acid-base balance

Acid-Base Balance

  • Mechanisms maintaining constant H+ concentration.

  • Acid: any molecule that releases H+.

  • Base: any molecule that binds H+.

  • Normal plasma H+ concentration: 35-45 nmol/L.

  • pH (-log [H+]) of blood: 7.36 – 7.44.

  • Acidosis: pH < 7.36.

  • Alkalosis: pH > 7.44.

H+ Balance

  • Carbonic acid originating from CO2: 20-22 mol/day.

  • Non-volatile acids: about 70 mmol/day.

    • Inorganic: sulfuric (oxidation of cysteine and methionine), phosphoric (metabolism of organic phosphates), nitric (NO oxidation).

    • Organic: Lactic, Acetoacetic, β-hydroxybutyric.

Blood Buffer Systems

  • Components include:

    • Carbonic buffer

    • Phosphate buffer

    • Plasma proteins

    • Hemoglobin.

Carbonic Buffer

  • Consists of HCO3- (base, 25 mmol/L) and H2CO3 (acid, about 1.2 mmol/L).

  • High concentration and buffering capacity.

  • Both components synthesized from CO2 produced in metabolic processes.

  • Better suited for acid buffering (HCO3-/H2CO3 ratio 20:1).

  • Operates in an open system (CO2 excreted by expiration).

Phosphate Buffer

  • Consists of H2PO4- (acid) and HPO42- (base).

  • Total concentration: 1.5 mmol/L.

  • Acid/base ratio (H2PO4-/HPO42-): about 1:4.

  • All phosphates originate from the diet.

Proteins as Buffers

  • Carboxyl groups COOH/COO- (pK 4.9 – mostly dissociated at physiological pH).

  • Amino groups –NH2/NH3+ (pK 8).

  • Total concentration of buffering groups: about 15 mmol/L.

Hemoglobin as Buffer

  • Mechanism is similar to plasma proteins.

  • High concentration (about 4 times higher than hemoglobin).

  • pK depends on O2 binding.

    • H-Hb/Hb- pK 8.25.

    • H+HbO2-HbO2- pK 6.95.

Bohr-Haldane Effect

  • Relation of HbO2 and H+:

    • HbO2 + H+ ↔ Hb + O2.

Contribution of Buffers to Blood Buffering Capacity (%)

  • Closed system:

    • Carbonic: 10%

    • Phosphate: 3%

    • Plasma proteins: 19%

    • Hemoglobin: 68%

  • Open system:

    • Carbonic: 3%

    • Phosphate: 1%

    • Plasma proteins: 6%

    • Hemoglobin: 21%

  • Blood buffering capacity:

    • Closed system: 24.2 mmol/L per pH unit.

    • Open system: 76.8 mmol/L per pH unit.

    • Open system with maximal ventilation: 118.5 mmol/L per pH unit.

Intracellular Buffers

  • Include:

    • Proteins.

    • Organic phosphates.

    • Less abundant: carbonic.

    • Tissue-specific: bone mineral matrix.

  • Intracellular pH is lower than extracellular pH and varies among cells.

Respiratory System in Acid-Base Balance

  • Removes CO2 (carbonic acid), the most abundant acid.

  • Regulates CO2 content in blood:

    • ↑ pCO2 increases ventilation.

    • ↓ pCO2 decreases ventilation.

pCO2 Levels

  • Arterial blood: 40 mmHg.

  • Venous blood: 45 mmHg.

  • CO2 concentration in the blood is proportional to pCO2.

  • O2 concentration in blood is NOT proportional to pO2 due to Hb's limited capacity to transport O2.

  • CO2 is transported as:

    • Plasma HCO3- (via erythrocyte carbonic anhydrase).

    • Bound to protein –NH2 groups (carbaminians).

    • Dissolved in plasma.

The Kidney and Acid-Base Balance

  • Absorption of filtered HCO3- (about 4500 mmol/day).

  • Secretion of H+ originating from non-volatile acids (70 mmol/day).

    • CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-.

H+ Excretion in Urine

  • Buffered by phosphate (70%).

  • Bound by NH3 (NH4+ – ammoniogenesis).

  • Free H+ (<0.1%).

  • Urine pH is about 5.5.

Henderson-Hasselbalch Equation

  • H2CO3 ↔ H+ + HCO3-.

  • HCO3- × H+ / K = H2CO3.

  • pK (-logK) = pH + log (H2CO3 / HCO3-).

  • pH = pK (=6.7) + log (H2CO3).

pH and Buffer System Response

  • Variations in pH will affect:

    • Respiratory acidosis: ↓ H+ and ↑ pCO2.

    • Metabolic acidosis: ↓ HCO3- and ↓ pCO2.

    • Respiratory alkalosis: ↑ H+ and ↓ pCO2.

    • Metabolic alkalosis: ↑ HCO3- and ↑ pCO2.

Compensatory Mechanisms

  • Respiratory abnormalities compensated by the kidneys (renal compensation).

  • Increased HCO3- production in acidosis or reduction in alkalosis.

  • Metabolic abnormalities compensated by the respiratory system.

  • Increased ventilation in acidosis or reduced ventilation in alkalosis.

Clinical Conditions

Respiratory Acidosis

  • Caused by: reduced alveolar ventilation (hypercapnia always accompanied by hypoxia).

  • Conditions include:

    • Depression of the respiratory center (e.g. medication overdose, stroke).

    • Spinal cord injury.

    • Polyneuropathies.

    • Myopathies affecting respiratory muscles.

    • Obstruction of the respiratory tract.

    • Reduced lung compliance or vital capacity (due to pneumonia, pneumothorax, pleural effusion).

Metabolic Acidosis

  • Causes:

    • Exogenous acids or acid precursors (e.g. methanol, ethylene glycol).

    • Overproduction of endogenous acids (e.g. ketoacidosis, lactic acidosis).

    • Excessive excretion of bases (diarrhea, fistulas).

    • Impaired excretion of non-volatile acids (acute or chronic kidney disease).

    • Anion gap calculation: AG = (Na+ + K+) - (Cl- + HCO3-).

Respiratory Alkalosis

  • Caused by hyperventilation due to:

    • Severe pain or stress.

    • Interstitial lung diseases.

    • High-altitude sickness.

    • Congenital heart diseases.

    • Pulmonary embolism.

  • Consequences: CNS abnormalities (hypoxia, vasoconstriction), tetany, hypokalemia.

Metabolic Alkalosis

  • Caused by:

    • Vomiting (loss of HCl).

    • Excess of aldosterone.

    • Administration of NaHCO3 for treating acidosis.