If you have ever wondered why anemia is very common in people with chronic diseases affecting the kidney or cancer, you need to take a close read. I will be explaining exactly how these conditions lead to normocytic anemia - a type of anemia where red blood cells are normal in size but reduced in number. Simple explanations will be given on the science behind this and why it matters.

Normocytic anemia in kidney disease, cancer and chronic infection is caused by an interruption in red blood cell production and lifespan, although the cells remain normal in size.

In chronic kidney disease, the kidneys don’t work as well as they should. One of their important jobs is to produce a hormone called erythropoietin. This hormone tells the bone marrow to make red blood cells. When the kidneys are damaged, they produce less of this hormone. As a result, the bone marrow doesn't get enough signal to make enough red blood cells, which leads to anaemia.

When someone has cancer, both the tumour and the body’s natural defence system (the immune system) release certain chemical signals called cytokines. These signals can slow down the bone marrow, which is the part of the body that makes red blood cells. They also affect how the body handles iron, making it harder to use. As a result, the body produces fewer red blood cells, leading to anaemia. This type of anaemia is common in people with cancer and is often not due to bleeding, but due to these changes inside the body.

In long-term infections, the body keeps fighting the illness by staying in a constant state of inflammation. This ongoing response doesn’t just stay in one area; it affects the whole body. During this time, the body releases certain chemicals that make it harder to use iron properly and slow down the bone marrow’s ability to make red blood cells. So, even if there’s enough iron in the body, it doesn’t get used well. This causes a drop in red blood cells, leading to normocytic anaemia.

In all these cases, the body struggles to maintain the normal red blood cell count, and this leads to normocytic anaemia. When one understands the details of how this condition leads to anaemia, it can help make the management and support of someone living with this disease better.

Understanding Normocytic Anaemia

Definition and Characteristics

Anaemia is a condition where there is a decrease in red blood cells, amount of haemoglobin or the collective volume of packed Red Blood Cells seen in hematocrit.¹ Red Blood Cells have the main function of carrying oxygen from the lungs to the body tissues and transporting carbon dioxide as a waste product from the body tissues to the lungs.

In the red blood cells, haemoglobin is a protein that helps carry oxygen throughout the body. Normocytic anaemia is when there are fewer red blood cells than normal, and even with that, these blood cells don't have the normal amount of haemoglobin.² It is characterised by red blood cells that are normal in size and colour, but the number is less than normal. It is also seen that the haemoglobin levels in these blood cells are reduced than the normal level.

Differences between Normocytic, Microcytic and Macrocytic Anaemia

These three types of anaemia are primarily differentiated by the effect it has on the size of the red blood cells. Mean corpuscular volume (MCV) is the term used to refer to the average size of the red blood cell.³

• For Normocytic Anaemia, MCV is 80- 100fL
• For Microcytic anaemia, MCV is less than 80fL
• Macrocytic Anaemia, MCV is more than 100fL

Therefore, Microcytic anaemia results in smaller and more pale red blood cells. It is mostly caused by a lack of iron, which is a very important component of haemoglobin. 

Macrocytic anaemia is characterised by red blood cells larger than normal. 

General Causes of Normocytic Anaemia 

There are three (3) main things that cause normocytic anaemia.

• Loss of blood due to injury sustained, internal bleeding, and heavy periods²
• Medical conditions that affect the ability of the body to produce enough red blood cells
• Medical conditions that cause the breakdown of red blood cells faster than normal. This is called hemolysis

Medical conditions that affect red blood cell production 

Anaemia of chronic diseases: Anaemia of chronic disease happens when a person has a long-term illness, and it affects how their body makes red blood cells. 

The bone marrow, which is like a factory that makes red blood cells, doesn’t work as well as it should. Also, the body either doesn’t make enough of a hormone called erythropoietin (which tells the bone marrow to make red blood cells), or the body doesn’t respond properly to it. On top of that, the red blood cells that are made don’t last as long as normal. All these issues together cause a lower number of red blood cells, leading to anaemia.

Endocrine deficiency: Some hormone problems in the body can lead to low red blood cell production. For example, when certain glands like the thyroid, adrenal, or pituitary glands are not working well (a condition called endocrine deficiency), the body may not make enough hormone called erythropoietin. This hormone is important because it helps the bone marrow produce red blood cells. Without enough of it, the bone marrow doesn’t get the signal it needs, and red blood cell production drops.

How Chronic Kidney Disease leads to Normocytic Anemia 

The Role of Kidneys in Erythropoiesis 

The kidneys naturally produce a hormone called erythropoietin. These hormones stimulate the production of red blood cells. It helps the body maintain a healthy amount of red blood cells. When the cells in the kidneys detect that there is low oxygen present in the blood, they increase the production of erythropoietin. Erythropoietin, in turn, makes the bone marrow make more red blood cells. On the other hand, when the kidney cells perceive that there is enough oxygen in the blood, there will be a reduced production of erythropoietin.⁵

Reduced Erythropoietin Production 

When the kidneys are damaged, it cannot produce as much erythropoietin as needed. This leads to low levels of erythropoietin. 

Iron Handling in Chronic Kidney Disease 

Iron is very important for the body, especially for making red blood cells. But having too much iron can be harmful, so the body carefully controls how much iron is used and stored.

In people with chronic kidney disease (CKD), this iron balance gets disturbed. The body doesn’t handle iron properly, which leads to problems in making enough red blood cells—this is one reason why anaemia is common in CKD. That’s why giving extra iron (iron supplements) is an important part of treating anaemia in these patients.⁶

Cancer and Normocytic Anaemia 

Impact of Chronic inflammation and cytokines

In cancer, chronic inflammation leads to the release of substances called cytokines. These cytokines disrupt the normal production of red blood cells by affecting how the bone marrow works and by blocking the proper use of iron in the body.⁷ Even though the red blood cells that are produced may be normal in size, their overall number is reduced. This results in normocytic anaemia, which is common in people with cancer. The anaemia is not caused by bleeding or iron deficiency, but by the body's response to long-term inflammation, which interferes with the normal processes that make red blood cells. 

Bone Marrow Suppression

Another major cause of cancer-related anaemia is bone marrow suppression due to chemotherapy, which reduces the marrow’s ability to produce red blood cells, leading to normocytic anaemia. Tumours can also invade the bone marrow or cause blood loss and destruction of red cells.⁸

Chronic Infections and Normocytic Anaemia 

In these infections, such as the Human Immunodeficiency Virus, Hepatitis and Tuberculosis, the body keeps fighting the illness by staying in a constant state of inflammation. This ongoing response doesn’t just stay in one area; it affects the whole body. During this time, the body releases certain chemicals that make it harder to use iron properly and slow down the bone marrow’s ability to make red blood cells. So, even if there’s enough iron in the body, it doesn’t get used well. This causes a drop in red blood cells, leading to normocytic anaemia.

Diagnosis and Clinical Features of Normocytic Anaemia 

How is Normocytic Anemia Diagnosed?

Blood tests help healthcare professionals to diagnose normocytic anaemia:²

• Complete blood count (CBC): Measures haemoglobin levels and evaluates overall blood health
• Peripheral blood smear: Used to identify the cause of anaemia
• Reticulocyte count: Assesses how well the bone marrow is producing red blood cells

Because normocytic anaemia often signals another health issue, further testing may be needed. For example, if kidney disease is suspected, additional blood, urine, or imaging tests may be performed.

Symptoms of Normocytic Anaemia 

Symptoms of normocytic anaemia often appear gradually. Some individuals may not experience noticeable changes at first. Possible signs are:

• Feeling tired or weak
• Lightheadedness
• Unusually pale skin
• Rapid heartbeat
• Difficulty breathing
• Skin that appears dry, pale, or bruises more easily than normal

Management Approaches 

Treating the Underlying Chronic Condition 

Managing normocytic anaemia begins with addressing the root condition causing it. For instance, if chronic kidney disease is responsible, treatment will focus on improving kidney function. As the primary condition is managed, the symptoms of anaemia may also improve.

The Use of Erythropoietin Stimulating Agents (ESAs)

In cases where anaemia is more severe, healthcare providers may prescribe medications that encourage the bone marrow to produce more red blood cells. These medications, known as erythropoietin-stimulating agents, help correct the reduced red cell production.

Conclusion

Normocytic anaemia is a type of anaemia where red blood cells appear normal in size but are reduced in number. It is often linked to chronic illnesses such as kidney disease, infections, inflammation, or cancer. The condition can result from decreased red cell production, increased destruction, or blood loss. Diagnosis involves blood tests like Complete Blood Count, peripheral smear, and reticulocyte count. Management focuses on treating the underlying cause and, in some cases, using erythropoietin-stimulating agents to boost red blood cell production. Early identification and proper management are essential to improve patient outcomes and reduce complications associated with normocytic anaemia.