In health, blood pH (which is used synonymously as extracellular pH) is maintained within a narrow range of approximately 7.35 to 7.45. Regulation of acid-base involves chemical buffering with extra- and intracellular buffers, control of partial pressure of carbon dioxide by altering respiration, and control of bicarbonate and hydrogen excretion by the kidneys. In general, rapid changes in acid-base can be achieved by changing respiration, whereas the kidney is involved in slower, more long-term regulation of acid-base status.
The major extracellular buffer of acids in the body is bicarbonate (HCO3–) followed by plasma proteins and bone. Intracellular buffers include proteins, organic phosphate, inorganic phosphate and hemoglobin (in erythrocytes). The partial pressure of carbon dioxide (pCO2) is controlled by ventilation. Gaseous carbon dioxide is removed from the body by hyperventilation; this results in hypocapnea (low pCO2). Conversely, decreased ventilation (hypoventilation) will retain carbon dioxide, resulting in hypercapnea (high pCO2). The kidney plays a central role in response to acid-base disturbances. Filtered bicarbonate is absorbed in the proximal convoluted tubules of the kidney and regenerates the bicarbonate lost in buffering acids produced by normal body metabolism. Hydrogen (H+) is excreted by both the proximal (PCT) and distal convoluted tubules (DCT) of the kidney. Excretion of hydrogen by the PCT is dependent on filtered phosphates and urea generated by the tubular epithelial cells. Excretion of hydrogen by the DCT is dependent on sodium resorption and exchanges for potassium.
Traditional interpretation of acid-base status involves the Henderson-Hasselbach equation, where pH is determined by the ratio of HCO3– to pCO2. Blood pH is normal when the ratio of HCO3– to pCO2 is 20:1. Respiratory factors affect pCO2, whereas non-respiratory, or metabolic factors, affect the HCO3–.
The non-traditional approach to acid-base status (strong-ion approach) involves independent and dependent variables. Independent variables are pCO2, strong ions (sodium and chloride) and nonvolatile weak acids (plasma proteins). These alter dependent variables, which are HCO3– and H+. This differs from traditional approaches to acid-base interpretation as it contends that any changes in HCO3– are secondary to changes in plasma proteins, respiration and electrolytes. In theory, it is a more physiologic approach to acid-base abnormalities, however, in practice, using non-traditional approaches does not substantially alter interpretations gleaned from traditional approaches.
These definitions may be useful when interpreting acid-base results.
Acidemia: A decrease in blood pH (or an increase in blood H+ concentration).
Alkalemia: An increase in blood pH (or a decrease in blood H+ concentration).
Acidosis: A pathophysiologic process causing accumulation of an acid (containing protons) or loss of a base (both will increase H+), which lowers the pH. This may or may not result in an acidemia. An acidosis can be respiratory or metabolic in origin, i.e. primary respiratory or metabolic acidosis.
Alkalosis: A pathophysiologic process causing accumulation of a base or loss of an acid (both will decrease H+), which increases the pH. This may or may not result in an alkalemia. An alkalosis can be respiratory or metabolic in origin, i.e. primary respiratory or metabolic alkalosis.
Primary acid-base disturbance: This is the major abnormality that will drive the direction of pH changes. For example, a primary metabolic acidosis will decrease the pH.
Secondary or compensatory acid-base disturbance: This is a compensatory response by the body in an attempt to normalize alterations in pH (specifically, H+) caused by the primary disturbance. A secondary or compensatory response does not usually return the pH to normal (exceptions are that the kidney can return the pH to normal in compensation for a chronic respiratory alkalosis or acidosis in dogs) and definitely does not cause overshooting of the pH. For example, a secondary or compensatory respiratory alkalosis to a primary metabolic acidosis will limit the decrease in pH caused by the primary metabolic acidosis but will not normalize the pH and will not cause the pH to be high.
Correction: This is when the body or the veterinarian (through some form of intervention) alleviates or corrects of the primary disturbance. The body cannot correct for a primary respiratory disturbance, i.e. we have to intervene. The kidney attempts to correct for a primary metabolic acid-base disturbance (as long as the kidney is not the cause of the disturbance in the first place), however this requires normal renal function and resolution of the primary disturbance that is causing the pH change in the first place. If the primary disturbance is self-limiting, renal excretion of acid or base in an acidemia or alkalemia, respectively, will correct the pH given time (3-5 days) once the disturbance is no longer driving down the pH (particularly if the pH was mild to begin with).
Simple (uncomplicated) disturbance: This indicates that there is a single primary acid-base disturbance. This may or may not be accompanied by the expected compensatory response.
Mixed disturbance: This indicates that there is more than one primary disturbance (two or three), e.g. a primary respiratory acidosis and primary metabolic acidosis. Note, that an animal cannot have a mixed respiratory disturbance, i.e. there cannot be a concurrent primary respiratory acidosis and a primary respiratory alkalosis; it is not physiologically possible. But an animal can have more than 1 primary metabolic disturbance, e.g. primary metabolic acidosis and primary metabolic alkalosis (and can certainly have an additional primary respiratory disturbance or a compensatory respiratory response).
Proton: H+. This dictates pH and is what the body wants to control. This is done via buffers and routes of excretion.
- In an acidemia, buffers (hemoglobin, proteins, serum/plasma bicarbonate or HCO3–) bind and neutralize protons or excrete them as carbonic (carbon dioxide or CO2) or chloride-containing non-carbonic (e.g. ammonium chloride or NH4Cl) acids, depending on the cause of acidemia.
- In an alkalemia, buffers (e.g. hemoglobin, albumin) release protons or excretion of protons is reduced in lungs and kidney (depending on the cause of alkalemia).
Carbonic acid: H2CO3
Also called a volatile acid, because when it dissociates into water and carbon dioxide, the carbon dioxide can be blown off as follows:
H2CO3 ↔ H+ + HCO3– ↔ CO2 + H2O.
Carbonic anhydrase is the enzyme that catalyzes these reversible reactions inside the cell and in plasma.
Noncarbonic acids: Non-volatile acids that cannot be blown off. These can either have chloride as the anion or another “unmeasured” anion for the proton (H+).
- Non-volatile acids that contain chloride as the anion: Some examples:
- Hydrochloric acid or HCl (gastric contents)
- NH4Cl (generated by proximal renal tubules via ammoniagenesis: NH3 + HCl = NH4Cl).
- Non-volatile acids that contain other anions but not chloride: Some examples:
- Lactic acid = CH3CH(OH)CO2H
- Acetoacetic acid (ketoacid) = CH3COCH2COOH
- Phosphates = H2PO4–, HPO42-
- Sulfates = H2SO4
Remember H+ is the acid. When it dissociates from its anion (as strong acids do easily), it is buffered or excreted by the body. Weak acids (e.g. albumin) release less protons than strong acids.
- Renal physiology page: Acid-base homeostasis