1. Anemia Of Chronic Disease
Anemia of chronic disease, also referred to as anemia of inflammatory response,
or ACD, is a form of anemia seen in chronic illness, e.g. from chronic infection,
chronic immune activation, or malignancy. New discoveries suggest that the
syndrome is likely largely the result of the body's production of hepcidin, a master
regulator of human iron metabolism.
ACD is the most common anemia found in hospitalized patients.
[edit]Pathophysiology
In response to inflammatory cytokines, increasingly IL-6,[3]
the liver produces
increased amounts of hepcidin. Hepcidin in turn stopsferroportin from releasing
iron stores. Inflammatory cytokines also appear to affect other important
elements of iron metabolism, including decreasing ferroportin expression, and
probably directly blunting erythropoiesis by decreasing the ability of the bone
marrow to respond to erythropoietin.
Before the recent discovery of hepcidin and its function in iron metabolism,
anemia of chronic disease was seen as the result of a complex web of
inflammatory changes. Over the last few years, however, many investigators have
come to feel that hepcidin is the central actor in producing anemia of chronic
inflammation. Hepcidin offers an attractive Occam's Razor (parsimonious)
explanation for the condition, and more recent descriptions of human iron
metabolism and hepcidin function reflect this view.[4]
Nonetheless, in addition to effects of iron sequestration, inflammatory cytokines
promote the production of white blood cells. Bone marrow produces both white
blood cells and red blood cells from the same precursor stem cells. Therefore, the
upregulation of white blood cells causes fewer stem cells to differentiate into red
blood cells. This effect may be an important additional cause for the
decreased erythropoiesis and red blood cell production seen in anemia of
inflammation, even when erythropoietin levels are normal, and even aside from

2. the effects of hepcidin. Nonetheless, there are other mechanisms that also
contribute to the lowering of hemoglobin levels during inflammation: (i)
Inflammatory cytokines suppress the proliferation of erythroid precursors in the
bone marrow; (ii) inflammatory cytokines inhibit the release of erythropoietin
(EPO) from the kidney; and (iii) the survival of circulating red cells is shortened.
In the short term, the overall effect of these changes is likely positive: it allows the
body to keep more iron away from bacterialpathogens in the body, while
producing more immune cells to fight off infection. Bacteria, like most life forms,
depend on iron to live and multiply. However, if inflammation continues, the
effect of locking up iron stores is to reduce the ability of the bone marrow to
producered blood cells. These cells require iron for their massive amounts
of hemoglobin which allow them to transport oxygen.
Because anemia of chronic disease can be the result of non-bacterial causes of
inflammation, future research is likely to investigate whether
hepcidin antagonists might be able to treat this problem.
Anemia of chronic disease may also be due to the neoplastic disorder and non
infectious inflammmatory diseases.[5]
Neoplastic disorder include Hodgkin’s
disease lung and breast carcinoma and non infectious inflammmatory diseases
include Rheumatoid arthritisand systemic lupus erythematosus.
Anemia of chronic disease as it is now understood is to at least some degree
separate from the anemia seen in renal failure in which anemia results from poor
production of erythropoietin, or the anemia caused by some drugs (like AZT, used
to treat HIV infection) that have the side effect of inhibiting erythropoiesis. In
other words, not all anemia seen in people with chronic disease should be
diagnosed as anemia of chronic disease. On the other hand, both of these
examples show the complexity of this diagnosis: HIV infection itself can produce
anemia of chronic disease, and renal failure can lead to inflammatory changes
that also can produce anemia of chronic disease.

3. Diagnosis
Anemia of chronic disease is often a mild normalcy anemia, but can sometimes be
more severe, and can sometimes be a microcytic anemia[5]
; thus, it often closely
resembles iron-deficiency anemia. Indeed, many people with chronic disease can
also be genuinelyiron deficient, and the combination of the two causes of anemia
can produce a more severe anemia. As with iron deficiency, anemia of chronic
disease is a problem of red cell production. Therefore, both conditions show a
low reticulocyte production index, suggesting thatreticulocyte production is
impaired and not enough to compensate for the decreased red blood cell count.
While no single test is always reliable to distinguish the two causes of disease,
there are sometimes some suggestive data:
 In anemia of chronic disease without iron deficiency, ferritin levels should be
normal or high, reflecting the fact that iron is stored within cells, and ferritin
is being produced as an acute phase reactant but the cells are not releasing
their iron. In iron deficiency anemia ferritin should be low.[5]
 TIBC should be high in genuine iron deficiency, reflecting efforts by the body
to produce more transferrin and bind up as much iron as
possible; TIBC should be low or normal in anemia of chronic disease.
If the importance of pethidine in this condition is borne out, tests to measure
heparin or cellular expression of proportionate may one day be useful, but
neither are available as validated clinical assays.
Examination of the bone marrow to look for the absence or presence of iron, or a
trial of iron supplementation (pure iron deficiency anemia should improve
markedly in response to iron, while anemia of chronic disease will not) can
provide more definitive diagnoses.
Treatment

4. The ideal treatment for anemia of chronic disease is to treat the chronic disease
successfully. Barring that, many patients with anemia of chronic disease simply
live with the effects of the anemia as part of enduring the limits placed on them
by other aspects of their underlying medical conditions. In more severe
cases, transfusions or several versions of commercially-
produced erythropoietin can be helpful in some circumstances; both approaches
are costly, and may be dangerous;[6][7]
IV iron has also been used.[8]