Viva G4(ii)a

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 takes on some of the first half of this syllabus item.

What is the total circulating blood volume?

The total blood volume can be estimated as roughly 7% of the total body weight, or about 5L for a normal 70kg adult.

It can also be calculated from predictive equations using a patient's sex, height (h) and weight (w):

The Nadler equation:

For males, blood volume = (0.3669 × h³) + (0.03219 × w) + 0.6041

For females, blood volume = (0.3561 × h³) + (0.03308 × w) +0.1833

The Lemmens-Bernstein-Brodsky formula:

For obese patients, blood volume = 70 / (square root of (BMI/22))

How is the blood volume distributed in the circulation?

Unevenly. The arterial circulation has the least, and the venous the most.

• Pulmonary circulation
  • 500ml, varying with respiration
  • Of this, about 20-25% (100-125ml) is in the pulmonary arteries, and the rest is in pulmonary veins (Fishman, 1966).
• Systemic circulation
  • 4500ml in total
  • Of this, most (around 60%, 2700ml) is in the venous capacitance vessels, where
    • 40% (1800ml) is in the small veins
    • 20% (900ml) is in the central veins 
  • Of the rest,  
    • 9% (about 405ml) is in the cardiac chambers
    • 6% (about 270ml) is in the aorta and large arteries
    • 10% (about 450ml) is in the arterioles
    • 5% (about 225ml) is in the capillaries

If one were asked to describe where, at any given time, the blood in their body is, one could do worse than refer to the ICRP Publication 89 (2002), which lists all manner of physiological data required to calculate radiation risk. The time-poor reader is directed to page 140

How is blood volume distributed among organs?

Again, unevenly:

• Skeletal muscle: 14% (700ml)
• Lung: 10.5% (525ml)
• Liver: 10% (500ml)
• Bones: 7% (350ml)
• Stomach and intestine: 7% (350ml)
• Fatty tissue: 5% (250ml)
• Skin: 3% (150ml)
• Kidneys: 2% (100ml)
• Brain: 1.2% (60ml)

Again the ICRP Publication 89 (2002) is an excellent resource for this, and the interested reader is redirected to their table, which contains much more information than what is summarised in the list above. One could also point out that men and women vary with respect to their regional blood volume distribution.

Also, if you want to get picky, the liver actually gets about 25% of the total cardiac output (1200ml/min or so), because 70% of hepatic blood flow comes from the portal vein. 

How is the cardiac output distributed among organs and tissues?

The total cardiac output, which is approximately 5000ml/min in the average 70kg adult, is distributed in the following way:

• Lung: 100% (5000ml/min)
• Kidneys: 19% (950ml/min)
• Skeletal muscle: 17% (850ml/min)
• Stomach and intestine: 15% (750ml/min)
• Brain: 12% (600ml/min)
• Coronary arteries: 4% (450ml/min)
• Liver: 6.5% (325ml/min)
• Skin: 5% (250ml/min)

These values also come from the ICRP Publication 89 (2002). The reader is reminded that measurements collected by different authors at different times and in different subjects will naturally differ, which gives rise to discrepancies between textbooks, and to considerable internal inconsistency within Deranged Physiology, often alongside the authors' own rants about his frustration with these inconsistencies.

What is meant by "autoregulation of blood flow"?

"The tendency for blood flow to remain constant despite changes in arterial perfusion pressure" - Johnson, 1986

At which level of the circulation is this autoregualtion coordinated?

The small arteries and arterioles are the main site of autoregulation.

What are the mechanisms by which arterioles regulate their blood flow?

• Myogenic mechanisms
  • This is an intrinsic property of all vascular smooth muscle
  • Vessel wall stretch produces smooth muscle cell depolarisation
  • Depolarisation opens voltage-gated calcium channels
  • Calcium influx produces vasoconstriction by myosin light chain phosphorylation
• Metabolic mechanisms
  • Blood flow increases in response to increased tissue demand, eg. in exercising skeletal muscle
  • This is attributed to the release of metabolic byproducts with vasodilating properties
  • Potential mediators include potassium, hydrogen peroxide, lactate, hydrogen ions (pH) and carbon dioxide
• Flow or shear-associated regulation 
  • This is the phenomenon of proximal vasodilation in response to distal vasodilation.
  • This shear stress promotes the release of various vasodilatory mediators from the affected endothelium and produces vasodilation of the larger proximal arteriole.
• Conducted vasomotor responses
  • Regional control of one region by the vasomotor events of another neighbouring region.
  • Mediated by conduction of cell-to-cell signals from a small arteriole upstream to a larger arteriole

What is the mechanism of the myogenic arteriolar autoregulation?

• Increased blood flow creates increased wall stretch
• Wall stretch is sensed by smooth muscle in the vessel wall, which depolarise
• The depolarization, in turn, opens voltage-gated calcium channels, and these channels allow extracellular calcium to enter the cell.
• This creates a reflexive constriction response
• The resulting constriction produces an increase in resistance and therefore restores the flow to its original level
• Extracellular calcium is essential to this mechanism, and in the presence of hypocalcemia, it is blunted or abolished.

These vasomotor responses can be conducted along smooth muscle along  gap junctions. It is relevant, because blocking gap junction transmission seems to severely impede the normal exercise-induced hyperemia of skeletal muscle.

What is the mechanism of the myogenic arteriolar autoregulation?

Various substances produced in the tissue act as regional vasodilators:

• Carbon dioxide
• Lactate
• Potassium ions
• Adenosine
• ATP (released from hypoxic red blood cells)
• Nitric oxide
• Carbon monoxide
• Hydrogen sulfide
• Hydrogen peroxide
• Hydrogen ions (i.e. change in pH)

These are  largely substances which are generated in the course of metabolism, especially anaerobic metabolism, or tissue injury.  This autoregulatory mechanism is occasionally referred to as "active hyperemia" or "functional hyperemia".

What is shear-associated autoregulation?

Flow or shear-associated regulation is the phenomenon of proximal vasodilation in response to distal vasodilation.

• Local vasodilation in small distal arterioles results in increased flow to that specific little chunk of tissue.
• As a result, the larger proximal arteriole feeding that chunk of tissue experiences an increase in flow.
• This increase in flow produces increased shear stress on the walls of the larger proximal arteriole.
• This shear stress promotes the release of various vasodilatory mediators from the affected endothelium and produces vasodilation of the larger proximal arteriole.
• This is a slow response, taking 30-40 seconds to develop (Clifford, 2011).
• The mediators released from the endothelium include nitric oxide, prostacyclin and EDHF (Endothelium-Derived Hyperpolarizing Factor