RBC Count: Diagnostic Significance and Clinical Insights
Author: Payal Bhandari, M.D.
Contributors: Nigella Umali Ruguain, Vivi Chador, Hailey Chin, Emilia Feria, Tejal
Key Insights
The Complete Blood Count (CBC) is a test that checks red blood cells (RBCs), white blood cells (WBCs), platelets (PLTs), and other blood components. RBCs carry oxygen, WBCs fight infections, and PLTs help with clotting. These are suspended in plasma, which makes up 55% of blood.
RBCs make up 45% of blood in adults and 60% in newborns. They contain hemoglobin, which gives blood its red color and carries oxygen. Blood is separated into plasma, a layer with WBCs and PLTs, and RBCs during testing.
The RBC Count Test measures the number of RBCs. A low count means anemia, and a high count may indicate polycythemia. This test helps diagnose blood disorders, infections, and cancers, and gives health insights.
Figure 1: Blood is divided into three parts: 55 percent is plasma, which comprises water (93 percent), salts, proteins, lipids, and glucose; 45 percent are RBCs; and 1 percent are WBCs and platelets.
What is the Red Blood Cell (RBC) Count Test?
The RBC count test examines how many red blood cells (RBCs; erythrocytes) comprise the total blood volume (RBCs and plasma). How much oxygen can be delivered to tissues depends on the number and function of RBCs.
Role of RBCs in the Body
Red blood cells (RBC) carry oxygen (O2) from the lungs to tissues and remove carbon dioxide (CO2) when we breathe out. They also help maintain the blood’s pH, which is important for all cells to work properly. To simplify this, think of RBCs like cars, with hemoglobin (Hb) as the driver. The hemoglobin picks up oxygen in the lungs and delivers it to the rest of the body.
Figure 2: RBCs’ main job is to carry oxygen (O2) to tissue and release the waste product, carbon dioxide (CO2) during exhalation. RBCs contain around 640 million hemoglobin molecules per cell.
About 98 to 99 percent of oxygen (O2) in the blood is carried by hemoglobin (Hb) in red blood cells (RBCs). Since oxygen doesn’t dissolve well in blood, less than 2 percent of the oxygen in arterial blood (the blood that carries oxygen from the heart to the body) is dissolved in plasma. Cells use oxygen, hydrogen (from water), and carbon (from glucose) to create energy (ATP). This process produces carbon dioxide (CO2) as a waste product, which is then removed from the body when we breathe out.
Figure 3: Oxygen binds to hemoglobin in red blood cells and is transported to tissue throughout the body.
Hypoxia happens when there isn’t enough oxygen or when the body needs more oxygen than it can get. This lack of oxygen makes it hard for cells to get enough energy to work properly. Hypoxia leads to the buildup of harmful molecules called reactive oxygen species (ROS), which can damage cells, change DNA, and affect healthy cell and microbiota growth.
Red Blood Cell Production and Life Cycle
Blood cells come from stem cells called hematopoietic stem cells (hemocytoblasts) in bone marrow. These cells become red blood cells (RBCs), platelets, and white blood cells (WBCs), with 60-70% turning into WBCs.
RBCs start as reticulocytes, which are bigger and have some ribosomal RNA (rRNA). As they mature, they shrink, lose their nucleus, and get a biconcave shape, helping them carry oxygen. RBCs use glucose for energy and don’t use the oxygen they carry. Once they run out of energy, they die.
Figure 4: Blood cells come from hematopoietic stem cells in bone marrow, mainly found in the skull, ribs, pelvis, and breastbone. The marrow makes red blood cells, platelets, and white blood cells (WBCs), which then turn into different types like monocytes, lymphocytes, eosinophils, neutrophils, and basophils.
Red blood cells (RBCs) live for about 120 days. When they get old or damaged, they are broken down by macrophages (a type of white blood cell) in the bone marrow, spleen, or liver. The harmful byproducts, like free hemoglobin and iron, are quickly removed from the blood, recycled, or eliminated from the body.
Figure 5: The Life Cycle of Red Blood Cells (RBCs; Erythrocytes) .
Red blood cells carry oxygen in the body. When oxygen levels drop, the kidneys release erythropoietin (EPO) to make more RBCs. The bone marrow creates new RBCs in 7 days using nutrients like iron and vitamins. RBCs carry oxygen for about 120 days before breaking down. Old RBCs are destroyed in the liver, spleen, and bone marrow. Their parts, like hemoglobin and iron, are recycled. Hemoglobin turns into bilirubin, which is processed and removed in bile, stool, or urine. Iron is stored or sent to the bone marrow for new RBCs, and globin is used to make amino acids.
Regulation of RBC Production
Red blood cell (RBC) levels are linked to how the body makes energy and proteins. Normally, the body gets energy from glucose, but during fasting or intense exercise, it switches to ketogenesis, which uses fat and muscle protein for energy.
In ketogenesis, fat is turned into glucose for the brain, reducing the need for carbs and protein. This helps stabilize blood sugar, save fat, and preserve muscle. It also supports RBC and hemoglobin production, which are needed for oxygen and energy. Ketogenesis can also occur in conditions like diabetes when glucagon is higher than insulin.
Figure 6: Cellular respiration is a process where cells convert energy from plants and microorganisms into molecules that store energy, like ATP, NADH, and FADH. During this process, cells also produce carbon dioxide as a waste product. The most energy is made in the mitochondria through a chain of reactions called the electron transport chain, which produces 34 ATP, plus 2 ATP from breaking down glucose and the Krebs cycle.
Figure 7: The breakdown of fats, proteins, and other substances in fat cells, liver, and muscles controls glucose and ketone production in the liver. Ketones provide energy during fasting, intense exercise, insulin shortage, or when the brain needs more energy. Ketones produce more energy (34 ATP) than glucose (2-4 ATP) and are influenced by the body’s circadian rhythm.
When the body can’t use fat for energy, the liver turns food into glucose, creating heat and reactive oxygen species (ROS), but little energy. High blood glucose causes sugar to attach to hemoglobin (in red blood cells) and thyroglobulin (which stores thyroid hormones). This causes:
Hemoglobin to break down, reducing the red blood cells’ ability to carry oxygen and shortening their lifespan.
Thyroglobulin to release thyroid hormones, which help cells get energy and stimulate red blood cell production.
Short-term fat metabolism issues raise red blood cell count, but long-term problems lower red blood cell production and speed up their destruction. A low red blood cell count (like in hemolytic anemia) is linked to poor fat and protein metabolism, fat breakdown, and thyroid overactivity, which causes inflammation and disrupts the body’s functions.
Clinical Significance of Low RBC Count
Anemia is when red blood cell (RBC) levels are low. This can happen if the body makes fewer RBCs, if blood’s liquid portion increases, or if RBCs lack enough hemoglobin (Hb) to carry oxygen. Without oxygen, cells can’t produce energy and may die.
Figure 8: Oxygen (O2) is crucial for energy production in cells. It pulls electrons through the electron transport chain in the mitochondria, creating a proton gradient. This gradient powers the production of adenosine triphosphate (ATP), the cell’s main energy source. In the presence of O2, electrons lose their charge as they move through the chain, allowing ATP to be created efficiently.
Figure 9: An absolute decrease in the RBC count lowers the concentration of oxygen delivered to tissues and the removal of the waste product carbon dioxide (CO2) by the lungs. Raising the blood CO2 and the acidity level (pH) prevents cells from harvesting enough energy to maintain normal physiological functions that are critical to sustaining quality and quantity of life.
Dehydration Increases RBC Destruction (Hemolysis) and Anemia
Blood is 90% water. Dehydration makes blood thicker and less able to carry oxygen. It also causes red blood cells (RBCs) to shrink, damaging them and shortening their lifespan. The brain senses this and triggers thirst and less urine production. Short-term dehydration raises RBC count, but long-term dehydration lowers it.
Figure 10: Water osmosis is the movement of water in and out of cells, based on solute concentration. In hypotonic cells, water moves in because there’s more solute inside, causing the cell to swell. In isotonic cells, water moves equally in and out since the solute concentration is balanced. In hypertonic cells, water moves out because there’s less solute inside, making the cell shrink.
Dehydration can happen due to:
Burns
Diarrhea
Overuse of diuretics or laxatives
Sweating from exercise or heat stroke
Not drinking enough water
Low breast milk intake in newborns
Excess blood loss can result from:
Heavy menstrual periods
Chronic inflammation (e.g., inflammatory bowel disease, stomach ulcers, celiac disease, or autoimmune disorders), which may increase the risk of infections and cancer
Blood loss from surgery or injuries
Frequent blood donations or draws
Dysbiosis, Nutritional Deficiencies, and Metabolic Disorders
Dehydration reduces blood flow to the digestive system and disrupts the balance of healthy gut bacteria (dysbiosis). Gut bacteria help with digesting food, absorbing nutrients, and removing waste. When the stomach takes longer to empty, it can lower stomach acid levels and worsen gut bacteria imbalance.
Figure 11: A healthy gut microbiota is key for digestion, nutrient absorption, and waste removal. Dysbiosis happens when good bacteria decrease, causing poor metabolism, less energy, and more inflammation. This leads to higher levels of harmful pathogens, proteins, and bad cholesterol in the blood.
Dysbiosis (an imbalance of gut bacteria) lowers the absorption of key nutrients like iron, zinc, and B vitamins. Without these nutrients, the body can’t make important proteins for digestion and energy. This causes undigested food in the small intestine, triggering inflammation and cell damage. Excess oxygen in the blood also oxidizes bad cholesterol, leading to atherosclerosis.
Figure 12: Atherosclerosis is when fat and scar tissue build up inside arteries, causing them to harden. This blocks blood flow, raises blood pressure, and can cause blood to back up into organs like the heart, liver, and legs, damaging them over time.
Atherosclerosis Induces Vascular Diseases, Autoimmune Disorders, Cancers, Infections, and Multi-Organ Depletion
Atherosclerosis is a condition where inflammation disrupts energy use and overactivates immune cells. Fat builds up in organs and blood vessels. White blood cells (WBCs), which fight infections, get distracted by repairing blood vessels. This causes the body to release proteins that affect hormones and inflammation.
If dehydration, gut issues, and low oxygen aren’t treated, atherosclerosis can cause autoimmune disorders and harm organs. The immune system may also help harmful cells, like viruses or cancer cells, damage tissue. This can increase the risk of metabolic problems, hormone imbalances, blood vessel diseases, infections, cancer, and organ damage, all linked to abnormal RBC levels and chronic inflammation .
Figure 13: Atherosclerosis causes blood vessel inflammation, increasing white blood cells (leukocytes) and platelets (thrombocytes). These cells help clear debris, repair injuries, and support infections and cancer. Tumor cells and pathogens use platelets to take in iron and hemin, helping them grow. Neutrophils release proteins to stabilize blood vessels and stop NK cells from destroying tumor cells. This allows tumor cells to activate platelets and form new blood vessels. White blood cell cytokines help pathogens produce toxins that damage red blood cells, steal nutrients, and promote infections and cancer growth.
Clinical Significance of High RBC Count
Polycythemia
Polycythemia is when the RBC count is too high. It can be caused by the bone marrow making too many RBCs or by dehydration, which temporarily increases the RBC count. Thick blood makes it harder to deliver oxygen, leading to RBC destruction and release of harmful byproducts like hemoglobin and iron. The body responds with inflammation, and white blood cells clear out these byproducts.
Figure 14: Polycythemia vera, or true polycythemia (vera meaning “true”), maybe due to an absolute increase in the number of RBCs produced by the bone marrow.
Low oxygen and heat trigger the production of EPO, TPO, and CFU-meg, which increase RBC and platelet production. Megakaryocytes (MKs), which become platelets, are too large to leave the bone marrow. Blood flow breaks off parts of MKs to form platelets. High levels of EPO, TPO, and CFU-meg lead to more RBCs and platelets. However, inflammation creates heat, damaging organs and lowering these levels. Sometimes, MKs escape to the lungs, where changes in oxygen turn them into platelets. This can cause excessive clotting, new blood vessels, and higher blood pressure. The lungs help remove extra MKs, reducing platelet production and protecting RBCs.
Figure 15: Low blood oxygen speeds up red blood cell death and triggers hormone production, leading to more RBCs and platelets. However, dehydration causes heat damage to organs, increasing red blood cell and platelet breakdown.
High Altitudes
At higher altitudes, the air pressure decreases, which means there are fewer oxygen molecules in each breath. This results in less oxygen available for the body to use. To compensate, the bone marrow produces more red blood cells (RBCs) to carry oxygen to the body’s tissues. As a result, people living at high altitudes tend to have a higher RBC count compared to those at sea level.
Prevalence and Statistics of Abnormal RBC Count
Anemia, or low red blood cell (RBC) count, affects one-third of the world. Acute anemia is caused by blood loss or fast RBC destruction, while chronic anemia often points to other health issues. The main cause is nutritional deficiencies, especially iron and B vitamins, which make up half of all anemias. This can be due to blood loss, poor diet, gut problems, or inflammation.
In the U.S., 44 to 57 out of 100,000 people have polycythemia (high RBC count), mainly those over 60. It’s rare in younger people. Polycythemia can be primary, like polycythemia vera (PV), caused by a JAK2 gene mutation that leads to too many RBCs and platelets. It can also be secondary, caused by low oxygen levels affecting organs like the bone marrow and kidneys.
Conclusion
The red blood cell (RBC) count is important for diagnosing serious health issues. High or low RBC counts can affect oxygen delivery to tissues and disrupt energy production. A high RBC count (polycythemia vera) can cause cancer and infections, while a low count (anemia) may be linked to inflammation, dehydration, nutrient shortages, and stress. These issues can lower RBC production, speed up RBC breakdown, and increase the risk of heart disease and organ damage.
Managing abnormal RBC counts involves lifestyle changes, better nutrition, stress relief, and supplements. If effective, medications may not be needed. Poor diet, sleep, and high stress harm blood flow, gut health, and nutrient absorption. A balanced approach is key to managing RBC levels and preventing disease.
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