Determining Disease Through White Blood Cells

White cells are the immune cells of the body. Also called leukocytes, they are useful in fighting infections and belong to five types. About 100 million white cells are produced by the body each day.

These include granulocytes, comprising neutrophils, basophils, and eosinophils, and the non-granular cells, comprising lymphocytes and monocytes. The former are produced in the bone marrow, as are monocytes, while the lymphocytes are produced in the lymphoid tissue.

Neutrophils makeup 45-75% of white cells in the circulation, and are the major first-line defense against infectious pathogens such as bacteria and some fungi. Lymphocytes make up 20-40%, with other white cells comprising small percentages.

A normal white cell count is between 4,000 to 11,000 cells per microliter of blood. Counts that are higher or lower than expected could indicate an underlying health condition. A higher count is referred to as leukocytosis, while low counts are called leukopenia.

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Causes of leukocytosis

Leukocytosis is defined as a white blood cell count greater than 11,000 per microliter of blood.

Leukocytes are raised in most infections and inflammatory conditions. Other causes may exist, such as the use of corticosteroids, lithium, and beta-agonists. The highest rise is seen with serious disorders such as leukemias, which are cancers of the bone marrow. In these conditions, immature white cells are sometimes released too early from the bone marrow, causing a shift to the left.

With marked leukocytosis in the absence of a discoverable infection, injury, or inflammation, a sample of blood is viewed under the microscope to look for immature cells, or myeloblasts. This is especially so if red cells and platelet are also abnormal.

The most common bone marrow disorders include acute leukemias, chronic leukemias, and myeloproliferative disorders.

An increase in the white cell count may involve one or more types of cell. When only the neutrophils are involved, it is called neutrophilic leukocytosis, while with a predominance of lymphocytes, lymphocytic leukocytosis is present.

Eosinophilia is defined as a peripheral blood eosinophil count > 500/microliter. Eosinopenia is not usually considered a problem though it may occur during Cushing’s syndrome, sepsis, and corticosteroid treatment.

Monocytes make up 1-10% of the blood cells, while basophils comprise <3%. Eosinophils make up less than 7%.

Causes of leukopenia

Leukopenia is a decrease in the number of white blood cells to fewer than 4,000 cells per microliter of blood.

Neutropenia is defined as a drop in circulating neutrophils below 1,500/microliter in Whites, but <1,200/microliter in Blacks.

Lymphocytopenia is referred to as <1,000 lymphocytes/microliter in adults, but since these cells comprise only 20-40% of the total white cell count, a drop in the total count is not always present.

Monocytopenia refers to the presence of <500 monocytes/microliter. These cells migrate into the tissues, where they become macrophages, engulfing and destroying foreign bodies and pathogens, as well as cell debris.

Low white cell counts may be caused by the underproduction of white cells in the bone marrow, sometimes following exposure to chemicals like benzene, or due to primary or secondary malignancies. The treatment of cancers by chemotherapy or radiation can also cause leukopenia due to reduced bone marrow synthesis of these cells.

Autoimmune disorders such as systemic lupus erythematosus, or rheumatoid arthritis, can also lead to the destruction of the body’s own white cells by antibodies created by the immune system.

Viral infections may also cause leukopenia, usually because of the rapid consumption of white cells faster than the rate of their production in the bone marrow. The human immunodeficiency virus (HIV) is known to target one type of lymphocyte, bearing the CD4 marker, leading to profound immunodeficiency.

Drugs such as some antibiotics are known to cause leukopenia by the destruction of white cells.

The presence of generalized malnutrition, or the deficiency of certain vitamins such as folic acid and vitamin B12 can also affect bone marrow production of white cells. This is the case with alcohol intake in excess as well because this can be associated with the deficiency of some B vitamins.

Hypersplenism is another cause of leukopenia since it is a source of lymphocytes. When hit by infections, clots, or disease, it can stop producing enough white cells.

These conditions are diagnosed in part by a differential count of the five types of white cells, indicating a higher possibility of a viral or bacterial infection, an allergy, or the presence of inflammation.

Neutrophil abnormalities

Neutrophilic leukocytosis is seen in infections when the body fights off invading pathogens or reacts to foreign particles. Bacteria, viruses, fungi, and parasites may all trigger such a rise.

It is also observable after injuries, during inflammatory disorders, and with the use of certain drugs like corticosteroids. The most alarming rise is typically seen with myeloid leukemias, with acute myeloid leukemia being associated with a higher percentage of immature cells in the blood.

Neutropenia is a potentially life-threatening condition. The most common cause is cancer chemotherapy or radiation.

The occurrence of frequent or unusual infection often raises the suspicion of neutropenia, which is diagnosed with a blood test, and sometimes a bone marrow biopsy.

Neutrophils may be decreased due to underproduction or over-consumption. The former may occur due to cancers of the bone marrow, influenza and other viral infections, tuberculosis and other bacterial infections, myelofibrosis where the bone marrow is replaced by fibrous tissue, or deficiencies of vitamin B12 or folate, as mentioned above.

Drugs, radiation, and chemotherapy are also causes of acute neutropenia. Some uncommon hereditary disorders such as cyclic neutropenia and chronic benign neutropenia are also known, as well as severe congenital neutropenia, a cluster of illnesses where neutrophils fail to mature, leading to high susceptibility to severe infections.

Lymphocytic leukocytosis

In this condition, total white cell counts are up because of increased numbers of lymphocytes. These cells protect against all types of pathogens. They are of three types, B cells, T cells, and Natural Killer (NK) cells.

Lymphocytosis occurs most commonly in viral infections like infectious mononucleosis, lymphomas, and lymphocytic leukemias. Certain autoimmune diseases may also be associated with increased lymphocyte counts.

Monocyte abnormalities

Low monocyte counts can be associated with a high risk of infection, which can be serious in patients with acetaminophen-induced liver damage, or burns. The causes include myelosuppression due to chemotherapy, certain mutations of the bone-forming cells, cancers of the lymphoid system, infections, treatment with steroids or immunoglobulins, and certain surgeries.

Monocytosis can occur with infectious mononucleosis, mumps, and measles, certain parasitosis, chronic infections, acute stress or trauma, systemic inflammations including autoimmune disorders, drug reactions, neutropenia, and after splenectomy.

Eosinophil abnormalities

Eosinophils are involved in primary defenses against parasitic infections, though their exact role is not clear. Raised eosinophil counts, therefore, indicate the presence of parasites, intracellular bacteria, or an allergic reaction, among many other conditions.

Prolonged eosinophilia is associated with tissue damage. The presence of Charcot-Leyden crystals, composed of phospholipase B

Eosinophil counts may go down with stress, with the use of beta-blockers, or corticosteroids. Some bacterial or viral infections also cause eosinopenia.

Basophil abnormalities

Basophil counts go down in thyrotoxicosis, acute allergies, and infections. Basophilia may be observed in hypothyroidism, myeloproliferative disorders, such as polycythemia vera. Increased basophil counts can cause itching in some cases.

References:

• Low White Blood Cell Count (2018). Retrieved from: https://my.clevelandclinic.org/health/symptoms/17706-low-white-blood-cell-count. Accessed on 6 October 2021.
• Overview of White Blood Cell Disorders (2020). Retrieved from: https://www.msdmanuals.com/home/blood-disorders/white-blood-cell-disorders/overview-of-white-blood-cell-disorders. Accessed on 7 October 2021.
• Abramson, N. et al. (2000). Leukocytosis: Basics of Clinical Assessment. Retrieved from: https://www.aafp.org/afp/2000/1101/p2053.html. Accessed on 7 October 2021.

Further Reading

• All Infectious Diseases Content
• Sex Differences in Infectious Diseases
• What is Reverse Zoonosis?
• How Does Travel Influence Spread of Disease?
• How to Prevent the Spread of Infectious Diseases

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.