Linda is a 53-year-old lady with no history of any chronic diseases. She presents to the urgent care clinic because of pain in the right upper abdominal region. She reports that she had similar pain about two years ago for the first time. Then, the pain occurred occasionally, especially after meals, but she did not pay any attention to it.  However, it got severe last week, then better after taking pain medications and keeping a diet. She did not take any medication since last week. She also noticed that her urine was dark yesterday as if it was tea. Her last bowel movement was two days ago.

On examination:

• Height: 172 cm, Weight: 75.3 Kg, BMI: 25.5
• Heart rate: 108/min, Respiratory rate: 28/min, Temperature: 37.0°C, O₂ SAT: 98%
• Tender epigastric region on palpation, yellowish discoloration of sclera and skin.

What is the most likely cause of this yellowish discoloration of sclera and skin?

Linda's laboratory investigation showed the following results:

• Blood analysis:
  • CBC:
    • RBCs: 4.7 x 10¹²/ L, Hemoglobin: 136 g/L, Hematocrit: 0.42,
    • MCV: 96 fL, MCH: 32 pg, RDW: 12.6%, Reticulocytes: 42 x 10⁹/ L (3.5%), ESR: 10 mm/hour,
    • WBC: 6.6 x 10⁹/l, (Neutrophils: 4.3 x 10⁹/L, Lymphocytes: 2.9 x 10⁹/L, Basophils: 0.08. x 10⁹/L, Eosinophils: 0.33 x 10⁹/L, Monocytes: 0.6 x 10⁹/L),
    • Platelet counts: 234 x 10⁹/L
  • Na: 142 mmol/L, K: 4.6 mmol/L,
  • Glucose: 5.9 mmol/L, BUN: 8.0 mmol/L, creatinine: 87.2 umol/L, uric acid: 223 mmol/L
  • Triglycerides: 2.6 mmol/L, Cholesterol total: 6.5 mmol/L, LDL: 4.2 mmol/L, HDL: 1.2 mmol/L,
  • Total bilirubin: 256 umol/L, conjugated bilirubin: 250 umol/L
  • AST: 49 U/L, ALT: 68 U/L, ALP: 711 IU/L, GGT: 289 IU/L, 5'-NT: 63 IU/L, albumin: 40 g/L, LDH: 188 U/L
  • INR: 1.0, Prothrombin time: 11 Sec
  • Viral serology: HBsAg: -ve, HCV AB: -ve, HAV IgG: -ve

• Urine analysis: color: dark brown, pH: 6.4, specific gravity: 1018, osmolarity: 631 mOsm/L; glucose, nitrates, ketones: negative, bilirubin: +++, bile salts: +, urobilinogen: negative, WBCs and RBCs: 4 and 0/HPF, squamous epithelial cells: 1-2/HPF, casts, bacteria, yeast: negative.

• Stool analysis: color: pale (clay-colored), urobilin: negative

You can notice that in Linda’s case, hyperbilirubinemia is caused by the accumulation of conjugated bilirubin in the blood.  What is the difference between conjugated and unconjugated bilirubin?

Have a look at the laboratory results again.

• CBC:
  • RBCs: 4.7 x 10¹²/ L, Hemoglobin: 136 g/L, Hematocrit: 0.42,
  • MCV: 96 fL, MCH: 32 pg, RDW: 12.6%, Reticulocytes: 42 x 10⁹/ L (3.5%), ESR: 10 mm/hour,
  • WBC: 6.6 x 10⁹/l, (Neutrophils: 4.3 x 10⁹/L, Lymphocytes: 2.9 x 10⁹/L, Basophils: 0.08. x 10⁹/L, Eosinophils: 0.33 x 10⁹/L, Monocytes: 0.6 x 10⁹/L),
  • Platelet counts: 234 x 10⁹/L
• Na: 142 mmol/L, K: 4.6 mmol/L,
• Glucose: 5.9 mmol/L, BUN: 8.0 mmol/L, creatinine: 87.2 umol/L, uric acid: 223 mmol/L
• Triglycerides: 2.6 mmol/L, Cholesterol total: 6.5 mmol/L, LDL: 4.2 mmol/L, HDL: 1.2 mmol/L,
• Total bilirubin: 256 umol/L, conjugated bilirubin: 250 umol/L
• AST: 49 U/L, ALT: 68 U/L, ALP: 711 IU/L, GGT: 289 IU/L, 5'-NT: 63 IU/L, albumin: 40 g/L, LDH: 188 U/L
• INR: 1.0, Prothrombin time: 11 Sec
• Viral serology: HBsAg: -ve, HCV AB: -ve, HAV IgG: -ve
• Urine analysis: color: dark brown, pH: 6.4, specific gravity: 1018, osmolarity: 631 mOsm/L; glucose, nitrates, ketones: negative, bilirubin: +++, bile salts: +, urobilinogen: negative, WBCs and RBCs: 4 and 0/HPF, squamous epithelial cells: 1-2/HPF, casts, bacteria, yeast: negative.
• Stool analysis: color: pale, clay-colored, urobilin: negative

What type of jaundice are Linda’s laboratory results showing? Explain.

What is the correct sequence of bilirubin metabolism? Put the steps of bilirubin metabolism in the correct order.

1. Biliverdin is converted into bilirubin in the RES.
2. Conjugated bilirubin is secreted into the bile.
3. Heme is broken down into biliverdin and iron.
4. Glucuronyl transferase converts unconjugated bilirubin into conjugated bilirubin.
5. Urobilinogen and stercobilinogen are oxidized into urobilin and stercobilin which are excreted in urine and stool.
6. Unconjugated bilirubin is transported to the liver by albumin.
7. Hemoglobin is released from damaged red blood cells.
8. Conjugated bilirubin is converted into urobilinogen and stercobilinogen by colon bacteria.
9. Hemoglobin is broken down into heme and globin.

Match the three types of jaundice with one of the underlying possible pathological conditions. (Select all that apply)

Prehepatic Hepatic Posthepatic

A.     Toxic hepatocellular damage B.     Gilbert’s syndrome C.     Hemolytic anemia D.     Cholelithiasis E.     Gastric ulcer F.      Pernicious anemia G.    Viral hepatitis