Blood System Response to Pathogenic Factors
Changes in the leukocyte differential directly depend on the nature of the offending pathogen. Various infectious agents and foreign entities trigger specific hematopoietic mechanisms:
- Allergic reactions are accompanied by the development of eosinophilia. The mechanism involves allergens stimulating lymphocytes, which actively release stimulators of eosinophilic leukopoiesis. These biologically active substances include interleukins (IL-5, IL-17), eosinophil chemotactic factor, and eotaxin.
- Bacterial infections (e.g., caused by streptococci or staphylococci) lead to potent stimulation of myelopoiesis. As a result, granulocytes are actively released into the peripheral blood, manifesting as pronounced neutrophilia.
- Viral infections (such as pertussis or hepatitis), as well as chronic/specific infections (tuberculosis, syphilis, brucellosis), stimulate lymphopoiesis, predictably causing lymphocytosis.
- Certain infectious diseases (rubella, malaria, infectious mononucleosis) specifically activate monocytopoiesis, which is reflected in the differential as monocytosis.
Relative and Absolute Changes
When analyzing blood cellular composition, it is critical to distinguish between two types of changes, as they carry entirely different diagnostic value:
- Relative changes are shifts in the percentage of a specific type of leukocyte relative to the total cell count (taken as 100%). In clinical terminology, this is described as relative neutropenia or neutrophilia, relative lymphopenia, or lymphocytosis.
- Absolute changes are fluctuations in the true content of leukocytes per unit volume of blood. Accordingly, terms include absolute neutropenia or neutrophilia, absolute lymphopenia, or lymphocytosis.
Evaluating the absolute count allows for the identification of a true cell deficit or excess. For instance, a decrease in the absolute cell count below the lower limit of normal (e.g., 0.8 × 10⁹/L against a normal range starting at 2.0 × 10⁹/L) unequivocally indicates absolute deficiency of that leukocyte pool in the body.
Leukocyte Differential Shifts and the Nuclear Shift Index
True (so-called regenerative) leukocytoses are always accompanied by proliferation of myeloid lineage cells and changes in the standard leukocyte ratio. Depending on the severity of leukocytosis and the appearance of immature forms in the circulation, various types of left shifts are distinguished.
To precisely quantify the ratio of mature to immature forms, the neutrophil nuclear shift index is used. This parameter reflects the ratio of the sum of all young cells to mature forms.
Calculation formula: Index = (Promyelocytes + Myelocytes + Metamyelocytes + Band neutrophils) / Segmented neutrophils
Clinical Interpretation of Combined Changes
Comprehensive analysis of the leukocyte differential, including changes in absolute cell counts and the direction of the shift, makes it possible to determine the presence and type of leukocytosis or leukopenia, assess the degree of shifts, and suggest their potential mechanism.
Characteristic combinations of changes:
- Regenerative (true) neutrophilic leukocytosis: an increase in total leukocyte count combined with absolute neutrophilia.
- Neutrophilic-eosinophilic leukocytosis: an elevated total leukocyte count accompanied by concurrent absolute neutrophilia and absolute eosinophilia.
- True lymphocytic leukopenia: a decreased total leukocyte count occurring against the background of absolute lymphopenia.
Evaluating the neutrophil nuclear shift is of paramount diagnostic significance. If neutrophilic leukocytosis is accompanied by a marked left shift, it reliably confirms its true (regenerative) nature. Conversely, the absence of a shift most often indicates a redistributive mechanism of neutrophilic leukocytosis or accompanies neutrophil leukopenia.