Hemoglobin

Marker Name: Hemoglobin

REFERENCE RANGES FOR HEMOGLOBIN:

Laboratory reference range:
Male and Female: 12.6–17.7 g/dL

Functional reference ranges:
Male: 14–15 g/dL
Female: 13.5–14.5 g/dL

DESCRIPTION:

Hemoglobin (Hb or Hgb) is the iron-containing metalloprotein in red blood cells (RBCs) that carries oxygen from the lungs to tissues throughout the body and gives red blood cells their characteristic color.^1,2 In red blood cells, hemoglobin also transports about 10 percent of the body’s carbon dioxide and is thought to play a role in nitric oxide delivery and regulation of vasomotor tone.^3,4 Hemoglobin is the main constituent of RBCs and makes up approximately 96 percent of RBC dry weight. Abnormal hemoglobin structure can affect RBC shape, which can impair function and flow through blood vessels.⁵ Outside of red blood cells, hemoglobin functions as an antioxidant and plays a role in iron metabolism.⁶

Hemoglobin is a tetrameric protein composed of two pairs of globin chains; most normal adult hemoglobin (HbA) consists of two alpha chains and two beta chains (α₂β₂).⁷ Within each globin chain is a central heme molecule that contains iron, which is the site of oxygen binding.⁸ Fully deoxygenated hemoglobin is slow to bind the first oxygen molecule. However, due to a phenomenon called cooperativity, each additional oxygen molecule bound increases the affinity of remaining binding sites for oxygen.⁴ Hemoglobin can bind up to four oxygen molecules.⁹

Hemoglobin exists in a taut form (T) and a relaxed form (R). The taut form has low oxygen affinity and releases bound oxygen; it is favored by conditions typically found in respirating tissue such as low pH, high CO₂ concentration, high 2,3-BPG concentration, and high temperature. The relaxed form has high oxygen affinity and is favored by the inverse conditions, which are typically found in lung alveoli. Therefore, hemoglobin generally binds oxygen in lungs and releases oxygen in respirating tissues where it is needed.^4,10 Hemoglobin oxygen binding can be impaired by competitive inhibitors such as carbon monoxide and hydrogen sulfide.^4,11

High hemoglobin can be caused by dehydration, high-altitude living, smoking, cor pulmonale, certain lung conditions, states of increased RBC production, and certain genetic disorders. A complete list of conditions that can cause increased hemoglobin levels is below.

Low hemoglobin can be caused by normal pregnancy, certain nutrient imbalances (e.g., iron deficiency, lead poisoning), ineffective erythropoiesis, hemolytic anemia, hypothyroidism, chronic kidney disease, liver disease, chronic inflammation, certain bone marrow disorders, porphyria, vasculitis, hypopituitarism, hypogonadism, and certain drugs. A full list of conditions and drugs that can cause decreased hemoglobin levels is provided below.

To determine the etiology of abnormal hemoglobin concentration, related iron markers should be considered, including serum iron, ferritin, TIBC, UIBC, iron saturation, and other markers in the complete blood count (CBC).

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^12,13

• Dehydration
• High-altitude living
• Smoking
• Cor pulmonale
• Severe lung conditions
  • Pulmonary fibrosis
  • Chronic obstructive pulmonary disease (COPD)
  • Emphysema
• States of increased red blood cell production
  • Treatment with erythropoietin (EPO)
  • Polycythemia vera
  • Renal neoplasm (e.g., renal cell carcinoma)
• Certain genetic disorders that cause:
  • Altered oxygen sensing¹⁴
  • Abnormal hemoglobin oxygen affinity¹⁵

Low in:^12-13,16-18

• Normal pregnancy
• Nutrient imbalances
  • Folate deficiency
  • Vitamin B6 deficiency
  • Vitamin B12 deficiency
  • Copper deficiency
  • Lead poisoning¹⁹
  • Iron deficiency^20-23
    • Inadequate dietary intake
    • Gastrointestinal malabsorption
    • Blood loss
  • Ineffective erythropoiesis (e.g., hereditary sideroblastic anemias, severe alpha and beta thalassemia, myelodysplastic syndrome (MDS) variants)^24-27
  • Hemolytic anemia (e.g., autoimmune hemolytic anemia, sickle cell anemia, malaria, etc.)
  • Hypothyroidism²⁸
  • Chronic kidney disease
  • Liver disease²⁹
  • Chronic inflammation (e.g., chronic infection, malignancy, rheumatologic disorders, inflammatory bowel disease, chronic immune activation)
  • Certain bone marrow disorders (e.g., leukemia, lymphoma, multiple myeloma, aplastic anemia)
  • Porphyria
  • Vasculitis³⁰
  • Hypopituitarism
  • Hypogonadism
  • Drugs³¹
    • Proton pump inhibitors
    • H₂ receptor blockers
    • Certain antibiotics (e.g., quinolones, tetracycline)
    • Excessive calcium supplementation
    • Chemotherapeutic agents
    • Antiretroviral drugs for HIV infection (e.g., azidothymidine)

FUNCTIONAL RANGE INDICATIONS:

High in:

• Dehydration

Low in:

• Functional (early-stage) anemias

References:

1. Maton, Anthea; Jean Hopkins; Charles William McLaughlin; Susan Johnson; Maryanna Quon Warner; David LaHart; Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1
2. https://labtestsonline.org/understanding/analytes/hemoglobin/tab/sample/
3. https://www.ncbi.nlm.nih.gov/pubmed/9435331
4. http://www.uptodate.com/contents/structure-and-function-of-normal-hemoglobins
5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC289318/
6. https://www.ncbi.nlm.nih.gov/pubmed/19717439
7. http://www.uptodate.com/contents/laboratory-diagnosis-of-the-hemoglobinopathies
8. http://www.medicinenet.com/hemoglobin/article.htm
9. Costanzo, Linda S. (2007). Physiology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7311-3.
10. http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.php#hemoglobin
11. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118656/
12. https://www.nlm.nih.gov/medlineplus/ency/article/003645.htm
13. https://labtestsonline.org/understanding/analytes/hemoglobin/tab/test/
14. http://www.haematologica.org/content/haematol/90/1/109.full.pdf
15. http://www.ncbi.nlm.nih.gov/pubmed/7419421
16. http://www.mayoclinic.org/symptoms/low-hemoglobin/basics/causes/sym-20050760
17. http://www.irondisorders.org/Websites/idi/files/Content/854256/HowdoIknow_Anemia__Converted_.pdf
18. http://www.uptodate.com/contents/approach-to-the-adult-patient-with-anemia
19. http://www.atsdr.cdc.gov/csem/csem.asp?csem=7&po=10
20. https://www.nlm.nih.gov/medlineplus/ency/article/000584.htm
21. http://www.uptodate.com/contents/anemia-caused-by-low-iron-beyond-the-basics
22. http://www.uptodate.com/contents/hematologic-complications-of-malignancy-anemia-and-bleeding
23. http://www.uptodate.com/contents/causes-and-diagnosis-of-iron-deficiency-anemia-in-the-adult
24. http://www.uptodate.com/contents/pathophysiology-of-the-sideroblastic-anemias
25. http://sickle.bwh.harvard.edu/sideroblastic.html
26. http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-the-thalassemias
27. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012757/
28. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915449/
29. http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-alcoholic-fatty-liver-disease-and-alcoholic-cirrhosis
30. http://www.nhlbi.nih.gov/health/health-topics/topics/vas/diagnosis
31. http://www.uptodate.com/contents/treatment-of-the-adult-with-iron-deficiency-anemia