12 Cerebrospinal Fluid Dynamics and Pathology

10.1055/b-0038-160242

12 Cerebrospinal Fluid Dynamics and Pathology

Deependra Mahato, Kevin Ray, John D. Cantando, Dan E. Miulli, and Javed Siddiqi

Abstract

The cerebrospinal fluid (CSF) is a vital fluid providing nutrients to brain tissue and removing products of metabolism and disease from the brain. The flow of CSF throughout the brain tissue is likewise as significant as the flow of blood through its vessels. CSF is so important that its rate of production and reabsorption is meticulously controlled. It is constantly made at roughly half a liter per day in the adult and removed at roughly the same rate. When the constituents of CSF, the flow of CSF, or the pressure of CSF is altered significantly there is disease, which can be recognized and treated.

Case Presentation

A 21-year-old woman was struck in the head by falling objects, resulting in a loss of consciousness. Her Glasgow Coma Scale (GCS) score was 7. A computed tomographic (CT) scan revealed a small amount of epidural intracranial air. There were multiple facial fractures, including fractures of the orbit and zygoma. An intraventricular drain and monitor were placed upon admission. During her hospital course the external ventricular drain was raised to 15 mm Hg after 5 days. She remained intubated. She developed fluid leakage from her nostrils.

See end of chapter for Case Management.

12.1 Introduction

Cerebrospinal fluid (CSF) is found within the four ventricles of the brain, the subarachnoid space, and the central canal of the spinal cord. It is also called liquor cerebrospinalis. ¹ CSF circulates a variety of chemicals and nutrients necessary for normal brain function and metabolism; it also acts as a shock absorber, cushioning the brain from both day-to-day activity and traumatic events.

12.2 Cerebrospinal Fluid Identification

Grossly, CSF should be a colorless, odorless, serous fluid. There is an estimated 70 to 160 mL of fluid in the central nervous system at any given time (~ 50% intracranial, 50% spinal). Certain pathological conditions will change both the chemical and the gross appearance of CSF. In the majority of cases, it is simple to ascertain whether fluid is CSF or not by a simple halo test described later in this chapter. If the source was suspicious for CSF then it is more likely. However, at times, especially when contaminated with other fluids, it is necessary to analyze the fluid for its constituents to determine if an unknown fluid is CSF, contains CSF, or is another bodily fluid. ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ ► Table 12.1 compares the composition of CSF with plasma. The following tests can determine if a fluid is CSF:

Glucose analysis: Analysis should be done immediately after collection to prevent fermentation. Nasal/lacrimal fluid or mucosal secretion will have < 5 mg/dL of glucose. A negative test is more reliable because, even with meningitis, the glucose level is usually 5 to 20 mg/dL and associated with other changes. However, there is a 45 to 75% chance of a false-positive ² , ³ , ⁶ , ⁷ , ⁹ , ¹⁰
Beta2-transferrin: This test can be performed only by electrophoresis of at least 0.5 mL of sample. Beta2-transferrin is found only in CSF and vitreous humor. (Note: This test is not reliable in patients with liver disease or in newborns. ¹¹ , ¹² )
Ring sign: Also known as the halo, this sign is particularly useful for blood-tinged samples. A drop of suspected fluid is placed on linen; as the fluid feathers out into the surrounding area, blood and mucus will stay centrally placed, and the CSF (which is less viscous) will continue spreading, creating a clear ring around the central colored area.

**Table 12.1** Chemical constituents of cerebrospinal fluid and plasma ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸
Constituent	Units	CSF	Plasma
Formation	mL/min	0.35	–
Osmolarity	mOsm/L	295	295
H₂O	%	99%	93%
Sodium	mEq/L	138–150	135–145
Potassium	mEq/L	2.2–3.3	4.1–4.5
Chloride	mEq/L	119–130	102–112
Calcium	mEq/L	2.1	4.8
Bicarbonate	mEq/L	22.0–23.3	24.0–26.8
Magnesium	mEq/L	2.3–2.7	1.7–1.9
Phosphorus	mg/dL	1.6	4.0
Ammonia	µg/dL	22–42	37–70
PCO₂	mm Hg	43–47	38–41
pH		7.33–7.35	7.41
PO₂	mm Hg	43	104
Glucose	mg/dL	45–80	90–110
Lactate	mEq/L	0.8–2.8	0.5–1.7
	mg/dL	10–20	6–13
Pyruvate	mEq/L	0.08	0.11
lactate: pyruvate		26	17.6
Glutamine	mg/dL	<20	>23
	µmol/L	552	641
Glutamate	µmol/L	26.1	61.3
GABA	µmol/L	3.5	29.8
Total protein	mg/dL	5–45, 5–15 ventricular,	7,000
		10–25 cisternal,
		15–45 lumbar
Albumin	mg/L	155	36,600
Prealbumin	mg/L	17.3	238
Amino acids	% blood	30	3.6–7.2
	mEq/L	0.72–2.62
IgG	mg/L	5–12	9870
RBCs	/mm³	0	3.6–5.4 M
WBCs	/mm³	<6/mm³; in children, up to 20/mm³	5,000–10,000
Oligoclonal bands		<2	0
GOT	U	7–49	5–40
LDH	U	15–71	200–680
CPK	U	0–3	0–12
BUN	mg/dL	5–25	6–28
Bilirubin	mg/dL	0	0.2–0.9
Iron	µg/dL	1.5	15
Abbreviations: BUN, blood urea nitrogen; CPK, creatine phosphokinase; CSF, cerebrospinal fluid; GABA, γ-aminobutyric acid; GOT, glutamic-oxaloacetic transaminase; IgG, immunoglobulin G; LDH, lactate dehydrogenase; RBC, red blood cell; WBC, white blood cell.

12.3 Chemical Regulators of Cerebrospinal Fluid

Constituents of CSF are affected by secretion and absorption rates of CSF, hormones, and chemicals. The secretion rates and effects of hormones and chemicals on CSF vary from the vascular to the ventricular side of the choroid plexus. ¹³ , ¹⁴ , ¹⁵ These are described in ► Table 12.2.

**Table 12.2** Hormone and chemical secretions in cerebrospinal fluid ¹³ , ¹⁴ , ¹⁵
Vascular side of choroid plexus Nonadrenergic sympathetic innervation (near CP epithelial cells and blood vessels) decreases CSF flow by 30%. Cholinergic input primarily near the third ventricle stimulates CSF production up to 100%. Endothelin binding sites are found in CP of lateral and third ventricles. Endothelin decreases blood flow and subsequently CSF production. Antidiuretic hormone (ADH) regulates norepinephrine, dopamine, and endorphin release within the ventricle. ADH has been shown to indirectly decrease plasma Na⁺. Ventricular side of choroid plexus 5-hydroxytryptamine (5HT) The CP contains 10 times the amount of 5HT receptors relative to other areas of the brain. It is released from the supraependymal nerve fibers into the CSF and interacts with the CP-5HT receptors. 5HT reduces the rate of CSF secretion. Melatonin binding sites are located in the fourth ventricle and stimulate CSF secretion. Carbonic anhydrase High concentrations within the CP increase CSF production by facilitating Na⁺ transport. L-dopa is the most abundant monoamine in the CSF. The CP has D1 receptors but lacks direct dopaminergic innervation. Dopamine effects on the CP are via the CSF, similar to 5HT. Norepinephrine is secreted by noradrenergic periventricular neurons in contact with the ventricles and decreases CSF production. It follows circadian variations similar to systemic circulation. Arginine vasopressin (AVP) is released by vasopressinergic neurons into the CSF, which stimulates CSF production. AVP in the CSF follows circadian variations, whereas plasma levels do not. The CP has V₁ receptors for AVP. AVP has been shown to indirectly lower plasma Na⁺. Arial natriuretic peptide (ANP) reduces CSF production. It is elevated in hydrocephalus cases. Evidence supports ANP involvement in the regulation of water and electrolyte passage across the blood–brain barrier. ANP has a direct negative effect on CSF production as substantiated by increased levels of ANP circulating within the CSF in hydrocephalic patients (both normal and high pressure). Systemically, ANP stimulates renal inhibition of Na⁺ and water absorption, leading to hyponatremia. Within the brain, ANP reduces the net flux of Na⁺ from the circulation by inhibiting the Na⁺/K +/Cl cotransport system that is known to decrease CSF production. ⁸ , ⁹
Abbreviations: CP, choroid plexus; CSF, cerebrospinal fluid.