So a couple of weeks ago we got a lovely gentleman through our doors who had a medical problem.  He was mid 60s and had a pneumonia, but was tolerating it pretty well.  He had HTN, and CLL.

 What irked our collective team noodle was his K+ of 8.9, his ECG was normal, and he wasn’t in renal failure.

No tenting, sineing, PR prolongation, or P wave abnormality, or weird block.

“No, the sample isn’t haemolysed” the lab told us.

The repeat came back 8.7. – not haemolysed (this time written in block capitals).

The VBG we did, and ran to ICU to analyse gave us a value of 8.2.

So we turned to google, pubmed, and litfl, and all learnt about pseudohyperkalaemia:

The commonest cause is sloppy venepuncture, but it can also occur in patients with thrombocytosis, or leucocytosis.  Effectively it is a measurement error that occurs if you have tonne of cells in the sample all gently, slowly lysing.

Our gentleman’s WCC was 200

Pseudohypokalaemia has also been reported with leucocytosis as well.  As always I suppose we should always interpret lab results in light of what the patient looks like in front of us.


Blood Gas Ninja III : Mind The Gaps

cuteninjNow we’ve covered the easy bits of acid base, the determinants of pH, and compensation. This week I’m covering all the weird and wonderful calculations you can do to help you potentially whittle down the diagnostic options.   You don’t have to calculate SID, SIG, or OG for every gas, but its useful to know how to, so when you need to, you can.

Anion Gap

anion gap

So a metabolic acidosis is caused by a decrease in SID, making the buffer base contract to maintain the law electrochemical neutrality.  This is usually because strong anions accumulate.  Now we don’t normally measure the strong anions, so we find them by calculating ‘gaps’.  Most of these ‘gaps’ were introduced before we started routinely measuring lactates, so I think it’s a point of contention whether lactate still counts as an ‘unmeasured’ anion, but for the purposes of what we’re talking about let’s call it a measured, unmeasured one!

Take your measured anions and subtract them from your measured cations.

Anion Gap = [Na+] + [K+] – [Cl-] – [HCO3]

If the anion gap is really large (>30) you have a metabolic acidosis.  Anion gaps get bigger if you have less HCO3, Cl.  Now the ‘gap’ itself, is this unmeasured component.  The anion gaps is affected by fluctuations in ATOT because A- which makes up ATOT is usually the biggest component of the gap in healthy individuals.  This means that if someone’s albumin, and sometimes phosphate are low, the size of their anion gap may be less, or normal, when in fact they’re got a rip roaring metabolic acidosis.

We can correct for albumin;

AGc  = AG + 2.5 (normal albumin in g/dl – observed albumin in g/dl)

 The normal range for Anion Gap and AGc is between 10 and 18 mEq/L

Causes of a high anion gap metabolic acidosis can be remembered by the mnemonic MUDPILESCAT and causes of a normal anion gap acidosis can be remembered by USED CRAP

Low Anion Gap Normal Anion GapUSED CRAP Elevated Anion GapMUDPILESCAT
  • Decreased albumin
  • Dilution
  • Multiple Myeloma
  • Hypercalcaemia
  • Hypermagnesaemia
  • Lithium OD
  • Polymixin B
  • Increased lipids
  • Iodide ingestion


  • Ureterenterostomy/Uretersigmoid  connection
  • Small Bowel fistula, steroid excess
  • Extra Chloride
  • Diarrhoea


  • Carbonic Anhydrase inhibitors, CaCl ingestion, cholestytramine ingestion
  • Renal Tubular Acidosis
  • Adrenal insufficicney, Ammonium Chloride ingestion
  • Pancreatic fistula, Parenteral nutrition
  • Methanol
  • Uraemia
  • DKA
  • Paraldehyde
  • Iron, Isoniazid
  • Lactate
  • Ethylene Glycol
  • Salicylates
  • Carbon Monoxide, Cyanide
  • Alcoholic Keotacidosis
  • Toluene


Strong Ion Difference:  [Na+] – [Cl]

This is a quick by the bedside estimate.  If you wanted to calculate a proper SID, you’d need a whole host of other measured values, but as you now know was makes up SID you can use this quick and dirty measure.

[SID] = [Na+] + [K+] + [Ca2+] + [MG2+] – [CL] – [Other Strong Anions].


<38  Low SID >38  High SID
Strong ion acidosis (probably hyperchloraemic acidosis).Renal Tubular AcidosisDiarrhoea Metabolic AlkalosisNG SuctionDiureticsHyperaldosteronism

Volume depletion


Strong Ion Gap

Remember Stewart?  Good.  In 1990 Jones proposed using Strong Ion Gap as a scanning tool for acid base disturbance.  This is found by taking SIDa, (apparent SID), from SIDe(effective SID)

SIDa = [Na+] + [K+] + [Ca2+] + [Mg2+] – [Cl-] – [Lactate]

SIDe = [A-] + [HCO3-]


What you are doing here is taking your strong ion difference, and taking it away from the buffer base, if you do this.  The normal SIG should be close to zero.  The SIG is NOT the AG, and it is not the same as the Standard Base Excess.

High SIG  (> than 2) Low SIG (less than -<2)
Increase in unmeasured strong anions

  • D –lactate
  • Ketoacids
  • Salicylate


Increase in unmeasured weak anions

  • Polygelinate (Gelspan etc)
  • Myeloma IgA


Increase in unmeasured strong cations (lithium)Increase in unmeasured weak cations

  • Myeloma
  • IgG

Increased Chloride

Increased Sodium


I think SIG is quite difficult to use, one of its big limitations is quite small errors in the lab will affect the SIG.  It’s also not really been studied enough to make it easy to work out routinely by the bedside.  Whereas things like the AGc have been around for decades.  Now some studies have shown that a high SIG is a very strong predictor of mortality [ROC 0.991 (95% I 0.972-0.998) ] but this was in penetrating trauma patients requiring vascular surgery (quite a narrow population).

[citation – Kaplan, Lewis J., and John A. Kellum. “Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury*.” Critical care medicine 32.5 (2004): 1120-1124.]


Osmolar Gap

Anion Gaps, SIDs, and SIGs can be useful for estimating charged particle concentrations within plasma.  What about uncharged molecules?  For this we need a different gap.

The osmolar gap is calculated by taking measured osmolality from the calculated osmolality.  It should normally be less than 10.  The osmolality is the measured.  You can use an osmolar gap calculation to look for molecules dissolved in the plasma that do not have a charge.

Osmole: A unit of osmotic pressure, the amount of a solute that dissolves in solution to form one mole of particles.

Osmolality:  number of osmoles dissolved in a kg of solvent [mass] (This is measured)

Osmolarity: number of osmoles dissolved in a litre of solvent [volume] (This is calculated)

Calculated Osmolarity =  (2 X Na+)  + Glucose + Urea

Osmolar Gap = Osmolality – Osmolarity

If we have a high osmolar gap, we can infer there is an excess of a weird dissolved molecule in the blood.  If you work in a department that doesn’t routinely measure ETOH, an elevated osmolar gap metabolic acidosis might be your only blood result that tells you they are sloshed (you may have worked this out in other ways).  Some calculators or equations add in alcohol to this equation too.

Causes of high osmolar gap:

  • Ethanol
  • Mannitol
  • Methanol
  • Ethylene Gylcol
  • Sorbitol
  • Polyethylene glycol
  • Propylene glycol (used to suspend lorazapam and diazepam IV solutions)
  • Glycine (think TURP)
  • Maltose
  • Lithium

Three words of caution

  • There are 2 types of osmometers, one works by using vapour pressure, the other using freezing point depression.  Only the freezing point depression method works accurately with volatile chemicals like methanol and ethanol.  Your lab could use either.  If they use vapour pressure osmometry you might get falsely normal results.
  • There are many different formulae for the OG, depending on local units of measurement. None of them are wrong, but all of them produce slightly different results.
  • An obtunded patient, with a high osmolar gap could have ingested more than one thing.


So in conclusion

We can use the Anion Gap to give us a better idea of the causes of metabolic acidosis.  SID and SIG can give us some further clarity in certain situations but there utility is nowhere near as good as the anion gap.  The Osmolar Gap gives us an indication of unmeasured uncharged molecules, but doesn’t tell us what they are.