Physiology · Blood, hemostasis and basic immunity

Polycythemia: physiological causes !

Mechanism
For completeness

Polycythemia means too many red cells. It is usually the body's answer to low oxygen, but it makes the blood thick.

Updated 2026-11-01

Also called: Erythrocytosis, High hematocrit

What it is

Polycythemia is a raised hemoglobin or hematocrit. It may be relative (less plasma, the same red cell mass) or absolute (more red cells). Absolute polycythemia is secondary when erythropoietin is raised, appropriately by hypoxia or inappropriately by a tumor, and primary when the marrow overproduces on its own, as in polycythemia vera.

How it works, step by step

Low O₂ delivery to the kidney (altitude, lung or heart disease) → HIF stabilized → EPO rises.
EPO expands the red cell mass over weeks → O₂ content rises toward normal despite low SaO₂.
At altitude, hyperventilation causes respiratory alkalosis, while 2,3-BPG rises and partly offsets the left shift.
Higher hematocrit raises viscosity → resistance rises (Poiseuille) → flow and O₂ delivery can fall at very high values.
Sluggish flow and more cell–wall contact favour thrombosis, headache and plethora.

Oxygen–hemoglobin dissociation curve

P50 27.7 mmHgArterial blood 97 %Mixed venous blood 73 %O₂ given up to the tissues 24 %

Right shift (P50 27.7 mmHg): Hb has less affinity and gives up more O₂ in the tissues. Acid, CO₂, heat and 2,3-BPG cause it.

Current curve
Normal curve (pH 7.40 · 37 °C)
Arterial blood (PO₂ 100)
Mixed venous blood (PO₂ 40)
O₂ given up to the tissues

The 'altitude' scenario: alkalosis from hyperventilation shifts the curve left, while higher 2,3-BPG pulls it back to the right.

Sorting polycythemia

Type	EPO	SaO₂	Example
Relative	Normal	Normal	Dehydration, diuretics
Secondary, hypoxic	High	Low	COPD, altitude, cyanotic heart disease
Secondary, non-hypoxic	High	Normal	EPO-secreting renal or liver tumor
Primary	Low	Normal	Polycythemia vera (JAK2)

Clinical notes

Andean populations living above ≈3000 m can develop chronic mountain sickness (Monge disease): excessive erythrocytosis with hypoxemia and pulmonary hypertension.
Smokers may have a high hemoglobin because carbon monoxide blocks O₂ binding and shifts the curve left, lowering O₂ release.
Reference hemoglobin and hematocrit are higher in Bogotá than at sea level; interpret a 'high' value with the altitude in mind.

Test yourself

Think of the answer, then tap the question to see it.

How do you tell appropriate from inappropriate secondary polycythemia?

Both have high EPO. In appropriate polycythemia SaO₂ or O₂ release is reduced (hypoxia drives EPO); in inappropriate polycythemia oxygenation is normal and a tumor or drug is making or mimicking EPO.

Why is EPO low in polycythemia vera?

The JAK2-mutated marrow makes red cells without EPO; the larger red cell mass improves renal O₂ delivery, so feedback suppresses EPO.

Why can a very high hematocrit reduce oxygen delivery?

O₂ content rises linearly with hematocrit, but viscosity rises much faster, so flow falls; beyond a point the drop in flow outweighs the gain in content.

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The structures of Durgical's 3D anatomy where it happens.

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 18.3 Erythrocytes (OpenStax (Rice University), 2022); Chronic Obstructive Pulmonary Disease (COPD) (StatPearls (NCBI Bookshelf), 2024); Complete Blood Count (CBC) (MedlinePlus (U.S. National Library of Medicine), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 33). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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