Central nervous system physiology and cerebral blood flow2012
Central nervous system physiology and cerebral blood flow Prepared dr tam weiyaw Supervisor DR WAN NAZA
Blood supply of the brain…• Derived from 2 internal carotid and 2 vertebral arteries which lie in the subarachnoid space• Two thirds of the brain is supplied by the internal carotids. - they ascend through the carotid canal in the petrous temporal bone ; enter the skull where they have tortuous course, ending by dividing into the anterior & middle cerebral arteries.• The anterior cerebral artery : - supply the superior and medial parts of the cerebral hemisphere - Linked by the ant communicating artery, making the anterior portion of the circle of willis.
• The middle cerebral arteries supply most of the lateral side of the hemisphere, and branches supply the internal capsule.• The blood supply to the other one third of the brain comes from the vertebral arteries. - branches from the subclavian artery. - ascend in the transverse foramina of the upper six cervical vertebrae and enter the skull by piercing the dura @ the foramen magnum
- they run on the medulla and join in front of the pons to form basilar art, which gives off the cerebellar arteries.• The basilar artery divides into the posterior cerebral arteries; : which supply the occipital lobe and medial side of the temporal lobe – The posterior communicating arteries form the anastomoses between the internal carotids and posterior cerebral arteries that completing circle of willis.
Circle of Willis• is a circle of arteries that supply blood to the brain and surrounding structures.• is composed of the following arteries: - Anterior cerebral artery (left and right) - Anterior communicating artery - Internal carotid artery (left and right) - Posterior cerebral artery (left and right) - Posterior communicating artery (left and right) - The basilar artery and middle cerebral arteries
• The arrangement of the brains arteries into the Circle of Willis creates redundancies or collaterals in the cerebral circulation.• If one part of the circle becomes blocked or narrowed (stenosed), blood flow from the other blood vessels can often preserve the cerebral perfusion to avoid the symptoms of ischemia.
Venous drainage of the brain…• Blood is drained into superficial and deep cerebral veins and veins of the posterior fossa.• The superficial veins drain the surface of the brain cortex and lie within the cortical sulci.• The deep cerebral veins drain the white matter, basal ganglia, diencephalon, cerebellum and brainstem.• The deep vein join to form the great cerebral vein.
• Emissary veins connect the veins near the surface of the skull to the diploic veins and venous sinuses.• All blood is drained into the meningeal sinuses, which mainly drain into the internal jugular vein.• The veins and sinuses of the brain lack valves; pressure of drainage vessels in the neck is directly transmitted to intracranial venous structures.
Formation of CSF…• CSF is present in the: - ventricles of the brain - cisterns around the brain - subarachnoid space around the brain and the spinal cord• Total volume of CSF is ~ 150mls; specific gravity is 1.002 to 1.009• The daily production is 500 to 600mls/day : turns over 3 – 4 times/day• Formed by: - modified ependymal cells in choroid plexus (>67%) - directly from the ependyma of the walls of the ventricle (<33%)
• the composition depends on filtration and diffusion from the cerebral vessels, plus facilitated diffusion and active transport, predominantly from the choroid plexus• formation is constant independent of ventricular pressure• Normal ICP is 5 to 15 mmHg• when pressure falls below ~ 7 cmH2O absorption ceases
Functions of CSF…1) Protective role due to water bath effect- Major fx in protecting brain from injury; act as a cushion with changes in position or movement - give 1400g brain an effective net weight only 50g- Allow brain to maintain its density without being impaired its own weight
2) Regulation in intracranial pressure- Protective role in buffering any rise in ICP by CSF translocation to the extracranial subarachnoid space3) Return of the interstitial protein to the circulation- Brain does not have lymph vessel- Interstitial protein can return to the circulation by absorption with CSF across the arachnoid villi
4)Role of CSF in control of respiration- Central chemoreseptor are sensitive to changes in H+ concentration- H+ act as indirect measure for PaCO2 and stimulate chemoreseptor- Changes in PaCO2, but not arterial PH, reflecting the ability of CO2 to cross blood brain barrier easily- As a result acute respiratory acidosis or alkalosis produces corresponding changes in CSF
CPP…• The pressure driving the flow of blood through the brain• Obtained from the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP) • CPP = MAP – ICP ( or CVP ; which one is higher )• Manipulation of CBF affect ICP ; hence CPP
• Under normal circumstances MAP of 90 mmHg and ICP of ~ 10 mmHg will give CCP of 80 mmHg• CPP less than 70 mm Hg lead to rapid decrease in jugularvenous bulb saturations representing an increased oxygen extraction by brain tissue• CPP of 30 – 40 mmHg is the threshold for critical ischaemia• CPP: – < 50mmHg slowing of the EEG – 25 – 40 mmHg isoelectric EEG – < 25 mmHg irreversible brain damage
INTRACRANIAL PRESSUREthe normal contents of the cranium are;• 1. brain - neural tissue & interstitial fluid ~ 1400g• 2. blood ~ 75 ml• 3. CSF ~ 75 ml (+75 ml spinal cord)• 4. ICP ~ 7-18 cmH2O ( 5 – 15 mm Hg )because each of these three components is relatively incompressible, the combined volume at any one time must be constant ® the Monro- Kellie doctrine
Cerebral blood flow (CBF)• CBF averages 50ml/100g/minute of brain tissue.• For an adult,this is equivalent to 750ml/minute,or about 15% of the resting cardiac out put , delivered to an organ that represents only about 2% of the body’s mass.• the gray matter of the brain has a higher cerebral blood flow (80ml/100g/minute) than the white matter (20ml/100g/minute)• The amount of CBF is critical:• If falls to 20ml/100g/min EEG slow; at 15ml/100g/min EEG is flat,and at 10ml/100g/min irreversible cerebral demage occurs.
Regulation of cerebral blood flow• Anesthetic drugs cause dose-related and reversible in many aspects of cerebral physiology; including CBF , CMR , electrophysiologic function(EEG)• Adult human brain weighs approximately 1350g and is about 2% of total body weight.• However , it receives 12% to 15% of cardiac output• This high flow rate is a reflection of the brain’s high metabolic rate.• At rest , brain consumes O2 at an average rate of 3.5mlof O2 per 100g of brain tissue per minute.• Whole brain O2 consumption(50ml/min) represents about 20% of total-body O2 utilization.
Normal values for CBF,CMR and other physiologic variables• Normal cerebral physiologic values CBF -GLOBAL 45-55ml/100g/min -CORTICAL(GRAY MATTER) 75-80ml/100g/min -SUBCORTICAL(WHITE ~20ml/100g/min MATTER) CMRO2 3.0~3.5ml/100g/min CVR 1.5~2.1 mmHg/100g/min CEREBRAL VENOUS PO2 32-44 mmHg CEREBRAL VENOUS SO2 55%- 70% ICP (SUPINE) 8-12mmHg
• Approximately 60% of the brain’s energy consumption is used to support electrophysiologic function.• The remainder of the energy consumed by the brain is involved in cellular homeostatic activities.• There are elaborate mechanisms for regulation of CBF.• These mechanisms , which include chemical , myogenic and neurogenic factors
Chemical regulation of Cerebral Blood Flow• Several factors , including changes in CMR , PaCO2 , and PaO2 , cause alterations in the cerebral biochemical environment that result in adjustment in CBF.
Cerebral Metabolic Rate(CMR)• Increase neuronal activity results in increased local brain metabolism , and this increase in CMR is associated with a well- matched , proportional change in CBF and is referred to as – flow-metabolism coupling.• Glutamate , released with increased neuronal activity , results in the synthesis and release of nitric oxide (NO) , A potent cerebral vasodilator that plays an important role in coupling of flow and metabolism.• Flow-metabolism coupling within the brain is a complex physiologic progress that is regulated , not by a single mechanism , but by a combination of metabolic , glial , neural , and vascular factors.
• FUNCTIONAL STATE.CMR is influenced by • CMR decreases during sleep and increasesseveral phenomena in during sensory stimulation , aruosal of anythe neurosurgical cause.environment • During epileptic activity , CMR increaseincluding… extremely,whereas regionally after brain injury and globally with coma,CMR may be substantially reduced. • ANESTHETIC DRUGS.1) The functional • In general,anesthetic drugs suppress CMR , state with ketamine and N2O being notable exception.2) Anesthetic drugs • TEMPERATURE. • The effects of hypothermia on the brain3) Temperature have been reveiwed in detail. • CMR decreases by 6%-7% per degree Celsius of temperature reduction.
PaCO2• CBF varies directly with Paco2. the effect is greatest within the range of physiologic Paco2 variation• CBF changes 1 to 2 ml/100g/min for each 1-mmHg change in Paco2 around normal Paco2 values.• The changes in CBF caused by Paco2 are dependent on pH alterations in the extracellular fluid of the brain.• NO(nitric oxide),in particular NO of neuronal origin, is an important although not exclusive mediator of C02-induced vasodilation.• The vasodilatory response to hypercapnia is also mediated in part by prostaglandins.• Note that in contrast with respiratory acidosis, systemic metabolic acidosis has little immediate effect on CBF because the BBB excludes hydrogen ion (H+) from the perivascular space.
PaO2• Changes in Pao2 from 60 to greater than 300mmHg have little influence on CBF. Below a Pao2 of 60 mmHg, CBF increases rapidly.• The mechanisms mediating cerebral vasodilation during hypoxia are not fully unserstood but may include neurogenic effects initiated by peripheral and neuraxial chemoreceptors,aw well as local humoral influences.
• Paco2 and Pao2 influence cerebral blood flow , whereas sympathetic and parasympathetic nerves play little or no role in the regulation of CBF• Changes in the Paco2 between about 20 and 80 mmHg produce corresponding changes in CBF• CO2 increases CBF by combining with water in body fluids to form carbonic acid , with subsequent dissociation to form hydrogen ions.• Hydrogen ions produce vasodilatation of cerebral vessels that is proportional to the increase in hydrogen ion concentration
• Any other acid that increases hydrogen ion concentration , such as lactic acid , also increases CBF• Increased CBF in response to increases in Paco2 serves to carry away excess hydrogen ions that would otherwise greatly depress neuronal activity• Unlike the continuous response of CBF to changes in Paco2,the response to Pao2 is a threshold phenomenon• If the Paco2 is maintained , CBF begins to increase when the Pao2 decreases below 50 mmHg or the cerebral venous Po2 decreases from its normal value of 35 mmHg to about 30 mmHg.
Myogenic regulation(AUTOREGULATION) of CBF• AOTUREGULATION refers to the capacity of the cerebral circulation to adjust its resistance to maintain CBF constant over a wide range of mean arterial pressure.• The limits of autoregulation occurring at MAP values of ~70 and 150mmHg(60 and 140mmHg Stoelting)• The lower limit of autoregulation(LLA) has been widely quoted as an MAP of 50mmHg.• Above and below the autoregulation plateau, CBF is pressure dependent(pressure passive) and varies linearly with CPP.• Autoregulation is influenced by various pathologic processes, as well as the time course over which the changes in CCP occur.• Even within the range over which autoregulaiton normally occurs, a rapid change in arterial pressure will result in a transient(3-4 minutes)alteration in CBF.• According to the myogenic hypothesis, changes in CPP lead to direct changes in the tone of vascular smooth muscle:this progress appears to be passive.
• CBF is closely autoregulated btw a mean arterial pressure of abt 60 and 140mmHg• As a result, changes in systemic blood pressure within this range will not significantly alter CBF• Chronic systemic hypertension shifts the autoregulation curve to the right such that decreases in CBF occur at a mean arterial pressure of >60 mmHg
• Autoregulation of CBF is attenuated or abolished by hypercapnia, arterial hypoxemia, and volatile anesthetics.• Autoregulaition is often abolished in the area surrounding an acute cerebral infarction.• Increases in mean arterial pressure above the limits of autoregulation can cause leakage of intravascular fluid through capillary membranes, resulting in cerebral edema.• Because the brain is enclosed in a solid vault, the accumulation of edema fluid increases intracranial pressure and compress blood vessels, decreasing cerebral blood flow and leading to destruction of brain tissue.
Neurogenic regulation of CBF• The cerebral vasculature is extensively innervated• The density of innervation declines with vessel size, and the greatest neurogenic influence appears to be exerted on larger cerebral arteries.• Evidence of the functional significance of neurogenic influences has been derived from studies of CBF autoregulation and ischemic injury• Hemorrhagic shock, a state of high sympathetic tone, results in a lower CBF at a given MAP than occurs when hypotension is produced with sympatholytic drugs, presumably because during shock, a sympathetically mediated vasoconstrictive effect shifts the power end of the “autoregulation” plateau to the right .• It is not clear what the relative contributions of humoral and neural mechanism are to this phenomenon;however,there is certainly a neurogenic component in somespecies because sympathetic denervation increases CBF during hemorrhagic shock.
Effect of blood viscosity on CBF• Blood viscosity can influence CBF.Hematocrit is the single most important determinant of blood viscosity• In healthy subjects,variation of the hematocrit within the normal range(33%-45%) probably results in only modest alterations in CBF• Beyond this range,changes are more substantial• In anemia, cerebral vascular resistance is reduced and CBF increases
Effect of anesthetics on CBFIntravenous anesthetic drugs Volatile anesthetics• Barbiturates • Halothane• Propofol• Etomidate• Narcotics• Benzodiazepines• Ketamine• Lidocaine
Effect of anesthetics on CBF• Intravaneous anesthetic drugs• The vast majority of intravenous anesthetics cause a reduction in both CMR and CBF.• Ketamine, which causes an increase in CMR and CBF, is the exception.
barbiturates• A dose-dependent reduction in CBF and CMR occurs with barbiturates.• With the onset of anesthesia, CBF and CMR02 are reduces by about 30%• When large doses of thiopental cause complete EEG suppression, CBF and CMR are reduced by about 50%• Further increases in the dose of barbiturate have no additional effect on CMR.
Barbiturate coma• is a temporary coma (a deep state of unconciousness) brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental.• Barbiturate comas are used to protect the brain during major neurosurgery, and as a last line of treatment in certain cases of status epilepticus that have not responded to other treatments.
Barbiturate coma• Barbiturates reduce the metabolic rate of brain tissue, as well as the CBF. With these reductions, the blood vessels in the brain narrow, decreasing the amount of volume occupied by the brain, and hence the intracranial pressure.• The hope is that, with the swelling relieved, the pressure decreases and some or all brain damage may be averted. Several studies have supported this theory by showing reduced mortality when treating refractory intracranial hypertension with a barbiturate coma.
Barbiturate coma• Some studies have shown that barbiturate- induced coma can reduce intracranial hypertension but does not necessarily prevent brain damage.• Furthermore, the reduction in intracranial hypertension may not be sustained.
Barbiturate coma• Some randomized trials have failed to demonstrate any survival or morbidity benefit of induced coma in diverse conditions such as neurosurgical operations, head trauma, intracranial anurysm rupture,intracranial hemorrhage, ischemic stroke, and status epilepticus.• If the patient survives, cognitive impairment may also follow recovery from the coma.
propofol• The effects of propofol on CBF and CMR appear to be quite similar to those of barbiturates.• Substantial reductions in both CBF and CMR after the administration of propofol• Surgical levels of propofol reduced regional CBF by 53% to 79% in comparison with the awake state.• When compared with isoflurane-fentanyl or sevoflurane- fentanyl anesthesia, a combination of propofol-fentanyl decreased subdural pressure in patients with intracranial tumors and decreased the arteriovenous oxygen content difference• Propofol effects reduces in CMR and secondarily decreases CBF,CBV and ICP
narcotics• Narcotics have relatively little effect on CNF and CMR in the normal , unstimulated nervous system• When changes do occur, the general pattern in one of modest reductions in both CBF and CMR
benzodiazepines• Cause parallel reductions in CBF and CMR• CBF and CMRO2 decreased by25% when 15mg of diazepam was given to head-injured patients• The effects of midazolam on CBF(but not CMR) have also studied in humans.• Foster and associates observed a 30%-34% reduction in CBF after the administration of 0.15mg/kg of midazolam to awake healthy human .• Veselis and coworkers ,using PET observed a global 12% reduction in CBF after a similar dose and noted that the decreases occurred preferentially in the brain regions associated with arousal, attention, and memory
ketamine• Among the intravenous anesthetics, ketamine is unique in its ability to cause increases in both CBF and CMR• PET studies in humans have demonstrated that subanesthetic doses of ketamine(0.2 to 0.3mg/kg)can increase global CMR by about 25%• Commercially available formulations of ketamine contain both the (s)-and (R) –ketamine enantiomers.• The (s)-ketamine enantiomer increases CMR substantially,whereas the (R) enantiomer tends to decrease CMR,particularly in the temporomedial cortex and in the cerebellum• These changes in CMR are accompanied by corresponding changes in CBF• The observed effects of ketamine on cerebral hemodynamics indicate that ketamine increase CMR and secondarily increases CBF, CO2 responsiveness is preserved
ketamine• The anticipated ICP correlate of the increasein CBF has been confirmed to occur in humans.• However , anesthetiv drugs(diazepam, midazolam, isoflurane/N20, propofol)have been shown to blunt or eliminate the increases in ICP or CBF associated with ketamine• Accordingly, although ketamine is probably best avoided as the sole anesthetic agent in patients with impaired intracranial compliance, it may be reasonable to use it cautiously in patients who are simultaneously receiving the other drugs mentioned earlier
Volatile anesthetics• The pattern of volatile anesthetic effects on cerebral physiology is a striking depature from that observed with the intravenous aneathetics, which generally cause parallel reductions in CMR and CBF.• All volatile anesthetics, suppress cerebral metabolism in a dose-related manner• Volatile anesthetics also possess intrinsic cerebral vasodilatory activity as a result of direct effects on vascular smooth muscle• The net effect of volatile anesthetics on CBF is therefore a balance between a reduction in CBF caused by CMR suppression and augmentation of CBF caused by the direct cerebral vasodilation .
Volatile anesthetics• When administered at a dose of 0.5 MAC,CMR suppression-induced reduction in CBF predominates, and net CBF decreases in comparison to the awake state.• At 1.0 MAC, CBF remains unchanged; at this dose, CMR suppression and vasodilatory effects are in balance.• Beyond 1.0 MAC, the vasodilatory activity predominates, and CBF increases significantly even though CMR is substantially reduced.• The important clinical consequences of administration of volatile anesthetics are derived from the increases in CBF and CBV– and consequently ICP – that can occur.• Of the commonly used volatile anesthetics, the order of vasodilating potency is approximately halothane >> enflurane > desflurane ~ isoflurane > sevoflurane.
Thank you References Miller’s AnesthesiaPharmacology&physiology(stoelting)