Pathophysiology of Brain & Body - USSJJQ-20-3

1. Pathophysiology of Brain & Body - USSJJQ-20-3 Venous Excess: a new approach to cardiovascular control and its teaching • BAJ Reddi & RHS Carpenter • J App Physiol, August 2004 • Pathophysiology of Brain & Body Tutorial

2. p356 • Circularity of the circulation • CO  VR  CO  VR • Mixing of ‘cause & effect’ • Independent vs dependent variables • Arterial vs venous • Arterial ‘distributive’, venous ‘collective’ • Arterial Pressure as ‘error signal’ • AP reflects supply vs demand • ↑ demand  vasoldilation  ↓ TPR (+ ↓ vol)  ↓ AP • Baroreceptors ↑ HR and ↑ vasoconstriction • ↑ AP (classic –ve feedback, sustained by error sig) • Control via venous side less obvious • However, all agree that CO influenced by venous side of circulation

3. p357 • Venous Return • Units? Quantity vs flow? • How is it measured? • If it’s flow into heart, then it must = CO • If it’s flow anywhere in venous system then = CO • So what use is it to talk about VR controlling heart when it is a consequence of CO? • Starling (1912) • Isolated heart • ↑ ven ‘head’  ↑ RAP (distension)  ↑ SV  ↑ CO • ‘guarantees’ that what is delivered to heart is expelled • (But it’s easy to think it’s the ↑ flow (VR) that is driving the ↑ CO)

4. p357-8 • Seeing ↑ CO ‘obviously’ implies ↑ VR • ↑ VR came to be seen as the cause rather than a consequence of this effect • Confusing as CO and RAP ‘easily’ measured • VR not so (no such thing as a venousreturnometer) • AP = CO x TPR • Equivalent relationship on venous side?? • Eg VP = VR x Venous resistance?? • Strictly, ‘pressure’ is ‘pressure difference’ • Can ignore difference on arterial side (aortic P >> capillary) • But pressure difference is important on venous side • Pressure at ‘start’ (venules) similar to ‘end’ (RAP)

5. p358 • AP = CO x TPR • Implies correct causal relationship • Aaaaaaargh! – dependant!!! • Eg CO = AP / TPR gives wrong impression • For venous side, Guyton’s VR curves imply… • VR = (MSFP – RAP) / Venous resistance • VR a consequence of RAP (all others being =) • But is this correct? • In the experiments, VR was the controlled (independent) variable, and RAP was the measured (dependent) variable • As ↑ flow, RAP ↓ • Curves led to the view that ↓ RAP, by ↑ (MSFP – RAP), ‘sucked’ more blood in • In reality, ↑ CO  shift in blood to the arterial side • which leads to a ‘venous deficit’ ↓ RAP • ie importance of ‘capacity’ and ‘volume’ – hooray!

6. p359 • Fig 1 • Must be true in the steady-state • But when things are changing, the mismatch between inflow and outflow will affect RAP • Summary of confusion… • ↑ RAP  ↓ VR (Guyton curves) • ↑ RAP  ↑ CO (Starling’s Law) • Yet VR = CO !!

7. p359-60 • Capacitance • Simple haemodynamic equations use pressure, flow, and resistance • Tend to ignore volumes and capacity • Not that important on the arterial side • Dominant feature on venous side • So VR = (MSFP – RAP) / Venous resistance misleading • Resistance is not very important • Ievenoconstriction  ↑ RAP  ↑ CO • Volume/capacity effects, not resistance, dominates

8. p360 • ‘Venous Excess’ as error signal • Volume, not flow, controls RAP (and so CO) • Any mismatch between VR and CO represents an accumulating/reducing volume which will affect RAP (and so CO) • Basis for keeping VR = CO • Figs 1b and 1c appear contradictory • But 1b superimposed on ‘classic’ Guyton curve • ‘cause and effect’ wrong • Fig 1c implies proper causal mechanism • ↑ VAR  ↑ RAP ( ↑ CO )

9. p361 • Exercise • ↑ CO shift blood to the arterial side • So VE goes negative • So how is RAP maintained/enhanced? • By ↓ venous capacity • Sympathetic venoconstriction • ‘Crushing’ action of muscle contraction • Haemorrhage • ↓ venous volume • ↓ venous volume due to ↑ HR shifting blood to the arterial side • Venous deficit ↓ SV • Sympathetic stimulation helps reverse deficit

10. p362 • Volume vs pressure as SV regulator • Volume, via ‘stretch’ changes heart function/hormone release • Pressure changes are the consequence of volume changes, so volume is the primary stimulus • Volume changes • ↓ CO  ↓ VR • But while the direction may be the same, the magnitude may not • So a positive VE will help bolster a failing heart