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
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
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
[HCO3－] pH=pKa+log [H2CO3] H2CO3 H+ + HCO3- 24 = 6.1+ log 1.2 20 = 6.1+ log 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
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+
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
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. ↓
pH acidosis alkalosis metabolic respiretory metabolic respiretory [HCO3-]↓ PaCO2↑ [HCO3-]↑ PaCO2↓ 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-DKA).
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 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
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.
Anion Gap (AG) • This is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. This test is most commonly performed in patients who present with altered mental status, unknown exposures, acute renal failure, and acute illnesses.
The normal value for the serum anion gap: • With potassium • The anion gap is calculated by subtracting the serum concentrations of chloride and bicarbonate (anions) from the concentrations of sodium and potassium (cations): • = ([Na+] + [K+]) − ([Cl−] + [HCO−= 20 mEq/L • Without potassium (daily practice) • Because potassium concentrations are very low, they usually have little effect on the calculated gap. Therefore, omission of potassium has become widely accepted.This leaves the following equation: • = [Na+] - ([Cl−] + [HCO−normal AG= 6-12 mEq/L.
For the urine anion gap, the most prominently unmeasured anion is ammonia. Healthy subjects typically have a gap of 0 to slightly normal (< 10 mEq/L). A urine anion gap of more than 20 mEq/L is seen in metabolic acidosis when the kidneys are unable to excrete ammonia (such as in renal tubular acidosis). If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting).
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 ↓