Acid base principles and disorders Biochemistry Nabil Bashir 4/2016

Acid base equilibrium CO2 + H2O ↔ HCO3- + H+ ↑ determines pH

maintained by kidneys ↓ CO2 + H2O ↔ HCO3- + H+ ↑ ↑ maintained by lungs determines pH

low value→high H+(Low PH) ↓ CO2 + H2O ↔ HCO3- + H+ ↑ Acid base equilibrium low value→high H+(Low PH) high value → low H+(high pH) ↓ CO2 + H2O ↔ HCO3- + H+ ↑ low value→low H+(high PH) high value→high H+(low PH)

Henderson-Hasselbalch Equation

Acid base equilibrium Normal HCO3=22-26 mEq/L <24> in venous blood Normal pCO2= 35-45 mmHg <40> arterial blood Normal pH= 7.35-7.45 arterial blood

Acidosis symptoms Hyperventilation Depression of myocardial contractility Cerebral vasodilation; increased cerebral blood flow. CO2 + H2O ↔ HCO3- + H+

CNS depression( very high CO2 levels) Hyperkalemia; high H+ shifts into cells in exchange for K+ Shift in oxygen hemoglobin dissociation curve; Bohr effect; low pH leads to hemoglobin releasing oxygen

Alkalosis symptoms Inhibition of respiratory drive: retain CO2 Depression of myocardial contractility Cerebral vasoconstriction; decrease in cerebral blood flow Hypokalemia Shift in hemoglobin dissociation curve

Acid- base problems Check the pH pH< 7.35 = acidosis pH > 7.45 –alkalosis 2. Check the HCO3 and pCO2 HCO3 from veinpuncture, normal 22-28 pCO2 from ABG; normal 35-45

3. Determine acid-base disorder Acidosis+ low HCO3= metabolic acidosis Acidosis+ high pCO2= respiratory acidosis Alkalosis+high HCO3= metabolic alkalosis Alkalosis+ low CO2= respiratory alkalosis CO2 + H2O ↔ HCO3- + H+

Step 1: what is acid base disorder? Metabolic acidosis, resp alkalosis,etc…. Step 2; Is there a second disorder? Is the compensation appropriate?

Compensatory changes Low HCO3=metabolic acidosis Compensation= lowering CO2 High HCO3= metabolic alkalosis Compensation= retain CO2 High CO2= resp acidosis Compensation= increasing HCO3 Low CO2= respiratory alkalosis compensation-= lowering HCO3 CO2 + H2O ↔ HCO3- + H+

Cause vs compensation Most acid-base disorders; abnormal HCO3 and abnormal Pco2 One is causing disorder Other is compensatory change Example 1: pH=7.30 (acidosis) HCO3 =low pCO2= = low Metabolic acidosis with respiratory compensation CO2 + H2O ↔ HCO3- + H+

Example 2: pH=7.30 (acidosis) HCO3 =high pCO2= = high respiratory acidosis with compensation Metabolic CO2 + H2O ↔ HCO3- + H+

Respiratory compensation Hyper or hypoventilation Changes pCO2 to compensate for metabolic disorders

Respiratory compensation Hyperventilation: Blows off CO2 Plasma CO2 levels fall Less H+ in blood pH rises CO2+H2O ↔HCO3+H+ Hypoventilation: Retains CO2 Plasma CO2 level rises More H+ in blood pH falls

Renal compensation Acidosis: Excess H+ filtered/secreted into nephron more Bicarb reabsorbed Urinary buffers excreted: -HPO4 -2 EXCRETED -NH3 excreted -these bind H+(buffers) -prevent severe drops in pH Alkalosis: -reverse of acidosis

Mixed disorders Two disorders at same time -metabolic acidosis and respiratory alkalosis/acidosis -metabolic acidosis and metabolic alkalosis -two metabolic acidosis -occurs in many pathological states -i.e. vomiting and diarrhea To uncover, determine expected response: -expected HCO3 for respiratory disorder -expected CO2 for metabolic disorder -use renal formulas to determine expected response If actual≠ expected →2nd disorder present

Mixed disorders If actual ≠ expected, determine abnormality i.e. if CO2 higher than expectedsecondary resp disorder i.e. HCO3 lower than expectedsecondary metab disorder Usual rules then apply for determining secondary disorders: High CO2 = acidosis Low CO2= alkalosis Low HCO3= acidosis High HCO3= alkalosis

Compensation formulas Winters formula Metabolic alkalosis formula Acute/chronic respiratory formula

Metabolic acidosis compensation Compensation respiratory alkalosis (lowering CO2) Hyper venttilation Winters formula: tells you expected increase in CO2 If actual CO2 ≠expected, mixed disorder pCO2= 1.5 (HCO3)+ 8 +/-2 EXAMPLE: pH=7.2 HCO3=9mEq/L pCO2= 22mmhg Expected CO2= 1.5(9)+8=22 +/-2 (20-24) No secondary disorder

Example 2: Ph= 7. 28 HCO3=12MEq/L pCO2= 40 mmhg Expected pCO2 =1 Example 2: Ph= 7.28 HCO3=12MEq/L pCO2= 40 mmhg Expected pCO2 =1.5(12) +8= 26 +/-2 =28-30 pCO2 > expected Concomitant respiratory acidosis

Metabolic alkalosis compensation Compensatory respiratory acidosis (to raise pCO2) Hypoventilation Rise pCO2 0.7 mmHg per 1.0 meq/L rise HCO3 If actual Pco2 ≠ expected, mixed disorder ΔpCO2 = 0.7 * ( Δ HCO3) Example: pH=7.5 HCO3=34 pCO2=47 ΔHCO3=34-24=10 Expected ΔpCO2=0.7(10)=7 ActualΔpCO2=47-40=7 No secondary disorder

Respiratory acidosis compensation Acute compensation: -minutes -intracellular buffers raise HCO3 -hemoglobin and other proteins -small rise in pH Chronic compensation -days -renal generation of large HCO3 -large increase in pH( but not back to normal)

Respiratory acidosis compensation Acute compensation: -1 meq/l rise HCO3 for every 10 mmHg increase pCO2 -ΔHCO3=ΔpCO2/10 Chronic compensation: -3.5 meq/l rise HCO3 for every 10 mmHg increase pCO2 -ΔHCO3= 3.5*ΔpCO2/10 Example: pH=7.15 pCO2 =80 Acute ΔHCO3=40/10=4 HCO3=28(24+4); pH7.17 (H-H) Chronic ΔHCO3=3.5*40/10=14 HCO3=38; pH=7.3

Respiratory alkalosis compensation Acute compensation -2 meq/l fall HCO3 for every 10 mmHg drop pCO2 -ΔHCO3=2*ΔpCO2/10 Chronic compensation -4meq decrease in HCO3 for every 10 decrease in Pco2 -ΔHCO3=4* ΔpCO2/10 Example: pH=7.65 pCO2=20 Acute ΔHCO3=2*20/10=4 HCO3=20, pH=7.63 Chronic ΔHCO3 =4*20/10=8 HCO3=16; pH=7.53

Compensation timeframe Respiratory compensation to metabolic disorders: -rapid -change in respiratory rate =minutes Metabolic compensation to respiratory disorders: -acute, mild compensation in minutes from cells -chronic, significant compensation in days from kidneys