A7. Acid-base disorders and management
Metabolic acidosis
| Metabolic acidosis | |
|---|---|
| Definition | A process decreasing pH due to metabolic process |
| Symptoms | Nonspecific symptoms. Hyperventilation. |
| Complications | Ventricular arrhythmia, heart failure |
| Types | High anion gap metabolic acidosis, normal anion gap metabolic acidosis |
| Causes | Uncontrolled diabetes mellitus (ketoacidosis), shock (lactic acidosis), chronic kidney disease |
| Treatment | Management of underlying cause. Bicarbonate if severe |
Metabolic acidosis is an acid-base disorder characterised by a metabolic pathological process which decreases the pH of the blood. If the acidosis is severe, it can overcome the body's defense against acidosis, causes the pH in the blood to fall below 7.35. This is called acidaemia.
Respiratory acidosis is similar but is rather due to a respiratory problem. Metabolic alkalosis is sort of the opposite of metabolic acidosis. Metabolic acidosis is the most common acid-base disorder.
Severe acidaemia is fatal due to ventricular arrhythmia or heart failure.
Types
There are two types of metabolic acidosis: Normal anion gap metabolic acidosis (NAGMA) and high anion gap metabolic acidosis (HAGMA). In both types there is decreased concentration of bicarbonate, as bicarbonate buffers the increased acid as part of the bicarbonate buffer system. The two types are not mutually exclusive; both can occur simultaneously.
Anion gap
The anion gap is a fancy term we use to include all anions in the serum that are not bicarbonate and chloride. The reason they’re called that is because the levels of these anions aren’t measured directly, but rather calculated by the following calculation:
Anion gap = [Na] – ([Cl–] + [HCO3–])
The reason this works is because we know that the plasma is electroneutral, meaning that there must be an equal amount of positive and negative charges. Almost all the positive charge in plasma comes from sodium, while the negative charges come from chloride, bicarbonate and other anions that aren’t measured in the lab, like lactate, phosphate, sulphate, proteins.
Acids in the blood usually exist in their anionic form. When there is an increased level of anions other than chloride and bicarbonate, we can assume that there is an increased level of acids as wells. The anion gap can be increased due to elevated levels of acids that are normally found in the body, like lactic acid or ketone bodies, or due to ingestion of compounds not usually found in the body, like ethylene glycol, etc. The extra acids increase the “gap”.
The anion gap is normal in case of increased loss of bicarbonate or decreased loss of H+. No extra acids means that there is no increased “gap”.
High anion gap metabolic acidosis
High anion gap metabolic acidosis (HAGMA) or elevated anion gap metabolic acidosis indicates a metabolic acidosis where the concentration of the anions that comprise the anion gap is increased. It occurs when there is overproduction or ingestion of organic acids or decreased acid excretion in the kidney. The concentration of HCO3– is reduced because of buffering. HAGMA is more common than NAGMA.
Normal anion gap metabolic acidosis
Normal anion gap metabolic acidosis (NAGMA) occurs when HCO3–, a base, is lost in significant amounts, and no excess acid accumulates in the blood. When bicarbonate is lost, chloride will be retained to uphold the electroneutrality. Because of the increased chloride it is sometimes called hyperchloraemic metabolic acidosis. One can distinguish between a hypokalaemic and a hyperkalaemic type of NAGMA, but this distinction is rarely used.
Etiology
Different etiologies produce different types of metabolic acidosis.
Etiology of HAGMA
- Lactic acidosis
- Ketoacidosis
- Ingestion of acids (methanol, ethylene glycol)
- End-stage kidney disease
Methanol and ethylene glycol are organic acids which can be ingested, usually accidentally. Methanol is a common byproduct of homemade alcohol production.
In end-stage chronic kidney disease, the kidney cannot excrete acidic compounds like phosphate, sulphate, urate, and hippurate, causing HAGMA. However, chronic kidney disease may also cause NAGMA.
Etiology of NAGMA
- Diarrhoea
- Renal tubular acidosis
- Chronic kidney disease
- Excessive saline infusion
Diarrhoea causes excessive loss of bicarbonate.
Renal tubular acidosis (RTA) is a collection of three rare disorders characterised by disorder of the renal tubules which cause metabolic acidosis.
Chronic kidney disease may cause NAGMA due to decreased capacity for retention (and therefore increased excretion) of bicarbonate.
Excessive rapid intravenous infusion of normal saline (0.9% NaCl) causes hyperchloraemic NAGMA, however usually a mild one. Because sodium chloride solutions do not contain bicarbonate but do contain chloride at a higher concentration than in the serum, a dilution of bicarbonate occurs, causing a decrease in bicarbonate concentration.
Lactic acidosis
Lactic acidosis is the most common cause of high anion gap metabolic acidosis, and is due to excess production of lactic acid, usually due to reduced oxygen delivery to peripheral tissues, which causes the tissues to switch from aerobic to anaerobic metabolism, which produces lactic acid. We distinguish two types of lactic acidosis, type A and type B.
Type A occurs when there is a global reduction in oxygen delivery due to circulatory shock or cardiopulmonary arrest. Type B occurs when there are other causes of increased lactic acid production, usually due to regional reduction in oxygen delivery or due to toxins impairing normal cellular metabolism.
The most common cause of type B lactic acidosis is improper use of metformin, an antidiabetic drug. Metformin changes cellular and intermediary metabolism in a way that makes tissues more likely to undergo anaerobic metabolism. Metformin-associated metabolic acidosis (MALA) may occur in case of metformin overdose, or if a person treated with metformin undergoes cellular stress. This can occur in case of kidney disease, liver disease, alcohol abuse, circulatory shock, surgery, or other severe acute illness. To prevent MALA, it's important to withold metformin treatment in case of such concomitant disease.
Ketoacidosis
Ketoacidosis refers to metabolic acidosis due to accumulation of ketone bodies, which are acidic. Ketone bodies are the body's "reserve fuel" when glucose availability is limited or available glucose cannot be metabolised. Accumulation of ketone bodies may occur in case of severe fasting, for example due to alcohol abuse, or due to uncontrolled or untreated type 1 diabetes mellitus. In type 1 DM, there is hyperglycaemia, so lack of glucose is not a problem. Instead, there is insulin deficiency, and insulin is required for cells to take in and metabolise glucose.
Pathophysiology
Compensatory mechanism
The body compensates for a metabolic acidosis in two ways: It stimulates increased rate and depth of breathing, called Kussmaul respiration. This increases the exhalation of CO2, which increases pH back towards the normal range. The respiratory compensation is rapid, occuring within 30 minutes of the acidosis, reaching its maximum after a day. For every 1 unit HCO3- respiratory compensation decreases pCO2 by approximately 1.2 mmHg.
The other compensatory mechanism is due to the kidneys. Kidneys respond to metabolic acidosis by increasing urinary excretion of acids and decreasing urinary excretion of bicarbonate. This mechanism is slow, taking a few days to kick in.
Clinical features
Acidosis causes nonspecific clinical features. Hyperventilation may be present. In severe cases, mental status may be altered.
Diagnosis and evaluation
Arterial blood gas is essential in the evaluation of acid-base disorders. It will give the pH, bicarbonate level, pCO2, pO2, and lactate levels. In metabolic acidosis, the bicarbonate level is abnormally low (< 22 mmol/L). If there is acidaemia, the pH is < 7.35.
The anion gap should be calculated to help narrow down the possible causes. The following formula is used:
Anion gap = [Na] – ([Cl–] + [HCO3–])
In case of acidosis, the body will compensate by hyperventilating. This decreases pCO2. It's important to evaluate pCO2 to determine whether respiratory compensation is effective or not. The pCO2 should be reduced to approximately [HCO3-] + 15. One may also subtract 7 from the pH and multiply by 100 to get the optimal pCO2 level. For example, if the pH is 7.23, the pCO2 should be 23 mmHg. If the pCO2 is not at the expected level, there is an impairment of the body's compensatory response to acidosis, or there may be a mixed acid-base disorder.
Management
As metabolic acidosis is not a disease of itself but rather a consequence, the underlying disease must be identified and treated. This will reverse the metabolic acidosis.
Administration of intravenous bicarbonate in case of acute metabolic acidosis is usually reserved for the most severe cases where pH < 7.1. However, there is controversy as to when exactly bicarbonate administration is indicated.
In case of chronic metabolic acidosis, usually due to chronic kidney disease, bicarbonate is indicated.
Complications
Severe acidaemia can cause fatal ventricular arrhythmia and depression of cardiac contractility, which may cause heart failure.
Metabolic alkalosis
| Metabolic alkalosis | |
|---|---|
| Definition | A process increasing pH due to metabolic process |
| Symptoms | Usually asymptomatic |
| Complications | Seizures, coma |
| Types | Chloride-responsive and chloride-resistant type |
| Causes | Vomiting, diuretics, hypokalaemia |
| Treatment | Management of underlying cause. Correction of hypokalaemia. Dialysis or HCl if severe |
Metabolic alkalosis is an acid-base disorder characterised by a metabolic pathological process which increases the pH of the blood. If the alkalosis is severe, it can overcome the body's defense against alkalosis, causes the pH in the blood to increase beyond 7.45. This is called alkalaemia.
Respiratory alkalosis is similar but is rather due to a respiratory problem. Metabolic acidosis is sort of the opposite of metabolic alkalosis. Metabolic alkalosis is an uncommon acid-base disorder.
Etiology
Metabolic alkalosis can be caused by excessive loss of hydrogen ion or due to excessive administration or retention of alkali.
- Loss of hydrogen ions
- Vomiting or excessive nasogastric suction
- Diuretics (loop or thiazides)
- Hyperaldosteronism (primary or secondary)
- Hypokalaemia
- Villous adenoma
- Administration of alkali
- Multiple blood transfusions (they contain citrate which is metabolised to bicarbonate)
- Milk-alkali syndrome
- Excessive administration/intake of alkali
- Contraction alkalosis
- Diuretics
- Rare disorders
- Bartter syndrome
- Gitelman syndrome
The most common causes overall are vomiting, nasogastric suction, and diuretic therapy.
Hypokalaemia
Main article: Hypokalaemia
Hypokalaemia can both cause and maintain metabolic acidosis by increasing bicarbonate retention in the kidney. This is secondary to the kidney reabsorbing potassium in exchange for hydrogen ions.
Milk-alkali syndrome
Milk-alkali syndrome is a possible causes of metabolic alkalosis. It occurs when large amounts of calcium (in milk or otherwise) is consumed with an alkali like bicarbonate or carbonate. The calcium causes hypercalcaemia, which reduces the excretion of bicarbonate as well as volume depletion, both of which lead to metabolic alkalosis.
Contraction alkalosis
Loss of fluid which is rich in sodium chloride but low in bicarbonate concentration may cause a form of metabolic alkalosis called contraction alkalosis. The bicarconate concentration increases not because of increased bicarbonate but because of decreased bicarbonate-poor volume (concentration = solute/volume). Contraction alkalosis is usually not significant to cause alkalaemia alone and is therefore usually one etiology of multiple.
Bartter syndrome and Gitelman syndrome
Bartter syndrome is a disorder of the renal tubule (tubulopathy) and a genetic disorder where the Na-K-2Cl cotransporter in the thick ascending loop is impaired. This is the same cotransporter that loop diuretics inhibits, so Bartter syndrome mimics chronic loop diuretic treatment.
Gitelman syndrome is another tubulopathy and also a genetic disorder where the Na-Cl cotransporter in the distal convoluted tubule is impaired. This is the same cotransporter that thiazide diuretics inhibits, and so Gitelman syndrome mimics chronic thiazide treatment.
Both syndromes cause hypokalaemia, metabolic alkalosis, and a reduction in plasma volume. As a result, there is increased activity of RAAS with secondary hyperaldosteronism.
Types
One may distinguish between two types of metabolic alkalosis depending on whether administration of chloride is effective in the treatment. Chloride-responsive metabolic alkalosis occurs due to vomiting, contraction alkalosis, and diuretics. Chloride-resistant metabolic alkalosis occurs due to hypokalaemia, hyperaldosteronism, Bartter syndrome, and Gitelman syndrome.
Pathophysiology
Alkalaemia may cause plasma proteins to bind more free calcium ions, causing the level of free calcium in the serum to decrease, effectively causing hypocalcaemia.
Alkalaemia also shifts the haemoglobin-oxygen dissociation curve to the left, which decreases tissue oxygenation.
Compensation
The initial compensation occurs to intracellular buffers like the haemoglobin buffers, and is relatively modest.
The healthy kidney can compensate for metabolic alkalosis by increasing its excretion of bicarbonate to a large degree. As such, for metabolic alkalaemia to occur, there is often a loss of kidney function. Renal compensation begins soon after the alkalosis, but it takes up to five takes to become complete.
Clinical features
Metabolic alkalosis is often asymptomatic, unless there are symptoms of the underlying cause or of concomitant hypokalaemia. In severe cases, there may be agitation.
Diagnosis and evaluation
Arterial blood gas is essential in the evaluation of acid-base disorders. It will give the pH, bicarbonate level, pCO2, pO2, and lactate levels. In metabolic alkalosis, the bicarbonate level is abnormally high (> 26 mmol/L). If there is alkalaemia, the pH is > 7.45. Hypokalaemia is often present with metabolic alkalosis.
The cause of metabolic alkalosis is often apparent by the anamnesis. If not, rare causes like hyperaldosteronism and genetic syndromes should be sought. Measurement of urine chloride may be helpful to narrow down the causes. Chloride-responsive metabolic alkalosis has a urine chloride concentration < 20 mmol/L, while chloride-resistant type has a concentration > 40 mmol/L.
Management
As metabolic alkalosis is not a disease of itself but rather a consequence, the underlying disease must be identified and treated. This will reverse the metabolic alkalosis.
Because hypokalaemia may cause and maintain metabolic alkalosis, any concomitant hypokalaemia should be treated by potassium supplementation. It's important to keep in mind the possibility of the serum potassium level being normal but there being an intracellular potassium deficit.
In chloride-responsive metabolic alkalosis, administration of isotonic saline (0.9% NaCl) may help correct the alkalosis.
In the most severe cases, dialysis (RRT) or administration of HCl may be used.
Complications
Severe metabolic alkalosis can cause seizures and coma.
Respiratory acidosis
| Respiratory acidosis | |
|---|---|
| Definition | A process decreasing pH due to abnormal ventilation |
| Symptoms | Depressed consciousness |
| Causes | Benzodiazepine or opioid overdose. Neuromuscular disorders. Emphysema. Interstitial lung disease. |
| Treatment | Treatment of underlying cause. Non-invasive or invasive ventilation. |
Respiratory acidosis is an acid-base disorder characterised by a respiratory pathological process which decreases the pH of the blood. If the acidosis is severe, it can overcome the body's defense against acidosis, causes the pH in the blood to fall below 7.35. This is called acidaemia.
Metabolic acidosis is similar but is rather due to a metabolic problem. Respiratory alkalosis is sort of the opposite of respiratory acidosis.
Respiratory acidosis occurs due to impaired ventilation (hypoventilation), which causes pCO2 to increase (hypercapnia). This is called hypercapnic respiratory failure.
Etiology
Respiratory acidosis occurs due to hypercapnic respiratory failure. Hypercapnic respiratory failure may occur due to (alveolar) hypoventilation or due to increased dead space.
Hypoventilation
Physiological ventilation requires a normal respiratory drive from the CNS, normal conduction of nerve impulses from the CNS to the respiratory muscles, normal function of the chest wall and respiratory muscles, normal conduction of air through the upper airways, and normal functioning of the lungs.
As such, hypoventilation may occur due to problems in several different organ systems. Problems with the central nervous system can impair the normal drive to ventilate, problems with the peripheral nervous system, respiratory muscles, chest wall, or upper airways may make the patient unable to breathe despite the respiratory drive, and problems with the lung can impair gas exchange to such a degree that any amount of ventilation is insufficient for gas exchange.
- Problems with the CNS
- Medications which decrease respiratory drive (benzodiazepines, alcohol, opioids)
- Stroke
- Encephalitis
- Impaired neuromuscular transmission
- Impaired function of chest wall
- Severe kyphosis or scoliosis
- Pectus excavatum
- Impaired airways (rarely causes hypoventilation by itself)
- Acute exacerbation of COPD or asthma
- Foreign body aspiration
- External airway obstruction (goitre, tumour)
Increased dead space (V/Q mismatch)
Increased dead spacing occurs when there is a ventilation/perfusion mismatch (V/Q mismatch) where regions of the lung are not perfused. When a part of the lung receives no perfusion, the alveoli in the area effectively become dead space (due to not having blood to exchange gas to). This can occur in case of:
- Pulmonary embolism (severe)
- Interstitial lung disease (severe)
Pathophysiology
Compensatory mechanism
The body cannot compensate for respiratory acidosis by stimulating ventilation, as ventilation is the problem in the first place. However, kidney compensation occurs similarly as for metabolic acidosis. Kidneys respond to acidosis by increasing urinary excretion of acids and decreasing urinary excretion of bicarbonate. This mechanism is slow, taking a few days to kick in.
Clinical features
Hypercapnia causes depressed consciousness, which may range from sluggishness to somnolence to coma.
Diagnosis and evaluation
Arterial blood gas is essential in the evaluation of acid-base disorders. It will give the pH, bicarbonate level, pCO2, pO2, and lactate levels. In respiratory acidosis, the pCO2 level is elevated (> 45 mmHg). If there is acidaemia, the pH is < 7.35.
When kidney compensation has kicked in, bicarbonate levels start to increase. Appropriate compensation causes an increase of approximately 4 units of bicarbonate per 10 mmHg elevation in pCO2.
Management
Treating the underlying cause is essential, but measures to improve hypoxaemia and hypercapnia are important as well, to prevent worsening. Oxygen supplementation, non-invasive ventilation, or invasive ventilation may be used.
Complications
Severe acidaemia can cause fatal ventricular arrhythmia and depression of cardiac contractility, which may cause heart failure. The usually co-present hypoxaemia may also cause similar complications.
Respiratory alkalosis
| Respiratory alkalosis | |
|---|---|
| Definition | A process increasing pH due to abnormal ventilation |
| Symptoms | Rarely symptomatic |
| Causes | Anxiety, pain |
| Treatment | Rarely requires |
Respiratory alkalosis is an acid-base disorder characterised by a respiratory pathological process which increases the pH of the blood. If the alkalosis is severe, it can overcome the body's defense against alkalosis, causes the pH in the blood to increase beyond 7.45. This is called alkalaemia.
Metabolic alkalosis is similar but is rather due to a metabolic problem. Respiratory acidosis is sort of the opposite of respiratory alkalosis.
Respiratory alkalosis occurs due to hyperventilation, which causes pCO2 to decrease (hypocapnia). Respiratory alkalosis is rarely as clinically significant as the other acid-base disorders.
Etiology
Any condition which causes hyperventilation, i.e. minute ventilation beyond what is necessary for the body, can cause respiratory alkalosis. This is due to the "washing out" of CO2 that occurs.
- Intentional hyperventilation
- Anxiety
- Pain or other distressing stimuli
- Pregnancy
- High altitude
Hypoxaemia causes hyperventilation as a compensatory reaction. If the arterial pO2 falls below 60 mmHg ventilation will be stimulated, which may normalise oxygen levels but wash out CO2.
Pathophysiology
CO2 is a cerebral vasodilator, so hypocapnia causes cerebral vasoconstriction, which reduces cerebral blood flow. This may cause syncope.
Alkalaemia may cause plasma proteins to bind more free calcium ions, causing the level of free calcium in the serum to decrease, effectively causing hypocalcaemia.
Alkalaemia also shifts the haemoglobin-oxygen dissociation curve to the left, which decreases tissue oxygenation.
Compensation
The initial compensation occurs to intracellular buffers like the haemoglobin buffers, and is relatively modest.
The healthy kidney can compensate for respiratory alkalosis by increasing its excretion of bicarbonate to a large degree. Renal compensation begins soon after the alkalosis, but it takes up to five takes to become complete.
Clinical features
Respiratory alkalosis is rarely clinically significant and rarely causes symptoms. It may cause symptoms like dizziness and syncope. The resulting hypocalcaemia may cause symptoms like perioral or extremity paraesthesia.
Diagnosis and evaluation
Arterial blood gas is essential in the evaluation of acid-base disorders. It will give the pH, bicarbonate level, pCO2, pO2, and lactate levels. In respiratory alkalosis, the pCO2 is low (< 35 mmHg). If there is alkalaemia, the pH is > 7.45.
The renal compensation to respiratory alkalosis reduces bicarbonate by 2-5 units for every 10 mmHg reduction in pCO2.
The cause of respiratory alkalosis is often apparent by the anamnesis.
Management
Treatment should be directed toward the underlying cause. If caused by anxiety, breathing into a bag may help.