Anaemia: Adaptive Mechanisms and Consequences


Human life depends on the availability of oxygen and its conversion into energy used by living cells. Reduced oxygen to tissues is referred to as hypoxia, and may result from decreased oxygen delivery or mitochondrial dysfunction. In the setting of tissue hypoxia due to anaemia or other causes, several adaptive and coordinated physiologic processes are initiated to maintain oxygen delivery and limit oxygen consumption. Mechanisms to increase oxygen delivery in the face of anaemia or global hypoxia include the stimulation of erythropoiesis, and increasing cardiac output. Oxygenation availability is further maximised by decreases in the haemoglobin‐oxygen binding affinity, increases in tissue oxygen extraction, and via changes in regional blood flow. Mild to moderate anaemia, especially if chronic, is generally well tolerated given these adaptive processes. In states of inflammation or chronic disease, down regulation of haemoglobin occurs and may represent an important adaptive mechanism.

Key Concepts:

  • Aerobic metabolism and human life depend on the availability of oxygen.

  • Anaemia results when the haemoglobin levels are below normal and, if severe, may result in tissue hypoxia.

  • Adaptive mechanisms exist to compensate for anaemia or other causes of tissue hypoxia so that oxygen delivery is maintained and balanced with oxygen consumption.

  • A major adaptive mechanism in response to anaemia is to increase production of the growth hormone erythropoietin, leading to the formation of red blood cells.

  • The anaemia associated with inflammation has features of an adaptive response, is generally well tolerated and rarely requires treatment.

Keywords: anaemia; erythropoietin; adaptive responses; hypoxia; oxygen sensing; erythropoiesis; oxygen delivery; anemia of chronic disease

Figure 1.

HIF‐1α is rapidly degraded under normoxic conditions via ubiquitin labelling and the proteasomal system. In hypoxic conditions, HIF is stabilized and protected from degradation. HIF functions as a transcription factor to activate several genes including VEGF, EPO and transferrin along with their individual receptors.

Figure 2.

Normal and right‐shifted oxygen dissociation curves. A right shift (reduced affinity) in the curve can be due to increased 2,3‐diphosphoglycerate (2,3‐DPG), increased temperature or acidosis.

Figure 3.

In inflammatory diseases, leucocytes and other cells release cytokines that act in several ways to lower haemoglobin levels: (a) Induction of hepcidin synthesis by the liver ( (IL‐6)). Hepcidin binds to ferroportin, the membrane ion channel that allows egress of iron from macrophages and from intestinal epithelial cells. Binding of hepcidin triggers internalisation and degradation of ferroportin, and consequently leads to sequestration of iron within the macrophages and enterocytes, limiting iron availability to erythroid precursors for production of haemoglobin. (b) Inhibition of erythropoietin release by the kidney (especially IL‐1β and (TNFα)), thus reducing the stimulus for hematopoietic proliferation. (c) Direct suppression of the proliferation of erythroid progenitors in the marrow (especially TNFα, (IFNγ), IL‐1β). (d) Augmentation of phagocytosis of red cells by (RES) macrophages (TNFα). Adapted from Zarychanski and Houston . Copyright by Canadian Medical Association.



Brannon ES, Merrill AJ, Warren JV and Stead EA (1945) The cardiac output in patients with chronic anemia as measured by the technique of right atrial cateterization. Journal of Clinical Investigation 24(3): 332–336.

Ebert BL and Bunn HF (1999) Regulation of the erythropoietin gene. Blood 94: 1864–1877.

Grocott MPW, Montgomery H and Vercueil A (2007) High altitude physiology and pathophysiology: implications and relevance for intensive care medicine. Critical Care 11(1): 203.

Hall JE (ed.) (2010) Transport of oxygen and carbon dioxide in blood and tissue fluids. Guyton and Hall Textbook of Medical Physiology, 12th edn, pp. 495–504. Philadelphia, PA: Saunders Elsevier.

Hoffbrand AV and Moss PAH (2011) Essential Haematology, 6th edn. Chichester, West Sussex: Wiley Blackwell.

Martin C, Yu AY, Jiang BH et al. (1998) Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia‐inducible factor 1. American Journal of Obstetrics and Gynecology 178: 527–534.

Metivier F, Marchais SJ, Guerin AP et al. (2000) Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrology Dialysis Transplantation 15(suppl. 3): 14–18.

Schumacker PT (2002) Hypoxia anoxia, and O2 sensing: the search continues. American Journal of Physiology ‐ Lung Cellular and Molecular Physiology 283: L918–L921.

Semenza GL (2009) Involvement of oxygen‐sensing pathways in physiologic and pathologic erythropoiesis. Blood 114(10): 2015–2019.

Thomas D (2004) The physiology of oxygen delivery. Vox Sanguinis 87(suppl. 1): S70–S73.

Tsui AK, Marsden PA, Mazer CD et al. (2011) Priming of hypoxia‐inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anaemia. Proceedings of the National Academy of Sciences of the USA 108(42): 17544–17549.

Voormolen N, Grootendorst DC, Urlings TA et al. (2010) Prevalence of anaemia and its impact on mortality and hospitalization rate in predialysis patients. Nephron Clinical Practice 115(2): c133–c141.

Weiskopf R, Viele M, Feiner J et al. (1998) Human cardiovascular and metabolic response to acute, severe isovolemic anaemia. Journal of the American Medical Association 279(3): 217.

Weiss G and Goodnough LT (2005) Anemia of chronic disease. New England Journal of Medicine 352(10): 1011–1023.

Winslow RM (2007) The role of haemoglobin oxygen affinity in oxygen transport at high Respiratory Physiology & Neurobiology 158(2–3): 121–127.

Zarychanski R and Houston DS (2008) Anaemia of chronic disease: a harmful disorder or an adaptive, beneficial response? Canadian Medical Association Journal 179(4): 333–337.

Further Reading

Lichtman MA, Kipps TJ and Seligsohn U (eds) (2010) Williams Hematology, 8th edn. New York: McGraw‐Hill.

Semenza GL (2012) Hypoxia‐inducible factors in physiology and medicine. Cell 148: 399–408.

Shander A, Javidroozi M, Ozawa S and Hare GM (2011) What is really dangerous: anaemia or transfusion? British Journal of Anaesthesia 107(suppl. 1): i41–i59.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Zarychanski, Ryan, Rimmer, Emily, and Houston, Donald S(Sep 2012) Anaemia: Adaptive Mechanisms and Consequences. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002157.pub2]