Cerebral blood flow (CBF)

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oxygen and glucose utilization

  1. Normal blood flow to the brain comes predominantly from the carotid arteries (80%) and only partially from the vertebral arteries (20%)
    1. brain receives 18% of cardiac output and 20% of oxygen supply
  2. Local CBF is very heterogenous and is determined mainly by neuronal activity (within 1 second of activation of that area and limited to less that 250 micrometers around the area of activation); normally there is coupling between the regional cerebral metabolic demand for oxygen and glucose generated by local neuronal activity and the volume of blood flowing through that tissue
  3. CBF = Cerebral perfusion pressure (CPP)/cerebrovascular resistance (CVR) = approximately 50 mL/100g tissue per minute in normal adult brain
    1. CPP = mean arterial pressure (MAP) – intracranial pressure (ICP); CPP should be kept above 60 mm Hg
    2. CVR is inversely proportional to blood viscocity (hematocrit of 30-32 is optimal balance between oxygen carrying capacity and viscocity) and proportional to the fourth power of the radius of the vessel (Poiseuille’sequation)
      1. This is thought to be determined by the concentration of endothelium-derived relaxing factor and nitric oxide (stimulation of guanylate cyclase by raised level of cGMP releasing nitric oxide and resulting in phosphorylation and muscle relaxation)
      2. Autoregulation is manifest as the lack of major fluctuation in CBF despite changes in mean arterial blood pressure between 60 and 150 mmHg
      3. CBF will increase precipitously with a PaO2 of 50 mm Hg
      4. Autoregulation can be affected by chronic hypertension which results in relative hypoperfusion at higher blood pressures
      5. All attempts are made to maintain CBF despite changes in CPP; initially CVR drops; as CPP drops further the oxygen extraction fraction increases to maintain oxygen metabolism (CMRO2); when the maximum oxygen extraction is reached then CMRO2 begins to decrease
        1. Functional impairment occurs at around 23 ml/100g per minute
        2. Evoked potential and synaptic transmission disappear at around 15 mL/100g
        3. cellular integrity is lost at around 10 mL/100g per minute
        4. Duration of ischemia is also important (longer than 2 hours at below 12 mL/100g per minute is probably irreversible)
  4. There is a flux of glucose back and forth across the blood brain barrier, only 25% of the glucose presented to the brain is extracted and half of that amount is returned to the blood
    1. apart from glucose, the only other sugar the brain utilizes directly is mannose which crosses the blood brain barrier, is converted to mannose-6-phophate and then fructose-6-phosphate replacing glucose in the glycolytic pathway
    2. glycolysis in the brain is stimulated by ammonia, potassium, cAMP and phosphate and is inhibited by ATP
  5. Under normal conditions about 36% of the available oxygen is extracted from the blood
    1. there is some relationship between these numbers and a relative reduction in CBF (i.e. the brain seems to tolerate about a 75% reduction in CBF and still maintain function)
    2. brain spends much of its energy maintaining ion gradients; there is only about a 25% reduction in CBF when a person is asleep indicating that maintenance of ion gradients (a function performed even during sleep) is consuming much of the energy
    3. brain consumes about 75 liters of oxygen and 115g of glucose each day
      1. glucose gets across the blood-brain barrier by both facilitated transfer and simple diffusion
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