Physiological compensatory

hemoglobin concentration.

mechanisms

for

decrease

in

1. Tissue oxygen delivery is also the major controlling factor of

erythropoiesis through the synthesis and release of erythropoietin
(EPO) by the proximal tubular cells or the peritubular interstitial cells
in the kidney. EPO synthesis is governed by the activation of hypoxia
inducible factor-1 (HIF-1), which controls the metabolic responses of
multiple gene products to hypoxia. HIF-1 binds and activates the
hypoxia-responsive transcriptional enhancer in the erythropoietin
gene regulatory region that upregulates EPO expression. EPO
stimulates erythroid precursor cells (CFU-E [colony-forming units
erythroid]), leading to increased proliferation and shortening of their
maturation time. The marrow responds to increased EPO maximally
in 4 to 7 days if enough iron is available. Erythropoiesis can be
increased by as much as a factor of 8. Typical of an endocrine loop
feedback mechanism, there is an inverse relation between the
hemoglobin and EPO levels measured in the blood (Fig. 2). Although
this relation holds true in simple iron deficiency, it is somewhat
distorted in the anemia associated with inflammation or chronic
disease, in which there may be a blunted EPO response. This has
made prediction of the hemoglobin response to treatment with
exogenous EPO unpredictable, except in limited circumstances
2. Decreased hemoglobin oxygen affinity Increased oxygen
extraction of anemic blood by the tissues produces increased
concentration of deoxyhemoglobin in the rbc, which stimulates the
production of 2,3-diphosphoglycerate (2,3-DPG). 2,3-DPG shifts the
hemoglobin-oxygen dissociation curve to the right, thus allowing the
tissues to more easily strip the hemoglobin of its precious electronaccepting
cargo:

3. Redistribution of blood flow In anemia selective vasoconstriction

of blood vessels subserving certain nonvital areas allows more blood
to flow into critical areas. The main donor sites who sacrifice their
aerobic lifestyle are the skin and kidneys. Shunting of blood away
from cutaneous sites is the mechanism behind the clinical finding of
pallor, a cardinal sign of anemia. Although the kidney can hardly be

thought of as a nonvital area, it receives (in the normal state) much

more blood flow than is needed to meet its metabolic requirements.
Although (by definition) total body red cell mass is decreased in
anemia, in the chronically anemic patient the total blood volume
paradoxically is increased, due to increased plasma volume. It is as
if the body were trying to make up in blood quantity what it lacks in
quality.
4. Increased cardiac output The heart can respond to tissue hypoxia
by increased cardiac output. The increased output is matched by
decreased peripheral vascular resistance and decreased blood
viscosity (thinner blood flows more freely than thick blood), so that
cardiac output can rise without an increase in blood pressure.
Generally, anemia must be fairly severe (hemoglobin < 7 g/dL)
before cardiac output rises.