this is part two of fluid electrolyte and acid base balance so here we're going to be looking at um some of the effects of aldosterone anti-diuretic hormone and atrial nettic hormone again and we'll also be looking at the acid base balance of all this we'll be looking at some of the buffers we'll be looking how the body compensates for changes in PH whether that's due to an alkalosis or an acidosis will exam that both those alterations in blood pH can be caused by a respiratory or a metabolic type problem and how the body responds to those um changes in PH and what the body can do to actually bring uh the pH back within the normal range so changes in blood volume are uh responsible for uh blood pressure changes right blood volume and blood pressure are uh very closely related and um this is just a brief review of how the r and angot tense and aldosterone system atrial ntic um hormone and the antidiuretic hormone all have a role in changing blood volume and therefore blood pressure so we know that when blood pressure is low the justto glomular apparatus of the kidney will respond to that by secreting the enzyme renin rein is a protease it will cleave angiotensinogen a plasma protein made by the liver into Angiotensin one Angiotensin one will be broken down by Angiotensin converting enzyme or Ace which is mostly found in the U blung endothelial cells in the and that protease will generate in Angiotensin 2 Angiotensin 2 is a vasoconstrictor it will also cause you to be thirsty it will also cause the adrenal cortex to release aldosterone aldosterone is going to uh cause sodium to be reabsorbed water will follow that sodium through osmosis that increas in blood volume will increase uh blood pressure which um will offset that decrease in blood pressure which was the signal to get reinan released so we know that atrial ntic peptide is made in the right atrium of the heart uh it's made when the right atrium is overstretched due to an increase in Venus return to the right side of the heart that um is viewed as an an over pressure ation I.E high blood pressure um so ANH atrial nettic hormone will then interfere with the ability of aldosterone to do its job and um basically cause sodium and water to be lost by the kidney so there's an increase in urine volume because we're not pulling that sodium back and water's not following that sodium and that water are lost in the urine due to the hormone made by this the heart atrial ntic hormone and then there's the effect of anti-diuretic hormone so anti-diuretic hormone is made by the hypothalamus it is released in response to low blood pressure and um and a uh and that's slow pre blood pressure will cause ADH to be secreted ADH will put more aquaporin in the collecting duct in the distal tubule of the kidney that allows water to leave the collecting duct basically that water leaves the urine goes into the interstitial fluid gets picked up by the peritubular capillaries in the vasera gets put into the blood supply at that point we've increased blood volume increasing blood pressure also uh ADH is a very good uh Vaso constrictor it will constrict blood vessels causing them to clamp down a little bit which will also increase blood pressure so blood osmolality gets controlled right it's a um you know normally around 300 Milli Osmos and and um we have areas in the um Hy in the brain which actually respond to osmolality directly uh they will increase uh ADH to be secreted uh which will increase water reabsorption at the collecting duct to bring blood pressure back up and those increases in water reabsorption will also decrease any increase in osmolality that is also being detected uh by these uh neuronal uh receptors and so we can you know control blood osmolality quite nicely when needed all right moving on to acid base balance so here we're talking about the control of the hydrogen ion concentration in the blood and therefore in the ex extracellular fluids the reason for this is most enzymes have a narrow PH range in which they work best and um many bodily functions are very sensitive to the pH that they're actually uh being uh well subjected to and uh we know that pH is just the measure of the hydrogen ion concentration the pH scale runs from 0 to 14 Zer being the most acidic 14 being the least acidic I.E the most basic so when dealing with an acid by definition according to our chemist friends right acids are compounds which will release the proton the hydrogen ion this thing into solution strong acids like hydrochloric acid they totally dissociate they totally Fall Apart part so hydrochloric acid will fall apart into the proton which is positively charged and the chloride ion which is negatively charged weak acids on the other hand they release some of their protons in the solution but they still don't completely dissociate um and some of them just stay in solution as the initial compound now bases on the other hand these things will remove the hydrogen ion the proton from solution quite often by adding the hydroxide ion the o with a minus sign ion uh to a solution now strong bases like sodium hydroxide these things uh totally dissociate so uh sodium hydroxide is often used in drain cleaners to dissolve um you know clogs in your plumbing away weak bases like weak acids don't totally uh reduce the concentration of hydrogen ions because they don't completely dissociate into ions and so um we can have weak acids and weak bases Now by utilizing weak acids and weak bases we can actually make a buffer so what a buffer is this is a compound which is in solution which prevents changes or prevents large changes in the hydrogen ion concentration uh basically they help stabilize the pH by either um releasing acid or um releasing protons right they bind up extra acids or release protons to keep the pH within a certain range and um physiologically there are a couple of buffers which are very important we'll go over some of them um but um you know chemically we can we've come up with a wide range of buffers for keeping um Solutions at various phes for various um investigative um studies so hydrochloric acid is a strong acid it totally falls apart into the hydrogen ion and the chloride ion sodium hydroxide is a strong base NaOH falls apart into the sodium ion and the hydroxide ion now carbonic acid are TR um is a weak acid right this is formed from um carbon dioxide and water but this will fall apart into the hydrogen ion and the bicarbonate ion most of our carbon dioxide which is transported in our blood right now is in the form of the bicarbonate ion and this double-headed arrow is very important because that indicates that these two sides of the equation are in equilibrium and um as opposed to the strong acid and strong bases right that arrow is only one directional that's because those compounds when they're put in a solution totally dissociate but a weak acid will dissociate it will release some protons but and um it's karion in this case bicarbonate for Carbonic acid but it is in equilibrium and therefore um if we were to we can move things from one side of this equation to the other that's what that double headed Arrow or actually indicates so chemical buffers they're really really good they work immediately and the body does use those but the body also has two physiological ways in which can change uh the pH of um bodily fluids these are physiological buffering systems and the first one is the respiratory system right it's quick to act it's very shortterm and basically it's by changing the respiratory rate and the depth of breathing we can uh change the pH of the blood that way the renal system is a much longer term uh buff physiological buffering system it works on the time frame of hours to days it's a very slow response uh because of that but it does allow us to um change uh physiological pH so chemical buffer systems so how do these work well first up is the carbonic acid carbonate bicarbonate system and so basically we get uh a weak acid formed by reacting CO2 with water right and so we know that um um water in CO2 will form carbonic acid H2 CO3 this compound and we know that this compound falls apart into the bicarbonate ion and the proton now if we increase the amount of protons in the solution right basically that's a decrease in PH by increasing all this that will force this whole reaction to go towards the left because excess protons will bu with the bicarbonate ion forming the uh carbonic acid if we have excess base around that will react with the acid to form the bicarbonate ion now this is an important uh control factor for extracellular pH it will very quickly respond to any additional CO2 in the area or lactate uh being formed from the increases in metabolism due to um say skeletal muscle working a little bit harder um if we're using fatty acids for um oxidative purposes right to generate ATP that's going to uh lead to an increase in Ketone body formation Ketone bodies are also very acidic uh and bicarbonate buffering system is uh very useful in keeping the pH within uh the normal range under those conditions or they by carbonate system can act when the large amounts of basic substances get uh put into the body as u in the case when you know someone is taking a lot of an acids and um you know this system is very important physiologically so inside the cell the proteins that are there um can uh act as buffers in the plasma proteins found in the blood are also important uh buffering systems found there um the hemoglobin if you remember when it binds um oxygen or releases oxygen it will bind or release a proton also so inside of the red blood cell hemoglobin is an important um buffering component again that's protein buffering systems and um proteins can do this because they've got a free carboxy end and a free Amino end um the carboxy end can release a proton and the amino end can basically absorb a extra proton as needed and so um this makes amino acids and therefore proteins very good at this buffering system because they can bind or release protons as needed to keep the um proton or the hydrogen ion concentration within the proper range phosphate buffering system is an important system inside the cell so it's an intracellular buffering system um and this can occur because we've got uh two different compounds one is a phosphate group with one hydrogen this structure the other one is that same structure but it has two hydrogen ions attached to it so if there's an excess of protons those protons will get absorbed by the phosphate with only one hydrogen attached to it forming H2 poo4 now if there's an excess of Base in the area we're going to release a proton from H2 P4 and get back hpo4 so this is an important uh intracellular buffer and um there are a large number of phosphate containing molecules inside of uh the cells including ATP the DNA and the RNA Are all uh very U large contributors to uh phosphate within the um cell but it's basically these two compounds here the uh H2 P4 and HP4 which act as the buffer inside the cell for the phosphate system so those were the chemical buffers now we have to talk about the physiological buffers and so basically this is a lot of this is through the carbonic acid bicarbonate buffering system again and so again you know we've got water and CO2 coming together um those on their own will form the carbonic acid which falls apart into the proton and the bicarbonate ion itself Carbonic and hydras is the enzyme which accelerates this reaction it accelerates this particular reaction the formation of carbonic acid from the water in the carbon dioxide so if carbon dioxide levels increase so if we get an increase in carbon dioxide side levels that's going to push everything this way and so increases in this water's readily available we're going to get more acid then that acid is just going to fall apart into more um protons floating around and more bicarbonate ions now if carbon dioxide decreases if this goes down this whole equation gets pushed leftward and so what that means is if we decrease carbon dioxide everything gets pushed this way and so in order to do that the proton has to bind to the bicarbonate to make the acid to reestablish this equilibrium here uh through Carbonic and hydrates and what we'll see is that we can basically trap this proton in a water molecule by getting rid of that CO2 by breathing it out which is really a neat trick so this leads to this conclusion that carbon dioxide levels in pH affect the resp respiratory centers in the brain and so if we hypo ventilate if we hold onto carbon dioxide right and basically not breathing quickly enough or deeply enough will increase blood carbon dioxide levels conversely breathing very rapidly and very deeply I.E hyperventilation will just blow off a lot of carbon dioxide and both of those conditions will have effects on blood pH as we'll see so we know that Carbonic and hydrates will take water and carbon dioxide form the um carbonic acid which then falls apart into the proton and the bicarbonate um so the enzyme doesn't affect the equilibrium it doesn't affect the balance it just speeds that balance up and um if there's a decrease in the pH of bodily fluids I.E if there's a buildup of the hydrogen ion right that affects the respiratory areas of the brain stem to increase the rate in depth of breathing so we're causing hyperv ventilation now that's going to cause CO2 to be lost faster than what it had been before and so this elimination of CO2 basically causes um the concentration of the hydrogen ion to decrease I.E the pH is going to come up because we're getting rid of this by trapping it in a water molecule when that carbon dioxide leaves Le so acidbase balance in the renal system so now we're not looking at the respiratory system but we're now looking at the kidneys and so basically what we can control here is how many protons are actually secreted into the filtrate and every time a proton is secreted into the filtrate we're going to reabsorb a bicarbonate ion into the extracellular fluid which basically uh both of these functions will increase extracellular pH and so we're going to pull this uh bicarbonate into the filtrate it gets returned to the extracellular fluid because there's a sorter there for sodium and the bicarbonate ion and um the rate at which this proton gets secreted will increase as bodily pH decreases or actually aldosterone increases due to the fact that um aldosterone's affecting the sodium and basically we're going to inhibit proton secretion when the urine pH Falls below 4.5 it never gets much below that and then um we've have buffering compounds in the filtrate itself which will then bind up that proton so it can't come back in those are going to be the bicarbonate ion phosphate ions and actually the compound ammonia itself which is a waste product of um well nitrogen uh metabolism so if we look at how this actually happens so we have CO2 in the tubular cells uh they have Carbonic an hydrates they make the carbonic acid and then the um antiporter system will push that proton into the filtrate and uh since it's an anti for sodium as that sodium is coming in it pushes that proton outward and then that uh proton in the filtrate will bind to bicarbonate ions in the uh filtrate itself or the phosphate ions down there or ammonia so at this point the sodium and the bicarbonate are moved out of the two tubular cell into the interstitial fluid fluids excuse me get picked up by the peritubular capillaries and distributed throughout the body at that at that point and so once the um hydrogen ion gets into the filtrate it gets uh filtered basically uh by bicarbonate ions that are already here phosphate ions which are in here and or uh by binding to ammonia compounds in the filtrate down here all right so uh what can cause acid base imbalances well first thing we need to know is that uh the pH of the blood in most bodily fluids varies between 7.35 and 7.45 5 so basically we're at 7.4 with minor various variations up and down if we go below 7.35 we're in an acidosis situation if we go above 7.45 we are alkalotic or an alkalosis type of situation so these situations we can have respiratory acidosis and respiratory alkalosis right and so these conditions can be traced back to a problem with the respiratory system any other cause of an acidosis or an alkalosis is basically defined as a metabolic acidosis or alkalosis so if we have an acidosis this is not a good condition because um the central nervous system is depressed when there are too many hydrogen ions around um this can lead to Comas and disorientation and all sorts of problems so we can get a um respiratory acidosis basically by uh not getting rid of CO2 build uh fast enough right we're not ventilating adequately so CO2 builds up um that uh is going to um cause uh Carbonic anhydrates to make more carbonic acid which falls apart into uh well protons and bicarbonate and the overall effect there is a lowering of the pH now buffers can help uh well deal with this for a very short time but eventually the kidneys are going to have to kick in uh increase the rate of proton excretion and uh reabsorb more bicarbonate uh to hopefully have a long-term effect to um decrease this uh respiratory acidosis if this is going to be a chronic type of situation where we are um not breathing adequately can also have metabolic acidosis right these are uh any condition which causes a decrease in uh the pH of the bodily fluids from a nonrespiratory uh source so uh poorly controlled diabetics often have very low blood phes due to the very large number of Ketone bodies that are required uh to run their muscle cells and their fat cells because the muscle cells and fat cells don't have access to the high levels of blood glucose that are available so again the buffers are the first line of um trying to maintain pH under these conditions the respiratory system under these conditions will respond by hyperventilation to blow off a lot of CO2 by getting rid of that Co CO2 we're getting rid of um basically those protons by trapping those protons in a water molecule and those water molecules can't come out of there because well there's no or there's a decrease amount of CO2 for them to react with the kidneys will also uh step up their excretion of protons and their reabsorption of bicarbonate from the um urine from the filtrate and so hopefully this will uh be able to fix this acidosis so now we have to look at the opposite problem not enough acid I.E too much base alkalosis and uh again the major effect is on the central nervous system it's not a uh but here we're getting an hyper excitability of the nervous system the peripheral nerves will react we get spasms from the muscles we can have Technic contractions and um actually lead to convulsions and or death uh basically from uh tetany of the respiratory muscles right if your diaphragm is contracted and doesn't relax to allow for proper ventilation right that's going to lead to death so we can have a respiratory alkalosis basically this is caused by hyperventilation right you're hyperventilating for some reason um you're blowing off way too much carbon dioxide you're getting rid of that acid essentially and therefore the blood pH is going to um come up um this may also occur if you are at high altitude uh for the first couple of days because you are hyperventilating to try to get more oxygen in but by doing that you're also blowing off more CO2 than what you should and the kidneys at this point are going to decrease the rate of secretion of the proton and uh they're going to um decrease the reabsorption of bicarbonate we can have a metabolic alkalosis and right so this is any condition other than respiratory which gets the blood above 7.45 right uh this can be caused by taking uh lots of and acids Andor severe vomiting can also cause this right you're vomiting up all that stomach acid and we're left with all of that bicarbonate from the alkaline tide of the stomach and that can lead to a um alkalosis again the buffers respond to this uh at first the respiratory system will respond to this by actually reducing respiration because we want to hold on to that carbon dioxide we want CO2 to build up that buildup of CO2 allows more CO2 to work and react with the water to make the carbonic acid to make um to fall apart into more protons to bring the pH uh back down and uh if possible the kidneys will respond by reducing the rate of proton secretion although um this is a little bit hard to do because the kidney really does want to get rid of protons so here's a nice table looking at uh acidosis is on the right hand side and alkalosis um I'm sorry acidosis is on the left alkalosis is on the right so respiratory acidosis right we're not eliminating enough CO2 all right this can be caused by as aixia problems with breathing we could be hypoventilation right uh right we've got problems with the respiratory centers in the central nervous system uh this could be due to trauma or shock or even renal failure Advanced Asthma can uh lead to respiratory acidosis also and empyema can also cause this for uh metabolic acidosis right we just have a large amounts of um bicarbonate from mucus secretion right severe diarrhea and vomiting can lower um intestinal contents of these compounds um we've got um you know large ingestion of say uh acidic drugs aspirin is very acidic things like that this can be a problem for uh patients who take a lot of uh aspirin for you know uh analgesic purposes if we're making a lot of Ketone bodies because we're burning a lot of uh fats for energy uh this can lead to metabolic acidosis this is a known problem with the keto diet and if there's not enough uh oxygen delivery to the tissues right we're going to um uh get an anerobic uh respiration type of situation right uh exercise heart failure Andor uh shock inadequate blood flow can all cause this for alkalosis right we've got respiratory alkalosis right we've got uh not enough CO2 levels in the blood basically because due to hyperventilation right we're just you know due to U say uh emotions or um you know uh being frightened things like that you know we just hyperventilating blowing off too much carbon dioxide and getting rid of too much acid essentially it's can also be caused by um basically uh low oxygen levels in the atmosphere that which will cause us to hyperventilate to try to get more oxygen in but that also causes more CO2 to get lost again this is the problem with going to high altitudes from metabolic uh alkalosis right we've got problems with um elimination of the proton or reabsorption of the bicarbonate in the kidneys or the stomach right we could have severe vomiting or acidic urine in response to uh excess aldosterone say or we can just be taking in large amounts of uh sodium by carbonate as a u a cure for um uh well heartburn things like that and so you know we have to keep the blood pH around 7.4 if the blood pH increases outside the range uh we're going to throw things off um pH centers in the brain will uh respond to these changes and they're going to decrease hydrogen ion secretion uh from the blood and increase by carbon production which will uh basically counteract this uh initial increase in uh pH and um you know we have to be careful about keeping everything at 7.4 essentially