vitamin K injection, patient has cholestatic jaundice, while in severe hepatocellular jaundice, the prothrombin time remains prolonged.
| V. Serological tests | | |
Virus A hepatitis is diagnosed by an elevated IgM anti-HAV. The best serological test to diagnose acute virus B hepatitis is IgM anti core antibody, since HBs Ag will be positive in asymptomatic carriers also. To diagnose virus Chepatitis, recombinant immunoblot assay II or RIBA-II is used to detect antibodies against C 100-3, 5-1-1, C22 or C33C antigens, IgM anti delta and IgM anti-HEV help to diagnose VDH and VEH respectively.
| VI. Radiology | | |
1) Plain abdominal radiograph
About 20% of gall stones may be detected by this.
2) Cholecystography
It is useful in detecting gall stones; but has been replaced by ultrasound. In Dubin Johnson syndrome, the gall bladder is not opacified.
3) EndoscopicRetrograde Cholangiography and percutaneous transhepatic cholangiography may be helpful in diagnosing cholestatic jaundice.
[TAG.2]VII. Imageology[/TAG.2]
1) Ultrasonography
This is the most important non-invasive investigation in the evaluation of cholestatic jaundice like gall stones and choledochal cysts. It detects gall stones upto 5mm in diameter accurately. It also detects focal liver diseases like tumours, abscesses and cysts, provided they are more than 2cm in diameter. It can identify generalized parenchymal disorders like cirrhosis and fatty change. It is also of great help in diagnosing portal hypertension.
2) Computed tomography
This will detect space occupying lesions like tumours, cysts, abscesses, as well as fatty liver. This will also help to identify the cause of cholestasis, as in lymph nodes compressing porta.
3) Cholescintigraphy
This is a very useful test to diagnose biliary atresia. The isotope used is 99m Tc-labelled mebrefenin. Even 24 hours after injecting the isotope IV, it cannot be detected in the intestine.
[TAG.2]VIII. Liver biopsy[/TAG.2]
Liver biopsy using Menghini needle, is a relatively safe procedure. As the morphologic features of specific liver disease are distinctive, liver biopsy enables us to make an etiologic diagnosis. Thus it helps to diagnose chronic hepatitis, cirrhosis, neonatal cholestasis, hepatic firbrosis etc. Peroxidase positive diastase resistant granules in the periportal hepatocytes are suggestive of alpha1-antitrypsin deficiency. The normal liver copper is 55 μg/g of dry liver tissue and is very high in Wilson's disease. The commonly used copperstains are rubeanic acid, rhodanine or orcein. Modified orcein technique is useful to demonstrate hepatocytes containing HBsAg (Shikata cells).
In Dubin-Johnson syndrome, the macroscopic liver tissue is hyperpigmented, and microscopy shows deposition of lipofuscin and melanin (black liver jaundice). Liver biopsy helps to diagnose inborn errors of metabolism like galactosemia, by quantitating the enzyme content of the liver.
[TAG.2]Management of hepatitis[/TAG.2]
1) Bed rest is important to prevent the chance of fulminant hepatitis.
2) Diet
Generally, no dietary restriction is needed. Patient should be allowed to take the diet he tolerates. Vitamin supplements are not necessary, except vitamin K, if the prothrombin time is prolonged.
3) Control of fever
It is better to avoid antipyretics like paracetamol, which are hepatotoxic, Hydrotherapy, i.e. sponging the whole body with warm water is the best way to control fever.
4) Control of vomiting
It is better to avoid antiemetics which are hepatotoxic. Persistent vomiting is a bad sign as the patient may develop fulminant hepatitis. Such patients must be hospitalised and given IV fluids.
5) Drugs
Corticosteroids and antiviral drugs (ribavirin, interferon, Phyllanthus amarus) have no established benefits in acute viral hepatitis.
| References | | |
| 1. | Isselbacher KJ, Kaplan LM. Jaundice, In: Harrison's Principles of Internal Medicine, Vol.1, 14th Ed, Edited by Fauci AS, Braunwald E, Isselbacher KJ, Mr Graw Hill, New York, 1998;249-255.  |
| 2. | Schaffner F. Jaundice, In: Bockus-Gastroenterology, Vol. 3, 5th Ed, Edited by Haubrich WS, Schaffner F, Berk JE, WB Saunders Co., Philadelphia, 1993;129-137. |
| 3. | Simon JN, Mathias TJ, Leary TP, et al. Identification of two flavi virus-like genomes in the GB hepatitis agent. Proc Natl Acad Sci 1995;92:3401-3405. |
| 4. | Linnen J, wages J Jr, Zhangkech ZY, et al. Molecular cloning and disease association of hepatitis G virus: A transfusion transmissible agent. Science 1996;271:505-508. |
| 5. | Pawlotsky JM, Dhumeaux D, Bagot M. Hepatitis C virus in Dermatology. Arch Dermatol. 1995;131:1185. |
| 6. | Cribier B, Petiau P, Keller F, et al. Porphyria cutanea tarda and hepatitis C viral infection : A clinical and virologic study. Arch Dermatol. 1995;131:801-804. |
| 7. | Finraycon NDC. Drugs and the liver. Med Int, 1994;6:455-459. |
| 8. | Lee WM. Drug-induced hepatotoxicity N Eng J Med 1995;1118-1125. |
| 9. | Schiff L. Jaundice-A clinical approach, In : Disease of Liver, Vol 1, 7th Ed, Edited by Schiff L, Schiff ER, JB Lippincott Co., Philadelphia, 1993;334-361. |
| 10. | Mc Intyre N. Symptoms and signs of liver disease, In : Oxford Text Book of Clinical Hepatology, 1st Ed, Edited by Mclntyre N, Benhamou JP, Bircher J, et al. Oxford University Press, Oxford, 1991;273-290. |
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