Nephrology Core Curriculum Simple Acid-Base Disorders

Acid-Base Introduction H + concentration is maintained within very narrow limits –Normal extracellular level is 40 nanomol/L 40 x Approximately one millionth the concentration of K +, Na +, Cl free H + (16 to 160 nanomol or pH ) is the only range compatible with life –Such low levels are necessary because, given its small size of the H + ion, it is highly reactive

Acid-Base Introduction Acid- Substance that can donate H+ ions Base- Substance that can accept H+ ions Two primary types of acid –Carbonic- generated from the metabolism of carbohydrates and fats Results in the generation of approximately 15,000 mmol of CO 2 per day –Non-carbonic- generated by the metabolism of proteins Results in the generation of approximately meq/day of acid on a normal diet

Acid-Base Introduction In respiratory acidosis why does bicarbonate increase?

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Carbonic Acid (H 2 CO 3 ) Buffer system CO 2 + H 2 O H 2 CO 3 H + + HCO molecules of CO 2 per molecule of H 2 CO 3 Can see, equilibrium tends to keep CO 2 as CO 2, that’s why carbonic anhydrase present in RBCs and kidney molecules of HCO 3 - per molecule of H 2 CO 3 So once formed, H 2 CO 3 immediately converts to bicarbonate and a hydrogen ion 2.1.

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Carbonic Acid (H 2 CO 3 ) Buffer system Because of these equilibrium constants, the net effect is: CO 2 + H 2 O H + + HCO 3 - Works well when you can control the CO 2 and shift the equation to the right. H + + HCO 3 - CO 2 + H 2 O 1.Add an acid 2. Combines with serum bicarbonate 3. Exhale carbon dioxide, driving equation to the right and removing all the acid 4. Kidney must later regenerate the used bicarb But what about respiratory acidosis (i.e. the inability to control the CO 2 )? 21 3

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis CO 2 CO 2 + H 2 O H 2 CO 3 (inc CO 2 drives to right) H 2 CO 3 H + + HCO 3 - Bicarb can’t buffer H 2 CO 3, because bicarb + H 2 CO 3 equals bicarb + H 2 CO 3 (H + + HCO 3 - ) + HCO 3 - (H + + HCO 3 - ) + HCO 3 - What happens instead is: H 2 CO 3 + Hemoblogin(Hb - ) HHb + HCO 3 -

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis CO 2 What happens instead is: H 2 CO 3 + Hemoblogin(Hb - ) HHb + HCO 3 - Net effect is for every molecule of CO2 retained, after the resulting H+ is buffered by the plasma proteins, one molecule of HCO3 is left over This is why the bicarbonate (a base) actually increases during respiratory acidosis -It is effectively an “anion gap” for respiratory acidosis Note: no renal involvement whatsoever at this stage. Acute compensation in respiratory acidosis would occur even in an anephric patient

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis CO 2 As a rule of thumb, the bicarbonate should increase 1 meq/L for every 10mm Hg increase in CO 2 above normal Note: not a one for one due to the differing units- meq/L vs. mmHg

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis ( CO 2 ), Acute Effect of Serum Buffering Ex. Increase PCO2 from 40 to 80 mmHg -Without buffering, H+ increases to 80 nanomol/L H + = 24 X PCO2/Bicarb = 24 X 80 / 24 = 80 Equals a pH of With buffering, 40 increase in CO2 causes a 4 increase in bicarbonate H + = 24 X PCO2/Bicarb = 24 X 80 /28 = 69 Equals a pH of 7.17 So it helps, but overall, not great

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis ( CO 2 ), Chronic At 4-5 days, the kidneys kick in and increase the bicarbonate 3.5meq/L per every 10 increase in PCO2 Ex. Increase PCO2 from 40 to 80 mmHg -With buffering, 40 increase in CO2 causes a 14 increase in bicarbonate H = 24 X PCO2/Bicarb = 24 X 80 /38 = 50 Equals a pH of 7. 3 (vs with acute serum buffering or 7.10 without buffering)

Acid-Base Bicarbonate/Carbon Dioxide Buffer System Respiratory Acidosis ( CO 2 ), Chronic Renal Measures– Why does the kidney increase bicarbonate which is an ineffective buffer? Why not just dump H+ -Kidney can’t excrete much free H + -pH of 4.5 (minimal urine pH)= urine H+ concentration 1000x serum, still only represents a free H + of 0.04meq/L -Given a daily acid production of 100meq, it would require: 100meq/0.04meq/L or 2500 liters of urine per day to excrete as free hydrogen -Net effect, kidney sees decreased pH, combines CO 2 + H 2 0 to make carbonic acid. It dumps the H + into the urine (converting NH 3 + to NH 4 + ) and the bicarbonate is returned to the serum H + is dumped, and bicarbonate increases (hence the 3.5meq increase per each 10mmHg increase in CO 2 )

Acid-Base Bicarbonate/Carbon Dioxide Buffer System The reverse of these actions occur in the face of respiratory alkalosis - CO 2 (acute) CO 2 + H 2 O H 2 CO 3 (dec CO 2 drives to left) H 2 CO 3 H + + HCO 3 - (H 2 CO 3 dec drives left) Bicarbonate drops because it is being used to generate H 2 CO 3 (which is ultimately converted to try and raise CO 2 ). The pH drops because H+ is also consumed. Serum buffers give up H+ to try and raise the pH. Net result is that HCO 3 drops 2meq/L per every 10 decrease in pCO 2

Acid-Base Bicarbonate/Carbon Dioxide Buffer System The reverse of these actions occur in the face of respiratory alkalosis - CO 2 (chronic) CO 2 + H 2 O H 2 CO 3 (dec CO 2 drives to left) H 2 CO 3 H + + HCO 3 - (H 2 CO 3 dec drives left) Kidney essentially “pisses” away bicarbonate (which is the equivalent of adding acid to the body). Thereby correcting the alkalosis Net result is that CHRONICALLY HCO 3 drops 5meq/L per every 10 decrease in pCO 2 - easy to remember, the change is bigger for alkalosis because it is easier to urinates the bicarb away rather than making new as in the case of acidosis induced changed

Acid-Base Compensation for Primary Acid-Base Disturbances DisorderPrimary ChangeCompensation Metabolic Acidosis HCO 3 - Winters, 1.2mmHg decrease in pCO 2 per 1meq/L fall in HCO 3 -, or pCO 2 = last 2 digits of pH Metabolic Alkalosis HCO %, or 0.7mm Hg increase in pCO 2 per 1meq/L rise in HCO 3 - Respiratory Acidosis -Acute pCO 2 1 meq/L per 10 mm Hg -Chronic pCO meq/L per 10 mm Hg Respiratory Alkalosis -Acute pCO 2 2 meq/L per 10 mm Hg -Chronic pCO 2 5 meq/L per 10 mm Hg

PCO 2 from 12-32, same as Winters

PCO 2 from 14-40, same as Winters

Acid-Base Compensation for Primary Acid-Base Disturbances DisorderPrimary ChangeCompensation Metabolic Acidosis HCO 3 - Winters, 1.2mmHg decrease in pCO 2 per 1meq/L fall in HCO 3 -, or pCO 2 = last 2 digits of pH Metabolic Alkalosis HCO %, or 0.7mm Hg increase in pCO 2 per 1meq/L rise in HCO 3 - Respiratory Acidosis -Acute pCO 2 1 meq/L per 10 mm Hg -Chronic pCO meq/L per 10 mm Hg Respiratory Alkalosis -Acute pCO 2 2 meq/L per 10 mm Hg -Chronic pCO 2 5 meq/L per 10 mm Hg

Metabolic Alkalosis Works even better

Acid-Base Cannot be performed in a vacuum, interpretation must take into account the history –Ex. pH 7.27, pCO2 70, Bicarb 31, PO2 35 What does this represent? –Next slide

Acid-Base Cannot be performed in a vacuum, interpretation must take into account the history –Ex. pH 7.27, pCO2 70, Bicarb 31, PO2 35 What does this represent? –pH decreased– Acidosis –PCO2 increased- Respiratory acidosis »If acute, bicarb should increase 1/10, or = 27 »If chronic, bicarb should increase 3.5/10, or = 35 »Intermediate value means this could be an acute respiratory acidosis transitioning to chronic, a chronic acidosis with superimposed metabolic acidosis, or a acute respiratory acidosis superimposed on a metabolic alkalosis None of these can be distinguished without the respective histories (or this assistance of a anion gap/potential bicarb determination)

Acid-Base Even a value that appears to be “ideal” compensation can actually be 3 disorders. Must use anion gap, potential bicarbonate, and history 1. COPD with chronic respiratory acidosis 2. Develops vomiting (contraction alkalosis) 3. Develops vomiting (contraction alkalosis)