COMMON ACID-BASE DISORDERS YOU SHOULD KNOW

Maintaining a stable pH within the narrow physiological range is critical for normal cellular function, enzyme activity, and overall homeostasis. Acid-base disorders arise when the balance between acid production and excretion is disrupted, leading to deviations in blood pH.

Biochemical Bases of Acid-Base Balance

Acid-base balance is maintained through the interplay of buffer systems and the regulatory actions of the lungs and kidneys.

• Definition of Acids and Bases:
  • An acid is a substance that can donate a hydrogen ion (H⁺). Strong acids (e.g., HCl) dissociate completely in solution, releasing many H⁺ ions. Weak acids (e.g., carbonic acid, H₂CO₃) only partially dissociate.
  • A base is a substance that can accept a hydrogen ion (H⁺) or donate a hydroxide ion (OH⁻). Bicarbonate (HCO₃⁻) is a key base in biological systems.
• The pH Scale:
  • pH is a measure of the acidity or alkalinity of a solution, defined as the negative logarithm of the hydrogen ion concentration: pH = -log₁₀[H⁺].
  • A lower pH indicates higher [H⁺] and greater acidity. A higher pH indicates lower [H⁺] and greater alkalinity.
  • The normal physiological blood pH range is tightly regulated between 7.35 and 7.45. Values below 7.35 indicate acidosis, and values above 7.45 indicate alkalosis.
• Sources of Acids in the Body:
  • Volatile Acid: Carbon dioxide (CO₂) is the primary volatile acid produced from cellular metabolism. CO₂ reacts with water to form carbonic acid (H₂CO₃), which then dissociates into H⁺ and bicarbonate (HCO₃⁻). This reaction is reversible and catalyzed by the enzyme carbonic anhydrase. CO₂ levels are regulated by respiration.
  • Non-Volatile (Fixed) Acids: These are acids produced from metabolism that are not in gaseous form and must be buffered and excreted by the kidneys. Examples include lactic acid (from anaerobic metabolism), ketoacids (from fat breakdown), sulfuric acid (from protein metabolism), and phosphoric acid (from phospholipid metabolism).
• Buffer Systems:
  • Buffers are substances that minimize changes in pH when acids or bases are added to a solution. They consist of a weak acid and its conjugate base.
  • In the body, buffers immediately respond to changes in H⁺ concentration, acting as the first line of defense.
  • Key buffer systems include:
    • Bicarbonate Buffer System: The most important extracellular buffer. It involves carbonic acid (H₂CO₃) and its conjugate base, bicarbonate (HCO₃⁻). The lungs regulate the CO₂ component, and the kidneys regulate the HCO₃⁻ component, linking this system to respiratory and metabolic control.
    • Phosphate Buffer System: Important intracellularly and in urine.
    • Protein Buffer System: Intracellular and extracellular proteins (including hemoglobin) can accept or donate H⁺ ions via their amino acid residues. Hemoglobin is particularly important in red blood cells for buffering H⁺ generated from CO₂ transport.
• Role of the Lungs (Respiratory Component):
  • The lungs rapidly regulate CO₂ levels through ventilation.
  • Increased ventilation (hyperventilation) expels more CO₂, shifting the H₂CO₃ ⇌ H⁺ + HCO₃⁻ equilibrium to the left, reducing H⁺ concentration and increasing pH (respiratory alkalosis).
  • Decreased ventilation (hypoventilation) retains CO₂, shifting the equilibrium to the right, increasing H⁺ concentration and decreasing pH (respiratory acidosis).
  • The partial pressure of carbon dioxide in arterial blood (PaCO₂) is the clinical measure reflecting the respiratory component. Normal PaCO₂ is typically 35-45 mmHg.
• Role of the Kidneys (Metabolic Component):
  • The kidneys are slower but more powerful regulators of acid-base balance, controlling bicarbonate levels and excreting fixed acids.
  • They reabsorb filtered bicarbonate in the tubules, preventing its loss in urine.
  • They generate new bicarbonate by excreting H⁺ ions, primarily buffered by phosphate and ammonia (forming ammonium ions, NH₄⁺).
  • They excrete fixed acids that cannot be exhaled.
  • The concentration of bicarbonate in plasma (HCO₃⁻) is the clinical measure reflecting the metabolic component. Normal plasma HCO₃⁻ is typically 22-26 mEq/L.
• The Henderson-Hasselbalch Equation:
  • This equation describes the relationship between pH, the bicarbonate buffer system, and PaCO₂: pH = pKₐ + log₁₀ ([HCO₃⁻] / [H₂CO₃])
  • Since H₂CO₃ is in equilibrium with dissolved CO₂ (H₂CO₃ ≈ 0.03 * PaCO₂), the equation is often written as: pH = 6.1 + log₁₀ ([HCO₃⁻] / (0.03 * PaCO₂))
  • This equation highlights that pH is directly proportional to the ratio of HCO₃⁻ (kidney/metabolic) to PaCO₂ (lung/respiratory). Changes in either component will affect pH.

Metabolic and Respiratory Acid-Base Disorders

Acid-base disorders are classified based on whether the primary disturbance is metabolic (affecting HCO₃⁻) or respiratory (affecting PaCO₂), and whether the resulting pH change is acidosis (low pH) or alkalosis (high pH). The body attempts to counteract the primary disturbance with compensation from the unaffected system.

• Metabolic Acidosis:
  • Definition: A primary decrease in plasma bicarbonate concentration ([HCO₃⁻]), leading to a decrease in pH.
  • Biochemical Basis/Causes:
    • Increased production of fixed acids (e.g., lactic acidosis, ketoacidosis from diabetes mellitus, starvation, or alcohol).
    • Decreased excretion of fixed acids by the kidneys (e.g., renal tubular acidosis, chronic kidney disease).
    • Loss of bicarbonate from the body (e.g., severe diarrhea, pancreatic fistulas, renal tubular acidosis).
    • Administration of acidic substances (e.g., acid infusions).
  • Compensation: Respiratory compensation occurs through hyperventilation, which decreases PaCO₂, shifting the bicarbonate buffer equation to the left to help raise pH.
  • Anion Gap: Metabolic acidosis is often categorized by the anion gap (AG), which is the difference between measured cations (Na⁺) and measured anions (Cl⁻, HCO₃⁻): AG = [Na⁺] – ([Cl⁻] + [HCO₃⁻]). A normal anion gap is 8-12 mEq/L. Metabolic acidosis with an increased anion gap usually results from the addition of unmeasured acids (like lactate, ketoacids, etc.), while normal anion gap acidosis suggests bicarbonate loss (e.g., diarrhea) or impaired renal bicarbonate reabsorption without accumulation of unmeasured anions.
• Metabolic Alkalosis:
  • Definition: A primary increase in plasma bicarbonate concentration ([HCO₃⁻]), leading to an increase in pH.
  • Biochemical Basis/Causes:
    • Loss of hydrogen ions (e.g., vomiting, nasogastric suction, hyperaldosteronism).
    • Gain of bicarbonate (e.g., administration of bicarbonate, citrate overload from transfusions, contraction alkalosis from loop/thiazide diuretics).
    • Potassium depletion (hypokalemia) can contribute by causing H⁺ to shift intracellularly and increasing renal H⁺ excretion.
  • Compensation: Respiratory compensation occurs through hypoventilation, which increases PaCO₂, shifting the bicarbonate buffer equation to the right to help lower pH. This compensation is limited by the hypoxic drive to breathe.
• Respiratory Acidosis:
  • Definition: A primary increase in arterial carbon dioxide partial pressure (PaCO₂), leading to a decrease in pH.
  • Biochemical Basis/Causes: Occurs due to hypoventilation, which impairs CO₂ elimination. Causes include:
    • Central nervous system depression (e.g., sedatives, opiates, head injury).
    • Neuromuscular disorders affecting respiratory muscles (e.g., Guillain-Barré syndrome, myasthenia gravis, spinal cord injury).
    • Airway obstruction (e.g., COPD exacerbation, asthma, foreign body).
    • Pulmonary disease (e.g., severe pneumonia, pulmonary edema).
    • Mechanical ventilation issues.
  • Compensation: Renal compensation occurs slowly (over days) by increased excretion of H⁺ and generation/retention of bicarbonate.
• Respiratory Alkalosis:
  • Definition: A primary decrease in arterial carbon dioxide partial pressure (PaCO₂), leading to an increase in pH.
  • Biochemical Basis/Causes: Occurs due to hyperventilation, which increases CO₂ elimination. Causes include:
    • Hypoxia (stimulates peripheral chemoreceptors, e.g., high altitude, pneumonia, pulmonary embolism).
    • Anxiety or pain (central stimulation of respiratory drive).
    • Fever, sepsis, salicylate toxicity.
    • Stimulation of central respiratory drive (e.g., brainstem lesions).
    • Iatrogenic (e.g., mechanical ventilation settings).
  • Compensation: Renal compensation occurs slowly (over days) by decreased excretion of H⁺ and decreased generation/increased excretion of bicarbonate.

Utility of Arterial Blood Gases (ABGs) in Acid-Base Disorders

Arterial blood gas analysis is the cornerstone for diagnosing and managing acid-base disorders. ABGs provide critical quantitative data about the patient’s respiratory function, metabolic status, and oxygenation.

• What ABGs Measure:
  • pH: The absolute measure of acidity or alkalinity.
  • PaCO₂ (Partial pressure of carbon dioxide): Reflects the respiratory component of acid-base balance (controlled by the lungs).
  • HCO₃⁻ (Bicarbonate concentration): Primarily reflects the metabolic component of acid-base balance (controlled by the kidneys). Note: HCO₃⁻ is often calculated from the pH and PaCO₂ using the Henderson-Hasselbalch equation, though some analyzers measure it directly.
  • PaO₂ (Partial pressure of oxygen) and SaO₂ (Oxygen saturation) are also measured, providing information on oxygenation, important for overall patient assessment but not directly for determining the acid-base disorder type.
• Interpreting ABGs: A Step-by-Step Approach
  1. Assess the pH: Is it normal (7.35-7.45), acidemic (< 7.35), or alkalemic (> 7.45)? This identifies the overall status but not necessarily the primary cause.
  2. Assess the PaCO₂: Is it normal (35-45 mmHg)? High PaCO₂ suggests respiratory acidosis. Low PaCO₂ suggests respiratory alkalosis. Think: Is the respiratory system attempting to explain the pH change?
  3. Assess the HCO₃⁻: Is it normal (22-26 mEq/L)? High HCO₃⁻ suggests metabolic alkalosis. Low HCO₃⁻ suggests metabolic acidosis. Think: Is the metabolic system attempting to explain the pH change?
  4. Determine the Primary Disorder:
     • If the pH is low (< 7.35) and PaCO₂ is high (> 45), the primary disorder is respiratory acidosis.
     • If the pH is low (< 7.35) and HCO₃⁻ is low (< 22), the primary disorder is metabolic acidosis.
     • If the pH is high (> 7.45) and PaCO₂ is low (< 35), the primary disorder is respiratory alkalosis.
     • If the pH is high (> 7.45) and HCO₃⁻ is high (> 26), the primary disorder is metabolic alkalosis.
     • (Note: One of the components, either PaCO₂ or HCO₃⁻, must deviate in the expected direction relative to the pH change to be the primary cause).
  5. Assess for Compensation: Once the primary disorder is determined, check if the other system (the one not primarily affected) is attempting to compensate by moving in the opposite direction relative to the pH change. For example, in metabolic acidosis, expect PaCO₂ to decrease (respiratory compensation). In respiratory acidosis, expect HCO₃⁻ to increase (renal compensation). Compensation attempts to bring the pH back toward normal but rarely achieves full correction (pH usually remains outside the normal range, although in compensated respiratory alkalosis or chronic respiratory acidosis, the pH may be closer to normal, or even within the low/high end of the normal range).
  6. Assess for Mixed Disorders (If necessary): If the values don’t fit a simple disorder with appropriate compensation, or if the pH is near-normal but both PaCO₂ and HCO₃⁻ are significantly abnormal in opposite directions (e.g., low PaCO₂ and low HCO₃⁻), a mixed disorder is likely present. This requires further analysis (see below).

Examples of Simple and Complex Acid-Base Disorders

Understanding simple disorders with compensation is foundational for identifying complex (mixed) disorders, which involve two or more primary disturbances occurring simultaneously.

• Simple Acid-Base Disorders (Primary Disorder with Appropriate Compensation):
  • Example 1: Simple Metabolic Acidosis (e.g., Diabetic Ketoacidosis – DKA)
    • ABG: pH low (< 7.35), HCO₃⁻ low (< 22), PaCO₂ low (< 35).
    • Explanation: Excess ketoacids increase fixed acids, consuming HCO₃⁻ (low HCO₃⁻). The low pH stimulates the respiratory center, causing hyperventilation (low PaCO₂ – respiratory compensation). The anion gap would typically be high in DKA.
  • Example 2: Simple Metabolic Alkalosis (e.g., Severe Vomiting)
    • ABG: pH high (> 7.45), HCO₃⁻ high (> 26), PaCO₂ high (> 45).
    • Explanation: Loss of gastric acid (HCl) leads to a net retention of HCO₃⁻ (high HCO₃⁻). The high pH suppresses the respiratory center, causing hypoventilation (high PaCO₂ – respiratory compensation).
  • Example 3: Simple Respiratory Acidosis (e.g., COPD Exacerbation)
    • ABG: pH low (< 7.35), PaCO₂ high (> 45), HCO₃⁻ high (> 26).
    • Explanation: Impaired ventilation retains CO₂ (high PaCO₂). This leads to a decrease in pH. If chronic, the kidneys compensate by retaining and generating more HCO₃⁻ (high HCO₃⁻). If acute, HCO₃⁻ may be normal or only slightly elevated as renal compensation is slow.
  • Example 4: Simple Respiratory Alkalosis (e.g., Anxiety Hyperventilation)
    • ABG: pH high (> 7.45), PaCO₂ low (< 35), HCO₃⁻ low (< 22).
    • Explanation: Hyperventilation blows off excess CO₂ (low PaCO₂), leading to an increase in pH. If acute, HCO₃⁻ may be normal or only slightly decreased. If chronic (less common from anxiety alone, but could be from chronic hypoxia), the kidneys compensate by excreting more HCO₃⁻ (low HCO₃⁻).
• Complex (Mixed) Acid-Base Disorders (Presence of Multiple Primary Disturbances): These occur when a patient has more than one acid-base problem simultaneously. ABGs in mixed disorders often show abnormalities in both PaCO₂ and HCO₃⁻ that cannot be explained by simple compensation alone.
  • Example 1: Metabolic Acidosis + Respiratory Alkalosis (e.g., Aspirin (Salicylate) Overdose)
    • ABG: pH can be low, normal, or high depending on the dominant process, but crucially, PaCO₂ is very low (<35) and HCO₃⁻ is very low (<22).
    • Explanation: Salicylates cause both: 1) Metabolic acidosis by interfering with cellular metabolism and causing accumulation of organic acids (low HCO₃⁻). 2) Respiratory alkalosis by directly stimulating the respiratory center in the brain (low PaCO₂). The compensatory response to metabolic acidosis would be low PaCO₂, and the compensatory response to respiratory alkalosis would be low HCO₃⁻. In salicylate overdose, both are primary causes driving the parameters in the same direction (low).
  • Example 2: Metabolic Acidosis + Respiratory Acidosis (e.g., Cardiac Arrest or Cardiopulmonary Failure)
    • ABG: pH very low (often < 7.0), PaCO₂ very high (> 45), HCO₃⁻ very low (< 22).
    • Explanation: Cardiopulmonary failure leads to both: 1) Respiratory acidosis due to inadequate ventilation and CO₂ retention (high PaCO₂). 2) Metabolic acidosis due to poor tissue perfusion leading to anaerobic metabolism and lactic acid production (low HCO₃⁻). Both primary disorders are driving the pH down.

Analyzing complex disorders often requires calculating expected compensation ranges or the anion gap and delta gap/delta-delta analyses to identify hidden concurrent processes.