Lactic Acidosis

Chapter 60 Lactic Acidosis



Jan P. Kovacic, DVM, DACVECC



KEY POINTS



• Lactate is synthesized from pyruvate and must be metabolized back to pyruvate to be removed. In anaerobic conditions, pyruvate cannot be used effectively in the Krebs cycle, so lactate levels rise.

• Lactic acid has an acidifying effect on plasma.

• Type A lactic acidosis is the hypoxic form. It occurs when there is inadequate oxygen delivery to the tissues.

• Type B lactic acidosis is the nonhypoxic form. It occurs when there are problems with cellular metabolism in aerobic conditions.

• Lactic acidosis occurs in health and disease. Elevations in lactate are common, but in health the lactate level is restored to normal very quickly after aerobic metabolism is restored.

• Normal lactate levels are less than 2 mmol/L.

• Persistently elevated lactate levels suggest a poor prognosis.


INTRODUCTION


Lactate is a 3-carbon molecule with a carboxyl group at one end that can accept a hydrogen ion to form lactic acid. The pKa for this hydrogen ion is 3.9. Like many of the organic acids of intermediate metabolism, lactic acid is dissociated completely at physiologic pH, and dissociation of the hydrogen ion leaves a strong anion. Consequently lactic acidosis can be recognized by changes in strong ion balance. According to the Stewart approach to acid-base analysis, strong anions force a change in aqueous solutions to increase hydrogen ion [H+] and decrease hydroxyl ion [OH−] concentrations and force a weak acid buffer such as carbonic acid to increase [H+] and decrease bicarbonate concentration [image].1-3 In the conventional approach to acid-base analysis, lactic acidosis is considered to be the consequence of the hydrogen ion production that occurs in conjunction with lactate metabolism. When the lactate anion is in association with another cation such as sodium, as it is in lactated Ringers solution, it does not have an acidifying effect.1,3,4


Lactate exists in two isomeric forms: d-lactate and l-lactate. d-Lactate is an important metabolic product of bacterial metabolism and has been reported to be clinically significant in man with short bowel syndrome, in cats fed propylene glycol, in cats with diabetes mellitus, and in a cat with exocrine pancreatic insufficiency.1,4,5 l-Lactate is the isomer produced metabolically in dogs and cats and is the isomer discussed in this chapter. Most hospital analyzers measure only the L-lactate isoform, so d-lactate will be recognized as a metabolic acidosis with an increased anion gap or strong ion gap that is not accounted for by routine lactate measurement. Serum can be submitted to laboratories for specific d-lactate analysis.4,5



LACTATE METABOLISM


Lactate is synthesized from pyruvate and can also be converted back to pyruvate. This reversible reaction is catalyzed by the enzyme lactate dehydrogenase.6 Lactate dehydrogenase has much greater binding affinity for l-lactate, so when d-lactate is present it is metabolized at a slower rate.


Lactate as an organic acid is unremarkable and behaves as do many other intermediary metabolites. What makes it remarkable is that it exists in a metabolic cul-de-sac with no way in or out except through pyruvate. During anaerobic metabolism when pyruvate is not efficiently metabolized via the Krebs cycle, lactate is formed in high concentration. This can occur with exercise or with disease. Lactate synthesis serves to regenerate nicotinamide adenine dinucleotide, an essential reducing equivalent for ongoing glycolysis. When aerobic conditions are restored, pyruvate is cleared, which opens the pathway for lactate to be metabolized back to normal levels. Lactate may also be transported in the blood and used in the liver under aerobic conditions for energy storage via gluconeogenesis and glycogen synthesis. This pathway involves reconversion of lactate to pyruvate in the liver (Cori cycle) under aerobic conditions to drive the Krebs cycle (Figure 60-1).4,6


image

Figure 60-1 Schematic of lactate metabolism in the cell. Under aerobic conditions with normal mitochondrial function, pyruvate enters the mitochondria and fuels the Krebs cycle. When pyruvate cannot enterthe mitochondrion it will be metabolized to lactate instead.


Lactate is produced primarily in skeletal muscle, gut, brain, skin, and red blood cells. During anaerobic conditions, most lactate is produced in skeletal muscle and the gut. Lactate is metabolized primarily by the liver and kidney.

Related posts:

  1. Aminoglycosides
  2. Gastrointestinal Protectants
  3. Blood Film Evaluation
  4. Hyperglycemic Hyperosmolar Syndrome

Stay updated, free articles. Join our Telegram channel
Tags:
Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Lactic Acidosis

Full access? Get Clinical Tree
Get Clinical Tree app for offline access