Acid-Base Balance and Mrs. Hira

Case Study: Mrs. Hira

• Mrs. Hira, a 75-year-old diabetic, has a long history of non-compliance with insulin.
• She was recently admitted to the hospital.
• ABG results:
  • pH = 7.26
  • PCO2 = 42 mmHg
  • HCO3− = 17 mg/dL

Lecture Objectives

• List volatile and non-volatile acids
• Describe the Henderson-Hasselbalch Equation
• Explain the mechanism of buffers in the human body
• Discuss normal pH regulation by buffers, respiratory, and renal systems
• Explain the anion gap and its biochemical significance
• Interpret Arterial Blood Gases (ABGs) values

The Body and pH

• Homeostasis of pH is tightly controlled.
• Extracellular fluid pH = 7.4
• Blood pH = 7.35–7.45
• pH < 6.8 or > 8.0 results in death.
• Acidosis (acidemia) occurs below 7.35.
• Alkalosis (alkalemia) occurs above 7.45.

Acids and Bases (Bronsted-Lowry Theory)

• Acids are H⁺ donors.
• Bases are H⁺ acceptors.
• Strong acids dissociate completely in solution (e.g., HCl, NaOH).
• Weak acids dissociate partially in solution (e.g., lactic acid, carbonic acid).

Buffers

• Function: Resist pH changes upon strong acid/base addition.
• Composition: Always exists as a pair:
  • Weak acid + salt of its conjugate base
  • Weak base + salt of its conjugate acid

Henderson-Hasselbalch Equation

• Used to determine the pH of blood or other buffer solutions.
• pH = pKa + log ([conjugate base]/[acid])

How Buffers Resist pH Change

• Buffer pH = pKa when [HA] = [A⁻]
• Weak acid (HA) and conjugate base (A⁻) react with added acid or base.
  • HCl (strong acid) reacts with weak base A⁻
  • NaOH (strong base) reacts with weak acid HA

Efficiency of a Buffer

• A buffer is most effective when [salt] = [acid].
• pH = pKa

Titration Curve for Weak Acids

• Shows the relationship between pH and added hydroxide.
• The buffering region is a key part of the pH-titration relationship.

Acids Produced in 24 Hours

• Metabolic reactions produce acids (e.g., lactic acid, pyruvic acid, acetoacetic acid, beta-hydroxybutyrate).
• Cellular respiration converts carbon dioxide to carbonic acid.
• Uric acid, oxaloacetic acid, and succinic acid are naturally produced.

pH Change and Enzymes

• Slight pH changes can be life-threatening, as enzymes function optimally only within narrow pH ranges.
• Acid-base balance affects electrolytes (Na⁺, K⁺, Cl⁻) and hormones.

Mechanisms of pH Regulation

• First line: Chemical buffer systems (bicarbonate, phosphate, protein).
• Second line: Physiological buffers: respiratory (CO2 excretion) and renal (H⁺ excretion).

Buffers in Body Fluids

• Bicarbonate: Major extracellular buffer (H₂CO₃/NaHCO₃).
• Phosphate: Major intracellular buffer (NaH₂PO₄/Na₂HPO₄).
• Proteins: Intracellular and extracellular buffers (including hemoglobin).

Bicarbonate Buffer System

• Major extracellular buffering system.
• Strong acid is fixed by bicarbonate ion converting to carbonic acid.
• Accounts for 65% of buffering in plasma.
• H⁺ + HCO₃⁻ <=> H₂CO₃
• OH⁻ + H₂CO₃ <=> HCO₃⁻+ H₂O

Normal Ratio in Blood

• HCO₃⁻ to H₂CO₃ ratio is normally 20:1.
• Allows blood pH to be 7.40.
• pH falls (acidosis) when bicarbonate decreases relative to carbonic acid.
• pH rises (alkalosis) when bicarbonate increases relative to carbonic acid.

Phosphate Buffer System

• Important intracellular buffer system.
• Strong acid is fixed by alkaline phosphate converting to acid phosphate.
• HCI + Na₂HPO₄ <=> NaH₂PO₄ + NaCl
• NaOH + NaH₂PO₄ <=> Na₂HPO₄ +H₂O

Protein Buffer System

• Most abundant buffer in intracellular fluid and blood plasma.
• Albumin is a key protein buffer.
• Amino acids in proteins can accept or donate H⁺.
• pKa = 7.4

Hemoglobin Buffer System

• Deoxygenated hemoglobin is a better proton acceptor than oxygenated hemoglobin.
• Carbonic anhydrase in red blood cells converts CO₂ to carbonic acid.
• CO₂ + H₂O <=> H₂CO₃ <=> H⁺ + HCO₃⁻
• Bicarbonate diffuses out of red blood cells.
• Deoxygenated hemoglobin accepts protons (H⁺ + Hb <=> H⁺Hb)

Carbon Dioxide Transport and Hemoglobin Buffering

• CO₂ transport in the blood and hemoglobin buffering are explained through a diagram.

Hemoglobin Buffer System—Continued

• Carbonic acid dissociates releasing bicarbonate ions into plasma in exchange for chloride ions (chloride shift).
• Hydrogen ions are buffered by hemoglobin molecules.
• This helps prevent major pH changes when plasma PCO₂ rises or falls.
• Most of hemoglobin's buffering action is due to the imidazole group of histidine.

Buffer Systems

• Buffers occur in intracellular (ICF) and extracellular fluid (ECF) compartments.
• ICF includes phosphate buffer, hemoglobin buffer, and amino acid buffers.
• ECF includes protein buffers, and carbonic acid-bicarbonate buffers.

Maintenance of Blood pH

• Blood buffers (bicarbonate, phosphate, and protein).
• Respiratory mechanism (using bicarbonate).
• Renal mechanism (using bicarbonate, phosphate, and ammonia).

Rates of Correction

• Buffers function almost instantly.
• Respiratory mechanisms take several minutes to hours.
• Renal mechanisms take several hours to days.

When Chemical Buffers Alone Cannot Prevent Changes in Blood pH

• Respiratory and renal systems act as a secondary defense against changes

Respiratory Mechanisms

• Lungs regulate volatile acids (e.g., carbonic acid).

Renal Mechanisms

• Kidneys regulate non-volatile acids (e.g., lactic acids, keto acids).

Arterial Blood Gas (ABG) Analysis

• Essential for diagnosing and managing patients' oxygenation, ventilation, and acid-base balance.
• Drawn from arteries (radial, brachial, femoral).
• ABG reports:
  • pH (H⁺ ion concentration)
  • PaCO₂ (dissolved CO₂ in blood)
  • HCO₃⁻ (metabolic effectiveness)
  • PaO₂ (O₂ content of blood)
  • SaO₂ (% of hemoglobin saturated)

Acid-Base Disorders

• Acid-base disorders are classified as metabolic or respiratory acidosis/alkalosis. -Metabolic acidosis: decreased bicarbonate -Respiratory acidosis: increased carbonic acid -Metabolic alkalosis: increased bicarbonate -Respiratory alkalosis: decreased carbonic acid

Anion Gap

• Biochemical tool for assessing acid-base problems, especially metabolic acidosis.
• Difference between measured cations (Na⁺ and K⁺) and measured anions (Cl⁻ and HCO₃⁻).
• In healthy individuals, the anion gap is typically around 15 mEq/L (range 8-18 mEq/L).
• Increased anion gap is associated with metabolic acidosis. Different types of metabolic acidosis could be associated with increased anion gap which includes renal failure, diabetic ketoacidosis, and lactic acidosis. A normal anion gap metabolic acidosis could be due to diarrhea or hyperchloremic acidosis. A low anion gap acidosis could be due to multiple myeloma.