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Author: Angie Warner, D.V.M.,D.Sc.

1. Learning Objectives:

  • Understand the importance of [H+] in normal physiologic function, and how acid is generated through tissue metabolism.
  • Be able to compare the effectiveness of buffering, compensation and correction in maintenance of acid-base homeostasis.
  • Define primary metabolic and respiratory acidosis and alkalosis and be able list disease processes that cause each.
  • Define base excess and anion gap.
  • Explain the role of compensation in maintenance of acid-base balance.
  • Be able to determine the primary acid-base abnormality when given patient pH, PaCO2, and HCO3.

2. [ H+ ]

2.1. Importance

  • Normal [ H+ ] is 0.00004 mEq/L, or 40x10 9 Eq/L, or 40 nEq/L.
  • H+ react with negatively charged regions of proteins. For example, association of H+ with protein molecules results in changes in charge distribution, structural configuration, and consequently in function.

2.2. Normal Range

  • A narrow range of 25 - 100 nEq/L or pH of 7.0 - 7.7 is compatible with normal body function and thus with life.

2.3. Expression as pH

  • pH is the negative log of [ H+ ], and the relationship between them is therefore inverse:
    • Decreased pH = increased [ H+ ] (acidemia)
    • Increased pH = decreased [ H+ ] (alkalemia)
  • The relationship is nearly linear over the range compatible with life.

2.4. Sources of Daily Acid Load

  • CO2 from oxidation of glucose and fatty acids during aerobic metabolism.
    • CO2 contributes to increased [H+] by the reaction: CO2 + H2O H2CO3 H+ + HCO3
    • formation of carbonic acid is catalyzed by carbonic anhydrase within red blood cells
    • carbonic acid readily dissociates yielding active H+
  • Metabolism of proteins and other substances generates acids (sulfur containing, lactic, phosphoric). 50 - 100 mEq H+ are generated daily with the usual human diet in this country.
  • The body has adapted to excrete a daily normal acid load plus compensate for any additional disturbances.

3. Mechanisms of Defense Against Changes in [H+]

3.1. Three Phases of Defense Against Loss of Acid Base Homeostasis

  • Buffering: immediate
  • Compensation: minutes-days
  • Correction: days or more

3.2. Buffers

H2CO3 / HCO3- is the major extracellular buffer CO2 CO2 + H2O H2CO3 H+ + HCO3

  • The equilibrium relationship of carbonic acid dissociation can be expressed by the Henderson Hasselbalch equation:

pH=6.10 + log [HCO3-]/0.03PCO2

The important relationship is the ratio of [HCO3-] to 0.03 PCO2, and a change in either will alter the pH.

[H+] = 24 PCO2 / [HCO3- ]

  • Other buffers exist, but since [H+ ] affects the equilibrium relationships of each buffer, analysis of the behavior of any one will predict that of all others in the solution:
    • therefore analysis of the equilibrium of the H2CO3 / HCO3- system is used to determine the acid-base balance of the individual
    • other extracellular buffers include inorganic phosphates and plasma proteins
    • the major intracellular buffer is hemoglobin in RBC

3.3. Pulmonary Regulation and Compensation for Acid-Base Balance: PCO2

  • CO2 CO2 + H2O HCO3 H+ + HCO3-
    • elimination of CO2 via alveolar ventilation allows very effective removal of H+ by shifting the equilibrium to the left
    • this allows H2CO3/HCO3- to act as a very effective buffer system
  • Changes in the rate of ventilation allow very rapid adjustments in plasma pH, and ventilation is responsive to arterial pH
    • chemoreceptors in the medulla, carotid body, and aortic arch respond to CSF and arterial pH, and control rate and depth of ventilation
  • Alveolar ventilation removes approximately 24,000 mEq of carbonic acid daily.

3.4. Renal Regulation

  • Regulation of Na+ and Cl- loss.
  • Regulation of free H2O loss.
  • Reabsorption of filtered HCO3-
    • nearly 100% of filtered bicarbonate can normally be recovered, which offsets the daily acid load
    • coupled with Na+ reabsorption

3.5. H+ secretion as titratable acid or as ammonia

  • Two mechanisms for net H+ excretion; maximal adaptation requires 4 - 6 days, however

4. Disturbances of Acid-Base Balance

4.1. Definitions

  • Acidosis = increased [H+ ]
    • respiratory (increased PCO2 )
    • metabolic (decreased [HCO3- ])
  • Alkalosis = decreased [H+]
    • respiratory (decreased PCO2 )
    • metabolic (increased [HCO3- ])

4.2. Assessment of Acid-Base Status

  • Traditionally arterial blood gas, bicarbonate, and base excess
    • normal ranges: pH 7.37 - 7.43; PCO2 36 - 44 mmHg; [HCO3- ] 22 - 26 mEq/L
  • Two (indirect) methods for determination of [HCO3- ]
    • derived from pH and PCO2
    • biochemical measurement of total blood CO2
    • total CO2 = dissolved CO2 + H2CO + HCO3-
  • Base excess: The mEq of acid that would be needed to bring 1 L of blood in the sample to a pH of 7.4, if the PCO2 were held at 40 mmHg
    • an evaluation of the non-respiratory (metabolic) component of acid base balance
    • a positive base excess indicates alkalemia
    • a negative base excess (base deficit) indicates acidemia
  • Anion gap: A calculated value that estimates the concentration of strong anions not accounted for by measurement of the inorganic ions in the sample (because body fluids are electrically neutral)
    • calculated as {[Na+] + [K+ ]} {[Cl ] + [HCO3-]}
      • normal value (without K+) = 12 - 14 mEq
      • normal value (with K+) = 17 - 19 mEq
    • an increased anion gap means unmeasured anions are present; candidates are ketoacids, lactate, sulfates, phosphate, and albumin
    • an increase in these unmeasured anions causes a metabolic acidosis. Metabolic acidosis with a normal anion gap is usually due to changes in [Cl- ]
  • Any disturbance of equilibrium begins with a primary respiratory or metabolic abnormality, and compensation can only be initiated through the opposite system
  • Compensatory mechanisms return pH toward normal, but generally do not completely correct pH
  • Return to homeostasis requires correction of the primary disturbance; the compensatory mechanisms only act to keep pH within the normal range at the expense of absolute levels of PCO2 and [HCO3- ]
  • The information obtained from the arterial blood gas can be plotted on an acid base map, which is helpful in assessment of the primary disorder and relative compensation

5. Simple Acid-Base Disturbances

5.1. Respiratory Acidosis

  • Impaired pulmonary elimination of CO2 due to alveolar hypoventilation
    • pulmonary disease resulting in inadequate ventilation: pulmonary edema, pneumonia, emphysema
    • impaired chest wall or respiratory muscle function: neuromuscular disease, thoracic trauma, scoliosis
    • severe CNS depression due to metabolic disease or depressant drugs
    • inadequate ventilation during anesthesia or artificial ventilation
  • Renal compensation via increased H+ excretion as titratable acid or ammonium ion
    • requires days for maximal effect
    • acute and chronic respiratory acidosis differ depending on the extent of renal compensation

5.2. Respiratory Alkalosis

  • Inappropriate CO2 elimination due to hyperventilation
    • hypoxia, pain or fear, gram negative sepsis, strenuous exercise, overzealous assisted ventilation, hypoxemia, hyperthermia, hypotension
  • Renal compensation consists of diminished HCO3- recovery
    • maximal response requires days, and the acute phase is poorly compensated

5.3. Metabolic Acidosis

  • HCO3- loss: Diarrhea or renal failure.
  • Retention of acid:
    • Renal failure: daily acid load not eliminated
    • Increased endogenous acid production: diabetic ketoacidosis, lactic acidosis
    • Exogenous acid load: ethylene glycol, methanol, salicylates
  • Respiratory compensation consists of increased ventilation and CO2 removal
    • Compensation is rapid as long as pulmonary function is normal

5.4. Metabolic Alkalosis

  • Acid loss: vomiting
  • HCO3- retention: volume depletion, K+ wasting diuretics
  • Respiratory compensation consists of hypoventilation in response to the rising pH, and pH is rapidly corrected

6. What Do I Do When I Get the Lab Data?

Check pH:
Is there acidemia or alkalemia?
Check PCO2:
Is there respiratory acidosis or alkalosis?
Check Base Excess:
Is there metabolic acidosis or alkalosis?
Since Overcompensation Never Occurs:
The primary abnormality will be in the same direction as the blood pH change, and compensation will be in the opposite direction (i.e. the pH change would have been greater if no compensation had occurred).
Don't Forget:
Combined respiratory and metabolic abnormalities can occur (i.e. pathology in both systems, and no compensation).
Look at your Patient and Assess:
Hydration status, disease process and pathophysiology; how do these evaluations affect your acid-base assessment?

7. References

  • Alexander E: Metabolic acidosis recognition and etiologic diagnosis. Hosp Pract, Jan, 1986.
  • DuBose TD: Clinical approach to patients with acid base disorders. Med Clin North America 67(1): 799 813, 1983.
  • deMoralis HS: Mixed acid base disorders. Part I. Clinical Approach. Compend Cont Ed Pract Vet 15: 1619 1626, 1993.
  • deMoralis HS: Mixed acid base disorders. Part II. Clinical disturbances. Compend Cont Ed Pract Vet 16: 477 486, 1994.
  • Garfinkel HB, et al: Bicarbonate, not 'CO2'. Arch Int Med 143: 2063 2064, 1983.
  • Kaehny WD: Respiratory acid base disorders. Med Clin North America 67(1): 915 932, 1983.
  • Leaf A, and Cotran RC: Renal Pathophysiology, 2nd ed., Oxford University Press, New York, 1980.
  • Levitsky MG: Pulmonary Physiology, McGraw Hill, New York, 1982.
  • Narins RG, Emmett M: Simple and mixed acid base disorders: a practical approach. Med 59: 161 187, 1980.
  • Rose BD: Clinical Physiology of Acid Base and Electrolyte Disorders, 2nd edition, McGraw Hill, New York, 1984.
  • Shapiro BA, Harrison RA, Walton JR: Clinical Application of Blood Gases, 3rd edition, Yearbook Medical Publishers, Inc., Chicago, 1982.
  • Szenci O, and Besser T: Changes in blood gas and acid-base values of bovine venous blood during storage. J Am Vet Med Assoc 197: 4471-474, 1990.