How does blood return from the feet back to the heart?

First, some general advice:It is not uncommon for medical interviews, particularly at Oxbridge, to test the interviewee's ability to think laterally, creatively or "outside of the box." When presented with an initially bizarre sounding question, it is important not to panic in the face of uncertainty, but to calmly collect your thoughts in a sequential manner and identify the crux of the question asked. AnswerThe heart is located in the superior half of the body, in the thorax. In terms of physics, this is an efficient location in the upright human, as it means that the heart is able to pump arterial blood to the extremities using relatively little energy, as the work done against gravity (for blood destined for the head/neck via the carotid arteries) is relatively low.  This is a perfectly economical system for delivering arterial blood, and is crucial for adequate cerebral perfusion at a pressure low enough so as to not cause vascular trauma. But, therein lies the problem for venous return - how does the blood reaching our lowest extremities somehow combat gravity and arrive once more at the heart? The first consideration one might have is that of the conservation of total mechanical energy (ME), assuming no energy losses. This would tell us that for a decrease in gravitational potential energy (GPE) upon descent of blood to the feet, there would be a compensatory increase in kinetic energy (KE), and in a complete series circuit, this could be reconverted to KE during its ascent, thus preserving total ME. Unfortunately, this idealised system is not applicable in our circulatory system - the velocity of blood actually slows down as it passes from the delivery vessels (arteries) to the resistance and exchange vessels (capillaries), as the total cross sectional area is greater for these smaller vessels arranged in parallel. Functionally, this increases the time available for diffusive exchange of metabolites. This is a reasonable starting point for the discussion. How then does the body achieve adequate venous return to match cardiac output?In a nutshell, one of the answers comes from consideration of the phenomenon of orthostatic intolerance. The classic example of this is that of the soldier standing motionless on parade and suddenly faints. In a patient in vertical position, venous pooling occurs in the leg vessels due to gravity, which can lead to a 20% loss of circulating volume and a relative hypovolaemia. If the individual is then also immobile, there will be no muscle pump to provide venous return, with a reduction in cerebral perfusion leading to cerebral hypoxia. When the individual faints and assumes a horizontal position, there is an improvement in venous return and immediate recovery of consciousness. Hence, the muscle pump is an essential return mechanism for venous blood, and a fallen soldier should in this circumstance not be helped back up!For bonus points, it is worth appreciating the soleus muscle, one of the three superficial muscles in the posterior compartment of the leg. This is a particularly important postural/anti-gravity muscle, as it is a slow twitch muscle that is capable of sustained contraction as it is resistant to fatigue, which enables our posture to be maintained. Furthermore, it possesses crucial function as a muscle pump, as it contains large venous sinuses which fill with blood when we are upright; upon contraction of the muscle, venous return to the heart is therefore facilitated. Without this action, postural hypotension would be a recurrent problem, and would be accompanied by dizziness, fatigue and varicose veins – this is evident in those with atrophy of the muscle, for example as a result of untreated compartment syndrome (which is of considerable risk in the leg due to the thick fascia overlying the muscles).But there is another, more subtle mechanism reinforcing venous return - the respiratory pump. Fluids generally flow down pressure gradients, a corollary of Darcy's law. Now suppose we could momentarily decrease the pressure in the right atrium - this would then set up a pressure gradient for venous blood to flow back up to the heart. Pressures in the right atrium and thoracic vena cava are very dependent on intrapleural pressure (P_pl ) - the pressure within the thoracic space between the organs (e.g. lungs/heart/vena cava) and the chest wall. During inspiration, the chest wall expands and the diaphragm descends, making the P_pl become more negative, which leads to expansion of the lungs, cardiac chambers and the thoracic venae cavae. This expansion causes the intravascular and intracardiac pressures to fall due to the inverse pressure-volume relationship (described by Boyle's Law). Because the pressure inside the cardiac chambers falls less than the P_pl, the transmural pressure (pressure inside the heart chamber minus the P_pl) increases, which leads to cardiac chamber expansion and an increase in cardiac preload (the end diastolic volume) and stroke volume by the Frank-Starling mechanism. Furthermore, as right atrial pressure falls during inspiration, the pressure gradient for venous return to the right ventricle increases, thereby facilitating the return of blood from the feet to the heart.Something to ponder: ExtensionWith the above explanation in mind, compare and contrast it with the possible physiological effects experienced by a human who is suspended upside-down for a prolonged period of time... How might their body respond differently?