WBC

White Blood Cells (WBCs)

Overview Classification Morphology WBC Count Variations Leukemia Properties Functions Mast Cell Pathological Variations Leukopoiesis

1 White Blood Cells

White blood cells (WBCs) or leukocytes are the colorless and nucleated formed elements of blood.

  • Leuko = white or colorless.
  • Compared to red blood cells (RBCs), WBCs are:
    • Larger in size
    • Lesser in number
  • Functionally, WBCs are as important as RBCs.
  • WBCs play an important role in the defense mechanism of the body by acting like soldiers and protecting the body from invading organisms.

WBC vs RBC

Feature WBC RBC
1. Color Colorless Red
2. Number Less; 4,000 to 11,000/cu mm More; 4.5 to 5.5 million/cu mm
3. Size Larger; maximum diameter of 18 μ Smaller; maximum diameter of 7.4 μ
4. Shape Irregular Disk shaped and biconcave
5. Hemoglobin Absent Present
6. Nucleus Present Absent
7. Granules Present in some types Absent
8. Types Many types Only one type
9. Lifespan Shorter; ranges from ½ to 15 days Longer; 120 days
10. Functions Defense and immunity Transport of oxygen and carbon dioxide; buffering action

2 Classification of White Blood Cells

Depending upon the presence or absence of granules in cytoplasm, white blood cells are classified into two groups:

1. Granulocytes

With granules

2. Agranulocytes

Without granules

Granulocytes

Depending upon the staining property of granules, granulocytes are classified into three types:

1. Neutrophils

Granules take both acidic and basic stains.

2. Eosinophils

Granules take acid stain.

3. Basophils

Granules take basic stain.

Agranulocytes

Agranulocytes have plain cytoplasm without granules.

Agranulocytes are of two types:

  1. Monocytes
  2. Lymphocytes

3 Morphology of White Blood Cells

Neutrophils

  • Neutrophils are also known as polymorphonuclear leukocytes because the nucleus is multilobed.
  • Number of lobes in the nucleus varies from 1 to 6.
  • Granules are fine or small in size.
  • When stained with Leishman’s stain, which contains acidic methylene blue, the granules take both the stains equally.
  • Therefore, the granules appear violet in color.
  • Diameter of neutrophil → 10 to 12 μ.
  • Neutrophils are ameboid and phagocytic in nature.
Morphological features
  • Fine granules with eosin and methylene blue stain
  • Multilobed nucleus

Eosinophils

  • Eosinophils have coarse (larger) granules in the cytoplasm.
  • Granules stain pink or reddish orange with eosin.
  • Normally, the nucleus is bilobed and spectacle shaped.
  • Rarely, trilobed nucleus may be present.
  • Diameter of this cell varies between 10 and 14 μ.
Morphological features
  • Coarse granules with eosin stain
  • Bilobed nucleus

Basophils

  • Basophils also have coarse granules in the cytoplasm.
  • Granules stain purple blue with methylene blue.
  • Nucleus is bilobed.
  • Diameter of this cell is 8 to 10 μ.
Morphological features
  • Coarse granules with methylene blue stain
  • Bilobed nucleus

Monocytes

  • Monocytes are the largest leukocytes.
  • Cytoplasm of monocyte is clear without granules.
  • Nucleus is:
    • Round
    • Oval
    • Horseshoe shaped
    • Bean shaped
    • Kidney shaped
  • Nucleus is placed either in the center of the cell or pushed to one side.
  • A large amount of cytoplasm is seen.
  • Diameter of monocyte → 14 to 18 μ.
Morphological features
  • Nucleus pushed to one side
  • Clear cytoplasm

Lymphocytes

  • Lymphocytes also do not have granules in cytoplasm.
  • Nucleus is oval, bean shaped or kidney shaped and occupies the whole of the cytoplasm.
  • A rim of cytoplasm may or may not be seen.
Morphological features
  • Clear cytoplasm
  • Nucleus occupying whole of cytoplasm

Types of Lymphocytes

Based on Size

1. Large (younger) lymphocytes

Diameter → 10 to 12 μ

2. Small (older) lymphocytes

Diameter → 7 to 10 μ

Based on Function

1. T lymphocytes

Concerned with cellular immunity.

2. B lymphocytes

Concerned with humoral immunity.

4 Normal White Blood Cell Count

1. Total Leukocyte Count (TC)

4,000 to 11,000/cu mm of blood.

2. Differential WBC Count (DC)

WBC Percentage Absolute Value
(per cu mm)		 Diameter (μ) Lifespan (days)
1. Neutrophils 50–70 3,000–6,000 10–12 2–5
2. Eosinophils 2–4 150–300 10–14 7–12
3. Basophils 0–1 0–100 8–10 12–15
4. Monocytes 2–6 200–600 14–15 2–5
5. Lymphocytes 20–30 1,500–3,000 7–12 ½–1

5 Applied Physiology: Variations in WBC Count

Leukocytosis

Leukocytosis is the increase in total WBC count.

Leukocytosis occurs in both:

  • Physiological conditions
  • Pathological conditions

Leukopenia

Leukopenia is the decrease in total WBC count.

Generally, the term leukopenia is used for pathological conditions of WBC count.

Physiological Variations in WBC Count

Condition WBC Count
1. Age Adults: 4,000 to 11,000/cu mm;
Children: 10,000 to 15,000/cu mm;
Infants: About 20,000/cu mm
2. Sex Slightly more in males than in females
3. Diurnal variation Early morning: Minimum; Afternoon: Maximum
4. Exercise Increases slightly
5. Sleep Decreases
6. Emotional condition Increases
7. Pregnancy Increases
8. Menstruation Increases
9. Parturition Increases

Pathological Variations in WBC Count

Leukocytosis

It occurs in the following pathological conditions:

  1. Infections
  2. Allergy
  3. Common cold
  4. Tuberculosis
  5. Glandular fever

Leukopenia

Leukopenia occurs in the following pathological conditions:

  1. Anaphylactic shock
  2. Cirrhosis of liver
  3. Disorders of spleen
  4. Pernicious anemia
  5. Typhoid and paratyphoid
  6. Viral infections

6 Leukemia

Variations in Differential Leucocyte Count

  • Differential leucocyte count varies in specific diseases.
  • Granulocytosis refers to an abnormal increase in granulocytes count.
  • Granulocytopenia refers to an abnormal decrease in granulocytes count.
  • Agranulocytosis is an acute pathological condition characterized by absolute lack of granulocytes, particularly neutrophils.
  • This condition is also called agranulosis or granulopenia.

Leukemia

Leukemia is a type of blood cancer characterized by production of large number of leukocytes including immature and abnormal leukocytes.

Leukocyte count becomes more than 10,000/cu mm.

Types

1. Acute lymphocytic or lymphoblastic leukemia

Characterized by rapid increase in number of lymphocytes.

2. Chronic lymphocytic or lymphoblastic leukemia

Characterized by gradual increase in number of lymphocytes.

3. Acute myeloid or myelogenous leukemia

Characterized by rapid increase in number of myeloid cells (granulocytes and monocytes).

4. Chronic myeloid or myelogenous leukemia

Characterized by gradual increase in number of myeloid cells.

Cause

Genetic mutation in DNA of bone marrow cells.

Risk Factors

  1. Previous chemotherapy or radiation therapy
  2. Exposure to high levels of radiation like radiation from nuclear reactor accident
  3. Long-term exposure to chemicals such as formaldehyde, benzene and other industrial chemicals
  4. Smoking
  5. Genetic disorders such as Down syndrome

Common Signs and Symptoms

  1. Persistent tiredness or weakness
  2. Weight loss
  3. Pain in bones or joints
  4. Lymph nodes swelling
  5. Frequent infections
  6. Anemia
  7. Bleeding
  8. Bruising
Bruising:

Skin discoloration due to injury of underlying soft tissue resulting in rupture of minute blood vessels and leakage of blood.

It occurs due to blow or injury, often on arms and legs.

7 Lifespan and Properties of White Blood Cells

Lifespan of White Blood Cells

  • Lifespan of WBCs is not constant.
  • It depends upon:
    • Demand in the body
    • Function of WBCs

Properties of White Blood Cells

1. Diapedesis

Diapedesis is a process by which leukocytes squeeze through the narrow blood vessels.

2. Ameboid Movement

Neutrophils, monocytes and lymphocytes show ameboid movement characterized by protrusion of cytoplasm and change in the shape.

3. Chemotaxis

Chemotaxis is the attraction of WBCs towards injured tissues by chemical substances released at the site of injury.

4. Phagocytosis

Neutrophils and monocytes engulf the foreign bodies by means of phagocytosis.

8 Functions of White Blood Cells

WBCs play an important role in defense mechanism.

WBCs protect the body from invading foreign bodies either by:

  • Destroying them
  • Inactivating them

However, in defense mechanism, each type of WBCs acts in a different way.

Functions of Neutrophils

  • Along with monocytes, neutrophils provide first line of defense against invading microorganisms.
  • Neutrophils wander freely throughout the body.
  • Neutrophils move by diapedesis towards the site of infection by means of chemotaxis.
  • Chemotaxis occurs due to attraction by some chemical substances called chemoattractants, which are released from infected tissues.
  • After reaching the area, neutrophils engulf the bacteria and destroy them by means of phagocytosis.

Pus and Pus Cells

  • Pus cells are dead WBCs killed by toxins released from bacteria during the battle between WBCs and bacteria.
  • Pus is a whitish yellow fluid formed in an area of infected tissue.
  • It consists of:
    • Dead WBCs
    • Bacteria or foreign bodies
    • Serum
    • Cellular debris

Functions of Eosinophils

  • Eosinophils provide defense to the body by acting against:
    • Parasitic infections
    • Allergic conditions such as asthma
  • Eosinophils are responsible for:
    • Detoxification
    • Disintegration and removal of foreign proteins
  • Eosinophils attack the invading organisms by secreting some cytotoxic substances which destroy invading organisms such as parasites.

Functions of Basophils

  • Basophils are involved in:
    • Healing processes
    • Acute hypersensitivity reactions (allergy)
  • Basophils execute their functions by releasing important substances from their granules such as:
    • Heparin
    • Histamine

Functions of Monocytes

  • Monocytes are the largest leukocytes.
  • Like neutrophils, monocytes are:
    • Motile
    • Phagocytic in nature
  • Monocytes wander freely through all tissues of the body and provide first line of defense along with neutrophils.
  • Monocytes are the precursors of tissue macrophages.
  • Mature monocytes stay in the blood only for few hours.
  • Afterwards, these cells enter the tissues from blood and become tissue macrophages.

Examples of Tissue Macrophages

  • Kupffer cells in liver
  • Alveolar macrophages in lungs
  • Macrophages in spleen

Functions of Lymphocytes

  • Lymphocytes are responsible for development of immunity.
  • Depending upon mode of action, lymphocytes are divided into two types:
    • T lymphocytes → concerned with cellular immunity
    • B lymphocytes → concerned with humoral immunity

9 Mast Cell

Mast cell is a large tissue cell resembling the basophil.
  • Generally, mast cells are found along the blood vessels and are prominently seen in areas such as:
    • Skin
    • Mucosa of lungs
    • Digestive tract
    • Mouth
    • Conjunctiva
    • Nose
  • Mast cells usually do not enter the bloodstream.
  • Mast cells are developed in bone marrow, but their precursor cells are different.
  • After differentiation, immature mast cells enter the tissues.
  • Maturation of mast cells takes place only after entering the tissue.

Functions of Mast Cell

  • Mast cell plays an important role in producing:
    • Hypersensitivity reactions such as allergy and anaphylaxis
  • When activated, mast cell immediately releases chemical mediators from its granules into the interstitium.

Mast Cell Mediators

1. Preformed Mediators

Preformed mediators are already formed and stored in secretory granules of mast cells.

  • Histamine
  • Heparin
  • Serotonin
  • Hydrolytic enzymes
  • Proteoglycans
  • Chondroitin sulfates

2. Newly Generated Mediators

Arachidonic acid derivatives such as:

  • Leukotriene C (LTC)
  • Prostaglandin
  • Cytokines
These are mediators produced by mast cells only during activation.

10 Pathological Variations in Different Leukocytes Count

Disorder Variation Causes
Neutrophilia or neutrophilic leukocytosis Increase in neutrophil count 1. Acute infections
2. Metabolic disorders
3. Injection of foreign proteins
4. Injection of vaccines
5. Poisoning by chemicals and drugs like lead, mercury, camphor, benzene derivatives
6. Poisoning by insect venom
7. After acute hemorrhage
Neutropenia Decrease in neutrophil count 1. Bone marrow disorders
2. Tuberculosis
3. Typhoid
4. Vitamin deficiencies
5. Autoimmune diseases
Eosinophilia Increase in eosinophil count 1. Allergic conditions like asthma
2. Blood parasitism (malaria, filariasis)
3. Intestinal parasitism
4. Scarlet fever
Eosinopenia Decrease in eosinophil count 1. Cushing’s syndrome
2. Bacterial infections
3. Stress
4. Prolonged administration of drugs like steroids and adrenocorticotropic hormone (ACTH) and epinephrine
Basophilia Increase in basophil count 1. Smallpox
2. Chickenpox
3. Polycythemia vera
Basopenia Decrease in basophil count 1. Urticaria (skin disorder)
2. Stress
3. Prolonged exposure to chemotherapy or radiation
Monocytosis Increase in monocyte count 1. Tuberculosis
2. Syphilis
3. Malaria
4. Kala-azar
5. Glandular fever
Monocytopenia Decrease in monocyte count 1. Prolonged use of immunosuppressant steroid
2. AIDS
3. Chronic lymphoid leukemia
Lymphocytosis Increase in lymphocyte count 1. Diphtheria
2. Infectious hepatitis
3. Mumps
4. Malnutrition
5. Rickets
6. Syphilis
7. Thyrotoxicosis
8. Tuberculosis
Lymphocytopenia Decrease in lymphocyte count 1. Acquired immunodeficiency syndrome (AIDS)
2. Hodgkin’s disease (cancer of lymphatic system)
3. Malnutrition
4. Radiation therapy
5. Steroid administration

11 Leukopoiesis

Leukopoiesis is the development and maturation of leukocytes.

Stages of Leukopoiesis

Committed pluripotent hematopoietic stem cell → Colony forming blastocyte → Colony forming unit
  • Erythrocytes (red blood cells)
  • Granulocytes/Monocytes
  • Megakaryocytes (platelets)

Granulocytes/Monocytes Pathway

Colony forming unit Granulocytes/Monocytes → Myeloblast → Promyelocyte

Neutrophil Pathway

Neutrophil myelocyte → Neutrophil metamyelocyte → Neutrophil

Basophil Pathway

Basophil myelocyte → Basophil metamyelocyte → Basophil

Eosinophil Pathway

Eosinophil myelocyte → Eosinophil metamyelocyte → Eosinophil

Monocyte Pathway

Myeloblast → Monoblast → Promonocyte → Monocyte

Lymphocyte Pathway

Lymphoid stem cell → Lymphoblast → Lymphocyte

12 Stem Cells and Factors Necessary for Leukopoiesis

Stem Cells

Committed pluripotent stem cell gives rise to leukocytes through various stages.

Factors Necessary for Leukopoiesis

  • Leukopoiesis is influenced by:
    • Hematopoietic growth factors
    • Colony stimulating factors (CSFs)

Colony-Stimulating Factors

Colony stimulating factors are proteins which cause the formation of colony-forming blastocytes.

Types of Colony-Stimulating Factors

1. Granulocyte-CSF (GCSF)

Secreted by monocytes and endothelial cells.

2. Granulocyte-monocyte-CSF (GMCSF)

Secreted by:

  • Monocytes
  • Endothelial cells
  • T lymphocytes
3. Monocyte-CSF (MCSF)

Secreted by:

  • Monocytes
  • Endothelial cells.
White Blood Cells (WBCs)