Cerebrospinal Fluid (CSF)

Dr Arun S

Formation
The cerebrospinal fluid is formed mainly in the choroid plexuses of the lateral, third, and fourth ventricles; some originates from the ependymal cells lining the ventricles and from the brain substance through the perivascular spaces.

Circulation
The circulation begins with its secretion from the choroid plexuses in the ventricles The fluid passes from the lateral ventricles into t third ventricle through the interventricular foramina It then passes into the fourth ventricle through the narrow cerebral aqueduct. The circulation is aided by the arterial pulsations of the choroid plexuses and by the cilia on the ependymal cells lining the ventricles. From the fourth ventricle, the fluid passes slowly through the median aperture and the lateral foramina of the lateral recesses of the fourth ventricle and enters the subarachnoid space

Count.
The fluid then moves through the cerebellomedullary cistern and pontine cisterns and flows superiorly through the tentorial notch of the tentorium cerebelli to reach the inferior surface of the cerebrum Some of the cerebrospinal fluid moves inferiorly in the sub arachnoid space around the spinal cord The cerebrospinal fluid not only bathes the ependymal and pial surfaces of the brain and spinal cord but also penetrates the nervous tissue along the blood vessels

Absorption
The main sites for the absorption of the cerebrospinal flu: are the arachnoid villi that project into the dural venous s nuses, especially the superior sagittal sinus arachnoid villi tend to be grouped together to form e " vations known as arachnoid granulations Structural. each arachnoid villus is a diverticulum of the subarachno: space that pierces the dura mater. The arachnoid divertict lum is capped by a thin cellular layer, which, in turn, is co ered by the endothelium of the venous sinus

CSF pressure
The normal pressure of CSF is 10 mmHg Regulation of CSF by the arachnoidal villi It work as one way valve to allow CSF to flow to the blood venous sinus .while it not allow the blood to flow backward in the opposite direction The villi allow CSF begin to flow into the blood when CSF pressure is 1.5 mmHg or more greater than the pressure in the blood venous sinus .

Some pathological condition

Increase of CSF pressure often caused by large tumor that elevate the CSF pressure by decreasing reabsorption of CSF back into the blood . CSF pressure also rises when hemorrhage or infection . In this case large number of red and white blood cells appear in CSF and They can cause blockage of small absorption channels throw the arachnoidal villi . Some congenital condition may cause high pressure of CSF caused by few number of arachnoidal villi or abnormal proprieties of the villi

Hydrocephalous
accumulation of cerebrospinal fluid (CSF) in the ventricles, or cavities, of the brain . two types : communicating hydrocephalous :  fluid flows from the ventricular system into the subarachnoid space.  In communicating type blockage is in the subarchnoid space by blockage of arachnoidal villi themselves .

Non communicating :  Fluid cant pass to the subarachnoid space  In this type is blockage of the aqueduct of sylvius . Obstruction of villi blockage CSF pressure hydrocephalous may lead to edema .

Function of CSF
Cushion and protect the CNS from trauma. Provides mechanical buoyancy and support for the brain Serves as reservoir and assistant in the regulation of the content of the skull Nourishes the CNS

Count. Function
Remove metabolic wastes from CNS Serves as pathway for pineal secretion to reach the pituitary gland. it protects against acute changes in arterial and venous blood pressure; it is involved in intra-cerebral transport, ex. hypothalamic releasing factors .

Composition of CSF
In addition to the major ions, CSF contains oxygen, sugars (e.g., glucose, fructose, polyols), lactate, proteins (e.g., albumin, globulins), amino acids, urea, ammonia, creatinine, lipids, hormones (e.g., insulin), and vitamins.

Substance Sodium (mEq/L) 140.0

Plasma 144.0

CSF

Potassium (mm/L)

4.6

2.9

Magnesium (mEq/L)

1.6

2.2

Calcium (mg/dL)

8.9

4.6

Chloride (mEq/L)

99.0

113.0

Bicarbonate (mm/L)

26.8

23.3

Inorganic phosphate (mg/dL)

4.7

3.4

Protein (g/dL)

6.8

0.028 (28mg/dL)

Glucose (mg/dL)

110.0

50 to 80

Osmolality

0.3

0.29

pH

7.4

7.3

PCO2 (mmHg)

41.1

50.5

Glucose
- the CSF glucose concentration is normally 60% of the plasma glucose concentration, and under nonpathological conditions, this ratio changes falling . proportionately in response to a rising or plasma glucose -This linear ratio of CSF to plasma glucose concentration decreases as the plasma glucose exceeds 500mg/dL. -- The reason for this decrease is unclear, but it may reflect the saturation of the carrier-mediated transport of glucose at high plasma concentrations. -- Although an elevated CSF glucose level (hyperglycorrachia) results from an elevated plasma glucose level, a decreased CSF glucose concentration (hypoglycorrachia) may be due to a variety of causes including hypoglycemia.

-The CSF glucose value often returns to normal before other CSF determinations (such as protein or lactate). -The CSF glucose level may take several weeks to return to normal despite the normalization of the protein concentration and cell count. - A CSF hypoglycorrhachia is seen in a number of CNS infections. The pathogenesis of CSF hypoglycorrhachia is multifactorial and may include an increased rate of macrovesicular glucose transport across arachnoid villi, increased glycolysis by leukocytes and bacteria, increased metabolic rate of the brain and spinal cord, and/or inhibition of glucose entry into the subarachnoid space caused by alterations in the membrane carrier system responsible for glucose transfer from blood to CSF.[

cont

Cont
actual CSF glucose concentration may be falsely low in the presence of hypoglycemia or may be incorrectly interpreted as normal when the patient is hyperglycemic (e.g., in diabetic patients). Therefore, the CSF glucose should always be compared with a simultaneous serum glucose that is drawn prior to lumbar puncture; the normal CSF:serum glucose ratio is approximately 0.6, and ratios less than 0.5 should be considered abnormal.
- The

Protein
-The majority of CSF protein is derived from the serum, and the CSF/serum albumin ratio is approximately 1:200. This ratio implies that the entry rate of protein from the serum to the CSF is approximately 200 times less than its exit rate. -The CSF protein concentration varies at different levels of the neuroaxis and generally increases from the cephalad to caudal levels. Elevation in lumbar CSF protein is a nonspecific but sensitive indicator of CNS disease. - The presence of 1000 RBCs in the CSF results in the increase of protein by 1mg/dL.

Cont
-A spinal-subarachnoid block can cause Froin's syndrome and is usually the result of a spinal cord tumor and can cause very significant elevations in CSF protein (greater than 1000mg/dL). -Protein concentrations of 100mg/dL or greater have sensitivity and specificity for bacterial meningitis of 82% and 98%, respectively, as compared with aseptic meningitis, and if the concentration is 200mg/dL, the sensitivity is 86% and the specificity is 100%. - A lower than normal CSF protein level may occur in young children (6 months to 2 years of age), in patients with pseudotumor cerebri, and in patients with unintended loss of CSF from frequent LPs, a lumbar drain, or a lumbar dural CSF leak.

Cont
- Certain proteins arise within the intrathecal compartment. Among these are immunoglobulins produced by CNS lymphocytes, transthyretin (produced by choroid plexus), and various structural proteins found in brain tissue (including glial fibrillary acidic, and myelin basic proteins). The last group of proteins and transthyretin are found only in trace amounts, whereas immunoglobulins compose a substantial. - The CSF protein concentration is also elevated in a number of CNS infections, presumably due to disruption of the blood-brain barrier, manifested morphologically by separation of intercellular tight junctions and increased numbers of pinocytotic vesicles in microvascular endothelial cells.

Normal and Pathological Findings - The general appearance of CSF is clear and colorless, because it is
more than 99% water. Color of CSF is observed only in pathological circumstances. - A yellowish tinge can be found with any cause of a markedly increased protein (greater than 200mg per 100mL). xanthochromic (yellow) - If there is no liver failure (jaundice can cause CSF to be yellow), xanthochromic CSF suggests that a subarachnoid hemorrhage has recently occurred [within days). The yellow color is due to bilirubin generated in the CNS by the breakdown of hemoglobin released from ABC's.

Cont
- Other causes for coloration of CSF include an elevated systemic bilirubin from liver disease; a brownish or gray coloration in the presence of CNS melanoma; and a greenish tinge related to leukemic meningeal infiltration.

- turbid - This indicates the presence of white cells and is suggestive of a CNS infection.

Specialized Tests
CSF lactate
Because the concentration of CSF lactate is dependent on CNS glycolysis,the measurement of this agent may be helpful in the diagnosis of bacterial meningitis. This concentration of lactate increases proportionally to the number of inflammatory cells in the CSF. A lactate concentration of 4.2mmol/L accurately predicted 24 out of 25 cases of bacterial meningitis. Increased lactate may also result from a cerebral hemorrhage, malignant hypertension, hepatic encephalopathy, diabetes mellitus, and hypoglycemic coma.

Cont
CSF glutamine :
The measurement of CSF glutamine can be a helpful test in diagnosing patients with confusion in the setting of hepatic encephalopathy.

This process helps protect the CNS from the effects of ammonia. Normally, the CSF concentration of ammonia is less than one half of arterial levels, but may increase dramatically in patients with hepatic failure.

cont
Various biogenic amines:
Various biogenic amines (and their metabolites) may be measured within the CSF, including dopamine (homovanillic acid [HVA]), serotonin (5-hydroxyindoleacetic acid [5-HIAA]), and norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]). Significant ventricular to lumbar gradients exist for HVA and 5-HIAA, although MHPG levels are nearly equivalent. Decreased lumbar CSF levels of HVA and 5-HIAA have been reported in patients with parkinsonism and Alzheimer's disease. Whereas decreased HVA levels have also been documented in the ventricular CSF of patients with dystonia.

Cont
enzymes in the CSF :

An elevated lactate dehydrogenase (LDH) may occur in bacterial meningitis. whereas adenosine deaminase (ADA) elevations can occur in tuberculous meningitis.

Summary Production , circulation and absorption of CSF

Pressure of CSF Pathological condition ( hydrocephalus ) Function of CSF Composition of CSF