Red Blood Cells

Red blood cells (RBCs), also known as erythrocytes, are essential to proper health and wellness.  

Red blood cells are specialized cells in the bloodstream responsible for transporting oxygen from the lungs to various tissues and organs in the body. They also play a key role in removing carbon dioxide, a waste product of cellular metabolism, from the tissues and transporting it back to the lungs for exhalation.

The primary function of red blood cells is to facilitate gas exchange by carrying oxygen from the lungs to tissues and organs and transporting carbon dioxide from the tissues back to the lungs for elimination. This process, known as oxygenation and deoxygenation, is vital for sustaining cellular metabolism and maintaining physiological balance.

In this article, we will explore the definition, function, lab tests, interpretation of test results, related biomarkers, and natural ways to support and optimize RBC levels and function. 

Definition and Function

What Are Red Blood Cells, or Erythrocytes in Blood?  [1., 13.]

Erythrocytes, or red blood cells (RBCs), are vital components of blood responsible for transporting gasses like oxygen and nutrients throughout the body. 

Their distinctive biconcave, discoid shape and lack of a nucleus enable them to maneuver through the cardiovascular system efficiently. 

Composed primarily of hemoglobin, which gives them their red color, RBCs play a crucial role in oxygen delivery to tissues and carbon dioxide removal. Their small size and unique shape optimize surface area for gas exchange and allow passage through narrow capillaries. 

With a lifespan of approximately 120 days, RBCs are continuously produced and cleared from circulation.

During circulation, RBCs encounter various physical and chemical stresses, particularly in the spleen, where they undergo scrutiny for deformities and aging-related changes. The spleen acts as a filter, identifying and removing defective or senescent RBCs through phagocytosis by macrophages in the splenic cords. 

Mechanisms involved in the recognition of aged RBCs by macrophages are still under investigation, with phosphatidylserine exposure being one proposed mechanism. Alterations in membrane phospholipids and cytoskeletal proteins may contribute to this process.

In addition to physiological processes like red cell senescence, pathological conditions can lead to abnormal RBC clearance, such as hemolysis. Hemolysis can occur intravascularly or extravascularly, with the spleen playing a major role in the latter. 

Reduced RBC deformability, oxidative damage, and antibody-mediated destruction are among the factors contributing to abnormal RBC clearance. 

Phagocytosis of opsonized RBCs by macrophages is a key aspect of the immune-mediated destruction process, involving interactions between antibodies, complement proteins, and Fc receptors on macrophages.

Laboratory Testing for Red Blood Cells

General Test Information and Sample Type

A red blood cell count is typically part of a complete blood count (CBC) with differential, which measures the types and numbers of cells in the blood including red blood cells, white blood cells, and platelets. 

A complete blood count (CBC) is commonly ordered to assess overall health and detect a wide range of conditions, including infections, anemia, and various blood disorders, by providing information on the quantity and quality of different types of blood cells.

This test is usually conducted using a blood sample obtained via venipuncture, where a healthcare professional collects a small amount of blood from a vein, typically in the arm. The blood sample is then analyzed in a laboratory to determine the amount of red blood cells present in the bloodstream.

A CBC contains the following information about red blood cells:

RBC count: indicates the quantity of red blood cells responsible for oxygen transport and carbon dioxide removal. Abnormal levels may indicate anemia or other conditions affecting blood flow.

Red cell distribution width (RDW): evaluates the variation in red blood cell size. Higher RDW values may indicate anemia or other underlying issues.

Hematocrit (HCT): represents the percentage of red blood cells in whole blood. Low levels could signify bleeding, iron deficiency, or other disorders, while elevated levels may result from dehydration or other conditions.

Hemoglobin (Hgb or Hb): measures the protein responsible for oxygen transportation in red blood cells. Abnormalities in hemoglobin levels may indicate various conditions, including anemia or lung disease.

Mean corpuscular volume (MCV): reflects the average size of red blood cells. Increased MCV suggests larger-than-normal cells, possibly due to vitamin B-12 or folate deficiency anemia, while decreased MCV may indicate other types of anemia, such as iron deficiency anemia.

Platelet (PLT) count: assesses the quantity of cell fragments crucial for blood clotting. Abnormal platelet levels may indicate an increased risk of bleeding or other underlying conditions.

Mean corpuscular hemoglobin (MCH): measures the amount of hemoglobin in red blood cells on average, providing further insight into oxygen-carrying capacity and potential abnormalities.

A manual assessment of red blood cells may also be done to check for changes in the size or shape of red blood cells beyond the typical CBC findings.  

No special preparation is typically required for this test, although in certain situations the ordering healthcare provider may request discontinuing certain medications or supplements. 

Interpreting Test Results

Reference Range of Red Blood Cells

The typical reference range for red blood cells is given as:  [6.]

Adult males: 4.5-5.9×106/mm3 (4.5-5.9×1012/L) 1

Adult females: 4-5.2×106/mm3 (4-5.2×1012/L) 1

Clinical Significance of High Levels of Red Blood Cells  [3., 12.]

A high concentration of red blood cells is also called erythrocytosis or polycythemia. Erythrocytosis refers to increased red blood cell (RBC) mass, reflected in elevated hemoglobin and hematocrit levels.

It includes subtypes like Polycythemia vera, which may involve overproduction of multiple cell lines.

Erythrocytosis is associated with increased risk of thrombotic events due to blood hyperviscosity.  Polycythemia vera can potentially progress to leukemia.

Polycythemia is differentiated as spurious and true polycythemia. 

Spurious Polycythemia

Spurious polycythemia refers to a condition characterized by an apparent increase in red blood cell (RBC) mass without an actual rise in the number of RBCs. Instead, it results from volume contraction or reduction in plasma volume, leading to a relative increase in hematocrit levels. In essence, it is a false elevation in hematocrit due to dehydration or other factors causing fluid loss, rather than a true increase in RBC production.

True Polycythemia

True polycythemia, also known as absolute polycythemia, refers to a condition characterized by a genuine increase in the number of red blood cells (RBCs) or the volume of circulating blood. This increase can result from either an absolute increase in red cell mass (absolute erythrocytosis) or a decrease in plasma volume (relative erythrocytosis). Absolute polycythemia can be further classified based on serum erythropoietin (EPO) levels into primary (low EPO levels) and secondary (high EPO levels) types. Primary polycythemia includes conditions like polycythemia vera, while secondary polycythemia can arise from factors such as chronic hypoxia, renal disorders, high altitude, or certain medications

Causes of increased red blood cells can include:  [12.]

Spurious Polycythemia: 

• Causes include severe dehydration and Gaisböck syndrome, which is usually seen in obese hypertensive male smokers.

True Polycythemia:

• Low serum EPO levels (Primary polycythemia):

• Polycythemia vera  [9.]some text
  • Polycythemia vera (PV) is a rare, chronic cancer characterized by the excessive production of red blood cells (erythrocytosis), as well as an increase in white blood cells and platelets. 
  • Caused by a mutation in the JAK2 gene, it leads to an increase in blood volume and viscosity, which can cause complications such as blood clots, stroke, and heart attack. 
  • Symptoms may include fatigue, headaches, itching (especially after a warm bath or shower), and a reddish or purplish complexion.

• Primary familial and congenital polycythemia

• High serum EPO levels (Secondary polycythemia):

• Chronic hypoxia
• Respiratory disorders (e.g., COPD, Pickwickian syndrome, uncontrolled asthma)
• Cyanotic heart diseases with right-to-left shunts
• Renal disorders (e.g., renal cysts, kidney cancer, renal artery stenosis, Bartter syndrome, focal sclerosing glomerulonephritis)
• Elevated carboxyhemoglobin (e.g., smokers, exposure to closed spaces with car exhaust)
• Hemoglobinopathies (e.g., high-affinity hemoglobins, methemoglobinemia)
• EPO-secreting tumors (e.g., hepatomas, uterine leiomyomas, cerebellar hemangiomas)
• Iatrogenic causes (e.g., erythropoietin analog administration, anabolic steroids, testosterone replacement therapy)

Neonatal Polycythemia:

• Compensatory increase in hematocrit due to relative tissue-level hypoxia in the intrauterine environment.
• Exacerbated by high affinity of fetal hemoglobin for oxygen.

Clinical Significance of Low Levels of Red Blood Cells

A low red blood cell count is indicative of anemia, typically iron deficiency anemia.  This occurs when the body’s stores of iron drop too low to maintain an adequate number of red blood cells in circulation.  

Other causes of low red blood cell counts include:  [2.]

Hemolysis: excessive breakdown of red blood cells in conditions like autoimmune hemolytic anemia leads to a decrease in red blood cell counts.

Chronic renal failure: impaired production of erythropoietin by the kidneys in chronic kidney disease results in reduced stimulation of red blood cell production in the bone marrow, leading to low red blood cell counts.

Hemorrhage: acute or chronic blood loss from sources such as gastrointestinal bleeding or trauma causes a depletion of red blood cells in circulation, resulting in low red blood cell counts.

Failure of marrow production: conditions like aplastic anemia or myelodysplastic syndromes hinder the normal production of red blood cells in the bone marrow, leading to low red blood cell counts.

Related Biomarkers

In addition to the red blood cell measurements and indices available as part of a complete blood count (CBC), other biomarkers to consider assessing the status of red blood cells may include:

Serum ferritin: represents the level of iron stores in the body. Levels below 30 ng/mL are generally considered diagnostic of iron deficiency, with values below 10-15 ng/mL being 99 percent specific for iron deficiency anemia.

% Transferrin saturation: indicates the proportion of transferrin (the protein that transports iron in the blood) that is saturated with iron. A transferrin saturation of under 20% generally indicates iron deficiency.

Serum iron: measures the amount of iron circulating in the blood. Low levels may indicate iron deficiency.

Total iron-binding capacity (TIBC) and unsaturated iron-binding capacity (UIBC): measures the capacity of transferrin to bind to iron. Elevated levels may indicate iron deficiency.

Natural Ways to Support Healthy Red Blood Cells

Balanced diet: consuming foods rich in iron, such as spinach, red meat, lentils, and fortified cereals, supports red blood cell production.  

Additionally, a varied diet containing vitamin B12, folate, and plenty of plant-based antioxidants supports healthy red blood cells and may reduce the risk of red blood cell aggregation and blood clot formation.  [8.]

Vitamin supplementation: ensuring adequate intake of vitamins essential for red blood cell production, such as vitamin B12 (found in fish, poultry, dairy, and fortified foods) and folate (found in leafy greens, beans, and citrus fruits), can support healthy red blood cells.  [5.]

Always speak with a licensed healthcare provider prior to initiating any new supplement therapy.   

Regular exercise: engaging in physical activity promotes red blood cell production.  [4.]

Avoiding tobacco and excessive alcohol: smoking and excessive alcohol consumption can negatively impact red blood cell production and function.  [14.]

Herbal remedies: some herbs such as nettle leaf and dandelion are believed to support healthy blood and may help in maintaining red blood cell health, although scientific evidence is limited and consulting a healthcare provider is recommended.  [10., 11.]

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