Bugging the blood pressure

In between Blobs, I teach science in The Institute: a shadowy college of further education in the Irish Midlands with links to Opus Dei and the Illuminati. It's coming up for five (5!) years now but the one course that has been mine through all that time is Human Physiology. My only qualification in this area is that I have a body, some curiosity and a preference for making sense of the world. Everything you need to know about Human Physiology is homeostasis:t he remarkable, and energetically costly, maintenance of things in equilibrium at a set point. Our core body temperature holds at 37^oC +/- 1 degree through a remarkable range of external conditions: bouncing starkers from a sauna to a snowbank does Finns no harm at all and the thermometer popped up a Finnish rectum stays steady at 37 throughout. The remarkable properties of dissolved carbon dioxide and the bicarbonate ion maintain the blood pH at a constant level of acidity. Circulating glucose, circulating sodium, circulating calcium are some of the substances whose set-point maintenance we understand well.

One definition or explanation of senility (the process of growing old, not necessarily associated with dementia or dribbling) is the breakdown of these precise regulatory mechanisms, so that the swings about the set-point are less subtle. Hand-tremor is a good example of this: when you young chaps hold a pint steady at the end of your arm, about 30 different muscles are acting against each other to stop the booze slopping down your shirt. This handy life skill, which you take for granted, is a bit of an ask for Pat the Salt my 92 y.o. father in law. One muscle will contract and its oppo will over-react, so his hands are less steady than they were when he was your age.

Now think about blood pressure; that has to be maintained in a wide variety of conditions. Asleep, your heart has it easy: pumping blood on the flat. When you stand up, immediately, your heart and arteries have to up their game for some metaphorical fell-running, the system is now being asked to pump blood up a 1.5m to 1.8m hill between ankles and head. Me, I now have to be careful springing out of bed in the night. Unless I meet the problem halfway by sitting on the edge of the bed for a moment, I am likely to feel a touch of faintness, a prelude to crashing to the ground in a heap

Obviously, the problem of normal blood pressure maintenance features largely in my Human Physiology course. That way my colleague, a real pharmacist, teaching Drug Actions and Uses can look at all the interventions that are possible when blood-pressure goes too high. BP is a regular cash cow for MegaPharm Inc. I'll get round to some of these drugs and how they work later - it's a fascinating insight into how scientific research works. Ignore the drugs and abnormally high blood pressure: that's a very modern problem. Let us rather look at how BP was kept UP in normal life for the super-thin, marathon-running, hunter-gatherer who came down from the trees and started walking upright 4 million years ago. Those chaps, and we are their descendants, were designed to keep blood pumping uphill to the head, without that you can't make decisions while running down a wildebeest.

There are two ways to increase pressure in a closed system: you can make the volume smaller or you can add more fluid . . . or both. And you can also increase cardiac output: make the ticker beat more frequently or with more force. Making the system smaller is largely about peripheral vaso-constriction, your small arteries are all surrounded by rings of muscle, contract these and blood pressure will increase. A nifty way of increasing the volume is to have the kidneys retain Na = sodium. These sodium ions suck water back from the kidney tubules to stop the salt from coming out of solution and forming crystals. That's so elegant a working solution! Sodium is maintained in equilibrium in the blood because we need it for muscle contraction and nerve signalling, using it to attract water is a secondary feature. Everything is interlinked, sometime in quite unexpected ways.

Hot Press, we had it all wrong. Or at least our understanding of sodium balance and blood-pressure as a physico-chemical problem to do with hydrostatics was laughably simplistic. Actually it's all in the microbiome innit? I've had multiple occasions to write about the intestinal flora / microbiome - the 2kg / 100 trillion cell / 10,000 species menagerie that we tote around in our guts . . . with out-stations up the nose, down the uterus, in yer armpit and all over our skin. It seems that, although salt intake is very closely related to blood-pressure (and this is why we are begged to use less salt in our food) some people don't seem to respond to dietary salt in that way. A group from Charité-Universitätsmedizin Berlin wondered whether the connexion between high salt diet and high blood pressure might have a microbial dimension.  The News & Views about the study from Nature 30 Nov 2017 [paywalled] is by David Relman a leading light in microbiome studies. Apparently the excess sodium leaks across the intestinal epithelium and inhibits the growth of one species of the normal flora of mice called Lactobacillus murinus. Apart from being rather sensitive to salt, these Lactobacilli metabolise a dietary amino acid tryptophan into indole. Indole leaks back across the epithelium and prevents the development of a class of key immuno-inflammation white blood cells called T_H17 lymphocytes. These lads have a tendency to blurf out a pro-inflammatory cytokine called IL17 (hence the name of the cell). IL17 is a small molecule that promotes inflammation which is an essential part of fighting off infections and pathogens and one of its effects is to  annoy the inside of arteries so they swell up . . . which increases blood pressure. You will have gotten lost on the roller-coaster of consequences, so here it is in tabular form:

Input	Output	Cell	Cytokine	Effect	Conseq.
Salt	Indole	TH17	IL17	Inflam	BP
up	down	up	up	up	up
down	up	down	down	down	down

Who designed such a Heath Robinson brown-paper and string system? Mrs and Mrs Evolution, that's who. It worked fine when we were all hunting about the Serengeti. Salt was in desperate short supply back then - there were fights at the salt-licks because everyone needed enough sodium to service their muscles and nerves. Now otoh it snows salt, so it's no wonder that the carefully crafted regulatory system are thrown all ahoo.