Volumen: 21 # Number : XXIII Congreso Argentino de Hematología
Publication Date : Noviembre Year: 2017
CONFERENCIA
NACIONAL
Dr. Miguel Ángel Etcheverry |
Iron overload
Authors: Chiappe G
Abstract: The organism in whole and each cell in particular
regulate iron disposal by income, not by outcome.
Only three cells: enterocytes, macrophages and
hepatocytes express ferroportin, the only known iron
exporter, on their vascular surface. All the other cells,
as well as the body itself, are incapable of eliminating
any iron excess. Each cell regulates iron admission
through the expression on its surface of transferrin
receptor-1 and divalent metal transporter-1, according
to its own iron requirements, expressed through
iron responsive proteins-1 and 2 (local regulation).
Systemic regulation of iron intake is managed by
hepcidin, whose synthesis, primarily in hepatocytes,
is controlled by plasmatic and hepatocyte iron
content, inflammation and degree of erythropoiesis.
Hepcidin blocks iron income into plasma through
ferroportin internalization and degradation. Systemic
iron overload must be firstly differentiated from
local iron misdistribution, which may or may not
be accompanied by iron overload. Systemic iron
overload may be primary, when there is a defect in
the synthesis of proteins involved in iron metabolism,
or secondary, when the iron enters in excess into the
organism through enteral (“physiological” hepcidin
underexpression secondary to hereditary or acquired
pathologies) or parenteral (transfusions) ways.
Secondary iron overload, often underdiagnosed, is
much more frequent than primary iron overload,
sometimes incorrectly overdiagnosed. Hereditary
hemochromatosis is, by far, the most frequent
primary iron overload syndrome, followed by a
perhaps not infrequent ferroportin disease. Among
hemochromatosic syndromes, HFE hemochromatosis
is the most common, with C282Y mutation as the
most important and H63D mutation as the most
frequent. Diagnosis must be supported on two pillars:
an important genetic background (homozygous HFE
C282Y or double heterozygous HFE C282Y/H63D)
and a coincident hemochromatosic profile with early
transferrin saturation and subsequent plasmatic
ferritin elevation, much higher iron deposition in liver
than in spleen on nuclear magnetic resonance, and
more parenchymal (hepatocytes) than macrophage
(Kupffer cells) iron accumulation on liver biopsy. This
adult hemochromatosis has a slow progression (years,
decades) and a low penetrance, as only about half of HFE C282Y homozygous patients will eventually
develop any iron profile alteration (stage 1) and
perhaps less than a quarter will even express clinical
manifestations (stage 2). Therefore it’s important the
routine control of transferrin saturation every 5-10
years from adolescence on in order to detect early iron
metabolism alterations and correct them before the
appearance of clinical complications. Treatment of
hereditary hemochromatosis requires the elimination
of iron excess through periodical phlebotomies (or
erythrocyte apheresis in severe cases, eventually with
the addition of erythropoietin). There is no need to
identify HFE hemochromatosic patients at stage 0
(genetic survey), but undoubtedly at stage 1 in order
to avoid any progression to stage 2.
Key words: iron overload,
hemochromatosis,
hyperferritinemia.
Pages :
|
