Cerebral physiology_neuro_Anesthesi.pptx

Anaestheisa for neurosurgery
cerebral physiology

1. Cerebral physiology by: Biruk A September,2021 9/29/2021 1

2. Outline Introduction Cerebral blood volume Cerebral Metabolic Rate Cerebral Blood Flow Cerebral perfusion pressure Intracranial pressure Conclusion 9/29/2021 2

3. Introduction 9/29/2021 3 The brain is a very complex organ which needs a continuous delivery of oxygen and nutrients. To sustain consciousness, satisfactory perfusion and adequate oxygen delivery is vital but it is equally essential to maintain a constant supply of glucose as the brain has no stores of glucose. Loss of consciousness ensues within seconds of ischaemia secondary to a reduction in cerebral blood flow (CBF), with permanent brain damage occurring with 3–8 min of insufficient blood supply. The brain also has a unique heterogeneous structure with areas of variable blood supply that is directly related to its function and metabolism.

4. Cerebral blood volume 9/29/2021 4 The brain receives its blood supply from the internal carotid and vertebral arteries which drain via the cerebral veins and dural venous sinuses into the internal jugular veins. The volume of blood in the whole brain is small and contained mainly in the venous sinuses and pial veins. The grey matter is composed of the cell bodies of the neurons which are involved with the complex functions of the human body and hence requires a larger proportion of the arterial blood supply. On the other hand, the white matter is essentially composed of axons which transmit impulses in between the neurons. As it is involved with less complicated functions than the grey matter, it needs a smaller fraction of the blood supply.

5. Cerebral blood volume… 9/29/2021 5

6. Cerebral blood flow 9/29/2021 6 Although the brain constitutes only 2% of body mass (1400 g), it receives a large proportion (12– 15%) of the resting cardiac output in the adult. The CBF is best described by the Hagen – Poiseuille equation for laminar flow, which demonstrates a direct relationship between flow, cerebral perfusion pressure (CPP), and calibre of cerebral vessels.

7. Cerebral blood flow… Where , ∆P = Cerebral perfusion pressure r = radius of the blood vessels η = viscosity of the fluid (blood) l = length of the tube (blood vessels) CBF will thus improve if the CPP increases and the cerebral vasculature is vasodilated . 9/29/2021 7

8. Cerebral perfusion pressure 9/29/2021 8 Perfusion pressure is the difference in the pressures between the arterial and venous circulation which dictates the blood flow to the organ. In the brain, the perfusion pressure or the CPP is affected by another pressure within the skull [i.e. intracranial pressure (ICP).

9. Cerebral perfusion pressure… 9/29/2021 9 In adults, CPP =MAP –(CVP + ICP) , where MAP is the mean arterial pressure and CVP the central venous pressure. In normal adults, the CPP is variable, usually ranging between 70 and 90 mm Hg and the CBF is constant. When the CPP decreases below 50 mm Hg, there is an increased risk of brain ischaemia affecting the electrical activity in the brain.

10. Cerebral perfusion pressure… 9/29/2021 10 The cerebrovascular resistance (CVR) is essentially the hindrance to the CBF determined predominantly by the calibre of the vessels. When cerebral vasodilatation occurs, the increase in the radius of the vessels not only decreases the CVR but also augments CBF. On the other hand, vasoconstriction of the cerebral vasculature will decrease CBF by increasing the CVR.

11. Cerebral perfusion pressure… CPP = MAP- (ICP +CVP ) CPP= MAP- ICP ,CVP ~ 0 CPP= 70-90mmHg MAP is the Driving Force ICP is the Resistance CPP will be affected by anything that changes the MAP or ICP. ↑ MAP : Cerebral vasoconstriction. ↓ MAP : Cerebral vasodilatation. 9/29/2021 11

12. Cerebral perfusion pressure… 9/29/2021 12

13. Cerebral perfusion pressure… 9/29/2021 13

14. Cerebral metabolic rate 9/29/2021 14 The cerebral metabolic rate (CMR) is the rate at which the brain utilizes metabolic substrates [e.g. oxygen (CMRO2), glucose ( CMRglu ), or generates by-products, e.g. lactate ( CMRlact )]. The brain has the highest metabolic requirements of any organ in the body which is reflected by its high blood flow. The brain oxygen consumption accounts for 20% of basal oxygen consumption (50 ml/ min ) at rest and relies, almost completely, on oxygen-dependent metabolism of glucose for energy production.

15. Cerebral metabolic rate… 9/29/2021 15 CMRO 2 =CBF x (A – V)O 2 content difference where A is the cerebral artery and V the cerebral veins. Because CBF is adjusted to meet the metabolic demand, oxygen by the grey matter is approximately five times more than by the white matter. Glucose is not only the main energy substrate for the brain but also a precursor for neurotransmitters, including g- aminobutyric acid, glutamate, and acetylcholine, and is therefore the substrate supply. Under aerobic conditions, oxidative phosphorylation produces 38 molecules of ATP for every molecule of glucose.

16. Cerebral metabolic rate… 9/29/2021 16 60% of the energy produced is utilized for the functioning of the neurons (i.e. the electrophysiologic fuction ), and the other 40% to maintain the integrity and homeostasis of the neuronal cells. The brain has very limited capacity for anaerobic metabolism and under these conditions, one molecule of glucose undergoes glycolysis to produce only two molecules of ATP.

17. Cerebral metabolic rate… 9/29/2021 17 CMRO 2 : Oxygen Brain requirements for metabolic activity Comprises 20% of total body oxygen consumption (250ml O 2 /min). CMRO 2 greatest in gray matter and lowest in white matter. CMRO 2 : 3.5 ml/100g/min ( 50ml/min) . Oxygen requirements for adult : 3.5 - 4ml/100g/min Oxygen requirements for children : 5.2ml/100g/min. 6 0% electrophysical activity and 40% basal cellular homeostasis .

18. Cerebral metabolic rate… 9/29/2021 18

19. Intracranial pressure 9/29/2021 19 The concept of ICP can best be understood if we compare the brain to a ‘closed box ’ or a fixed and rigid container. The Monro – Kellie hypothesis states that the volume of the brain and its constituents inside the bony cranium is fixed and cannot be compressed. a ) the brain is enclosed in the non-expandable cranium; b) brain parenchyma is nearly incompressible; c) the blood volume of the intracranial vault is nearly constant; and d) a continuous outflow of venous blood from the intracranial vault is required to make room for incoming arterial blood.

20. Intracranial pressure… 9/29/2021 20 The intracranial contents can be theoretically divided into three compartments: brain volume =85%, cerebrospinal fluid (CSF) = 10% (150 ml) and blood = 5% (50– 75 ml) In adults, ICP is normally 8–12 mm Hg when supine and is posture-dependent, being lowest in the upright position. Increase in ICP above a critical level is not tolerated and it results in a decrease in the CPP of the brain and can also cause local compression of brain tissue and ultimately herniation .

21. Control of ICP 9/29/2021 21 Volume buffering (pressure – volume relationship) Blood and CSF provide the main protection to the brain when the intracranial volume increases. There is an initial compensation which prevents major changes in the intracranial compliance with minimal increases in ICP. In the presence of intracranial pathology, the volume of one component within the cranium increases (e.g. haematoma, brain swelling) and, when the compensatory mechanisms are exhausted, there is a marked increase in ICP with a reduction in CPP and cerebral ischaemia .

22. Volume buffering (pressure– volume relationship)... 9/29/2021 22

23. Volume buffering (pressure– volume relationship)... 9/29/2021 23 Blood, despite being the smallest volume compartment within the cranium, has the most significant role in compensation for ICP changes as the cerebral venous volume can be changed very promptly and hence ICP can be modified almost immediately. Cerebral blood volume (CBV) can be increased by increasing the amount of blood flow that enters the cranium (e.g. by venodilation , or by hindering its venous drainage, e.g. head down position, jugular vein obstruction, increase in intrathoracic pressures).

24. Volume buffering (pressure– volume relationship)... 9/29/2021 24 CSF is the fluid present extracellularly between the arachnoid and pia mater and in the ventricles. It is produced mainly by the choroid plexus at a rate of 0.3 –0.4 ml/ min (500 ml/ day ) and reabsorbed by the arachnoid granulations into the venous circulation. The production of CSF is constant, but if re-absorption is hampered or there is a mechanical obstruction to the CSF outflow, its volume increases causing an increase in ICP.

25. Volume buffering (pressure– volume relationship)... 9/29/2021 25 CSF plays an important role in compensating for increases in ICP by ‘spatial compensation’ by displacing CSF into the spinal canal. Spatial compensation occurs slowly and is significant in tumours which expand gradually but provides limited compensation for acute and sudden increase in ICP.

26. Control of CBF and CBV 9/29/2021 26 Various factors affect CBF and CBV which in turn control ICP. Autoregulation Arterial carbon dioxide tension Arterial oxygen tension Flow metabolism coupling Neurogenic control Temperature and Rheology Cardiac output

27. Control of CBF and CBV… 9/29/2021 27

28. Autoregulation 9/29/2021 28 CBF = CPP/ CVR The conventional view of autoregulation is that the cerebral circulation adjusts its resistance to maintain CBF relatively constant over a wide range of mean arterial pressure (MAP) values . In normal human subjects, CBF is autoregulated between 50 mm Hg (lower limit of autoregulation , LLA) and 150 mm Hg (upper limit of autoregulation , ULA).

29. Autoregulation … 9/29/2021 29 Autoregulation is believed to occur via a myogenic mechanism whereby an increase in MAP increases the transmural vessel tension causing depolarization of vascular smooth muscle and constriction of the vessels. The reverse happens when the MAP and transmural tension decreases. It occurs between MAP of 50–150 mm Hg, is an almost instant process (occurs within 1–10 s of change in pressure), and is mediated primarily by an endothelium-derived relaxing factor and nitric oxide (EDRF/NO).

30. Autoregulation … 9/29/2021 30 Above and below the autoregulatory plateau, CBF becomes pressure-dependent and directly changes with changes in MAP. Pressures above 160mmHg Disrupts BBB Cerebral edema Haemorrhage In chronic arterial hypertension, the upper and lower limits of autoregulation are both displaced to higher levels, shifting the curve to the right. In hypertensive patients, cerebral hypoperfusion occurs at higher values of MAP compared with healthy individuals.

31. Autoregulation … 9/29/2021 31

32. Autoregulation … 9/29/2021 32 At the lower limit of autoregulation , cerebral vasodilation is maximal , and below this level the vessels collapse and CBF falls passively with falls in MAP. At the upper limit, vasoconstriction is maximal and beyond this the elevated intra luminal pressure may force the vessels to dilate, leading to an increase in CBF and damage to the blood-brain-barrier.

33. Autoregulation … 9/29/2021 33

34. Flow-metabolic coupling 9/29/2021 34 CBF is very variable across the brain and largely dependent on neuronal activity. Increase in activity, either regional or general, causes an increase in the CMR which in turn results in proportional increases in blood flow. This method of matching oxygen or glucose delivery to metabolic requirements is termed as ‘flow-metabolism coupling’.

35. Flow-metabolic coupling 9/29/2021 35

36. Flow-metabolic coupling… 9/29/2021 36

37. Flow-metabolic coupling… 9/29/2021 37

38. Flow-metabolic coupling… 9/29/2021 38 While volatile anaesthetic agents are intrinsic vasodilators, they also decrease CMRO 2 in a dose-dependent manner. Therefore, in the presence of intact flow-metabolism coupling, volatiles cause a coupled decrease in both CMRO 2 and CBF. The decrease in CBF caused by coupling is opposed by the vasodilatory effect of these agents, ultimately resulting in either no change or small decrease in CBF at low minimum alveolar concentration (MAC). However, CBF increases with MAC after metabolic suppression is maximal.

39. Flow-metabolic coupling… 9/29/2021 39 At 0.5 MAC, isoflurane , desflurane , and sevoflurane minimally delay, but preserve the cerebral autoregulation , whereas at 1.5 MAC autoregulation is considerably reduced by isoflurane and desflurane . Sevoflurane , in contrast, produces much lesser cerebral vasodilation and delays but preserves the autoregulatory response even at 1.5 MAC, making it the favoured volatile agent during neuroanaesthesia .

40. Flow-metabolic coupling… 9/29/2021 40

41. Arterial Carbon dioxide tensions 9/29/2021 41 CBF varies directly with PaCO 2 especially within the range of physiologic variation of PaCO 2 . CBF changes 1 to 2 mL /100 g/min for each 1 mm Hg change in Paco2 around normal Paco2 values. Under normal circumstances, the sensitivity of CBF to changes in Paco2 (ΔCBF/ΔPaco2) is positively correlated with resting levels of CBF . The role of MAP in the CO2 responsiveness of the cerebral circulation is highlighted by the impact of modest and severe hypotension. When hypotension is severe, a cerebrovascular response to changes in PaCO2 is not observed.

42. Arterial Carbon dioxide tensions 9/29/2021 42

43. Arterial Carbon dioxide tensions… 9/29/2021 43

44. Arterial Carbon dioxide tensions… 9/29/2021 44

45. Arterial Carbon dioxide tensions… 9/29/2021 45 At normotension , the relationship between PaCO2 and CBF is almost linear. At a PaCO2 80mmHg CBF is approximately doubled. No further increase in flow is possible at this point as the arterioles are maximally dilated . Conversely at 20mmHg flow is almost halved and again cannot fall further as the arterioles are maximally vasoconstricted . Arteriolar tone has an important influence on how PaCO 2 affects CBF.

46. Arterial Carbon dioxide tensions… 9/29/2021 46 Î in PCO 2 leads to diffusion of CO2 from arterial blood to the brain tissue. Hydration of CO2, H 2 0+ CO2 ↔ H 2 co3 ↔ Hco3- + H +, in the brain tissue . The H + is believed to cause vasodilation resulting increasing CBF. NB: this elevated blood flow removes CO2 and H+ From the brain to maintain normal range of cerebral tissue PH ,essential for normal neuronal activity.

47. Arterial Carbon dioxide tensions… 9/29/2021 47 The response of the cerebral vessels to CO2 can be utilized to help manage patients with raised ICP , for example after TBI. Hyperventilation reduces PaCO 2 → Vasoconstriction → reduces CBV & ICP. Too much hyperventilation, excessive reduction in PaCO 2, vasoconstriction can reduce CBF to the point of causing or worsening cerebral ischaemia . Clearly hypercapnia and the resulting vasodilatation and increase in ICP must be avoided. PaCO2 is therefore, best maintained at low-normal levels to prevent raising ICP (35-40mmHg).

48. Arterial oxygen tension 9/29/2021 48 Changes in PaO2 from 60 to more than 300 mm Hg have little influence on CBF. A reduction in PaO2 below 60 mm Hg rapidly increases CBF. Below a PaO2 of 60 mm Hg, there is a rapid reduction in oxyhemoglobin saturation. The relationship between oxyhemoglobin saturation and CBF is inversely linear.

49. Arterial oxygen tension… 9/29/2021 49

50. Arterial oxygen tension… 9/29/2021 50 A reduction in arterial oxygen content, and therefore cerebral oxygen delivery, can be achieved either by a reduction in PaO2 (hypoxemic hypoxia) or by a reduction in hemoglobin concentration ( anemia , hemodilution ). Both hemodilution and hypoxemic hypoxia lead to cerebral vasodilation and an increase in CBF. Of the two variables, however, hypoxemic hypoxia is a far more potent variable in CBF augmentation than hemodilution .

51. Arterial oxygen tension… 9/29/2021 51 Deoxyhemoglobin plays a central role in hypoxia induced increases in CBF by causing the release of NO and its metabolites, as well as ATP . The rostral ventrolateral medulla (RVLM) serves as an oxygen sensor within the brain. Stimulation of the RVM by hypoxia results in an increase in CBF (but not CMR), and lesions of the RVLM suppress the magnitude of the CBF response to hypoxia. The response to hypoxia is synergistic with the hyperemia produced by hypercapnia and acidosis. At high PaO2 values, CBF modestly decreases. At 1 atmosphere of oxygen, CBF is reduced by approximately 12%.

52. Arterial oxygen tension… 9/29/2021 52

53. Arterial oxygen tension… 9/29/2021 53 Hypoxia acts directly on cerebral tissue To promote the release of adenosine, and prostaglandin that contribute significantly to cerebral vasodilatation. Hypoxia also acts directly on cerebrovascular smooth muscle Produce hyperpolarisation and reduce calcium uptake, both mechanisms enhancing vasodilatation.

54. PaCO 2 &PaO 2 … 9/29/2021 54

55. Neurogenic Control 9/29/2021 55 The cerebral vasculature receives its postganglionic sympathetic nerve supply from the superior cervical ganglion which contains norepinephrine and neuropeptide Y. Excessive sympathetic activity causes vasoconstriction and shifts the autoregulation curve to the right (e.g. during chronic hypertension) and offers some protection against hypertension-induced increases in CBF (which can in certain circumstances lead to a breakdown of the BBB). During shock, a sympathetically mediated vasoconstrictive effect shifts the lower end of the autoregulatory curve to the right.

56. Neurogenic Control … 9/29/2021 56 The parasympathetic innervation arises from the sphenopalatine and the otic ganglia. They contain acetylcholine and vasoactive intestinal peptide which may lead to cerebral vasodilatation which is particularly prominent in hypotensive states. A third group of sensory fibres originate from the trigeminal ganglion which express vasodilators like substance P and calcitonin .

57. Rheology 9/29/2021 57 In normal healthy individuals, changes in haematocrit and blood viscosity have minimal effects on CBF. Under ischaemic conditions, low CPP causes a low flow state resulting in compensatory vasodilation and, during these circumstances, decreasing the viscosity of blood may improve CBF. However , a reduction in haematocrit also lowers the oxygen content of blood which may exacerbate an ischaemic insult .

58. Rheology … 9/29/2021 58 In patients with focal cerebral ischemia, a hematocrit of 30% to 34% will result in optimal delivery of oxygen. However, manipulation of viscosity in patients with acute ischemic stroke is not of benefit in reducing the extent of cerebral injury. Therefore, viscosity is not a target of manipulation in patients at risk as a result of cerebral ischemia, with the possible exception of those with hematocrit values higher than 55%.

59. Temperature 9/29/2021 59 The CMR decreases by 6% to 7% per degree Celsius of temperature reduction. In addition to anesthetic drugs, hypothermia can also cause complete suppression of the EEG (at approximately 18°C-20°C). However, in contrast to anesthetic drugs, temperature reduction beyond that at which EEG suppression first occurs does produce a further decrease in the CMR. This decrease occurs because anesthetic drugs reduce only the component of the CMR associated with neuronal function , whereas hypothermia decreases the rate of energy utilization associated with both electrophysiologic function and the basal component related to the maintenance of cellular integrity.

60. Temperature… 9/29/2021 60 The CMRO2 at 18°C is less than 10% of normothermic control values, which may explain the brain’s tolerance for moderate periods of circulatory arrest at these and colder temperatures. Hyperthermia has an opposite influence on cerebral physiologic function . Between 37°C and 42°C, CBF and CMR increase. However, above 42°C , a dramatic reduction in cerebral oxygen consumption occurs, an indication of a threshold for a toxic effect of hyperthermia that may occur as a result of protein (enzyme) denaturation .

61. Temperature… 9/29/2021 61 The CMRO2 decreases 7% for each 1 O C fall in body temperature and is paralleled by a similar reduction in CBF At 27°C, CBF is approximately 50% of normal. By 20°C, CBF is about 10% of normal. Decrease in temperature causes vasoconstriction, CBV and ICP are reduced.

62. Temperature… 9/29/2021 62

63. Cardiac output & CBF 9/29/2021 63 The conventional view of cerebral hemodynamics is that perfusion pressure (MAP or CPP) is the primary determinant of CBF and that the influence of cardiac output is limited. More recent data suggest that cardiac output impacts cerebral perfusion. An analysis of the pooled data from investigations indicates that a reduction in cardiac output of approximately 30% leads to a decrease in CBF by about 10%. the available data suggest that CO does influence CBF and that this effect may be of particular relevance in situations in which circulating volume is reduced and in shock states.

64. An integrated contemporary view of cerebral autoregulation 9/29/2021 64 The conventional view of cerebral autoregulation is that CBF is held constant as MAP increases between the lower limit and ULA. The currently available data, however, indicate that this view is now outmoded and is in need of revision. CBF and the cerebral vasculature are influenced by a variety of variables. CO is increasingly being recognized as an important determinant of CBF.

65. Integrated contemporary view… 9/29/2021 65 Arterial blood gas tensions affect vasomotor tone, and both hypercarbia and hypoxia attenuate autoregulation . The contribution of the sympathetic nervous system is of importance in the cerebrovascular response to hypertension. At the same time, sympathetic nerves reduce the vasodilatory capacity of the cerebral vessels during hypotension. A variety of medications can impact autoregulation , either through modulation of sympathetic nervous system activity or by direct reduction of vasomotor tone.

66. Integrated contemporary view… 9/29/2021 66 Anesthetics modulate autoregulation by a number of means, including suppression of metabolism, alteration of neurovascular coupling to a higher flow–metabolism ratio, suppression of autonomic neural activity, and by direct effect on cerebral vasomotor tone, and alteration of cardiac function and systemic circulatory tone. Cerebrovascular tone and CBF are therefore under the control of a complex regulatory system. Given the multitude of factors that determine the capacity of the cerebral circulation to respond to changes in perfusion pressure, the premise that cerebral autoregulation is static is now untenable.

67. Integrated Contemporary view… 9/29/2021 67 Rather, cerebral autoregulation should be viewed as a dynamic process and that the morphologic form of the autoregulatory curve is the result of the integration of all the variables that affect cerebrovascular tone in an interdependent manner . In a review of the available data from investigations in humans, the range of pressures that defined the LLA spanned from 33 mm Hg to as high as 108 mm Hg.

68. Integrated regulation of CBF 9/29/2021 68

69. Conclusion 9/29/2021 69 The brain is enclosed in a rigid box with a fixed volume and an increase in the volume of any of its constituents will lead to an increase in intracranial pressure (ICP). The volume of venous blood in the cerebral vasculature is small but very important as it can provide immediate compensation for increases in ICP

70. Conclusion … 9/29/2021 70 The cerebrospinal fluid provides the largest compensation for raised ICP but changes occur slowly. Volatile anaesthetic agents increase the ratio of cerebral blood flow and cerebral metabolism. Maintaining sufficient cerebral blood flow to meet metabolic demands after a neurological insult is important to prevent secondary ( ischaemic ) brain injury.

71. Thank you !!! 9/29/2021 71