The MUDPALES mnemonic for raised anion gap acidosis was drilled
into me from medical school. However recently
after working through each category I became stumped when nothing ticked the
box to identify the cause.
into me from medical school. However recently
after working through each category I became stumped when nothing ticked the
box to identify the cause.
The lady I had been asked to see was in her 80s and had
fractured her hip. On admission she had
normal renal function and acid base status.
Post-operatively she was started on regular analgesia including
paracetamol (acetaminophen) and developed a Staphlococcus Aureus wound cellulitis treated with flucloxacillin. Over the following 2 weeks she developed a
raised anion gap acidosis and positive urinary anion gap. Renal function, lactate and ketones were normal.
fractured her hip. On admission she had
normal renal function and acid base status.
Post-operatively she was started on regular analgesia including
paracetamol (acetaminophen) and developed a Staphlococcus Aureus wound cellulitis treated with flucloxacillin. Over the following 2 weeks she developed a
raised anion gap acidosis and positive urinary anion gap. Renal function, lactate and ketones were normal.
A cause of metabolic acidosis not in MUDPILES is
pyroglutamic acidosis. Pyroglutamic acid
(also called 5-oxoproline) is a by-product in the gamma-glutamyl cycle. This pathway is involved in the synthesis of glutathione,
and is shown above from a recent paper.
pyroglutamic acidosis. Pyroglutamic acid
(also called 5-oxoproline) is a by-product in the gamma-glutamyl cycle. This pathway is involved in the synthesis of glutathione,
and is shown above from a recent paper.
Glutathione provides negative feedback on the cycle by
inhibiting the enzyme gamma-glutamyl-cysteine synthase. An acquired deficiency in glutathione, as
with alcohol or paracetamol, results in loss of this negative feedback and
increased production of 5-oxoproline leading to a metabolic acidosis. Other drugs affect the cycle at different
points including flucloxacillin which inhibits 5-oxoprolinase similarly resulting
in build-up of 5-oxoproline.
inhibiting the enzyme gamma-glutamyl-cysteine synthase. An acquired deficiency in glutathione, as
with alcohol or paracetamol, results in loss of this negative feedback and
increased production of 5-oxoproline leading to a metabolic acidosis. Other drugs affect the cycle at different
points including flucloxacillin which inhibits 5-oxoprolinase similarly resulting
in build-up of 5-oxoproline.
Urine amino acid screens show high levels of 5-oxoproline,
though this test is not always available.
Our patient improved with withdrawal of paracetamol and flucloxacillin
and oral bicarbonate which was stopped after a week. Some cases have been treated with N-acetylcysteine
to replenish glutathione levels.
though this test is not always available.
Our patient improved with withdrawal of paracetamol and flucloxacillin
and oral bicarbonate which was stopped after a week. Some cases have been treated with N-acetylcysteine
to replenish glutathione levels.
I think this is probably an under-recognised cause of
metabolic acidosis with many of the risk factors being prevalent in our inpatients
(poor nutrition, chronic alcohol use, renal failure, infection, paracetamol use). A different mnemonic for causes of raised
anion gap metabolic acidosis may be helpful like GOLD MARK:
metabolic acidosis with many of the risk factors being prevalent in our inpatients
(poor nutrition, chronic alcohol use, renal failure, infection, paracetamol use). A different mnemonic for causes of raised
anion gap metabolic acidosis may be helpful like GOLD MARK:
·
G – glycols (ethylene and propylene)
G – glycols (ethylene and propylene)
·
O – 5-oxoproline (pyroglutamic acid)
O – 5-oxoproline (pyroglutamic acid)
·
L – L-lactate
L – L-lactate
·
D – D-lactate
D – D-lactate
·
M – methanol, ethanol
M – methanol, ethanol
·
A – aspirin/salicylates
A – aspirin/salicylates
·
R – renal failure
R – renal failure
K – ketones
Post by Ailish Nimmo