STUDY - Technical - New Dacian's Medicine
Acidosis
and Alkalosis (1)
Translation Draft
I'll start with little clarification regarding the normal acid-base balance. Systemic arterial pH is maintained between 7.35 and 7.45 by intra and extracellular buffer chemical systems, as well as by respiratory and renal regulation mechanisms. Control of the arterial pressure of CO2 (PaCO2) through the central nervous system, as well as control of plasma bicarbonate in the kidneys, causes a stabilisation of the arterial pH by excretion or retention of acids or bases.
Metabolic and respiratory components that regulate systemic pH are described by the Henderson-Hasselbalch equation (which I will not describe here). In most situations, CO2 production and excretion are in balance and normal PaCO2 is maintained around 40 mmHg. Low CO2 excretion produces hypercapnia, and excessive excretion causes hypocapnia.
However, in these situations the production and excretion are balanced again and a new value of PaCO2 is established. So PaCO2 is primarily regulated by respiratory nerve factors and not as a result of CO2 production. Hypercapnia is more commonly the result of hypoventilation than of increased CO2 production. The increase or decrease in PaCO2 is a disorder of respiratory nervous control or is caused by compensatory changes in response to the primary decrease in the plasma concentration of HCO3-.
Primary changes in PaCO2 may cause acidosis or alkalose, as PaCO2 is above or below the normal value of 40 mmHg (acidosis or respiratory alkalose, respectively). Primary modification of PaCO2 involves cell buffering and renal adaptation, a slow process that becomes more effective as time goes on. Primary changes in plasma HCO3- as a result of metabolic or renal factors cause compensatory changes in ventilation, which decrease the variations in blood pH that would otherwise occur.
These respiratory variations refer to secondary or compensatory changes since they occur in response to primary metabolic changes. Kidneys regulate HCO3-plasma through three major mechanisms: 1. "reabsorption" of HCO3-filtered, 2. titrable acid formation and 3. excretion of NH4-filtered, renal tubes must therefore secrete 4,000 mmoli hydrogen ions. 80 or 90% of HCO3- are reabsorbed into the proximal tube. Distal nephron reabsorbs the remaining and secreted protons, which come from metabolism, to maintain systemic pH.
Although this amount of protons, 40-60 mmoli/ day is small, it is necessary to be secreted to prevent chronic positivity of the H-balance and metabolic acidosis. This amount of secreted protons is represented in the urine by titrable acidity and NH4+ ions. Production and excretion of NH4+ are altered in chronic renal failure, hyperpotasemia and renal tubular acidosis. In short, these regulating responses, including chemical buffering, respiratory system and HCO3 regulation through the kidneys, work together to maintain a systemic arterial pH between 7.35 and 7.45.
Let us address the diagnosis of different general types of imbalances. The most common imbalances are simple acid-base conditions such as acidosis or metabolic alkalose and respiratory acidosis or alkalose. Because compensation is not complete, the pH in simple imbalances is abnormal. More complicated clinical situations are found in mixed acid-base imbalances.
Let's start with simple acid-base imbalances. Primary respiratory disorders (primary changes of PaCO2) involve secondary metabolic responses (secondary changes in HCO3-), and primary metabolic changes require predictable respiratory responses. Primary changes in PaCO2 or HCO3- affect systemic pH and cause acidosis or alkalose. To illustrate this, metabolic acidosis caused by a decrease in endogenous acids (e.g. ketoacidosis) decreases bicarbonate in extracellular fluid, thus decreasing extracellular pH.
As a result, PaCO2 is expected to decrease by 1.25 mmHg for each mmol/l decrease in HCO3-. So a patient with metabolic acidosis and HCO3- about 12 mmoli/ l is expected to have a PaCO2 between 24 and 28 mmHg. PaCO2 values below 24 or greater than 28 mmHg define a mixed imbalance (metabolic acidosis and respiratory alkalosis or metabolic alkalosis and respiratory acidosis). Another way to specify the appropriateness of the Response HCO3- or PaCO2 is to use an acid-base diagram.
But important to note, most commonly we will have to deal with mixed acid-base imbalances. They are defined as conditions that coexist independently, not necessarily as compensatory responses, and are often observed in patients in intensive care units. As with simple acid-base imbalances, differential diagnosis for each of the mixed conditions should be considered in the light of the clinical context.
Mixed respiratory and metabolic acidosis or mixed respiratory and metabolic alkalose can lead to extremely dangerous pH levels. A patient with diabetic ketoacidosis (metabolic acidosis) may develop an independent respiratory problem leading to acidosis or respiratory alkalosis. Patients with underlying lung disease may not respond to metabolic acidosis with an adequate fan response due to severe respiratory failure.
Thus, the overlap of respiratory acidosis over metabolic acidosis can lead to severe acidicemia with severe development. When acidosis and metabolic alkalose coexist in the same patient, pH may be normal or almost normal. When pH is normal, an increase in the "anionic hole" denotes the presence of metabolic acidosis. A diabetic patient with ketoacidosis may have renal dysfunction leading to simultaneous metabolic acidosis.
Patients who have ingested an overdose of drug combinations such as sedatives and salicylates may experience mixed disorders as a result of the acidobasic response to each drug (metabolic acidosis associated with respiratory acidosis or respiratory alkalosis respectively). Even more complex are triple acidobasic disorders. For example, patients with metabolic acidosis caused by alcoholic ketoacidosis may develop metabolic alkalose through vomiting over which the respiratory alkalose caused by hyperventilation from hepatic dysfunction or ethanolic abstinence overlaps.
In the case of diagnosis of acid-base imbalances, account should be taken of the fact that the collection of arterial blood samples is carried out without the use of a large amount of heparin. When determining the concentration of gases in the arterial blood in the clinical laboratory, both pH and PaCO2 are measured, and HCO3 is calculated by the Henderson-Hasselbalch equation. This calculated value should be compared with HCO3- measured (total CO2) with electrolytes.
These two values must differ by not more than 2 mmoli/l. If the difference is greater, these two values should not be taken into account simultaneously, with the possibility of a laboratory error or an error in the calculation of HCO3-. After checking the blood acidobasic values we can accurately identify the acidobasic imbalance. The most common causes of acid-base imbalance should be retained during anamnesis as indications of etiology. For example, chronic renal failure belongs to the causes of metabolic acidosis, and chronic vomiting frequently produces metabolic alkalosis.
Patients with pneumonia, sepsis or heart failure frequently have respiratory alkalose, and patients with chronic obstructive pulmonary disease or those with overdose seds frequently have respiratory acidosis.
The anamnesis of ingested drugs is important because thiazid and ansa diuretics can cause metabolic alkalosis, and carbonic anhydrase inhibitors, acetazolamide, can cause metabolic acidosis. Blood collection for the determination of electrolytes and for the dosing of gases in the arterial blood is done simultaneously before the start of therapy, since an increase in HCO3- occurs in both metabolic alkalose and respiratory acidosis. In contrast, a decrease in HCO3- occurs in metabolic acidosis and respiratory alkalose.
Metabolic acidosis leads to hyperpotasemia as a result of cellular exchange of H+ with K+ or Na+. For each decrease in blood pH by 0.1, plasma K+ increases by 0.6 mmoli/ l. This relationship is not invariable. Diabetic ketoacidosis, lactic acidosis, diarrhoea and renal tubular acidosis are commonly associated with K+ deplation.
Let's see now what's with the anionic hole (anionic hiatus) that we mentioned earlier. All assessments of acid-base imbalances should include a simple calculation of the anionic hole (GA), representing those non-measurable plasma anions (normally 10-12 mmoli/L) and calculated as the difference between the na+ existing and the existence of Cl- + NCO3-. Anions that cannot be measured include anionic proteins, phosphates, sulphates and organic anions.
When acid anions, such as acetoacetate and lactate accumulate in extracellular fluid, GA increases, causing a high GA acidosis. An increase in GA may be due to a decrease in immeasurable cations (calcium, magnesium, potassium) or an increase in immeasurable anions. In addition, GA may increase secondary to an increase in anionic albumin either by increasing the concentration of albumin or by alkalose that alters albumin load.
A decrease in GA can be given by: 1. increase in non-measurable cations, 2. the presence of abnormal cations in the blood, such as lithium (lithium poisoning) or cationic immunoglobulins (plasmocellular dyssia), 3. a decrease in the concentration of plasma anionic albumin, 4. a decrease in the actual anionic load of albumin by acidosis or 5. hyperviscosity and severe hyperlipemia which may lead to an underestimation of sodium and chlorine levels.
In the face of a normal serum albumin, a high GA is frequently given by acids that do not contain chlorine but contain organic anions (phosphates, sulphates), organic (cetoacids, lactate, uremic organic anions), exogenous (salicylates or toxins ingested with organic acid production) or unidentified anions. By definition, an acidosis with high GA has two characteristics: a low HCO3 and a high GA. The latter is present even if the overlap of an additional acid-base imbalance alters HCO3-independent.
A metabolic acidosis with high GA present simultaneously with a chronic respiratory acidosis or metabolic alkalose is a situation in which HCO3 may be normal or even increased. However, GA is increased and Cl is low. Similarly, normal values for HCO3-, PaCO2 and pH do not imply the absence of an acid-base imbalance.
For example, an alcoholic may develop metabolic alkalosis with pH 7.55, PaCO2 48 mmHg, HCO3- ed 40 mmoli/ l, Na+ of 135, Cl- 80 and K+ of 2.8. If such a patient develops an overlapping alcoholic ketoacidosis with a beta-hydroxybutyrate concentration of 15 mM, the arterial pH will decrease to 7.4, HCO3- to 25 mmoli/ l and PaCO2 to 40 mmHg. Although blood gases are normal, GA is increased to 26 mmoli/ l, indicating mixed suffering with alkalose and metabolic acidosis.
Ready for today! Tomorrow we'll talk about metabolic acidosis.
I'll start with little clarification regarding the normal acid-base balance. Systemic arterial pH is maintained between 7.35 and 7.45 by intra and extracellular buffer chemical systems, as well as by respiratory and renal regulation mechanisms. Control of the arterial pressure of CO2 (PaCO2) through the central nervous system, as well as control of plasma bicarbonate in the kidneys, causes a stabilisation of the arterial pH by excretion or retention of acids or bases.
Metabolic and respiratory components that regulate systemic pH are described by the Henderson-Hasselbalch equation (which I will not describe here). In most situations, CO2 production and excretion are in balance and normal PaCO2 is maintained around 40 mmHg. Low CO2 excretion produces hypercapnia, and excessive excretion causes hypocapnia.
However, in these situations the production and excretion are balanced again and a new value of PaCO2 is established. So PaCO2 is primarily regulated by respiratory nerve factors and not as a result of CO2 production. Hypercapnia is more commonly the result of hypoventilation than of increased CO2 production. The increase or decrease in PaCO2 is a disorder of respiratory nervous control or is caused by compensatory changes in response to the primary decrease in the plasma concentration of HCO3-.
Primary changes in PaCO2 may cause acidosis or alkalose, as PaCO2 is above or below the normal value of 40 mmHg (acidosis or respiratory alkalose, respectively). Primary modification of PaCO2 involves cell buffering and renal adaptation, a slow process that becomes more effective as time goes on. Primary changes in plasma HCO3- as a result of metabolic or renal factors cause compensatory changes in ventilation, which decrease the variations in blood pH that would otherwise occur.
These respiratory variations refer to secondary or compensatory changes since they occur in response to primary metabolic changes. Kidneys regulate HCO3-plasma through three major mechanisms: 1. "reabsorption" of HCO3-filtered, 2. titrable acid formation and 3. excretion of NH4-filtered, renal tubes must therefore secrete 4,000 mmoli hydrogen ions. 80 or 90% of HCO3- are reabsorbed into the proximal tube. Distal nephron reabsorbs the remaining and secreted protons, which come from metabolism, to maintain systemic pH.
Although this amount of protons, 40-60 mmoli/ day is small, it is necessary to be secreted to prevent chronic positivity of the H-balance and metabolic acidosis. This amount of secreted protons is represented in the urine by titrable acidity and NH4+ ions. Production and excretion of NH4+ are altered in chronic renal failure, hyperpotasemia and renal tubular acidosis. In short, these regulating responses, including chemical buffering, respiratory system and HCO3 regulation through the kidneys, work together to maintain a systemic arterial pH between 7.35 and 7.45.
Let us address the diagnosis of different general types of imbalances. The most common imbalances are simple acid-base conditions such as acidosis or metabolic alkalose and respiratory acidosis or alkalose. Because compensation is not complete, the pH in simple imbalances is abnormal. More complicated clinical situations are found in mixed acid-base imbalances.
Let's start with simple acid-base imbalances. Primary respiratory disorders (primary changes of PaCO2) involve secondary metabolic responses (secondary changes in HCO3-), and primary metabolic changes require predictable respiratory responses. Primary changes in PaCO2 or HCO3- affect systemic pH and cause acidosis or alkalose. To illustrate this, metabolic acidosis caused by a decrease in endogenous acids (e.g. ketoacidosis) decreases bicarbonate in extracellular fluid, thus decreasing extracellular pH.
As a result, PaCO2 is expected to decrease by 1.25 mmHg for each mmol/l decrease in HCO3-. So a patient with metabolic acidosis and HCO3- about 12 mmoli/ l is expected to have a PaCO2 between 24 and 28 mmHg. PaCO2 values below 24 or greater than 28 mmHg define a mixed imbalance (metabolic acidosis and respiratory alkalosis or metabolic alkalosis and respiratory acidosis). Another way to specify the appropriateness of the Response HCO3- or PaCO2 is to use an acid-base diagram.
But important to note, most commonly we will have to deal with mixed acid-base imbalances. They are defined as conditions that coexist independently, not necessarily as compensatory responses, and are often observed in patients in intensive care units. As with simple acid-base imbalances, differential diagnosis for each of the mixed conditions should be considered in the light of the clinical context.
Mixed respiratory and metabolic acidosis or mixed respiratory and metabolic alkalose can lead to extremely dangerous pH levels. A patient with diabetic ketoacidosis (metabolic acidosis) may develop an independent respiratory problem leading to acidosis or respiratory alkalosis. Patients with underlying lung disease may not respond to metabolic acidosis with an adequate fan response due to severe respiratory failure.
Thus, the overlap of respiratory acidosis over metabolic acidosis can lead to severe acidicemia with severe development. When acidosis and metabolic alkalose coexist in the same patient, pH may be normal or almost normal. When pH is normal, an increase in the "anionic hole" denotes the presence of metabolic acidosis. A diabetic patient with ketoacidosis may have renal dysfunction leading to simultaneous metabolic acidosis.
Patients who have ingested an overdose of drug combinations such as sedatives and salicylates may experience mixed disorders as a result of the acidobasic response to each drug (metabolic acidosis associated with respiratory acidosis or respiratory alkalosis respectively). Even more complex are triple acidobasic disorders. For example, patients with metabolic acidosis caused by alcoholic ketoacidosis may develop metabolic alkalose through vomiting over which the respiratory alkalose caused by hyperventilation from hepatic dysfunction or ethanolic abstinence overlaps.
In the case of diagnosis of acid-base imbalances, account should be taken of the fact that the collection of arterial blood samples is carried out without the use of a large amount of heparin. When determining the concentration of gases in the arterial blood in the clinical laboratory, both pH and PaCO2 are measured, and HCO3 is calculated by the Henderson-Hasselbalch equation. This calculated value should be compared with HCO3- measured (total CO2) with electrolytes.
These two values must differ by not more than 2 mmoli/l. If the difference is greater, these two values should not be taken into account simultaneously, with the possibility of a laboratory error or an error in the calculation of HCO3-. After checking the blood acidobasic values we can accurately identify the acidobasic imbalance. The most common causes of acid-base imbalance should be retained during anamnesis as indications of etiology. For example, chronic renal failure belongs to the causes of metabolic acidosis, and chronic vomiting frequently produces metabolic alkalosis.
Patients with pneumonia, sepsis or heart failure frequently have respiratory alkalose, and patients with chronic obstructive pulmonary disease or those with overdose seds frequently have respiratory acidosis.
The anamnesis of ingested drugs is important because thiazid and ansa diuretics can cause metabolic alkalosis, and carbonic anhydrase inhibitors, acetazolamide, can cause metabolic acidosis. Blood collection for the determination of electrolytes and for the dosing of gases in the arterial blood is done simultaneously before the start of therapy, since an increase in HCO3- occurs in both metabolic alkalose and respiratory acidosis. In contrast, a decrease in HCO3- occurs in metabolic acidosis and respiratory alkalose.
Metabolic acidosis leads to hyperpotasemia as a result of cellular exchange of H+ with K+ or Na+. For each decrease in blood pH by 0.1, plasma K+ increases by 0.6 mmoli/ l. This relationship is not invariable. Diabetic ketoacidosis, lactic acidosis, diarrhoea and renal tubular acidosis are commonly associated with K+ deplation.
Let's see now what's with the anionic hole (anionic hiatus) that we mentioned earlier. All assessments of acid-base imbalances should include a simple calculation of the anionic hole (GA), representing those non-measurable plasma anions (normally 10-12 mmoli/L) and calculated as the difference between the na+ existing and the existence of Cl- + NCO3-. Anions that cannot be measured include anionic proteins, phosphates, sulphates and organic anions.
When acid anions, such as acetoacetate and lactate accumulate in extracellular fluid, GA increases, causing a high GA acidosis. An increase in GA may be due to a decrease in immeasurable cations (calcium, magnesium, potassium) or an increase in immeasurable anions. In addition, GA may increase secondary to an increase in anionic albumin either by increasing the concentration of albumin or by alkalose that alters albumin load.
A decrease in GA can be given by: 1. increase in non-measurable cations, 2. the presence of abnormal cations in the blood, such as lithium (lithium poisoning) or cationic immunoglobulins (plasmocellular dyssia), 3. a decrease in the concentration of plasma anionic albumin, 4. a decrease in the actual anionic load of albumin by acidosis or 5. hyperviscosity and severe hyperlipemia which may lead to an underestimation of sodium and chlorine levels.
In the face of a normal serum albumin, a high GA is frequently given by acids that do not contain chlorine but contain organic anions (phosphates, sulphates), organic (cetoacids, lactate, uremic organic anions), exogenous (salicylates or toxins ingested with organic acid production) or unidentified anions. By definition, an acidosis with high GA has two characteristics: a low HCO3 and a high GA. The latter is present even if the overlap of an additional acid-base imbalance alters HCO3-independent.
A metabolic acidosis with high GA present simultaneously with a chronic respiratory acidosis or metabolic alkalose is a situation in which HCO3 may be normal or even increased. However, GA is increased and Cl is low. Similarly, normal values for HCO3-, PaCO2 and pH do not imply the absence of an acid-base imbalance.
For example, an alcoholic may develop metabolic alkalosis with pH 7.55, PaCO2 48 mmHg, HCO3- ed 40 mmoli/ l, Na+ of 135, Cl- 80 and K+ of 2.8. If such a patient develops an overlapping alcoholic ketoacidosis with a beta-hydroxybutyrate concentration of 15 mM, the arterial pH will decrease to 7.4, HCO3- to 25 mmoli/ l and PaCO2 to 40 mmHg. Although blood gases are normal, GA is increased to 26 mmoli/ l, indicating mixed suffering with alkalose and metabolic acidosis.
Ready for today! Tomorrow we'll talk about metabolic acidosis.
A weekend full of joy,
tranquility, understanding, love and gratitude!
Dorin, Merticaru