1. Department of Biochemistry
Acid and Base Balance
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. 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
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
in Plasma
in RBC
H2CO3 / HCO3-
35%
18%
HHb / Hb-
HPro / Pro- 7%
H2PO4- / HPO42- 5%
Total
42%
58%

8. Bicarbonate buffer Predominant buffer system
Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3)
HCO3- : H2CO3: Maintain a 20:1 ratio
= = 7.4
pH=pKa+lg
[HCO3－]
[H2CO3]
= 6.1+ lg 24
1.2 20 1
H2CO H+ + HCO3-

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. 2. Respiratory mechanisms
CO2
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. acidosis alkalosis pH respiretory [HCO3-]↓ [HCO3-]↑ PaCO2↑ PaCO2↓
metabolic
HCO3－

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

22. 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).

23. 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

25. Respiratory Acidosis
Carbonic acid excess caused 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

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

28. 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

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

31. 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.

32. Compensation of Respiratory Alkalosis
Kidneys conserve hydrogen ion
Excrete bicarbonate ion

34. 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.

35. 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 ↓