Definition and Background
The white blood cells (WBCs), also called leukocytes, are the army of our body. They provide surveillance and protect us from our micro-enemies (bacteria, viruses, parasites). The normal white blood cells count ranges between 4,000 and 11,000 cells per microliter. When WBCs are less than 4,000 cells per microliter, the condition is called leukopenia (-penia meaning deficiency), and when they are more than 11,000 cells per microliter, it is called leukocytosis.
Types of white blood cells
Neutrophils: They are the most common WBCs in our blood. They are so named because of the “neutral” staining properties of their cytoplasmic granules. The neutrophils have multilobed nucleus having 2-5 lobes. These cells counteract and digest bacteria and fungi, and are often the first-responders. They increase in acute inflammatory states.
Eosinophils: The eosinophils are so named because their cytoplasmic granules stain bright red and take eosin on the hematoxylin and eosin (H&E) stain. These cells are involved in the killing of parasites and participate in allergic responses.
Basophils: The basophils are small cells and are hallmarks of allergic reactions in our body. They secrete histamine and other chemicals that produce symptoms of allergy such as pruritis (itching). They control the body’s immune response. They are so named because they stain dark blue on H&E staining.
The term “Granulocytes” is used to collectively refer neutrophils, eosinophils, and basophils, as these cells contain multiple granules in their cytoplasm.
Lymphocytes: These cells contain large nucleus covering almost all the cell leaving a rim of cytoplasm behind. These cells are further broadly divided into B-cells, T-cells and natural killer cells, with the former type responsible for the production of antibodies that defend the body against various infections.
Monocytes: These white blood cells possess the longest lifespan amongst other white blood cells; they become macrophages within the tissues. Their nucleus is bean-shaped.
Normal blood count of leukocytes
- Neutrophils – 2000-7000/microliter (40–75%)
- Lymphocytes – 1000-3000/microliter (20–40%)
- Monocytes – 200-1000/microliter (2–10%)
- Eosinophils – 20-500/microliter (1–6%)
- Basophils – 20-100/microliter (<1–2%)
This can be remembered by the mnemonic “Never Let Monkeys Eat Bananas”, with the neutrophils being the most common WBC, followed by lymphocytes, monocytes, eosinophils and the basophils.
The etiological reasons for high white blood count (Leukocytosis):
- Acute leukemia (ALL and AML)
- Chronic leukemia (CLL and CML)
- Severe allergic reactions
- Corticosteroids and epinephrine therapy
- Smoking and alcohol abuse
- Polycythemia vera
- Emotional or physical stress
The etiology of low white blood cells count (Leukopenia):
- Viral infections (disrupting bone marrow stem cell production)
- Chemotherapy (immunosuppressive effect)
- Radiation therapy
- Drug effects (e.g. antibiotics such as trimethoprim-sulfamethoxazole, chloramphenicol)
- Congenital diseases impairing bone marrow function (e.g. Kostmann’s syndrome)
- Aplastic anemia
- Autoimmune diseases (lupus and rheumatoid arthritis and other autoimmune disorders)
- Malnutrition and vitamin deficiencies
Neutropenia is defined as the deficiency of circulating neutrophils. When the absolute neutrophil count (ANC) < 1500 cells/microliter then it is labeled as neutropenia. It is divided into mild, moderate, and severe neutropenia depending upon the ANC.
- Mild neutropenia: It is present when the ANC is 1000-1500 cells/µL.
- Moderate neutropenia: it is present when the ANC is 500-1000/µL.
- Severe neutropenia: It is present when the ANC is less than 500 cells/µL.
The neutropenia is always associated with severe infections, as the body loses its ability to protect against the pathogenic agents. This condition usually manifests with these symptoms:
- Sore mouth (oral mucosa is always affected manifesting in gingival pain and swelling)
- Skin abscesses (impetigo)
- Otorhinolaryngeal infections (recurrent sinusitis and otitis)
- Respiratory infection (cough, breathlessness)
The risk of infection in neutropenic patients is directly related to both the severity and duration of the neutropenia.
The term agranulocytosis refers to a virtual absence of circulating neutrophils. This term is often applied when the ANC is <100/μL. Hence, the “agranulocytosis” is used to describe more severe neutropenia. The agranulocytosis is associated with recurrent infections and may manifest with the following symptoms:
- Sever malaise
- High-grade fever, possibly with chills and confusion
- Painful stomatitis (bleeding and friable mucosa)
- Pharyngitis, with difficulty in swallowing
The neutrophilia is defined as increased number of circulating neutrophils. This condition is often associated with acute inflammatory states such as bacterial infections, trauma, stroke, and myocardial infarctions, or it may be a consequence of a shift of cells from the marginal to the circulating pool (shift neutrophilia) in response to certain events (e.g. corticosteroid use).
Shift neutrophilia is a transient condition that lasts for 20-30 minutes due to various reasons, such as excessive physical loads, seizures, paroxysmal tachycardia attacks, epinephrine or corticosteroid use. The quantitative properties do not change, as the inflow of the cells remains the same.
True neutrophilia occurs due to acute inflammatory states such as bacterial infections. When the utilization of neutrophils increases, the bone marrow cell production intensifies, shooting numerous immature forms of neutrophils stipulating left shift in the complete blood counts.
This white blood cells disorder is associated with the decreased number of lymphocytes. It usually occurs due to:
- Severe viral infections such as dengue fever (suppressing the bone marrow function)
- Myelodysplastic syndrome
The lymphocytosis means increased number of circulating lymphocytes. The lymphocytes play an important part in viral infections and chronic inflammatory states including chronic infections, hence lymphocytosis is seen in:
- Acute viral infections (e.g. infectious mononucleosis, CMV, measles, mumps infections)
- Some bacterial infections (e.g. pertussis)
- Chronic bacterial infections (e.g. tuberculosis, brucellosis)
- Acute lymphoblastic leukemia
- Chronic lymphocytic leukemia
Monocytosis is defined as increased number of circulating monocytes. The monocytes are often increased in chronic inflammatory conditions, similar to the lymphocytes. These conditions are:
- Chronic Infections (e.g. tuberculosis, brucellosis, subacute infective endocarditis)
- Cancers such as Hodgkin’s lymphoma and leukemia
- Autoimmune diseases such as SLE and rheumatic arthritis
- Recovery phase of acute infection
Eosinophilia means increased number of circulating eosinophils. This condition may occur in the following settings:
- Parasitic and fungal diseases (e.g. ascariasis, trichinosis, aspergillosis)
- Allergies (Asthma, eczema)
- Autoimmune diseases
- Churg-Strauss syndrome
- Drug allergies
- Eosinophilic leukemia
- Hypereosinophilic syndrome
Basophilia means increased number of circulating basophils. The isolated basophilia is a very uncommon condition and may be seen in myeloproliferative disorders such as chronic myelogenous leukemia (CML).
The right answers can be found below the references.
1. A 12-years-old patient complains of painful swallowing, bleeding gums, high-grade fever, and severe fatigue after insignificant physical load. The patient is confused, drowsy, and asks for water every 10 minutes. Physical examination reveals pallor, diffuse petechial rash on the skin surfaces. There are recurrent infectious diseases in the history: impetigo, pertussis, hepatitis A and frequent flu. There are purulent plaques on the pharyngeal glands. What is the most probable white blood cells disorder may present here?
2. An increase in the total blood granulocyte pool (TBGP) stands for true neutrophilia. What white blood cells stipulate this condition and what is the most probable triggering factor for this condition?
- Immature granulocytes/ infection
- Mature granulocytes/ infection
- Immature lymphocytes/ cancer
- Mature lymphocytes/ cancer
- None of above
3. The laboratory saliva study presents Epstein- Barr virus in 29 years old male immune compromised patient; he is a drug addict, with proved pneumococcal pneumonia. What white blood cells disorder are the most probable in this clinical case?
- None of above