Heme Derivatives

Heme derivatives are essential for oxygen transport, electron transfer, and various enzymatic processes. Accurate lab testing of these compounds is critical for diagnosing and managing a wide range of conditions

Biochemical Theory and Physiology

• Heme Structure and Function
  • Porphyrin ring complex with iron (Fe2+)
  • Essential for hemoglobin, myoglobin, cytochromes, and other heme proteins
• Heme Synthesis
  • Complex pathway producing heme, primarily in bone marrow and liver
  • Key enzymes: ALA synthase, ALA dehydratase, ferrochelatase
• Heme Degradation
  • Breakdown of heme into biliverdin, bilirubin, and eventually excreted products
  • Key enzymes: Heme oxygenase, biliverdin reductase, UDP-glucuronosyltransferase (UGT)
• Iron Metabolism
  • Iron is a crucial component of heme and is tightly regulated
  • Absorption, transport (transferrin), storage (ferritin)

Laboratory Test Procedures

• Bilirubin
  • Diazo Method: Total, Direct (Conjugated), and Indirect (Unconjugated) Bilirubin
  • Jendrassik-Grof Method: Modification of the Diazo method to reduce interference
• Urine Bilirubin
  • Dipstick Method: Qualitative detection of conjugated bilirubin
• Urine Urobilinogen
  • Ehrlich’s Reagent Method: Semi-quantitative detection of urobilinogen
• Iron Studies
  • Serum Iron: Measurement of iron in serum
  • Total Iron-Binding Capacity (TIBC): Measurement of the blood’s capacity to bind iron
  • Transferrin Saturation: Calculated as (Serum Iron / TIBC) x 100
  • Ferritin: Immunoassay for measuring ferritin concentration
• Porphyrin Analysis
  • HPLC: Separation and quantification of porphyrins in urine, blood, or feces
• Fecal Occult Blood Test (FOBT)
  • Guaiac-Based FOBT (gFOBT): Detection of heme’s peroxidase activity
  • Fecal Immunochemical Test (FIT): Uses antibodies for human hemoglobin

Test Result Interpretation

• Bilirubin
  • Elevated Total Bilirubin: Hyperbilirubinemia
  • Increased Direct Bilirubin: Biliary obstruction, liver disease
  • Increased Indirect Bilirubin: Hemolysis
• Urine Bilirubin
  • Positive: Biliary obstruction, liver disease
• Urine Urobilinogen
  • Increased: Hemolysis, liver disease
  • Decreased: Biliary obstruction
• Iron Studies
  • Decreased Serum Iron, Ferritin, and Transferrin Saturation; Increased TIBC: Iron Deficiency Anemia
  • Increased Serum Iron, Ferritin, and Transferrin Saturation; Decreased TIBC: Hemochromatosis
• Porphyrin Analysis
  • Elevated levels of specific porphyrins in urine, blood, or feces: Porphyria
• Fecal Occult Blood Test (FOBT)
  • Positive: Gastrointestinal bleeding

Disease State Correlation

• Liver Diseases
  • Hepatitis: Elevated Total Bilirubin, Direct Bilirubin, ALT, and AST
  • Cirrhosis: Elevated Bilirubin, Decreased Albumin, Prolonged PT
  • Biliary Obstruction: Elevated Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase (ALP), and Gamma-Glutamyl Transferase (GGT)
• Hemolytic Anemias
  • Elevated Total Bilirubin (Indirect), Increased Reticulocyte Count, Decreased Haptoglobin
• Porphyrias
  • Elevated levels of specific porphyrins and porphyrin precursors in urine, blood, or feces
• Iron Deficiency Anemia (IDA)
  • Decreased Hemoglobin, Hematocrit, Serum Iron, and Ferritin; Increased TIBC
• Hemochromatosis
  • Elevated Serum Iron, Transferrin Saturation, and Ferritin
• Lead Poisoning
  • Elevated Blood Lead Levels, Elevated Zinc Protoporphyrin (ZPP), Anemia
• Anemia of Chronic Disease (ACD)
  • Decreased Hemoglobin, Serum Iron, and TIBC; Normal or Increased Ferritin

Key Considerations for Accurate Results

• Pre-analytical variables
• Interfering substances
• Analytical limitations
• Reference ranges based on a patient’s age and sex

Overall Approach

• Connect the Dots: Integrate biochemical knowledge with lab data, patient history, and clinical exam
• Continual Learning: Stay up-to-date on guidelines and best practices
• Clinical Significance: Understanding heme metabolism and its relationship to disease is critical for accurate diagnosis and treatment