Internal Medicine/Acidosis and Alkalosis

Acid-Base Homeostasis

The body keeps the pH of systemic arterial blood in the range of 7.35 to 7.45 through a combination of extracellular and intracellular chemical buffering, along with regulatory mechanisms involving the respiratory and renal systems. The central nervous system (CNS) and respiratory system control arterial CO2 levels (Paco2), while the kidneys manage plasma bicarbonate levels. This regulation maintains the arterial pH by either excreting or retaining acids or bases. The interaction between the metabolic and respiratory factors responsible for systemic pH regulation is described by the Henderson-Hasselbalch equation.

Under normal conditions, CO2 production and elimination are balanced, maintaining a steady-state Paco2 at approximately 40 mmHg. Hypoventilation results in hypercapnia (high Paco2), while hyperventilation leads to hypocapnia (low Paco2). However, the production and elimination of CO2 are regulated primarily by neural respiratory factors and are not directly controlled by the rate of CO2 production. Hypercapnia typically occurs due to hypoventilation rather than an increase in CO2 production. Any significant deviation in Paco2 levels usually reflects alterations in neural respiratory control or compensatory changes in response to primary changes in plasma bicarbonate levels.

Diagnosing Common Types of Acid-Base Disorders

The most frequently encountered clinical acid-base disturbances include metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis, each occurring individually. Recognizing these basic acid-base disorders necessitates an understanding of the limits of physiological compensation for a primary disturbance.

Simple Acid-Base Disorders: Primary changes in Paco2 (respiratory disturbances) trigger compensatory metabolic responses (alterations in [HCO3-]), and primary metabolic disturbances result in predictable compensatory respiratory responses (changes in Paco2). These compensatory responses tend to bring the pH closer to, but not exactly to, the normal range. An exception is chronic respiratory alkalosis, which, if prolonged, may return the pH to the normal range. In metabolic acidosis resulting from increased endogenous acid production, such as ketoacidosis or lactic acidosis, the extracellular fluid's [HCO3-] decreases, lowering the extracellular pH. This stimulates medullary chemoreceptors, increasing ventilation and restoring the [HCO3-] to Paco2 ratio and pH towards, though typically not reaching, normal levels. The degree of respiratory compensation for metabolic acidosis can be estimated using the Winter's equation: Paco2 = (1.5 × [HCO3-]) + 8 ± 2.
Mixed Acid-Base Disorders: Mixed acid-base disorders, where independently coexisting disorders occur, are often seen in critically ill patients and can lead to severe pH imbalances. The diagnosis of mixed acid-base disorders involves considering the anion gap (AG), which is calculated as AG = Na+ - (Cl- + HCO3-). The AG is an essential indicator, with an average normal value of approximately 10 mmol/L, used to assess the presence of high-AG metabolic acidosis, which may result from the accumulation of various non-chloride-containing acids. The presence of an elevated AG denotes metabolic acidosis, even when [HCO3-] or pH appears normal. Correcting the AG is essential if hypoalbuminemia is present by adding 2.5 mmol/L for each g/dL of albumin below the normal value of 4.5 g/dL.
Examples of Mixed Acid-Base Disorders: Various scenarios can lead to mixed acid-base disorders, such as high-AG metabolic acidosis with concomitant respiratory disorders or metabolic disturbances. Additionally, there are instances of metabolic alkalosis combined with respiratory acidosis or alkalosis. Detection of mixed high-AG acidosis or metabolic alkalosis is crucial when evaluating complex cases, as it requires assessing the interplay between AG and HCO3-.

Approach to Diagnosing Acid-Base Disorders

Diagnosing acid-base disorders follows a systematic approach involving several steps. These include simultaneously obtaining arterial blood gas (ABG) and electrolyte measurements, ensuring the accuracy of [HCO3-] on both ABG and electrolyte panels, evaluating the AG, understanding the various causes of high-AG acidosis, and estimating the compensatory responses based on specific relationships between Paco2 and [HCO3-] detailed in a table.

When assessing acid-base disorders, special attention should be given to the anion gap (AG). Calculated as AG = Na+ - (Cl- + HCO3-), the AG measures the unmeasured anions present in plasma and is typically within the range of 6-12 mmol/L. A high AG most often indicates the accumulation of non-chloride-containing acids, but it can be caused by other factors like changes in unmeasured cations, exogenous cations, or alterations in plasma anion albumin concentration. Correcting the AG is necessary when hypoalbuminemia is present, with 2.5 mmol/L added for each g/dL of albumin below the normal value of 4.5 g/dL. Understanding the AG helps identify high-AG acidosis, which results from various conditions involving the buildup of different acid types, such as inorganic, organic, exogenous, or unidentified anions. Even if [HCO3-] or pH is within the normal range, a high AG can signify the presence of metabolic acidosis. Comparing the decline in [HCO3-] (ΔHCO3-: 25 - patient's [HCO3-]) with the increase in AG (ΔAG: patient's AG - 10) is a useful approach when dealing with high-AG metabolic acidosis, especially when pH and [HCO3-] appear normal.

Metabolic Acidosis

Metabolic acidosis is a complex acid-base disturbance characterized by an abnormal decrease in the pH of the blood and body fluids. It can manifest in various forms, with the two primary classifications being High Anion Gap Acidosis (HAGA) and Non-Anion Gap Acidosis (NAGA).

Causes of High Anion Gap Acidosis

High Anion Gap Acidosis (HAGA) encompasses a broad spectrum of conditions, each with distinct pathophysiological mechanisms:

Lactic Acidosis: This subtype is classified into two major types: Type A and Type B. Type A results from inadequate tissue oxygenation, such as during severe shock or hypoxia, while Type B arises from non-hypoxic causes, often secondary to medications, toxins, systemic diseases, or inborn errors of metabolism.
Ketoacidosis: Diabetic Ketoacidosis (DKA) and Alcoholic Ketoacidosis (AKA) are classic examples. DKA typically occurs in uncontrolled diabetes mellitus, marked by hyperglycemia and ketone production. AKA develops in chronic alcoholics, where alcohol metabolism disrupts the balance of acids and bases.
Toxin Ingestion: Ethylene Glycol (EG) and Methanol intoxication stand out as notable culprits. These toxic alcohols are metabolized to glycolate and formaldehyde, respectively, generating an accumulation of organic acids that drive metabolic acidosis.
Renal Failure: Kidney dysfunction, particularly acute renal failure, hinders acid excretion, leading to the accumulation of acidic substances in the bloodstream.
Sepsis: Severe infections, such as sepsis, can precipitate Lactic Acidosis Type A. Inflammatory processes and septic shock impair tissue perfusion, causing cells to shift towards anaerobic metabolism, yielding lactic acid as a byproduct.

Lactic acidosis is a crucial component of HAGA, characterized by elevated blood lactate levels and metabolic acidosis. Further details include:

Type A Lactic Acidosis: Occurring due to tissue hypoxia, Type A lactic acidosis emerges when tissues experience oxygen deprivation, prompting anaerobic glycolysis. This type is primarily associated with conditions like severe shock, cardiac arrest, and sepsis.
Type B Lactic Acidosis: Type B encompasses a diverse array of causes unrelated to tissue hypoxia. Medications (e.g., metformin), toxins, malignancies, and certain systemic diseases can all precipitate Type B lactic acidosis.
Treatment: Addressing the underlying cause remains the cornerstone of lactic acidosis management. In cases of severe acidosis, sodium bicarbonate may be administered cautiously, as its efficacy remains debated.

Diabetic Ketoacidosis (DKA), a classic example of HAGA, predominantly occurs in individuals with uncontrolled diabetes mellitus:

Elevated Glucose Levels: DKA is often heralded by markedly elevated blood glucose concentrations, driven by insulin deficiency and excessive counterregulatory hormone release.
Ketone Production: Insufficient insulin leads to unrestrained lipolysis, resulting in an abundance of ketones, such as acetoacetate and beta-hydroxybutyrate, leading to metabolic acidosis.
Treatment: Managing DKA necessitates a multifaceted approach involving insulin administration, fluid resuscitation, correction of electrolyte imbalances (particularly potassium), and addressing underlying precipitating factors like infections.

Alcoholic Ketoacidosis (AKA) is a form of high anion gap metabolic acidosis occurring in chronic alcoholics:

Inadequate Food Intake: AKA is often tied to malnutrition, with alcoholics experiencing poor dietary intake leading to depletion of glycogen stores and a switch to fatty acid oxidation.
Fluid and Electrolyte Imbalance: Chronic alcohol use can lead to dehydration and electrolyte derangements, such as hypokalemia, contributing to AKA.
Treatment: Management centers around fluid repletion, thiamine supplementation to prevent Wernicke's encephalopathy, glucose administration to prevent hypoglycemia, and addressing any concomitant electrolyte imbalances.

Other causes:

Ethylene glycol (EG) and methanol ingestion can result in high anion gap acidosis, often necessitating rapid identification and intervention:
- Suspicion and Diagnosis: A critical aspect is recognizing the combination of an elevated anion gap and osmolar gap, serving as an early indication of EG or methanol intoxication.
- Metabolites and Acidosis: The toxic alcohols and their metabolites, including glycolate and formaldehyde, contribute to the elevated anion gap and acidosis.
- Treatment: Immediate intervention involves intravenous fluids, administration of thiamine and pyridoxine, fomepizole or ethanol therapy, and hemodialysis when specific criteria, such as severe acidosis or end-organ damage, are met.

Propylene Glycol: Propylene glycol, used as a vehicle in intravenous medications, can accumulate in critically ill patients, leading to high-gap acidosis. Early recognition involves discontinuing the implicated infusion and considering fomepizole therapy.
Isopropyl Alcohol: Ingested isopropyl alcohol can be rapidly absorbed, leading to potentially fatal outcomes even with small quantities. Treatment includes supportive care, fluid resuscitation, and hemodialysis for severe cases with hemodynamic instability.

Pyroglutamic Acidosis: Pyroglutamic acidosis is relatively uncommon and can occur in the setting of acetaminophen overdose or in malnourished or critically ill patients receiving acetaminophen. It is associated with the accumulation of 5-oxoproline (pyroglutamic acid).
Metabolic Acidosis in CKD: As chronic kidney disease (CKD) progresses, metabolic acidosis transitions from hyperchloremic acidosis in moderate CKD (stage 3) to high anion gap acidosis in advanced CKD (stages 4 and 5). This shift arises due to impaired filtration and reabsorption of organic anions by dysfunctional nephrons, leading to a net retention of acid in the body.
- Treatment: Managing metabolic acidosis in CKD is essential for preserving bone health, mitigating muscle wasting, and slowing the progression of kidney dysfunction. Oral alkali replacement, often with sodium bicarbonate or sodium citrate, is the primary intervention.

Non-Anion Gap Acidosis

Non-Anion Gap Acidosis (NAGA) presents unique challenges, with several potential etiologies:

Gastrointestinal Bicarbonate Loss: Conditions like diarrhea, external pancreatic or small-bowel drainage, and surgical procedures like ureterosigmoidostomy can result in excessive bicarbonate loss from the gastrointestinal tract.
Renal Acidosis: NAGA can occur due to various renal causes, such as proximal renal tubular acidosis (RTA) or distal RTA. Proximal RTA (Type 2) is often associated with glycosuria, aminoaciduria, and phosphaturia (Fanconi syndrome), while distal RTA (Type 1) is marked by hypokalemia and nephrocalcinosis.
Drug-Induced Hyperkalemia: Medications like potassium-sparing diuretics, trimethoprim, pentamidine, ACE inhibitors, ARBs, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, and heparin can elevate potassium levels and lead to NAGA.

Treatment of Non-Anion Gap Acidosis

In cases of non-Anion Gap (AG) acidosis resulting from bicarbonate loss through the gastrointestinal tract, the administration of sodium bicarbonate (NaHCO3) can be carried out either intravenously or orally. The choice between these routes depends on the severity of the acidosis and concurrent volume depletion. However, addressing proximal renal tubular acidosis (RTA), particularly Type 2, can pose a significant treatment challenge. This is because administering oral alkali exacerbates the excretion of bicarbonate and potassium through the urine.

In instances of proximal RTA (Type 2), it is often necessary to supplement potassium. A suitable approach is to prescribe an oral solution containing sodium and potassium citrate, with each 5 mL of the solution consisting of citric acid (334 mg), sodium citrate (500 mg), and potassium citrate (550 mg). Commercial products like Virtrate or Cytra-3 serve this purpose.

On the other hand, when dealing with classical distal RTA (Type 1), the correction of hypokalemia takes precedence. Once this has been achieved, alkali therapy should commence. Two effective options are sodium citrate (Shohl's solution) or sodium bicarbonate tablets (each containing 650 mg of sodium bicarbonate, equivalent to 7.8 milliequivalents of bicarbonate). These treatments aim to correct and maintain the serum bicarbonate concentration within the range of 24 to 26 milliequivalents per liter (meq/L).

Patients with Type 1 RTA often respond well to chronic alkali therapy. This intervention carries several benefits, including a reduction in the frequency of nephrolithiasis (kidney stones), improvements in bone density, the restoration of normal growth patterns in children, and the preservation of kidney function in both adults and pediatric patients.

However, in the case of Type 4 RTA, a dual therapeutic approach is necessary. It involves correcting the metabolic acidosis using the same strategies applied in classical distal renal tubular acidosis (Type 1 RTA). Simultaneously, attention must be given to rectifying hyperkalemia or elevated plasma potassium levels. Achieving normokalemia, or normal potassium levels in the blood, enhances the excretion of net acid in the urine, leading to significant improvement in the metabolic acidosis.

Management of Type 4 RTA may include the chronic administration of oral sodium polystyrene sulfonate, usually in the form of 15 grams of powder prepared as an oral solution. This treatment is typically administered once daily, 2 to 3 times per week, and it's worth noting that the preparation excludes sorbitol due to palatability concerns, as patient compliance can be challenging.

As an alternative, the non-absorbed calcium-potassium cation exchange polymer, patiromer, can be considered for patients with Type 4 RTA and concurrent hyperkalemia. This option is preferred due to its better taste. It's supplied as 8.4-gram packets of powder for suspension, with dosing adjusted at weekly intervals based on the plasma potassium levels. The maximum daily dose should not exceed 25.2 grams.

Additionally, dietary adjustments are vital, and patients should consume a low-potassium diet, avoiding potassium-rich foods or supplements, including salt substitutes. All medications that retain potassium should be discontinued, and, if necessary, a loop diuretic may be prescribed to aid in potassium excretion.

In cases where isolated hypoaldosteronism is confirmed, patients may require fludrocortisone therapy. However, the specific dose can vary depending on the underlying cause of the hormone deficiency. It's crucial to approach fludrocortisone administration cautiously, particularly in patients with edema and hypertension, as it has the potential to worsen these conditions. When prescribed, it is often administered in combination with furosemide to mitigate possible aggravation of these symptoms.

Metablolic Alkalosis

Metabolic alkalosis is characterized by an elevated arterial pH, an increase in the serum bicarbonate concentration ([HCO3-]), and a rise in Paco2 due to compensatory alveolar hypoventilation (as shown in Table 55-1). This condition is often accompanied by hypochloremia and hypokalemia. The elevation in arterial pH serves as a diagnostic indicator, as respiratory acidosis is characterized by decreased pH, despite both conditions having elevated Paco2 levels. Furthermore, metabolic alkalosis can frequently co-occur with other acid-base disorders, including respiratory acidosis, respiratory alkalosis, or metabolic acidosis.

Metabolic Alkalosis: Etiology and Pathogenesis

Metabolic alkalosis results from either a net gain of bicarbonate ([HCO3-]) or the loss of nonvolatile acid, typically hydrochloric acid (HCl) through processes like vomiting. During vomiting, when HCl is lost from the stomach, the small bowel fails to initiate HCO3- secretion, causing an accumulation of HCO3- in the extracellular fluid. This phase is referred to as the "generation stage" of metabolic alkalosis since the loss of acid triggers alkalosis. Once vomiting ceases, the "maintenance stage" begins, as secondary factors prevent the kidneys from appropriately excreting HCO3-.

Maintenance of metabolic alkalosis signifies a kidney failure to eliminate excess HCO3- from the extracellular compartment. The kidneys retain the surplus alkali rather than excreting it when:

Volume deficiency, chloride deficiency, and potassium deficiency occur concurrently with reduced glomerular filtration rate (GFR), resulting in low urine chloride levels.
Hypokalemia is present due to autonomous hyperaldosteronism, leading to normal urine chloride levels.

In the first scenario, saline-responsive metabolic alkalosis can be corrected by restoring extracellular fluid volume (ECFV) through intravenous administration of sodium chloride (NaCl) and potassium chloride (KCl). Conversely, in the latter situation, treatment may involve pharmacologic or surgical interventions rather than saline administration, as it is considered saline-unresponsive metabolic alkalosis.

Metabolic Alkalosis: Differential Diagnosis

To determine the cause of metabolic alkalosis, various factors need to be assessed, including the ECFV status, blood pressure in both recumbent and upright positions (to detect orthostasis), serum potassium concentration ([K+]), urine chloride concentration ([Cl–]), and, in some cases, the renin-aldosterone system. For example, the presence of chronic hypertension and chronic hypokalemia in a patient with alkalosis may suggest mineralocorticoid excess or the use of diuretics. If plasma renin activity is low, and urine chloride levels exceed 20 milliequivalents per liter (meq/L) in a patient not taking diuretics, primary mineralocorticoid excess may be indicated. In cases where hypokalemia and alkalosis coexist in a normotensive, non-edematous patient, possible causes include Bartter's or Gitelman's syndrome, magnesium deficiency, vomiting, alkali ingestion, or diuretic usage. Here, the measurement of urine electrolytes (particularly urine chloride) and screening for diuretics are advisable. If urine is alkaline with elevated [Na+]u (urine sodium), [K+]u (urine potassium), and low [Cl–]u, the diagnosis often points to vomiting (either overt or surreptitious) or alkali ingestion. However, if the urine is relatively acidic with low concentrations of Na+, K+, and Cl–, possibilities include prior vomiting, the posthypercapnic state, or previous diuretic use. If sodium, potassium, and chloride concentrations in the urine are not reduced, one should consider magnesium deficiency, Bartter's or Gitelman's syndrome, or current diuretic ingestion. Bartter's syndrome can be distinguished from Gitelman's syndrome by the presence of hypocalciuria in the latter disorder.

Metabolic Alkalosis Associated with ECFV Contraction, K+ Depletion, and Secondary Hyperreninemic Hyperaldosteronism

Metabolic Alkalosis: Alkali Administration

Chronic alkali administration to individuals with normal renal function typically does not result in alkalosis. However, in patients with concurrent hemodynamic disturbances linked to effective ECFV depletion (e.g., heart failure), alkalosis can develop due to a reduced capacity to excrete HCO3- or an increased reabsorption of HCO3-. Such patients may receive sodium bicarbonate (NaHCO3) orally or intravenously, intravenous citrate loads (from whole blood transfusions or therapeutic apheresis), or antacids combined with cation-exchange resins like aluminum hydroxide and sodium polystyrene sulfonate. Interestingly, nursing home residents who receive enteral tube feedings are at a higher risk of developing metabolic alkalosis compared to those on regular diets.

Gastrointestinal Origin: Metabolic alkalosis can arise from gastrointestinal losses of hydrogen ions (H+) during vomiting or gastric aspiration. This simultaneous loss of H+ leads to the addition of HCO3- into the extracellular fluid. During active vomiting, the filtered load of bicarbonate reaching the kidneys increases acutely, surpassing the proximal tubule's capacity for HCO3- absorption. Consequently, excessive HCO3- reaches the distal nephron, where the ability to reabsorb HCO3- is limited, resulting in the excretion of alkaline urine, which stimulates potassium secretion. Once vomiting subsides, the persistent volume, potassium, and chloride depletion promote HCO3- reabsorption, maintaining the alkalosis. Correcting the contracted ECFV with NaCl and addressing potassium deficits with KCl resolves the acid-base disorder by restoring the kidney's capacity to excrete excess bicarbonate.

Renal Origin: Diuretics, such as thiazides and loop diuretics like furosemide, bumetanide, and torsemide, increase salt excretion and acutely decrease the ECFV without altering the total body bicarbonate content. The serum bicarbonate concentration ([HCO3-]) rises because the reduced ECFV effectively "contracts" around the plasma [HCO3-] (resulting in contraction alkalosis). Chronic diuretic administration tends to induce alkalosis by increasing distal salt delivery, which stimulates both potassium (K+) and hydrogen ion (H+) secretion. The maintenance of this alkalosis is supported by continued ECFV contraction, secondary hyperaldosteronism, K+ deficiency, and the direct impact of diuretic use (as long as diuretics are administered). To reverse the alkalosis, discontinuing diuretics and administering isotonic saline to correct the ECFV deficit are necessary.

Solute Losing Disorders: Bartter's Syndrome and Gitelman's Syndrome: These conditions can result in metabolic alkalosis.

Non-Reabsorbable Anions and Magnesium Deficiency: The administration of significant quantities of penicillin derivatives, such as carbenicillin or ticarcillin, introduces non-reabsorbable anions into the distal tubule. This raises the transepithelial potential difference in the collecting tubule, subsequently enhancing H+ and K+ secretion. Magnesium (Mg2+) deficiency can occur with chronic use of thiazide diuretics, alcoholism, malnutrition, or in cases of Gitelman's syndrome. Mg2+ deficiency intensifies hypokalemic alkalosis by promoting distal acidification through renin stimulation, thus enhancing aldosterone secretion.

Potassium Depletion: Chronic potassium (K+) deficiency resulting from extreme dietary K+ insufficiency, diuretic usage, or alcohol abuse can initiate metabolic alkalosis by increasing urinary net acid excretion. Hypokalemia directly upregulates the generation of ammonium (NH4+) in the kidneys (ammoniagenesis). Furthermore, chronic K+ deficiency enhances the H+, K+-ATPases in the distal tubule and collecting duct, increasing K+ reabsorption and H+ secretion simultaneously. Alkalosis linked to severe K+ deficiency does not respond well to salt administration but is corrected by addressing the K+ deficiency. Often, potassium depletion occurs alongside magnesium deficiency in malnourished alcoholics.

After Treatment of Lactic Acidosis or Ketoacidosis: When an underlying trigger for lactic acid or ketoacid generation is corrected, such as volume restoration for shock or severe volume depletion or insulin therapy, the lactate or ketones are metabolized to produce an equivalent amount of HCO3-. The addition of exogenous HCO3- sources can exacerbate this, leading to a surplus of HCO3- ("rebound alkalosis").

Posthypercapnia: Prolonged carbon dioxide (CO2) retention in chronic respiratory acidosis enhances renal HCO3- absorption and the generation of new HCO3- (increased net acid excretion). Metabolic alkalosis arises from the sustained elevation in [HCO3-] when the elevated Paco2 returns abruptly toward normal.

Metabolic Alkalosis Associated with ECFV Expansion, Hypertension, and Mineralocorticoid Excess

Increased aldosterone levels can result from autonomous primary adrenal overproduction or secondary aldosterone release due to renal overproduction of renin. Mineralocorticoid excess enhances net acid excretion and may lead to metabolic alkalosis, typically exacerbated by accompanying K+ deficiency. Salt retention and hypertension are attributed to the upregulation of the epithelial Na+ channel (ENaC) in the collecting tubule in response to aldosterone. Kaliuresis persists due to mineralocorticoid excess and ENaC stimulation, which raises transepithelial voltage, facilitating K+ excretion. Prolonged K+ deficiency may lead to polydipsia and polyuria.

Liddle's Syndrome: Liddle's syndrome results from a rare inherited gain-of-function mutation in genes that regulate the ENaC in the collecting duct. This monogenic form of hypertension is marked by volume expansion, which subsequently suppresses aldosterone production. Patients typically present with hypertension, hypokalemia, and metabolic alkalosis. Symptoms associated with metabolic alkalosis include mental confusion, obtundation, a predisposition to seizures, paresthesias, muscular cramping, tetany, aggravation of arrhythmias, and hypoxemia in chronic obstructive pulmonary disease. Hypokalemia and hypophosphatemia may also be present.

Treatment of Metabolic Alkalosis

The primary goal of therapy is to address the underlying stimulus for HCO3- generation. Correcting the primary causes, such as primary aldosteronism or Cushing's syndrome, can reverse hypokalemia and alkalosis. Factors contributing to the inappropriate increase in HCO3- reabsorption, such as ECFV contraction or K+ deficiency, should also be eliminated. K+ deficits should always be corrected. If ECFV contraction is present, isotonic saline is recommended to reverse the alkalosis. In cases where congestive heart failure or similar conditions prevent saline infusion, acetazolamide (125-250 mg IV), a carbonic anhydrase inhibitor, may be administered to accelerate renal HCO3- loss in patients with adequate renal function. However, acetazolamide may cause urinary K+ losses and subsequent hypokalemia, which should be addressed. Dilute hydrochloric acid IV (0.1 N HCl) has been proposed for extreme cases of metabolic alkalosis but is associated with hemolysis and must be infused slowly into a central vein. This preparation is generally not readily available and must be prepared in the pharmacy, making its use inadvisable due to the potential for serious errors or harm. In Liddle's syndrome, therapy should include a potassium-sparing diuretic (amiloride or triamterene) to inhibit ENaC and correct both hypertension and hypokalemia.

Respiratory Acidosis and Alkalosis

Respiratory acidosis occurs due to severe pulmonary disease, respiratory muscle fatigue, or ventilatory control abnormalities. It is characterized by an increase in Paco2 (carbon dioxide levels) and a decrease in pH. In acute respiratory acidosis, there is a compensatory increase in bicarbonate (HCO3-) levels, while in chronic respiratory acidosis, the kidneys adapt to increase HCO3- levels further. The clinical symptoms vary depending on the severity and duration of respiratory acidosis, underlying diseases, and the presence of hypoxemia. Rapidly rising Paco2 can cause anxiety, dyspnea, confusion, and even coma, while chronic hypercapnia can lead to sleep disturbances, memory loss, and other neurological symptoms.

Various factors, including drugs, injuries, or diseases, can depress the respiratory center and lead to respiratory acidosis. Chronic respiratory acidosis can result from obstructive lung diseases or restrictive disorders involving the chest wall and lungs. Diagnosis involves measuring Paco2 and arterial pH, along with a detailed medical history and physical examination. Additional pulmonary function tests can help identify underlying lung disease, while investigations for nonpulmonary causes include drug history, hematocrit measurement, and assessment of upper airway, chest wall, pleura, and neuromuscular function.

Treatment depends on the severity and onset of respiratory acidosis. Acute respiratory acidosis requires simultaneous management of the underlying cause and restoration of adequate alveolar ventilation, which may involve tracheal intubation and mechanical ventilation. Care must be taken when administering oxygen to avoid worsening acidosis. Chronic respiratory acidosis aims to improve lung function, and gradual reduction of elevated Paco2 levels may be necessary. It is essential to address the primary condition contributing to respiratory acidosis.

Respiratory alkalosis occurs when alveolar hyperventilation lowers Paco2 and increases the HCO3-/ Paco2 ratio, resulting in increased pH. This can happen due to various causes, such as hyperventilation syndrome, certain drugs, diseases, or metabolic conditions. The symptoms of respiratory alkalosis depend on its duration and severity, ranging from dizziness and confusion to cardiovascular effects. Chronic respiratory alkalosis is commonly seen in critically ill patients and often requires addressing the underlying disease. Diagnosis involves measuring arterial pH and Paco2 levels, and treatment focuses on managing the underlying disorder, such as psychological stress in the case of hyperventilation syndrome.

In summary, respiratory acidosis and alkalosis result from disturbances in the body's acid-base balance due to respiratory factors. Their clinical presentation and management depend on the underlying causes and the severity of the condition, with treatment primarily directed at addressing the root cause of the imbalance.