Description- Biochemical and metabolic functions occur most optimally within a narrow pH range (7.357.45). Acidosis and alkalosis, therefore, have significant physiologic impact such as neurophysiologic dysfunction as well as decreased inotropy, enzyme activity, cerebral and myocardial microperfusion, and catecholamine efficacy. Additionally, the oxyhemoglobin curve shifts and electrolyte abnormalities occur.
- Acidbase buffering systems within the body serve to keep the physiologic concentration of hydrogen ions (H+) constant; they serve as a reservoir or cushion. There are several systems that provide overlap and graduated lines of defense against pH disturbances. They include chemical (bicarbonate, proteins, phosphate), respiratory, renal, liver, and bone buffering systems.
- Despite their large capacity, when buffering systems fail or are overwhelmed, pH and physiologic abnormalities manifest. The pH range required for compatibility with life is between 6.8 and 7.8.
- Acids are compounds that contain hydrogen and release H+ when dissolved in solution; they are proton producers or "donors." The terms "strong" and "weak" refer to the donor's "willingness" or "ability" to donate the H+. A strong acid readily dissociates its H+ from the conjugate base (A-; anion). A weak acid does not easily donate its H+ and will exist mostly in the HA form.
- Bases are compounds that contain hydroxide and release hydroxide ion (OH-) when dissolved in solution; they are OH- producers, or conversely H+ acceptors. A strong base readily dissociates its OH- from the conjugate acid (C+; cation). A weak base does not easily donate its OH- and will exist mostly in its COH form.
- The concentration of H+ in distilled water is very small (0.0000001 mol/L, or 10-7 mol/L). The concept of pH provides a useful way of describing these small values in a comprehensible manner; pH is a negative logarithm of the concentration of H+ (equation 1). A decrease in pH signifies an increase of H+ and vice versa.
- pH = log 1/[H+]
- [H+] = 0.0000001 = pH of 7
- Neutralization of acids and bases occur when they bind to a conjugate base or acid, respectively. An example of this is H+ + OH- H2O, where the free H+ and OH- disappear and the pH does not change. This is the concept behind buffering systems.
- Buffering capacity describes the capability of a buffering system to neutralize acid or base. The capacity increases when there is an increase in the number of buffer molecules ready to bind additional H+ (or OH-).
- Chemical buffering systems are the body's first line of defense against acidbase abnormalities. They act within seconds to minutes, with the purpose of minimizing changes in pH when an acid or base is added. Buffering solutions comprise either a weak acid and its conjugate base or a weak base and its conjugate acid.
- Bicarbonate (HCO3-) and carbonic acid (H2CO3) are abundant in the extracellular fluid (ECF) making this the most important buffer system in the ECF for noncarbonic acids (1). The CO2/HCO3- buffer ratio is 1:20; however, the ability for CO2 to be eliminated by ventilation changes it from a "closed" to an "open" system. Alveolar ventilation self-adjusts to keep the pCO2 constant. Additionally, the renal system is capable of adjusting the HCO3- concentration.
- Proteins are important buffers of the intracellular space because they contain both acidic and basic groups to combine with H+ or OH-.
- Hemoglobin molecules buffer H+ from carbonic acids; it has a buffering capacity 56 times that of plasma proteins. The hemoglobin molecule can bind either O2 (oxyhemoglobin) or H+ (deoxyhemoglobin) at any given time, but not both; additionally, binding of one results in release of the other (this exchange/trade is known as the Bohr effect). This is physiologically advantageous; in the the peripheral circulation where H+ is increased from tissue metabolism, O2 is unloaded to the tissue.
- Amino groups of intracellular proteins have pK values close to the physiologic pH, rendering these substances important intracellular buffers.
- Phosphate exists in several compartments: Blood/intravascular, intracellular, and urine. With a pKa of 6.9, H2PO4- readily binds to H+. Intracellularly, phosphate is present in high concentrations, and plays an important buffering role. However, in extracellular compartments, its low concentration relegates it to a more minor role. Phosphates also contribute to H+ excretion in the renal tubules.
- Respiratory system: During aerobic metabolism, the mitochondria generate ATP while producing CO2 as a byproduct. CO2 is capable of easily diffusing across lipid cell membranes into the blood stream and erythrocytes because it is not ionized or charged. Inside erythrocytes, CO2 is converted into HCO3- via carbonic anhydrase. HCO3- is unable to diffuse out of the erythrocyte due to its ionization (cannot cross the lipid membrane); instead it is stored and transported from peripheral tissues to the lungs. When reaching the lungs, HCO3- within the erythrocyte gets reversed to CO2 and diffuses into the alveolar space to be exhaled.
- Alveolar ventilation and respiratory drive are adjusted by brainstem centers in response to changes in pH. Because alveolar ventilation is easily increased and decreased, the range of shifting the CO2 elimination up and down is large and the response is very fast. In addition, this is facilitated by the almost linear CO2-binding curve in blood.
- Renal system: Although the kidneys are slower to respond to changes in pH, they have a tremendous buffering capacity. At the glomerulus and Bowman's capsule, HCO3- and H+ are filtrated from the blood into the renal tubule.
- In the lumen:
- H+ can combine with titratable acids (HPO4-, SO4-, NH3) and be excreted.
- H+ can bind to HCO3- via carbonic anhydrase (present in the lumen) to form H2O and CO2. The CO2 readily diffuses into the renal cells and out to the capillaries (~85% of the filtrated bicarbonate is reabsorbed in the proximal tubules).
- Aldosterone also stimulates direct H+ excretion in the collecting ducts.
- Liver metabolism: Although hepatic metabolism produces HCO3-, CO2, and NH4+ byproducts, these compounds are consumed and "buffered" during urea synthesis. In the event of incomplete consumption, NH4+ is released into the circulation, where it is either consumed during glutamine synthesis (which in turn facilitates renal tubular H+ excretion) or excreted in the urine. Additionally, the liver eliminates H+ with the cleavage of lactic acid, acetoacid, and citric acid.
- Bone: Functions as a buffer via ionic exchange (acute) and dissolution of bone crystal (chronic). Bone "takes up" H+ in exchange for calcium, sodium, and potassium in acidemic states. In alkalemic states, it releases HCO3-, CO3-, or HPO4-. Ionic exchange does not involve bone breakdown and deals with acute acidosis. Chronic intracellular acidosis in osteoclasts causes an intracellular hypocalcemia and osteoclast stimulation. The result is bone breakdown involving the release of calcium carbonate via direct physiochemical breakdown of crystal, which is independent of parathyroid hormone.
- GI tract: Small bowel and pancreatic exocrine secretions reverse gastric acids but are of minor importance for the systemic buffering of the whole body.
- Changes in pH are communicated between the ICF and the ECF via CO2 transfer across the cell membrane and protoncation exchange mechanisms. It should be noted that only the extracellular space is clinically accessible for monitoring of test parameters.
- Regulatory organs for maintenance of acidbase balance include the:
- Lungs exhaling and excreting CO2 by adapting the alveolar ventilation to normalize PaCO2
- Circulation matching oxygen delivery to oxygen demands
- Kidneys excreting and reabsorbing acidbase relevant substances
- Liver providing metabolism and synthesis of glutamine and proteins
Physiology/PathophysiologyAcidbase imbalances result from the failure of the total of the buffering systems. Depending on the details of the underlying cause, various outcomes of failure of the buffering system can be described:
- Metabolic acidosis or alkalosis
- Respiratory acidosis or alkalosis
- Partial metabolically compensated respiratory acidosis or alkalosis
- Partial respiratory compensated metabolic acidosis or alkalosis
- Mixed acidase abnormalities can involve 2 abnormalities.
- Patients commonly present to the operating room with disturbances in their acidbase equilibrium, or are at-risk for abnormalities that can increase morbidity and mortality such as:
- Hyperventilation and hypoventilation
- Anemia
- Fluid loss
- Malnutrition with low albumin
- Hyperkalemia and hypokalemia
- Gastric drainage
- Conditions in which the physiologic buffer systems fail can demand therapeutic and pharmacologic interventions, requiring exact diagnosis of the nature of the acidbase disturbance. These include the following:
- Blood gas analysis with pH, PCO2, [HCO3-], and base excess (BE). BE is the amount of acid or base needed to titrate the patient's blood to a pH of 7.4.
- Anion gap
- THAM (trome thamine) can be used when patients are unable to exhale sufficient amounts of CO2 either spontaneously or with mechanical ventilation. About 30% of THAM has a pH = 7.40 and is not ionized, being able to penetrate cells and act intracellularly. THAM actively binds hydrogen ions (H+) and cations of fixed or metabolic acids and increases bicarbonate. THAM is not recommended in patients with hyperkalemia or hyponatremia.
- Sodium bicarbonate and THAM are equal in their ability to alkalinize; the latter is shorter lasting. Treatment of metabolic alkalosis focuses mainly on treating the underlying pathophysiologic problem.
- Carbonic anhydrase inhibitors, which cause renal excretion of HCO3-, are also an option.