Anaemia: Adaptive Mechanisms and Consequences

Abstract

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 (interleukin‐6 (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 tumour necrosis factor‐α (TNFα)), thus reducing the stimulus for hematopoietic proliferation. (c) Direct suppression of the proliferation of erythroid progenitors in the marrow (especially TNFα, interferon‐γ (IFNγ), IL‐1β). (d) Augmentation of phagocytosis of red cells by reticuloendothelial system (RES) macrophages (TNFα). Adapted from Zarychanski and Houston . Copyright by Canadian Medical Association.

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Further Reading

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