Department of Biochemistry Acid and Base Balance Department of Biochemistry

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

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

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

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

Principal buffers in blood in Plasma in RBC H2CO3 / HCO3- 35% 18% HHb / Hb- HPro / Pro- 7% H2PO4- / HPO42- 5% Total 42% 58%

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

Bicarbonate buffer HCl + NaHCO3 ↔ H2CO3 + NaCl NaOH + H2CO3 ↔ NaHCO3 + H2O

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

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

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

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

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

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.

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. ↓

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

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

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).

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

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

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

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

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

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.

Compensation of Respiratory Alkalosis Kidneys conserve hydrogen ion Excrete bicarbonate ion

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.

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 ↓