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Buffer Systems of the Body

Dr. M. Sasvári: Medical Chemistry Lectures 6. Buffer Systems of the Body. 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.

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Buffer Systems of the Body

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  1. Dr. M. Sasvári: Medical Chemistry Lectures 6. Buffer Systems of the Body MedChem 6

  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 MedChem 6

  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) MedChem 6

  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: MedChem 6

  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- MedChem 6

  6. 6.9=7.2 + log [HPO42-]:[H2PO4-] = 1 : 2 Average charge of phosphoric acid (Pi) What is the average charge of Pi at pH=6.9 ? pK values of phosphoric acid are: 2.1, 7.2 and 12.3. [HPO42-] 6.9 – 7.2 = -0.3=+ log (x) x =0.5 = 1/2 [H2PO4-] average charge: [1(-2)+2(-1)]/3=1.33 (-) MedChem 6

  7. 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] MedChem 6

  8. [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 ? MedChem 6

  9. 1.2 meqv/L H2O + CO2 HCO3-+ H+ 24 meqv/L Acid capacity is larger than base capacity! (HCO3-) >>>> (CO2) Acid /base capacity? MedChem 6

  10. H2CO3 HCO3-+ H+ H2O + CO2 ? e.g. 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 MedChem 6

  11. 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 MedChem 6

  12. CO2 CO2 + H2O H2CO3 H+ + HCO3- + Hb- Cl- HbH HCO3- Cl- Stabilization of [HCO3-] by the RBC MedChem 6

  13. 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) MedChem 6

  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) MedChem 6

  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 MedChem 6

  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) MedChem 6

  17. BLOOD KIDNEY URINE H2CO3 H+ NH3 NH4+ Amino acids Role of the kidney HCO3- Re-absorption of bicarbonate ion Excretion of H+ (NH4+) MedChem 6

  18. CO2 + H2O HCO3- + H+ Proteins (Hb) H2CO3 Ventilation H+ Kidney Final excretion of acids The super-buffer of the blood Temporal pH stabilization by red blood cells MedChem 6

  19. H2CO3 HCO3-+ H+ + Hb-  HbH H2O + CO2 Respiratory acidosis Problem with ventilation Increase in HCO3- with slight decrease in pH MedChem 6

  20. SUMMARY Buffer systems of the body Important terms: Intracellular and extracellular buffer systems of the body, average charge of phosphoric acid at various pH, components of the bicarbonate buffer in the blood, role of the ventilation in pH stabilization role of the red blood cells in pH stabilization, role of the kidney in pH stabilization, metabolic acidosis, metabolic alkalosis, respiratory acidosis, total acidity of the urine MedChem 6

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