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Hemoglobin – Hb

Physiological role and pathophysiology, reference intervals and the most likely causes of abnormalities

Hemoglobin – Hb

Reference interval Hb – examples
Hemoglobin : structure & function
Why measure ctHb ?
Causes of decreased ctHb
Symptoms of decreased ctHb
Causes of increased ctHb 
Symptoms of increased ctHb

The concentration of total hemoglobin (ctHb) in blood includes oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb), as well as the dysfunctional hemoglobin species that are incapable of binding oxygen: carboxyhemoglobin (cCOHb) (see COHb), methemoglobin (cMetHb) (see MetHb) and sulfhemoglobin (cSulfHb). Thus:

The rare sulfHb is not included in the reported ctHb in most oximeters.

Reference interval Hb – examples

Hemoglobin : Structure and function

A small amount (<2 %) of the oxygen transported in blood is dissolved in blood plasma, but most of it (>98 %) is transported bound to the protein hemoglobin, contained within erythrocytes. The hemoglobin molecule (∼280 million per erythrocyte) is composed of four polypeptide chains, the ”globin” portion of the molecule. Each of these chains has an attached flat ringed molecule called heme. At the center of each heme group is an iron atom in the ferrous state (Fe2+) [18] that forms a reversible bond with an oxygen molecule [19] resulting in a structural change of the hemoglobin molecule, thereby increase hemoglobins affinity for oxygen on the remaining binding sites. Each hemoglobin molecule has the capacity to bind up to four oxygen molecules and can, theoretically, be 0, 25, 50, 75 or 100 % saturated with oxygen. The binding of hemoglobin with oxygen (see sO2) occurs in the pulmonary capillaries, so that blood leaving the lungs and throughout the arterial system is normally close to 100 % saturated with oxygen. Each gram of hemoglobin can carry up to 1.34 mL of oxygen.  Assuming a normal hemoglobin concentration of 150 g/L, and a normal sO2 of 98 %, the oxygen-carrying capacity of hemoglobin in arterial blood is (1.34 × 0.98 × 150) ~200 mL O2/L blood. Due to the low solubility of oxygen in water, a maximum of only 3 mL O2/L blood can be carried dissolved in blood plasma. Thus, hemoglobin increases the oxygen-carrying capacity of blood from around 3 to ∼200 mL O2/L blood, and adequate oxygenation of tissue cells depends crucially on maintaining an adequate amount of hemoglobin in blood.

For otherwise healthy individuals the critical ctHb value below which tissue (anemic) hypoxia inevitably occurs is <3.1 mmol/L (5.0  g/dL) [20]; this critical ctHb is higher for those with cardiovascular or respiratory disease that limits their ability to compensate for decreased ctHb [20].

In the tissue microvasculature conditions (pH, pCO2, temperature etc.) favor the release of oxygen from O2Hb to cells, so that venous blood returning from the tissues to the lungs typically contains hemoglobin that is ∼75 % saturated with oxygen (ctHb in venous blood comprises ∼75 % O2Hb and ∼25 % HHb) [21].

In addition to its prime oxygen-carrying function, hemoglobin serves a minor role in the carriage of carbon dioxide (CO2) in blood [22]. HHb can also bind hydrogen ions and this buffering action determines a role for hemoglobin in maintaining the pH of blood within normal limits.

Dyshemoglobin

Around 1 – 3 % of the measured ctHb is incapable of transporting oxygen reflecting the trace presence of COHb (see COHb) and MetHb (see MetHb). This lack of function is reflected in their collective name: The dyshemoglobins [8, 9]. Given that MetHb and COHb normally constitute less than 3 % of ctHb in healthy individuals, their effect on the oxygen-carrying capacity of hemoglobin is minimal. However, a pathological increase in either MetHb or COHb decreases the oxygen-carrying capacity of blood. If this increase is sufficiently severe the resulting reduction in the oxygen carrying capacity of blood and concomitant tissue hypoxia is potentially fatal. A normal ctHb indicates that the oxygen-carrying capacity of blood is sufficient to meet the tissue demand for oxygen; that is not the case if dyshemoglobins are increased.

Why measure ctHb?

  • It allows the diagnosis of anemia and assessment of its severity
  • It is a necessary parameter for calculating the concentration of total oxygen content in blood (see ctO2) and thereby assessing the risk of tissue hypoxia
  • It is the principal index for assessing the clinical need for red blood cell transfusion

 

Causes of decreased ctHb

Anemia is the clinical syndrome that results from decreased ctHb. A diagnosis of anemia is seen in woman if ctHb <7.1 mmol/L (11.4  g/dL) and in men if ctHb <8.3 mmol/L (13.4  g/dL) [17].

The many causes of anemia include:

  • Blood loss (hemorrhage)
  • Iron deficiency
  • Vitamin B12 and/or folate deficiency
  • Increased red cell destruction (hemolytic anemia)
  • Chronic inflammatory disease, cancer, chronic kidney disease
  • Impaired erythrocyte production in the bone marrow (aplastic anemia, leukemia)
  • Prematurity (a major risk factor for anemia during the neonatal period)
  • Hemoglobinopathies (e.g. sickle cell anemia or thalassemia)

 

Symptoms of decreased ctHb 

The principal pathological effect of anemia is decreased delivery of oxygen to the tissue cells and risk of tissue hypoxia (anemic hypoxia), but the extent to which this causes symptoms depends on several factors [17], including:

Severity of the anemia:
Patients with mild anemia (ctHb >6.2  mmol/L (10.0  g/dL)) usually have no symptoms, but severe anemia (ctHb <3.7  mmol/L (6.0  g/dL))
is almost always symptomatic

Coexisting disease:
The normal physiological (compensatory) response to anemia, which ensures, so far as is possible, continued delivery of oxygen to the tissues despite decreased ctHb, depends on functioning respiratory and cardiovascular systems

Those with coexisting respiratory and/or cardiovascular disease are particularly vulnerable to the effects of anemia, and more likely to manifest symptoms.

Symptoms include:

  • Pallor
  • Increased heart rate (tachycardia), palpitations
  • Shortness of breath, particularly on exertion
  • Tiredness and lethargy
  • Dizziness, fainting
  • Headaches

 

Causes of increased ctHb 

Hemoglobin at higher-than-normal levels can be observed in people living at high altitudes [23].

Other infrequent causes are:

  • Polycythemia vera
  • Chronic lung disease (e.g. emphysema)
  • Certain tumors
  • Dehydration
  • Drug abuse (e.g. erythropoietin (EPO) by athletes)
  • Smoking

 

Symptoms of increased ctHb

  • Weakness
  • Fatigue
  • Headache
  • Itching
  • Bruising
  • Joint pain
  • Dizziness
  • Abdominal pain
  • Shortness of breath
  • Chronic cough
  • Sleep disturbance (sleep apnea)
  • Poor exercise tolerance

 

 

References

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Ref.: Acute care testing handbook. Radiometer Medical ApS, 2700 Brønshøj, Denmark, 2014.

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