564 Chapter 16
Thalassemia is any of a family of hemoglobin diseases found
predominantly among people of Mediterranean ancestry. In alpha
thalassemia, there is decreased synthesis of the alpha chains of
hemoglobin, whereas in beta thalassemia the synthesis of the beta
chains is impaired. Beta thalassemia can be caused by over 200 dif-
ferent point mutations in DNA, as well as by rare DNA deletions.
This diversity of mutations produces a wide range of clinical symp-
toms. One of the compensations for thalassemia is increased syn-
thesis of gamma chains, resulting in the retention of large amounts
of hemoglobin F (fetal hemoglobin) into adulthood. However,
patients with b -thalassemia require regular blood transfusions.Muscle Myoglobin
Myoglobin is a red pigment found exclusively in striated mus-
cle cells (chapter 12, section 12.4). In particular, slow-twitch,
aerobically respiring skeletal fibers and cardiac muscle cells
are rich in myoglobin. Myoglobin is similar to hemoglobin,Inherited Defects in Hemoglobin
Structure and Function
A number of hemoglobin diseases are produced by congenital
(inherited) defects in the protein part of hemoglobin. Sickle-cell
anemia, a disease that occurs almost exclusively in people of Afri-
can heritage, is carried in a recessive state by 8% to 11% of the
African American population. This disease occurs when a person
inherits the affected gene from each parent and produces hemoglo-
bin S instead of normal hemoglobin A. Hemoglobin S differs from
hemoglobin A in that one amino acid is substituted for another (a
valine for a glutamic acid) in the beta chains of hemoglobin, due
to a single base change in the DNA of the gene for the beta chains.
Under conditions of low P^ O 2 , when the hemoglobin is
deoxygenated, hemoglobin S polymerizes into long fibers. This
causes the red blood cells to have their characteristic sickle
shape ( fig. 16.36 ). It also reduces their flexibility, which hin-
ders their ability to pass through narrow vessels and thereby
reduces blood flow through organs. The long fibers of hemoglo-
bin S also damage the plasma membrane of red blood cells and
promote hemolysis, which leads to a variety of complications.
Further, the damaged red blood cells can injure the vascular
endothelium and cause additional symptoms of sickle-cell dis-
ease. Sickle-cell anemia is treated with the drug hydroxyurea,
which stimulates the production of hemoglobin gamma chains
instead of beta chains. As a result, the production of red blood
cells containing fetal hemoglobin (hemoglobin F) is favored,
with fewer red blood cells containing hemoglobin S. A patient
who does not respond to hydroxyurea may receive a bone mar-
row transplant if a sibling or other suitable donor is available.
Bone marrow transplantation has significant risks, but offers the
possibility that the person’s sickle-cell disease can be cured.
CLINICAL APPLICATION
Physiological jaundice of the newborn is a yellowing of
the skin, sclera, and mucous membranes that commonly
occurs in newborns at about two to four days of age and
lasts about two weeks. The yellowing is caused by the
pigment bilirubin, produced from heme derived from the
hemoglobin of destroyed red blood cells (chapter 18; see
fig. 18.22). Production of bilirubin is elevated in the new-
born because fetal red blood cells containing hemoglobin F
have shorter life spans than adult red blood cells containing
hemoglobin A, and are rapidly destroyed after birth. Also,
in the fetus, bilirubin passes through the placenta because
it is lipid soluble, but after birth it must be converted into a
water-soluble form known as conjugated bilirubin so that it
can be excreted in the bile. However, it takes time for the
newborn’s liver to produce sufficient amounts of the conju-
gating enzyme. Physiological jaundice of the newborn is not
usually dangerous, but if bilirubin concentrations become
too great, the baby may be placed under special blue lights.
This phototherapy converts the unconjugated bilirubin into
water-soluble derivatives that can be excreted.Figure 16.36 Sickle-cell anemia. ( a ) Normal red blood
cells. ( b ) Sickled red blood cell as seen in the scanning electron
microscope.(a)(b)