Erythron pathophysiology- what does it really mean?

ABSTRACT

AIM: To identify the meaning of erythron
Pathophysiology and its relationship in the diagnosis of
anaemia.

METHODS: Relevant information were
consulted in various papers in an attempt to identify the issues
on erythron Pathophysiology.

CONCLUSION: The conclusion was that when we
talk about erythron Pathophysiology, it means the disorder of
erythrocytes or red blood cells that can be seen in clinical
practice and this can be manifested in many forms.

KEYWORDS: Erythron, Pathophysiology,
Anaemia

Corresponding Author: Peter Ubah
Okeke

Student, School of Science &
Engineering,

Atlantic International University,
Honolulu- Hawaii

www.aiu.edu

Term paper

INTRODUCTION

Erythron is the name given to the collection of all
stages of erythrocytes throughout the body and this includes the
developing precursors in bone marrow and the circulating mature
erythrocytes in the peripheral blood, therefore erythron is the
entirety of erythroid cells in the body. However, pathophysiology
refers to the manner in which a disorder (in this case
erythrocytes) translates into clinical symptoms. For the purpose
of this assignment we concentrate on disorders of iron and heme
metabolism and under this heading, general concepts in anemia and
iron deficiency anemia will be discussed.

General concepts
in anemia

Anemia may result whenever red blood cell (RBC)
production is impaired, RBC life span is shortened or there is
frank loss of cells. The anemias associated with iron typically
are categorized as anemias of impaired production. The formation
of RBCs requires many constituents, chief among them being the
components for the production of hemoglobin (Hb): iron, heme and
globin. Depending on the cause, lack of available iron results in
iron deficiency anemia or the anemia of chronic inflammation.
Inadequate availability of heme results in a relative excess
manifested in sideroblastic anemias, while inadequate globin
production results in the thalassemias. Iron is absorbed from the
diet in the small intestine, carried by transferrin to a cell in
need, and incorporated into the muscles where it is held as
ferritin until incorporated into its final functional
molecule.

That functional molecule may be a heme-based cytochrome,
muscle myoglobin or developing RBCs (Hb), iron may be unavailable
for incorporation into heme because of inadequate stores of body
iron or merely because of impaired mobilization. The anemia
associated with inadequate stores is termed iron deficiency,
whereas the anemia resulting from impaired mobilization is anemia
of chronic inflammation due to its association with chronic
inflammatory conditions, such as rheumatoid arthritis. When the
iron supply is adequate and mobilization is unimpaired, but an
intrinsic RBC defect prevents incorporation of iron into heme,
the resulting anemia is termed sideroblastic, referring to the
presence of iron in the developing RBCs.

Iron deficiency
Anemia

Iron deficiency anemia develops when the intake of iron
is inadequate to meet a standard level of demand when the need
for iron expands or when there is chronic loss of Hb from the
body.

Inadequate
intake

Iron deficiency anemia can develop as the erythron is
slowly starved for iron. Each day, approximately l mg of iron is
lost from the body mainly in the mitochondria of desquamated skin
and sloughed intestinal epithelium Hallberg (1981). When the diet
is consistently inadequate in iron, over time the body`s stores
of iron become depleted. Ultimately, RBC production slows as a
result of the inability to produce Hb. With approximately 1% of
cells naturally dying each day, the anemia becomes apparent when
the production rate cannot replace lost cells.

Increased
need

Iron deficiency also can develop when the level of iron
intake becomes inadequate to meet the needs of an expanding
erythron. This is the case in periods of rapid growth such as
infancy, childhood and adolescence. Pregnancy and nursing place
similar demands on the mother"s body to provide iron for the
developing fetus or nursing infants and herself. In each of these
instances, what had previously been an adequate intake of iron
for the individual becomes inadequate as the need for iron
increases.

Chronic blood
loss

A third way iron deficiency develops is with excessive
loss of Hb from the body. This loss occurs with slow hemorrhage
or hemolysis. Any condition in which there is a slow low-level
loss of RBCs may result in iron deficiency.

For women, heavy menstrual bleeding can constitute a
chronic loss of blood leading to iron deficiency as can bleeding
associated with fibroid tumors. For women or men gastro
intestinal bleeding from ulcers or tumors, loss of blood via the
urinary tract with kidney stones or tumors also can lead to iron
deficiency. Persons with chronic intravascular hemolysis such as
paroxysmal nocturnal hemoglobinuria, can lead to iron deficiency
due to the loss of iron in Hb passed into the urine.

Pathogenesis

Iron deficiency anemia develops slowly, progressing
through stages that physiologically blend one into the other but
are useful delineations for understanding disease progression
Suominem et al (1998).

Iron is distributed among three compartments:

• 1. The storage compartment, principally as
  ferritin in the bone marrow, macrophages and liver
  cells.

• 2. The transport compartment of serum
  transferrin.

• 3. The functional compartment of Hb, myoglobin,
  and cytochromes. Hb and intra cellular ferritin constitute
  nearly 95% of the total distribution of iron Andrews
  (2003).

For a period of time as iron intake lag behind loss,
essentially normal iron status continues. Absorption of iron
through the intestine is accelerated in an attempt to meet the
relative increased demand for iron, but this is not apparent in
laboratory tests or patient symptoms. The person appears
apparently healthy but as the negative iron balance continues
however, a stage of iron depletion develop.

Stage 1

This is characterized by a progressive loss of storage
iron. The body"s reserve of iron is sufficient to maintain the
transport and functional compartments through this phase. So RBC
development is normal. There is no evidence of iron deficiency in
the peripheral blood picture and the patient experiences no
symptoms of anemia. If ferritin levels are measured, they are
low, indicating the decline in stored iron, which also could be
detected in an iron stain of the marrow. Without evidence of
anemia, neither of these tests would be performed and individuals
appear healthy. Dallman et al (1980) estimated that nearly 50% of
U.S. infants are in this phase of iron deficiency.

Stage 2

This stage two of iron deficiency is defined by the
exhaustion of the storage pool of iron. For a time RBC production
continues as normal, relying on the iron available in the
transport compartment. Anemia as measured relative to the
reference range of Hb, is still not evident, although an
individual"s Hb may begin dropping. Other iron-dependent tissues
such as muscles may begin to be affected, but the symptoms may be
nonspecific. Ferritin estimation and serum iron are still low.
Whereas total iron binding capacity (TIBC) (that is transferin)
increases. Free erythrocytes protoporphyrin (FEP), the porphyrin
into which iron is inserted to form heme, begins to accumulate.
Transferrin receptors increase on the surface of iron-starved
cells as they are trying to capture as much available iron as
possible.

Stage 3

Iron deficiency in this stage is frank anemia. The Hb
and hematocrit (HCT) are low relative to the reference ranges
having thoroughly depleted storage iron and diminshed transport
iron, developing RBCs are unable to develop normally. The number
of cell divisions per precursor increases because hemoglobin
accumulation in the developing cells is slowed allowing more time
for cell divisions. The result is first smaller cells with
adequate Hb concentration, although ultimately even these cannot
be filled with Hb. These cells become microcytic and
hypochronic.

Ferritin levels are exceedingly low. Other iron studies
also are abnormal and the FEP and transferrin receptors levels
increase. In this phase, the patient experiences the nonspecific
symptoms of anemia, typically fatigue and weakness especially
with exertion. Pallor is evident, sore tongue (glossitis) and
angular chelosis are seen. Koilonychia may also be seen if the
deficiency is long standing, patient may also experience cravings
for non food items called pica. The cravings may include things
such as dirt, clay, laundry starch or most commonly ice
specifically called pagophagia.

Epidemiology

Menstruating women are at especially high risk. If women
of childbearing age are not properly supplemented, pregnancy and
nursing can lead to a loss of nearly 900 mg of iron. Succeeding
pregnancies can exacerbate the problem leading to iron deficient
fetuses Green et al (1968). Growing children also are at high
risk. Cow"s milk is not a good source of iron and infants need to
be placed on supplemented formular by about age 6 months when
their fetal stores of iron become depleted. This assumes infants
were able to establish adequate stores from their mothers in
utero. Even though breast milk is a better source of iron than
cow"s milk, Saarinen et al (1977), it is not a consistent source
Siimes et al (1979). Iron supplementation also is recommended for
breast fed infants after 6 months of age.

Iron deficiency is relatively rare in men and
postmenopausal women because the body conserves iron so
tenaciously and these individuals lose only about 1
mg/dl.

Gastro intestinal disease, such as ulcers, tumors
hemorrhoids, should be suspected for iron deficient patient in
either of these groups if the diet is known to be adequate in
iron.

Iron deficiency is associated with infection by
hookworms. The worm attaches to the intestinal wall and literally
sucks blood from the gastric vessels.

Soldiers and long distance runners also can develop iron
deficiency. Marching anemia develops when RBCs are hemolyzed by
foot pounding trauma and iron is lost as Hb in the urine Beutler
et al (1960). The amount lost in the urine can be so little that
it is not apparent on visual inspection.

Laboratory
Diagnosis

The tests can be grouped into three general
categories:

• Screening

• Diagnostic

• Specialized

Screening test
for iron deficiency anemia

When iron deficient erythropoiesis is occurring, the
complete blood count begins to show evidence of microcytosis and
hypochromia. Hb is decreased and RBC distribution with (RDW)
greater than 15% would be expected and may precede the decrease
in Hb Thompson et al (1988). For patients in high-risk groups,
the elevated RDW can be an early and sensitive indicator of iron
deficiency Mcclure S et al (1985).

As the Hb continues to fall, microcytosis and
hypochromia become more prominent with progressively declining
values for mean cell volume (MCV), mean cell hemoglobin (MCH) and
mean cell hemoglobin concentration (MCHC). The RBC count
ultimately becomes decreased as does the Hematocrit.

Diagnosis of iron
deficiency

Iron studies remain the back bone for diagnosis of iron
deficiency. They includes assay of serum iron, total iron binding
capacity(TIBC), transferring saturation and ferritin.

It is important that iron studies are drawn fasting and
early in the morning. Iron shows a diurnal variation with levels
dropping throughout the day Sinniah et al (1969) and iron
absorbed from a meal can falsely elevate levels Crosby &
O"Neil-Cutting (1984).

Specialized
laboratory diagnosis

Free erythrocyte protoporphyrin (FEP) accumulates when
iron is unavailable. In the absence of iron, FEP may be
preferentially chelated with zinc to from zinc protoporphyrin
(ZPP) Lamola et al (1975). The FEP and the Zinc chelate can be
assayed fluorometrically. Serum transferrin receptors (STFR) also
can be assayed using immunoassay.

Conclusion: It is very clear that erythron
Pathophysiology includes anaemia and other abnormalities of
erythrocytes that can be seen in clinical practice, from the
formation, metabolic and the catabolic aspects of red blood
cells. Specific case study could have specific clinical and
laboratorial diagnosis.

References

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Beutlere et al (1960); Iron therapy in chronically
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Croshy WH & O"Neil-Cutting MA (1984); A Small dose
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Dallman PR et al (1980); iron deficiency in infancy and
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Green R et al (1968); Body iron excretion in man: a
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Hallberg L (1981); Bioavailability of dietary iron in
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Kathryn Doig (2007); Disorders of iron and heme
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Mcclure S et al (1985); Improved detection of early iron
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Saarinen Um et al (1977); Iron absorption in infants:
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of serum ferritin. J pediatr 91: 36-39

Siimes MA et al (1979); Breast milk iron: a declining
concentration during the course of lactation. Acta pediatr Scand
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Sinniah R et al (1969); Diurnal Variations of the serum
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Suominen P et al (1998); Serum transferring receptor and
transferrin receptor-ferritin index identify healthy subjects
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Thompson WG et al (1988); Red cell distribution width,
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2128

Autor:

Peter Ubah Okeke

2011