Neutrophil function and abnormal results

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Neutrophils are a type of white blood cells (white blood cells or granulocytes) that, among other functions, protect us from infection. They make up approximately 40% to 60% of the white blood cells in our body and are the first cells to appear in situ when we experience a bacterial infection. The normal (absolute) neutrophil count is between 2,500 and 7,500 neutrophils per microliter of blood. Neutrophil counts can be high in infections, due to increased production in the bone marrow, as in leukemia, or due to physical or emotional stress. Low neutrophil counts can also be a sign of disease in conditions like leukemia, certain infections, vitamin B12 deficiency, chemotherapy, etc.

Get Medical Information / Laura Porter

Function

Neutrophils make up the majority of blood cells produced by the bone marrow. They are our "first responders", playing the role of the first line of defense against infectious organisms that enter our bodies.

These cells are the first cells to appear in situ when we experience bacterial infections. Damage to cells results in the release of "chemokines" that attract neutrophils to the site in a process called chemotaxis. Neutrophils are better known to the casual observer as an important component of pus.

Neutrophils become foreign invaders by "eating" them (a process called phagocytosis) or by capturing them in a cell in a process called endocytosis. As soon as a foreign organism is inside the neutrophil, it is "processed" by enzymes, which leads to the destruction of the organism. Neutrophils also help regulate the general immune response.

Neutrophils have a very short lifespan, averaging just 8 hours, but our bodies produce around 100 billion of these cells every day. Once released from the bone marrow, about half of these cells are present along the lining of blood vessels and the other half in body tissues.

Anatomy and structure

Neutrophils can be clearly seen under the microscope as cells with 2 to 5 characteristic lobes in the nucleus , which stain pink or purple with neutral tints. The term "PMN" or polymorphonuclear leukocyte refers to this discovery.

Neutrophils, leukocytes, and the immune system

If you hear about leukocytes and neutrophils, it can be confusing. If neutrophils are just one type of white blood cell, why do oncologists talk interchangeably about low white blood cell count and low neutrophil count in chemotherapy (chemotherapy-induced neutropenia )? The simple answer is that low neutrophil counts, in particular, can be the most dangerous to a person's susceptibility to infection .

All blood cells (white blood cells, red blood cells, and platelets) are made in the bone marrow, the spongy tissue in the central region of the bones, such as the thigh. In the bone marrow, all of these cells arise as cells of the same type, known as hematopoietic stem cells.

These stem cells then differentiate into different types of cells in a process known as hematopoiesis . Since all of these cells start from a common stem cell, processes that damage the bone marrow, such as chemotherapy, often affect all the different types of blood cells. This is called bone marrow suppression chemotherapy .

In addition to red blood cells and platelets, there are several types of white blood cells. Leukocytes develop in two different directions. A stem cell can develop along the lymphoid line , eventually leading to the formation of T and B lymphocytes, or along the myeloid line . A myeloid cell can become a neutrophil, eosinophil, monocyte, or basophil .

Neutrophils start out as myeloblasts, which develop into promyelocytes, myelocytes, metamyelocytes, streaks, and then mature neutrophils .

Number of neutrophils

The neutrophil count is monitored as part of a complete blood count . The normal neutrophil count, or absolute neutrophil count, is usually between 2,500 and 7,500 neutrophils per microliter.

Neutrophil levels below 2500 are called neutropenia, although the degree of reduction is significant. ANC less than 1000 is very serious, and it can seriously predispose someone to infections.

In your blood test report, neutrophils can be divided into two categories: segmented or mature neutrophils and immature neutrophils known as streaks. In severe infections, the bone marrow is stimulated to release more neutrophils (immature neutrophils), resulting in more bands on your report.

When healthcare providers check a complete blood count (CBC) or white blood cell count (WBC), they are also looking for an increase or decrease in the expected neutrophil count. Therefore, neutrophil testing is a very important part of the laboratory evaluation of the disease.

Neutrophil appearance

Neutrophil appearance, or "morphology," can also be helpful in diagnosing disease. While a complete blood count determines the number of white blood cells, a peripheral blood smear is often done to determine morphology to see the specific characteristics that may be present in neutrophils. For example, toxic granulations can be observed in neutrophils in severe infections, hypersegmented neutrophils (more than 5 lobes) in vitamin B12 and folic acid deficiencies, etc.

Causes of neutrophilia

Thinking about the function of neutrophils makes it easier to understand the increase in their number. Mechanisms that can increase the number of these white blood cells include:

Reagent

In reactive neutrophilia, there is an increase in the number of neutrophils in response to infection or stress. Stress hormones in our bodies cause the release of larger than normal amounts of these cells from the bone marrow.

Proliferative

Proliferative neutrophilia means an increase in the number of neutrophils due to an increase in their production in the bone marrow. It is seen more frequently in cancers such as acute myeloid leukemia. In this case, the type of white blood cell is usually abnormal, and although there are more neutrophils, they do not work as well as "normal" neutrophils .

Demarcation

Neutrophils often "live" attached to the lining of blood vessels. These neutrophils can become "narrowed" and circulate in the bloodstream due to stress, infection, and sometimes exercise. The release of neutrophils through the blood vessels into the bloodstream is one reason why the white blood cell count can sometimes rise rapidly (new neutrophils take longer to form or release from the bone marrow).

Conditions that can cause neutrophilia

Some specific causes of an increased neutrophil count (neutrophilia) include:

  • Infections
  • Stress
  • Cancers associated with blood cells, such as leukemia.
  • Autoimmune diseases such as rheumatoid arthritis.
  • Wounds and burns
  • Of smoking
  • The pregnancy
  • Thyroiditis
  • Eclampsia

Immature neutrophils (stripes) in the blood.

Most of the neutrophils in our blood are mature neutrophils. Immature neutrophils can be found in a blood smear if the body is under stress and there is an increased need for more neutrophils. When this happens, more immature neutrophils can enter the bloodstream from the bone marrow before reaching maturity. Your healthcare provider may mention that you have more streaks, or even less mature neutrophils, in your blood test.

On the other hand, increased production of immature neutrophils can occur in conditions such as myelodysplastic syndromes and leukemias such as acute promyelocytic leukemia .

Causes of neutropenia

Your neutrophil count may drop on its own or, conversely, along with other types of blood cells. The term pancytopenia refers to a decrease in the three main types of blood cells; red blood cells (called anemia), platelets (called thrombocytopenia), and white blood cells.

Mechanisms that can lead to a low neutrophil count can include:

Decreased or absent bone marrow production

The bone marrow can slow or stop the production of white blood cells, for example, when the bone marrow is damaged, as with chemotherapy, or there is a vitamin deficiency that causes insufficient production.

Penetration into the bone marrow

When the bone marrow is "absorbed" by cells such as cancer cells, it is called an infiltration of the bone marrow. The bone marrow can also become trapped in scar tissue (fibrosis) in conditions such as myelofibrosis .

Demand for more neutrophils

More neutrophils may be needed, for example, to fight infection or in response to injury. Initially, in most bacterial infections, the number of neutrophils increases. However, in severe infections, low neutrophil counts can occur because the immune system is suppressed by the infection.

Decreased survival of neutrophils.

While infections generally cause an increase in the neutrophil count, overwhelming infection, as well as infections caused by certain viruses and rickettsiosis, can result in decreased neutrophil survival and a low neutrophil count. Neutrophils can also face immune destruction due to antibodies directed against themselves in conditions such as lupus.

Destruction of neutrophils already produced.

Neutrophils that have been released from the bone marrow and circulating in the body can be destroyed in several ways. This can occur in autoimmune conditions in which antibodies (autoantibodies) are produced that directly destroy neutrophils.

Cyclic neutropenia

This rare condition, known as cyclic neutropenia, can be genetic or acquired and is characterized by periodic periods of low white blood cell counts and normal white blood cell counts .

The importance of low neutrophil counts

The severity of a low neutrophil count depends on several factors, particularly the degree of neutropenia. You are probably familiar with the stories of "bubble babies," babies born with severely weakened immune systems, but there are many stages in between.

Low neutrophil counts are one of the serious side effects of chemotherapy . When these cells are limited in number or function, or both, our bodies are less able to fight infections, even bacteria that generally do not cause serious infections.

Conditions that can cause neutropenia.

A decrease in the number of neutrophils may be associated with the above mechanisms:

  • Chemotherapy
  • Aplastic anemia
  • Exposure to radiation
  • Myelodysplasia
  • Blood-related cancers that invade the bone marrow, such as leukemia.
  • Viral infections
  • Suppressive infections (sepsis)
  • Rickettsial infections
  • Typhoid fever
  • Hypersplenism
  • Drug reactions: for example, penicillin, ibuprofen, and phenytoin.
  • Hyperglycemia
  • Vitamin B12 deficiency (megaloblastic anemia) and folate deficiency
  • Kostmann's neutropenia (a genetic disorder that affects young children)
  • Idiosyncrasy (meaning that no one knows for sure why the neutrophil count is low)

Diagnostics

If the neutrophil count deviates from the norm in a general blood test, further testing is necessary. This usually begins with a medical history and physical examination, taking into account the possible causes of the abnormalities. A peripheral (differential) smear is usually the next step and can detect any other visible abnormalities in the blood cells, including neutrophils (for example, the presence of immature neutrophils not usually found in the blood, called blasts). A complete blood count can also be repeated to rule out a laboratory error.

Additional tests will depend on the possible causes of the deviation from the norm and may include:

  • Bone marrow examination: to evaluate the origin of cells in the bone marrow.
  • Tests for infection
  • Blood tests such as thyroid function tests, vitamin B12 levels, and more.

Examples: Olivia's neutrophil count was low after chemotherapy, so her oncologist recommended that she start taking antibiotics to prevent infection.

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