Integrated Circulatory Physiology --- A brief glance!

Why do we have a circulatory system?

It is absurdly obvious that complex multicellular organisms are lumbered with a circulatory system (and all its accompanying ills) because it must be there to provide nutrients and oxygen to distant cells, and to remove waste products. Extending our trite teleological argument a bit, it makes absolutely no sense for the normal heart to be anything other than a subservient pump, pumping to meet the needs of the periphery! Thus we must look to the periphery, and the demands of the organs, in order to establish the normal regulatory mechanisms that govern the output of the heart. A vast amount of experimental evidence supports this contention (See for example Guyton et al.). To understand circulatory physiology we must first appreciate that we are looking at a system. We cannot hope to grasp what is going on if we simply observe isolated components without consideration of the whole. Unfortunately there are literally hundreds of factors that influence circulatory function. Even complex computer simulations hardly come up to scratch in modelling the cardiovascular system.

We have already looked at myocardial function and its regulation - we must now consider this in the context of the whole system and how it functions. We should not regard the roles of the periphery and of the heart as antagonistic, but rather as complementary. Also bear in mind that the heart has finite resources - in circumstances where it is grossly overloaded or diseased, it may well become a potent limiting factor in circulatory performance.

How much can the heart pump?

Although resting cardiac output is about five litres per minute, we know that the normal heart can nearly triple this to about 12-15 l/min. Guyton has described this discrepancy as the difference between the actual output and the permissible amount of output. Why the difference? It is clear that there must be some restraining factor, "holding the heart back", as it were. Physiologists have traditionally talked about "venous return", and given long lists of factors that enhance or diminish this magical quantity. Let's consider the simplest possible view of the circulation:
For the time we will concentrate on the periphery (the systemic circulation). This has two limbs, arterial and venous. It is clear that each limb must have a resistance and a capacitance. We define the resistance in an analogous way to the definition of resistance in electrical circuits - R=V/I - we observe the flow obtained when we apply a given driving pressure across the section we are examining, and the resistance is the ratio of the two:

resistance = pressure / flow

In a similar analogy, we can define the capacitance as the change in volume per unit pressure.

capacitance = V / P

Armed with these simple definitions, let's consider what will happen if we vary them (again, only considering the systemic section, moving blood from the left heart to the right heart). Let us pretend for a moment that all the normal complex mechanisms regulating the circulation are paralysed. The following are intuitively clear:

In our simple model, we have already found two potent factors that regulate flow through the system - alterations in resistance and in "capacitance". It is clear that we can alter the effective "capacitance" in two ways - lowering the blood volume, or increasing the true capacitance of the system. Note that changes in resistance and/or capacitance can be made to both the venous and arterial limbs.

"Venous return"

It is clear from the above that there must be a driving pressure that corresponds to each rate of flow of blood through the circulation. If this driving pressure is insufficient, or the resistance to flow is immense, then "venous return" will diminish. If the driving pressure is great and resistance is low, then flow will correspondingly increase.

What effect will this have on the heart? From our previous discussion of myocardial function, we know that generally the more preload is applied to the heart, the more vigorously it will pump, and the greater the volume that will be ejected (afterload remaining constant). This is the simplest way we can integrate venous return and cardiac output. The peripheral tissues, and indeed all factors that control myocardial function have three powerful mechanisms for controlling cardiac output - they could modulate peripheral resistance, peripheral capacitance, or intravascular volume. It is the delicate interplay between these factors that governs cardiovascular function!

Clearly, certain portions of the circulation may be more amenable to certain modifications - the venous capacitance is far greater than arterial, so if we wish to alter capacitance it is 'logical' to alter it on the venous limb; likewise the principle source of resistance in the systemic circulation is in the arterioles, so it is there that a change in resistance will usually have maximal effect.

It is also apparent that should we artificially oppose the pressure driving blood towards the heart, that at a certain level of pressure, flow towards the heart will cease. Classically, this concept has been made very confusing, with the driving force being called "vis a tergo", and almost any opposing force being termed "vis a fronte".

Guyton has fortunately examined factors governing venous return in immense detail. He has even provided quantitation, where previously there was only confusion. Before we examine his work, however, we need to establish one more point..

A Physiological Reference Point

Clearly, if we are to measure pressures within the cardiovascular system, we need some sort of reference point. Small variations in pressure (particularly in the pressure governing venous return) can have enormous consequences on flow. It also makes sense to choose a "denominator" or reference point that is minimally affected by changes in the posture of the animal or man that we are investigating. Experimenting on a large number of dogs, Guyton found a consistent physiological pressure reference point at which the right atrial pressure didn't vary more than 1mmHg - the point was at the opening of the tricuspid valve into the right ventricle. His explanation as to why pressure here varies so little is instructive - if the pressure at this point rises, right ventricular filling increases, output is enhanced by the normal Starling mechanism, and the pressure will then drop. The converse also holds.

{ As an aside, in dogs, the physiological pressure reference point is midway between the sides of the chest transversely, 61.4% of the thickest part of the chest anterior to the back, and 76.7% of the distance from the suprasternal notch moving down to the tip of the xiphoid. What are the corresponding coordinates in man? }

Impeding Venous Return

If we arrange an experimental setup where we can increase right atrial pressure(RAP), hence impeding venous return, what will happen? The obvious answer is that all sorts of reflexes will come into play, perturbing our results. Guyton has extensively investigated a model where vascular tone is maintained at a normal level in the face of total abolition of reflexes by high spinal anaesthesia. He has demonstrated the surprising result that:

For every 1mmHg rise in RAP, venous return decreases 14%

What this means practically is that a pressure of 7mmHg is sufficient to entirely stop venous return, provided no compensatory reflexes are allowed to come into play!


  1. Guyton AC, Jones CE & Coleman TG. 1973 Circulatory Physiology: Cardiac OUtput and its Regulation. 2ed WB Saunders Co.