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Acid and Base Balance Department of Biochemistry 1 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 2 3 The body produces more acids than bases • Acids take in with foods. • Cellular metabolism produces CO2. • Acids produced by metabolism of lipids and CO2 proteins. Volatile acid H2CO3 CO2+ H2O CO2 CO2 (H+ 15 –20 mol /d) Fixed acid H2SO4 H3PO4 Uric acid Lactic acid Ketone body (H+ < 0.05 –0.10 mol /d) 4 Maintenance of blood pH • Three lines of defense to regulate the body’s acid-base balance – Blood buffers – Respiratory mechanism – Renal mechanism 5 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 6 Principal buffers in blood H2CO3 / HCO3- in Plasma in RBC 35% 18% HHb / HbHPro / Pro- 35% 7% H2PO4- / HPO42Total 5% 42% 58% 7 Bicarbonate buffer • Predominant buffer system • Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) • HCO3- : H2CO3: Maintain a 20:1 ratio pH=pKa+lg H2CO3 H+ + HCO3- [HCO3-] [H2CO3] = 6.1+ lg = 6.1+ lg 24 1.2 20 1 = 6.1+1.3 = 7.4 8 Bicarbonate buffer • HCl + NaHCO3 ↔ H2CO3 + NaCl • NaOH + H2CO3 ↔ NaHCO3 + H2O 9 Phosphate buffer • Major intracellular buffer • NaH2PO4-Na2HPO4 • H+ + HPO42- ↔ H2PO4- • OH- + H2PO4- ↔ H2O + HPO4210 Protein Buffers • Include plasma proteins and hemoglobin • Carboxyl group gives up H+ • Amino Group accepts H+ 11 2. Respiratory mechanisms CO2 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 12 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 13 Rates of correction • Buffers function: almost instantaneously • Respiratory mechanisms: take several minutes to hours • Renal mechanisms: may take several hours to days 14 15 16 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. 17 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. ↓ 18 pH acidosis HCO3- alkalosis metabolic respiretory metabolic respiretory [HCO3-]↓ PaCO2↑ [HCO3-]↑ PaCO2↓ 19 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 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 25 Compensation for Respiratory Acidosis • Kidneys eliminate hydrogen ion (H+ and NH4+) and retain bicarbonate ion 26 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 28 Compensation for Metabolic Alkalosis • Hypoventilation to retain CO2 (hence H2CO3↑) • Renal excretes more HCO3-, retain H+. 29 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. 31 Compensation of Respiratory Alkalosis • Kidneys conserve hydrogen ion • Excrete bicarbonate ion 32 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. 34 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 ↓ 35