Viva G4(ii)b

This viva tests Section G4(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the distribution of blood volume and flow in the various regional circulations and explain the factors that influence them, including autoregulation. These include, but not limited to, the cerebral and spinal cord, hepatic and splanchnic, coronary, renal and uteroplacental circulations."

Specifically, this viva is all about cerebral blood flow autoregulation.

Describe the blood supply of the brain.
  • Blood flow to the brain is about 50ml per 100g of tissue per minute,
  • or about 600-700ml/min in total for a standard 1400g brain,
  • or 12-14% of normal cardiac output. 
  • It is conveyed there mainly by the carotids, which supply about 85-75% of the total. The other 15-25% is vertebral arteries.

If you want to go full nerd, here is a granular diagram of how the blood flow is distributed

Blood flow distribution in the cerebral circulation

The DO2/VO2 ratio for the brain is normally about 3:1, i.e. the brain is supplied with

about three times as much oxygen as is required for its normal resting function.

What is meant by the term "cerebral perfusion pressure"?

Cerebral perfusion pressure = MAP - ICP

How does central venous pressure influence cerebral perfusion pressure?

Where ICP is lower than the CVP, the CVP is the determinant of cerebral perfusion pressure:

CPP = MAP - CVP

The effects of increasing the CVP from 0 to 30 mmHg will have the same functional effect as decreasing MAP from 60 to 30 mmHg: the CPP will drop in both cases, and cerebral blood flow will suffer

Is the cerebral arterial vascular resistance high, or low?
  • Cerebral vascular resistance is usually extremely low. 
  • The usually measured cerebral vascular resistance values are 0.3-1.4 Woods units (Jalan et al, 2001)
  • For comparison with other ortgans:
    • the vascular resistance of the kidney measures  2.8 WU,
    • the myocardium 7.9 WU,
    • abdominal skin about 200 WU  (Karlsson et al, 2003).
What factors affect cerebral vascular resistance?

In the most generic sense, they are the diameter of the cerebral vessels and the viscosity of the blood, all other parameters being essentially the same.

= (8 η) / πr4

where 

  • = length of the vessel
  • η = viscosity of the fluid
  • r = radius of the vessel

The specific physiological parameters that affect cerebral blood flow are discussed below

How does blood viscosity affect cerebral blood flow?
  • Generally blood viscosity is sufficiently stable that one can dismiss it from the list of factors that influence cerebral blood flow
  • Extremely increased viscosity, eg. in hyperviscosity syndromes such as HHS or multiple myeloma, can decrease cerebral blood flow.
  • Tripling the viscosity generally has the effect of halving the cerebral blood flow  (Lenz et al, 2007)
How is the blood flow of the brain regulated?
  • Cerebral metabolic demand is the main regulator of regional cerebral blood flow.
  • The specific regulatory factors are mainly metabolic byproducts and metabolic substrates:
    • Carbon dioxide concentration in the brain parenchyma
    • pH of the blood
    • Lactate
    • Potassium
    • Oxygen
  • When cerebral metabolic demand is high (substrate levels are low, metabolite levels are high), cerebral blood flow will be higher at any given perfusion pressure because cerebral vascular resistance will decrease.
  • where cerebral metabolic demand is stable and perfusion pressure is changing, the same mechanisms ensure that blood flow remains constant and matched to demand,

relationship of MAP, O2 and CO2 effects on cerebral blood flow

How does mean arterial pressure influence cerebral blood flow?

The candidate needs to be able to reproduce and label this diagram:

cerebral blood flow autoregulation

This relationship is highly variable among healthy human subjects.

What are the mechanisms by which cerebral autoregulation is achieved?

There are several:

  • Autonomic nervous system (sympathetic)
  • Endothelial regional mechanisms  dependent on nitric oxide, endothelium-dependent hyperpolarization factor (EDHF), the eicosanoids, and the endothelins
  • Myogenic autoregulation
  • Metabolic autoregulation
What is the effect of PaCO2 on cerebral blood flow?

CO2 increases cerebral blood flow by acting as a vasodilator:

  • Change of periarteriolar pH leads to a change in nitric oxide synthase activity;
  • Nitric oxide synthase catalyses intracellular cGMP production;
  • cGMP acts as a second messenger to affect a change in intracellular ionised calcium availability
  • The upshot of all this is a decreased cerebral vascular resistance
  • If the resistance is decreased but the pressure difference remains the same, the flow increases.
  • The increase in flow is by about 1-2ml/100g/min for every 1mmHg increase in CO(Raichle, Posner & Plum, 1970). Conversely, blood flow decreases as CO2 decreases. Obviously, this is undesirable if your brain is swollen and/or perfusion-compromised. Hence the neurointensivists' obsession with maintaining a stable (low-normal) CO2 in patients with various intracranial catastrophes.  
  • Hypocapnia does the opposite
  • The lower threshold for autoregulation does not appear to be affected
  • The effect has a plateau, i.e. beyond a certain CO2 level no further increase in cerebral blood flow will occur
  • Hypercapnia combined with hypoxia has a magnified effect on cerebral blood flow (i.e under hypoxic conditions, the effect of the same PaCO2 value will be greater)
How does PaCO2 influence cerebral blood flow autoregulation?

Beyond a CO2 of 55-60 mmHg, autoregulation becomes impaired:

rough relationship of cerebral blood flow autoregulation and PaCO2

How does PaCO2 influence cerebral blood flow autoregulation?

Cerebral blood flow is relatively stable over a wide range of oxygen levels.

relationship of cerebral blood flow and PaO2

  • Only at around 50 mmHg PaO2 does the cerebral vascular resistance finally drop.
  • It then continues to decrease almost exponentially
  • Experimental animals had a 700% increase in CBF at PaO2 of around 25 mmHg, corresponding to sats of 50%.
What pathologies can affect cerebral blood flow autoregulation?

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