Pathophysiology
Summary
Polycythemia is marked by elevated hemoglobin, hematocrit, and RBC count. As these metrics can be influenced by plasma volume, polycythemia is divided into two categories: relative polycythemia and absolute polycythemia.
Relative polycythemia is a consequence of reduced plasma volume, leading to an apparent increase in hemoglobin, hematocrit, and RBC count without a physiological need for more RBCs. This results in typical erythropoietin (EPO) levels and is the more common type.
Absolute polycythemia is due to increased RBC production that affects hemoglobin, hematocrit, and RBC mass—a independent of plasma volume. Primary polycythemia is an absolute polycythemia that originates from bone marrow processes that lead to excess RBC production.
Primary polycythemia, or polycythemia vera, arises from an abnormal bone marrow process that produces an excessive number of RBCs. Polycythemia vera is associated with a JAK2 gene mutation, especially V617F, that persistently triggers the STAT pathway and results in unchecked hematopoietic cell growth. This can lead to various complications, including increased blood viscosity and a heightened risk of thrombosis.
Clinically, polycythemia vera results in increased RBCs count, thrombocytosis, and granulocytosis. Symptoms include a ruddy facial complexion, or facial plethora, hepatosplenomegaly, & increased risk of arterial & venous thrombosis. Other symptoms include headaches & vision issues, GI discomfort, hyperuricemia & gout, aquagenic pruritus from histamine release following a warm shower.
Myelofibrosis can manifest as a late-stage complication of polycythemia vera and is characterized by the bone marrow becoming densely populated by fibroblasts and collagen. This shift leads to pronounced hepatosplenomegaly due to extramedullary hematopoiesis. Severe progression of polycythemia vera can evolve into acute myelogenous leukemia (AML, identifiable by the uncontrolled proliferation of myeloblasts.
Secondary polycythemia is characterized by excessive RBC production due to heightened EPO levels and is classified into physiologic secondary polycythemia and inappropriate secondary polycythemia
Physiologic secondary polycythemia occurs in the setting of hypoxia, which increases the synthesis of EPO and subsequent RBC production. Conditions inducing this form include COPD, obstructive sleep apnea, cyanotic congenital heart disease, and high altitudes.
Inappropriate secondary polycythemia primarily arises from tumors like renal cell carcinoma that aberrantly produce EPO outside the kidneys. Inappropriate secondary polycythemia shows normal oxygen saturation levels since EPO secretion isn't linked to hypoxia.
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FAQs
Relative polycythemia is characterized by an apparent increase in hemoglobin, hematocrit, and red blood cell (RBC) count due to a decrease in plasma volume. In this condition, the total RBC mass remains unchanged, and erythropoietin (EPO) levels are normal because there's no physiological demand for additional RBCs. On the other hand, absolute polycythemia involves an actual increase in RBC production, leading to elevated hemoglobin, hematocrit, RBC count, and RBC mass. Depending on its cause, EPO levels in absolute polycythemia can either increase or decrease.
Primary polycythemia, commonly known as polycythemia vera, arises from an abnormal bone marrow process that produces an excessive number of RBCs. This condition is often associated with mutations in the JAK2 gene and can lead to various complications, including increased blood viscosity and a heightened risk of thrombosis. Secondary polycythemia, on the other hand, results from elevated erythropoietin (EPO) levels, typically due to hypoxia or inappropriate EPO production from non-kidney sources, such as certain tumors.
Polycythemia vera manifests with symptoms of an overabundance of RBCs. Patients may exhibit a ruddy complexion, termed facial plethora, due to tissue congestion. Common symptoms include headaches, dizziness, vision changes, abdominal pain, and itching, especially after exposure to warm water. The condition can also lead to hyperuricemia and increase the risk of gout. Furthermore, the increase in the number of RBCs heightens the risk of both arterial and venous thrombosis.
Chronic hypoxia, or prolonged oxygen deficiency, is a primary driver for physiologic secondary polycythemia. In response to reduced oxygen levels in tissues, the kidneys increase erythropoietin (EPO) production, prompting the bone marrow to produce more RBCs. Several conditions can induce chronic hypoxia and subsequently secondary polycythemia, including COPD, obstructive sleep apnea, cyanotic congenital heart disease, and residing at high altitudes where oxygen levels are lower.
Renal cell carcinoma is the predominant cause of inappropriate secondary polycythemia. This type of cancer can induce excessive erythropoietin (EPO) production independent of hypoxia. Unlike physiological triggers of polycythemia, where EPO production responds to decreased oxygen levels, in inappropriate secondary polycythemia resulting from renal cell carcinoma, oxygen saturation remains normal.
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