Toxic Acidoses

Toxins that can produce HAGMA include:

Many of these occur as part of defined toxidromes, and are covered under:

Pyroglutamic Acidosis

Pyroglutamic acidosis is a rare HAGMA that:

Pathophysiology in brief:

Pyroglutamic acid (5-oxyproline) is produced:
- From a variety of amino acids during normal cell metabolism
- During cyclical consumption and production of glutathione
In glutathione depletion, enzymatic upregulation causes ↑ 5-oxyproline production
5-oxyprolinase inhibition results in progressive ↑ in 5-oxyproline levels

Occurs due to the combination of:
- Glutathione depletion
  - Paracetamol
  - Malnutrition
  - Frailty
  - Sepsis
- 5-oxyprolinase inhibition
  - Flucloxacillin
  - Vigabatrin
- Renal failure
  ↓ Clearance of pyroglutamic acid.
Requires direct measurement of 5-oxyprolinase in blood or urine to confirm diagnosis
Limited availability of testing means diagnosis is mostly contingent on clinical suspicion.
Is managed supportively:
- Cease causative agents
- Await renal clearance
  Dialysis and diuresis are also effective.

Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.