Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VII. General Characteristics of CSF in Disease
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one white blood cell per 100 red blood cells is subtracted
( Rand et al. , 1990b ). A more accurate formula takes into
account the actual white blood cell and red blood cells
counts of the patient and hence compensates for any significant
alterations in these counts ( Fishman, 1992 ):
WWBC
F
WBCB
RBC
RBC
where W is the white blood cell count of the fluid before
blood was added (i.e., the corrected count), WBC F is the
total white blood cell count in the bloody fluid, WBC B
is the white blood cell count in the peripheral blood per
microliter, and RBC F and RBC B are the numbers of red
blood cells per microliter in the CSF and blood, respectively.
Despite all of these elaborate corrections, our own
experience is that many thousands of red blood cells in
contaminated samples of CSF will frequently be observed
without any accompanying white blood cells, suggesting
that these correction factors may not be valid. This empirical
observation has been made by others ( de Lahunta,
1983 ). This lack of validity has been proven by several
studies ( Novak, 1984 ; Wilson and Stevens, 1977 ). In one
article, blood contamination appeared to have little effect
on white blood cell numbers, and the above correction
formula was considered unreliable. The authors evaluated
91 samples from both normal and diseased animals where
there were numerous red blood cells but no white blood
cells. Some of the red blood cell counts exceeded 15,000
RBC/ μ L, but white blood cells were still absent ( Wilson
and Stevens, 1977 ). In another article, the authors concluded
that the standard computations frequently overcorrect
white blood cell counts in blood contaminated CSF,
and the magnitude of the overcorrection may obscure
disease in some instances—in eight infants with marked
blood contamination but proven bacterial meningitis, correction
computations normalized or overcorrected the
white blood cell counts ( Novak, 1984 ). The mechanism
of this overcorrection was not defined, but it is clear that
the presence of low numbers of neutrophils should not be
immediately discounted when red cells are concurrently
found ( Christopher et al. , 1988 ).
A study of feline CSF ( Rand et al. , 1990a ) also found
that values for CSF total protein, lactate dehydrogenase,
creatine kinase, IgG ratio, and γ -globulin percentage were
affected by blood contamination. The CSF total protein
value of blood-contaminated CSF may be corrected using
the formula for white blood cell correction given previously
but substituting the total protein levels of the bloody
CSF and the serum for the corresponding white blood cell
counts ( Kjeldsberg and Knight, 1993 ). In people, bloody
contamination of CSF with as little as 0.2% serum (equivalent
to about 5000 to 10,000 RBC/ml) elevates the IgG
index ( Fishman, 1992 ).
B
F
VI I. GENERAL CHARACTERISTICS OF
CSF IN DISEASE
A . Physical Characteristics: Clarity, Color,
and Viscosity
Normal CSF is clear and colorless, and has the consistency
of water. In pathological conditions the clarity, color, or
consistency may change.
1 . Clarity
Cloudy or turbid CSF is usually due to pleocytosis; about 200
WBC/ μ l or 400 RBC/ μ l will produce a visible change. With
these low levels of cellularity, the CSF may appear opalescent
or slightly hazy. Microorganisms, epidural fat, or myelographic
contrast agent may also produce hazy or turbid CSF.
2 . Color
Although the term xanthochromia means yellow color, it has
often been used to describe pink CSF as well. The color of
CSF is most usefully described as (1) pink or orange, (2) yellow,
or (3) brown. These colors correspond to the major pigments
derived from red cells: oxyhemoglobin, bilirubin, and
methemoglobin. Oxyhemoglobin is red in color, but after dilution
in the CSF it appears pink or orange. Oxyhemoglobin is
released from lysed red cells and may be detected in the CSF
supernatant about 2 h after red cells enter the CSF. The level
of oxyhemoglobin reaches its peak about 36 h later and disappears
over the next 4 to 10 days. Bilirubin is yellow in color.
Bilirubin is derived from hemoglobin and is formed by macrophages
and other leptomeningeal cells that degrade the hemoglobin
from lysed red blood cells. Bilirubin is detected about
10 h after red cells enter the CSF, reaches a maximum at about
48 h, and may persist for 2 to 4 weeks. Bilirubin is also the
major pigment responsible for the abnormal color of CSF with
a high protein content. Methemoglobin in CSF is dark yellowbrown.
Methemoglobin is a reduction product of hemoglobin
characteristically found in encapsulated subdural hematomas
and in old, loculated intracerebral hemorrhages ( Fishman,
1992 ; Kjeldsberg and Knight, 1993 ). Occasionally the CSF
may be black tinged CSF in animals with melanin-producing
tumors in the nervous system.
Causes of a CSF color change other than red cell contamination
include icterus resulting from liver disease or
hemolytic disease, markedly increased CSF total protein
level, and drug effects. Both free and conjugated bilirubin
may be present in the CSF, although the amount of bilirubin
in the CSF does not correlate well with the degree of
hyperbilirubinemia. If the CSF protein level is increased, the
color change will be greater because of increased amounts
of the albumin-bound bilirubin. High CSF protein content
alone can impart a yellow color to the CSF ( Fishman, 1992 ;
Kjeldsberg and Knight, 1993 ). The drug rifampin imparts an