Cerebral Circulation — Blood Flow Control

Cerebral Blood Flow

• CBF = CPP / CVR (Cerebral Perfusion Pressure / Cerebral Vascular Resistance)
• CBF 15% resting CO → ~750ml/min or 50ml/100g brain tissue/min
  • Gray Matter: 75–80 mL/100 g/min – Significantly higher due to the high metabolic activity and dense synaptic connections
  • White Matter: 20–30 mL/100 g/min
• Abnormal CBF
  • CBF<50ml/100g/min → cellular acidosis
  • CBF<40ml/100g/min → impaired protein synthesis
  • CBF <30ml/100g/min → cellular oedema
  • CBF <20ml/100g/min → failure of cell membrane ion pumps, loss of transmembrane electrochemical gradients
  • CBF <10ml/100g/min → cell death

Determinants of CBF

• CPP
  • Net pressure gradient driving blood flow through the cerebral circulation
  • CPP = MAP – ICP
    • MAP = CO x SVR; CO = HR x SV; SVR = MAP / CO
    • ICP dependent on: brain, blood, CSF
• CVR

Regulated by 4 primary factors:

• Cerebral metabolism
  • flow-metabolism coupling: ­
    ↑ metabolic demand → ↑ CBF + substrate delivery
  • Controlled by vasoactive metabolic mediators:
    H+ ions, K, CO2, adenosine, glycolytic intermediates, NO
• CO₂ and O₂
  • CO₂
    • At normotension: relationship between PaCO₂ and CBF = almost linear
    • ↑ ­PaCO₂ → cerebral arteriolar vasodilation → ↓ CVR + ­↑ CBF
      • 2~4% increase for every 1mmHg increase in CO2
    • ↓ PaCO₂ → cerebral arteriolar vasoconstriction → ­↑ CVR + ↓ CBF
    • Initial stimulus = ↓ brain ECF pH
    • Effects regulated by: NO, prostanoids, K channels, intracellular [Ca²⁺]
  • PaO2
    • little effect at normal PaO₂
    • PaO₂ <60mmHg → cerebral arteriolar vasodilation → ­­↑ CBF
    • Mechanism: hypoxia acts on →
      • cerebral tissue to promote release of adenosine → cerebal vasodilation
      • cerebrovascular smooth muscle → hyperpolarisation → ↓ Ca²⁺ uptake → vasodilation
• Autoregulation
  • Constant across CPP 50-150mmHg
    • CPP >150mmHg: CBF µ CPP
    • CPP <50mmHg: CBF <50ml/100g brain tissue/min → ischaemia
  • Stimulus to autoregulation = CPP (not MAP)
  • autoregulation curve R shifted in HTN; L in neonates
  • Mechanism:
    • Myogenic mechanism: arterioles vasoconstrict in response to ↑ ­wall tension + vasodilate in response to ↓ wall tension → ↓ or ↑­ CVR
    • May involve adenosine
    • Can be impaired in SAH, tumour, stroke, head injury
• Neurohumeral factors
  • Relative lack of humoral + autonomic control on normal cerebrovascular tone
  • Main action of SY nerves = vasoconstriction
• Other factors
  • Blood viscosity: directly related to HCt; ↓ viscosity → ↑ ­CBF as per Hagen-Poiseuille law
  • Temperature: ↓ CMRO₂ by 7% for each ↓ 1°C in temp
  • Drugs
    • E.g. barbiturates ↓ cerebral metabolism
    • Volatile agents → ↓ tension cerebral vascular smooth muscle → vasodilation + ­CBF

Kerr 2018

Answer by Kerr