Question 20

College Answer

Overall, this question was poorly answered with a high failure rate. A good answer gave a normal value, iterated that CBF is held relatively constant by autoregulation, and proceeded to divide factors affecting CBF into categories with an explanation/description of each. Those factors with the greatest influence were expected to have more accompanying information (e.g., pressure/myogenic autoregulation, metabolic). Systemic factors such as MAP, O2, CO2 were expected to be mentioned with detail of the impact (i.e., key values, relationships demonstrated with a description and/or labelled graph). Local factors within the brain such as H+ concentration/pH, metabolic activity (including the impact of temperature, inclusion of mediators, regional variation based on activity & grey versus white matter) were also expected to be mentioned. Few answers mentioned impact of pH change independently of CO2. Few answers mentioned how CO2 changes the pH of CSF and that over time, this impact is buffered/reduces. The role of the sympathetic nervous system was required to be mentioned although not explored in detail (although many answers overstated the importance of the SNS on CBF or gave a simplistic concept such as increased SNS activity increases CBF). Many answers focussed on descriptions of the Monro-Kelly doctrine and ICP to the exclusion of the aforementioned factors or included detail on factors influencing MAP which were not required (and irrelevant when within the autoregulation range). Many answers were simplistic: e.g., increase MAP increase CPP therefore increase CBF, or by stating CO2/O2 without mentioning a relationship or the limits/patterns of the relationship. Many answers failed to separate the effect of systemic PaO2 and PaCO2 from metabolic autoregulation.

Discussion

• Cerebral blood flow is supplied by the carotid (70% and vertebral (30% arteries)
• It is usually 50ml/100g/min, or 14% on normal cardiac output
• It is described by the Ohm equation,  Q = (P_a- P_v) / R, where
  • (P_a- P_v)  is the cerebral perfusion pressure (CPP)
  • R is the cerbral vascular resistance 
• Cerebral perfusion pressure = MAP - (ICP or CVP, whichever is higher)
  • The higher the ICP (or CVP), the lower the CPP, if the MAP remains stable
• Cerebral resistance (R)  = (8 l η) / πr⁴, where
  • l = length of the vessel
  • η = viscosity of the blood
  • r = radius of the cerebral vessels, which is the main variable susceptible to regulation
• Cerebral autoregulation is a homeostatic process that regulates and maintains cerebral blood flow (CBF) constant and matched to cerebral metabolic demand across a range of blood pressures.
• It is affected by:
  • PaCO₂: increased PaCO₂ leads to increased CBF 
    • At a PaCO₂ of around 70 mmHg, the CBF is basically doubled (Kety & Schmidt, 1947) 
  • PaO₂:  PaO₂ falling below 50 mmHg leads to exponentially increased CBF.
    • At a PaO₂ of around 20 mmHg, CBF may increase up to 700% (Jóhannsson and Siesjö, 1975),
  • MAP: CBF is stable over a range of MAP between 50 and 150 mmHg.
    • As MAP decreases below around 60 mmHg, CBF cannot be maintained
    • As MAP increases beyond around 150 mmHg, cerebral autoregulation fails and CBF increases in proportion to the increase in pressure 
• These relationships can be described graphically:
  

Harper, A. MURRAY. "Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex." Journal of neurology, neurosurgery, and psychiatry 29.5 (1966): 398.

Phillips, Stephen J., and Jack P. Whisnant. "Hypertension and the brain."Archives of internal medicine 152.5 (1992): 938-945.

Paulson, O. B., S. Strandgaard, and L. Edvinsson. "Cerebral autoregulation." Cerebrovascular and brain metabolism reviews 2.2 (1989): 161-192.

Busija, David W., and Donald D. Heistad. Factors involved in the physiological regulation of the cerebral circulation. Springer Berlin Heidelberg, 1984.

Kety, Seymour S., and Carl F. Schmidt. "The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men." The Journal of clinical investigation 27.4 (1948): 484-492.

Jóhannsson, Halldór, and Bo K. Siesjö. "Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia." Acta physiologica Scandinavica 93.2 (1975): 269-276.