Concept of the Erythron and Normal Erythrocytes
The erythron system includes all erythroid cells: from the earliest committed progenitors and morphologically recognizable nucleated cells (both proliferating and non-proliferating) to reticulocytes and mature erythrocytes. Differentiation and maturation of these cells occur in the bone marrow. Progenitor cells originate from pluripotent stem cells, undergoing 5 to 10 cell divisions.
In healthy individuals, erythrocytes are round and pink with a central area of pallor (normochromia). Normally, the cell population is distributed as follows:
- Normocytes (diameter 7.5 µm) constitute the vast majority at 68%.
- Microcytes (less than 7.0 µm) account for about 15%.
- Macrocytes (greater than 7.9 µm) make up approximately 17%.
Megalocytes are classified separately as giant cells with a diameter exceeding 11 µm.
Classification of Absolute Erythrocytosis
Absolute erythrocytoses result from the reactive enhancement of normal erythropoiesis, which predictably leads to an increase in total red blood cell mass. Based on their pathogenesis, they are divided into four main groups:
- Compensatory (hypoxia-driven): develop in response to generalized tissue hypoxia. This can occur with arterial hypoxemia or as isolated tissue hypoxia (where arterial oxygen saturation remains normal). The primary source of erythropoietin in this setting is the kidneys.
- Dysregulatory renal: triggered by local renal ischemia. The kidneys actively secrete erythropoietin, but this process does not serve a beneficial compensatory function for the organism.
- Dysregulatory paraneoplastic: erythropoietin is secreted directly by a tumor, which also lacks physiological utility.
- Primary: a group of hereditary disorders where the mechanism involves enhanced erythropoietin production or reduced sensitivity of renal oxygen receptors to oxygen.
Relative Erythrocytosis and Cell Morphology
Unlike absolute forms, relative (hemoconcentration) erythrocytoses are not associated with an actual increase in cellular mass. They occur when the circulating plasma volume decreases. As a result, formed elements predominate over plasma, while the total red blood cell mass remains unchanged.
Under various pathological conditions, the morphological characteristics of erythrocytes can alter:
- Poikilocytosis — the presence of cells of varying shapes in the blood.
- Anisocytosis — variation in cell size. The degree of variation is assessed by RDW (red cell distribution width). The mechanisms driving size alterations differ: microcytosis is linked to impaired hemoglobin synthesis (decreased concentration), macrocytosis results from impaired DNA synthesis, and megalocytosis is accompanied by a marked increase in cell size and elevated hemoglobin concentration.
- Anisochromia — abnormal variation in erythrocyte coloration.
- The appearance of intracellular inclusions.
Erythrocyte Sedimentation Rate (ESR) Dynamics
Changes in the physicochemical properties of blood directly affect the ESR.
An increased ESR is caused by alkalosis, anemia, hypercholesterolemia, elevated levels of fibrinogen and C-reactive protein, as well as dysproteinemia and paraproteinemia. Clinically, accelerated sedimentation is observed in infectious-inflammatory and rheumatic diseases, liver and kidney pathologies, diabetes mellitus, and thyrotoxicosis. ESR also rises sharply in malignancies (multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphomas with paraproteinemia).
A decreased ESR is provoked by acidosis, hyperbilirubinemia, elevated bile acid levels, and a hematocrit exceeding 50%. This is typical for erythrocytoses and any clinical conditions accompanied by marked hemoconcentration.