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Hemoglobin is a protein-based component of red blood cells whose primary role is to transfer the oxygen from the lungs to the rest of the body.

3331425437_626530463b.jpgHemoglobin is the reason why red blood cells appear red, although oxygen-rich blood is noticeably brighter than the depleted blood returning to the heart and lungs. Fresh hemoglobin is produced in the bone marrow as needed.

The Structure Of Hemoglobin

A hemoglobin molecule is a group of four globular protein subunits, and each of these subunits is composed of a protein chain tightly associated with a non-protein heme group. Medical knowledge proves that each protein chain arranges in a set of alpha-helix structural segments connected in a particular arrangement called myoglobin fold. This folding pattern contains a pocket which is perfectly suitable to bind the heme group strongly. [1]

What Exactly Is This Heme Group?

A heme group consists of an iron atom (Fe) held in a heterocyclic ring, known as a porphyrin. This iron atom is the exact site of oxygen binding. An iron atom bonds with four nitrogens in the center of the ring and two additional bonds perpendicular to the plane on each side can be formed with the iron to form the fifth and sixth positions, one connected strongly to the protein, the other available for binding with oxygen. [1]

Types Of Hemoglobins In Humans

In the embryo:

  • Gower 1 (ξ2ε2)
  • Gower 2 (α2ε2) (PDB 1A9W)
  • Hemoglobin Portland (ξ2γ2)

In the fetus:

  • Hemoglobin F (α2γ2) (PDB 1FDH) -  Hemoglobin F is the predominant hemoglobin during fetal development

In adults:

  • Hemoglobin A (α2β2) (PDB 1BZ0) - This is the designation for the normal hemoglobin that exists after birth.
  • Hemoglobin A2 (α2δ2) - This is a minor component of the hemoglobin found in red cells after birth
  • Hemoglobin F (α2γ2) [2]

The creation of hemoglobin

Like all proteins, the exact copy or blueprint for hemoglobin exists in DNA, and normally, every individual has four genes that code for the alpha protein, or alpha chain. Two other genes code for the beta chain. The alpha chain and the beta chain are made in precisely equal amounts, despite the differing number of genes. The protein chains join in developing red blood cells and remain together for the life of the red cell. The fact is that virtually, hemoglobin forms a hunger for oxygen molecules. [3]

Heme synthesis

Heme is synthesized in a complex series of steps involving enzymes in the mitochondrion and in the cytosol which are two organelles of the cell. First one is a molecule called 5-aminolevulic acid (ALA) which is transported to the cytosol where a series of reactions produce a ring structure called coproporphyrinogen III and then it returns to the mitochondrion where an additional reaction produces protoporphyrin IX. The enzyme ferrochelatase inserts iron into the ring structure of protoporphyrin IX to produce heme. [3]

Globin synthesis

Two globin chains combine to form hemoglobin. One of the chains is designated alpha and the second chain is called "non-alpha." This is because there are many variables which influence the nature of the non-alpha chain in the hemoglobin molecule. [3]

For example:

  • The fetus has a distinct non-alpha chain called gamma.
  • After birth, a different non-alpha globin chain, called beta, pairs with the alpha chain.
  • The combination of two alpha chains and two non-alpha chains produces a complete hemoglobin molecule

Physiology Of Blood And Hemoglobin Circulation

Whenever the blood travels into the lungs, these hemoglobin proteins attract whatever oxygen is available, and this oxygenated blood then travels throughout the entire bloodstream, releasing oxygen into the various muscles and organs all around the body. When the body spends these red blood cells, the body transfers them to the gastrointestinal system for disposal, and new red blood cells with hemoglobin take their place in the bloodstream. [4]

How Is Hemoglobin Measured?

There are several methods for measuring hemoglobin, and most of them are done by machines designed to perform several different tests on blood. In these machines, the red blood cells are broken down to get the hemoglobin into a solution. Machines expose the free hemoglobin to specific chemicals that contain cyanide which binds tightly to the hemoglobin molecule to form cyanmethemoglobin. By shining a light through the solution and measuring how much light is absorbed, the machines determine the amount of hemoglobin. [5]

Normal Values Of Hemoglobin

Hemoglobin levels are expressed as the amount of hemoglobin in grams per deciliter of blood, and the normal ranges for hemoglobin depend on a person's age and, beginning in adolescence, the sex of the person.

The normal ranges are:

  • Newborns: 17-22 gm/dl
  • One (1) week of age: 15-20 gm/dl
  • One (1) month of age: 11-15gm/dl
  • Children: 11-13 gm/dl
  • Adult males: 14-18 gm/dl
  • Adult women: 12-16 gm/dl
  • Men after middle age: 12.4-14.9 gm/dl
  • Women after middle age: 11.7-13.8 gm/dl [6]
(Amount of hemoglobin in grams (gm) per deciliter (dl) of whole blood.)

How Is The Test Performed?

Hemoglobin levels are amongst the most commonly performed blood tests, usually as part of a full blood count or complete blood count. The test is rather simple. The technician draws blood from a vein; from the inside of the elbow or the back of the hand, and the puncture site is cleaned with antiseptic. He or she inserts a small needle into the vein and collects the blood in an air-tight vial or a syringe. During the procedure, the band is removed to restore circulation, and once the tech collects the blood, they will remove the needle. 

Test Results

Lower-than-normal hemoglobin may indicate:

  • Anemia (various types)
  • Erythropoietin deficiency (from kidney disease)
  • Red blood cell destruction associated with transfusion reaction
  • Bleeding
  • Lead poisoning
  • Malnutrition
  • Nutritional deficiencies of iron, folate, vitamin B-12, vitamin B-6
  • Over hydration

Higher-than-normal hemoglobin may indicate:

  • Congenital heart disease
  • Cor pulmonale
  • Pulmonary fibrosis
  • Polycythemia vera
  • Increased RBC formation associated with excess erythropoietin [7, 8]

What Does A Low Hemoglobin Level Mean?

We also refer to low hemoglobin as anemia. There are many reasons for anemia. Some of the more common reasons are:

  • Loss of blood (traumatic injury, surgery, bleeding colon cancer)
  • Nutritional deficiency (iron, vitamin B12, folate)
  • Bone marrow problems (replacement of bone marrow by cancer suppression by chemotherapy drugs, kidney failure)
  • Abnormal hemoglobin (sickle cell anemia) [7,8]

Possible Causes Of Elevated Hemoglobin

A high hemoglobin count usually suggests that you have too many red blood cells. This condition is also called erythrocytosis. It can lead to several complications because it can impair circulation and result in abnormal clotting. [9]

An elevated hemoglobin concentration is usually the result of 2 mechanisms:

  • Increased red blood cell production as a compensatory mechanism when blood oxygen carrying capacity is compromised to meet the demand of tissue
  • Contracted plasma volume resulting in an appearance of greater red cell volume

Causes of an elevated hemoglobin count may include:

  • Living at high altitudes - The higher the altitude is, the lower the oxygen level is in the air, which forces the body to produce more hemoglobin to bind as much oxygen as possible!
  • Smoking - Several studies done in the past with volunteer smokers have proven that significant percentage of the smokers have the elevated hemoglobin level, although the mechanism is still unknown. Some experts believe that it could be because of the low level of “pure” oxygen in the smoker’s lungs. So, this could be an adaptive mechanism on low oxygen levels.
  • Dehydration - Dehydration produces falsely high hemoglobin which disappears when individual restores a proper fluid balance.
  • Congenital heart disease
  • Cor pulmonale - Failure of the right side of your heart due to high blood pressure in the arteries of your lungs (pulmonary hypertension)
  • Pulmonary fibrosis - A condition characterized by scarring or thickening of the tissue between the air sacs (alveoli) in your lungs
  • Polycythemia vera - Polycythemia vera is a rare bone marrow disease in which body makes too many red blood cells.
  • Anabolic steroid use

The Symptoms Of Elevated Hemoglobin And Possible Complications

Although much of the clinical focus has been on anemia as a condition where there is a lack of hemoglobin, there are also problems at the high end.

The most notable consequence is high blood viscosity.

Several studies have proven that the relation between hemoglobin and blood viscosity is linear when the hematocrit is <0.50 (equivalent to a hemoglobin value of 160 g/L). [10

Above this hemoglobin concentration, the relation becomes exponential, which means that a small increase in hemoglobin or hematocrit results in a substantial increase in viscosity. Once hemoglobin levels reach 180 g/L, the blood viscosity reaches a level that impairs microcirculation, and an inadequate amount of oxygen travels to tissues, similar to cases of severe anemia. [10]

Symptoms

Peripheral cyanosis and impaired mental function resulting from compromised cerebral blood circulation are the two most common symptoms of elevated hemoglobin. Additionally, because of the poor blood flow, the risk of thromboembolism increases significantly.

Treatment

High hemoglobin is not considered to be a particular disorder among medical professionals. Therefore, we treat it as a symptom of some other underlying disease. That’s why treating the underlying disease will probably lower your hemoglobin level.

A high hemoglobin count is usually found when your doctor has ordered tests to help diagnose a condition you're already experiencing. Talk to your medical provider about what blood test results mean. In some cases, your doctor should be able to indicate the cause of your illness from the existing tests, or she may suggest additional blood and other tests.