Erythrocyte physiology and hemoglobin metabolism
Normally, an erythrocyte is an anucleated cell in the shape of a biconcave disk with a diameter of 7–8 µm (normocyte). This shape is physiologically justified: it creates the maximum surface area to volume ratio, ensuring the most efficient gas exchange with tissues. The circulation time of an erythrocyte in the blood is 100–120 days.
Physiological hemolysis (destruction of old erythrocytes) occurs predominantly in the spleen, as well as in the liver and bone marrow. The process of hemoglobin breakdown includes the following stages:
- Cleavage of hemoglobin into heme and globin.
- Globin metabolism: the protein moiety is broken down into amino acids.
- Heme metabolism: breaks down into iron and protoporphyrin.
- Iron pathway: binds to the protein transferrin and is transported to the bone marrow, liver, and muscles for reutilization.
- Protoporphyrin pathway: converts into carbon monoxide (CO) and biliverdin. Then biliverdin is reduced to free (unconjugated) bilirubin.
- Transport and conjugation: free bilirubin binds to albumin and is carried by the bloodstream to the liver. There it conjugates with glucuronic acid, forming direct (conjugated) bilirubin.
- Excretion: as part of bile, direct bilirubin enters the intestine, where it is transformed into urobilinogens.
- Elimination: the bulk is excreted in feces, a smaller part is reabsorbed back into the blood and excreted by the kidneys with urine.
Classification of erythrocytosis
According to their origin, all erythrocytoses are divided into two large groups:
- Primary erythrocytoses: erythremia (polycythemia vera) and familial (hereditary) forms.
- Secondary erythrocytoses:
- Absolute (true increase in erythrocyte mass).
- Relative (hemoconcentration and redistribution).
Etiology and pathogenesis of erythremia
The main cause of erythremia development is carcinogenic agents, and the leading risk factor is a decrease in the efficiency of the body's antitumor resistance mechanisms.
Key links of pathogenesis:
- Under the action of a carcinogen, neoplastic transformation occurs in the genome of a myeloproliferative cell.
- In the hematopoietic tissue, the pool of proliferating tumor precursor cells of myelopoiesis increases sharply.
- Genetic mutations affect the gene whose product is responsible for signal transduction from hematopoietic factor receptors.
- Due to this mutation, hematopoietic cells acquire hypersensitivity to the action of hematopoietic factors.
- As a result, the division rate of myeloid cells increases manifold, despite the fact that the level of stimulators (in particular, erythropoietin) remains within the normal range.
Note: In addition to neoplastic Vaquez's disease, there are familial inherited non-myeloproliferative disorders. They are caused by non-neoplastic transformation of the erythroid lineage, but are also accompanied by an increased erythrocyte count, hypervolemia, and signs of true polycythemia.
Hematological manifestations (Vaquez's disease)
In erythremia, the main pathological changes are localized in the bone marrow and peripheral blood.
Bone marrow changes: Panmyelosis is observed — total neoplastic proliferation of myeloid cells and accelerated iron metabolism. At the final stages of the disease, exhaustion occurs: post-erythremic myelofibrosis develops, leading to pancytopenia (decrease in all formed elements).
Peripheral blood changes: A polycythemia symptomatology complex is formed (pancytosis — increase in all hematopoiesis lineages):
- Erythroid lineage: marked erythrocytosis, reticulocytosis (due to the release of tumor cells), erythrocyte hypochromia, elevated hematocrit and hemoglobin levels above normal.
- Platelet lineage: thrombocytosis.
- Leukocyte lineage: leukocytosis.
Physicochemical shifts and systemic consequences: Excess cells lead to hypervolemia (plethora) and a sharp increase in blood viscosity. This causes severe systemic consequences: cardiovascular dysfunction, dysfunction of other organs, and the development of life-threatening thrombohemorrhagic complications.
Briefly: answers to topical questions
What mutation is the main cause of polycythemia vera?
For polycythemia vera, the WHO diagnostic criteria indicate mutations in the JAK2 gene:
- JAK2 V617F mutation;
- mutation in exon 12 of the JAK2 gene.
In the study guide on erythremia, pathogenesis is described as mutations in a gene whose product is involved in signal transduction from hematopoietic factor receptors. Because of this, hematopoietic cells become excessively sensitive to hematopoietic factors, and the proliferation rate of myeloid cells increases even with a normal level of stimulators. The erythropoietin level in erythremia is within the normal range.
To recall the peripheral blood picture in erythremia, use the rule "Pancytosis = E+W+P": Erythrocytes, White blood cells (Leukocytes), and Platelets increase, as well as hemoglobin and hematocrit.
Class and exam questions
Why do bone marrow cells actively divide in polycythemia vera (erythemia) if erythropoietin levels are normal?
The mutation affects genes responsible for signal transduction from receptors. As a result, hematopoietic cells become excessively sensitive to normal concentrations of hematopoietic factors and proliferate uncontrollably.
What happens to the bone marrow in the final stages of erythremia?
Post-erythremic myelofibrosis develops. The tumor tissue is replaced by connective tissue, leading to pancytopenia — a critical decrease in the count of all formed blood elements.
How do familial erythrocytoses differ from Vaquez's disease?
Familial inherited disorders are caused by non-neoplastic transformation of erythroid lineage cells, although they are also accompanied by hypervolemia and an increased erythrocyte count per unit volume of blood.
What else to study on this topic
- Mechanisms of development of secondary absolute and relative erythrocytoses
- Detailed biochemical pathway of bilirubin conjugation in the liver
- Pathogenesis of thrombohemorrhagic complications in polycythemia
- Impact of hypervolemia and increased viscosity on the cardiovascular system
Master the entire topic in the "Pathophysiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Erythrocytosis and Erythremia" and 4,913 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 135 video lessons on the subject
Other topics in "Chapter 21. Typical Pathology Forms of the Blood System"
Free video lessons: pathophysiologyShort lessons with lecture notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.