Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
1Activity
0 of .
Results for:
No results containing your search query
P. 1
Fisiologia Cerebral Aplicada

Fisiologia Cerebral Aplicada

Ratings: (0)|Views: 61 |Likes:
Published by Vlady78

More info:

Published by: Vlady78 on Aug 29, 2013
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

05/18/2014

pdf

text

original

 
 Applied cerebral physiology 
Christopher Taylor Nicholas Hirsch
 Abstract 
The brain uses large amounts of glucose for its basal energy require-ments, and these are further increased during cerebral activation. Inorder that glucose can provide this energy, a plentiful and uninterruptedsupply of oxygen is necessary. Cerebral blood flow is therefore critical for normal cerebral function. Its control is dictated by local intrinsic metabolicneeds as well as extraneous factors such as arterial blood pressure, arte-rial carbon dioxide and oxygen tension, temperature and neural factors.This article reviews cerebral metabolism and cerebral blood flow andtechniques by which both can be monitored.
Keywords
Cerebral autoregulation; cerebral blood flow; cerebralmetabolism; intracranial pressure
Cerebral metabolism and blood flow
The primary function of the brain is the generation of nerveaction potentials in response to stimulation, and this function isaffected by the movement of ions against electrical gradients andthe release and regeneration of neurotransmitters at synapses.These functions require a large amount of energy in the form of adenosine triphosphate (ATP). Under normal conditions, themetabolic fuel is almost exclusively glucose and an appropriatesupply of oxygen is needed for the oxidative processes involved.This article outlines the mechanisms by which the brain receivesits vital supply of glucose and oxygen and balances these againstits demands (Table 1).
Cerebral metabolism
Mass for mass, the brain consumes more energy than any othertissue in the body. Under basal conditions, about 60% of thisenergy is used to fuel the Na
þ
/K
þ
-ATPase ion pumps, whichmaintain the ionic gradients across neuronal membranes.During increased neuronal activity, this demand is furtherincreased. Glucose is the major source of this energy and thus,under normal conditions the brain’s respiratory quotient isapproximately 1. It enters the brain by active transport acrossthe blood
e
brain barrier via the transporter GLUT 1 in cerebralcapillaries and is then distributed to the cells of the centralnervous system (CNS) by various transporter molecules (i.e.GLUT 1 to astrocytes, GLUT 3 to neurones and GLUT 5 tomicroglial cells). These glucose transporters are up-regulated inhypoxic conditions. Glucose uptake is high in brain tissue andthe cerebral metabolic rate for glucose (CMRGl) is about 30
m
g/100 g/min, which represents approximately 25% of the body’stotal glucose consumption. Whilst the level of the brain’sglucose requirement is impressive, its reserves are not. Hypo-glycaemia soon results in cerebral cellular dysfunction, man-ifested as anxiety and confusion, which soon progresses toconvulsions and coma. The symptoms seen reflect the greatersusceptibility of cortical structures to hypoglycaemia comparedwith the brainstem. Whilst cerebral cells do contain glycogen,this (and all available glucose) is exhausted within 2 min if cerebral blood flow (CBF) ceases.Following uptake into cerebral cells, about 70% of the glucoseis oxidized to carbon dioxide and water in the glycolytic andtricarboxylic acid (TCA) pathways, and together with oxidativephosphorylation within mitochondria, provides the ATP neces-sary for energy supplies. The remainder is converted to aminoacids, proteins and lipids.Under hypoxic conditions astrocytes metabolize glucoseanaerobically by glycolysis to form lactate, generating enough
Learning objectives
After reading this article, you should understand the:
C
importance of an uninterrupted supply of oxygen and glucosefor normal cerebral metabolism
C
fundamentals of the regulation and measurement of cerebralblood flow
C
concept of intracranial pressure and how it affects cerebralperfusion pressure.
Normal cerebral physiological values
CBF 750 ml/min or 15% of cardiac outputCBF (global) 50 ml/100 g/minGrey matter 90 ml/100 g/minWhite matter 20 ml/100 g/minCMRO
2
(grey matter) 3 ml/100 g/minCMRO
2
(white matter) 1 ml/100 g/minCMRGl (global) 30
m
g/100 g/min or 25% of total bodyconsumption
CBF, cerebral blood flow; CMRO
2
, cerebral metabolic rate for oxygen; CMRGl,cerebral metabolic rate for glucose.
Table 1
Christopher Taylor 
MRCP FRCA
is a Consultant Neuroanaesthetist at theNational Hospital for Neurology and Neurosurgery, London. He quali- fied from University College London medical school in 1996. He hasa specialist interest in neuroanaesthesia and neurocritical care medi-cine. Conflicts of interest: none declared.
Nicholas Hirsch
FRCA FRCP 
is a Consultant Neuroanaesthetist at theNational Hospital for Neurology and Neurosurgery, London, and Honorary Lecturer at the Institute of Neurology. He qualified from Guy’sHospital in 1978 and trained in anaesthesia in London and at YaleUniversity. His research interests involve neuroanaesthesia and neurocritical care medicine. Conflicts of interest: none declared.
NEUROSURGICAL ANAESTHESIA
343
Ó
2010 Elsevier Ltd. All rights reserved.
 
ATP to allow glutamate uptake. The lactate released into theextracellular space is actively taken up by neurones and con-verted to pyruvate, which then enters the tricarboxylic acid(TCA) cycle to generate more energy aerobically. This lactate isthought to be a vital energy substrate during neuronal activationand for recovery of synaptic function following hypoxic injury; ithas a monocarboxylate transporter (similar to glucose), whichallows active transport across the blood
e
brain barrier.During prolonged fasting the brain uses ketone bodies (endproducts of fatty acid metabolism in the liver) as an alternativefuel. They are exported from the liver and actively taken up bythe brain. There, they are broken down to acetyl coenzyme A(acetyl-CoA), which is oxidized via the TCA cycle to yield energy.Under such conditions the brain is capable of regeneratingglucose (gluconeogenesis) from alternative substrates such asglycerol, glutamine and glycine.
Cerebral blood flow
Normal aerobic cerebral metabolism requires a plentiful anduninterruptedsupply of oxygen. Blood reaches the brain via theanterior paired internal carotid arteries and posterior pairedvertebral arteries. About 70% of the total CBF is supplied by thecarotid arteries. These anterior and posterior circulations arejoined at the circle of Willis in the base of the brain but it isimportant to note that this anastomosis is incomplete in 50% of individuals.Although the brain constitutes only 2% of the total bodymass, it receives 15% of the cardiac output (750 ml/min inadults). Resting CBF is approximately 50 ml/100 g/min. The flowis not evenly distributed. Grey matter, which is metabolicallymore active, receives approximately 90 ml/100 g/min and inthese regions the rate of oxygen consumption, termed the cere-bral metabolic rate for oxygen (CMRO
2
), is about 3 ml/100 g/min. White matter receives about 20 ml/100 g/min and itsCMRO
2
is approximately 1 ml/100 g/min. The level of CBF iscritical. Complete interruption of CBF produces loss of consciousness within seconds as does a reduction of CBF toapproximately 20 ml/100 g/min. Neuronal conversion to anaer-obic metabolism occurs below 18 ml/100 g/min and the elec-troencephalogram becomes flat. Brain cell death (infarction)takes place at about 3 h with flows of 10 ml/100 g/min and after30 min at flows of 5 ml/100 g/min.
Cerebral perfusion pressure (CPP)
The perfusion pressure (i.e. the arteriovenous pressuregradient) in the brain is more complex than that of other organsbecause it is confined within an incompressible vault. It isdependent on the pressure difference between the mean arterialpressure (MAP) or the driving pressure (measured at brainlevel) and the intracranial pressure (ICP) or the pressure thatneeds to be overcome to supply adequate blood to the brain.This pressure difference is known as the CPP. A normal CPP is70
e
80 mmHg; the threshold for critical ischaemia is 30
e
40mmHg. As can be seen from the equation below, even atnormal levels of MAP, an elevated ICP of more than 20 mmHgwill compromise CPP and therefore reduce cerebral blood flow.This emphasizes the importance of maintaining an adequateMAP in circumstances such as head injury to ensure adequateperfusion.CerebralPerfusionPressure
¼
MeanArterialPressure
À
IntracranialPressure
Intracranial pressure
The contents of the skull are brain parenchyma (80%), blood(9%), CSF (6%) and interstitial fluid (5%). After fusion of thecranial sutures, the brain becomes contained within a rigid bonebox. Normal intracranial pressure is 7
e
12 mmHg and is deter-mined by the balance between the rate of CSF formation andabsorption (the latter depending on the venous sinus pressureand the resistance of the arachnoid villi). ICP is a dynamicpressure and fluctuations occur with arterial pulsations, position,respiration, coughing and straining (Figure 1).The Monro
e
Kellie doctrine states that because intracranialvolume is fixed, an increase in volume of one of the componentscontained within the skull, unless accompanied by a reduction involume of the other components, will lead to a rise in ICP.Initially, as the brain volume increases, compensation occurs bymovement of CSF into the spinal compartment, accompanied byan increase in absorption, a decrease in CSF production anda reduction in cerebral blood volume; this limits the rise in ICP.However, as these compensatory mechanisms are overwhelmed,intracranial compliance falls, and ICP rises dramatically withfurther small increases in intracranial volume (Figure 2). Even-tually, if unchecked, rises in ICP will cause brainstem compres-sion with hypertension, bradycardia and irregular respiration(Cushing’s reflex).AnaesthetistsinstitutevariousmethodstoreduceICPacutelyinhigh-risk patients with critically high ICPs. With the exception of 
    I    C    P    (   m   m    H   g    )
Time (seconds)
Cardiac pulsationRespiratory variation
010155
Dynamic intracranial pressure (ICP) trace
Figure 1
NEUROSURGICAL ANAESTHESIA
344
Ó
2010 Elsevier Ltd. All rights reserved.
 
surgical CSF drainage or decompression, methods for the controlof ICP depend on either reducing intracranial blood volume orreducing interstitial fluid volume. Reduction of intracranial bloodvolume can be achieved by reducing arterial carbon dioxidetension (PaCO
2
), which promotes cerebral vessel vasoconstric-tion,orbyincreasingvenousdrainagewithahead-uppositionandproviding adequate sedation and muscular relaxation, whichreduce intrathoracic pressure. Interstitial fluid volume reductioncan be achieved by fluid restriction or by the administration of diuretics (e.g. mannitol and furosemide) or corticosteroids.Conversely, poor anaesthetic technique may result in a dramaticrise in ICP in patients with existing raised ICP.
CSF
CSF is an ultrafiltrate of plasma that circulates freely throughoutthe cerebral ventricles and the central canal of the spinal cord. It isformed (and reabsorbed) at the rate of about 500 ml/day byenergy-dependent and perfusion-related processes in the choroidplexuses and the cerebral ventricles. CSF then flows through theforamen of Monro to the third ventricle, into the fourth ventriclevia the aqueduct of Sylvius and then into the cisterna magna andsubarachnoid spaces via the medial foramen of Magendie and thelateral foramen of Luschka. Ultimately CSF is reabsorbed throughthe subarachnoid villi into the cerebral venous sinuses as a resultof the pressure gradient between CSF and sinus (see article onCerebrospinal Fluid and its Circulation, pp 355
e
356 of this issue).If the rate of formation of CSF exceeds the rate of reabsorption(e.g. if blockage of the CSF circulation is present) hydrocephalusoccurs and results in increased ICP.The blood
e
brain barrier exists between the bloodstream andthe CNS and prevents transfer of potentially harmful substancesreaching the brain. This semi-permeable barrier consists of threecellular layers: the vascular endothelium and its basementmembrane, the astrocytes and pericytes. The endothelial cellshave very few pinocytic vesicles and are sealed by tight junctions(zona occludens) with no anatomical gaps. This provides a highelectrical resistance barrier.The existence of the blood
e
brain barrier explains the differ-ence between the constituents of plasma and CSF. CSF proteincontent is very low compared with plasma (0.2
versus
60 g/litre),and increased levels in CSF indicate disruption to the barrier.Similarly, concentrations of potassium, calcium, glucose, ureaand lymphocytes are lower in CSF.The passage of substances across the blood
e
brain barrier isdirectly proportional to their lipid solubility and is facilitated byactive transport mechanisms but is inversely proportional tomolecular weight, ionic charge and degree of plasma
e
proteinbinding. Lipophilic substances (carbon dioxide, oxygen, volatileanaesthetic agents) pass freely, unlike large-molecular-weightmolecules(e.g.proteins)andhighlychargedmoieties(e.g.sodiumions). Proteins and drugs (e.g. penicillin) cannot cross the barrierunlessitisinflamed(e.g.inmeningitis).Theintegrityofthebarriercan be examined by the intravenous injection of radioactiveisotopesboundtoprotein;scanningtechniquescanthenbeusedtodetermine whether the radioactive label is escaping from cerebralvessels. Ruptured aneurysms and increased permeability attumour sites may be detected using such techniques.Water moves freely across the blood
e
brain barrier, depend-ing on osmotic gradients. Sudden changes in plasma osmolalitysecondary to changes in electrolyte or glucose concentrations cantherefore lead to potentially problematic fluid shifts in the brain.This emphasizes the importance of correcting sodium andglucose abnormalities slowly. The blood
e
brain barrier is dis-rupted by a number of processes, including hypertension, stroke,trauma, status epilepticus, hypercarbia, hypoxia, and especiallyinflammation (chemical, infective or autoimmune). Whendisruption occurs, fluid movement becomes largely dependenton hydrostatic gradients.
Control of cerebral blood flow
Various mechanisms exist that allow an adequate basal CBF tosupply the substrate demands of the brain. However, in addition,local regulatory mechanisms direct blood flow to regions of thebrain that are particularly active (i.e. blood flow is coupled tolocal metabolic needs). Furthermore, other physiological vari-ables influence CBF (Box 1).
Flow
e
metabolism coupling and local chemical regulators
Local neuronal activity causes an increase in CMRO
2
and CMRGland is accompanied by an increased regional CBF to matchglucose and oxygen use with delivery. The parallel change in CBFwith CMRO
2
and CMRGl is known as flow
e
metabolism coupling.There is evidence to suggest that CBF may be modulated bychanges in glucose consumption rather than oxygen consump-tion under hypoxic conditions. The regulatory changes involvedin flow
e
metabolism coupling have a short latency (about 1second), where transient changes in the concentration of localmetabolic mediators seem to determine the fine control of regional CBF by affecting vascular tone.
    I    C    P    (   m   m    H   g    )
Intracranial volume(arbitrary units)
ICP, intracranial pressure; P, pressure; V, volume
Δ
P
2
Δ
P
1
Δ
V
2
Δ
V
1
0203010
Intracranial pressure-volume curve
Figure 2
NEUROSURGICAL ANAESTHESIA
345
Ó
2010 Elsevier Ltd. All rights reserved.

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->