Blood
Cell Cycle
The
normal red blood cell is a biconcave disk approximately to 7.5µ in diameter. It
is the major component of the cellular compartment of the blood, with a
circulating life of about 100 to 120 days.
The
primary role of RBC is to deliver oxygen to the tissues for metabolism and
carry dissolved carbon dioxide to the lungs for release into the air. The red
cell depends on the hemoglobin molecule to for transport of these gases.
The
number of erythrocytes in the blood ranges form 3.8 to 5.9 million cells per
microliter of blood, with a hemoglobin concentration ranging form 17 to 17g/dl
and a hematocrit of 35% to 52%.
This
normal range is broad for it cover men and women young and old, and with people
living at altitude. Induced erythropeiesis, leading to the expansion of red
cell mass, occurs in response to hypoxia, blood loss, and a variety of hormones
and diease states.
The
most potent stimulator of erythropoiesis is erythropoietin.
Erythropoietin
is a hormone produced by the kidney in response to hypoxia. This hormone
stimulates the pluripotent stem cells in the bone marrow to become mature.
The
bone marrow is capable of increasing the production of red cells by 5 to 10
times normal under the influence of erythropoietin. However, because of the
limiting factor of iron in diet the increase is only two to three times normal.
In
patients with chronic renal failure or after a nephrectomy, the ability to
generate a erythropoietin response is slower.
Red
Blood Cell Life and death
The
red blood cell does not possess the structures required for DNA synthesis nor,
for transcription and translation of proteins. Cellular life depends the cells
ability to generate ATP through the utilization of glucose. Without the pathway
for ATP generation, the cell would not be able to maintain its membrane
integrity, and ionic gradients. The ability to maintain hemoglobin in its
reduced form for the transport and delivery of oxygen would also be limited.
Glucose
is the primary fuel of the erythrocyte. It enters the cell through diffusion
from the plasma, and through glycolysis ultimately is converted to lactate and
pyruvate.
This
process uses 2 moles of ATP and produce 4 moles of ATP, for a net gain of 2 ATP
molecules. The rate limiting step is controlled by the activity of
phosphofructokinase, which converts fructose 6-phosphate to fructose 1,6
phosphate. This enzyme is inhibited by high concentrations of ATP, which signal
the “fed” state.
Conversely,
high concentrations of AMP signal an “energy starved” state favouring continued
glycolysis.
The
energy generated by glycolysis is utilized by the Na+ -K+ ATPase pump to
regulate cell membrance potentials.
Maintenance
of the appropriate redox potential is essential for the red blood cell to
complete its function of oxygen delivery.
The
red cell ultimately dies as its enzyme systema burn out.
The
inability to continue glycolysis to maintain membrane gradients leads to
changes in membrane permability and ultimately to cell destruction. More than
90% of red cells with altered membrane are destroyed by the macrophages of the
reticuloendothelial system (spleen, liver and marrow).
As
the cells are destroyed, the hemoglobin molecule is further degraded. The iron
is largely conserved, redistributed to the marrow, and incorporated into new
hemoglobin
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