Disorders of Granulocytes and Monocytes

Introduction to Disorders of Granulocytes and Monocytes

  • Nonmalignant disorders of granulocytes include general increases or decreases in leukocyte counts and qualitative defects in killing ability.
  • Laboratory tests assess disorders of granulocytes and monocytes.

Quantitative Disorders

Definitions

  • Leukocytosis: An increase in concentration or percentage of any leukocyte in peripheral blood: neutrophils, eosinophils, basophils, monocytes, or lymphocytes.
  • Leukocytopenia: A decrease in total leukocyte count.

Causes of Leukocytosis

  • Various conditions can cause nonmalignant leukocytosis, such as:
    • Increased movement of immature cells from the bone marrow.
    • Mobilization of cells from the maturation-storage compartment to peripheral blood.
    • Movement of mature cells from the marginating pool to the circulating pool.
    • Decrease in mature cells moving from circulation into tissues.

Pathophysiology of Granulopoietic Alterations

  • Neutrophil production occurs in the bone marrow.
  • Life cycle phases of a neutrophil: bone marrow (BM), blood, and tissue.
  • Mitotic compartment: Comprising myeloblast, promyelocyte, and myelocyte, capable of division and differentiation.
  • Maturation compartment: Includes metamyelocytes, bands, and mature neutrophils, capable of differentiation only.
  • Neutrophils flow into:
    • Circulating Granulocyte Pool (CGP)
    • Marginating Granulocyte Pool (MGP)

Granulocyte Pool Equilibrium

  • Total Blood Granulocyte Pool (TBGP) = CGP + MGP.
  • CGP and MGP maintain a constant state of equilibrium.
  • Estimate of CGP size: Multiply neutrophil count per mm³ by the total circulating blood volume.

Disorders Associated with Quantitative Increases

  • Various disorders leading to increases in leukocytes include:
    • Neutrophilia: Resulting from infections, inflammation, stress, certain drugs, and types of leukemia.
    • Eosinophilia: Related to allergic disorders and infections.
    • Basophilia: Related to chronic inflammatory disorders and certain leukemias.
    • Monocytosis: Associated with chronic infections and inflammatory states.
Examples of Related Disorders to Leukocytic Increases or Decreases

  • Neutrophilia associated with:

    • Inflammatory conditions
    • Infection
    • Physical stimuli (heat or cold)
    • Surgery
    • Burns
    • Stress
    • Certain medications and hormonal changes

  • Causes of Neutropenia (Leukocytopenia):

    • Stem cell failure in BM injury
    • Malignancies infiltrating marrow
    • Destruction due to megaloblastic anemia
    • Nutritional deficiencies (starvation, anorexia)
    • Chemicals/drugs causing suppression
    • Cyclic neutropenia
    • Splenic entrapment or immune-mediated destruction.

Morphological Abnormalities of Mature Granulocytes

Types of Abnormalities

  • Abnormalities noted in stained smears such as:
    • Nuclear Abnormalities:
    • Hypersegmentation: Segmented neutrophils with more than five lobes; associated with B12 or folic acid deficiencies.
    • Pelger-Huët Anomaly: Hyposegmentation, benign anomaly despite abnormal nuclear maturation.
    • Pyknotic Nucleus: A sign of cell dysfunction.
    • Cytoplasmic Abnormalities:
    • Toxic Granulation: Dark granulation in neutrophils, associated with infections and burns.
    • Döhle Bodies: Light blue inclusions indicative of stress responses, linked to infections and drug therapies.
Detailed Descriptions of Abnormalities

  • Toxic Granulation:

    • Prominent dark granulation in neutrophils during infections, burns, or malignancies.

  • Hypersegmentation:

    • Associated with deficiencies in B12 or folic acid; results in enlarged oval erythrocytes.

  • Pelger-Huët Anomaly:

    • Indicates abnormal nucleic acid metabolism; typically benign with normal cell function.

  • Döhle Bodies:

    • Ribosomal RNA aggregates signaling infection stress; associated with various conditions (viral infections, burns).

Genetic and Acquired Disorders Affecting Granulocytes

May-Hegglin Anomaly

  • Characterized by Döhle body-like inclusions, large poorly granulated platelets, and thrombocytopenia.
  • May lead to abnormal bleeding tendencies, with half of patients asymptomatic.

Chédiak-Higashi Syndrome

  • Hereditary disorder with large granules indicating poor lysosomal development.
  • Neutrophils exhibit impaired chemotaxis leading to frequent infections.

Alder-Reilly Inclusions

  • Purple-red granules in neutrophils, indicate mucopolysaccharidosis similar to toxic granulation.

Ehrlichia

  • Caused by endocellular bacteria, infects leukocytes, noted for forming morulae.

Qualitative Disorders

Types of Qualitative Disorders

  • Defective chemotaxis and microbicidal activity.
  • Monocyte-macrophage disorders.
Defective Locomotion and Chemotaxis
  • Significant in conditions like diabetes, Chédiak-Higashi, and high IgE levels (Job's syndrome).
  • Example Disorders: Lazy leukocyte syndrome, leukocyte adhesion deficiency.
Defects in Microbicidal Activity
  • Disorders that impair the ability to kill ingested microorganisms, e.g., Chronic Granulomatous Disease (CGD), myeloperoxidase deficiency.

Other Functional Anomalies of Neutrophils

  • Over 15 hereditary defects and 30 additional disorders described, one including lactoferrin deficiency.
  • Results in susceptibility to pyogenic infections, with potential for severe skin abscesses.

Monocyte-Macrophage Disorders

  • Gaucher’s Disease:

    • Disturbance in lipid metabolism due to glucocerebrosidase deficiency, characterized by unique morphological appearance in macrophages.

  • Niemann-Pick Disease:

    • Similar to Gaucher’s, but caused by sphingomyelinase deficiency leading to foamy macrophages due to sphingomyelin accumulation.