Principles of Acid-Base Balance

Endogenous Acid Production and Chemical Classification

• Daily endogenous acid production varies by age and physiological state:

  • Adults typically produce $1\,mEq/kg/day$.
  • Children produce between $2$ and $3\,mEq/kg/day$.
  • Catabolism significantly increases these production levels.

• Acids are categorized into two primary types:

  • Volatile Acids: These constitute the largest percentage of total acid production. They are derived from $CO_2$, which is a byproduct of fat and carbohydrate metabolism. The chemical conversion follows the formula: $CO_2 + H_2O \rightleftharpoons H_2CO_3$. Because $CO_2$ is a gas regulated by the lungs, these are termed volatile.
  • Non-volatile Acids: These represent a smaller percentage of acid production and are derived from protein metabolism. They are non-carbonic, do not involve $CO_2$, and are not regulated by the lungs. Regulation occurs via the kidneys. Examples include sulfuric acid and phosphoric acid.

Fundamental Principles of Acids, Bases, and pH

• Definitions of chemical species:

  • Acids: Molecules or ions that donate hydrogen ions ($H^+$ or protons) in chemical reactions. Strong acids, such as $HCl$, dissociate freely into $H^+$ and an anion. Weak acids, such as $H_2CO_3$, dissociate minimally.
  • Bases: Molecules or ions that accept $H^+$ in chemical reactions, effectively removing them from the solution. Examples include $HCO_3^- + H^+ \rightleftharpoons H_2CO_3$ and $HPO_4^{2-} + H^+ \rightleftharpoons H_2PO_4^-$. Strong bases (e.g., $OH^-$) react strongly with protons, while weak bases (e.g., $HCO_3^-$) react weakly.

• The pH Scale:

  • Hydrogen ion concentration is expressed as pH, which stands for "Puissance hydrogen" (power of hydrogen).
  • The scale is defined as the negative logarithm of the hydrogen ion concentration ($[H^+]$).
  • A pH of $7$ is neutral ($H^+ = OH^-$), as seen in pure water ($HOH$).
  • pH values less than $7$ are acidic; values greater than $7$ are basic/alkaline.

• Biological pH Levels:

  • Normal arterial blood pH: $7.4$ (range of $7.35$ to $7.45$).
  • Acidosis/Acidemia: Blood pH below $7.35$.
  • Alkalosis/Alkalemia: Blood pH above $7.45$.
  • Normal venous blood pH: $7.35$.
  • Theoretical limits for life: approximately $7.0$ to $7.7$.

The Henderson–Hasselbalch Equation and Compensation

• The relationship between pH, bicarbonate, and carbon dioxide is described by the Henderson–Hasselbalch equation:

  • $pH = 6.1 + \log\left(\frac{[HCO_3^-]}{PaCO_2 \times 0.03}\right)$
  • In this equation, $HCO_3^-$ represents renal regulation (kidneys) and $CO_2 \times 0.03$ represents respiratory regulation (lungs).
  • To maintain a physiological pH of $7.4$, a ratio of $20:1$ (base to acid) must be preserved. As long as this ratio is maintained, the pH remains stable.

• Compensation is the physiological response to maintain normal pH by either increasing/decreasing base to balance an acid change, or increasing/decreasing acid to balance a base change.

• Practice Calculation:

  • Given: $HCO_3^- = 24\,mEq/L$ and $pCO_2 = 40\,mmHg$.
  • Calculation: $\frac{24}{40 \times 0.03} = \frac{24}{1.2} = 20$.
  • Result: $pH = 6.1 + \text{common log of } 20 = 6.1 + 1.30 = 7.4$.

Systems of Acid-Base Regulation

• Buffer Systems (Extracellular and Intracellular):

  • These respond within a fraction of a second to pH changes.
  • Bicarbonate–Carbonic Acid System: The most important system. It involves the reaction: $CO_2 \uparrow + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$. This system minimizes pH shifts by converting strong acids/bases into weak ones. For example, $HCl + HCO_3^- \rightarrow H_2CO_3 + \text{Salt}$, or $NaOH + H_2CO_3 \rightarrow NaHCO_3 + H_2O$.
  • Protein Buffers: These are powerful and plentiful. They include albumin, other extracellular proteins, and hemoglobin in red blood cells. Amino acids within these proteins can accept or donate $H^+$. Conditions like hypoalbuminemia or anemia can impair this buffering capacity.

• Respiratory System:

  • Acute regulation occurs within $1$ to $12$ minutes.
  • Chronic regulation occurs over $1$ to $2$ days.
  • The system controls the $CO_2$ portion of the pH equation. Higher $CO_2$ shifts pH toward acidic; lower $CO_2$ shifts it toward alkaline.
  • Central medullary chemoreceptors monitor $CSF$ pH. When $CO_2$ diffuses into the $CSF$, pH drops, stimulating an increase in the rate and depth of ventilation to exhale more $CO_2$.

• Renal System:

  • Responds within hours to days.
  • It is the most powerful regulatory system and can function for extended periods.
  • The kidneys can excrete urine with a pH range of $4.5$ to $8$. Acidic urine results from excess $H^+$ excretion (common in meat-heavy diets), and alkaline urine results from excess $HCO_3^-$ excretion.

Specific Renal Mechanisms for Acid-Base Balance

• Bicarbonate Reabsorption:

  • Approximately $99\%$ of filtered bicarbonate is reabsorbed in the renal tubules.
  • This process maintains current balance but does not add new bicarbonate to the body.
  • For every $H^+$ secreted into the tubular lumen for excretion, one bicarbonate ion and one sodium ion are reabsorbed into the peritubular capillary (PTC).

• Synthesis of New Bicarbonate:

  • Active Secretion of $H^+$: Found in the late distal tubules via primary active transport. This leads to the synthesis and reabsorption of new bicarbonate into the PTC.
  • Phosphate Buffering: The system uses $HPO_4^{2-}$ (base phosphate) and $H_2PO_4^-$ (acid phosphate). When bicarbonate is unavailable, $HPO_4^{2-}$ combines with $H^+$ to form $H_2PO_4^-$, which is excreted as sodium dihydrogen phosphate ($NaH_2PO_4$).
  • Ammonia–Ammonium Chloride system: This is a highly powerful buffer in renal tubules that generates significant amounts of new bicarbonate. The process depends on the enzyme glutaminase. In acidic states, glutaminase becomes more active, resulting in higher $H^+$ secretion and more new bicarbonate reabsorption. In alkaline states, activity decreases.

Ion Movement and Clinical Consequences

• Movement of $H^+$ and $K^+$ across cell membranes:
  • Acidosis: $H^+$ moves into cells, and $K^+$ moves out of cells to maintain electrical neutrality, leading to hyperkalemia. This is most likely in metabolic acidosis.
  • Alkalosis: $H^+$ moves out of cells, and $K^+$ moves into cells, potentially causing hypokalemia (primarily seen in metabolic alkalosis).
  • These shifts are less significant in primary respiratory disorders.

Clinical ABG Assessment and Analysis

• Normal Arterial Blood Gas (ABG) Values:

  • pH: $7.4$ (range $7.35$–$7.45$)
  • $PaCO_2$: $40\,mmHg$ (range $35$–$45\,mmHg$)
  • $HCO_3^-$: $24\,mEq/L$ (range $22$–$26\,mEq/L$)
  • Base Deficit/Base Excess (BD/BE): $-2$ to $+2$

• Total Venous $CO_2$ Content:

  • Used as a substitute for $HCO_3^-$.
  • Approximately $65$–$70\%$ of total venous $CO_2$ is bicarbonate.
  • It is usually slightly higher than arterial bicarbonate and must be measured near the time of ABG collection to be useful.

• Sequential Analysis Steps:

  1. pH: Determine if the state is acidemia ($<7.4$) or alkalemia ($>7.4$). Note that pH can be normal if fully compensated.
  2. $PaCO_2$: If abnormal, check for primary respiratory problems. High $PaCO_2$ with low pH indicates respiratory acidosis; low $PaCO_2$ with high pH indicates respiratory alkalosis.
  3. $HCO_3^-$: If abnormal, check for metabolic problems. Low bicarb with low pH indicates metabolic acidosis; high bicarb with high pH indicates metabolic alkalosis.
  4. Compensation: Identify adjustments in the non-primary system attempt to return pH toward $7.4$.

Anion Gap Analysis in Metabolic Acidosis

• The Anion Gap (AG) is the difference between major measured cations and major measured anions:

  • $AG = Na^+ - (HCO_3^- + Cl^-)$ or $AG = (Na^+ + K^+) - (HCO_3^- + Cl^-)$
  • Normal AG range: $12 enemy 18\,mEq/L$.
  • Normal AG metabolic acidosis is hyperchloremic.
  • High AG metabolic acidosis is hypochloremic, indicating the presence of unmeasured anions.

• Causes of High Anion Gap Metabolic Acidosis and their anions:

  • Shock or Cardiac Arrest: Lactate
  • Renal Failure: Various renally excreted anions
  • Lactic Acidosis: Lactate
  • Diabetic Ketoacidosis (DKA) or Malnutrition/Starvation: Ketone bodies
  • Salicylate Overdose
  • Ethylene glycol (antifreeze) poisoning: Ethylene glycol metabolites

Mathematical Determination of Primary Disorder vs. Compensation

• Calculation of Percentage Change:

  1. Find the difference between the patient's value and the normal value (e.g., $40\,mmHg$ for $PaCO_2$ or $24\,mEq/L$ for $HCO_3^-$).
  2. Divide this difference by the normal value to find the percent change.
  3. The system with the larger percent change is the primary problem.
  4. The system with the smaller percent change represents the degree of compensation or contribution.

• Example 1:

  • Results: pH $7.30$, $PaCO_2\,30\,mmHg$, $HCO_3^-\,12\,mEq/L$.
  • Percent Change: $PaCO_2$ is $25\%$ (10/40); $HCO_3^-$ is $50\%$ (12/24).
  • Interpretation: Primary metabolic acidosis with partial respiratory alkalosis compensation.

• Example 2:

  • Results: pH $7.26$, $PaCO_2\,50\,mmHg$, $HCO_3^-\,12\,mEq/L$.
  • Percent Change: $PaCO_2$ is $25\%$ (10/40); $HCO_3^-$ is $50\%$ (12/24).
  • Interpretation: Mixed respiratory and metabolic acidosis.

• Example 3 (Diabetic Ketoacidosis Case):

  • Vitals/Labs: BP $80/40$, HR $188$, RR $24$ (deep), glucose $704\,mg/dl$, $K^+\,6.2$, total venous $CO_2\,6$.
  • ABGs: pH $7.1$, $PaCO_2\,17$, $HCO_3^-\,4$.
  • Calculations: $PaCO_2$ change $57.5\%$, $HCO_3^-$ change $83.3\%$. $AG = 124 - (4+92) = 28$.
  • Interpretation: High AG metabolic acidosis (DKA) with partial respiratory compensation.

Clinical Caveat: Error Recognition

• If ABG results do not align with the patient’s clinical history, physical exam, and overall condition, consider the possibility of laboratory error.
• Scenario for consideration:
  • Patient H&P is negative (no findings).
  • ABG report: pH $7.35$, $PaO_2\,47\,mmHg$, $PaCO_2\,49\,mmHg$, $HCO_3^-\,28\,mEq/L$.
  • This situation requires re-evaluation of the specimen or clinical correlation before making management decisions.