The term hemoglobin combines the Greek word "heme" (meaning blood) with the Latin word "globulin" (meaning sphere).
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]
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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
The types of hemoglobins present in humans depends on their developmental stage.
In an embryo, we will see:
- Gower 1 (ξ2ε2)
- Gower 2 (α2ε2) (PDB 1A9W)
- Hemoglobin Portland (ξ2γ2)
In a 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 in humans 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 the human 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 blood 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. The first step is a molecule called 5-aminolevulic acid (ALA). This molecule is transported to the cytosol, where a series of reactions produce a ring structure called coproporphyrinogen III. It thent 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, an molecule that contains iron by definition. [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, binding the oxygen to themselves in the process. This oxygenated blood then travels throughout the entire bloodstream, releasing oxygen into the various muscles and organs all around the body. Once this cycle is complete, hemoglobin transports carbon dioxide to the lungs, and the process can start afresh.
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 Are Hemoglobin Levels Measured?
There are several methods for measuring hemoglobin levels, and most of them are done by machines designed to perform several different tests on the 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 in an individual's bloodstream. [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 biological sex of the person.
The normal ranges of hemoglobin 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]
How Is A Hemoglobin Level Test Performed?
Hemoglobin levels are amongst the most commonly performed blood tests, usually carried out 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, a band is placed and then removed to restore circulation, and once the tech collects the blood, they will remove the needle.
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Hemoglobin Level Test Results
Lower-than-normal hemoglobin levels 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 medical complications because erythrocytosis can impair circulation and result in abnormal blood 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 High Hemoglobin Levels
Causes of an elevated hemoglobin count may include:
- Living at high altitudes - The higher the altitude, the lower the oxygen level in the air, which forces the body to produce more hemoglobin to bind as much oxygen as possible! This is a normal and healthy compensatory mechanism.
- Smoking - Several studies done in the past with volunteer smokers have proven that a significant percentage of smokers have elevated hemoglobin levels, although the mechanism that causes this 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.
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