Buffer Systems of the Body

1. Dr. M. Sasvári: Chemistry Lectures Buffer Systems of the Body Chem Eq 7

2. pH of the blood-plasma 7.38 7.42 pH = 7.4 ALKALOSIS ACIDOSIS The major body water components • Extracellular fluid (Blood plasma + interstitial fluids) • Intracellular fluids Chem Eq 7

3. The most important buffer systems in our body • bicarbonate/carbonic acid (extracellular) phosphate buffer (intracellular) the Histidine side chain of proteins (Hemoglobin in RBC) Chem Eq 7

4. pKa=7.2 H2PO4- HPO42- + H+ [HPO42-] [H2PO4-] pH = 7.2 + log The phosphate buffer system: The most important intracellular buffer system  Henderson-Hasselbalch equation: Chem Eq 7

5. O O O O O - O - O - O - - O - P - O - P - O - - P - O - H O - P - O - Forms of intracellular phosphates Inorganic phosphate (phosphoric acid) pyrophosphate PPi Pi • Phosphate group is present: • on ATP • on the intracellular sugars • and their catabolic products phosphoryl (phosphate) group -PO32- Chem Eq 7

6. CO2 + H2O H2CO3 H2CO3HCO3-+ H+ CO2HCO3-+ H+ pH = pK + log The bicarbonate/carbonic acid system Carbonic acid carbondioxide bicarbonate Henderson-Hasselbalch equation: [HCO3-] a1 [CO2] Chem Eq 7

7. [CO2] = 1.2 meqv/L [CO2]=0.03 pCO where p= partial pressure 2 pH = 6.1+ log 20 24 24 = = 1 1.2 1.2 [HCO3-] [CO2] Normal values [HCO3-]= 24 meqv/L Henderson-Hasselbalch equation: = 7.4 ? Chem Eq 7

8. low H2O + CO2 HCO3-+ H+ high Acid capacity is larger! Calculation of acid capacity: 24 – x 5.1 = 6.1+ log 1.2 + x (HCO3-) >>>> (CO2) Acid /base capacity? Chem Eq 7

9. H2CO3 HCO3-+ H+ H2O + CO2 ? x=12 meqv 24 – 12 pH = 6.1+ log = 6.06 1.2 + 12 Why is the bicarbonate buffer a super-buffer for the blood? H+ x meqv 24 meqv 24- x 1.2meqv 1.2+ x Chem Eq 7

10. H2CO3 HCO3-+ H+ H+ x meqv H2O + CO2 = 7.1 24 - 12 pH = 6.1+ log 1.2+ 0 Effect of Ventilation 24 meqv 24- x 1.2meqv CO2 concentration is stabilized by ventilation ACIDOSIS: Hyperventilation ALKALOSIS: Hypoventilation Chem Eq 7

11. Graphical representation: The pH-bicarbonate diagram Constant CO2 concentration (normal ventilation) [CO2]=1.2 meqv (p = 40 Hgmm) 24 meqv Clinical test: Assay of [bicarbonate] in the serum  pH from the graph ACIDOSIS (hyperventilation) ALKALOSIS (hypoventilation) Chem Eq 7

12. CO2 CO2 + H2O H2CO3 H+ + HCO3- + Hb- Cl- HbH HCO3- Cl- Stabilization of [HCO3-] by the RBC Chem Eq 7

13. CO2 + H2O HCO3- + H+ Hemoglobin RBC Ventilation The super-buffer of the blood Temporal pH stabilization by the compensational mechanisms of the red blood cells All the concentrations of the equation are nearly constant Chem Eq 7

14. Sources of acids and bases • Metabolic acidosis: • normal metabolism: • lactic acid (exercise) • acetoacetic acid (starvation) • phosphoric acid (energy) • diet (~60 meqv acid / day) HCO3- depletion (sever diarrhea) Metabolic alkalosis: normal metabolism: - diet: Na-salts of weak acids (fruits, vegetables) Abnormal loss of acids (prolonged vomiting) Chem Eq 7

15. Forms of H+ excretion HPO42- + H+ H2PO42- pKa= 7.2 NH3 + H+ NH4+ pKa= 9.3 Final removal of acids: Kidney pH of the urine ~ 6 range: 4.4 < pH > 8.0 Calculation: The lowest pH of the urine is 4.4 50 meqv [H+] excretion would need Extractable amount of acids: approximately 50 meqv / day (normal) 1250 L volume of urine ???????? Diabetic ketoacidosis (pH of the urine is ~4.4) acetoacetic acid pK=3.6 b-OH-butyric acid pK=4.7 Chem Eq 7

16. Total acidity of the urine Titrable acidity [H+] (Titration back to pH = 7.4) NH4+ content major urinary acid (could reach 500 meqv/day in acidosis) Final removal of basis in alkalosis: HCO3- secretion (kidney) Chem Eq 7

17. BLOOD KIDNEY URINE H2CO3 H+ NH3 NH4+ Amino acids Role of the kidney HCO3- Re-absorption of bicarbonate ion Excretion of H+ (NH4+) Chem Eq 7

18. CO2 + H2O HCO3- + H+ Proteins (Hb) H2CO3 Ventilation H+ Kidney Excretion The super-buffer of the blood Chem Eq 7

19. H2CO3 HCO3-+ H+ + Hb-  HbH H2O + CO2 Respiratory acidosis Problem with ventilation Increase in HCO3- with slight decrease in pH Chem Eq 7