Alterations in Red Blood Cells
The Red Blood Cell
; The mature red blood cell, the erythrocyte, is a non-nucleated, biconcave disk. This shape increases
the surface area available for diffusion of oxygen and allows the cell to change in volume and shape
without rupturing its membrane. A cytoskeleton of proteins attached to the lipid bilayer provides this
unique shape and flexibility.
; The function of the red blood cell, facilitated by the hemoglobin molecule, is to transport oxygen to
the tissues. Hemoglobin also binds some carbon dioxide and carries it from the tissues to the lungs. ; The two major types of normal hemoglobin are adult hemoglobin (HbA) and fetal hemoglobin (HbF).
HbA consists chains.
; HbF is the predominant hemoglobin in the fetus from the third through the ninth month of gestation.
It has a pair of chains substituted for the has a high
affinity for oxygen. This facilitates the transfer of oxygen across the placenta. HbF is replaced within
6 months of birth with HbA.
; The rate at which hemoglobin is synthesized depends on the availability of iron for heme synthesis.
A lack of iron results in relatively small amounts of hemoglobin in the red blood cells. The amount
of iron in the body is approximately 35 to 50 mg/kg of body weight for males and less for females.
Body iron is found in several compartments.
Approximately 15% to 20% is stored in the bone marrow, liver, spleen, and other organs. Iron in the ;
hemoglobin compartment is recycled. As red blood cells age and are destroyed in the spleen, iron
from their hemoglobin is released into the circulation and transported to the bone marrow for use in
production of new red cells or to the liver and other tissues for storage.
; Dietary iron helps to maintain body stores. Iron, principally derived from meat, is absorbed in the
small intestine, especially the duodenum
Red Cell Production
; Erythropoiesis is the production of red blood cells. After birth, red cells are produced in the red bone
marrow. Until age 5 years, almost all bones produce red cells to meet growth needs. After this period,
bone marrow activity gradually declines.
; After 20 years of age, red cell production takes place mainly in the membranous bones of the
vertebrae, sternum, ribs, and pelvis. With this reduction in activity, the red bone marrow is replaced
with fatty yellow bone marrow.
; Erythropoiesis is governed for the most part by tissue oxygen needs. Any condition that causes a
decrease in the amount of oxygen that is transported in the blood produces an increase in red cell
production. The oxygen content of the blood does not act directly on the bone marrow to stimulate
red blood cell production. Instead, the decreased oxygen content is sensed by the kidneys, which
then produce a hormone called erythropoietin.
; Normally, the kidneys produce approximately 90% of erythropoietin, with the remaining 10% being
released by the liver. In the absence of erythropoietin, as in kidney failure, hypoxia has little or no
effect on red blood cell production.
Red Cell Destruction
; Mature red blood cells have a life span of approximately 4 months or 120 days. As the red blood cell
ages, a number of changes occur. Metabolic activity in the cell decreases, and enzyme activity
decreases; adenosine triphosphate (ATP) decreases, and the cell membrane becomes more fragile.
Once the red cell membrane becomes fragile, the cell ruptures during passage through narrowed
places in the circulation.
; The destruction of red blood cells is facilitated by a group of large phagocytic cells found in the
spleen, liver, bone marrow, and lymph nodes. These phagocytic cells ingest the hemoglobin from the
ruptured cells and break it down in a series of enzymatic reactions. During these reactions, the amino
acids from the globulin chains and iron from the heme units are salvaged and reused. The bulk of the
heme unit is converted to bilirubin, the pigment of bile, which is insoluble in plasma and attaches to
the plasma proteins for transport.
; Bilirubin is removed from the blood by the liver and conjugated with glucuronide to render it water
soluble so that it can be excreted in the bile. The plasma-insoluble form of bilirubin is referred to as
unconjugated bilirubin; the water-soluble form is referred to as conjugated bilirubin.
Red Cell Metabolism and Hemoglobin Oxidation
The red blood cell, which lacks mitochondria, relies on glucose and the glycolytic pathway for its metabolic needs. The enzyme-mediated anaerobic metabolism of glucose generates the ATP needed for normal membrane function and ion transport.
; Red blood cells can be studied by means of a sample of blood. In the laboratory, automated blood
cell counters rapidly provide accurate measurements of red cell content and cell indices. The red
blood cell count (RBC) measures the total number of red blood cells in 1 mm3 of blood. The
percentage of reticulocytes (normally approximately 1%) provides an index of the rate of red cell
production. The hemoglobin (grams per 100 mL of blood) measures the hemoglobin content of the
; The major components of blood are the red cell mass and plasma volume. The hematocrit measures
the volume of red cell mass in 100 mL of plasma volume. To determine the hematocrit, a sample of
blood is placed in a glass tube, which is then centrifuged to separate the cells and the plasma. The
hematocrit may be deceptive because it varies with the quantity of extracellular fluid, rising with
dehydration and falling with overexpansion of extracellular fluid volume.
; Anemia is defined as an abnormally low hemoglobin level, number of circulating red blood cells, or
both, resulting in diminished oxygen-carrying capacity of the blood. Anemia usually results from
excessive loss (i.e., bleeding) or destruction (i.e., hemolysis) of red blood cells or from deficient red
blood cell production because of a lack of nutritional elements or bone marrow failure.
; Anemia is not a disease, but an indication of some disease process or alteration in body function.
The manifestations of anemia can be grouped into three categories: (1) impaired oxygen transport
and recruitment of compensatory mechanisms; (2) alterations in hemoglobin levels and red cell
number and appearance; and (3) signs and symptoms associated with the pathologic process that is
causing the anemia.
; Manifestations of anemia are caused by the decreased presence of hemoglobin in the blood (pallor),
tissue hypoxia due to deficient oxygen transport (weakness and fatigue), and recruitment of
compensatory mechanisms (tachycardia and palpitations) designed to increase oxygen delivery to
Blood Loss Anemia
; With anemia caused by bleeding, iron and other components of the erythrocyte are lost from the
body. Blood loss may be acute or chronic.
; Acute blood loss is accompanied by a loss of vascular volume and carries with it a risk of
hypovolemia and shock. The red cells are normal in size and color. Hemodilution caused by
movement of fluid into the vascular compartment produces a fall in red blood cell count, hemoglobin,
; The hypoxia that results from blood loss stimulates red cell production by the bone marrow. If the
bleeding is controlled and sufficient iron stores are available, the red cell concentration returns to
normal within 3 to 4 weeks.
; Chronic blood loss does not affect blood volume but instead leads to iron-deficiency anemia when
iron stores are depleted. Because of compensatory mechanisms, patients commonly have no
symptoms until the hemoglobin level is less than 8 g/dL. The red cells that are produced have too
little hemoglobin, giving rise to microcytic hypochromic anemia.
; Hemolytic anemia is characterized by the (1) premature destruction of red cells, (2) retention in the
body of iron and the other products of hemoglobin destruction, and (3) marked increase in
erythropoiesis within the bone marrow.
; Because of the red blood cell’s shortened life span, the bone marrow usually is hyperactive, resulting
in an increase in the number of reticulocytes in the circulating blood. As with other types of anemias,
the person experiences easy fatigability, dyspnea, and other signs and symptoms of impaired oxygen
transport. The person may also have an increase in serum bilirubin and mild jaundice.
Sickle Cell Disease (Anemia)
; Persons with sickle cell disease experience problems associated with severe hemolytic anemia,
chronic hyperbilirubinemia, and vaso-occlusion. Chronic hemolysis produces rather severe anemia,
with hematocrit levels ranging from 18% to 30%.
; Vaso-occlusion accounts for the most severe complications of sickle cell disease. An acute pain
episode results from vessel occlusion and can affect almost any part of the body. Common sites
obstructed by sickled cells include the abdomen, chest, bones, and joints. Multiple areas are
frequently involved simultaneously,
; In contrast to sickle cell anemia, the thalassemias result from absent or defective synthesis of the α
or the β chains of hemoglobin. The β-thalassemias represent a defect in β-chain synthesis, and the α-
thalassemias represent a defect in α-chain synthesis.
; The defect is inherited as a mendelian trait, and a person may be heterozygous for the trait and have
a mild form of the disease or be homozygous and have the severe form of the disease.
Anemias of Deficient Red Cell Production
Anemia may result from the decreased production of erythrocytes by the bone marrow. A deficiency of nutrients for hemoglobin synthesis (iron) or DNA synthesis (cobalamin or folic acid) may reduce red cell production by the bone marrow.
; Iron deficiency is a common worldwide cause of anemia affecting persons of all ages. The anemia
results from dietary deficiency, loss of iron through bleeding, or increased demands. Because iron is
a component of heme, a deficiency leads to decreased hemoglobin synthesis and consequent
impairment of oxygen delivery.
; Iron balance is maintained by the absorption of 0.5 to 1.5 mg daily to replace the 1 mg lost in the
; The usual reason for iron deficiency in adults is chronic blood loss because iron cannot be recycled
to the pool. In men and postmenopausal women, blood loss may occur from gastrointestinal bleeding
because of peptic ulcer, intestinal polyps, hemorrhoids, or cancer. Excessive aspirin intake may
cause undetected gastrointestinal bleeding.
; The manifestations of iron-deficiency anemia are related to lack of hemoglobin and impaired oxygen
transport. Depending on the severity of the anemia, fatigability, palpitations, dyspnea, angina, and
tachycardia may occur.
; The treatment of iron-deficiency anemia is directed toward controlling chronic blood loss, increasing
dietary intake of iron, and administering supplemental iron. Ferrous sulfate, which is the usual oral
replacement therapy, replenishes iron stores in several months. Parenteral iron (iron dextran) therapy
Cobalamin (Vitamin B12)-Deficiency Anemia
; Vitamin B12 is found in all foods of animal origin. Dietary deficiency is rare and usually found only
in strict vegetarians who avoid all dairy products as well as meat and fish. It is absorbed by a unique
process. After release from the animal protein, vitamin B12 is bound to intrinsic factor, a protein
secreted by the gastric parietal cells
; An important cause of vitamin B12 deficiency is pernicious anemia, resulting from a hereditary
; Other causes of vitamin B12 deficiency anemia include gastrectomy, ileal resection, &
malabsorption syndromes in which vitamin B12 and other vitamin B compounds are poorly
; Aplastic anemia (i.e., bone marrow depression) describes a primary condition of bone marrow stem
cells that results in a reduction of all three hematopoietic cell lines—red blood cells, white blood
cells, and platelets—with fatty replacement of bone marrow. Pure red cell aplasia, in which only the
red cells are affected, rarely occurs.
; Anemia results from the failure of the marrow to replace senescent red cells that are destroyed and
leave the circulation, although the cells that remain are of normal size and color. At the same time,
because the leukocytes, particularly the neutrophils, and the thrombocytes have a short life span, a
deficiency of these cells usually is apparent before the anemia becomes severe.
; Among the causes of aplastic anemia are exposure to high doses of radiation, chemicals, and toxins
that suppress hematopoiesis directly, or through immune mechanisms. Chemotherapy and irradiation
commonly result in bone marrow depression.
Chronic Disease Anemias
; Anemia often occurs as a complication of chronic infections, inflammation, and cancer. Chronic
diseases commonly associated with anemia include AIDS, osteomyelitis, rheumatoid arthritis, and
Hodgkin’s disease. It is theorized that the short life span, deficient red cell production, and low
serum iron are caused by actions of macrophages and lymphocytes in response to cell injury. ; Chronic renal failure almost always results in a normocytic, normochromic anemia, primarily
because of a deficiency of erythropoietin. Uremic toxins also interfere with the actions of
erythropoietin and red cell production.
; They also cause hemolysis and bleeding tendencies, which contribute to the anemia. Until recently,
dialysis and red cell transfusions constituted the only therapy.
; Polycythemia is an abnormally high total red blood cell mass with a hematocrit greater than 54% in
males and 51% in females. It is categorized as relative, primary, or secondary. In relative
polycythemia, the hematocrit rises because of a loss of plasma volume without a corresponding
decrease in red cells.
; This may occur with water deprivation, excess use of diuretics, or gastrointestinal losses. Relative
polycythemia is corrected by increasing the vascular fluid volume.
In polycythemia vera, the manifestations are related to an increase in the red cell count, hemoglobin ;
level, and hematocrite with increased blood volume and viscosity. Commonly reported symptoms
include headache, dizziness, and some difficulty with hearing and vision because of decreased
cerebral blood flow. Hypertension is common, the result of an increase in blood viscosity. ; The goal of treatment in primary polycythemia is to reduce blood viscosity. This can be done by
. withdrawing blood by means of periodic phlebotomy to reduce red cell volume