Types of disturbances

 
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The different types of acid-base disturbances are differentiated based on:

  • Origin: Respiratory or metabolic
  • Primary or secondary (compensatory)
  • Uncomplicated or mixed: A simple or uncomplicated disturbance is a single or primary acid-base disturbance with or without compensation. A mixed disturbance is more than one primary disturbance (not a primary with an expected compensatory response).

There are four primary types of acid-base disorders: metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. Combinations of these primary disturbances result in a mixed disturbance (note, that you cannot have a primary respiratory acidosis and a primary respiratory alkalosis; the lungs can create only one primary disturbance).

In general, primary disturbances can be distinguished from secondary or compensatory responses by the pH and degree and direction of change of the acid-base parameters. For example, an acidemia indicates that there is an acidosis occurring. If the bicarbonate and base excess are low, it indicates a primary metabolic acidosis. If the pCO2 is high, it indicates a primary respiratory acidosis. If the bicarbonate and base excess are low and the pCO2 is high, it indicates a mixed primary metabolic acidosis (low bicarbonate or base excess) and primary respiratory acidosis (high pCO2). In the latter scenario, the pH would be expected to be quite low (acidemia).

Acid-base disturbances have profound effects on the body. Acidosis results in arrythmias, decreased cardiac output, depression, and bone demineralization. Alkalosis results in tetany and convulsions, weakness, polydipsia and polyuria.

Metabolic acidosis

A metabolic acidosis is the most common acid-base disturbance encountered in sick small animals and horses. A metabolic acidosis is identified by a decreased bicarbonate (HCO3) and base excess (BE) on a blood gas analysis, and a decreased HCO3 on the chemistry panel.

Metabolic acidosis can be caused by:

Metabolic acidosis

Metabolic acidosis gamblegram

  • Consumption of bicarbonate by a noncarbonic acid: Called a high anion gap- or titration acidosis, because the noncarbonic acid increases the anion gap (it is an unmeasured anion) and the bicarbonate is titrating the accumulated acid. An alternative term is a “buffer ion” acidosis (Constable 2014). Electroneutrality is maintained because the unmeasured anion (UA) is making up for the decrease in bicarbonate (HCO3) (see gamblegram).
  • Loss of bicarbonate or gain of chloride: Called a normal anion gap- or hyperchloremic acidosis. An alternative term is a “strong ion” acidosis (Constable 2014). Loss of bicarbonate results in retention of chloride to maintain electroneutrality (which rules!!). The anion gap does not change, because there is no accumulation of a noncarbonic acid (think of chloride as the accumulating acid) (see gamblegram).

These causes/types of acidosis can be differentiated on clinical history (processes responsible for the acidosis), corrected chloride (Clcorr) and anion gap (AG).

Titration metabolic acidosis

Titration acidosis

Titration acidosis equations

Bicarbonate can be consumed or titrated by a noncarbonic acid that is produced in the body or is an exogenous toxin. Examples of acids produced in the body are lactate (from anaerobic metabolism), ketones (diabetes mellitus, ketosis), and acids (phosphates, sulfates) normally excreted by the kidneys. Examples of exogenous toxins are salicylate, methanol, ethylene glycol and their metabolites. The acids (anions) neutralize/buffer/consume the HCO3, maintaining electroneutrality, therefore the Clcorr is normal. Noncarbonic acids are unmeasured anions and will increase the AG. Thus, titration results in a high anion gap metabolic acidosis. With an uncomplicated high anion gap metabolic acidosis, the decrease in HCO3 is roughly equivalent to the increase in AG or unmeasured anions (UA).

A titration or high anion gap acidosis is a primary acid-base disorder (i.e. it does not occur in compensation to a primary respiratory acid-base disorder). It is the most common acid-base disturbance in most species (except ruminants).

Causes of a titration metabolic acidosis include:

  • All species: Common acid-base disturbance in most species, except for ruminants.
    • L-lactate (hypovolemia from fluid losses causing decreased tissue perfusion or anemia, both leading to anaerobic metabolism in tissues)
    • Uremia (renal azotemia or post-renal azotemia – particularly in acute renal injury but can see with chronic kidney disease; may also see with a very severe prerenal azotemia).
  • Small animals:
    • Ketoacidosis
    • Toxic metabolites (e.g. ethylene glycol, salicylates).
  • Cattle:
    • Ketoacidosis (type I ketosis)
    • D-lactate acidosis (calves, particularly due to fermentation of carbohydrates by bacteria in the colon with intestinal-associated diarrhea or ruminal acidosis from excessive milk intake). Note that D-lactate will not be measured with point of care analyzers that provide lactate measurements (these only detect L-lactate).
  • Camelids: Ketoacidosis.

Bicarbonate loss or chloride gain metabolic acidosis

  • Bicarbonate loss: Bicarbonate is usually lost through the gastrointestinal tract or kidneys. Causes include vomiting of intestinal contents (pancreatic/intestinal secretions are rich in bicarbonate), secretory diarrhea, inability to swallow saliva (ruminants, in particular, have lots of bicarbonate in salivary secretions), and renal tubular acidosis. Intestinal loss from secretory diarrhea is the most common cause of this type of primary acid-base disturbance and is the most frequent cause of a bicarbonate loss acidosis in ruminants, particularly calves. Since HCO3 is an anion, the body maintains electroneutrality by increasing or retaining Cl, another anion. Thus, an acidosis due to HCO3 loss is usually accompanied by a corrected hyperchloremia. The AG will be normal because unmeasured anions are not increased. Thus, loss of HCO3 usually causes a hyperchloremic normal anion gap metabolic acidosis. With an uncomplicated hyperchloremic metabolic acidosis, the decrease in HCO3 is roughly equivalent to the increase in corrected Cl.However, it should be noted that some authors attribute the hyperchloremic metabolic acidosis in calves due to loss of sodium in excess of chloride (Constable 2014).
  • Chloride gain: Think of chloride as an “acid”. This principally occurs with the administration of solutions with an imbalance of sodium and chloride (more chloride than sodium) and occurs with infusion of 0.9% saline and administration of calcium chloride to cattle (Constable 2014). It is surprising to think about an isotonic solution such as 0.9% NaCl being acidifying, however this does occur and is nicely explained based on the strong ion difference of the infused solution by Constable (2014). An alternative way to consider the acidifying effect of 0.9% saline, is that normally in plasma, sodium exceeds chloride (roughly 138-147 mEq/L versus 92-102 mEq/L in cattle). However, by giving equal amounts of sodium and chloride, you are actually giving more chloride than is normally present in plasma, creating a “hyperchloremic” or acidifying step (a simplistic but hopefully helpful) explanation.

The presence of a hyperchloremic normal anion gap metabolic acidosis (low bicarbonate, high Clcorr) does not mean the acidosis is a primary disorder. A hyperchloremic metabolic acidosis can be secondary (or in compensation for) a primary respiratory alkalosis. Whether a hyperchloremic metabolic acidosis is primary or secondary to a respiratory acidosis requires clinical assessment of the patient and knowledge of the underlying disease (e.g. a dog that has small intestinal diarrhea likely has a primary hyperchloremic metabolic acidosis from bicarbonate losses into the intestinal tract). If there is a primary respiratory alkalosis with a compensatory hyperchloremic metabolic acidosis, there will be a clinical disease or condition causing hyperventilation, the blood pH will be more alkaline than acidic (because alkalosis is the primary disturbance) and the pCO2 will be quite low (remember, compensation usually does not return the pH to normal). Kidney function must also be normal for an animal to be able to compensate for a primary respiratory alkalosis.

Causes of a bicarbonate loss acidosis include:

  • All species: 
    • Primary: Secretory diarrhea. Most common metabolic acid-base disturbance in calves (Constable 2014), uncommon in other species. Administration of low SID fluids (e.g. 0.9% NaCl).
    • Secondary: Compensation for a primary respiratory alkalosis. Uncommon. Requires normal renal function.
  • Small animals:
    • Primary: Renal tubular acidosis, vomiting of intestinal contents (uncommon – pancreatic secretions are rich in bicarbonate).
  • Cattle:
    • Primary: Loss of saliva (choke, rabies).

Metabolic alkalosis

A metabolic alkalosis is identified by an increased HCO3 and base excess (BE) on a blood gas analysis, and an increased HCO3 and/or decreased Clcorr on the chemistry panel. Metabolic alkalosis is caused by:

Metabolic alkalosis

Metabolic alkalosis gamblegram

  • Loss of an acid (H+): This is usually accompanied by loss of Cl without concomitant loss of Na+) or loss of Cl in excess of Na+ (chloride is an “acid” and sodium is a “base”). This will cause (and is recognized by) a decreased Clcorr.
  • Gain of a base or bicarbonate or loss of chloride: Gain of bicarbonate (e.g. administration of bicarbonate in fluids) can cause a metabolic alkalosis, but this is a far less common cause than loss of an acid.

Once metabolic alkalosis is established, other conditions associated with the primary process causing the alkalosis will perpetuate or maintain the alkalosis, specifically hypovolemia, hypochloremia, and hypokalemia.

Metabolic alkalosis due to acid loss

Gastric HCl

Gastric HCl production

H+ is usually lost through the gastrointestinal tract (primarily vomiting of gastric contents, see image to the right) or urinary tract (e.g. hyperaldosteronism; aldosterone promotes activity of the hydrogen ATPase pump in the luminal membrane of collecting tubules, resulting in hydrogen excretion in the urine). For each milliequivalent of H+ secreted, an equivalent amount of HCO3 will be generated (see image to right). Since H+ is concurrently lost with Cl in disorders causing hydrogen loss (except for hyperaldosteronism), these patients typically have a low Clcorr.  Excessive loss of Cl (with respect to Na+) will also result in a metabolic alkalosis as HCO3 increases to maintain electroneutrality. This can occur with loop and thiazide diuretics (for more information, see renal physiology page relating to sodium absorption) or excess sweating in horses (lose potassium chloride). In an uncomplicated metabolic alkalosis, the increase in HCO3 is usually proportional to the decrease in Clcorr and the AG is normal. A metabolic alkalosis is a common acid-base abnormality in ruminants with abomasal outflow obstruction (e.g. displaced abomasum) and in small animals with vomiting of gastric contents.  This type of alkalosis usually responds to chloride supplementation, except for hyperaldosteronism (which is very rare).

Causes of metabolic alkalosis include:

  • All animals
    • Secondary: Renal excretion of hydrogen (distal tubules) or ammonium chloride (proximal tubules) in compensation for a primary respiratory acidosis
  • Small animals:
    • Primary: Vomiting of gastric contents (most common cause), renal losses (e.g.) loop or thiazide diuretics. Other causes are rare.
  • Horses:
    • Primary: Excessive sweating (loss of KCl), ileus, gastric ulcers.
  • Cattle:
    • Primary> Sequestration of abomasal contents (displaced abomasa, abomasal atony, proximal duodenal obstruction). Most common acid-base disturbance in adult cattle but not calves.

Metabolic alkalosis due to base gain

Administration of NaHCO3 (e.g. treatment of metabolic acidosis) or organic anions (which are metabolized to HCO3, e.g. citrate in massive blood transfusions), may cause a metabolic alkalosis, particularly under conditions of volume depletion or renal dysfunction.

The presence of a metabolic alkalosis (high bicarbonate, low Clcorr) does not mean the metabolic alkalosis is a primary disorder. A metabolic alkalosis can be secondary to (or in compensation for) a primary respiratory acidosis. Whether a metabolic alkalosis is primary or secondary to a respiratory acidosis requires clinical assessment of the patient and knowledge of the underlying disease. For instance, if there is a clinical disease causing hypoventilation in a dog and the dog is acidemic (or pH is trending low towards acidemia), with a high pCO2, then there is a primary respiratory acidosis with secondary or compensating metabolic alkalosis. In contrast, a dog that is vomiting gastric contents likely has a primary metabolic alkalosis (in this case, the pH will be alkaline or trending towards alkaline). Remember compensation does not usually correct pH to normal and over-compensation does not occur. Normal renal function is also required for an animal to be able to compensate for a primary respiratory acidosis.

A metabolic alkalosis due to gain of base is uncommon (and usually iatrogenic).

Metabolic summary

The following table provides a summary of the changes in the blood gas (pH, HCO3, BE) and biochemical panel (HCO3, AG, Clcorr) with primary metabolic acid-base disturbances, based on the type of disturbance.

Disturbance HCO3
BE
AG Clcorr Effect on pH
Titration metabolic acidosis normal
Bicarbonate loss metabolic acidosis normal
Metabolic alkalosis normal

 

Respiratory acidosis

A respiratory acidosis is identified by an increased pCO2 and low pH (or tendency towards a low pH) on a blood gas analysis. As mentioned previously, the chemistry panel will not provide any information on the respiratory component of acid-base status. A respiratory acidosis is caused by decreased ventilation or gas exchange in the alveoli, which can be secondary to neurologic (affecting the medullary respiratory center), musculoskeletal (affecting the diaphragm and thoracic wall), pulmonary, and cardiac disorders. The most common causes are primary pulmonary disease, ranging from upper airway obstruction to pneumonia. Note that pneumonia alone unlikely to cause a respiratory acidosis (since pCO2 diffuses so readily across alveolar walls) unless the lung involvement is extensive or there is concurrent respiratory muscle fatigue from a prior hypoxic or pain-induced hyperventilation. Diseases or drugs that inhibit the medullary respiratory center also produce a profound respiratory acidosis, e.g. general anesthesia.

Causes of a respiratory acidosis include:

  • All species:
    • Primary: Respiratory obstruction (uncommon), severe pulmonary disease (usually accompanied by muscle fatigue), inadequate ventilation during anesthesia (iatrogenic).
    • Secondary: Compensation for a primary metabolic alkalosis.

Respiratory alkalosis

A respiratory alkalosis is identified by a decreased pCO2 and high pH (or tendency towards one) on a blood gas analysis. A respiratory alkalosis is caused by hyperventilation. Ventilation is stimulated by central and peripheral (carotid or aortic bodies) chemoreceptors.

  • Central chemoreceptors: Respond to pH changes in cerebrospinal fluid (CSF) and hypercapneic hypoxia (characterized by decreased oxygen and increased carbon dioxide). Changes in CSF parallel changes in blood when there are respiratory disturbances, due to the ready diffusibility of carbon dioxide; pH does not usually change in CSF with a primary metabolic acidosis, since hydrogen cannot diffuse into the CSF.
  • Peripheral chemoreceptors: Respond to hypoxemia (low pO2) , increased partial pressure of carbon dioxide (pCO2, i.e. respiratory acidosis), and acidemia (low pH, i.e. the respiratory alkalosis is occurring in compensation for a primary metabolic acidosis). Hypoxemia can be due to respiratory, cardiac or hematological (e.g. anemia, carbon monoxide poisoning) disorders.  Hyperventilation can also be stimulated by pain (nociceptors), stretch (e.g. lung disease), stress, or anxiety.

Causes of respiratory alkalosis include:

  • All species:
    • Primary: Any cause of hyperventilation (e.g. hypoxemia, pneumonia causing pain, anxiety).
    • Secondary: Compensation for a primary metabolic acidosis (common).

Respiratory summary

The following table provides a summary of the changes in the blood gas (pH, pCO2) with primary respiratory acid-base disturbances, based on the type of disturbance. Note, that a respiratory disturbance cannot be detected from a biochemical panel and a respiratory disturbance does not alter BE.

Disturbance pCO2 Effect on pH
Respiratory acidosis
Respiratory alkalosis

Mixed disorders

A mixed acid-base disturbance is defined as the presence of more than one primary disturbance. There could be two or even three primary acid-base disturbances. Note that it is incorrect to use this term for a single primary disturbance with the appropriate compensatory response. A mixed acid-base disturbance is quite common in animals and should be suspected in these situations:

  • The pH is normal but there is an abnormal pCO2 and/or bicarbonate. (Remember that compensation rarely results in a normal pH).
  • The change in pH is greater than can be attributed to one disorder alone.
  • The pCO2 and HCO3change in opposite directions (compensatory responses should parallel the primary change).
  • The expected compensatory response is:
    • Not present
    • Opposite to that which is expected (parallel changes are expected)
    • Exceeds that which is expected. For example, in a primary metabolic acidosis, the expected response is a respiratory alkalosis. If the pCO2 is normal or increased, there is a concurrent respiratory acidosis. The pH would be lower than expected for a metabolic acidosis alone, because the combined respiratory and metabolic acidosis has an additive effect on lowering the pH.
  • The degree of change in acid-base results is not proportional.
    • There are easy formulas used to assess for these proportional changes. These formulas depend on whether there is an elevated anion gap or not. For all these formulas, the change in test result is compared to the midpoint of the reference interval for the test.
      • Change in AG = Measured AG – Normal AG
      • Change in bicarbonate = Measured bicarbonate – Normal bicarbonate
      • Change in chloride = corrected chloride
    • Assessment of proportional changes
      • In an uncomplicated titration high anion gap metabolic acidosis, the increase in the AG is roughly proportional to the decrease in HCO3 and Clcorr should be normal.
      • In an uncomplicated hyperchloremic metabolic acidosis, the decrease in HCO3 is roughly proportional to the increase in Clcorr and the AG should be normal.
      • In an uncomplicated metabolic alkalosis, the increase in HCO3 is roughly proportional to the decrease in Clcorr and the AG is usually normal.

Any deviations from that listed above suggest the likelihood of a mixed-acid disturbance. Remember that changes in serum proteins (mostly albumin) may impact the AG (and should be considered when using these guidelines).

For example,

  • High anion gap metabolic acidosis: In an uncomplicated high anion gap acidosis, the change in AG is equivalent to the change in bicarbonate.
    • If the decrease in bicarbonate is greater than the increase in anion gap, this indicates that there is a mixed disturbance, with something lowering the bicarbonate greater than expected. In this instance, this is compatible with a mixed high anion gap and hyperchloremic (normal anion gap) acidosis, e.g. renal failure, resolving diabetic ketoacidosis, secretory diarrhea with anaerobic metabolism causing a lactic acidosis. Other potential explanations for these changes are:
      • Titration acidosis with false decrease in anion gap due to decreased unmeasured anions (low albumin) or increased unmeasured cations (monoclonal immunoglobulins).
      • Mixed titration acidosis AND chronic respiratory alkalosis. The body will compensate for the alkalosis by retaining chloride in the kidneys (hyperchloremic acidosis). This will only occur if the alkalosis is the dominating disturbance.
  • If the decrease in bicarbonate is less than the increase in anion gap, this can indicate that there is a mixed disturbance, with something preventing the bicarbonate from being as low as it should be. This is compatible with a mixed high anion gap acidosis and metabolic alkalosis, e.g. gastric dilatation volvulus syndrome in dogs (lactic acidosis with sequestration of chloride-rich fluid), renal failure with vomiting/diuretics, vomiting gastric contents and diabetic ketoacidosis or lactic acidosis. In this case, the bicarbonate and chloride will be low and the anion gap will be high. Other potential explanation for these changes are:
    • Non acidotic high anion gap (bicarbonate is normal or high): Animal has a high anion gap for other reasons, such as increased negative charge on proteins (e.g. alkalemia, carbenicillin therapy and dehydration causing increased albumin)
    • Mixed titration metabolic acidosis AND respiratory acidosis, e.g. cardiopulmonary arrest. The respiratory acidosis will cause a compensatory metabolic alkalosis, as long as the kidneys are functionally normally and can excrete acid.
  • Normal anion gap metabolic acidosis or metabolic alkalosis: In an uncomplicated normal anion gap acidosis or a metabolic alkalosis, the change in chloride is equivalent to the change in bicarbonate
    • If the decrease in chloride is greater than the increase in bicarbonate, this indicates that there is a mixed disturbance, with something decreasing the bicarbonate. In this instance, this is compatible with a mixed normal anion gap acidosis and a metabolic alkalosis. This can occur renal failure with vomiting/diuretics, vomiting and diarrhea, and liver disease.
    • If the increase in chloride is less than the decrease in bicarbonate, this indicates that there is a mixed disturbance, with something enhancing the decrease in bicarbonate. This is compatible with a mixed high anion gap and normal anion gap acidosis.

Some examples of mixed acid-base disturbances and the changes that ensue are shown in the table below. Note that not all possible combinations are shown in this table.

HCO3 pCO2 AG Clcorr Disorders Expected pH
Primary titration metabolic acidosis (low HCO3  high AG) AND respiratory acidosis (high pCO2) AND primary or compensatory metabolic alkalosis (low Clcorr) N to
(depending on if the alkalosis is primary or secondary)
N N Primary titration metabolic acidosis (high AG) AND metabolic alkalosis (low Clcorr) N, ,
(depends on dominating disturbance)
N Primary metabolic alkalosis (high HCO3, low Clcorr) AND respiratory alkalosis (low pCO2) ↑↑
↓↓ Primary titration AND loss metabolic acidosis (very low HCO3, high AG, high Clcorr), compensatory respiratory alkalosis (low pCO2)

The most common mixed acid-base disturbances are:

  • Small animals: Titration metabolic acidosis (ketoacidosis, uremic acidosis, lactic acidosis) and metabolic alkalosis (vomiting of gastric contents frequently accompanies these disorders).
  • Ruminants: Titration metabolic acidosis (lactic acidosis) and metabolic alkalosis (sequestration of hydrochloric acid due to abomasal atony or vomiting of gastric contents in adult cattle; titration metabolic acidosis (lactic acidosis) and hyperchloremic (bicarbonate loss) metabolic acidosis (secretory diarrhea) in calves.
  • Horses: Uncommon.
  • Camelids: Uncommon.

Related links

  • Laboratory detection: Use of laboratory tests to diagnose acid-base disturbances, including more information on bicarbonate measurement and the anion gap calculation.
  • Quick test interpretation: A guide to interpreting blood gas results.
  • Chloride: Measurement of chloride and interpretation of changes in chloride.
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