Today’s edition of the New England Journal of Medicine (September 19th 2019, pages 1097-8) carries a two-page explanation of the power and the reach of the humble tweetorial by the outstanding exponent of the art, @Tony_breu of Harvard Medical School. DOI: 10.1056/NEJMp1906790. Tony cites his own first venture into this new route to publication, which was entitled “Why do patients with acute hemorrhage become anemic?” The first problem with such open-access publication is absence of pre-publication peer review. Indeed, the author does not even have to be sober before hitting the TWEET key. Does post-publication review by readers offset that disadvantage? Tony offered a hypothesis rather than a physiological answer to his question, and I did at the time offer Tony a tweeted correction, but Tony does not mention the danger of misinformation being perpetuated via the unedited Tweetorial. Of course, misinformation also finds its way into peer-reviewed and edited publishing channels, but some checks and balances are present.
Our Authority as teachers is boosted by our claimed Affiliation. In this instance, a retired anaesthetist currently fly fishing in Hampshire, England, is daring to challenge the teaching of a practising physician at Harvard Medical School. Should our Affiliations influence our readers confidence in what we teach? I wish to thank a friend who tells me “You are a Legend in Italy”, but in the rest of the world? In case you are not a tweetorial user, I reproduce below my own (correcting) tweetorial.
1. Why do patients with acute hemorrhage become anemic? @tony_breu asked this question as the first of his excellent threads on June 6th 2018 and recently reported the success of tweetorials in NEJM. Unfortunately, his explanation was wrong.
2. We can start at tony’s #8; “8/ When a patient has a decrease in capillary pressure, the Starling Equation suggests that fluid will move from the interstitial space into the vascular space… The plasma is “diluted” by fluid shifting from the interstitium.” https://pic.twitter.com/E2T2xZVEe0
3. Familiar to all, but the Figure to Forget according to Charles Michel. A nice hypothesis, but sustained absorption (ISF to Plasma) has never been seen in a continuous capillary that lacks an independent source of protein-poor solvent.
4. Starling himself anticipated the problem; as ISF solvent and proteins move towards the plasma, the protein concentration on the tissue side of the capillary barrier rises and the colloid osmotic pressure difference (plasma-ISF COP) falls.
5. Absorption is therefore limited to transient occurrence after abrupt change in the Starling forces and filtration occurs along the whole length of a continuous capillary in steady state. https://ncbi.nlm.nih.gov/pubmed/20200043
6. Yellow is the pre-hemorrhage steady state; green is transient absorption state as capillary pressure falls and Jv becomes negative; red is the subsequent “new” steady state of reduced filtration after subglycocalyx COP has risen.
7. from my book – “Nine subjects had about 12% of their blood volume removed, which did not change heart rate or blood pressure in these fit young men. Over the following four hours, their plasma volume was almost completely restored at the expense of interstitial fluid volume.”
8. “The average plasma volume refill rate was found to be around 1 ml min-1. Moore (Ann Surg 1966) and his contemporaries believed this was due to net capillary reabsorption.”
9. “It has since been demonstrated that thoracic duct lymph flow and protein return rate are significant contributors to blood volume and plasma protein restitution after haemorrhage” (Lloyd SJ, Shock 1996)
10. “In awake sheep with lymphatic cannulation, hypotensive hypovolaemia induced enhanced lymphatic pumping.” (Boulanger BR, Circ Shock 1994)
11. “The interpretation today therefore is that transendothelial filtration rate Jv fell following reduction of Pcap to become 1 ml min-1 less than the enhanced lymph flow rate Qlymph. This would account for the absence of hypoalbuminaemia during post-haemorrhage plasma refill.”
12. there are other contributors. If there is fluid in the intestinal lumen it can be absorbed to boost plasma volume, and the hepatic interstitial fluid is essentially plasma and can enter the blood stream through discontinuous fenestrated liver endothelial cells when Pcap is low.
13. “It has recently been shown that arginine vasopressin kickstarts erythrocyte production as part of its defence of blood volume. After acute haemorrhage the erythropoietin response only commences when plasma volume compensation leads to anaemia…,
14. … while the vasopressin response is triggered by hypovolaemia. Erythropoietin response is slow because it stimulates early erythrocyte progenitors. Vasopressin response is rapid because it promotes maturation of the existing intermediate erythrocyte precursors.”
This is clearly a topic that deserves further debate, and I look forward to hearing Comments. My own final thought; I would LOVE to teach Starling physiology at Harvard Medical School. Any chance of an invite Tony? Please?? I’m willing to grovel???