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

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770<br />

Chapter | 26 Cerebrospinal Fluid<br />

(Thomson et al. , 1989, 1990 ). Lastly, the CSF <strong>of</strong> animals with<br />

neurological disease is not always abnormal ( Tipold et al. ,<br />

1995 ). Only occasionally does CSF analysis provide a specific<br />

diagnosis ( Kjeldsberg and Knight, 1993 )—for example,<br />

if infectious agents (bacteria or fungi) or neoplastic cells are<br />

observed. In most situations, the chief utility <strong>of</strong> CSF analysis<br />

is to assist in the diagnostic process by excluding the likelihood<br />

<strong>of</strong> certain disease processes being present. As is the case<br />

with all tests <strong>of</strong> relatively low specificity, examination <strong>of</strong> CSF<br />

is most useful when the results are correlated with the history,<br />

clinical findings, imaging studies, and ancillary laboratory<br />

studies. As stated by Fankhauser (1962) , “ It is futile to make<br />

a diagnosis based solely on the CSF findings and particularly<br />

on single alterations <strong>of</strong> it. Only the entire picture <strong>of</strong> all findings<br />

linked with the other clinical symptoms is <strong>of</strong> value in<br />

reaching a diagnosis . ”<br />

II . FUNCTIONS OF CEREBROSPINAL FLUID<br />

Cerebrospinal fluid has four major functions: (1) physical<br />

support <strong>of</strong> neural structures, (2) excretion and “ sink ” action,<br />

(3) intracerebral transport, and (4) control <strong>of</strong> the chemical<br />

environment <strong>of</strong> the central nervous system. Cerebrospinal<br />

fluid provides a “ water jacket ” <strong>of</strong> physical support and buoyancy.<br />

When suspended in CSF, a 1500-gm brain weighs only<br />

about 50 gm. The CSF is also protective because its volume<br />

changes reciprocally with changes in the volume <strong>of</strong> intracranial<br />

contents, particularly blood. Thus, the CSF protects the<br />

brain from changes in arterial and central venous pressure<br />

associated with posture, respiration, and exertion. Acute or<br />

chronic pathological changes in intracranial contents can<br />

also be accommodated, to a point, by changes in the CSF<br />

volume ( Fishman, 1992 ; Milhorat, 1987 ; Rosenberg, 1990 ).<br />

The direct transfer <strong>of</strong> brain metabolites into the CSF provides<br />

excretory function. This capacity is particularly important<br />

because the brain lacks a lymphatic system. The lymphatic<br />

function <strong>of</strong> the CSF is also manifested in the removal <strong>of</strong> large<br />

proteins and cells, such as bacteria or blood cells, by bulk<br />

CSF absorption (see Section II.D). The “ sink ” action <strong>of</strong> the<br />

CSF arises from the restricted access <strong>of</strong> water-soluble substances<br />

to the CSF and the low concentration <strong>of</strong> these solutes<br />

in the CSF. Therefore, solutes entering the brain, as well as<br />

those synthesized by the brain, diffuse freely from the brain<br />

interstitial fluid into the CSF. Removal may then occur by<br />

bulk CSF absorption or, in some cases, by transport across the<br />

choroid plexus into the capillaries ( Davson and Segal, 1996 ;<br />

Fishman, 1992 ; Milhorat, 1987 ; Rosenberg, 1990 ).<br />

Because CSF bathes and irrigates the brain, including<br />

those regions known to participate in endocrine functions,<br />

the suggestion has been made that CSF may serve<br />

as a vehicle for intracerebral transport <strong>of</strong> biologically<br />

active substances. For example, hormone releasing factors,<br />

formed in the hypothalamus and discharged into the<br />

CSF <strong>of</strong> the third ventricle, may be carried in the CSF to<br />

their effective sites in the median eminence. The CSF may<br />

TABLE 26-1 Composition <strong>of</strong> the Brain–Fluid<br />

Interfaces<br />

Interface Cell Type Junction Type<br />

Blood-brain<br />

Blood-CSF<br />

Blood-CSF<br />

CSF-blood<br />

CSF-brain<br />

also be the vehicle for intracerebral transport <strong>of</strong> opiates<br />

and other neuroactive substances ( Davson and Segal, 1996 ;<br />

Fishman, 1992 ; Milhorat, 1987 ; Rosenberg, 1990 ).<br />

An essential function <strong>of</strong> CSF is the provision and maintenance<br />

<strong>of</strong> an appropriate chemical environment for neural<br />

tissue. Anatomically, the interstitial fluid <strong>of</strong> the central nervous<br />

system and the CSF are in continuity (see Section II.A);<br />

therefore, the chemical composition <strong>of</strong> the CSF reflects and<br />

affects the cellular environment. The composition <strong>of</strong> the<br />

CSF (and the interstitial fluid) is controlled by cells forming<br />

the interfaces, or barriers, between the “ body ” and the neural<br />

tissue. These semipermeable interfaces, the blood-brain<br />

barrier, the blood-CSF barrier, and the CSF-brain barrier,<br />

control the production and absorption <strong>of</strong> CSF and provide<br />

a fluid environment that is relatively stable despite changes<br />

in the composition <strong>of</strong> blood ( Davson and Segal, 1996 ;<br />

Fishman, 1992 ; Milhorat, 1987 ; Rosenberg, 1990 ).<br />

III . CSF FORMATION, CIRCULATION, AND<br />

ABSORPTION<br />

The brain (and the spinal cord) as an organ is isolated in<br />

many ways from the body and the systemic circulation. This<br />

isolation is accomplished anatomically by several interfaces<br />

between brain tissue and systemic fluids ( Table 26-1 ). At<br />

these interfaces, selective carriers and ion pumps transport<br />

electrolytes and essential nutrients and thereby control the<br />

brain’s microenvironment. A substantial portion <strong>of</strong> this control<br />

is achieved through the formation, circulation, and absorption<br />

<strong>of</strong> CSF at these brain-fluid interfaces ( Davson and Segal,<br />

1996 ; Fishman, 1992 ; Milhorat, 1987 ; Rosenberg, 1990 ).<br />

A . Anatomy <strong>of</strong> Brain-Fluid Interfaces<br />

1 . Blood-Brain Barrier<br />

Brain capillary<br />

endothelium<br />

Choroid plexus<br />

epithelium<br />

Arachnoid cells<br />

Arachnoid villi<br />

Ependyma<br />

Pia mater<br />

Modifi ed from Rosenberg (1990) .<br />

Tight junction<br />

Apical tight junction<br />

Tight junction<br />

Valve<br />

Gap junction<br />

Gap junction<br />

The important blood-brain (and blood-spinal cord) interface<br />

is formed by the endothelial cells <strong>of</strong> the intraparenchymal<br />

capillaries. In most areas <strong>of</strong> the brain and spinal cord,

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