A 23-year-old woman with sickle cell anemia (Hb SS) has had 12 transfusions. She now has right upper quadrant pain, pale stools and dark urine. Results three months ago, when well: total bilirubin 3.6 mg/dL [62 µmol/L], direct bilirubin 0.4 mg/dL [7 µmol/L], hemoglobin 8.2 g/dL [82 g/L], reticulocytes 9%. Today: total bilirubin 9.8 mg/dL [168 µmol/L], direct bilirubin 6.4 mg/dL [109 µmol/L], hemoglobin 8.0 g/dL [80 g/L], reticulocytes 10%, ALP 390 U/L (reference 40-130), GGT 310 U/L (below 50), ALT 72 U/L (below 40), urine bilirubin positive. Today's jaundice is best explained by:

Bile duct obstruction by a pigment stone

A hemolytic crisis raising bilirubin load

Acute viral hepatitis after transfusion

Gilbert syndrome added to chronic hemolysis

Acute intermittent porphyria is caused by a partial deficiency of:

Porphobilinogen deaminase (HMBS)

Heme derivatives: interpretation and disease correlation

16 ASCP MLS practice questions on Heme derivatives: interpretation and disease correlation, part of Chemistry. The first 16 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 23-year-old woman with sickle cell anemia (Hb SS) has had 12 transfusions. She now has right upper quadrant pain, pale stools and dark urine. Results three months ago, when well: total bilirubin 3.6 mg/dL [62 µmol/L], direct bilirubin 0.4 mg/dL [7 µmol/L], hemoglobin 8.2 g/dL [82 g/L], reticulocytes 9%. Today: total bilirubin 9.8 mg/dL [168 µmol/L], direct bilirubin 6.4 mg/dL [109 µmol/L], hemoglobin 8.0 g/dL [80 g/L], reticulocytes 10%, ALP 390 U/L (reference 40-130), GGT 310 U/L (below 50), ALT 72 U/L (below 40), urine bilirubin positive. Today's jaundice is best explained by:
1. AA hemolytic crisis raising bilirubin load
2. BAcute viral hepatitis after transfusion
3. CGilbert syndrome added to chronic hemolysis
4. DBile duct obstruction by a pigment stone
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Answer: D · Bile duct obstruction by a pigment stone
Indirect bilirubin is total minus direct: 3.6 - 0.4 = 3.2 mg/dL [55 µmol/L] at baseline and 9.8 - 6.4 = 3.4 mg/dL [58 µmol/L] today. So the unconjugated load from hemolysis is unchanged, which fits the stable hemoglobin and reticulocytes, and almost the whole rise is conjugated bilirubin. ALP and GGT several times the upper limit, only a mild ALT rise, bilirubinuria and pale stools make a cholestatic, post-hepatic picture. Chronic hemolysis produces calcium bilirubinate (pigment) gallstones, which can pass into and block the common bile duct. Ultrasound or MRCP would confirm the obstruction.
- A: Indirect bilirubin (3.4 versus 3.2 mg/dL), hemoglobin and reticulocytes are unchanged.
- B: Acute hepatitis raises ALT into the hundreds or thousands; here ALP and GGT dominate.
- C: Gilbert syndrome raises unconjugated, not conjugated, bilirubin.
Question 2 · Hard
A 36-year-old woman has had fragile skin and blisters on the backs of her hands for years, worse in summer. Two weeks after starting carbamazepine she develops severe abdominal pain, vomiting, a pulse of 120/min, weakness in both arms and a serum sodium of 127 mmol/L. Results: urine porphobilinogen 46 mg/g creatinine (reference below 2), urine ALA raised; plasma porphyrin fluorescence emission peak at 626 nm; fecal porphyrins raised, with protoporphyrin greater than coproporphyrin. The diagnosis that fits best is:
1. APorphyria cutanea tarda
2. BHereditary coproporphyria
3. CVariegate porphyria
4. DAcute intermittent porphyria
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Answer: C · Variegate porphyria
A raised porphobilinogen with abdominal pain, tachycardia, motor neuropathy and hyponatremia confirms an acute porphyria attack, here triggered by carbamazepine. Of the acute porphyrias, variegate porphyria and hereditary coproporphyria can also cause blistering skin like that of PCT. Variegate porphyria is due to partial protoporphyrinogen oxidase deficiency: fecal protoporphyrin exceeds coproporphyrin, and plasma fluorescence peaks at about 626 nm because porphyrin is bound to plasma protein. That plasma peak is the most useful single screening test for variegate porphyria. PCT gives a plasma peak nearer 620 nm and never causes neurovisceral attacks.
- A: PCT causes no acute attacks, and its porphobilinogen is normal.
- B: Hereditary coproporphyria shows mainly fecal coproporphyrin III, not protoporphyrin.
- D: AIP causes no skin lesions, and its fecal porphyrins and plasma fluorescence are usually normal.
Question 3 · Easy
Acute intermittent porphyria is caused by a partial deficiency of:
1. AFerrochelatase
2. BPorphobilinogen deaminase (HMBS)
3. CUroporphyrinogen decarboxylase
4. DALA dehydratase
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Answer: B · Porphobilinogen deaminase (HMBS)
Acute intermittent porphyria (AIP) is an autosomal dominant deficiency of porphobilinogen (PBG) deaminase, also called hydroxymethylbilane synthase. When heme demand rises, ALA and PBG build up and cause attacks of abdominal pain and neurologic symptoms. Because the block comes before any porphyrins form, AIP does not cause skin photosensitivity. A markedly raised urine PBG during an attack is the key test.
- A: Ferrochelatase deficiency causes erythropoietic protoporphyria.
- C: Uroporphyrinogen decarboxylase deficiency causes porphyria cutanea tarda.
- D: ALA dehydratase is inhibited by lead and is deficient only in the rare ALAD porphyria.
Question 4 · Hard
A thriving, exclusively breastfed 3-week-old has total bilirubin 14.0 mg/dL (239 µmol/L) and direct bilirubin 0.5 mg/dL (8.6 µmol/L). Hemoglobin is normal, the DAT is negative and the newborn thyroid screen was normal. The most likely cause is:
1. ABreast milk jaundice
2. BABO hemolytic disease
3. CDubin-Johnson syndrome
4. DBiliary atresia
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Answer: A · Breast milk jaundice
Breast milk jaundice is a prolonged unconjugated hyperbilirubinemia in a healthy, well-fed infant, appearing after the first week and lasting for weeks. Factors in some mothers' milk slow bilirubin conjugation and increase its reabsorption from the gut. The direct fraction is normal, there is no hemolysis, and hypothyroidism has been excluded. Breastfeeding usually continues, with bilirubin monitored.
- B: Hemolytic disease would usually show anemia or a positive DAT and appears in the first days.
- C: Dubin-Johnson syndrome causes conjugated, not unconjugated, hyperbilirubinemia.
- D: Biliary atresia raises direct (conjugated) bilirubin and gives pale stools.
Question 5 · Medium
Serum indirect bilirubin is raised, direct bilirubin is normal, urine bilirubin is negative and urine urobilinogen is increased. This pattern is most consistent with:
1. ADubin-Johnson syndrome
2. BCommon bile duct obstruction
3. CHemolytic anemia
4. DAcute viral hepatitis
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Answer: C · Hemolytic anemia
Increased red cell breakdown delivers more unconjugated bilirubin than the liver can clear, so the indirect fraction rises. Unconjugated bilirubin is bound to albumin and not filtered, so urine bilirubin stays negative. The liver still conjugates and excretes more bilirubin into the gut, which raises urobilinogen formation and urine urobilinogen. Haptoglobin, LD and the reticulocyte count help confirm hemolysis.
- A: Dubin-Johnson syndrome raises direct bilirubin, which appears in the urine.
- B: Bile duct obstruction raises direct bilirubin and lowers urobilinogen.
- D: Hepatitis raises both fractions and makes urine bilirubin positive.
Question 6 · Hard
A 3-year-old living in an old house has microcytic anemia with coarse basophilic stippling. Zinc protoporphyrin and urine ALA are raised; urine porphobilinogen is normal. The most likely cause is:
1. AIron deficiency anemia
2. BAcute intermittent porphyria
3. CErythropoietic protoporphyria
4. DLead poisoning
Answer and explanation in LearnFree account
Question 7 · Hard
A 5-day-old has total bilirubin 24.0 mg/dL (410 µmol/L), almost all unconjugated, with no hemolysis. It persists for weeks and does not fall with phenobarbital. The most likely diagnosis is:
1. AGilbert syndrome
2. BCrigler-Najjar syndrome type I
3. CCrigler-Najjar syndrome type II
4. DPhysiologic neonatal jaundice
Answer and explanation in LearnFree account
Question 8 · Medium
A 55-year-old man who drinks heavily has fragile skin with blisters on the backs of his hands. Urine uroporphyrin is markedly raised and urine porphobilinogen is normal. Which condition fits best?
1. AErythropoietic protoporphyria
2. BAcute intermittent porphyria
3. CPorphyria cutanea tarda
4. DLead poisoning
Answer and explanation in LearnFree account
Question 9 · Easy
Kernicterus in a newborn is caused by brain deposition of which substance?
1. AUrobilinogen
2. BConjugated bilirubin
3. CUnconjugated bilirubin
4. DDelta bilirubin
Answer and explanation in LearnFree account
Question 10 · Medium
A 6-year-old has burning pain and redness of sun-exposed skin within minutes of going outdoors. There are no blisters, and urine porphyrins are normal. The most likely diagnosis is:
1. AErythropoietic protoporphyria
2. BPorphyria cutanea tarda
3. CCongenital erythropoietic porphyria
4. DAcute intermittent porphyria
Answer and explanation in LearnFree account
Question 11 · Medium
Total bilirubin is 3.2 mg/dL (55 µmol/L) and direct bilirubin is 0.4 mg/dL (7 µmol/L). The indirect bilirubin is:
1. A2.8 mg/dL (48 µmol/L)
2. B0.4 mg/dL (7 µmol/L)
3. C8.0 mg/dL (137 µmol/L)
4. D3.6 mg/dL (62 µmol/L)
Answer and explanation in LearnFree account
Question 12 · Hard
A 26-year-old woman has severe abdominal pain, constipation and a serum sodium of 126 mmol/L, three days after starting a barbiturate. Her skin is normal. Urine porphobilinogen is markedly raised and fecal porphyrins are normal. Which diagnosis fits best?
1. ALead poisoning
2. BVariegate porphyria
3. CHereditary coproporphyria
4. DAcute intermittent porphyria
Answer and explanation in LearnFree account
Question 13 · Medium
Chronic mild conjugated hyperbilirubinemia, normal liver enzymes and a black-pigmented liver on biopsy suggest:
1. ACrigler-Najjar syndrome type II
2. BDubin-Johnson syndrome
3. CGilbert syndrome
4. DRotor syndrome
Answer and explanation in LearnFree account
Question 14 · Hard
A 60-year-old woman has dark urine and pale stools. Total bilirubin 4.5 mg/dL (77 µmol/L), direct bilirubin 3.6 mg/dL (62 µmol/L), urine bilirubin positive, urine urobilinogen absent. What are the indirect bilirubin and the type of jaundice?
1. A0.9 mg/dL (15 µmol/L); prehepatic
2. B0.9 mg/dL (15 µmol/L); posthepatic
3. C8.1 mg/dL (139 µmol/L); posthepatic
4. D3.6 mg/dL (62 µmol/L); hepatic
Answer and explanation in LearnFree account
Question 15 · Medium
A 22-year-old man notices yellow eyes after two days of fasting with a cold. Total bilirubin is 2.6 mg/dL (44 µmol/L), almost all unconjugated; liver enzymes, CBC and reticulocyte count are normal. What is the most likely cause?
1. ADubin-Johnson syndrome
2. BCrigler-Najjar syndrome type I
3. CGilbert syndrome
4. DHemolytic anemia
Answer and explanation in LearnFree account
Question 16 · Hard
A 5-week-old breastfed infant is still jaundiced and has pale stools. Total bilirubin is 7.5 mg/dL (128 µmol/L) and direct bilirubin is 4.5 mg/dL (77 µmol/L). What is the most likely explanation?
1. ACrigler-Najjar syndrome type II
2. BBiliary atresia
3. CGilbert syndrome
4. DBreast milk jaundice
Answer and explanation in LearnFree account

Heme derivatives: interpretation and disease correlation

Acute intermittent porphyria is caused by a partial deficiency of:

A thriving, exclusively breastfed 3-week-old has total bilirubin 14.0 mg/dL (239 µmol/L) and direct bilirubin 0.5 mg/dL (8.6 µmol/L). Hemoglobin is normal, the DAT is negative and the newborn thyroid screen was normal. The most likely cause is:

Serum indirect bilirubin is raised, direct bilirubin is normal, urine bilirubin is negative and urine urobilinogen is increased. This pattern is most consistent with:

A 3-year-old living in an old house has microcytic anemia with coarse basophilic stippling. Zinc protoporphyrin and urine ALA are raised; urine porphobilinogen is normal. The most likely cause is:

A 5-day-old has total bilirubin 24.0 mg/dL (410 µmol/L), almost all unconjugated, with no hemolysis. It persists for weeks and does not fall with phenobarbital. The most likely diagnosis is:

A 55-year-old man who drinks heavily has fragile skin with blisters on the backs of his hands. Urine uroporphyrin is markedly raised and urine porphobilinogen is normal. Which condition fits best?

Kernicterus in a newborn is caused by brain deposition of which substance?

A 6-year-old has burning pain and redness of sun-exposed skin within minutes of going outdoors. There are no blisters, and urine porphyrins are normal. The most likely diagnosis is:

Total bilirubin is 3.2 mg/dL (55 µmol/L) and direct bilirubin is 0.4 mg/dL (7 µmol/L). The indirect bilirubin is:

A 26-year-old woman has severe abdominal pain, constipation and a serum sodium of 126 mmol/L, three days after starting a barbiturate. Her skin is normal. Urine porphobilinogen is markedly raised and fecal porphyrins are normal. Which diagnosis fits best?

Chronic mild conjugated hyperbilirubinemia, normal liver enzymes and a black-pigmented liver on biopsy suggest:

A 60-year-old woman has dark urine and pale stools. Total bilirubin 4.5 mg/dL (77 µmol/L), direct bilirubin 3.6 mg/dL (62 µmol/L), urine bilirubin positive, urine urobilinogen absent. What are the indirect bilirubin and the type of jaundice?

A 22-year-old man notices yellow eyes after two days of fasting with a cold. Total bilirubin is 2.6 mg/dL (44 µmol/L), almost all unconjugated; liver enzymes, CBC and reticulocyte count are normal. What is the most likely cause?

A 5-week-old breastfed infant is still jaundiced and has pale stools. Total bilirubin is 7.5 mg/dL (128 µmol/L) and direct bilirubin is 4.5 mg/dL (77 µmol/L). What is the most likely explanation?