What are the causes of profound compensated metabolic acidosis?

From the Guidelines

Profound compensated metabolic acidosis is primarily caused by conditions that lead to excessive acid accumulation or bicarbonate loss, with respiratory compensation, and the most significant cause is a diet low in fruits and vegetables and high in animal protein, leading to an imbalance between nonvolatile acids and alkali, as evidenced by a 2017 study 1.

Causes of Metabolic Acidosis

The main causes of profound compensated metabolic acidosis include:

• Diabetic ketoacidosis, where insulin deficiency leads to fatty acid metabolism and ketone production
• Lactic acidosis from tissue hypoxia in shock, sepsis, or severe exercise
• Renal tubular acidosis, where the kidneys fail to excrete acid properly
• Severe diarrhea causing bicarbonate loss through the GI tract
• Certain poisonings like methanol, ethylene glycol, or salicylate overdose
• Starvation ketoacidosis can develop after prolonged fasting

Pathogenesis and Compensation

The pathogenesis of these conditions involves a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone, as described in a 2004 study on hyperglycemic crises in diabetes 1. Compensation occurs through increased respiratory rate and depth (Kussmaul breathing), as the body attempts to eliminate carbon dioxide and raise pH.

Laboratory Findings and Treatment

Laboratory findings typically show a low pH, low bicarbonate, and low pCO2 with an elevated anion gap in most cases. Treatment must address the underlying cause while supporting acid-base balance, often requiring intravenous fluids, electrolyte replacement, and in severe cases, sodium bicarbonate administration, as recommended in a 2000 study on clinical practice guidelines for nutrition in chronic renal failure 1. Increasing fruit and vegetable intake is a crucial step in managing metabolic acidosis, as it helps to balance nonvolatile acids and alkali, and may be more beneficial than sodium bicarbonate supplementation alone, as shown in a 2017 study 1.

From the Research

Causes of Metabolic Acidosis

The causes of metabolic acidosis can be categorized into two main types: high anion gap and hyperchloremic (or normal anion gap) metabolic acidosis.

• High anion gap metabolic acidosis is caused by the accumulation of endogenous acids that consume bicarbonate, such as:
  • Lactic acidosis 2, 3, 4, 5
  • Ketoacidosis 2, 4, 5, 6
  • Renal failure 4, 5
  • Intoxication with ethylene glycol, methanol, salicylate, pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean (gjenkolism) 4
• Hyperchloremic (or normal anion gap) metabolic acidosis is caused by the loss of bicarbonate from the gastrointestinal tract or the kidney, such as:
  • Gastrointestinal bicarbonate loss 4, 5
  • Renal tubular acidosis 4, 5
  • Drug-induced hyperkalemia 4
  • Early renal failure 4
  • Administration of acids 4
  • Unbalanced electrolyte preparations 3
  • SGLT2 inhibitors, such as empagliflozin, which can induce euglycemic diabetic ketoacidosis under certain circumstances 6

Profound Compompard Metabolic Acidosis

Profound compensated metabolic acidosis can occur when the body's compensatory mechanisms are able to maintain a normal blood pH despite a significant reduction in serum bicarbonate concentration.

• This can be seen in cases of chronic metabolic acidosis, where the kidneys are able to increase the production of acid excreting ions, such as ammonium, to compensate for the loss of bicarbonate 5
• However, the exact causes of profound compensated metabolic acidosis are not explicitly stated in the provided studies, and further research would be needed to fully understand this condition.