section 19.2
Phospholipids and Glycosphingolipids in Clinical Medicine
409
evaluate fetal lung maturity when early delivery is planned.
One such measurement is that of lecithin to sphingomyelin
(L/S) ratio in amniotic fluid. In a normal pregnancy, the L/S
ratio is less than
1
before the 31 st week, rises to about
2
by
the 34th week, to about 4 at the 36th week, and to about
8
at term (39 weeks). The change is due to an increase
in lecithin synthesis rather than a decrease in synthesis
of sphingomyelin. These values vary in normal gestations
and in abnormal pregnancies (due to maternal, fetal, or
placental disorders), the ratio may be elevated or reduced
without regard to gestational age. A low L/S ratio is not
inevitably associated with RDS. While an L/S ratio greater
than 2 is associated with the absence of serious RDS, one
lower than
2
is not uniformly predictive of the develop-
ment of RDS.
Pulmonary surfactant in amniotic fluid can also be mea-
sured by its ability to generate stable foam in the presence
of ethanol. This
foam stability test
(FST), or shake test,
correlates well with the L/S ratio and with fetal lung ma-
turity. In some instances, in the presence of an L/S ratio
of less than 2, the FST has indicated lung maturity (with-
out subsequent respiratory distress). This discrepancy may
be due to the presence of surfactants other than lecithin
that stabilize the neonatal alveoli, namely, phosphatidyl-
glycerol (PG) and phosphatidylinositol (PI). These acidic
phospholipids are synthesized in stepwise fashion during
the last trimester of normal pregnancy.
The test for PG employs thin-layer chromatographic
separation or a slide agglutination test using an antisera
specific for PG. The advantage of PG measurement is that
its value is not altered by the blood, meconium, vaginal se-
cretions, or other contaminants, whereas the L/S is altered
by the same contaminants. However, a disadvantage of
PG determination in the assessment of fetal lung maturity
is its late appearance (after 35 weeks of gestation) dur-
ing pregnancy. Other amniotic fluid tests of lung maturity
include measurement of lamellar bodies, either by mea-
suring optical absorbance at 650 nm or by actual counting
by procedures using standard hematological counters. An
optical density of 0.15 or greater and a lamellar body count
of 30,000-50,000//rL indicate pulmonary maturity. A
fluorescent polarization technique which consists of com-
petitive binding of a fluorescent probe to albumin and sur-
factant is employed in the assessment of fetal lung matu-
rity. The net polarization for the albumin bound probe
yields a high value, whereas a surfactant-bound probe
yields a low value. A value of 55 mg of surfactant or
greater per gram of albumin indicates maturity. In unantic-
ipated premature births, the risk of RDS can be assessed
by measurement of surfactant in gastric aspirates from
the newborn, since the newborn swallows amniotic fluid
in utero.
A number of factors (such as hypoxia and acidosis) de-
press phospholipid synthesis, and administration of glu-
cocorticoids to mothers accelerates the rate of fetal lung
maturation. The fetal lung undergoes an abrupt transition
from a P
0 2
of about 20 mm Hg to a Po
2
of 100 mm Hg.
This change from a hypoxic to a relatively hyperoxic con-
dition may lead to increased production of potentially cy-
totoxic O
2
metabolites such as superoxide radical (
0
2-),
hydrogen peroxide (H
2
O
2
), hydroxyl radical (OH-), sin-
glet oxygen ( '
0 2
), and peroxide radical (ROO). The an-
tioxidant enzyme system consists of superoxide dismu-
tase, glutathione peroxidase, and catalase (see Chapter 14).
In addition to these enzymes, other potential antioxidants
are vitamin E, ascorbate, /1-carotene, and thiol compounds
(e.g., glutathione, cysteine). Infants born immaturely are
particularly susceptible to deficiency of both surfactant
and antioxidant defense. Administration of surfactant and
the antioxidant enzymes using liposome technology has
potential application in the management of RDS. Admin-
istration of surfactant to the lungs of very premature infants
through an endotracheal tube has reduced morbidity and
mortality from RDS.
Catabolism and Storage Disorders of Sphingolipids
There are four groups of glycosphingolipids: cerebro-
sides, sulfatides, globosides, and gangliosides. Cerebro-
sides contain a single sugar residue linked to ceramide,
which is an N-acylsphingosine. Sulfatides contain a sulfate
group attached to sugar residue. Globosides contain two or
more sugar residues and an N-acetylgalactosamine group
linked to ceramide. Gangliosides (G) contain oligosac-
charide chains that contain sialic acid residues. They
are classified based upon the number of sialic acid
(N-acetylneuraminic acid, NANA) residues they contain
and the sequence of sugar residues. GM, Go, GT and
G q
contain gangliosides with one, two, three, and four sialic
acid residues, respectively. The number associated with
M, D, T, and Q signifies the sequence of sugar residues:
1. Represents Gal-NacGal-Gal-Glc-ceramide;
2. Represents NacGal-Gal-Glc-ceramide;
3. Represents Gal-Glc-ceramide. Thus, the structure of
ganglioside Gmi, is:
G a l — N a c G a l — G a l — G lc — C e r a m id e
I
N A N A
( s ia lic a c id )
Sphingolipids are in a continuous state of turnover. They
are catabolized by lysosomal enzymes by stepwise re-
moval of sugar residues beginning at the nonreducing end
