Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 32

Blood as a Circulatory Fluid & the Dynamics of Blood & Lymph Flow 527

In humans, most of the biliverdin is converted to
bilirubin
(Figure 32–9) and excreted in the bile (see Chapter 29). The
iron from the heme is reused for hemoglobin synthesis.
Exposure of the skin to white light converts bilirubin to
lumirubin, which has a shorter half-life than bilirubin.
Photo-

therapy

(exposure to light) is of value in treating infants with

jaundice due to hemolysis. Iron is essential for hemoglobin

synthesis; if blood is lost from the body and the iron defi-

ciency is not corrected,

iron deficiency anemia

results. The

metabolism of iron is discussed in Chapter 27.

BLOOD TYPES

The membranes of human red cells contain a variety of

blood

group antigens,

which are also called agglutinogens. The

most important and best known of these are the A and B anti-

gens, but there are many more.

THE ABO SYSTEM

The A and B antigens are inherited as mendelian dominants,

and individuals are divided into four major blood types on

this basis. Type A individuals have the A antigen, type B have

the B, type AB have both, and type O have neither. The A and

B antigens are complex oligosaccharides that differ in their

terminal sugar. An H gene codes for a fucose transferase that

adds a terminal fucose, forming the H antigen that is usually

present in individuals of all blood types (Figure 32–10). Indi-

viduals who are type A also express a second transferase that

catalyzes placement of a terminal N-acetylgalactosamine on

the H antigen, whereas individuals who are type B express a

transferase that places a terminal galactose. Individuals who

are type AB have both transferases. Individuals who are type

O have neither, so the H antigen persists.

Antibodies against red cell agglutinogens are called aggluti-

nins. Antigens very similar to A and B are common in intesti-

nal bacteria and possibly in foods to which newborn

individuals are exposed. Therefore, infants rapidly develop

antibodies against the antigens not present in their own cells.

Thus, type A individuals develop anti-B antibodies, type B

individuals develop anti-A antibodies, type O individuals

develop both, and type AB individuals develop neither (Table

32–4). When the plasma of a type A individual is mixed with

type B red cells, the anti-B antibodies cause the type B red

CLINICAL BOX 32–2

Abnormalities of Hemoglobin Production

There are two major types of inherited disorders of hemoglo-

bin in humans: the hemoglobinopathies, in which abnor-

mal globin polypeptide chains are produced, and the thalas-

semias and related disorders, in which the chains are normal

in structure but produced in decreased amounts or absent

because of defects in the regulatory portion of the globin

genes. Mutant genes that cause the production of abnormal

hemoglobins are widespread, and over 1000 abnormal he-

moglobins have been described in humans. In one of the

most common examples, hemoglobin S, the α chains are

normal but the β chains have a single substitution of a valine

residue for one glutamic acid, leading to sickle cell anemia

(Table 32–3). When an abnormal gene inherited from one

parent dictates formation of an abnormal hemoglobin (ie,

when the individual is heterozygous), half the circulating he-

moglobin is abnormal and half is normal. When identical ab-

normal genes are inherited from both parents, the individual

is homozygous and all the hemoglobin is abnormal. It is the-

oretically possible to inherit two different abnormal hemo-

globins, one from the father and one from the mother. Stud-

ies of the inheritance and geographic distribution of

abnormal hemoglobins have made it possible in some cases

to decide where the mutant gene originated and approxi-

mately how long ago the mutation occurred. In general,

harmful mutations tend to die out, but mutant genes that

confer traits with survival value persist and spread in the

population. Many of the abnormal hemoglobins are harm-

less; however, some have abnormal O 2 equilibriums, while

others cause anemia. For example, hemoglobin S polymer-

izes at low O 2 tensions, and this causes the red cells to be-

come sickle-shaped, hemolyze, and form aggregates that

block blood vessels. The sickle cell gene is an example of a

gene that has persisted and spread in the population due to

its beneficial effect when present in heterozygous form. It

originated in Africa, and confers resistance to one type of

malaria. In some parts of Africa, 40% of the population is het-

erozygous for hemoglobin S. There is a corresponding preva-

lence of 10% among African Americans in the United States.

Hemoglobin F decreases the polymerization of deoxygen-

ated hemoglobin S, and hydroxyurea stimulates production

of hemoglobin F in children and adults. It has proved to be a

very valuable agent for the treatment of sickle cell disease. In

patients with severe sickle cell disease, bone marrow trans-

plantation has also been shown to have some benefit.

FIGURE 32–8 Development of human hemoglobin chains.

50

40

30

20

10

0

3 6 Birth 3 6

α chain

δ chain

β chain (adult)

and ζ chains

(embryonic)

γ chain

(fetal)

Gestation (months) Age (months)

∋

Globin chain synthesis (% of total)