CHAPTER 32
Blood as a Circulatory Fluid & the Dynamics of Blood & Lymph Flow 525back to hemoglobin. Congenital absence of this system is one
cause of hereditary methemoglobinemia.
Carbon monoxide reacts with hemoglobin to form
car-
bon monoxyhemoglobin (carboxyhemoglobin).
The affin-
ity of hemoglobin for O
2
is much lower than its affinity for
carbon monoxide, which consequently displaces O
2
on
hemoglobin, reducing the oxygen-carrying capacity of blood
(see Chapter 36).
HEMOGLOBIN IN THE FETUS
The blood of the human fetus normally contains
fetal hemo-
globin (hemoglobin F).
Its structure is similar to that of he-
moglobin A except that the
β
chains are replaced by
γ
chains;
that is, hemoglobin F is
α
2
γ
2. The
γ
chains also contain 146
amino acid residues but have 37 that differ from those in the
β
chain. Fetal hemoglobin is normally replaced by adult hemo-
globin soon after birth (Figure 32–8). In certain individuals, it
fails to disappear and persists throughout life. In the body, its
O
2
content at a given P
O 2
is greater than that of adult hemo-
globin because it binds 2,3-BPG less avidly. Hemoglobin F is
critical to facilitate movement of O
2
from the maternal to the
fetal circulation, particularly at later stages of gestation
where oxygen demand increases (see Chapter 34). In young
embryos there are, in addition,
ζ
and
ε
chains, forming Gower 1
FIGURE 32–4
Human red blood cells and fibrin fibrils.
Blood
was placed on a polyvinyl chloride surface, fixed, and photographed
with a scanning electron microscope. Reduced from
×
2590.
(Courtesy
of NF Rodman.)
TABLE 32–2
Characteristics of human red cells.
a
Male Female
Hematocrit (Hct) (%) 47 42
Red blood cells (RBC)
(10
6
/
μ
L)5.4 4.8Hemoglobin (Hb) (g/dL) 16 14
Mean corpuscular volume
(MCV) (fL) =Hct
×
10
RBC (10
6
/
μ
L)87 87Mean corpuscular
hemoglobin (MCH) (pg) =Hb
×
10
RBC (10
6
/
μ
L)29 29Mean corpuscular
hemoglobin concentration
(MCHC) (g/dL)=
Hb
×
100
Hct34 34Mean cell diameter
(MCD) (
μ
m)= Mean diameter
of 500 cells in
smear7.5 7.5a
Cells with MCVs > 95 fL are called macrocytes; cells with MCVs < 80 fL are called
microcytes; cells with MCHs < 25 g/dL are called hypochromic.
CLINICAL BOX 32–1
Red Cell Fragility
Red blood cells, like other cells, shrink in solutions with an
osmotic pressure greater than that of normal plasma. In so-
lutions with a lower osmotic pressure they swell, become
spherical rather than disk-shaped, and eventually lose their
hemoglobin
(hemolysis).
The hemoglobin of hemolyzed
red cells dissolves in the plasma, coloring it red. A 0.9% so-
dium chloride solution is isotonic with plasma. When
os-
motic fragility
is normal, red cells begin to hemolyze when
suspended in 0.5% saline; 50% lysis occurs in 0.40–0.42%
saline, and lysis is complete in 0.35% saline. In
hereditary
spherocytosis
(congenital hemolytic icterus), the cells are
spherocytic in normal plasma and hemolyze more readily
than normal cells in hypotonic sodium chloride solutions.
Abnormal spherocytes are also trapped and destroyed in
the spleen, meaning that hereditary spherocytosis is one of
the most common causes of
hereditary hemolytic ane-
mia.
The spherocytosis is caused by mutations in proteins
that make up the membrane skeleton of the erythrocyte,
which normally maintain the shape and flexibility of the red
cell membrane, including
spectrin,
the transmembrane
protein band 3, and the linker protein,
ankyrin. The condi-
tion can be cured by splenectomy, but this is not without
other risks. Red cells can also be lysed by drugs and infec-
tions. The susceptibility of red cells to hemolysis by these
agents is increased by deficiency of the enzyme glucose 6-
phosphate dehydrogenase (G6PD), which catalyzes the ini-
tial step in the oxidation of glucose via the hexose mono-
phosphate pathway (see Chapter 1).
This pathway gener-
ates dihydronicotinamide adenine dinucleotide phosphate
(NADPH), which is needed for the maintenance of normal
red cell fragility. Severe G6PD deficiency also inhibits the
killing of bacteria by granulocytes and predisposes to se-
vere infections.