Understanding The Pathophysiology Of Anemia

Anemia is the decrease in the blood's total amount of red blood cells (RBCs), where hemoglobin or hematocrit is below normal. It is a common condition where the body cannot deliver enough oxygen to the body tissues. 

Generally, anemia results from decreased RBC production, issues with RBC production, blood loss, increased RBC destruction, or poor RBC maturation. The pathophysiology of anemia is key to understanding when the condition starts developing, early diagnosis, and prevention.

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What is the pathophysiology of anemia?

At a biological level, anemia results from an imbalance between erythrocyte loss subject to production or issues with hemoglobin. This occurs due to the following: 

Absolute anemias:

  • Decreased red cell production: Acquired, hereditary

  • Increased red cell destruction: Acquired (mechanical, antibody-mediated, hypersplenism, RBC membrane disorders, chemical injury), hereditary

  • Blood loss and blood redistribution

Relative anemias:

  • Macroglobulinemia, pregnancy, athletes, postflight astronauts

The pathophysiology of anemia differs significantly depending on the underlying etiology. For example, restoring blood volume with intracellular and extracellular fluid in acute hemorrhagic anemia dilutes the remaining RBCs and can cause anemia. 

The bone marrow produces RBC and releases it into circulation. An imbalance in production to destruction or removal of RBC can result in anemia.

What are the causes of anemia?

In 2010, about one-third of the world's population had anemia. The bone marrow is a soft tissue in the middle of the bones. It produces almost all blood cells. Although several areas of the body contribute to the maturation of red blood cells, the bone marrow does most of the work.¹

Healthy red blood cells usually last for about 120 days. Different body parts then flush out old blood cells. Your kidneys produce erythropoietin (EPO), a hormone that signals your bone marrow to produce more red blood cells.

Hemoglobin is the protein that carries oxygen inside red blood cells. Red blood cells get their color from it. Hemoglobin levels in those with anemia are insufficient. Your body needs specific nutrients, minerals, and vitamins to produce enough hemoglobin and red blood cells. Folic acid, vitamin B12, and iron are three essential ones. 

The cause of anemia can also result in the bone marrow response being hypoproliferative or hyperproliferative. 

Here are the causes of anemia:

Genetic disorders

Several different genes can cause various kinds of hereditary anemia. Most individuals are born with genetic disorders that can cause specific types of anemia, such as Fanconi anemia, thalassemia, and sickle cell anemia.

Nutritional anemia

Different vitamins and minerals, including some micronutrient deficiencies, may cause anemia. Nutritional anemia is a common problem if the body fails to absorb sufficient specific nutrients. 

Nutritional deficiency leads to low levels of hemoglobin, low red blood cell count, or red blood cells that don't function properly. 

Here are the types of nutritional anemia.

  • Pernicious anemia: This autoimmune disorder hinders your body from absorbing vitamin B12 and is one of the causes of vitamin B12 deficiency.

  • Iron-deficiency anemia: This condition occurs when the body lacks enough iron to produce hemoglobin. Red blood cells deliver oxygen throughout your body thanks to a protein called hemoglobin.

  • Megaloblastic anemia: This form of vitamin deficiency anemia develops when a person is deficient in vitamin B12 or vitamin B9 (folate), leading to impaired nucleic acid metabolism.

Inflammation and infection

Anemia of inflammation, also known as anemia of chronic disease, develops due to an ongoing infection or disease. Anemia of chronic disease is thought to be an evolutionary strategy to limit iron availability to invading microbes. 

Specific diseases like COVID-19, HIV/AIDS, or rheumatoid arthritis can affect how the body manages iron and related proteins.

What are the primary mechanisms of anemia?

Anemia is a disease that affects up to one-third of people worldwide. Most times, it is minor and asymptomatic. Anemia is classified as either chronic or acute. Chronic anemia is a decline in RBCs or hemoglobin due to chronic diseases, iron, or other nutritional deficiencies. Acute anemia occurs when RBCs/Hb drop abruptly, usually by acute hemorrhage or hemolysis.²

Here are some mechanisms leading to anemia.

Red blood cell destruction

All areas of your body receive oxygen thanks to RBCs and hemoglobin. Your blood cannot supply sufficient oxygen to all your tissues and organs if you have anemia. Also, your body can't function as well as it should without enough oxygen.

Hemolytic anemia occurs when there is an excessive increase in the hemolytic process. This overshoots the capability of the bone marrow to produce RBC.

Specific conditions could cause hemolysis to occur too often or too fast. These include blood transfusion complications, hemoglobinopathies, enzyme deficiencies, hypersplenism, drugs and toxins, Wilson disease, mechanical damage, or autoimmune conditions.

Defective or inefficient erythropoiesis

Inefficient/defective erythropoiesis leads to a series of circumstances. This can cause anemia, bone marrow expansion, hemolysis, or iron deficiency.

Megaloblastic anemias are defined by inefficient erythropoiesis, meaning there is reduced efficiency of cell division and nuclear-cytoplasmic dyssynchrony. Ineffective erythropoiesis is the production of defective erythroid precursor cells.

Who is at risk of developing anemia?

Anemia prevalence increases with age and is more common in pregnant women, the elderly, and women of reproductive age. Several individuals risk anemia due to infections, chronic diseases, intestinal disorders, poor diet, and other conditions. 

Children below five years, specifically infants and children below two years old, are also vulnerable to anemia. ³

How is anemia diagnosed?

Anemia diagnosis starts with your family health history and your health history, plus a physical exam. 

Here are some examples of tests that a healthcare professional may recommend:

  • Serum iron levels: A serum iron test can show if the cause of your anemia is iron deficiency. It's a blood test that measures the total amount of iron in your blood.

  • Folic acid test: This blood test measures your folate levels to determine if it's too low.

  • Complete blood count (CBC): You can know your hemoglobin levels through the CBC blood test. It can also show if the levels of platelets or white blood cells are normal and if the bone marrow is producing a sufficient amount of new red blood cells, amongst other things.

  • Vitamin B12 test: This is a blood test that measures the levels of your vitamin B12. It determines if the levels are too low.

  • Reticulocyte count: A reticulocyte test measures the levels of reticulocytes (immature red blood cells). Through it, your doctor will know if your bone marrow is producing enough new erythrocytes (red blood cells).

  • Ferritin test: This test analyzes iron stores in your body.

  • Bone marrow tests: Bone marrow biopsy or aspirate tests determine if your bone marrow is functioning as it should. It's also helpful if a doctor suspects conditions like aplastic anemia, leukemia, or multiple myeloma.

  • Peripheral smear

A history of exposure to toxic substances at work or home could indicate an environmental cause. A family history of specific types of anemia, like sickle cell anemia, might help.

What are the complications of anemia?

Anemias can cause severe complications if it's not treated, depending on the exact cause. These include: 

  • Gallstones

  • Thromboembolism

  • Impaired muscular performance

  • Heart problems, like a heart attack or failure, angina, enlarged heart, and arrhythmias

  • Developmental delays in children

  • Peripheral nerve damage

  • Pregnancy complications, such as low birth weight or premature birth

You should see your doctor to avoid potential complications if you develop symptoms or signs of anemia. In most cases, treatment of anemia is easy.

How to prevent anemia

Iron is necessary for the production of hemoglobin for RBCs. An iron-rich and nutritious diet helps prevent common anemia. Heme is a vital component of hemoglobin that helps convey oxygen; folate is necessary for heme production.

The lowdown

Anemia occurs when a reduced number of RBCs/Hb are circulating in the body. This can reduce an individual's oxygen availability, leading to symptoms like shortness of breath, fatigue, chest pain, etc.

Common causes of anemia include impaired or lower RBC production, blood loss, and destruction. Your doctor will conduct tests to detect anemia. Anemia prevention may include dietary changes.

Frequently asked questions

What is the concept of anemia?

Anemia is the decrease in the oxygen-carrying capacity of blood due to the reduction in hemoglobin concentration and/or RBC volume. It can make you feel weak and tired. 

What are the types of anemia?

There are numerous types of anemia, each with its telltale causes. Common types of anemia include:

  • Iron-deficiency anemia

  • Pernicious anemia

  • Hemolytic anemia

  • Aplastic anemia

  • Anemia of inflammation, or chronic disease

What are the main causes of anemia?

Your risk of anemia increases if you consume a diet persistently deficient in iron, vitamin B12, and folate. People with intestinal problems such as celiac disease or Crohn's disease that interferes with the absorption of nutrients in the small intestine run the risk of developing anemia. 

Most individuals may develop anemia due to specific chronic diseases or inherit some specific types of anemia.

What are the compensatory mechanisms of anemia?

Hemodynamic and non-hemodynamic mechanisms of anemia function to compensate for anemia. Increased oxygen extraction and increased erythropoietin production are the non-hemodynamic mechanisms.

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