2011 – Updating my Lecture for The Royal College of Anaesthetists FRCA Revision Course, and wondering how to explain the fact that I can manage critically ill patients with serum albumin so low that the lab have to reanalyse the samples, yet there is no oedema and the circulation of blood is quite adequate. I come across the paper that made me cry Eureka!
J. Rodney Levick, C. Charles Michel. MICROVASCULAR FLUID EXCHANGE AND THE REVISED STARLING PRINCIPLE. Cardiovascular Research, Volume 87, Issue 2, 15 July 2010, Pages 198–210.
“Microvascular fluid exchange (flow Jv) underlies plasma/ interstitial fluid (ISF) balance and oedematous swelling.”
“Sum-of-forces evidence and direct observations show that microvascular absorption is transient in most tissues; slight filtration prevails in the steady state, even in venules. This is due in part to the inverse relation between filtration rate and ISF plasma protein concentration; ISF colloid osmotic pressure (COP) rises as Jv falls.”
“The low rate of filtration and lymph formation in most tissues can be explained by standing plasma protein gradients within the intercellular cleft of continuous capillaries (glycocalyx model) and around fenestrations. Narrow breaks in the junctional strands of the cleft create high local outward fluid velocities, which cause a disequilibrium between the subglycocalyx space COP and ISF COP.”
I borrow a copy of Levick’s Introduction to Cardiovascular Physiology, and in Chapters 9-11 I discover an account of the microcirculation that is at odds with anything else I have read. I telephone Professor Clough (Physiology Professor at the Medical School, Southampton) and offer to buy her a Costa coffee if she will tell me about Rodney Levick and Charles Michel. I get straight to the point – are they mad? She assures me they are both in full possession of their marbles, and tells me she has been teaching the revised Starling Principle to Southampton Undergraduates for many years. I am dumbfounded. These young people have come to Anaesthesia & Critical Care having been taught ‘good’ fluid physiology, then my clinical colleagues and I have undone all her good work. I further confer with my son, who has a PhD in biosciences, and realise we have to introduce the revised Starling Principle to clinicians who have totally failed to notice the evolving science.
2012 – Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. By 2023 this paper has been Cited more than 500 times, not always accurately or even appropriately. Nonetheless, even detractors accept that the proposed paradigm for prescribers of intravenous fluid has been given a firmer footing in physiological science. Also at this time my son (a neuroscientist) drew my attention to developments in the Starling physiology of the central nervous system, cerebrospinal fluid and a “glymphatic system”.
2014 – H3 Symposium. A Joint Meeting of Clinicians and Physiologists at Hodgkin Huxley House, London, home of the Physiological Society. The Introduction by Prof Geraldine Clough (University of Southampton) explains the original crystalloid – colloid controversy emerging on the battlefields of the Great War. Prof Charles Michel (Imperial College London) gives an authoritative account of how the Starling principle came to be revised, and concludes with modelling of the effect of a bolus of isotonic crystalloid solution (a) while capillary pressure is normal and (b) while capillary pressure is low. View the opening session on YouTube. Other lectures from the day are also available.
2016 – If the clinician’s challenge is to keep fluid in the intravascular space, the rational prescriber has to understand that large molecules and solvent ENTER the blood stream via the lymphatic system and LEAVE the blood stream via the microvasculature. The RCoA invited me to submit this educational overview of Plasma volume, tissue oedema, and the steady-state Starling principle.
2016 & 2020 Springer invited me to contribute to a multi-author textbook Perioperative Fluid Management. Amongst the chapters you will find two masterpieces of the science by my physiology friends Charles Michel, Roy Curry and Kenton Arkill. And one by me. I’m afraid you have to buy these.
2017 – I delivered a series of lectures to the International Veterinary Emergency and Critical Care Symposium, held in Nashville TN. You can read my Lecture Notes here;
- ASYMMETRY IN CAPILLARY FILTRATION: THE STEADY-STATE STARLING PRINCIPLE
- ENDOTHELIAL GLYCOCALYX
- ENDOTHELIITIS AND SEPSIS
- Plasma Volume and Tissue Edema: Balancing Two Extracellular Fluid Circulations of Albumin and Its Solvent
- Introduction to RSE and GM Paradigm for Rational Fluid Prescribing
- VENOUS EXCESS: A DIFFERENT APPROACH TO MONITORING THE CIRCULATION OF BLOOD.
2022 – Explaining the fluid physiology of the cerebral circulation has long been confusing, with the discovery of “non-lymphatic” glymph pathways in an organ said to have no lymphatics evolving to this admirable in-depth Review;
Martin Kaag Rasmussen,* Humberto Mestre,* and Maiken Nedergaard. Fluid transport in the brain. Physiological Reviews.
The authors make an important observation about brain fluid transport that is equally appropriate to fluid transport in general;
“Several times through history, hypotheses and models of brain fluid transport have been taken as fact, and this static thinking has delayed new discoveries and prevented important scientific questions from being asked and investigated. How do we prevent our current understanding of brain fluid transport from petrifying, and how can we ensure that scientists approach the field with an open mind, making a critical examination of old literature and creatively testing new and old hypotheses by designing original experiments?”2.5 Outstanding Questions.