 Goed, nou, we hebben dit model looked at the erect in the supine patient. But there's some problems because we send people in space and we notice what we explain now doesn't really happen. So what are the problems we're dealing with? We do notice that the GFR, the blood flow rate through the glomeruli increased by about 19% that gets a bit of a problem for us. Because the urinary output actually drops. Now we just said if you lie down your urinary output by the physiological methods that we mentioned should actually be going up and it actually decreases by quite a bit. There's no diuresis and there's no natriuresis. So where does this come from? Now there are a few confounding problems. Remember some astronauts decide to do what they call fly dry. In other words they will restrict the fluid intake before they go up. They don't want that introduction of motion sickness is nauseous. There's various reasons why they do that. The urinary problems, although they can urinate in the space suit. Remember they'll be in a position lying down with the hips and the knees flexed by 90 degrees for up to two and a half hours even up to four hours before a launch can be aborted. So they don't want to urinate in the suit and there's a ability to do that. They don't want it in the fly dry. Even those that don't are not going to still see even those that take in normal amounts of fluid still see this urinary output decrease. So that's contrary to what we just said should happen physiologically at least if we look at what happens in the erect and supine positions. Another little problem just by the way to get a bit distracted is obviously there's a problem with the fly dry as well in as much as they will have volume at depletion and in an emergency if they do have to get up in a boat and get out quickly they will develop orthostatic hypertension as they try and get up quickly. Remember they carry a full space suit with all the life support systems which can be about 45 kilograms that they carry so that might be a problem with the fly dry. Anyway, even if they don't there seems to be still this decrease in urinary output. There's certainly no diuresis as we would expect there to be. We would expect there to be but there's none. There's no diuresis to drive this diuretic process and we actually we said well the ADH should go down but we see well this ADH actually goes up so what's going on here and the first levels go down. Now those two don't go together either. So say for instance you're in the desert and you've lost your way and you don't have enough water you are going to become thirsty. The hyposmolar nature of your plasma is going to drive the thirst and you're going to try and hold the urine back to maintain that. So your ADH is certainly going to go up but you're going to get thirsty. Now you don't get thirsty but your ADH goes up so those two don't go together at all and certainly there is definitely a decreased thirst in microgravity. And another thing that happens is that the insensible losses go down. Now we know when it gets cold in winter times you actually start urinating more. Some people actually have to get up at night urinating in winter time because they don't have the insensible losses so they have to excreted by the urine. So these two don't go together either. So how can we explain some of these things? Now remember there is this fluid redistribution. Certainly there is what's called the chicken leg or the bird leg and the puffy face syndrome. In other words they can be 10% of more decrease in the thigh volume so there is lots of interstitial volume definitely in the legs and volume in the basculature of the legs as well so the legs actually get thinner and anything above the level of the heart now remember there is a substantial amount of volume below there is more volume below then there is above the cardiac level but anyway you do get that redistribution in the puffy face so there is this fluid redistribution but it certainly doesn't have the effects One of the major things that was found was that there is a decrease in the interstitial pressure in the microgravity the chest cavity and abdominal cavity will expand so there is less of a pressure inside these two cavities In other words, I mean there are catheters that will play central venous catheters and we noticed that even though there is a larger volume that goes in the preload there is actually a decrease in central venous pressure so you go from one gene you go into zero gene with all that blood coming back to the heart there is actually a decrease in the central venous pressure and let's explain by this we think it's explained by this there is a decrease in the interstitial pressure as the chest cavity and the abdomen distends so there is trans vessel and trans cardiac pressures increase In other words, the pressure inside the vessel inside the heart and then the pressure inside the thoracic cavity because this drops down so much due to the expansion of the chest and there is more volume coming in here there is more pressure differential there which allows for this vessel distension and atria distension even more and hence the pressure falls there it doesn't increase as we think it does now we do think that the central blood volume there is a lot more volume inside the central blood system central area now central blood volume is increased and that is what drives down the thirst we know this because you can do experiments where the blood where the canis actually hyper osmola in the thirst level still go down we should go up remember the guy in the desert his thirst goes up because of that hyper osmolarity but even if you do that in zero gene increase in central blood volume will drive down the mechanisms that induce feeling of thirst now the ADH we should go down and this actually goes up now there is a bit of a problem here remember you go from one gene to zero gene very quickly there is no, it doesn't take days to happen it's within and there is a lot of stress effects on that launch and the G's that take place there so we think it's this increased stress effect that actually increases that ADH and not necessarily natural physiological effects just of the distribution of volume now there is initially an increase in this ATL and antiuretic peptide or factor but it's overwritten initially at least by this mechanism and eventually within a few days it starts falling so that drive for a possible diuresis just disappears so we maintain this issue of not diuresi so where does all this blood volume go where does all this plasma volume go there's actually up to 70% decrease in plasma volume in astronauts in microgravity or COG so where does all of this water now go it's not coming out by the urine the sensible losses is definitely down so where does it go well remember they do take in there is a decrease in thirst and there's definitely a decrease in fluid intake but what we do notice is that the total body water stays about the same now you might say well the puffiness there may be it's because it's indistributed in the extracellular space but certainly that appears not to be the case either as there are measurements to show that the extracellular volume also depletes so where does it go is the only place left for it to go is the intracellular capacity that increases so that water goes to the intracellular space so there is ionic issues with that specifically potassium we know there's not a sodium shift so there's a bit of potassium shift and we'll look at this a bit later there's a potassium shift and we'll look at that later but certainly increased intracellular capacity and we know there's an enormous intracellular volume capacity does exist now the one place where water doesn't accumulate is the red blood cell and the red blood cell mass actually goes down it goes down and there's definitely a decrease in the erithropotin EPO production so you don't make as much red blood cells for therefore the red blood cell mass goes down but there also seems to be a preferential destruction of younger red blood cells and they are large and they carry more volume in zero G so except for the red blood cells it's definitely increased in intracellular water accumulation so this picture looks a lot of encounter in two different what we would expect and then the pines and then astronauts things look a little bit different