Red Blood Cells: How Do They Deliver Oxygen?

Imagine you are looking after Amina, who has been admitted with heavy menstrual bleeding. She looks pale, becomes breathless walking to the bathroom and her heart rate is 112 beats per minute. Her haemoglobin is 68 g/L.

Then you look at the observation chart. Her oxygen saturation is 98% on room air.

That can feel as though the numbers are contradicting each other. If she is short of breath because her haemoglobin is so low, why is the oxygen saturation normal?

The answer sits inside the red blood cell. Pulse oximetry tells you about the proportion of available haemoglobin that is carrying oxygen. It does not tell you how much haemoglobin the patient has. Amina can therefore saturate the haemoglobin she has perfectly well while still having far less oxygen-carrying capacity than usual.

Red blood-cell physiology explains how both results can be true at the same time.

The red blood cell is built around one job: moving respiratory gases

A mature red blood cell, or erythrocyte, looks remarkably simple. It has no nucleus and no mitochondria. Most other cells would be badly disadvantaged by losing those structures, but for an erythrocyte the loss is part of its specialisation. More of the cell can be devoted to haemoglobin, and because the cell does not use mitochondria for aerobic respiration, it does not consume the oxygen it is transporting.

A red blood cell has its characteristic biconcave disc shape, with a thin centre and thicker outer rim. This gives it a high surface-area-to-volume ratio and keeps much of the cell contents close to the membrane, helping oxygen diffuse rapidly into and out of the cell. The shape also contributes to flexibility. An erythrocyte is roughly 7 to 8 micrometres across at rest, yet it still has to pass through very narrow capillaries and splenic spaces. Its membrane and cytoskeleton allow it to deform as it travels through these spaces and then recover its usual shape rather than behaving like a rigid disc.

Inside that flexible cell is haemoglobin. Each haemoglobin molecule contains haem groups with iron that can bind oxygen reversibly. In the lungs, oxygen diffuses across the alveolar-capillary membrane and into red cells, where it binds to haemoglobin. The oxygenated blood then travels through the left side of the heart and into the systemic circulation.

At the tissues, haemoglobin needs to do the opposite. It has to let oxygen go.

That release is influenced by the local environment. In metabolically active tissue, carbon dioxide production rises, hydrogen ion concentration can increase and temperature may be higher. These changes reduce haemoglobin's affinity for oxygen and favour unloading. The oxyhaemoglobin dissociation curve describes this changing affinity. In the lungs, haemoglobin readily binds oxygen; in active tissues, the local conditions favour oxygen release.

Now return to Amina's saturation of 98%. Pulse oximetry estimates the percentage of haemoglobin binding sites occupied by oxygen. If nearly all of her available haemoglobin is oxygenated, the saturation can be excellent. But arterial oxygen content depends heavily on the amount of haemoglobin present as well as its saturation. With a haemoglobin of 68 g/L, Amina has considerably less haemoglobin available to carry oxygen than someone with a normal haemoglobin concentration. Her pulse oximeter cannot show you that deficit.

Her tachycardia now makes more sense. Oxygen delivery to tissues depends on both arterial oxygen content and blood flow. When oxygen-carrying capacity falls, increasing cardiac output is one way the body can try to preserve oxygen delivery. A patient may therefore be tachycardic, breathless, dizzy or fatigued despite a normal SpO₂.

Every circulating red cell is part of a much bigger life cycle

Amina's circulating red cells cannot divide and manufacture replacements. New erythrocytes have to come from bone marrow.

Erythropoiesis begins with haematopoietic stem and progenitor cells and progresses through increasingly specialised erythroid precursors. As the developing cell matures, it accumulates haemoglobin and eventually loses its nucleus. The young cell released from marrow is a reticulocyte. Over the next day or so it completes maturation in the circulation.

The kidney helps decide when production needs to increase. Specialised oxygen-sensing mechanisms respond to reduced renal tissue oxygenation by increasing erythropoietin, usually shortened to EPO. EPO supports the survival and development of erythroid progenitor cells in bone marrow. The response takes time because the marrow has to produce and mature new cells, but it provides an elegant feedback system: reduced oxygen availability creates a signal that can increase future red-cell production.

Chronic kidney disease can therefore contribute to anaemia. Damaged kidneys may not generate an adequate erythropoietin response, but renal anaemia is not simply an ‘EPO problem’. Iron availability, inflammation, shortened red-cell survival, blood loss and other factors can contribute, so the mechanism still needs to be considered in the individual patient.

The marrow also needs the right raw materials. Iron is required for haem synthesis. Vitamin B12 and folate are important for normal DNA synthesis during cell development. If one part of the production system is restricted, the red cells reaching the circulation may change in number, size or haemoglobin content.

The mean cell volume, or MCV, adds information about the average size of the circulating erythrocytes. It tells you the average size of circulating erythrocytes. A low MCV can support a microcytic pattern, often associated with iron-restricted haemoglobin synthesis, while a raised MCV can occur with vitamin B12 or folate deficiency, alcohol-related disease, some medicines and marrow disorders. Neither result gives you a diagnosis on its own. It helps build a pattern that can direct further investigation.

Reticulocytes answer a different question. If a patient is anaemic, is the marrow trying to replace what has been lost? After blood loss or increased red-cell destruction, an appropriate marrow response can increase reticulocyte production. If the reticulocyte response is unexpectedly poor, attention turns towards impaired production or inadequate resources. A reticulocyte count therefore gives information about the marrow response rather than simply describing the mature red cells already in circulation.

Mature erythrocytes circulate for around 120 days before ageing, damaged or abnormal cells are removed predominantly by macrophages in the spleen, liver and other reticuloendothelial tissues. Their components are not simply thrown away. Iron can be recovered and returned to the body's iron pool for reuse, while haem breakdown contributes to bilirubin production. The red-cell life cycle therefore links marrow, kidney, circulation, spleen, liver and iron metabolism.

What does the red-cell story look like at the bedside?

Go back to Amina. Her haemoglobin is 68 g/L, but that number is only the beginning of the assessment.

You would want to know whether the fall is acute or chronic. A patient whose haemoglobin has gradually declined may have had time to develop cardiovascular and physiological compensation. A rapid fall from acute bleeding creates a different problem, particularly because circulating volume may also be falling. Symptoms, haemodynamic observations, ongoing blood loss, comorbidities and the patient's overall trajectory matter alongside the laboratory result.

The rest of the full blood count can start to tell the story. MCV may suggest a pattern. Reticulocytes, if measured, can indicate whether the marrow is responding. Previous haemoglobin values can show whether the change is new. Iron studies, vitamin B12, folate, renal function, markers of haemolysis and investigations for blood loss may then be used according to the clinical picture.

Haemoglobin is reported as a concentration, so plasma volume also influences the measured value. Plasma volume therefore influences the value. Significant fluid loss can concentrate circulating blood, while expansion of plasma volume can dilute measured haemoglobin. This does not make the laboratory result meaningless, but it is one reason blood results should be interpreted alongside fluid balance, bleeding, intravenous fluids and the patient's condition rather than in isolation.

If transfusion is being considered, the decision is not simply ‘haemoglobin below X equals blood’. NICE's blood transfusion guideline, updated in 2026, recommends restrictive red-cell transfusion thresholds for many patients who do not have major haemorrhage, acute coronary syndrome or a requirement for regular transfusions for chronic anaemia. It also recommends clinical reassessment after each single-unit transfusion in adults without active bleeding. The haemoglobin result is therefore considered alongside symptoms, bleeding, comorbidities and the wider clinical picture when transfusion is being considered. See NICE NG24.

So if you meet Amina on placement, do not let the 98% saturation reassure you away from the rest of the picture. Look at her. Ask about dizziness, chest discomfort, breathlessness and bleeding. Follow the heart rate and blood pressure. Look at the haemoglobin trend and the rest of the blood count. Escalate deterioration appropriately.

Amina's pulse oximeter is accurately showing that most of her available haemoglobin is oxygenated. Her haemoglobin result shows that there is much less of it available to carry oxygen.

References

Moras, M., Lefevre, S.D. and Ostuni, M.A. (2017) ‘From erythroblasts to mature red blood cells: organelle clearance in mammals’, Frontiers in Physiology, 8, 1076. Available online.

Jelkmann, W. (2020) ‘The many facets of erythropoietin physiologic and metabolic response’, Frontiers in Physiology, 10, 1534. Available online.

Nitzan, M., Romem, A. and Koppel, R. (2014) ‘Pulse oximetry: fundamentals and technology update’, Medical Devices, 7, pp. 231–239. Available online.

Otto, J.M. et al. (2017) ‘Hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia’, Haematologica, 102(9), pp. 1477–1485. Available online.

NICE (2026) Blood transfusion (NG24). NICE.