Published May 09, 2023 by

Neutrophils: Normal Counts, High and Low Values

 

General Description

The production of neutrophils takes place in the bone marrow. Once the release of these cells into the blood stream is concrete, they are destined for the sector of the body where their intervention would be necessary.

It is important to mention that neutrophils are the white blood cells (also called leukocytes) of greater presence in the blood of people. Indeed, 70% of an individual's white blood cells can be neutrophils.

White blood cells or leukocytes are a type of blood cell whose function is to defend the body against infections, pathogens and tumor cells.

There are several types of leukocytes: lymphocytes, monocytes, eosinophils, basophils and neutrophils.

What are neutrophils?

Neutrophils are the most abundant type of leukocytes or white blood cells.

They are characterized by the multilobulated form of their nucleus and for helping in the first place to the points of acute inflammation in response to the signals that produce damaged cells and cells of the immune system. In this way, neutrophils constitute a large proportion of the early cellular infiltrate in tissues with inflammation, being the largest component of the purulent exudate.

Neutrophils constitute the first line of defense against invading microorganisms. They use strategies such as phagocytosis of pathogens and the release of antimicrobial factors.

It is also a type of cell capable of stimulating the response of other immune cells.

The participation of neutrophils makes it possible to create an antimicrobial environment in the place where inflammation has occurred, which contributes to the death of pathogens.


Valuation of neutrophils

From a blood analysis or complete blood count, it is possible to estimate the number of different cells that make up the blood. It is a very useful test in case of clinical situations of infection and chronic illnesses.

Functions and types

Among the actions carried out by neutrophils is the segregation of enzymes that allow the destruction of pathogenic microorganisms. Neutrophils can even phagocytose the microbes that are causing the infection.

If the organism needs a very high quantity of neutrophils before a bacterial infection, numerous immature neutrophils are generated that receive the name of cayados. These neutrophils, which are also called en band, remain in the bone marrow as a reserve.

On the other hand, segmented neutrophils are found, and the mature ones are the ones that are most abundant in the blood. Its function consists of transferring to the fabrics to fight against the action of the germs.


Particular features

The nucleus of neutrophils presents segmented chromatin in different lobes, although this segmentation does not appear in stray neutrophils. The cytoplasm, on the other hand, has many lytic enzymes.

It should be noted that neutrophils cannot be stained with basic or acidic dyes: this property derives its name. Under a microscope these leukocytes appear with a pale pinkish hue.


Normal and abnormal values

Normal neutrophil values ​​are around 2,000-7,500/mL, representing 45-75% of total leukocytes. Aunque in analytical studies we can study their absolute number, it is frequent to study their relative number in relation to the rest of blood cell count.

Age is the determining factor for the number of neutrophils that must be found in the blood. Note that these two values ​​are not directly proportional; for example: understood as quantity per microliter of blood, babies have between 4000 and 14 000, 10-year-old children have between 1400 and 6000 and adults between 1500 and 7000.

If the count gives a value that exceeds the normal maximum, if there is neutrophilia, it will take place in cases of:

* infections: in particular caused by bacteria, although they can also be the cause of parasites and viruses, such as pneumonia or appendicitis;

* non-infectious chronic inflammations: rheumatic fever or arthritis, among others;

* emotional and physical origin: excessive exercise, stress, smoking, strokes or embarrassment;

* drugs: generally corticosteroids;

* blood cancer: chronic granulocytic (or myelogenous) leukemia, which causes an increase in white blood cells in the medulla.

When a low count of neutrophils is obtained in a laboratory analysis, the patient suffers from neutropenia. This disorder is due to one of the following causes:

* infections: among the most common ones are infantile viral infections (chickenpox, rubeola, measles), viral hepatitis and bacterial infections (tuberculosis, brucellosis);

* congenital diseases: Kostmann syndrome, cyclic neutropenia, Schwachman Diamond syndrome, benign chronic neutropenia, Chediak Higashi syndrome;

* chemotherapy: chlorambucil, cyclophosphamide;

* blood problems: aplastic anemia.


Determining factors

The number of neutrophils in the blood can be affected by different factors, as well as we have seen until now. With regard to drugs, in addition to the already mentioned corticosteroids, we must add antipsychotics and lithium, all with the same consequence: an increase in normal values.

With regard to the decrease, we have talked about chemotherapy, but clozapine, methimazole, rituximab and procainamide can also be produced. Of course, these medications are not indicated arbitrarily, but they have very specific functions: we are talking about antipsychotics, antibiotics, antithyroids and antiarrhythmics, products that many times save the life of the patient. For this reason, the solution is not as simple as eliminating them from the treatment.


High neutrophils

The increase in the number of neutrophils, also known as neutrophilia, can happen due to several situations, the main ones being:
*Infections;
*Inflammatory disorders;
*Diabetes;
*Uremia;
*Eclampsia in pregnancy;
*Hepatic necrosis;
*Chronic myeloid leukemia;

*Myeloproliferative syndromes;

*Bleeding;

*Burn;
*Electric shock;
*Cancer.

Neutrophilia can also happen due to physiological conditions, such as in newborns, during childbirth, after episodes of repeated vomiting, fear, stress, use of drugs with adrenaline, anxiety and after excessive physical activity. Thus, if the neutrophil count is high, the doctor may order other diagnostic tests to correctly identify the cause and initiate the appropriate treatment. See more about neutrophilia.


Low neutrophils

A decrease in the number of neutrophils, also called neutropenia, can happen due to:
*Aplastic, megaloblastic or iron deficiency anemia;
*Leukemia;
*Hypothyroidism;
*Use of medications;
*Autoimmune diseases such as Systemic Lupus       Erythematosus;
*myelofibrosis;
*Cirrhosis.

In addition, there may be neonatal neutropenia in case of severe viral or bacterial infection after birth. Children with Down syndrome also tend to have low neutrophils without any health problems.


Representation of neutrophils

Neutrophils have a characteristic multilobed nucleus. Chemotaxis agents that attract neutrophils to sites of infection include:

Protein fragments released when complement is activated (eg, C5a);

Factors derived from the fibrinolytic and kinin systems;

Products of other leukocytes and platelets;

Products of certain bacteria.



Neutrophils have a large arsenal of enzymes and antimicrobial proteins stored in two main types of granules:

The primary granules (azurophils) are lysosomes that contain acid hydrolases, myeloperoxidase and muramidase (lysozyme); they also contain antimicrobial proteins, including defensins, seprocidins, cetelicidins and bacterial permeability-inducing protein (BPI)
and
Secondary granules (specific for neutrophils) contain lactoferrin and lysozyme.

During phagocytosis, lysosomes containing antimicrobial proteins fuse with vacuoles containing ingested microorganisms (called phagosomes), forming phagolysosomes, where destruction of the organisms occurs.

Neutrophils also release granules and cytotoxic substances into the extracellular environment when they are activated by immune complexes (antibodies linked to their specific antigens) through their Fc receptors. This is an important example of collaboration between the natural and acquired immune systems, being an important mechanism in immune complex diseases (type III hypersensitivity).


Development of neutrophils

Monocytes and neutrophils develop from a common precursor cell, the CFU-granulocyte macrophage (CFU-GM) cell. Myelopoiesis (the development of myeloid cells) begins in the liver of the human fetus around the 6th week of gestation.

CFU-GMs mature under the influence of colony-stimulating factors (CSFs) and various interleukins. These factors, which are relevant for the upregulation of hematopoiesis, are:

Derived primarily from stromal cells (connective tissue cells) in the bone marrow; They are also produced by mature forms of differentiated myeloid and lymphoid cells.


Neutrophil expression

The undifferentiated hematopoietic stem cell marker, CD34, like other early markers of this lineage, does not exist on neutrophils and mature mononuclear phagocytic cells. Other markers can also be lost during differentiation in one way, but maintained in another.

For example, the common precursor of monocytes and neutrophils, the UFC-GM cell, expresses major histocompatibility complex (MHC) II molecules, but only monocytes continue to express significant levels of this marker.

It is important to point out that CFU-GM go through different stages of differentiation until they become neutrophils. As CFU-GM differentiates in the neutrophil pathway, we can distinguish several distinct morphological stages. Myeloblasts differentiate into promyelocytes and myelocytes, which mature and are released into the circulation as neutrophils.

The unique pathway of differentiation of CFU-GM in mature neutrophils results from the acquisition of specific receptors for growth and differentiation factors in progressive stages of their development. Differentiation surface markers disappear or are expressed in cells as they develop into granulocytes. For example, class II MHC molecules are found in GM-CFU, but there are no mature neutrophils.

It is difficult to assess the functional activity of the different stages of granulocyte development, however it is most likely that only when the cells are mature is their functional potential fulfilled.

There is some evidence that neutrophil activity, as measured by phagocytosis and chemotaxis, is lower in fetal life than in adult life. However, this may be partially due to lower levels of opsonins in fetal serum and not due to cell characteristics.