Acid and Base Balance

1. Acid and Base Balance Zhihong Li（李志红） Department of Biochemistry

2. The Body and pH • Homeostasis of pH is tightly controlled • Extracellular fluid = 7.4 • Blood = 7.35 – 7.45 • < 7.35: Acidosis (acidemia) • > 7.45: Alkalosis (alkalemia) • < 6.8 or > 8.0: death occurs

4. CO2 CO2 The body produces more acids than bases • Acids take in with foods. • Cellular metabolism produces CO2. • Acids produced by metabolism of lipids and proteins. CO2 H2CO3 CO2+ H2O Volatile acid (H+ 15 –20 mol /d) H2SO4 H3PO4 Uric acid Lactic acid Ketone body (H+ < 0.05 –0.10 mol /d) Fixed acid

5. Maintenance of blood pH • Three lines of defense to regulate the body’s acid-base balance • Blood buffers • Respiratory mechanism • Renal mechanism

6. Buffer systems • Take up H+ or release H+ as conditions change • Buffer pairs – weak acid and a base • Exchange a strong acid or base for a weak one • Results in a much smaller pH change

7. Principal buffers in blood

8. [HCO3－] pH=pKa+lg [H2CO3] H2CO3 H+ + HCO3- 24 = 6.1+ lg 1.2 20 = 6.1+ lg 1 = 6.1+1.3 = 7.4 Bicarbonate buffer • Predominant buffer system • Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) • HCO3- : H2CO3: Maintain a 20:1 ratio

9. Bicarbonate buffer • HCl + NaHCO3↔ H2CO3 + NaCl • NaOH + H2CO3 ↔ NaHCO3 + H2O

10. Phosphate buffer • Major intracellular buffer • NaH2PO4-Na2HPO4 • H+ + HPO42-↔ H2PO4- • OH- + H2PO4- ↔ H2O + HPO42-

11. Protein Buffers • Include plasma proteins and hemoglobin • Carboxyl group gives up H+ • Amino Group accepts H+

12. CO2 CO2 2. Respiratory mechanisms • Exhalation of CO2 • Rapid, powerful, but only works with volatile acids • H+ + HCO3-↔ H2CO3 ↔ CO2 + H20 • Doesn’t affect fixed acids like lactic acid • Body pH can be adjusted by changing rate and depth of breathing

13. 3. Kidney excretion • Most effective regulator of pH • The pH of urine is normally acidic (~6.0) • H+ ions generated in the body are eliminated by acidified urine. • Can eliminate large amounts of acid (→H+) • Reabsorption of bicarbonate (HCO3-) (←HCO3-) • Excretion of ammonium ions(NH4+) (→NH4+) • If kidneys fail, pH balance fails

14. Rates of correction • Buffers function: almost instantaneously • Respiratory mechanisms: take several minutes to hours • Renal mechanisms: may take several hours to days

17. Acid-Base Imbalances • pH< 7.35: acidosis • pH > 7.45: alkalosis • The body response to acid-base imbalance is called compensation • The body gears up its homeostatic mechanism and makes every attempt to restore the pH to normal level. • May be complete if brought back within normal limits • Partial compensation if range is still outside norms.

18. Acid-Base Imbalances • Acidosis- a decline in blood pH ↓ • Metabolic acidosis: due to a decrease in bicarbonate. ↓ • Respiratory acidosis: due to an increase in carbonic acid. ↑ • Alkalosis- a rise in blood pH ↑ • Metabolic alkalosis: due to an increase in bicarbonate.↑ • Respiratory alkalosis : due to a decrease in carbonic acid. ↓

19. pH acidosis alkalosis metabolic respiretory metabolic respiretory [HCO3-]↓ PaCO2↑ [HCO3-]↑ PaCO2↓ HCO3－

20. Compensation • If underlying problem is metabolic, hyperventilation or hypoventilation can help: respiratory compensation. • If problem is respiratory, renal mechanisms can bring about metabolic compensation.

21. Metabolic Acidosis • Bicarbonate deficit (↓)- blood concentrations of bicarb drop below 22mEq/L (milliequivalents / liter) • Causes: • Loss of bicarbonate through diarrhea or renal dysfunction • Accumulation of acids (lactic acid or ketones) • Failure of kidneys to excrete H+ • Commonly seen in severe uncontrolled DM (ketoacidosis).

22. Compensation for Metabolic Acidosis • Hyperventilation: increased ventilation • Renal excretion of H+ if possible • K+ exchanges with excess H+ in ECF • H+ into cells, K+ out of cells

23. Respiratory Acidosis • Carbonic acid excesscaused by blood levels of CO2 above 45 mm Hg. • Hypercapnia – high levels of CO2 in blood • Causes: • Depression of respiratory center in brain that controls breathing rate – drugs or head trauma • Paralysis of respiratory or chest muscles • Emphysema

24. Compensation for Respiratory Acidosis • Kidneys eliminate hydrogen ion (H+ and NH4+) and retain bicarbonate ion

25. Metabolic Alkalosis • Bicarbonate excess↑ - concentration in blood is greater than 26 mEq/L • Causes: • Excess vomiting = loss of stomach acid • Excessive use of alkaline drugs • Certain diuretics • Endocrine disorders: aldosterone ↑ • Heavy ingestion of antacids

26. Compensation for Metabolic Alkalosis • Hypoventilation to retain CO2 (hence H2CO3↑) • Renal excretes more HCO3-, retain H+.

27. Respiratory Alkalosis • Carbonic acid deficit↓ • pCO2 less than 35 mm Hg (hypocapnea) • Most common acid-base imbalance • Primary cause is hyperventilation • Hysteria, hypoxia, raised intracranial pressure, excessive artificial ventilation and the action of certain drugs (salicylate) that stimulate respiratory centre.

28. Compensation of Respiratory Alkalosis • Kidneys conserve hydrogen ion • Excrete bicarbonate ion

29. Mixed acid-base disorders • Sometimes, the patient may have two or more acid-base disturbances occurring simultaneously. • In such instances, both HCO3- and H2CO3 are altered.

30. Points • Blood = 7.35 – 7.45; • < 7.35: Acidosis, > 7.45: Alkalosis • Three lines of defense to regulate the body’s acid-base balance • Blood buffers:Bicarbonate buffer, Phosphate buffer, Protein Buffers • Respiratory mechanisms: Exhalation of CO2 • Renal mechanism: eliminate acid, Reabsorption of HCO3- • Acidosis- blood pH ↓(Causes, Compensation) • Metabolic acidosis: bicarbonate ↓ • Respiratory acidosis: carbonic acid ↑ • Alkalosis- blood pH ↑ (Causes, Compensation) • Metabolic alkalosis: bicarbonate↑ • Respiratory alkalosis : carbonic acid ↓