1. Central Nervous System Physiology Dr Tony Morrissey Speciality Doctor Anaesthetics 25/09/13

2. What will be covered CNS – CSF – BBB – Cerebral blood flow – ICP – Brain metabolism

3. CSF Definition Function Appearance Production Circulation Absorption Normal constituents

4. CSF – Definition The CSF is a specialized extracellular fluid in the ventricles and the subarachnoid space. – Power and Kam, Principles of physiology for the anaesthetist

5. CSF – Function Mechanical protection by buoyancy – Effective weight reduced from 1400 g to 47 g Maintenance of constant ionic environment Acid-base regulation – Esp. via control of respiration Nutritional

6. CSF – Appearance Clear colourless liquid

7. CSF – Production (1) Formed: – 70% in choroid plexus – 30% around blood vessels and ventricular walls Volume of CSF: 150 ml Rate of formation – 550 ml/day – 0.4 ml/min – Turnover 4 times per day

8. CSF – Production (2) Fenestrated capillaries – ultrafiltrate Transport – Hydrostatic pressure and bulk flow: H 2 O – Active transport: Na +, K +, H + – Facilitated transport: glucose – Passage through junctions and vesicles: protein

9. CSF – Circulation From lateral ventricles to 3 rd ventricle: – Foramina of Monro From 3 rd to 4 th ventricles: – Aqueduct of Sylvius Leaves 4 th ventricle to cisterna magna: – Foreman of Magendie – Foramen of Luschka From cisterna magna – Superiorly: subarachnoid space around cerebellum – Caudally: spinal subarachnoid space – Cephalad to basilar cisterns

10. CSF – Absorption Absorbed into venous blood Arachnoid villi: – Dural walls of sagittal and sigmoid sinuses (85-90 %) – Dural walls of dural sinusoids on dorsal nerve roots (10-15 %) Mean CSF pressure: 15 cmH 2 O Pressure in superior sagittal sinus: 9 cmH 2 O

11. CSF – Normal constituents SubstanceUnitCSFPlasmaRatio CSF/Plasma Na + meq/kg H 2 O147.0150.0.98 K+K+ meq/kg H 2 O2.94.6.62 Cl - meq/kg H 2 O113.099.01.14 HCO 3 - meq/L25.124.81.01 PCO 2 mmHg50.239.51.28 pH7.337.4 Proteinmg/dL20.06000.00.003 Glucosemg/dL64.0100.0.64

12. Blood-Brain Barrier Definition Morphology Function Factors affecting rate of transfer

13. BBB – Definition A physiological boundary between the bloodstream and central nervous system, preventing transfer of substances from plasma to brain. – Yentis et al, Anaesthesia and Intensive Care A-Z

14. BBB – Morphology Capillary endothelial cells have: – Tight junctions between adjacent cells – Absence of fenestrations – High content of mitochondria Perivascular area of closely applied foot processes of astrocytes

15. BBB – Function Provides favourable environment for nervous tissue function – Protects brain from potentially toxic substances – Allows free access of metabolic substrates Prevention of escape of NT into general circulation

16. BBB – Factors affecting rate of transfer Ion channels Facilitated diffusion Active transport Pinocytosis Factors influencing rate of diffusion: – Molecular size – Concentration gradient – Ionization – Lipid solubility – Protein binding

17. Cerebral Blood Flow What is it in ml/min, ml/100g/min, as % of CO Measurement What factors affect it? Autoregulation

18. CBF – Numbers 14 % of cardiac output 700 ml/min 50 ml/100g brain tissue/min

19. CBF – Measurement Applying the Fick principle – Kety-Schmidt technique N 2 O 10% breathed for 10-15 min Jugular venous concentration assumed to be same as brain concentration Detection of radioactive decay Regional flow measured by Doppler

20. CBF – Factors affecting Arterial PCO 2 Arterial PO 2 MAP Cerebral metabolic rate for oxygen Drugs

21. CBF – Arterial PCO 2 http://www.trauma.org/archive/neuro/icpcontrol.html

22. CBF – Arterial PO 2

23. CBF – Autoregulation The phenomenon where CBF is kept constant over a MAP range of 50-150 mmHg. Power and Kam, Principles of physiology for the anaesthetist Thought to be through myogenic response in vascular smooth muscle. – As pressure rises smooth muscle constricts Causing reduced flow – As pressure fall smooth muscle relaxes Causing increased flow

24. http://www.neuroicu.info/brainspinalcordbloodflow.htm

25. CBF – coupled to metabolism Regional CBF varies with local metabolic rates Local metabolic factors: – H + – K + – Adenosine – Phospholipid metabolites – Glycolytic metabolites – NO

26. Intracranial Pressure Definition Monro-Kellie doctrine

27. ICP – Definition Pressure exerted by the CSF in the frontal horns of the lateral ventricles of the brain. Yentis et al, Anaesthesia and Intensive Care A-Z Normally 7-17 mmHg supine. CPP=MAP – ICP

28. Monro-Kellie doctrine Skull is a rigid closed container. Its contents is incompressible. Contents made up of: – Blood 50-70 ml (5-7 %) – CSF 50-120 ml (5-12 %) – Brain 1.4 kg (80-85 %) ICP depends on volume of intracranial contents

29. Monro-Kellie doctrine http://www.trauma.org/archive/neuro/icp.html

30. Brain metabolism Cerebral function is totally dependent on oxidative phosphorylation of glucose to provide ATP. Uses 20% of resting total body O 2 consumption (brain 2 % total body weight) Sensitivity to hypoxia: – Lack of storage – High metabolic rate