Introduction to Cerebral Physiology 

The Brain 

The brain is the major constituent of the cranial vault. It is encased by the rigid skull and bathed in cerebrospinal fluid. In order to have adequate nerve function the brain requires a blood-brain barrier that excludes certain substances from the nervous system. The blood brain barrier is characterized by the presence of tight endothelial junctions (zona occludens), absence of vessel fenestrations, and close proximity of the astrocytes to the blood vessels. In pathologic conditions, the blood brain barrier becomes disrupted, allowing entrance of pathogens in the the central nervous system as well as penetration of pharmacologic agents. The presence of the blood brain barrier eliminates the need for lymphatic drainage from the brain. Disruption of the barrier leads to increase in extracellular water (vasogenic edema) or intracellular water (cytotoxic edema) 

The Cerebrospinal Fluid

The craniospinal axis contains about 150ml of CSF at any given time of which 75 ml are in the brain. Normally CSF is produced at a constant rate of approximately 0.5 ml / min as a result of active secretion mediated by Na / K ATPase and by carbonic anhydrase. Most of the CSF is produced by the lateral ventricles and the 4th ventricle, and reabsorbed into the venous circulation by mainly via the arachnoid villa situated within the dural walls of the sagittal and sigmoid sinuses. Under pathological conditions this gradient may be altered, and in the face of increased venous pressure CSF reabsorption may be impaired. In addition, infectious and hemorrhagic diseases affecting the ventricular system may lead to impaired reabsorption of CSF. 

The CSF has several crucial functions; it helps maintain a constant supply of glucose and provides for a stable environment for neurotransmitters to function. It protects the brain by providing a cushion for it and reducing its inertia when the head is moved rapidly. 

The Blood

The brain receives a constant blood supply via the paired carotid arteries anteriorly, and the paired vertebral arteries posteriorly. Under normal conditions there is approximately 150 ml of blood in the skull, with most of the blood (about 100 ml) bein in the venous system. Although the cerebral blood volume is relatively small, the cerebral blood is significantly high considering the size of the brain compared to other organs. The brain receives 25% of the cardiac output even though it is only 2% of the body's weight. IN pathologic conditions the cerebral blood volume (CBV) may be increased and therapeutic efforts aimed at reducing the CBV may reduce intracranial pressure. 

When impaired cerebral blood flow reaches critical levels it triggers a series of biochemical events termed collectively the "ischemic cascade". Briefly, ischemia leads to cellular depolarization, calcium influx, glutamate release, acidosis, activation of lipases, proteases, and nucleases which act in concert to aggravate ischemic injury and ultimately cause neuronal death. This injury may be aggravated by a series of factors often present in the ICU environment such as hypotension, hypo/hyperglycemia, and fever. For such reasons, controlling glucose and fever are common practices in the NeuroICU. Cerebral blood flow is closely linked to metabolic demands and CBF increases when metabolic demands increase (fever, seizures) and decreases when metabolic demands decrease (sedation, deep coma). Therapeutic efforts in the ICU are aimed at achieving a balance between cerebral metabolic needs and energy supply. Clinicians increase cerebral perfusion pressure, oxygen content, and Hb levels in an effort to improve supply, and treat intracranial pressure, fever, and seizures in an effort to reduce demand.

The main determinants of CBF in the brain are systemic blood pressure, cerebral metabolic rate, and PaCO2. As outlined before, CBF is determined partially by the cerebral perfusion pressure, which is the difference between the mean arterial pressure and the intracranial pressure (ICP) or the jugular venous pressure (whichever is highest). Since in most pathologic circumstances the ICP is higher than the jugular venous pressure, this value is usually not considered in this equation. In normal subjects, CBF falls when CPP is less than 50-60mm Hg. Therefore increases in ICP can lead to reductions in CBF by compromising CPP (CPP = MAP - ICP). On the other hand, increases in ICP with corresponding increases in MAP (pharmacologically or spontaneously) may not affect CPP and CBF. In addition, CBF is also controlled by PaCO2 and to a lesser degree by PaO2. PaCO2 affects vessel caliber and CBF over a wide range of values (20 - 60 mmHg). The relation between PaCO2 and CBF is almost linear with dramatic increases in CBF seen when CO2 rises with hypoventilation, and marked decreases in CBF seen when PaCO2 declines with hyperventilation. More precisely, the perivascular pH (reflected by serum PaCO2) influences the tone of the vessels within the brain, with low CO2 leading to vasoconstriction, and elevated CO2 leading to vasodilation. Since bicarbonate does not diffuse freely into the perivascular space in the brain, it does not influence cerebral blood vessel caliber. NeuroICU clinicians use this physiologic property to their advantage by manipulating CO2 levels using mechanical ventilation to reduce intracranial pressure.

The effects of CO2 on CBF are short-lived as the brain quickly compensates for changes in PaCO2 by transcellular flow of hydrogen and bicarbonate (local) and by lactate production. Such compensation occurs within minutes, and the effect of hyperventilation is usually lost within 4 hrs. In patients with head trauma, hyperventilation has a complex effect on CBF and ICP, with ICP returning to baseline before CBF has normalized. When used as a therapeutic maneuver, hyperventilation should be used only transiently while other therapeutic measures to control ICP are instituted. 

Like most other organs in the body, the brain has a measurable pressure that has clinical importance only in diseased states. The Monroe-Kellie doctrine states that the skull is a rigid container enclosing the brain, the cerebral blood,, and the spinal fluid. Since the contents of the cranial vault are relatively incompressible, any additional volume added to the vault will lead to increases in pressure. Normal intracranial pressure is less than 15mm Hg with minor cyclical variations associated with coughing, valsalva, etc. The ICP is considered to be pathologically elevated when sustained elevations > 20 mm Hg occur. Although the brain has some mechanisms to mitigate rises in ICP, they are usually insufficient tp prevent ICP spikes. the main compensatory mechanisms are the displacement of cerebrospinal fluid out of the ventricular system (mainly down the spinal canal) and the compression of the cerebral blood vessels (mainly veins). As mentioned previously, both mechanisms are weak attempts at compensating increases in volume within the cranial vault, and in most acute cases they are ineffective.