Acid-base Acid-base balancebalanceD-r GeorgievaD-r Georgieva

Hydrogen ion Hydrogen ion concentration, pHconcentration, pH

Nearly all biochemical reactions in the Nearly all biochemical reactions in the body are dependent on maintenance of body are dependent on maintenance of a physiological hydrogen ion a physiological hydrogen ion concentration.concentration.

Hydrogen ion concentration is more Hydrogen ion concentration is more commonly expressed as pH.commonly expressed as pH.

The pH of a solution is defined as The pH of a solution is defined as negative logarithm of [H+].negative logarithm of [H+].

Normal arterial pH is 7.40. pH between Normal arterial pH is 7.40. pH between 6,8 and 7,8 is compatible with life.6,8 and 7,8 is compatible with life.

Acids and basesAcids and bases An acid is a compound that contains An acid is a compound that contains

hydrogen and reacts with water to form hydrogen and reacts with water to form hydrogen ions.hydrogen ions.

A base is a compound that produces A base is a compound that produces hydroxide ions in water.hydroxide ions in water.

Biological compounds are either weak Biological compounds are either weak acids or wake bases.acids or wake bases.

In physiological solutions the [H+] can be In physiological solutions the [H+] can be predicted using three variables: the SID, predicted using three variables: the SID, the pCO2 and the total weak acid the pCO2 and the total weak acid concentration [Atot]. concentration [Atot].

Strong ion difference Strong ion difference (SID)(SID)

The SID is the sum of all the strong, The SID is the sum of all the strong, completely or almost completely completely or almost completely dissociated, cations (Na+, K+, dissociated, cations (Na+, K+, Ca2+, Mg2+) minus the strong Ca2+, Mg2+) minus the strong anions (Cl-, lactate-, etc).anions (Cl-, lactate-, etc).

Conjugate pairsConjugate pairs

Weak acid HA can act as an acid by Weak acid HA can act as an acid by donating an H+ and A-can act as a base donating an H+ and A-can act as a base by taking up H+. A- is therefore often by taking up H+. A- is therefore often reffered to as the conjugate base of HA.reffered to as the conjugate base of HA.

A similar concept can be applied for A similar concept can be applied for weak bases.weak bases.

B + H+ ↔ BH+B + H+ ↔ BH+

B - weak base; BH+ - conjugate acid of B - weak base; BH+ - conjugate acid of B. B.

Buffer Buffer

A solution that contains a weak acid and its A solution that contains a weak acid and its conjugate base or a weak base and its conjugate base or a weak base and its conjugate acid (conjugate pairs).conjugate acid (conjugate pairs).

Buffers minimize any change in [H+] by Buffers minimize any change in [H+] by readily accepting or giving up hydrogen ions.readily accepting or giving up hydrogen ions.

Buffers are most efficient in minimizing Buffers are most efficient in minimizing changes in the [H+] of a solution when changes in the [H+] of a solution when pH=pK.pH=pK.

The conjugate pairmust be present in The conjugate pairmust be present in significant quantities in solution to act as an significant quantities in solution to act as an effective buffer.effective buffer.

Clinical disordersClinical disorders

Disorder Disorder Primary Primary changechange

CompensatorCompensatory responsey response

Respiratory Respiratory

AcidosisAcidosis

Alkalosis Alkalosis ↑↑PaCO2PaCO2

↓↓PaCO2PaCO2↑↑HCO3-HCO3-

↓↓HCO3-HCO3-

MetabolicMetabolic

AcidosisAcidosis

Alkalosis Alkalosis ↓↓HCO3-HCO3-

↑↑HCO3-HCO3-↓↓PaCO2PaCO2

↑↑PaCO2PaCO2

Terminology Terminology The suffix “-osis” is used to denote any The suffix “-osis” is used to denote any

pathological process that alters arterial pathological process that alters arterial pH.pH.

Any disorder that tends to lower pHis an Any disorder that tends to lower pHis an acidosis, whereas one tending to increase acidosis, whereas one tending to increase pH is termed an alkalosis.pH is termed an alkalosis.

If the disorder primary affects PaCO2, it is If the disorder primary affects PaCO2, it is termed respiratory.termed respiratory.

Secondary compensatory responses Secondary compensatory responses should be referred to as just that and not should be referred to as just that and not as an “-osis”. For ex. metabolic acidosis as an “-osis”. For ex. metabolic acidosis with respiratory compensation.with respiratory compensation.

When only one pathological process When only one pathological process occurs by itself, the acid-base occurs by itself, the acid-base disorder is considered to be simple.disorder is considered to be simple.

The presence of two or more The presence of two or more primary processes indicates a mixed primary processes indicates a mixed acid-base disorder.acid-base disorder.

The suffix “-emia”is used to denote The suffix “-emia”is used to denote the net effect of all primary the net effect of all primary processes and compensatory processes and compensatory physiological responses on arterial physiological responses on arterial blood pH.blood pH.

The term “acidemia” signifies a pH The term “acidemia” signifies a pH < 7,35 while “alkalemia” signifies a < 7,35 while “alkalemia” signifies a pH > 7,45.pH > 7,45.

Compensatory Compensatory mechanisms mechanisms

Immediate chemical buffering.Immediate chemical buffering. Respiratory compensation Respiratory compensation

(whenever possible).(whenever possible). Slower but more effective renal Slower but more effective renal

compensatory response that may compensatory response that may nearly normalize arterial pH even if nearly normalize arterial pH even if the pathological process is still the pathological process is still present. present.

Body buffersBody buffers

Bicarbonate: the most important Bicarbonate: the most important buffer in the extracellular fluid buffer in the extracellular fluid compartment.compartment.

Hemoglobin.Hemoglobin. Other intracellular proteins.Other intracellular proteins. Phosphates: important urinary Phosphates: important urinary

buffer.buffer. Ammonia: important urinary buffer.Ammonia: important urinary buffer.

The bicarbonate buffer is effective The bicarbonate buffer is effective against metabolic but not against metabolic but not respiratory acid-base disturbances.respiratory acid-base disturbances.

Hemoglobin is capable of buffering Hemoglobin is capable of buffering both carbonic (CO2) and both carbonic (CO2) and noncarbonic (nonvolatile) acids.noncarbonic (nonvolatile) acids.

Pulmonary compensationPulmonary compensation Changes in alveolar ventilation Changes in alveolar ventilation

responsible for pulmonary compensation responsible for pulmonary compensation of PaCO2 are mediated by of PaCO2 are mediated by chemoreceptors within the brain stem.chemoreceptors within the brain stem.

These receptors respond to changes in These receptors respond to changes in cerebrospinal fluid pH.cerebrospinal fluid pH.

Minute ventilation increases 1-4 l/min for Minute ventilation increases 1-4 l/min for every 1 mmHg increase in PaCO2.every 1 mmHg increase in PaCO2.

PaCO2 can be expected to increase 0,25-1 PaCO2 can be expected to increase 0,25-1 mmHg for each 1 mEq/l increase in mmHg for each 1 mEq/l increase in [HCO3].[HCO3].

Renal compensation to Renal compensation to acidemiaacidemia

Increased reabsorption of the filtered Increased reabsorption of the filtered HCO3-.HCO3-.

Increased excretion of titratable acids.Increased excretion of titratable acids. Increased production of ammonia.Increased production of ammonia. Although these mechanisms are Although these mechanisms are

probably activated immediately, their probably activated immediately, their effects are generally not appreciable effects are generally not appreciable for 12-24h and may not be maximal for for 12-24h and may not be maximal for up to 5 days. up to 5 days.

Base excessBase excess

The amount of acid or base that The amount of acid or base that must be added for blood pH to must be added for blood pH to return to 7,4 and PaCO2 to return to return to 7,4 and PaCO2 to return to 40 mmHg at full O2 saturation and 40 mmHg at full O2 saturation and 37 M C37 M C

Represents the metabolic component Represents the metabolic component of an acid-base disturbance.of an acid-base disturbance.

A positive value indicates metabolic A positive value indicates metabolic alkalosis, whereas a negative value alkalosis, whereas a negative value reveals metabolic acidosis.reveals metabolic acidosis.

Respiratory acidosisRespiratory acidosis

It is treated by reversing the It is treated by reversing the imbalance imbalance betweenCO2productionand alveolar betweenCO2productionand alveolar ventilation.ventilation.

During chronic respiratory acidosis, During chronic respiratory acidosis, plasma [HCO3-] increases plasma [HCO3-] increases approximately 4 mEq/l for each 10 approximately 4 mEq/l for each 10 mmHg increase in PaCO2 above mmHg increase in PaCO2 above 40mmHg. 40mmHg.

Metabolic acidosisMetabolic acidosis

Primary decrease in [HCO3-].Primary decrease in [HCO3-]. Mechanisms:Mechanisms: Consumption of HCO3- by a strong Consumption of HCO3- by a strong

nonvolatile acid.nonvolatile acid. Renal or gastrointestinal wasting of Renal or gastrointestinal wasting of

bicarbonate.bicarbonate. Rapid dilution of the extracellular fluid Rapid dilution of the extracellular fluid

compartment with a bicarbonate – free fluid.compartment with a bicarbonate – free fluid. Diarrhea is the most common cause of Diarrhea is the most common cause of

hyperchloremic metabolic acidosis.hyperchloremic metabolic acidosis.

Respiratory alkalosisRespiratory alkalosis

Primary decrease in PaCO2.Primary decrease in PaCO2. An inappropriate increase in alveolar An inappropriate increase in alveolar

ventilation relative to CO2 ventilation relative to CO2 production.production.

Plasma [HCO3-] usually decreases 2 Plasma [HCO3-] usually decreases 2 mEq/l for each 10 mmHg acute mEq/l for each 10 mmHg acute decrease in PaCO2 below 40 mmHg.decrease in PaCO2 below 40 mmHg.

Metabolic alkalosisMetabolic alkalosis

Primary increase in plasma [HCO3-].Primary increase in plasma [HCO3-]. Most cases can be divided into:Most cases can be divided into: 1. associated with NaCl deficiency 1. associated with NaCl deficiency

and extracellular fluid depletion, and extracellular fluid depletion, often described as chloride sensitive.often described as chloride sensitive.

2. associated with enhanced 2. associated with enhanced mineralocorticoid activity, commonly mineralocorticoid activity, commonly reffered to as chloride resistant.reffered to as chloride resistant.

Vomiting or continuous loss of Vomiting or continuous loss of gastric fluid by gastric drainage can gastric fluid by gastric drainage can result in marked metabolic alkalosis, result in marked metabolic alkalosis, eztracellular volume depletion, and eztracellular volume depletion, and hypokalemia.hypokalemia.

The combination of alkalemia and The combination of alkalemia and hypokalemia can precipitate severe hypokalemia can precipitate severe atrial and ventricular arrhythmias.atrial and ventricular arrhythmias.

For a respiratory disturbance, every 10 For a respiratory disturbance, every 10 mmHg change in CO2 should change mmHg change in CO2 should change arterial pH by approximately 0,08 U in the arterial pH by approximately 0,08 U in the opposite direction.opposite direction.

During metabolic disturbance, every 6 During metabolic disturbance, every 6 mEq change in HCO3 also changes mEq change in HCO3 also changes arterial pH by 0,1 in the same direction.arterial pH by 0,1 in the same direction.

If the change in pH exceeds or Is less than If the change in pH exceeds or Is less than predicated, a mixed acid-base disorder is predicated, a mixed acid-base disorder is likely to be present.likely to be present.

Changes in temperature affect Changes in temperature affect measurements of PCO2 and PO2 measurements of PCO2 and PO2 directly and measurements of Ph directly and measurements of Ph indirectly.indirectly.

Both PCO2 and PO2 therefore Both PCO2 and PO2 therefore decrease during hypothermia, but pH decrease during hypothermia, but pH increases because temperature does increases because temperature does not appreciably alter [HCO3-]: PaCO2 not appreciably alter [HCO3-]: PaCO2 decreases, but [HCO3-] is unchanged.decreases, but [HCO3-] is unchanged.

Acidosis: anesthetic Acidosis: anesthetic considerationsconsiderations

Acidemia can potentiate the depressant Acidemia can potentiate the depressant effectsof most sedatives and anesthetic effectsof most sedatives and anesthetic agents on central nervous and circulatory agents on central nervous and circulatory systems.systems.

Because most opioids are weak bases, Because most opioids are weak bases, acidosis can increase the fraction of the acidosis can increase the fraction of the drug in the nonionized form and facilitate drug in the nonionized form and facilitate penetration of the opioid into the brain.penetration of the opioid into the brain.

Increased sedation and depression of Increased sedation and depression of airway reflexes may predispose to airway reflexes may predispose to pulmonary aspiration.pulmonary aspiration.

The circulatory depressant effects of both The circulatory depressant effects of both volatile and intravenous anesthetics can volatile and intravenous anesthetics can also be exaggerated.also be exaggerated.

Halothane is more arrhythmogenic.Halothane is more arrhythmogenic. Succinylcholine should be avoided in Succinylcholine should be avoided in

acidotic patients with hyperkalemia.acidotic patients with hyperkalemia. Respiratory but not metabolic acidosis Respiratory but not metabolic acidosis

augments nondepolarizing neuromuscular augments nondepolarizing neuromuscular blockade and may prevent its antagonism blockade and may prevent its antagonism by reversal agents.by reversal agents.

Alkalemia: anesthetic Alkalemia: anesthetic considerationsconsiderations

Respiratory alkalosis appears to Respiratory alkalosis appears to prolong the duration of opioid-prolong the duration of opioid-induced respiratorydepression induced respiratorydepression (because of the increased protein (because of the increased protein binding of opioids).binding of opioids).

Cerebral ischemia can occur from Cerebral ischemia can occur from marked reduction in cerebral blood marked reduction in cerebral blood flow during respiaratory alkalosis, flow during respiaratory alkalosis, particularly durinh hypotension.particularly durinh hypotension.

The combination of alkalemia and The combination of alkalemia and hypokalemia can precipitate severe hypokalemia can precipitate severe atrial and ventricular arrhythmias.atrial and ventricular arrhythmias.

Potentiation of nondepolarizing Potentiation of nondepolarizing neuromuscular blockade is reported neuromuscular blockade is reported with alkalemia but may be with alkalemia but may be moredirectly related to concomitant moredirectly related to concomitant hypokalemia. hypokalemia.

Thank you!Thank you!