APPROACH TO JAUNDICE

Dr. G. RAJKOTI REDDY DNB MEDICINE RESIDENT.

1. Entomology2. Definitions3. Biochemistry4. Pathophysiology5. History taking6. Clinical examination7. Investigations8. Case

Entomology:.

Definitions:Jaundice, or icterus, is a yellowish discoloration of tissue resulting from the deposition of bilirubin.

Hyperbilirubinemia, a blood level that exceeds1 mg of bilirubin per dL (17 μmol/L),when the blood concentration reaches 2 to 2.5 mg of bilirubin per dL, it diffuses into the tissues, which turn yellow, a condition termed jaundice or icterus.

Definitions Not all jaundice are yellow (icterus).

Huffman, Christopher et al. The American Journal of Medicine , Volume 122 , Issue 9 , 820 - 822

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Definitions Yellow discoloration of skin not always jaundice. carotenoderma is the yellow color imparted to the skin of healthy individuals who ingest excessive amounts of vegetables and fruits that contain carotene, such as carrots, leafy vegetables, squash, peaches, and oranges.carotenoderma the pigment is concentrated on the palms, soles, forehead, and nasolabial folds. sparing of the sclerae.

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DefinitionsThyroid hormones are necessary for hepatic conversion of carotene to vitamin A, and the accumulation of carotene in the bloodstream (carotenemia) in hypothyroidism is responsible for the yellowish tint of the skin.

quinacrine (anti protozoal, anti rheumatoid, intrapleural sclerosing agent) and excessive exposure to phenols can cause yellow discoloration of skin.

DefinitionsBile is made up of the bile acids, bile pigments, and other substances dissolved in an alkaline electrolyte solution that resembles pancreatic juice.

The glucuronides of the bile pigments, bilirubin and biliverdin, are responsible for the golden yellow color of bile.

Biochemistry

. methylene bridge

Biochemistrymacrophage

liver.UDP-glucuronosyltransferase

bound to albumin

• physiologic jaundice of the newborn,• Gilbert’s syndrome,• Crigler-Najjar syndrome 1&2

Biochemistry

mutation gene encoding Multi Resistant Protein 2• Dubin – Johnson s yndrome• Rotor syndrome

Biochemistryphysiologic jaundice of the newborn, which results from delayed developmental expression of B-UGT and generally resolves rapidly in the neonatal period.

Gilbert’s syndrome typically present when isolated hyperbilirubinemia is detected as an incidental finding on routine multiphasic biochemical screening, and clinical jaundice is uncommon. Serum bilirubin levels may rise 2- to 3-fold with fasting or dehydration but are generally below 4 mg/dL.

Continue..In type I CriglerNajjar syndrome, B-UGT activity is absent, and marked unconjugated hyperbilirubinemia is evident shortly after birth. Because unconjugated bilirubin can cross the bloodbrain barrier, patients with type I Crigler-Najjar syndrome accumulate bilirubin in the brain (kernicterus), and the resulting neurotoxic effects can lead to death in the neonatal period.Phototherapy is required to prevent kernicterus, and liver transplantation can be lifesaving.

Continue..type II Crigler-Najjar syndrome have reduced (but not absent) B-UGT activity, and serum bilirubin levels are lower than in patients with type I Crigler-Najjar syndrome. Patients with type II Crigler-Najjar syndrome are not ill during the neonatal period and may not be diagnosed until early childhood.Most patients with type II Crigler-Najjar syndrome can be treated successfully with phenobarbital.

Continue...B-UGT is inhibited competitively by the retroviral protease inhibitors atazanavir and indinavir, which produce hyperbilirubinemia in more than 25% of patients who receive these agents; patients with Gilbert’s syndrome are at higher risk for this complication.Two autosomally inherited disorders, Dubin-Johnson syndrome and Rotor’s syndrome, are associated with conjugated or mixed hyperbilirubinemia.

Continue..Dubin-Johnson syndrome, an absence of expression or altered trafficking of MRP2 impairs secretion of conjugated bilirubin into the bile canaliculus.Combined deficiency of OATP1B1 and OATP1B3 results in Rotor’s syndrome and impaired re-uptake of conjugated bilirubin.

Biochemistry

dipyrrylmethene azopigments that absorb maximally at 540nm

Continue..The delta fraction (delta bilirubin) is formed in serum when hepatic excretion of bilirubin glucuronides is impaired and the glucuronides accumulate in serum. By virtue of its tight binding to albumin, the clearance rate of delta bilirubin from serum approximates the half-life of albumin (12–14 days) rather than the short half-life of bilirubin (about 4 h).

Continue..Conjugated bilirubin is filtered at the glomerulus, and the majority is reabsorbed by the proximal tubules; a small fraction is excreted in the urine. Any bilirubin found in the urine is conjugated bilirubin. The presence of bilirubinuria implies the presence of liver disease. A urine dipstick test (Ictotest) gives the same information as fractionation of the serum bilirubin and is very accurate.

Pathophysiology

β-glucuronidases

PathophysiologyHyperbilirubinemia may be due to ① excess production of bilirubin ② decreased uptake of bilirubin into hepatic

cells ③ disturbed intracellular protein binding or

conjugation ④ disturbed secretion of conjugated bilirubin

into the bile canaliculi, ⑤ intrahepatic or extrahepatic bile duct

obstruction.

un conjugated raised

conjugated raised

isolated or ± with elevated LFT

Approach to patient Yellow discoloration of skin. Under natural light. Sclera, high elastic tissue, high affinity for

bilirubin. Involvement of palms and soles, sclera sparing

suggestive of carorenoderma. Involvement of scleral serum bilirubin least

3mg/dl

Continue.. A careful history and physical examination with

routine biochemical and haematological tests is essential.

The place of special tests such as ultrasound, liver biopsy and cholangiography will depend on the category of jaundice.

HistoryOnset - Cholestatic jaundice may develop slowly with an antecedent history of pruritus for months or years.

Pyrexia with rigors strongly suggests cholangitis associated with gallstones or biliary stricture

HistoryAssociated dyspepsia and intolerance of dietary fat support a diagnosis of choledocholithiasis.

Nausea, anorexia and an aversion to smoking (in smokers) which have preceded the onset of jaundice by a few days suggest viral hepatitis or drug jaundice.

HistoryPersistent central back pain which causes the patient to lean forward usually indicates pancreatic carcinoma.

Progressive weight loss favours an underlying carcinoma or a marked chronic pancreatitis.

Jaundice occurring in seriously ill hospitalized patients is often caused by sepsis and/or shock, or drug

Historyprevious drug treatment co - amoxiclavulanic acid may precede onset of

jaundice by several weeks. Cholestatic jaundice may persist for many months

following adverse reactions to certain drugs, including erythromycin, flucloxacillin and chlorpromazine.

Herbal drugs.

HistoryInjections include blood tests, drug abuse, tuberculin testing, dental treatment and tattooing, and any parenterally administered therapy including blood or plasma transfusions.

Consumption of food like shellfish.

Travel to areas where hepatitis is endemic should be noted.

HistoryOccupation should be noted, particularly employment involving alcohol or contact with water carrying risk of Weil ’s disease.

Family history is important with respect to jaundice, hepatitis and anaemia. Positive histories are helpful in diagnosing haemolytic jaundice, congenital hyperbilirubinemia and hepatitis.

Physical examinationAge and sex. A parous, middle - aged, obese female is likely to develop gallstones. The probability of malignant biliary obstruction increases with age. Drug jaundice is very rare in childhood. The incidence of type A hepatitis decreases as age advances but no age is exempt from type B, D and C.

Physical examinationAnaemia may indicate haemolysis, cancer or cirrhosis. Gross weight loss suggests cancer or severe malabsorption. The patient with haemolytic jaundice is a mild yellow colour, with hepatocellular jaundice is orange and with prolonged biliary obstruction has a deep greenish hue

Physical examinationSlight intellectual deterioration with minimal personality change suggests hepatocellular jaundice.

Fetor hepaticus and ‘ flapping ’ tremor indicate impending hepatic coma.

Physical examinationchronic cholestasis, scratch marks, melanin pigmentation, finger clubbing, xanthoma on the eyelids (xanthelasma), extensor surfaces and palmar creases, and hyperkeratosis may be found.cirrhosis - include vascular spiders, palmar erythema, white nails and loss of secondary sexual hair.

Physical examinationPurpuric spots, most often noticed on forearms, axillae or shins, may be related to the thrombocytopenia of cirrhosis.

Bruising may indicate a clotting defect.

Some findings may be pathognomonic of a specific disorder (e.g., Kayser-Fleischer rings in Wilson disease).

Abdominal examination. • large nodular liver- cancer. small liver - cirrhosis

(extrahepatic cholestasis in which the liver is enlarged and smooth). • The edge may be tender in hepatitis, congestive

heart failure, alcohol-ism and• choledocholithiasis the gallbladder area may be

tender and Murphy ’s sign positive. • splenomegaly occurs with haemolytic states,portal

hypertension. • Ascites may be due to cirrhosis or to malignant

disease within the abdomen.

InvestigationsEssential laboratory tests in the patient with jaundice include serum total bilirubin, alkaline phosphatase, aminotransferases, complete blood count, and prothrombin time

Any bilirubin found in the urine is conjugated bilirubin. The presence of bilirubinuria implies the presence of liver disease.

InvestigationsEnzyme tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are helpful in differentiating between a hepatocellular process and a cholestatic process.Patients with a hepatocellular process generally have a rise in the aminotransferases that is disproportionate to that in ALP, whereas patients with a cholestatic process have a rise in ALP that is disproportionate to that of the aminotransferases.

InvestigationsA low albumin level suggests a chronic process such as cirrhosis or cancer, normal albumin level suggestive of more accurate process.

patients with alcoholic hepatitis typically have an AST-to-ALT ratio of at least 2:1, and the AST level rarely exceeds 300 U/L. Patients with acute viral hepatitis and toxin-related injury severe enough to produce jaundice typically have aminotransferase levels >500 U/L, with the ALT greater than or equal to the AST.

Investigationshepatitis A IgM antibody assay, a hepatitis B surface antigen and core IgM antibody assay, a hepatitis C viral RNA test, and, depending on the circumstances, a hepatitis E IgM antibody assay.

USG The absence of biliary dilation suggests intrahepatic cholestasis,The distal common bile duct is a particularly difficult area to visualize by ultrasound because of overlying bowel gas

InvestigationsAppropriate next tests include CT, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS).

ERCP is the “gold standard” for identifying choledocholithiasis. Beyond its diagnostic capabilities, ERCP allows therapeutic interventions, including the removal of common bile duct stones and the placement of stents.

InvestigationsLiver biopsy provides precise information regarding lobular architecture and the extent and pattern of hepatic inflammation and fibrosis and is most helpful for patients with persistent and undiagnosed jaundice. liver biopsy permits the diagnosis of viral hepatitis, fatty liver disease, hemochromatosis, Wilson disease, PBC, granulomatous hepatitis, and neoplasms.

Jaundice in PregnancyIntrahepatic cholestasis of pregnancy typically• occurs in the third trimester and presents with pruritus

and occasionally with jaundice. Cholestasis generally resolves within 2 weeks of delivery and often recurs with subsequent pregnancies.• Acute fatty liver of pregnancy, which typically occurs in

the third trimester and is associated with hepatocellular injury. Jaundice, when present, is usually accompanied by nausea, abdominal pain, and evidence of liver failure. Liver biopsy microvesicular steatosis. The disorder may be fatal unless obstetrical delivery is performed promptly.

Jaundice in the Critically Ill Patient• Predisposing factors include hepatic ischemia,

blood transfusions, hepatotoxic drugs, parenteral nutrition, and occult sepsis.• kidney injury may further contribute to impairment

of conjugated bilirubin elimination.• Notably, even if other clinical parameters improve,

there may be a lag in the resolution of jaundice.

Case24 yr/F, unmarried, fashion designer from mahesh Nagar, Hyderabad.H/O no CO-MORBIDS

P/w • fever with chills 4days, (4days may not cholestatic, no rigors

may not cholangitis)• nausea, vomiting and anorexia 4days ( may be viral)• H/O outside food (may infective)• no weight loss (chronic unlikely)• no travel

Case• no family history (may not hemolytic, isolated hyper bilirubin less likely) • not on any drugs

O/e• icterus sclera ( may TB >3mg/DL)• no fever, BP 100/60, PR 60/min, Spo2 97% on room air.• no pallor (hemolysis less likely)• normal orientation, no flaps (he unlikely)• no skin pigmentation, xanthoma and hyperkeratosis (chronic unlikely)• novascular spider, no pruritic spot (Cirrhosis unlikely)• normal iris (no kf ring)

CaseP/a • no organic megaly, no acitis ( hemolysis, Cirrhosis

unlikely)Investigations: ( no hemolysis, hepatocellular JAUNDICE)CBP:• HB 13.6• WBC 6890• Plt 2.19lak• ESR 06.

LFT: TB 4.5 (DIRCT 2.7, IN 1.8)ALP 106ALT 5660AST 5840ALB 3.6

PT 19.4INR 1.63

CaseViral screen - HAV positiveUSG no ductal dialatation was suggestive of hepatitis.

Treated with uesodeoxycholic ascid, Liveril forte.

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