Acid-Base balance. Acid : is the substance that donates H+, base : is the substance which receives or removes that H+.

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Lionel Clifford Patterson
5 years ago
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1 Acid-Base balance Introduction : We usually suffer from metabolic acidosis more than alkalosis, acidosis means that there is an increase in H+ concentration in plasma and thus interstial fluid ;because both have the same concentrations of electrolytes. Acidosis(too much H+) is a very serious condition since it suppresses CNS enzymes leading to coma, on the other hand alkalosis (too little H+) causes over-excitation of CNS leading to convolutions that may take place in respiratory muscles leading to death.what explains the two previous conditions is that every enzyme has its own optimal PH (below or above this value will disrupt enzyme activity) Kidney is the most important organ in acid-base balance. Acid : is the substance that donates H+, base : is the substance which receives or removes that H+. Acids can be weak or strong, the strong ones almost dissociate completely like HCl (one mole of HCl gives one mole of H+ and one mole of Cl-), while the weak ones dissociate incompletly like H2CO3(H2CO3 HCO3 + H). Also bases can be classified in the same manner (strong and weak) PH stands for power of H+ concentration,ph= - log [H+] *In mathematics we use log to express too large or too small numbers [H+] in ECF is very low ( less than [Na+] by 3.5million times, but still Having a very significant effect on our body). - [H + ] = 40 nanomolar [Na + ] = 145 millimolar - ph = -log [40x10-9 ] ~ ph of 7 is ten times more than ph of 8 in terms of [H + ],we conclude that the more the PH is inversely proportional with [H+]**.

2 Normally, plasma has 40 nanomolar of H+ (PH=7.4) BUT our body still can tolerate 4 times above(160 nanomolar,ph=6.8) or below (10 nanomolar,ph=8) this normal concentration. SO,the normal range of PH is [6.8-8], outside this range is not compatible with life. Our body is prepared to deal with acids more that bases, if acids reach plasma, body can deal with them while body can't fight against bases entering the plasma. - As we have seen before body can tolerate 4 times more or less than normal [H+], but this is not true for other electrolytes, if we took potassium for example a two times increase or decrease in concentration is considered incompatible with life, these conditions is termed severe hyperkalemia and severe hypokalemia,respectively - The same thing is applied to Na+ Acid can be classified into two classed : 1/volatile 2/ non-volatile Volatile acids : We produce 200ml CO2 every minute Recall respiratory exchange ratio = rate of CO2 exhalation/ rate of O2 inhalation = 200/250=0.8 We produce or exhale 300 Liter of CO2 daily which corresponds to 10 mol H+ CO2 is regarded as masked acid because this equation (CO2 + H2O H2CO3 HCO3 + H+) and is called VOLATILE ACID,

3 Although 10 mol of H+ is too extremely high,we don't care about them because respiratory system can get rid of them, SO there is no problem with volatile acid when respiratory system works properly. The problem usually resides in non-volatile acids 2/ non-volatile acids (fixed) a. phosphoric acid : produced by breakdown of phosphoproteins, phospholipids and nucleic acids b. sulfuric acid : certain amino acids contain sulfur such as cysteine and methionine c. acetoacetic acid d. hydroxybutyric acid e. kreps cycle acids non- volatile acids are produced at a rate of 1mmole/kg/day so for an 80 kg man, 80mmol of H+ would be produced daily, those 80mmol of nonvolatile acids if we added them to the ECF which equals 14L ;each Liter would have approximately 5mMolar of H + {80mM/14L} 5mMolar = 5x10-3 M [H + ] ph = -log [H + ] = 2-3 (not compatible with life) so adding H+ OF nonvolatile acid TO plasma will shift PH to value that's incompatible with life

4 IF we combine a strong acid with a weak base we would produce a weak acid which will change the PH of solution slightly since weak acids dissociate incompletely HCl (strong acid)+ NaHCO3 (weak base) NaCl + H2CO3 combining a strong base with a weak acid would produce a weak base NaOH + H2CO3 NaHCO3 + H2O - because we produce approximately 80mmol of volatile acids we also need 80mmol of HCO3 - daily to neutralize them into weak acids - but [HCO3 - ] = 24mmol/L, ECF = 14L so all in all we have 24x14 = 336mmol (total HCO3 IN BODY) because we use 80mmol daily, this amount is enough only for four days OR 5 days in maximum (336/80=4.25days), so at the end of 5th day no HCO3 is available in the body and any additional acids coming to plasma won't be buffered shifting the PH of plasma. normal person with normal diet and physical activity have tendency toward acidosis caused by production of non-volatile acids. our body deals with these non-volatile acids by buffers which protect against acidosis BUFFERS : is an aqueous solution consisting of a mixture of a weak acid and its conjugate base, (or vice versa).

5 buffers tight H+ BUT will not remove them from body (e.g H+ Will bind HCO3- Forming H2CO3 which need to be excreted from the body by other mechanisms ) CO2 + H2O H2CO3 HCO3 + H+ when we add 80meq H+ we shift the equation to the left leading to formation CO2 which is washed out by lungs This graph is called alveolar ventilation curve, acidosis causes lung to hyperventilate in order to wash out excess CO2 while alkalosis suppress ventilation to retain more CO2. The curve is not linear that's mean "one unit decrease in PH have more effect in ventilation than the same unit increase in PH ) this is explained by the following :

6 Acidosis causes hyperventilation which increase alveolar PO2 up to 140 mmhg but this won't add significant O2 to plasma (we can't hyper saturate Hb), so there is no opposing effect of hyperoxia Alkalosis suppresses ventilation which decreases Alveolar PO2 down to 60 mmhg, this decrease in PO2(Hypooxia ) will act as an opposing force to drive hyperventaltion. So Alkalosis can't express itself fully in term of its effect on ventilation In order to have linear correlation between [H+] and alveolar ventilation we should stabilize alveolar PO2 to remove the effect of hypoxia on ventilation. AS we have mentioned before, the problem in our body is the acids coming into plasma, the solution for this problem is buffer which is available in limited amounts in our body (this is overcomed by kidney ) The role of kidney is represented by the following : 1- kidney must absorbs 100% of the filtered HCO3-, 2- It should adds HCO3- to the plasma (renal veins should have 80mm ofhco3 more than that in renal artery/kidney is not just advice that clean the blood from waste products but it adds significantly to the blood such as hormones,erythropoietin and HCO3-,Buffer components are weak acid with its salt(conjugate base of this weak acid) We have three buffers in our body :

7 1) bicarbonic acid : H2CO3(give H+/ HCO3 - (bind H+) 2) phosphate H2PO4 - /HPO4 3) proteins what determine the strength of a buffer? 1. absolute concentration 2. pka 3. renewing capacity Bicarbonic acid buffer : H2CO3 HCO3 + H Pka (disassociation constant) - ph = pka + log [A - ]/[HA] Henderson Hasselbalch equation - ph = log [HCO3] / [H2CO3] - we usually use CO2 instead of H2CO3 - [CO2]= PCO2*0.03 to convert mmhg to molarity (CO2 can be used instead of H2CO3) ph = log 24 / 40*0.03 = =7.4 ph = log 24 / 1.2 = =7.4 In this case base conc. [HCO3-] more than acid conc. [H2CO3] by20 times (24/1.2) which is something we like to have, because it makes the buffer strong (the major threat in out body is having excess acids,we need high conc. Of base to deal with them) as relative conc, of base to that of acid increases, the strength of buffer increases.

8 Pka : it's the PH of the solution when the conc. of base equal to that of acid "major determinant of the strength of the buffer" - ph = pka + log [A - ]/[HA] [A-]=[HA] - ph = pka + log 1 -- ph = pka The above X-axis represents percentage of base while the below x-axis represents percentage of acid Adding base will shift PH to alkaline value (shift to the right) Adding acids will shift PH to acidic value ( shift to the left) If we added a substance to buffer solution that its color is changed in response to changes in PH ( to the red in case decrease in PH) then we add acid to this solution the color will not change in color until we reach critical point at which PH is shifted and the color of that substance is changed When the PH of solution is around the PKa (one unit above or below)of the buffer, it will work with maximum capacity. - meaning that its maximum buffering capacity of HCO3-/H2CO3 is betweenph (its PKa =6.1)

9 - going above or below these values would be beyond the buffering capacity of carbonic acid and would change the PH of solution - PH of plasma is 7.4 when PKa of carbonic acid buffer is far away from its maximum capacity so in term of PKa carbonic acid buffer is not considered as strong buffer - But in term of concentration carbonic acid(24mmol ) is stronger than phosphate buffer. Buffering is the main function of carbonic acid buffer - 2/Phospate buffer : - pka of H2CO3 = 6.1 pka of H2PO4 = 6.8 which means that phosphoric acid is better as a buffer from H2CO3 in terms of pka - phosphoric acid can act also as an intracellular buffer because: - -its PKa is very close the PH of the intracellular fluid which is different from ECF and it's around 7 Phosphate is concentrated inside the cell (70mmol) - Phosphoric acid can act as a buffer in renal tubule due the following: - a/after absorption of water from renal tubules to the blood phosphate become more concentrated - b/ph of tubular fluid is around 6.5 which is close the PKa of phosphate buffer We have 700g-800g phosphate in our body most of it is inside the bone,some resides in soft tissue and less than 0.1% in ECF,SO BUFFERNING IS NOT THE MAIN FUNCTION OF PHOSPHATE. Protein buffer: In term of concentration it's the strongest buffer because its concentration is higher that the two previous buffers

10 70% of our buffering strength is coming from proteins pka of most proteins is around 7(close to plasma PH) but the problem that proteins are hindered in intracellular compartment - but proteins can't be renewed that's why buffering is not the main function of peripheral proteins The most important determinant of buffer strength is the renewal ability The only buffer that can be renewed is bicarbonate buffer that's why it's regarded as the most important buffer in our body Bicarbonate conc. Can be changed by respiratory system (through affecting CO2) AND by renal system. Notes reg arding the previous lecture : there are 180 literes filtered / day. Urine output is 1.5 L/day kidneys reabsorb more than 99% of filtered water : 60% in the proximal convoluted tubules 15% in the descending loop of henle 0% in the ascending limb and early distal 10% in Late distal 9.3 % in the collecting tubules About 0.7 is secreted Remember that ADH plays a role in the establishment of hyperosmolar medium in the interstium by increasing the reabsorbtion of urea from collectecting tubules. Osmolar clearance : C osmolar = Ux * V / Px = 600 x 1 /300 = 2 ml/min

11 To calculate water clearance : C water = urine output C osmolar = 1-2 =-1 this indicates the kindneys secrete more osmoles than water **log 10 = 1 log(x *10) = log(x) +log 10 so ten times increase in the H+ concentration will decrease the ph by 1 Good luck

Physiology lecture (8): Acid Base regulation

Physiology lecture (8): Acid Base regulation If we add hydrogen, we have three lines of defense against a mild change in ph: 1) Buffers, instantaneous, within a fraction of milliseconds. 2) The lung, takes