cerebrospinal fluid physiology and effects

Physiology of CSF

1. Cerebrospinal fluid physiology Dr. VARUN.S 1 st YEAR PG

2. Introduction CSF is found in the cerebral ventricles and cisterns and in the subarachnoid space surrounding the brain and spinal cord. Most of the CSF is formed by the choroid plexuses of the lateral ventricles. Smaller amounts are formed directly by the ventricles’ ependymal cell linings, and yet smaller quantities are formed from fluid leaking into the perivascular spaces surrounding cerebral vessels

3. Normal levels In adults, normal total CSF production is about 21 mL/h (500 mL/d), yet total CSF volume is only about 150 mL CSF is renewed about four times every 24 hours. Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases

4. Functions of CSF Support - The CSF supports the weight of the  b rain . T he entire brain density is cushioned, protecting it from crushing into the bony cranium. Shock absorber – It protects the brain from damage during head trauma. Maintains stable intrinsic CNS temperature Biochemical constituents and electrolytes maintain the osmotic pressure responsible for normal CSF pressure which is essential to maintaining normal cerebral perfusion Biochemical waste products diffuse into the CSF which drains into  lymphat ic  circulation. The CSF contains glucose, proteins, lipids, and electrolytes, providing essential CNS nutrition. T he CSF contains immunoglobulins and mononuclear cells.

5. CSF secretion - Choroidal Sixty to seventy-five percent of CSF is produced by the choroid plexuses of the lateral ventricles and the tela choroidea of the third and fourth ventricles. The choroidal secretion of CSF involves two processes The first step consists of passive filtration of plasma from choroidal capillaries to the choroidal interstitial compartment according to a pressure gradient. The second step consists of active transport from the interstitial compartment to the ventricular lumen across the choroidal epithelium, involving carbonic anhydrase and membrane ion carrier proteins.

6. Cytoplasmic carbonic anhydrase catalyses the formation of H+ and HCO3 ions from water and CO2. The carrier proteins of basolateral membranes of choroidal cells exchange H+ and HCO3− ions for Na+ and Cl− ions. ATP-dependent ion pumps of the apical membrane expel Na+, Cl−, HCO3 − and K+ ions towards the ventricular lumen. Water transport, facilitated by aquaporins I of the apical membrane, follows the osmotic gradients generated by these pumps. The NaK2Cl cotransporter of the apical membrane generates ion transport in both directions and participates in regulation of CSF secretion and composition

7. Extra choroidal Extrachoroidal secretion is derived from extracellular fluid and cerebral capillaries across the blood-brain barrier. This pathway appears to play a minimal role under physiological conditions. CSF can also be derived from the ependymal epithelium

8. Cerebral blood flow Cerebral blood flow (CBF) varies with metabolic activity. Total CBF in adults averages 750 mL/min (1520% of cardiac output). Flow rates below 20 to 25 mL/100 g/min are usually associated with cerebral impairment CBF rates below 20 mL/100 g/min typically produce a flat (isoelectric) EEG Rates below 10 mL/100 g/min are usually associated with irreversible brain damage.

9. Methods to measure Direct methods Positron emission tomography xenon washout computed tomography perfusion scans

10. Indirect methods Transcranial Doppler An ultrasound probe is placed in the temporal area above the zygomatic arch, which allows insonation of the middle cerebral artery. Normal velocity in the middle cerebral artery is approximately 55 cm/s. Velocities greater than 120 cm/s can indicate cerebral artery vasospasm following subarachnoid hemorrhage or hyperemic blood flow. Near-infrared spectroscopy

11. Brain tissue oximetry It measures the oxygen tension in brain tissue through the placement of a bolt with a Clark electrode oxygen sensor Normal brain tissue oxygen tension varies from 20 to 50 mm Hg. Brain tissue oxygen tensions less than 20 mm Hg warrant interventions values less than 10 mm Hg are indicative of brain ischemia.

12. CSF anomalies

13. Chiari malformation Congenital condition in which there is an abnormality in the development of the back of the brain and skull. This results in movement or displacement of the back part of the brain, the cerebellum and / or the brainstem from the skull into the spinal space in the neck. It can lead to obstruction to normal flow of cerebrospinal fluid (CSF) It results in headaches, and development of other neurosurgical conditions, such as hydrocephalus and syringomyelia .

14. Hydrocephalus The most significant disorder of the CSF flow is hydrocephalus. Hydrocephalus is caused by excessive amounts of CSF It is either caused by increased production ( hypersecretory hydrocephalus ), an obstruction of its flow ( non-communicating or obstructive hydrocephalus) , or by impaired absorption through the arachnoid villi ( malabsorptive hydrocephalus ).

15. Syringomyelia Syringomyelia i s a fluid-filled cavity within the spinal cord. It is a disabling condition that causes progressive weakness and numbness in the arms and legs as the spinal cord cavity enlarges.

16. Subarachnoid Hemorrhage Subarachnoid Hemorrhage (SAH) is the leakage of blood into the subarachnoid space where it mixes with the CSF. SAH is most commonly caused by trauma . Nontraumatic SAHs being caused by aneurysm rupture, arteriovenous malformations and vasculitis.

17. Regulation of cerebral blood flow

18. Cerebral perfusion pressure Cerebral perfusion pressure (CPP) is the difference between MAP and intracranial pressure (ICP) (or central venous pressure [CVP], if it is greater than ICP). MAP – ICP (or CVP) = CPP. CPP is normally 80 to 100 mm Hg. Patients with CPP values less than 50 mm Hg often show slowing on the EEG, whereas those with a CPP between 25 and 40 mm Hg typically have a flat EEG. Sustained perfusion pressures less than 25 mm Hg may result in irreversible brain damage.

19. Autoregulation the brain normally tolerates a wide range of blood pressure with little change in blood flow. The cerebral vasculature rapidly (10–60 s) adapts to changes in CPP. Decreases in CPP result in cerebral vasodilation, whereas elevations induce vasoconstriction. In normal individuals, CBF remains nearly constant between MAPs of about 60 and 160 mm Hg. the lower limit of this autoregulation may be increased in some patients.

20. Pressures above 150 to 160 mm Hg can disrupt the blood–brain barrier and may result in cerebral edema and hemorrhage. The cerebral autoregulation curve is shifted to the right in patients with chronic arterial hypertension. Both upper and lower limits are shifted. Studies suggest that long-term antihypertensive therapy can restore cerebral autoregulation limits toward normal.

21. Respiratory gas tensions The most important extrinsic influences on CBF are respiratory gas tensions—particularly PaCO2. CBF is directly proportionate to PaCO2 between tensions of 20 and 80 mm Hg Blood flow changes approximately 1 to 2 mL/100 g/min per millimeter of mercury change in PaCO2. Only marked changes in PaO2 alter CBF. hyperoxia may be associated with only minimal decreases (–10%) in CBF severe hypoxemia (PaO2 <50 mm Hg) greatly increases CBF

22. Temperature CBF changes 5% to 7% per 1°C change in temperature. Hypothermia decreases both CMR and CBF whereas hyperthermia has the reverse effect

23. Viscocity A decrease in hematocrit decreases viscosity and can improve CBF a reduction in hematocrit also decreases oxygen-carrying capacity and thus can potentially impair oxygen delivery. Elevated hematocrit, as is seen with marked polycythemia, increases blood viscosity and can reduce CBF.

24. Intracranial pressure The cranial vault is a rigid structure with a fixed total volume, containing brain (80%), blood (12%), and CSF (8%). Any increase in one component must be offset by an equivalent decrease in another to prevent a rise in ICP. ICP means supratentorial CSF pressure measured in the lateral ventricles or over the cerebral cortex It is normally 10 mm Hg or less.

25. Intracranial elastance is determined by measuring the change in ICP in response to a change in intracranial volume. Normally, small increases in the volume of one component are initially well compensated. A point is eventually reached, however, at which further increases produce precipitous rises in ICP. Major compensatory mechanisms include (1) an initial displacement of CSF from the cranial to the spinal compartment (2) an increase in CSF absorption (3) a decrease in CSF production (4) a decrease in total cerebral blood volume

26. Increased ICP Sustained elevations in ICP can lead to catastrophic herniation of the brain. Herniation may occur at one of four sites (1) the cingulate gyrus under the falx cerebri (2) the uncinate gyrus through the tentorium cerebelli (3) the cerebellar tonsils through the foramen magnum (4) any area beneath a defect in the skull ( transcalvarial ).

27. Effects of anesthetic agents on csf

28. Inhalational agents Volatile anesthetics affect both formation and absorption of CSF. Halothane impedes absorption of CSF, but it only minimally retards formation. Isoflurane , on the other hand, facilitates absorption and is therefore an agent with favorable effects on CSF dynamics.

29. Nitrous oxide The effects of nitrous oxide are influenced by other agents or changes in CO2 tension. when combined with intravenous agents, nitrous oxide has minimal effects on CBF, CMR, and ICP. Adding this agent to a volatile anesthetic, it can increase CBF. When given alone, nitrous oxide causes cerebral vasodilation and can potentially increase ICP.

30. Barbiturates Barbiturates produce dose dependent decreases in CMR and CBF until the EEG becomes isoelectric. Barbiturates facilitate absorption of CSF. The resultant reduction in CSF volume, combined with decreases in CBF and cerebral blood volume, makes barbiturates highly effective in lowering ICP. Their anticonvulsant properties are also advantageous in neurosurgical patients who are at increased risk of seizures.

31. Opioids Opioids generally have minimal effects on CBF, CMR, and ICP Increases in ICP have been reported in some patients with intracranial tumors following the administration of opioids

32. Etomidate Etomidate decreases the CMR, CBF, and ICP in much the same way as barbiturates. Etomidate also decreases production and enhances absorption of CSF Reports of seizure activity following etomidate suggest that the drug is best avoided in patients with a history of epilepsy.

33. Propofol Propofol reduces CBF and CMR, similar to barbiturates and etomidate . Although it has been associated with dystonic and choreiform movements, propofol seems to have significant anticonvulsant activity. Its short elimination half-life makes it a useful and most used induction drug for neuroanesthesia .

34. Benzodiazepines Benzodiazepines lower CBF and CMR, but to a lesser extent than barbiturates, etomidate , or propofol . Benzodiazepines also have useful anticonvulsant properties. Midazolam is the benzodiazepine of choice in neuroanesthesia because of its short half-life.

35. Ketamine Ketamine is the only intravenous anesthetic that dilates the cerebral vasculature and increases CBF (50–60%). Ketamine may also impede the absorption of CSF without affecting formation. Increases in CBF, cerebral blood volume, and CSF volume can potentially increase ICP markedly in patients with decreased intracranial compliance.

36. Other Drugs Intravenous lidocaine decreases CMR, CBF, and ICP, but to a lesser degree than other agents. Dexmedetomidine reduces both CBF and CMR. Vasopressors increase CBF only when mean arterial blood pressure is below 50 to 60 mm Hg or above 150 to 160 mm Hg.

37. References Miller’s anaesthesia edition 9 Morgan and Mikhail’s clinical Anaesthesiology Edition 7 Stoelting’s pharmacology and physiology in a anaesthetic practice Stoelting’s anaesthesia and coexisting diseases Guyton and Hall textbook of medical physiology

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