central nervous system physiology dr tony morrissey speciality doctor anaesthetics 25/09/13

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

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Central Nervous SystemPhysiologyDr Tony Morrissey

Speciality Doctor Anaesthetics25/09/13

What will be covered

• CNS– CSF– BBB– Cerebral blood flow– ICP– Brain metabolism

CSF

• Definition• Function• Appearance• Production• Circulation• Absorption• Normal constituents

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

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

CSF – Appearance

• Clear colourless liquid

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

CSF – Production (2)

• Fenestrated capillaries– ultrafiltrate

• Transport– Hydrostatic pressure and bulk flow: H2O– Active transport: Na+, K+, H+

– Facilitated transport: glucose– Passage through junctions and vesicles: protein

CSF – Circulation

• From lateral ventricles to 3rd ventricle:– Foramina of Monro

• From 3rd to 4th ventricles:– Aqueduct of Sylvius

• Leaves 4th 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

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 cmH2O

• Pressure in superior sagittal sinus: 9 cmH2O

CSF – Normal constituentsSubstance Unit CSF Plasma Ratio

CSF/PlasmaNa+ meq/kg H2O 147.0 150.0 .98

K+ meq/kg H2O 2.9 4.6 .62

Cl- meq/kg H2O 113.0 99.0 1.14

HCO3- meq/L 25.1 24.8 1.01

PCO2 mmHg 50.2 39.5 1.28

pH 7.33 7.4

Protein mg/dL 20.0 6000.0 0.003

Glucose mg/dL 64.0 100.0 .64

Blood-Brain Barrier

• Definition• Morphology• Function• Factors affecting rate of transfer

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

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

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

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

Cerebral Blood Flow

• What is it in ml/min, ml/100g/min, as % of CO• Measurement• What factors affect it?• Autoregulation

CBF – Numbers

• 14 % of cardiac output• 700 ml/min• 50 ml/100g brain tissue/min

CBF – Measurement

• Applying the Fick principle– Kety-Schmidt technique• N2O 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

CBF – Factors affecting

• Arterial PCO2

• Arterial PO2

• MAP• Cerebral metabolic rate for oxygen• Drugs

CBF – Arterial PCO2

http://www.trauma.org/archive/neuro/icpcontrol.html

CBF – Arterial PO2

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

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

CBF – coupled to metabolism

• Regional CBF varies with local metabolic rates• Local metabolic factors:– H+

– K+

– Adenosine– Phospholipid metabolites– Glycolytic metabolites– NO

Intracranial Pressure

• Definition• Monro-Kellie doctrine

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

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

Monro-Kellie doctrine

http://www.trauma.org/archive/neuro/icp.html

Brain metabolism

• Cerebral function is totally dependent on oxidative phosphorylation of glucose to provide ATP.

• Uses 20% of resting total body O2 consumption (brain 2 % total body weight)

• Sensitivity to hypoxia:– Lack of storage– High metabolic rate