Blood Brain Barrier (BBB)

Transcription

1 Cerebral Blood Flow, Cerebral Spinal Fluid, and Brain Metabolism Part Two Guyton Chapter 61 Morgan & Mikhail, 4 th ed, Chapter 25 (or Morgan & Mikhail 5 th ed, Chapter 26) Blood Brain Barrier (BBB) Cerebral blood capillaries are unique in that the junctions between the vascular endothelial cells are nearly fused ( tightjunctions ) The fused endothelial walls constitute barriers between the blood and the brain = Blood Brain Barrier Protects the brain from sudden changes in osmolarity or [electrolyte] 1

2 Blood Brain Barrier (BBB) Movement of a substance across the BBB governed by: size, lipid solubility, degree of protein binding BBB allows easy passage of lipid-soluble substances (CO 2, O 2, most anesthetics, ETOH) and water into the brain Most ions (Na +, Cl -, H +, K + ), proteins, and large organic molecules (mannitol, glucose) penetrate the BBB poorly Blood Brain Barrier the caveat Water moves freely XS BBB Movement of ions, glucose, mannitol impeded Rapid changes in [electrolyte] or [glucose] produce osmotic gradients between plasma and brain 2

3 Blood Brain Barrier the caveat Acute hypertonicity of plasma causes net movement of water out of the brain, while acute hypotonicity causes net movement of water into brain when marked, these effects can cause rapid fluid shifts in the brain. Thus, marked abnormalities in serum Na + or glucose should generally be corrected slowly. Disease disrupts BBB Blood Brain Barrier CVA, head trauma, infection, toxins (CRF), severe HPTN, seizure activity Disrupt BBB Increase access of drugs, toxins 3

4 Meninges of the Brain 3 membranes provide protection to brain and spinal cord 1. Dura mater 2. Arachnoid mater 3. Pia mater Essentially no barrier from CSF and brain Arachnoid villi Falx cerebri Cerebral Spinal Fluid (CSF) Major function is to protect brain and spinal cord against trauma Other functions of CSF: Regulate ECF environment of neurons Provide nutrition to neurons/neuroglia Carry products of metabolism (CO2) and neurotransmitters away from nerves 4

5 Cerebral Spinal Fluid (CSF) CSF is found within the ventricles of the brain, in the cisterns around the brain, and in the SAS surrounding the brain and spinal cord all theses chambers are connected to each other Normal CSF production = 21 ml/h (500 ml/day), yet total CSF volume = 150 ml Cerebral Spinal Fluid (CSF) 5

6 CSF Choroid plexuses of lateral ventricles Interventricular foramina of Monro Third ventricle Cerebral aqueduct of Sylvius Fourth ventricle Foramina of Luschka (2) Foramina of Magendi (1) Cisterna magna Most of the CSF is formed by choroid plexusesof the 4 cerebral ventricles (mainly the 2 lateral ventricles) After circulating, CSF is absorbed into venous sinuses by arachnoid villi or granulations returning CSF to circulation 6

7 Cerebral Spinal Fluid CSF compared with the plasma Isotonic Potassium Bicarbonate Glucose Essentially no protein Clear and colorless No blood cells Specific gravity = Intracranial Pressure (ICP) Normal ICP = < 10 mmhg S/S ICP: headache, N/V Cushing s Triad ( CNS ischemic response ) BP HR irregular respiration ICP is, by convention, measured in the subarachnoid space over the cerebral cortex or in the lateral ventricles 7

8 Intracranial Pressure The cranial vault is a rigid structure with a fixed volume, consisting of: Tissue (80%) Blood (12%) CSF (8%) Monroe-Kellie Doctrine any increase in one component must be offset by an equivalent decrease in another to prevent a rise in ICP. ICP is normally regulated by absorption of CSF into the arachnoid villi, which act as pressure valves that open when the ICP increases Intracranial Pressure Compensatory Mechanisms 1. Initial displacement of CSF from cranium spinal compartments 2. CSF absorption 3. CSF production 4. Displacement of cerebral blood volume Treatment Mannitol g/kg Loop diuretics (Lasix IV, mg/kg) Head-up 30 Control BP Hyperventilate Restrict fluids 8

9 Cerebral Perfusion Pressure (CPP) CPP = MAP -ICP Normal CPP = mmhg Moderate to severe increases in ICP (>30 mmhg) can significantly compromise the CPP and CBF, even in presence of normal MAP Cerebral Perfusion Pressure CPP = MAP -ICP If CVP > ICP, substitute CVP in equation Adequate CPP usually maintained with MAP > 60T CPP < 50 T = EEG slowing CPP < 25 T = irreversible damage 9

10 Cerebral Perfusion Pressure and Patient Position MAP at base of brain mmhg lower than arm Another 9 mmhg lower at top of brain e.g. MAP at arm = 90 mmhg; MAP at cerebral cortex = 65 mmhg 1 mmhg in MAP for every 1.25 cm above the heart Cerebral Dynamics - anesthesia Luxury perfusionis the combination of neuronal metabolic demand and CBF associated with volatile anesthetics These effects may be desirable during induced hypotension or cases that the risk of global ischemia Barbiturates and hyperventilation ( CO2) cause vasoconstriction in normal or healthy areas of the brain. Blood flow is shunted from healthy to diseased areas, a process called the Robin Hood effect or reverse steal or inverse steal 10

11 Cerebral Dynamics - anesthesia In contrast to their potentially beneficial effect during global ischemia (luxury perfusion) circulatory steal (intracerebral steal)is possible with volatile anesthetics in the setting of focal ischemia. Volatile agents (also hypercarbia, NTG, NTP) increase blood flow in normal areas of the brain, but not in ischemic areas, where arterioles already are maximally vasodilated (ischemic vasomotor paralysis). This may result in redistribution of blood flow away from ischemic to normal areas. Volatile Inhalational Agents Isoflurane Desflurane Sevoflurane Opioids IV Anesthetics Barbiturates Propofol Etomidate Ketamine all CBF and ICP all CMRO2 CO2 responsiveness preserved autoregulation impaired in dosedependent manner minimal effects on CMRO2, CBF, and ICP autoregulation preserved CO2 responsiveness preserved all or have minimal effects on ICP, except for Ketamine all or have minimal effects on CBF, except for Ketamine autoregulation preserved CO2 responsiveness preserved 11

12 Brain Metabolism CMRO2 CMRO2 = 50 ml/min; constitutes 20% of body s total O2 consumption The metabolic rate of the brain is 7X average BMR in body Most of the metabolism used to generate ATP for Na/K+ pumps; each time neuron conducts AP, RMP must be restored Seizures CMRO2 Obligate Requirement for O2 Neuronal activity has second-by-second requirement for O2 to generate sufficient ATP Brain Metabolism Glucose for brain energy Under nl conditions, glucose supplies almost all of brain s energy requirements exception starvation Brain accounts for 50-70% of the body s total glucose consumption mg/100 gm/m (about 150 gm/day) Acute, sustained hypoglycemia equally as devastating as hypoxia Special feature: transport of glucose into the neuron not dependent on insulin Paradoxically, hyperglycemia can exacerbate brain injury associated with global and focal ischemia accelerates cerebral acidoisis and cellular injury *** avoid dextrose containing solutions in normoglycemic patients with brain injury 12

13 Brain Protection Hypothermia Barbiturates Methylprednisolone Avoid hyperglycemia Maintain normocarbia Maintain O2 carrying capacity Maintain normal or slightly increased BP 13