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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • A disruption of acid–base homeostasis producing increased H+ concentration, which is reflected by acidemia (decreased blood pH) and low plasma HCO3– concentration
  • Normal plasma HCO3– concentration is ≅24 mEq/L
  • Normal blood pH ranges from 7.35 to 7.45

Pathophysiology!!navigator!!

  • H+ is regulated by intracellular and extracellular buffering, respiratory buffering (i.e. variation of CO2 levels via changes in ventilation), and regulation of HCO3– via renal excretion of H+
  • Renal H+ excretion is accomplished by direct secretion of limited amounts of H+, increased generation of ammonium ions, and titration to phosphates and urates (titratable acidity)
  • Resorption of HCO3– occurs when H+ is secreted, 90% in the proximal tubule and the remainder in the distal nephron
  • Buffering of H+ occurs rapidly and is accomplished by proteins, phosphates, and HCO3–
  • The most important buffer is HCO3–
  • Respiratory compensation responds within minutes
  • Definitive regulation of H+ and HCO3– concentrations is accomplished by the kidney
  • Renal processing of acidosis begins within hours but may take days to normalize pH
  • Inability to excrete H+, loss of HCO3–, increased production of H+, and accumulation of acids are the major mechanisms producing metabolic acidosis
  • Hyperproteinemia (i.e. weak acids) and overhydration (i.e. dilutional acidosis) also produce metabolic acidosis via alteration of the balance between strong cations and anions

Systems Affected!!navigator!!

Respiratory

  • Chemoreceptors sense low pH in blood or CSF and stimulate hyperventilation to increase elimination of CO2 and increase pH
  • Decreased respiratory muscle strength can lead to hypoventilation and worsening acidosis

Cardiovascular

  • Hyperkalemia secondary to acidemia may cause arrhythmias and decreased cardiac contractility
  • Vasodilation of arterioles; constriction of veins
  • Vascular effects may be offset by catecholamine effects

Neuroendocrine

  • CNS depression
  • CSF acidosis in acute situations

Renal

The kidney responds to low arterial pH by increasing H+ excretion and generating increased concentrations of HCO3– to bring the systemic pH back to normal.

Metabolic

  • Decreased affinity for O2—hemoglobin binding, enhancing release of O2 to tissues
  • Increased protein catabolism
  • Increased ionized Ca2+ concentration

Genetics!!navigator!!

Fanconi syndrome may be heritable in Quarter Horses.

Signalment!!navigator!!

Any breed, age, or sex.

Signs!!navigator!!

  • Dependent on the underlying cause
  • Weakness, depression, and tachypnea are clinical signs of metabolic acidosis

Causes!!navigator!!

  • Loss of HCO3– from the GI tract (e.g. colitis)
  • RTA results in HCO3– loss both directly and indirectly, depending on the type of tubular dysfunction
  • Aminoaciduria, lactic aciduria, and glucosuria is suggestive of Fanconi syndrome
  • Renal failure results in an inability to excrete H+ and accumulation of uremic acids
  • Lactic acidosis can result from anaerobic metabolism, which occurs secondary to decreased tissue perfusion. Hypovolemia from severe dehydration (e.g. diarrhea, sweating, decreased intake), fluid sequestration (e.g. ascites, pleural effusion, internal diarrhea), or hemorrhage leads to decreased tissue perfusion. SIRS produces acidosis via several mechanisms, including hypotension (decreased tissue perfusion), decreased cardiac contractility, tissue ischemia, fluid shifts, hypoxemia, and hepatic damage
  • Chronic causes of hypoxemia produce lactic acidosis
  • Grain overload produces metabolic acidosis via production of lactic acid, fluid sequestration in the GI tract, and secretion into the GI tract
  • High-intensity anaerobic exercise and rhabdomyolysis results in production of lactate, which can result in transient metabolic acidosis
  • Malignant hyperthermia is uncommon but has occurred in anesthetized horses and results in severe lactic acidosis
  • Acute or endstage hepatic failure may result in metabolic acidosis due to failure of the liver to metabolize lactic acid
  • Asphyxia at parturition may decrease perfusion, which can result in lactic acidosis
  • Ingestion of exogenous acids (e.g. salicylates, ethylene or propylene glycol) is uncommon
  • Proteins are weak acids; conditions producing significant hyperproteinemia (e.g. chronic infection, immune-mediated disease, plasma cell myeloma, lymphoma) produce metabolic acidosis
  • Total parenteral nutrition can lead to metabolic acidosis when cationic (e.g. lysine, arginine) or sulfur-containing amino acids are metabolized as H+ is formed

Risk Factors!!navigator!!

  • Patients with chronic renal failure or chronic hypoxemia (e.g. severe equine asthma) may be at greater risk for acidosis with progression of their primary problem
  • Horses on acetazolamide for hyperkalemic periodic paralysis may develop acidosis more readily, as acetazolamide is a carbonic anhydrase inhibitor that causes increased HCO3– excretion
  • Highly anionic diets can induce metabolic acidosis in equids

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Some causes of metabolic acidosis can be identified on physical examination (e.g. diarrhea, hypovolemia, colic with ischemic lesions)
  • Decreased HCO3– concentrations are also seen in conditions with chronic respiratory alkalosis; PCO2 is low if compensation is occurring, but pH will be normal or mildly increased

Laboratory Findings!!navigator!!

Drugs That May Alter Laboratory Results

  • Excessive anticoagulant may falsely decrease results via dilution
  • Excessive Na+ heparin (acidic) may falsely decrease HCO3– concentrations

Disorders That May Alter Laboratory Results

With poor peripheral perfusion, results of blood gas analysis on samples taken from peripheral vessels may not reflect the overall systemic condition. Appropriate reference ranges must be used (venous vs. arterial).

CBC/Biochemistry/Urinalysis!!navigator!!

  • Measurement of serum electrolytes and protein concentrations is important to determine the cause and to guide treatment
  • Calculation of the AG may be useful, especially in mixed acid–base disorders
  • Proportionate changes in Na+ and Cl– concentrations occur with alterations of fluid balance
  • Normal Na+ concentrations with hypochloremia or hyperchloremia indicate acid–base imbalance
  • Albumin/protein concentrations are not considered when calculating the AG; however, because proteins are weak acids, hyperproteinemia (e.g. dehydration, chronic inflammation, neoplasia) can contribute to metabolic acidosis
  • Urinalysis and fractional excretion of electrolytes, in combination with serum creatinine and blood urea nitrogen concentrations, are useful in cases of renal dysfunction

Horses with Hyperchloremia and Normal AG

  • Loss of HCO3–—diarrhea, type 2 RTA, and primary respiratory alkalosis; however, severely affected colitis patients often are acidotic and low in Na+, K+, Cl–, and HCO3– because of water intake after isotonic fluid loss
  • Salt poisoning
  • Cl– retention—renal failure, type 1 or 4 RTA, and acetazolamide therapy

Horses with Increased AG

Accumulation of unmeasured anions, such as:

  • Lactate—hypovolemia, hypotension from SIRS, hypoxemia, third space fluid loss, anaerobic exercise, rhabdomyolysis, liver failure, malignant hyperthermia
  • Phosphates, sulfates, and organic acids—renal failure, toxic ingestion

Other Laboratory Tests!!navigator!!

Total CO2

  • Closely approximates HCO3– concentration because most CO2 is carried in the blood as HCO3–
  • Respiratory alkalosis also decreases TCO2; differentiation can only be made with blood gas analysis
  • Analyze rapidly with minimal room-air exposure as CO2 will decrease

Blood Gas Analysis

  • Needed to determine primary change in blood pH
  • Decreased blood pH indicates acidemia. A concurrent decrease in HCO3– indicates primary metabolic acidemia. An accompanying decrease in PCO2 indicates respiratory compensation
  • Decreased HCO3– with increased blood pH indicates compensation for a respiratory alkalosis
  • Determine if hypoxemia is contributing to lactic acidemia
  • Blood gas parameters must be assessed against appropriate reference ranges for the sample taken
  • Blood lactate—elevation indicates contribution to metabolic acidemia

Imaging!!navigator!!

Ultrasonography can be useful in evaluating colitis, ascites, and pleural effusion, as well as cardiac, renal, and hepatic architecture.

Pathologic Findings!!navigator!!

Dependent on the underlying cause.

Treatment ⬆ ⬇

TREATMENT

Directed at the primary cause.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Isotonic fluid therapy is usually sufficient to correct lactic acidosis from hypovolemia in mild cases
  • With severe hypovolemia, therapy may include hypertonic saline, colloids, or blood transfusion followed by crystalloid fluid administration
  • Alkalinizing therapy is reserved for patients with a pH < 7.2 that persists following rehydration
  • NaHCO3– is most frequently utilized
  • NaHCO3– deficit (mEq) is calculated as !!calculator!!follows—base deficit × body weight (kg) × 0.3 (extracellular fluid space (0.5 in foals))
  • A negative BE, or 24 minus HCO3–, can be used for the base deficit
  • In acute cases, half the deficit can be given over 30 min, in fluids, or as a 5% solution to adults
  • Isotonic HCO3– (1.3%) is a good choice in neonates or severely affected adults
  • Correction to a pH > 7.2 and BE ≥ – 5 is usually adequate

Precautions!!navigator!!

  • Use HCO3– therapy cautiously in patients with respiratory compromise, because the CO2 that is generated may not be eliminated, causing a further decrease in pH
  • Na+ load may affect blood volume in neonates and patients with compromised renal, neurologic, or cardiac function
  • Rebound alkalosis or cerebral acidosis is reported from overdose or rapid administration of HCO3– since both CO2 and H2CO3 cross the blood–brain barrier

Possible Interactions!!navigator!!

HCO3– cannot be mixed with Ca2+.

Alternative Drugs!!navigator!!

Oral rehydration solutions (4–8 L PO every 2 h in adults without ileus).

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Serial blood gas analysis to evaluate efficacy of therapy.

Possible Complications!!navigator!!

  • Hyperkalemia
  • Cardiac arrhythmias, hypotension
  • Severe, untreated metabolic acidosis with a pH < 7.0 may result in death

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Hyperchloremia
  • Hyperkalemia
  • Respiratory alkalosis

Age-Related Factors!!navigator!!

  • Asphyxia during parturition in neonates
  • Conditions associated with premature neonates

Pregnancy/Fertility/Breeding!!navigator!!

Metabolic acidosis may decrease uterine blood flow and result in placental insufficiency.

Abbreviations!!navigator!!

  • AG = anion gap
  • BE = base excess
  • CNS = central nervous system
  • CSF = cerebrospinal fluid
  • GI = gastrointestinal
  • PCO2 = partial pressure of carbon dioxide
  • RTA = renal tubular acidosis
  • SIRS = systemic inflammatory response syndrome
  • TCO2 = total carbon dioxide

Suggested Reading ⬆ ⬇

Fielding L. Crystalloid and colloid therapy. Vet Clin North Am Equine Pract 2014;30(2):415–425.

Hall JE.Guyton and Hall: Textbook of Medical Physiology, 13e. Philadelphia, PA: Elsevier Inc., 2016:497–556.

Ohmes CM, Davis EG, Beard LA, et al. Transient Fanconi syndrome in Quarter Horses. Can Vet J 2014;55:147–151.

Author(s) ⬆ ⬇

Author: Sara L. Connolly

Consulting Editor: Sandra D. Taylor

Acknowledgment: The author and editor acknowledge the prior contribution of Jennifer G. Adams.

Additional Further Reading ⬆

Click here for Additional Further Reading