Cerebrospinal, Pleural and Ascitic Fluids
This chapter looks at various important biological fluids and how their biochemical analysis can be useful clinically.
CEREBROSPINAL FLUID
In adults, the total volume of cerebrospinal fluid (CSF) is about 135 mL, produced at a rate of 500 mL/day. This is predominantly formed by plasma ultrafiltration through the capillary walls of the choroid plexuses in the brain’s lateral ventricles. These plexuses also actively secrete small amounts of substances such as chloride.
The fluid passes from the lateral, through the third and fourth ventricles, into the subarachnoid space between the pia and subarachnoid mater, from where much is reabsorbed into the circulation by arachnoid villi. The remaining fluid flows through the subarachnoid space, completely surrounding the brain and spinal cord; thus it supports and protects these structures against injury. Like lymph, CSF removes waste products of metabolism.
Cerebrospinal fluid circulates very slowly, allowing contact with cells of the central nervous system (CNS). The uptake of glucose by these cells probably results in lower concentrations relative to plasma. Concentrations of analytes in the CSF should always be compared with those in plasma because alterations in the latter are reflected in the CSF even when CNS metabolism is normal.
Flow is slowest, and therefore contact longest, in the lower lumbar region, where the subarachnoid space comes to an end; therefore, the composition of CSF from lumbar puncture is different from that of cisternal or ventricular puncture.
Examination of the cerebrospinal fluid
Although biochemical investigation of the CSF is important, so is microbiological and cytological examination. Textbooks of microbiology and cytology should be consulted for further diagnostic details if required.
CASE 1
A 17-year-old female student was admitted to hospital with fever, neck stiffness, headache, photophobia and a purpuric rash. She had the following cerebrospinal fluid (CSF) laboratory results:
CSF glucose 2.0 mmol/L (concomitant plasma glucose 5.6 mmol/L)
CSF protein 0.98 g/L(< 0.4 g/L)
Cerebrospinal fluid microscopy showed elevated leucocytes, and Gram staining showed gram-negative Meningococcus.
DISCUSSION
A lumbar puncture to obtain CSF is potentially a dangerous, invasive investigation. It carries the risk of cerebral herniation, bleeding and infection. In this case, meningitis was suspected, which was confirmed by the CSF results. Note the raised protein and low glucose concentrations relative to plasma due to bacteria. The presence of bacteria is confirmed by microscopy. Meningococcus can rapidly cause death, and is associated with massive haemorrhagic adrenal destruction, as in Waterhouse-Friderichsen syndrome.
Sample collection
Cerebrospinal fluid is usually collected by lumbar puncture. This procedure may be dangerous if the intracranial pressure is raised (potentially lethal brainstem herniation through the foramen magnum may occur), and the clinician should therefore check that there is no papilloedema before proceeding; sometimes brain imaging, for example computerized tomography (CT) scanning, may be indicated. Small-bore needles may reduce the risk of post-lumbar puncture headache.
Usually a total of about 5 mL of CSF should be collected as 1-2 mL aliquots into sterile containers and sent first for microbiological examinations; if
necessary, any remaining specimen can then be used for biochemical analysis. If a CSF glucose concentration is indicated, 0.5 mL should be collected into a fluoride tube and promptly sent to the laboratory with a blood sample taken at the same time. The CSF is potentially highly infectious and must be handled and transported with care.
necessary, any remaining specimen can then be used for biochemical analysis. If a CSF glucose concentration is indicated, 0.5 mL should be collected into a fluoride tube and promptly sent to the laboratory with a blood sample taken at the same time. The CSF is potentially highly infectious and must be handled and transported with care.
Appearance
Normal CSF is completely clear and colourless; slight turbidity is most easily detected by visual comparison with water.
Spontaneous clotting
Clotting occurs when there is excess fibrinogen in the specimen, usually associated with a very high protein concentration. This finding occurs with tuberculous meningitis or with tumours of the CNS.
Colour
A bright red colour may result from damage to a blood vessel during lumbar puncture (traumatic tap) or a recent haemorrhage into the subarachnoid space.
If CSF is collected as three separate aliquots, blood staining will be progressively less in the aliquots if bleeding is due to the lumbar puncture itself, whereas all aliquots would be expected to be bloody if there was a subarachnoid bleed.
Xanthochromia is defined as a yellow coloration of the CSF and results from altered haemoglobin, the colour appearing several days after a subarachnoid haemorrhage and, depending on the extent of the bleeding, lasting for up to a week or more or jaundice (which will be clinically obvious and may impart a yellow colour to the CSF).
Visual appraisal of CSF is not sufficiently sensitive to detect subtle degrees of xanthochromia for the diagnosis of subarachnoid haemorrhage. In such cases spectrophotometric examination of CSF is important. Spectrophotometric analysis may reveal an oxyhaemoglobin absorption peak of 413-415 nm; bilirubin shows an additional peak at 450-460 nm. This test is particularly useful in patients with subarachnoid haemorrhage who have a negative brain CT scan. The presence of methaemoglobin or bilirubin is strongly suggestive of a subarachnoid haemorrhage, as oxyhaemoglobin alone is not necessarily confirmatory because it may simply reflect a ‘bloody’ CSF tap. The test should be done at least 12 h after initiation of headache. CSF bilirubin can, however, also be raised when serum bilirubin is elevated.
Turbidity
Turbidity is usually due to infection or high CSF protein content. It may also occur after haemorrhage.
Biochemical estimations
The following are the most commonly requested CSF biochemical tests.
Glucose
The CSF glucose concentration is slightly lower than that in plasma and, under normal circumstances, is rarely less than 50 per cent of the plasma concentration. Provided that CSF for glucose assay has been preserved with fluoride, an abnormally low glucose concentration occurs in the following:
Hypoglycaemia The CSF glucose concentration parallels that of plasma, although there is a delay before changes in plasma glucose concentrations are reflected in the CSF. Hypoglycaemia may cause coma and low CSF glucose concentrations in the absence of any primary cerebral abnormality (see Chapter 12). Both plasma and CSF concentrations must be measured.
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