Acid and Base Balance Department of Biochemistry 1
Acid and Base Balance Department of Biochemistry 1
The Body and p. H • • • Homeostasis of p. H 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
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The body produces more acids than bases • Acids take in with foods. • Cellular metabolism produces CO 2. • Acids produced by metabolism of lipids and CO 2 proteins. Volatile acid H 2 CO 3 CO 2+ H 2 O CO 2 (H+ 15 – 20 mol /d) Fixed acid H 2 SO 4 H 3 PO 4 Uric acid Lactic acid Ketone body (H+ < 0. 05 – 0. 10 mol /d) 4
Maintenance of blood p. H • 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 p. H change 6
Principal buffers in blood H 2 CO 3 / HCO 3 - in Plasma in RBC 35% 18% HHb / Hb. HPro / Pro- 35% 7% H 2 PO 4 - / HPO 42 Total 5% 42% 58% 7
Bicarbonate buffer • Predominant buffer system • Sodium Bicarbonate (Na. HCO 3) and carbonic acid (H 2 CO 3) • HCO 3 - : H 2 CO 3: Maintain a 20: 1 ratio H 2 CO 3 H+ + HCO 3 - p. H=p. Ka+lg = 6. 1+ lg [HCO 3-] [H 2 CO 3] 24 1. 2 20 1 = 6. 1+1. 3 = 7. 4 8
Bicarbonate buffer • HCl + Na. HCO 3 ↔ H 2 CO 3 + Na. Cl • Na. OH + H 2 CO 3 ↔ Na. HCO 3 + H 2 O 9
Phosphate buffer • Major intracellular buffer • Na. H 2 PO 4 -Na 2 HPO 4 • H+ + HPO 42 - ↔ H 2 PO 4 • OH- + H 2 PO 4 - ↔ H 2 O + HPO 4210
Protein Buffers • Include plasma proteins and hemoglobin • Carboxyl group gives up H+ • Amino Group accepts H+ 11
2. Respiratory mechanisms CO 2 • Exhalation of CO 2 • Rapid, powerful, but only works with volatile acids • H+ + HCO 3 - ↔ H 2 CO 3 ↔ CO 2 + H 20 • Doesn’t affect fixed acids like lactic acid • Body p. H can be adjusted by changing rate and depth of breathing 12
3. Kidney excretion • Most effective regulator of p. H • The p. H 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 (HCO 3 -) (←HCO 3 -) • Excretion of ammonium ions(NH 4+) (→NH 4+) • If kidneys fail, p. H 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
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Acid-Base Imbalances • p. H< 7. 35: acidosis • p. H > 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 p. H 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 p. H ↓ – Metabolic acidosis: due to a decrease in bicarbonate. ↓ – Respiratory acidosis: due to an increase in carbonic acid. ↑ • Alkalosis- a rise in blood p. H ↑ – Metabolic alkalosis: due to an increase in bicarbonate. ↑ – Respiratory alkalosis : due to a decrease in carbonic acid. ↓ 18
p. H acidosis HCO 3- alkalosis metabolic respiretory [HCO 3 -]↓ Pa. CO 2↑ [HCO 3 -]↑ Pa. CO 2↓ 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 22 m. Eq/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 CO 2 above 45 mm Hg. • Hypercapnia – high levels of CO 2 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 NH 4+) and retain bicarbonate ion 26
Metabolic Alkalosis • Bicarbonate excess↑ - concentration in blood is greater than 26 m. Eq/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 CO 2 (hence H 2 CO 3↑) • Renal excretes more HCO 3 -, retain H+. 29
Respiratory Alkalosis • • Carbonic acid deficit↓ p. CO 2 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 HCO 3 - and H 2 CO 3 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 CO 2 – Renal mechanism: eliminate acid, Reabsorption of HCO 3 - • Acidosis- blood p. H ↓(Causes, Compensation) – Metabolic acidosis: bicarbonate ↓ – Respiratory acidosis: carbonic acid ↑ • Alkalosis- blood p. H ↑ (Causes, Compensation) – Metabolic alkalosis: bicarbonate↑ – Respiratory alkalosis : carbonic acid ↓ 35
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