Cerebral physiology & monitoring By Dr. Ahmed Mostafa Assist. Prof. of anesthesia and I.C.U.

Cerebral physiology

& monitoringBy

Dr. Ahmed MostafaAssist. Prof. of anesthesia and

I.C.U

CEREBRAL BLOOD FLOW AND METABOLISM

- The brain accounts for 20% of basal oxygen consumption and for 25% of basal glucose consumption, despite representing only 2% of body mass.

- Whole-brain oxygen consumption is 3.5 ml/100 g/min or about 50 ml/min.

- The brain is a very vascular organ and receives 15–20% of cardiac output at rest.

CEREBRAL BLOOD FLOW AND METABOLISM(cont.)

- This equates to a cerebral blood flow (CBF) of 50 ml/100 g/min.

- Blood flow to grey matter is more than twice that to white matter.

- Preservation of the functional integrity of the brain involves maintenance of ionic gradients and the synthesis, transport, and reuptake of neurotransmitters. These are all highly energy demanding processes.


- In general terms, about 60% of the brain’s energy requirements are used to maintain electrophysiological function and 40% for cellular homeostasis.

- 90% of cerebral energy requirements are met by glucose, but there are no significant stores within the brain.


- If cerebral blood flow is interrupted, glucose supplies become exhausted after about 3 minutes and cerebral oxygen delivery is immediately compromised.

- Reduction in CBF below 20 ml/100 g/min results in disruption of electro-physiological functions of ‘brain and loss of consciousness.


- When CBF falls to below 10 ml/100 g/min, cellular homeostasis cannot be maintained. The cell membrane pump fails, Na+ and Ca2+ ions and water enter the cell, which swells and dies.

- Because of the unique sensitivity of the brain to ischaemia, it has a degree of luxury perfusion that allows a lower oxygen extraction ratio than other organs. This means that the venous blood returning from the brain is still 60–75% saturated with oxygen.

Control of cerebral blood flow

Myogenic regulation (pressure auto-regulation)

• Pressure auto-regulation is the phenomenon that allows CBF to remain constant despite changes in cerebral perfusion pressure (CPP).

• CPP is related to mean arterial blood pressure (MAP) and intracranial pressure (ICP) in the following manner:

CPP=MAP—ICP

Control of cerebral blood flow (Cont.)


• Occurs because of an intrinsic characteristic of cerebral arteriolar smooth muscle secondary to changes in intraluminal pressure.

• Myogenic reflexes are sensitive to changes in trans-mural pressure and not to changes in flow.



• The response begins within seconds of a change in CPP and is complete between 10 s and 2 minutes.

• The normal MAP limit for pressure auto-regulation is between 50 and 150 mmHg.



Factors affecting cerebral auto-regulation:

1. Arterial hypertension.

2. Increases in intracranial pressure or cerebral venous pressure. (CPP=MAP—ICP)

3. Hypoxaemia.

4. Changes in PaCO2.



Factors affecting cerebral auto-regulation:

5. Intracranial pathology.

6. Volatile anaesthetic agents.


Metabolic regulation

a-Flow-metabolism coupling:

- CBF is closely matched to the brain's local metabolic requirements for glucose and oxygen.

- The most important factor in the local control of CBF.



a-Flow-metabolism coupling:

- Increase in CMR resulting in an exactly coupled increase in CBF.

- Sensitivity of cerebral arterioles to certain metabolites such as K+, H+, and lactate has been implicated as a mechanism for this effect.



b- Arterial carbon dioxide tension (PaCO2):

Effects of PaCO2 on cerebral blood flow (CBF). CBF changes in a linear fashion with between 3.3 and 10.0 kPa.



b- Arterial carbon dioxide tension (PaCO2):

- Carbon dioxide is a potent cerebral vasodilator.

- CBF changes linearly by about 30% for each 1 kPa change in PaCO2 between about 3.3 (25 mmHg) and

10.6 kPa (80 mmHg).

- There is no further increase in CBF above 10.6 kPa due to maximal vasodilatation.



c- Arterial oxygen tension:

CBF increases rapidly when PaO2 falls below 7.5kPa (57

mmHg) and almost doubles when < 3.0 kPa (22.8 mmHg). However, there is some recent evidence that the threshold for hypoxic vasodilatation may be higher than previously imagined and may occur when falls below 90%.



c- Arterial oxygen tension:


Graph of autoregulatory control of cerebral blood flow (CBF) and vascular diameter, in response to changes in mean arterial pressure (MAP), arterial partial pressure of oxygen

(PO2), and arterial partial pressure of carbon dioxide (PCO2).


Neurogenic regulation

- The cerebral vasculature has extensive autonomic innervation.

- Constriction of cerebral vessels occurs because of sympathetic stimulation via fibres arising in the superior cervical and stellate ganglia. The neurotransmitters mediating this effect include noradrenaline, serotonin, and neuropeptide Y.



Parasympathetic stimulation causes cerebral vasodilatation via fibres originating in the sphenopalatine, otic ganglia, and internal carotid mini-ganglion. The neurotransmitters responsible for vasodilatation include acetylcholine, vasoactive intestinal peptide, and nitric oxide.



- There is also a sensory innervation arising from the first division of the trigeminal ganglion and from other somatosensory pathways originating in the thalamus.

- The cerebral vessels also contain opioid receptors that appear to modulate other vaso-regulatory mechanisms, particularly under conditions of stress.



- It is likely that neurogenic factors produce rapid adjustment of CBF to metabolic demands and that chemical and metabolic intermediates are responsible for maintaining these changes.

- Sympathetic nerves have a role in the maintenance of CBF during hypoxaemia and hypertension, but the exact physiological role of parasympathetic nerves is less.


Blood viscosity

- CBF is strongly influenced by blood viscosity of which the haematocrit is the most important determinant.

- CBF does not change within the 35–45%, but increases when the haematocrit falls below 35%. The balance between oxygen-carrying capacity and CBF is optimal in terms of cerebral oxygen delivery with a haematocrit around 30%.

How you would monitor cerebral blood flow?

• Kety–Schmidt method: (by CF Schmidt and SS Kety)

- The first method for quantitative determination of global CBF in 1944.

- This is an application of Fick’s principle, which states that flow is equal to the amount of a substance taken up or excreted by an organ, divided by the arterio-venous concentration difference. (A–V difference.)

How you would monitor cerebral blood flow? (cont.)

• Kety–Schmidt method:The subject breathes 10% N2O for 10 min, during which time paired peripheral arterial and jugular venous bulb samples are taken. At the end of 10 min the concentrations are equal, at which point the venous concentration is the same as brain. The speed at which the arterial and venous curves equilibrate is a measure of nitrous oxide delivery to the brain.


Recently two groups have proposed new techniques for quantitative determination of global CBF at the bedside.• Continuous jugular thermodilution.• Double-indicator method: based on injections

of dye and iced water providing non- continuous measurements.

Both methods have not yet gained widespread recognition and their usefulness is currently being evaluated.


• Intra-carotid injection technique:- A modification of the Kety–Schmidt

technique.- Intra-carotid injection of radioactive Xenon133 which

has the following advantages:1- Freely diffusible inert gas.2- Interferes only moderately with cerebral metabolism3- Eliminated rapidly and completely via the lungs.4- Can be used by inhalation.- Quantitative CBF data are calculated based on washout curves.


• Intra-carotid injection technique:


• Intra-carotid injection technique:Disadvantages:- The equipment is bulky.- Patients exposed to ionizing radiation.- Correction of CBF and O2 extraction ratio

(OER)should be made to normal BP and Normal PaCO2 as modest reductions in PaCO2 will increase cerebral vascular resistance, OER and reduce CBF.


• Thermal diffusion:- Monitors focal cortical blood flow. - A probe is inserted through a burr hole and

placed on a cortical region of interest. The probe typically consists of two small gold plates, one of which is heated.

- Local cortical blood flow is calculated from the temperature difference between the two plates


• Thermal diffusion:- The measurements are continuous.- Recently, a modification of this technique

using an intra-parenchymal probe incorporating thermistors has been evaluated in brain-injured patients. It provides continuous quantitative real-time data for a volume of approximately 5 cm3 around the tip of the probe.


• Jugular oximetry:- Provides non-quantitative global data and is

the methods which are used most often in I.C.U.

- It cannot directly measure CBF.- It is measured by a fiber optic oxymetric

catheter placed in the jugular blub under x-ray.

- The average normal values = 55 - 75%


• Jugular oximetry:If it is:> 75 % Hyperemia.< 50 % Cerebral hypoperfusion.< 40 % Cerebral ischemia.


• Jugular oximetry:


• Jugular oximetry:

Lateral cervical spine radiograph showing appropriate positioning of the SjO2 catheter above the lower border of the C1 vertebra (arrow tip is actually within the jugular foramen).


• Transcranial Doppler Ultrasonography: This gives a measure of the velocity of red cells flowing through large cerebral arteries, most commonly the middle cerebral, and can be used in clinical practice. The velocity can give an index of flow provided that the diameter of the artery is determined independently, and provided this diameter changes little (as is the case with the major cerebral arteries).


• Transcranial Doppler ultrasonography:


• Transcranial Doppler ultrasonography:

Typical printout of signal from the middle cerebral artery.

y-axis, blood flow velocity in cm.s-1.


• Positron emission tomography (PET):

This (research) technique monitors the uptake by different areas of the brain of 2-deoxyglucose, which is labelled with a positron emitter.• Scintillography and SPECT scanning:These techniques use radioactive xenon to trace regional blood flow, with or without enhancement by computed tomography (CT) or magnetic resonance (MR) imaging.

Intracranial pressure

- The intracranial pressure (ICP) is defined as the pressure exerted by the CSF in the lateral ventricles of the brain; in the normal adult, it is 10–15 mmHg.

- The intracranial compartment consists of brain approximately 83%, CSF approximately 11%, and blood approximately 6%.

Intracranial pressure (cont.)

- Brain tissue is essentially incompressible, so any rise in ICP will cause CSF and blood to be expressed out of the cranium.

- The change in volume of one compartment to compensate for a change in another is known as spatial compensation.

- CSF plays the biggest role in spatial compensation because it can be expelled from the intracranial cavity into the ‘reservoir’ of the spinal theca.


- Reduction of cerebral venous blood volume is also able to play a role in spatial compensation and can be used therapeutically to reduce ICP in patients with head injuries.

Cerebrospinal fluid

- CSF surrounds the brain and spinal cord in the subarachnoid space. It acts as a supporting cushion and as a pathway for nutrients and chemical mediators.

- It is formed by active secretion, involving Na+/K+-ATPase and carbonic anhydrase, from blood in the choroid plexus of the lateral and third ventricles at a rate of 0.4 ml/min.

Cerebrospinal fluid (cont.)

- The choroid plexus produces 450–500 ml of CSF each day, but most of this is reabsorbed through the arachnoid villi into dural venous sinuses to maintain a circulating volume of about 150 ml.

- The absorption of CSF is a passive process regulated by the pressure gradient between CSF and the venous sinuses.


CSF Plasma

Sodium (mmol/l) 144–152 136–148

Potassium (mmol/l) 2.0–3.0 3.8–5.0

Calcium (mmol/l) 1.1–1.3 2.2–2.6

Chloride (mmol/l) 123–128 95–105

Bicarbonate (mmol/l) 24–32 24–32

Glucose (mmol/l) 2.5–4.5 3.0–5.0

Protein (g/l) 0.2–0.3 60–80

pH 7.39 7.4

Composition of cerebrospinal fluid (CSF) compared with plasma

How you would monitor intracranial pressure?1. Intra-ventricular catheter:- It is the standard methods.- A catheter is inserted into one of the lateral

ventricles and connected to an external pressure transducer.

- The external auditory meatus is the reference point for zeroing a transducer and repetitive zeroing may be performed after insertion of the catheter.

How you would monitor intracranial pressure?1. Intra-ventricular catheter:Disadvantages:2. Infection: 6 - 11%.3. The insertion of ventricular catheters may be

difficult in patients with severe brain swelling.

How you would monitor intracranial pressure?1. Intra-ventricular catheter.2. Intraparenchymal probe.3. Subarachnoid probe.4. Epidural probe.5. Lumbar CSF pressure.6. Tympanic membrane displacement.7. Transcranial Doppler.

How you would monitor intracranial pressure?

Possible sites of ICP monitoringa: intra-ventricular drain; b: intra-parenchymal probe; c: epidural probe;

d: subarachnoid probe.

How you would monitor intracranial pressure?Typical system for ICP measurement via an intra-ventricular drain: a: connection with drain.b: zero (should be positioned at height of patient’s ear) and three-way stopcock for connection with pressure transducer.c: drip chamber, adjustable in height over zero for CSF drainage. Depending on stopcock position (b) either pressure measurements or CSF drainage are possible; and d: CSF reservoir.

How you would monitor intracranial pressure?

Blood-brain barrier

- It has become apparent that the blood-brain barrier (BBB) not only isolates the brain from the blood but also plays a pivotal role in maintaining the constancy of the internal milieu of the brain.

- Specialized tight junctional complexes between the endothelial cells of cerebral capillaries effectively eliminate gaps between cells and prevent free diffusion of blood borne substances into the brain.

Blood-brain barrier (cont.)

- A number of the proteins responsible for this barrier have been identified and the endothelium of the BBB is a complex and dynamic system rather than an inert barrier.

- The BBB plays a crucial role in transport of nutrients, neuro-modulation, and osmoregulation.


- This is achieved by preventing entry into the brain of substances that could interfere with neurotransmission and also by regulating the transport of those compounds that are essential for the maintenance of normal brain function.

- Passage of substances across the BBB is predominantly a function of lipid solubility and the presence of active transport systems.


- The BBB acts as a semipermeable membrane that effectively maintains control of ionic distribution in the brain extracellular fluid.

- Sympathetic nerves protect BBB function, particularly during changes in arterial PaO2

and systemic blood pressure.


- Four areas of the brain lie outside the BBB. These areas are collectively called the circumventricular organs and function as neurohumeral areas that allow substances secreted by neurones to enter the circulation directly, or as chemoreceptor zones where substances in the circulating blood can trigger changes in brain substance.


- The circumventricular organs are the posterior pituitary and adjacent median eminence, the area postrema, the supraoptic crest and the subfornical organ.

- The posterior pituitary gland releases oxytocin and vasopressin directly into the circulation and the area postrema acts as the chemoreceptor trigger zone that initiates vomiting in response to chemical changes in the plasma.

Thank you

Dr. Ahmed Mostafa

Cerebral physiology & monitoring By Dr. Ahmed Mostafa Assist. Prof. of anesthesia and I.C.U.

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