3.3 Acid-Base Balance

Acid-Base Balance

• Acid-Base Balance is crucial for homeostasis
• pH regulation is important since most biochemical reactions are pH dependent

Chemistry of Acids, Bases, and Buffers

• Acid: a molecule that releases a hydrogen ion (proton) in solution
• Base: a molecule that can accept a hydrogen ion in solution; a strong base
• Strong acid: completely dissociates
• Weak acid: has a strong conjugate base
• Sources of acids in the body: cellular metabolism
  • CO2 formed by metabolism is hydrated to H2CO3, resulting in a large total H+ load
  • Most CO2 excreted by lungs
  • Small remaining quantities of H+ excreted by kidneys

pH Regulation

• pH is a measure of the [H+] in a solution
• pH = - log [H+]
• Increase [H+] decreases pH
• Decrease [H+] increases pH
• Body attempts to regulate blood pH to 7.40
• Normal pH = 7.35-7.45
• pH limits under pathologic conditions = 6.9- 7.8
• Acidosis/acidemia occurs at a pH < 7.35
• Alkalosis/alkalemia occurs at a pH > 7.45

Buffer Systems of the Body

• Three mechanisms that resist pH changes are:
  1. Lungs remove volatile acids (~20,000 mmol CO2/day)
  2. Kidneys remove fixed acids (~ 100 mEq/day)
  3. Buffers reversibly bind hydrogen ions to minimize changes in H+ concentration/ pH
• Three major acid-base buffer systems in the blood:
  • Carbonic acid- Bicarbonate System (most important)
  • Proteins (mainly hemoglobin) (second most important)
  • Phosphate (glucose-1-phosphate and ATP)
• Additional buffers:
  • Bicarbonate buffer system is the major buffer of interstitial fluid
  • Bone salts of hydroxyapatite can buffer H+ ions in chronic acidosis

Respiratory Control of Acid-Base Balance

• Respiratory system controls:
  • CO2 directly by altering ventilation to change PaCO2 (volatile acid)
  • [H+1] indirectly by controlling CO2/H2CO3 via the carbonic acid reaction
• Respiratory correction of imbalance occurs within minutes
• Incomplete correction since the original source of H+ hasn't been eliminated

Renal Regulation of Acid-Base Balance

• Renal regulation occurs by altering the excretion of fixed acids and HCO3 retention
• Renal compensation for acidosis occurs by:
  1. Increased H+ secretion into the tubular fluid
  2. Decreased HCO3- reabsorption
• Compensation for acid-base imbalances takes hours to days
• Powerful - can completely compensate for acid-base imbalances
• Returns ECF pH to normal

Acid-Base Abnormalities

• Acid-base abnormalities produce changes in pH, PCO2, and plasma bicarbonate
• Primary problems:
  • Respiratory acidosis
  • Respiratory alkalosis
  • Metabolic acidosis
  • Metabolic alkalosis
• Compensation:
  • Respiratory acidosis: metabolic compensation (kidneys excrete H+ ions/conserve HCO3)
  • Respiratory alkalosis: metabolic compensation (kidneys excrete HCO3-)
  • Metabolic acidosis: respiratory compensation (increased alveolar ventilation)
  • Metabolic alkalosis: respiratory compensation (decreased alveolar ventilation)

Anion Gap

• Acidosis with a large anion gap indicates an increased plasma concentration of anions other than chloride and bicarbonate or a decreased plasma concentration of K+, Ca++, and Mg++

• Anion gap = Major cations - Major anions = 8-12 mEq/L

• Anion gap >14 mEq/L = Anion gap acidosis

• Anion gap < 14 mEq/L = Non-anion gap acidosis

• Treat underlying cause### Acid-Base Balance

• Some CO2 is not buffered in the plasma, producing small amounts of H+ ions in venous blood, making it slightly more acidic (pH 7.35) compared to arterial blood (pH 7.4)

• The phosphate buffer system has two components: dihydrogen phosphate (H2PO4-) and monophosphate (HPO4-2), but it is weaker than the bicarbonate system and has smaller amounts of components

Respiratory Regulation of Acid-Base Balance

• The respiratory system assists in regulating pH by controlling PaCO2, as tissues constantly produce CO2, equivalent to an acid
• Hyperventilation causes respiratory alkalosis, resulting in an increase in blood pH due to a loss of CO2
• Hypoventilation causes respiratory acidosis, resulting in a decrease in blood pH due to an increase in [H+1]

Acid-Base Abnormalities

• Acid-base abnormalities produce changes in pH, PCO2, and plasma bicarbonate
• Normal values:
  • pH: 7.35-7.45
  • PaCO2: 35-45 mmHg
  • HCO3-: 22-26 mEq/L
• Compensation:
  • Full compensation restores pH to normal value
  • Partial compensation moves pH towards normal, but pH remains abnormal
  • Mixed disorders are possible (e.g., type 1 diabetes with respiratory failure)

Respiratory Acidosis

• Caused by impaired alveolar ventilation, resulting in increased CO2 production or decreased CO2 elimination
• Consequences:
  • Increased respiratory rate and effort
  • Cardiac output increases to compensate for acidosis
  • Kidney excretes H+ ions and conserves HCO3-
• Metabolic compensation takes hours to days

Respiratory Alkalosis

• Caused by alveolar ventilation exceeding CO2 production, resulting in decreased PaCO2
• Consequences:
  • Decreased respiratory rate and effort
  • Cardiac output decreases to compensate for alkalosis
  • Kidney excretes HCO3-
• Metabolic compensation occurs quickly, but may take longer to reverse

Metabolic Acidosis

• Caused by ingestion, infusion, overproduction, or decreased renal excretion of H+ ions, or loss of bicarbonate ions
• Causes:
  • Increased HCO3 loss
  • Gain of nonvolatile acid
  • Increased mineralocorticoid
• Respiratory compensation: decreased alveolar ventilation, increasing PaCO2
• Treatment: treat underlying cause, acetazolamide increases renal excretion of HCO3, spironolactone is a mineralocorticoid antagonist, and dialysis

Metabolic Alkalosis

• Caused by ingestion, infusion, overproduction, or increased renal retention of HCO3-, or loss of H+ ions
• Causes:
  • Increased HCO3 gain
  • Loss of nonvolatile acid
  • Decreased mineralocorticoid
• Respiratory compensation: increased alveolar ventilation, decreasing PaCO2

Hypoxia

• 4 main causes:
  • Hypoxemic hypoxia: reduced PO2 of arterial blood
  • Anemic hypoxia: reduced functioning hemoglobin available for oxygen transport
  • Ischemic or hypoperfusion hypoxia: low blood flow prevents adequate O2 delivery
  • Histotoxic hypoxia: toxic agents prevent cellular utilization of O2