Jaundice : An approach.
Jaundice
•
•

•

Yellowish discoloration of tissue resulting from
the deposition of bilirubin.
Slight increases in serum b...
• A second place to examine is underneath the
tongue.
• Another sensitive indicator of increased serum
bilirubin is darken...
History
• The duration of jaundice;
• Presence of any accompanying symptoms
such as arthralgias, myalgias, rash, anorexia,...
• Jaundice associated with the sudden onset of severe right
upper quadrant pain and shaking chills suggests
choledocholith...
Physical Examination
• Assessment of the patient's nutritional status.
• Stigmata of chronic liver disease, including spid...
• Jugular venous distention, a sign of right-sided
heart failure, suggests hepatic congestion.
• Right pleural effusion, i...
• Patients with cirrhosis may have an enlarged left
lobe of the liver, which is felt below the xiphoid,
and an enlarged sp...
• Severe right upper quadrant tenderness with
respiratory arrest on inspiration (Murphy's
sign) suggests cholecystitis or,...
Measurement of Serum Bilirubin
• Based on the van den Bergh reaction.
• Bilirubin is exposed to diazotized sulfanilic acid...
• The indirect fraction is the difference between
the total and the direct bilirubin and provides an
estimate of the uncon...
DELTA FRACTION
• Direct-reacting bilirubin fraction includes conjugated
bilirubin that is covalently linked to albumin.
• ...
Urine Bilirubin
• Unconjugated bilirubin is always bound to
albumin in the serum, and is not found in the
urine.
• Any bil...
Hyperbilirubinemia.
• (1) overproduction of bilirubin;
• (2) impaired uptake, conjugation, or excretion
of bilirubin
• (3)...
Determine..
1. whether the hyperbilirubinemia is
predominantly conjugated or unconjugated
in nature.

2. whether other bio...
Isolated Elevation of Serum Bilirubin
Unconjugated Hyperbilirubinemia.
(Direct <15%)
• The critical determination is wheth...
Inherited disorders:
•
•
•
•
•

spherocytosis,
sickle cell anemia,
thalassemia,
pyruvate kinase deficiency
glucose-6-phosp...
• In these conditions, the serum bilirubin rarely
exceeds (5 mg/dL).
• Higher levels may occur when there is
coexistent re...
Acquired hemolytic disorders
• Microangiopathic hemolytic anemia (e.g.,
hemolytic-uremic syndrome),
• paroxysmal nocturnal...
DRUGS..
• rifampicin
• probenecid,
• cause unconjugated hyperbilirubinemia by
diminishing hepatic uptake of bilirubin
Bilirubin UDPGT deficiency
• Crigler-Najjar type I (complete absence)is an
exceptionally rare condition found in neonates
...
• Gilbert's syndrome is also marked by the
impaired conjugation of bilirubin due to
reduced bilirubin UDPGT activity to
ap...
Conjugated Hyperbilirubinemia
• Dubin-Johnson syndrome and
• Rotor's syndrome.
• Present with asymptomatic jaundice, typic...
Elevation of Serum Bilirubin with
Other Liver Test Abnormalities
• In a patient with unexplained jaundice,certain tests are
useful in initial evaluation. These include:

•
•
•
•
•

Total ...
• Patients with a hepatocellular process generally have a
disproportionate rise in the aminotransferases compared to the
A...
Hepatocellular Conditions
• Viral hepatitis (Hepatitis A,B,C,D,E, HSV, EBV,CMV).
• Alcohol.
• Drug (Dose dependent: Parace...
• Patients with alcoholic hepatitis typically have an
AST:ALT ratio of at least 2:1. The AST rarely exceeds 300
U/L.
• Pat...
Cholestatic Conditions
• Distinguish intrahepatic from extrahepatic cholestasis.

•

History, physical examination, and la...
• The distal common bile duct is a particularly
difficult area to visualize by ultrasound
because of overlying bowel gas.
...
• Both Hepatitis B and C can cause a cholestatic
hepatitis .Hepatitis A, alcoholic hepatitis, EBV,
and CMV may also presen...
• Primary sclerosing cholangitis is characterized by the
destruction and fibrosis of larger bile ducts.
• 95% of patients ...
• Cholestasis of pregnancy occurs in the second
and third trimesters and resolves after delivery.
Its cause is unknown, bu...
Extrahepatic cholestasis

• MALIGNANT.
• BENIGN.
Malignant
•
•
•
•

Ca pancreas
Ca gallbladder,
Ampullary carcinoma.(Has the highest surgical cure rate)
Cholangiocarcinoma...
Benign
•
•
•
•
•
•
•

Choledocholithiasis(Commonest cause)
Primary sclerosing cholangitis
Postoperative biliary structures...
Jaundice
Jaundice
Jaundice
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Jaundice

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Jaundice

  1. 1. Jaundice : An approach.
  2. 2. Jaundice • • • Yellowish discoloration of tissue resulting from the deposition of bilirubin. Slight increases in serum bilirubin are best detected by examining the sclerae, which have a particular affinity for bilirubin due to their high elastin content. The presence of scleral icterus indicates a serum bilirubin of at least 3 mg/dL.
  3. 3. • A second place to examine is underneath the tongue. • Another sensitive indicator of increased serum bilirubin is darkening of the urine. • Patients often describe their urine as tea- or colacolored. • Bilirubinuria indicates an elevation of the direct serum bilirubin fraction and, therefore, the presence of liver disease
  4. 4. History • The duration of jaundice; • Presence of any accompanying symptoms such as arthralgias, myalgias, rash, anorexia, weight loss, abdominal pain, fever, • pruritus, • changes in the urine and stool. • Alcohol consumption.
  5. 5. • Jaundice associated with the sudden onset of severe right upper quadrant pain and shaking chills suggests choledocholithiasis and ascending cholangitis. • parenteral exposures, including transfusions, intravenous and intranasal drug use, tattoos, and sexual activity • exposure to any medication, either physician-prescribed, over-the-counter, complementary or alternative medicines such as herbal and vitamin preparations, or other drugs such as anabolic steroids. • • • • recent travel history; exposure to people with jaundice; exposure to possibly contaminated foods; occupational exposure to hepatotoxins
  6. 6. Physical Examination • Assessment of the patient's nutritional status. • Stigmata of chronic liver disease, including spider nevi, palmar erythema, gynecomastia, caput medusae, Dupuytren's contractures, parotid gland enlargement, and testicular atrophy. • An enlarged left supraclavicular node (Virchow's node) or periumbilical nodule (Sister Mary Joseph's nodule) suggests an abdominal malignancy
  7. 7. • Jugular venous distention, a sign of right-sided heart failure, suggests hepatic congestion. • Right pleural effusion, in the absence of clinically apparent ascites, may be seen in advanced cirrhosis. • KF rings may be present in cornea in wilsons disease.
  8. 8. • Patients with cirrhosis may have an enlarged left lobe of the liver, which is felt below the xiphoid, and an enlarged spleen. • A grossly enlarged nodular liver or an obvious abdominal mass suggests malignancy. • An enlarged tender liver: 1. viral or alcoholic hepatitis; an 2. infiltrative process such as amyloid; 3. acutely congested liver secondary to right-sided heart failure
  9. 9. • Severe right upper quadrant tenderness with respiratory arrest on inspiration (Murphy's sign) suggests cholecystitis or, occasionally, ascending cholangitis. • Ascites in the presence of jaundice suggests either cirrhosis or malignancy with peritoneal spread.
  10. 10. Measurement of Serum Bilirubin • Based on the van den Bergh reaction. • Bilirubin is exposed to diazotized sulfanilic acid • The direct fraction is that which reacts with diazotized sulfanilic acid in the absence of an accelerator substance such as alcohol.(Conjugated Bilirubin) • The total serum bilirubin is the amount that reacts after the addition of alcohol.
  11. 11. • The indirect fraction is the difference between the total and the direct bilirubin and provides an estimate of the unconjugated bilirubin in serum • With the van den Bergh method, the normal serum bilirubin concentration usually is (<1 mg/dL). • Up to 30%, (0.3 mg/dL), of the total may be direct-reacting (conjugated) bilirubin.
  12. 12. DELTA FRACTION • Direct-reacting bilirubin fraction includes conjugated bilirubin that is covalently linked to albumin. • By virtue of its tight binding to albumin, the clearance rate of albumin-bound bilirubin from serum approximates the half-life of albumin, 12–14 days, rather than the short halflife of bilirubin, about 4 hours. Resulting in: 1. Some patients with conjugated hyperbilirubinemia do not exhibit bilirubinuria . 2. The elevated serum bilirubin level declines more slowly than expected in some patients who otherwise appear to be recovering satisfactorily.
  13. 13. Urine Bilirubin • Unconjugated bilirubin is always bound to albumin in the serum, and is not found in the urine. • Any bilirubin found in the urine is conjugated bilirubin. • The presence of bilirubinuria implies the presence of liver disease
  14. 14. Hyperbilirubinemia. • (1) overproduction of bilirubin; • (2) impaired uptake, conjugation, or excretion of bilirubin • (3) regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ducts
  15. 15. Determine.. 1. whether the hyperbilirubinemia is predominantly conjugated or unconjugated in nature. 2. whether other biochemical liver tests are abnormal.
  16. 16. Isolated Elevation of Serum Bilirubin Unconjugated Hyperbilirubinemia. (Direct <15%) • The critical determination is whether: 1. the patient is suffering from a hemolytic process resulting in an overproduction of bilirubin (hemolytic disorders and ineffective erythropoiesis) or 2. from impaired hepatic uptake/conjugation of bilirubin (drug effect or genetic disorders).
  17. 17. Inherited disorders: • • • • • spherocytosis, sickle cell anemia, thalassemia, pyruvate kinase deficiency glucose-6-phosphate dehydrogenase deficiency.
  18. 18. • In these conditions, the serum bilirubin rarely exceeds (5 mg/dL). • Higher levels may occur when there is coexistent renal or hepatocellular dysfunction. or. • in acute hemolysis such as a sickle cell crisis.
  19. 19. Acquired hemolytic disorders • Microangiopathic hemolytic anemia (e.g., hemolytic-uremic syndrome), • paroxysmal nocturnal hemoglobinuria, • spur cell anemia, • immune hemolysis. • parasitic infections including malaria and babesiosis.
  20. 20. DRUGS.. • rifampicin • probenecid, • cause unconjugated hyperbilirubinemia by diminishing hepatic uptake of bilirubin
  21. 21. Bilirubin UDPGT deficiency • Crigler-Najjar type I (complete absence)is an exceptionally rare condition found in neonates and characterized by severe jaundice,kernicterus, frequently leading to death in infancy or childhood. • Crigler-Najjar type II (Deficiency)is somewhat more common than type I. Patients live into adulthood with serum bilirubin levels that range from (6–25 mg/dL).
  22. 22. • Gilbert's syndrome is also marked by the impaired conjugation of bilirubin due to reduced bilirubin UDPGT activity to approximately 1/3 of normal. • very common, with a reported incidence of 3– 12%. • unconjugated hyperbilirubinemia with serum levels almost always < (6 mg/dL).
  23. 23. Conjugated Hyperbilirubinemia • Dubin-Johnson syndrome and • Rotor's syndrome. • Present with asymptomatic jaundice, typically in the second generation of life. • Dublin Johnson: altered excretion of bilirubin into the bile ducts. • Rotor's syndrome : problem with the hepatic storage of bilirubin.
  24. 24. Elevation of Serum Bilirubin with Other Liver Test Abnormalities
  25. 25. • In a patient with unexplained jaundice,certain tests are useful in initial evaluation. These include: • • • • • Total and direct serum bilirubin with fractionation, aminotransferases, alkaline phosphatase, albumin prothrombin time tests.
  26. 26. • Patients with a hepatocellular process generally have a disproportionate rise in the aminotransferases compared to the ALP. • Patients with a cholestatic process have a disproportionate rise in the ALP compared to the aminotransferases. • A low albumin level suggests a chronic process such as cirrhosis or cancer. • An elevated prothrombin time indicates 1. vitamin K deficiency due to prolonged jaundice and malabsorption of vitamin K or 2. significant hepatocellular dysfunction. • The failure of the prothrombin time to correct with parenteral administration of vitamin K indicates severe hepatocellular injury.
  27. 27. Hepatocellular Conditions • Viral hepatitis (Hepatitis A,B,C,D,E, HSV, EBV,CMV). • Alcohol. • Drug (Dose dependent: Paracetamol ; Idiosyncratic:isoniazid) • Environmental toxins(Wild mushrooms—Amanita phalloides) • Wilsons Disease • Autoimmune Hepatitis.
  28. 28. • Patients with alcoholic hepatitis typically have an AST:ALT ratio of at least 2:1. The AST rarely exceeds 300 U/L. • Patients with acute viral hepatitis and toxin-related injury typically have aminotransferases > 500 U/L, with the ALT greater than or equal to the AST. • While ALT and AST values less than 8 times normal may be seen in either hepatocellular or cholestatic liver disease, values 25 times normal or higher are seen primarily in acute hepatocellular diseases. • Patients with jaundice from cirrhosis can have normal or only slight elevations of the aminotransferases.
  29. 29. Cholestatic Conditions • Distinguish intrahepatic from extrahepatic cholestasis. • History, physical examination, and laboratory tests are often not helpful. • The next appropriate test is an ultrasound. • The absence of biliary dilatation suggests intrahepatic cholestasis, while the presence of biliary dilatation indicates extrahepatic cholestasis. • False-negative results 1. Partial obstruction of the common bile duct 2. Cirrhosis or primary sclerosing cholangitis (PSC) where scarring prevents the intrahepatic ducts from dilating.
  30. 30. • The distal common bile duct is a particularly difficult area to visualize by ultrasound because of overlying bowel gas. • CT, magnetic resonance cholangiography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). • ERCP is the "gold standard" for identifying choledocholithiasis. ERCP allows for therapeutic interventions, including the removal of common bile duct stones and the placement of stents.
  31. 31. • Both Hepatitis B and C can cause a cholestatic hepatitis .Hepatitis A, alcoholic hepatitis, EBV, and CMV may also present as cholestatic liver disease. • DRUGS: 1. Pure cholestasis—anabolic and contraceptive steroids 2. Cholestatic hepatitis—chlorpromazine, imipramine erythromycin, Penicillins, cotrimoxazole… Chronic cholestasis—chlorpromazine and prochlorperazine 3.
  32. 32. • Primary sclerosing cholangitis is characterized by the destruction and fibrosis of larger bile ducts. • 95% of patients with PSC, both intra- and extrahepatic ducts are involved. But may present as intrahepatic cholestasis . • Approximately 75% of patients with PSC have inflammatory bowel disease. • Primary biliary cirrhosis is an autoimmune disease. • there is a progressive destruction of interlobular bile ducts. • Diagnosis is made by the presence of the antimitochondrial antibody that is found in 95% of patients.
  33. 33. • Cholestasis of pregnancy occurs in the second and third trimesters and resolves after delivery. Its cause is unknown, but the condition is probably inherited. Cholestasis can be triggered by estrogen administration. • • • • • • • Infiltrative disease:(TB, Lymphomas, Amyloiosis) Infections: (Malaria, Leptospirosis) Sepsis, Paraneoplastic (stauffers syndrome), GVHD Total Parenteral Nutrition. Inherited familial forms. Veno occlusive Diseases.
  34. 34. Extrahepatic cholestasis • MALIGNANT. • BENIGN.
  35. 35. Malignant • • • • Ca pancreas Ca gallbladder, Ampullary carcinoma.(Has the highest surgical cure rate) Cholangiocarcinoma (associated with PSC, appears similar to it and thus difficult to diagnose) • Malignant involvement of the porta hepatis lymph nodes.
  36. 36. Benign • • • • • • • Choledocholithiasis(Commonest cause) Primary sclerosing cholangitis Postoperative biliary structures Mirizzi's syndrome Parasitic disease (ascariasis) Chronic pancreatitis AIDS cholangiopathy

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