For todays post I have taken a couple of undergraduate physiology textbooks off my shelf and done a little compare & contrast exercise in order to see where today’s received wisdom about cardiac output regulation and extracellular fluid dynamics comes from. Prof. Guyton passed away in 2003, so the posthumous 11th Edition of “Textbook of Medical Physiology” (2006) has to be his last word on the subject. More than 600 papers and 40 books place him amongst the most famous and influential of physiologists, but Guyton never gave credence to the steady-state Starling principle and unfortunately misinformed hundreds of thousands of students all over the world that “The lymphatic system represents an accessory route through which fluid can flow from the interstitial spaces into the blood”. He dismissed the glycocalyx as an inert layer of mucopolysaccharides adherent to the endothelial cell. The Second Edition of “An Introduction to Cardiovascular Physiology” (1995) shows us that a decade earlier Prof. Levick was teaching students at St George’s Hospital in London about the structure of the glycocalyx, the fibre matrix model of capillary permeability, and the fact, so essential to current critical care practice, that there is a vital extra-vascular circulation of fluid and protein:
“Lymph vessels return capillary ultrafiltrate and plasma proteins to the bloodstream at emptying points into the neck veins, and some fluid also returns to the blood in lymph nodes. This completes the extravascular circulation of fluid and protein and secures the homeostasis of tissue volume.”
The figure below will be well known to clinical practitioners and illustrates the lymphatic circulation;
Both Professors present the student with Guyton’s classic “venous return” analysis; but they differ in their interpretation. Prof. Guyton points to the demonstrated straight line relationship between venous return and central venous pressure, and hypothetically extrapolates it to a non-existent point where venous return = 0 and the corresponding value of CVP is given the grand name of systemic filling pressure (Psf). If it has a name, it has to exist, right? From a series of low, normal and high venous return vs CVP curves each hypothetically extrapolated to venous return = 0, he claims to prove “the effects on the venous return curve caused by increasing or decreasing Psf.”
The diagram above is Levick’s version; he calls the extrapolated and hypothetical CVP at which venous return = 0 the mean circulatory pressure MCP, but never mentions it again! Prof. Levick offers students a Caution in his Textbook 2e (1995). Ever the gentleman, he names no names but says:
“Venous return is the flow of blood into the right side of the heart, and it is driven by the pressure drop between the capillaries and central veins. In the intact circulation, venous return must equal cardiac output in the steady state because the circulation is a closed system of tubes: any inequality can only be transient. In general, it is better to avoid the notion that venous return “controls” cardiac output, because this is a circular (literally) and unhelpful viewpoint. In the steady state, venous return is the cardiac output, simply observed in veins rather than arteries. Venous return is thus directly dependent on cardiac output. Central venous pressure by contrast is an independent variable (it can be adjusted by venous tone) and can regulate the stroke volume. Venous return “controls” cardiac output only in the sense that transient inequalities between the two alter the CVP.”
Possibly frustrated that no one seems to be listening to him, Prof. Levick ups the intensity of the Caution in Textbook 5e (2009)
“CVP, not ‘venous return’, is the true regulator of stroke volume. Students (and some professionals) sometimes get into an awful muddle by trying to explain the the control of cardiac output in terms of venous return rather than filling pressure… Imagine a plot of cardiac output as a function of venous return; it would be a straight line of slope 1.0!”
After reading this post, does the Mississipi analysis float your boat, or are you Tooting for St Georges?
What is the fluidphysiology.org position? I think the most logical construct, and so the easiest to teach and learn, adopts Reddi & Carpenter’s venous excess concept driving the CVP which, as Prof. Levick insists, is the immediate determinant of stroke volume.
Post Scriptum: Professor John Hall, University of Mississipi Medical Centre, has taken Guyton’s Textbook to it’s 13th Edition now; not having access to it, I don’t know if the steady-state Starling principle has at last been taken up or if the Guyton analysis has been revised. I understand from mutual friends that Professor Levick is now retired and has no intention of giving us another Edition of his Textbook. Perhaps his publishers need to commission someone to continue his educational work.