Altered Acid-Base Balance

Introduction to Acid-Base Balance

• Regulation Importance: pH levels are closely regulated because they affect all functional proteins and biochemical reactions within the body.

• Normal pH of Body Fluids:

  • Arterial Blood: $pH\,7.4$

  • Venous Blood and Interstitial Fluid (IF): $pH\,7.35$

  • Intracellular Fluid (ICF): $pH\,7.0$

• Terminology for pH Imbalance:

  • Alkalosis or Alkalemia: Occurs when arterial pH is greater than $7.45$.

  • Acidosis or Acidemia: Occurs when arterial pH is less than $7.35$.

Pathophysiology of pH Extremes

• Acidemia and Acidosis: When blood pH decreases below $7.35$, acidemia exists. The resulting physiological state is termed acidosis.

• Alkalemia and Alkalosis: When blood pH increases above $7.45$, alkalemia exists. The resulting physiological state is termed alkalosis.

• Severe Acidosis (pH below 7.0): This state can be deadly due to three primary mechanisms:

  1. CNS Deterioration: Central nervous system function fails, leading to the person becoming comatose.

  2. Cardiac Failure: Cardiac contractions become weak and irregular; symptoms of heart failure may emerge.

  3. Circulatory Collapse: Peripheral vasodilation results in a dramatic drop in blood pressure.

• Severe Alkalosis: This is also dangerous, though serious clinical cases are relatively rare compared to acidosis.

Sequential Regulation of Hydrogen Ion Concentration

Hydrogen ion concentration is regulated by three systems acting in sequence:

1. Plasma (Chemical) Buffer Systems: The first line of defense; acts rapidly (near instantaneously).

2. Respiratory Buffer System: Acts within $1$ to $3$ minutes to adjust pH.

3. Renal Buffer System: The most potent system, but requires hours to days to effect significant pH changes.

Chemical Buffer Systems

• Definition: A system of one or more compounds that act to resist pH changes when a strong acid or base is added.

  • Binding: Binds to $H^+$ if pH drops.

  • Release: Releases $H^+$ if pH rises.

• Three Major Systems:

  1. Bicarbonate Buffer System

  2. Phosphate Buffer System

  3. Protein Buffer System

Physiological Buffering Systems: Respiratory and Renal

• General Functions:

  • Regulate the total amount of acid or base in the body.

  • Act more slowly than chemical buffers but possess a much higher capacity.

• Unique Renal Role: Only the kidneys can eliminate non-volatile (fixed) acids produced by cellular metabolism to prevent metabolic acidosis. These acids include:

  • Phosphoric acid.

  • Uric acid.

  • Lactic acid.

  • Ketones.

• Renewal: The kidneys also regulate blood levels of alkaline substances and renew chemical buffers.

Respiratory Regulation of Hydrogen Ions

• Carbon Dioxide Equilibrium: The respiratory system eliminates $CO_2$ (an acid). A reversible equilibrium exists in the blood:

  • $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$

• Reaction Shifts:

  • CO2 Unloading: The reaction shifts to the left, and $H^+$ is incorporated into $H_2O$.

  • CO2 Loading: The reaction shifts to the right, and $H^+$ is buffered by proteins.

• Response to pH Changes:

  • Acidosis (Low pH): Triggers an increased respiratory rate to increase the excretion of $CO_2$ and decrease $H_2CO_3$ levels.

  • Alkalosis (High pH): Triggers a decreased respiratory rate to retain $CO_2$ and increase $H_2CO_3$ levels.

Renal Mechanisms of Acid-Base Balance

• Key Mechanisms:

  1. $H^+$ elimination and $HCO_3^-$ conservation.

  2. Tubular buffer systems (specifically phosphate and ammonia).

  3. Potassium/Hydrogen ($K^+/H^+$) exchange.

  4. Chloride/Bicarbonate ($Cl^-/HCO_3^-$) exchange.

• The Anion Gap: A calculation of major measurable cations and anions in plasma used as an indication of acid-base balance.

  • Formula: $\text{Anion Gap} = Sodium - [Chloride + Bicarbonate]$

  • Normal Value: Approximately $12\,mEq/L$ (typical range: $10$–$14\,mEq/L$).

Classification of Acid-Base Balance Abnormalities

• Respiratory Abnormalities: Caused by the failure of the respiratory system to balance pH.

  • Primary Indicator: Blood $PCO_2$.

• Metabolic Abnormalities: Includes all abnormalities other than those caused by blood $PCO_2$ levels.

  • Primary Indicator: Abnormal $HCO_3^-$ levels.

Respiratory Acidosis and Alkalosis

• Adequacy of Respiratory Function: Indicated by $PCO_2$ levels. Normal range is $35$–$45\,mmHg$.

• Respiratory Acidosis:

  • Value: PCO_2 > 45\,mmHg.

  • Cause: Decrease in ventilation or gas exchange, leading to $CO_2$ accumulation in the blood.

  • Characteristics: Falling blood pH and rising $PCO_2$.

• Respiratory Alkalosis:

  • Value: PCO_2 < 35\,mmHg.

  • Cause: Hyperventilation (often due to stress or pain); $CO_2$ is eliminated faster than it is produced.

Metabolic Acidosis and Alkalosis

• Metabolic Acidosis: Characterized by low blood pH and low $HCO_3^-$.

  • Causes:

    1. Increased production of non-volatile acids (e.g., fasting, ketoacidosis, lactic acidosis).

    2. Decreased secretion of acids by the kidneys (leads to renal failure).

    3. Increased loss of bicarbonate (e.g., diarrhea, gastrointestinal suction).

    4. Increase in $Cl^-$ (e.g., excessive chloride reabsorption in the kidney, sodium chloride infusion).

• Metabolic Alkalosis: Characterized by rising blood pH and rising $HCO_3^-$. This is much less common than metabolic acidosis.

  • Causes:

    1. Decreased $H^+$ ions (e.g., vomiting, gastric suction).

    2. Increased $HCO_3^-$ (e.g., intake of excess base).

    3. Loss of $Cl^-$ ions (e.g., vomiting, gastric suction).

Clinical Effects and Compensation

• Critical Limits:

  • pH below 6.8: Leads to CNS depression, coma, and death.

  • pH above 7.8: Leads to nervous system excitation, muscle tetany, nervousness, convulsions, and death (often from respiratory arrest).

• Compensatory Mechanisms:

  • If one physiological system fails, the other attempts to compensate.

  • Respiratory Compensation: Corrects metabolic acid-base imbalances.

    • Acidosis: High $H^+$ stimulates respiratory centers; breathing rate/depth increases; $PCO_2$ falls below normal.

    • Alkalosis: Slow, shallow breathing allows $CO_2$ accumulation; PCO_2 > 45\,mmHg.

  • Renal Compensation: Corrects respiratory acid-base imbalances.

    • Respiratory Acidosis (Hypoventilation): Kidneys retain $HCO_3^-$; indicated by high $HCO_3^-$ levels.

    • Respiratory Alkalosis (Hyperventilation): Kidneys do not reabsorb $HCO_3^-$ or actively secrete it; indicated by decreasing $HCO_3^-$ levels.

Diagnostic Interpretation Using Blood Values

• Step 1: Check the pH:

  • Acidosis: pH < 7.35

  • Alkalosis: pH > 7.45

• Step 2: Check the PCO2 (Normal: 35–45 mmHg):

  • Acidosis: PCO_2 > 45\,mmHg

  • Alkalosis: PCO_2 < 35\,mmHg

• Step 3: Check the Bicarbonate (Normal: 22–26 mEq/L):

  • Acidosis: HCO_3^- < 22\,mEq/L

  • Alkalosis: HCO_3^- > 26\,mEq/L

• Step 4: Match PCO2 or HCO3 with pH (RO-ME Mnemonic):

  • Respiratory Opposite (RO):

    • When pH is up and $PCO_2$ is down = Alkalosis.

    • When pH is down and $PCO_2$ is up = Acidosis.

  • Metabolic Equal (ME):

    • When pH is up and $HCO_3^-$ is up = Alkalosis.

    • When pH is down and $HCO_3^-$ is down = Acidosis.

• Step 5: Determine Compensation:

  • Compensated: pH is NORMAL, but both $PCO_2$ and $HCO_3^-$ are ABNORMAL.

  • Partially Compensated: pH is ABNORMAL, and both $PCO_2$ and $HCO_3^-$ are ABNORMAL.

  • Uncompensated: pH is ABNORMAL, and either $PCO_2$ OR $HCO_3^-$ is ABNORMAL.