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Human Physiology · Blood and immunity

Red Cells, Haemoglobin and Anaemia

Red cells carry almost all the oxygen in blood. When there are too few, or too little haemoglobin, every tissue is short of oxygen and exercise becomes hard. This page explains how red cells are made and controlled, the role of iron, the types of anaemia, and what training and treatment can change.

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Part 6 · Blood and Immunity · Chapter 26 of 47

Learning objectives

By the end of this page you should be able to:

  • Describe the structure and lifespan of red cells and the role of haemoglobin.
  • Explain the erythropoietin feedback loop.
  • Describe iron absorption, recycling and the role of hepcidin.
  • Classify anaemia and list common causes.
  • Explain how anaemia limits exercise and how altitude and iron treatment change red cell status.
  • Adapt exercise for patients with anaemia.

Why it matters

Anaemia is common in older adults, after surgery, in kidney disease, cancer and heart failure, and in menstruating women and endurance athletes. It causes fatigue and breathlessness and limits rehabilitation.

Knowing the cause tells you what to expect: a patient with iron deficiency may improve with treatment, while a patient with B12 deficiency may also have nerve damage affecting balance.

Red cells and haemoglobin

Red cells are biconcave discs about 7.5 μm across, without a nucleus or mitochondria. Their shape gives a large surface for gas exchange and lets them fold through capillaries narrower than themselves.

Each red cell contains about 270 million haemoglobin molecules. Each haemoglobin has four haem groups, each with an iron atom that binds one oxygen molecule (Chapter 18).

MeasureTypical adult rangeMeaning
HaemoglobinMen about 130–170 g/L; women about 120–150 g/LOxygen-carrying protein
Red cell countAbout 4.5–6 × 1012/L (men)Number of cells
Mean cell volume (MCV)About 80–100 fLAverage cell size
FerritinVaries by lab; low values mean low storesIron stores (rises in inflammation)

Making red cells

Figure 1 · How red cell production is controlled

Erythropoietin feedback loop Low oxygen in the kidney triggers release of erythropoietin, which stimulates the bone marrow to make more red cells over about a week. More haemoglobin improves oxygen delivery and switches off the signal. Red cells live about 120 days. Kidney senses low O2anaemia, altitude, lung diseaseErythropoietin (EPO)hormone in bloodBone marrowmore red cells madeMore haemoglobinbetter O2 deliveryreleasesabout 7 daysswitches offthe signalRed cell lifespan about 120 daysold cells removed by spleen and liver;their iron is recycled
A negative feedback loop. Kidney disease reduces EPO, which is why anaemia is common in chronic kidney disease. Altitude switches the loop on [2].

Red cells are made in the bone marrow from stem cells. When the kidney senses low oxygen, it releases erythropoietin (EPO), which speeds production. New red cells appear in the blood after about a week, and they live about 120 days.

Production also needs iron, vitamin B12 and folate. Kidney disease lowers EPO; marrow disease, chemotherapy and nutritional deficiency also reduce output.

Iron

Figure 2 · The iron cycle

Iron absorption, transport, use, recycling and storage Dietary iron is absorbed in the duodenum, about 1 to 2 milligrams a day, and carried in plasma by transferrin to the bone marrow for new haemoglobin. Macrophages recycle about 20 to 25 milligrams a day from old red cells. Excess is stored as ferritin. The hormone hepcidin blocks absorption and release. Dietabsorbed in duodenumabout 1–2 mg/dayPlasma ironcarried by transferrinBone marrownew haemoglobinRed cellsmost body ironMacrophagesrecycle old red cellsabout 20–25 mg/dayStoresferritin in liverHepcidin blocksabsorption and releaserises for hours after hard exercise [1]
Recycling dominates. Daily absorption is small, so losses from bleeding, menstruation or high training loads with raised hepcidin can deplete iron [1].

The body absorbs only a little iron each day and relies on recycling from old red cells. The liver hormone hepcidin controls the flow: it blocks absorption from the gut and release from stores.

Sim and colleagues note that iron deficiency affects about 15–35% of female athlete cohorts and 5–11% of male cohorts [1]. Hepcidin rises for some hours after hard exercise, which can reduce iron absorption [1]. Menstrual losses, low intake and sweat and gut losses add to the risk.

Anaemia

Anaemia is a haemoglobin concentration below the normal range for age and sex. It reduces oxygen content (Chapter 18), so the heart must pump more blood to deliver the same oxygen.

Figure 3 · Classifying anaemia by cell size

Microcytic, normocytic and macrocytic anaemia with common causes Three panels with red cells of increasing size. Microcytic anaemia, with small cells, is usually iron deficiency. Normocytic anaemia is seen in acute blood loss, chronic disease and kidney disease. Macrocytic anaemia, with large cells, suggests vitamin B12 or folate deficiency. Microcyticsmall cells (low MCV)iron deficiencythalassaemiachronic blood lossNormocyticnormal-size cellsacute blood losschronic diseasekidney disease (low EPO)Macrocyticlarge cells (high MCV)vitamin B12 deficiencyfolate deficiencyalcohol, some drugsB12 deficiency can also damage nerves: numbness, poor balance, weakness
Cell size points to the cause. Mean cell volume (MCV) on the blood count is the first clue.
FeatureExplanation
Fatigue, reduced exercise toleranceLess oxygen delivered to muscle
Breathlessness on exertionTissues reach their limit sooner
Fast heart rate, palpitationsHeart raises output to compensate
PallorLess haemoglobin in skin vessels
Normal pulse oximetrySaturation is normal; content is low

Watch out

A pulse oximeter reading of 98% does not rule out a severe shortage of oxygen-carrying capacity. Always check haemoglobin in a patient who is unexpectedly breathless or tired.

Altitude and red cells

Living at altitude lowers arterial oxygen, which raises EPO and red cell production. Levine and Stray-Gundersen sent competitive runners to live at 2,500 m for four weeks [2].

Figure 4 · Altitude raises red cell mass

Effects of four weeks of altitude living on red cell mass, aerobic capacity and performance Three results. Red cell mass increased about 9 per cent and maximal oxygen uptake about 5 per cent in both altitude groups. Five-kilometre time improved by 13.4 seconds only in runners who lived high and trained low. Red cell mass+9%Maximal oxygen uptake+5%5,000 m time (live high, train low)13.4 s fasterFour weeks at 2,500 m in competitive runners; red cell and oxygen gains in both altitude groups [2]
More haemoglobin, more aerobic capacity. Gains in maximal oxygen uptake tracked the rise in red cell mass [2].

Red cell mass rose about 9% and maximal oxygen uptake about 5% in both altitude groups [2]. Only runners who lived high but trained low improved their 5 km time, because they could keep their training speed [2].

Iron deficiency in heart failure

Iron is needed not only for haemoglobin but also for muscle mitochondria. Anker and colleagues randomised 459 patients with heart failure and iron deficiency to intravenous iron or placebo [3].

Figure 5 · Treating iron deficiency in heart failure

Symptom and functional class outcomes with intravenous iron in heart failure Paired bars. Fifty per cent reported being much or moderately improved with intravenous iron versus 28 per cent with placebo. Forty-seven per cent were in NYHA class I or II at 24 weeks versus 30 per cent. 28%Placebo50%IV ironMuch or moderately improved30%Placebo47%IV ironNYHA class I or II at 24 weeks
Iron matters even without anaemia. Benefits were similar with and without anaemia, and walking distance and quality of life improved [3].

Intravenous iron improved symptoms, functional class, six-minute walk distance and quality of life, with or without anaemia [3]. Rates of death and adverse events were similar between groups [3].

Practical skill · exercising patients with anaemia

Check the latest haemoglobin and follow local thresholds for activity after surgery or chemotherapy. Start with lower intensity, use rating of perceived exertion and heart rate, and allow longer rests. Stop for chest pain, dizziness or marked breathlessness.

Clinical relevance for the physiotherapist

  • Post-operative anaemia. Expect lower exercise tolerance; progress gradually.
  • Endurance athletes. Fatigue and poor performance may reflect iron deficiency, especially in women [1].
  • Heart failure. Iron deficiency limits function; IV iron can improve walking distance [3].
  • Kidney disease. Low EPO causes anaemia; treatment may improve exercise capacity.
  • B12 deficiency. Assess sensation and balance as well as fitness.

Assessment and application

FindingInterpretationAction
Hb 85 g/L two days after hip replacement, dizzy on standingPost-operative anaemiaGradual mobilisation; postural BP; inform team
Female runner, falling performance, low ferritinIron deficiency [1]Medical and dietetic review
Heart failure patient with low ferritin, short walk distanceIron deficiency limiting function [3]Raise with team; IV iron may help
Numb feet, unsteady gait, large red cellsPossible B12 deficiencyReport; balance assessment and safety

Common mistakes

  • Using oxygen saturation to judge oxygen-carrying capacity.
  • Assuming iron deficiency only matters if haemoglobin is low [3].
  • Ignoring hepcidin and training load when thinking about athletes’ iron [1].
  • Missing neurological signs of B12 deficiency.
  • Expecting altitude to help if training quality falls [2].

Exam preparation

Long answer

Describe erythropoiesis and its regulation. Classify anaemia.

  • Sites and stages of red cell production.
  • EPO feedback loop (Figure 1).
  • Requirements: iron (Figure 2), B12, folate.
  • Classification by MCV (Figure 3).
  • Effects on exercise; altitude [2]; iron in heart failure [3].

Short notes

  • Erythropoietin.
  • Iron metabolism and hepcidin [1].
  • Iron deficiency anaemia.
  • Live high–train low [2].

Viva and practical

  • “Where is EPO made?” — mainly the kidney.
  • “Why can an anaemic patient have normal saturation?” — saturation is a percentage, not an amount.
  • “What does altitude do to red cell mass?” — increases it [2].
  • OSCE: plan an exercise session for a patient with Hb 90 g/L.

Current evidence

Exam and traditional teaching

Anaemia is treated as a haemoglobin number; iron matters only for red cells.

What the evidence adds

Iron deficiency is common in athletes and is influenced by exercise-induced hepcidin [1].

Correcting iron deficiency improves function in heart failure even without anaemia [3]; altitude raises red cell mass and aerobic capacity [2].

What the student should understand

Oxygen delivery depends on haemoglobin, and haemoglobin depends on iron, EPO and nutrition. Ask about all three when a patient is unexpectedly tired.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. Iron deficiency in athlete cohorts is most common in:
  1. (A) Male sprinters
  2. (B) Female and endurance athletes
  3. (C) Weightlifters only
  4. (D) No group; it never occurs

Answer: (B) About 15–35% of female athlete cohorts are deficient, versus about 5–11% of males [1].

Q2. Which hormone, raised after exercise, reduces iron absorption?
  1. (A) Insulin
  2. (B) Hepcidin
  3. (C) Erythropoietin
  4. (D) Cortisol

Answer: (B) Exercise-induced increases in hepcidin alter iron metabolism in athletes [1].

Q3. In the live high–train low study, red cell mass increased by about:
  1. (A) 0%
  2. (B) 9%
  3. (C) 40%
  4. (D) 90%

Answer: (B) Both altitude groups increased red cell mass by about 9% [2].

Q4. Maximal oxygen uptake in the altitude groups increased by about:
  1. (A) 5%
  2. (B) 50%
  3. (C) 0%
  4. (D) 25%

Answer: (A) VO2max rose about 5%, in proportion to red cell mass [2].

Q5. Which group improved 5,000 m time in that study?
  1. (A) Live low–train low
  2. (B) Live high–train high
  3. (C) Live high–train low
  4. (D) All equally

Answer: (C) Only the high–low group improved, by about 13.4 s [2].

Q6. In FAIR-HF, intravenous iron in heart failure with iron deficiency:
  1. (A) Worsened symptoms
  2. (B) Improved symptoms, functional class, walking distance and quality of life
  3. (C) Only worked in anaemic patients
  4. (D) Raised mortality

Answer: (B) Benefits were seen with or without anaemia [3].

Q7. The proportion reporting being much or moderately improved with IV iron versus placebo was:
  1. (A) 50% vs 28%
  2. (B) 28% vs 50%
  3. (C) 10% vs 10%
  4. (D) 90% vs 5%

Answer: (A) Patient Global Assessment improved in 50% versus 28% [3].

Q8. The FAIR-HF trial defined iron deficiency partly as ferritin below:
  1. (A) 10 μg/L
  2. (B) 100 μg/L
  3. (C) 1,000 μg/L
  4. (D) 5 μg/L

Answer: (B) Ferritin < 100 μg/L, or 100–299 with transferrin saturation < 20% [3].

Q9. Which statement about altitude and red cells is correct?
  1. (A) Altitude lowers red cell mass
  2. (B) Altitude exposure stimulates red cell production
  3. (C) Altitude has no effect on red cells
  4. (D) Altitude only affects plasma

Answer: (B) Moderate altitude acclimatisation increased red cell mass [2].

Q10. A practical consequence of hepcidin rising after exercise is that iron supplements may be absorbed better:
  1. (A) Immediately after hard training
  2. (B) In the morning before or soon after training rather than hours later
  3. (C) Never
  4. (D) Only at night after meals

Answer: (B) Timing iron intake around the post-exercise hepcidin rise is among the recommendations discussed [1].

Quick review

Key takeaways

  • Red cells live about 120 days; EPO from the kidney drives production.
  • Iron is mostly recycled; hepcidin controls absorption and rises after exercise [1].
  • Anaemia types by MCV: microcytic, normocytic, macrocytic.
  • Anaemia lowers oxygen content despite normal saturation.
  • Altitude raises red cell mass and VO2max [2].
  • IV iron improves function in heart failure with iron deficiency [3].

Further reading

SourceWhy it earns its place
Sim M et al. — Eur J Appl Physiol, 2019Iron and the athlete [1]
Levine BD, Stray-Gundersen J — J Appl Physiol, 1997Altitude and red cell mass [2]
Anker SD et al. — NEJM, 2009Iron in heart failure [3]

References

  1. Sim M, Garvican-Lewis LA, Cox GR, et al. Iron considerations for the athlete: a narrative review. European Journal of Applied Physiology. 2019;119(7):1463–1478. doi:10.1007/s00421-019-04157-y PMID 31055680 Review
  2. Levine BD, Stray-Gundersen J. “Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. Journal of Applied Physiology. 1997;83(1):102–112. doi:10.1152/jappl.1997.83.1.102 PMID 9216951 Randomised controlled trial
  3. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. New England Journal of Medicine. 2009;361(25):2436–2448. doi:10.1056/NEJMoa0908355 PMID 19920054 Randomised controlled trial

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