Resident lecture on NAGMA

One hour lecture on NAGMA. Just some small changes edits from the last time I gave it. It is one of the few lectures that is still in PowerPoint. It is due for a complete overhaul. It also needs a slide on the treatment of RTA that covers the amount of bicarbonate in a 650 mg tablet (8 mmol) and the fact that distal (type 1) RTA requires a limited amount of bicarbonate (at most 1 mmol/kg). This is appropriate for residents and medical students.

If you are interested in ward teaching and RTA, take a look at this post by Robert Centor.

Also this is a nice article on the issue of saline having a pH of 5.5, covering both the reason (its the PVC bag) and the implications (none).

NAGMA (PPT)

Acid-Base Chapters (Chapters 10-16) from Fluids

Chapter 10: Introduction to Acid-Base

Chapter 11: Introduction to Metabolic Acidosis
Chapter 12: Non-Anion Gap
Chapter 13: Anion Gap Metabolic Acidosis
Chapter 14: Metabolic Alkalosis
Chapter 15: Respiratory Acidosis
Chapter 16: Respiratory Alkalosis

Delta anion gap. Not as good as we think it is.

One of the concepts that is regularly taught in the evaluation of acid-base status is determining if there are multiple acid base disorders by evaluating the ratio of the delta anion gap/delta bicarbonate.

I teach this concept as determining what the bicarbonae would be in the absence of or prior to the anion gap.

The concept comes from the idea that for every mEq of bicarbonate that is consumed by the strong acid (other anion) the anion gap should rise by one. So if the bicarb is 16, a delta of 8, we would expect an anion gap of 20, a normal anion gap of 12 plus the delta bicarbonate of 8. This is a ∆AG/∆Bicarb of one.

If the patient had a pre-existing metabolic alkalosis with a bicarbonate of 30, then the patient would have a bicarbonate of 22 and an anion gap of 20. This would give ∆AG/∆Bicarb of 8/2 or 4.
If the patient had a pre-existing metabolic acidosis (non-anion gap) with a bicarbonate of 16, then the patient would have a bicarbonate of 8 and an anion gap of 20. This would give ∆AG/∆Bicarb of 8/16 or 0.5.
Concurrent metabolic alkalosis leads to ratios over 1 and preexisting metabolic acidosis (non-anion gap) yield a ratio below 1.
I had always been suspicious of this because the assumption of the one for one change in anion gap and bicarbonate. This didn’t seem to be very biologic. Turns out my suspicion was justified as numerous studies (Androgue, Elisaf) have shown that the ratio does not hold up.
In this paper by Paulson et al they found:
[Some authors] suggested that mixed disturbances should be considered if the ratio is less than 0.8 or greater than 1.2. Paulson, applying this rule to a group of normal control subjects and patients with simple metabolic acidosis, noted that the formula erroneously categorized 56% [specificity of 44%] of this group as mixed disturbances. Use of the 95% confidence interval of ±8 mEq/L increased the specificity to 97% but with a poor sensitivity of only 27%.
That’s terrible. Why torture the brains of medical students with this type of worthlessness.
Good review here.

More metabolic acidosis than you can shake a stick at…

The set up

28 year old under going treatment for metastatic testicular cancer presents with a history of recurrent kidney stones.

pH 7.13
pCO2 22
pO2 96

Na 138

Cl 114
BUN 14

K 3.2
HCO3 8
Cr 1.0
glucose 96

urine lytes:
Na 56
Cl 78
K 12
Measured osmolality 292

Step one


Determine the primary acid-base disorder. The pH, bicarbonate and pCO2 are all moving in the same direction (down in this case). When all the Henderson-Hasselbalch variables are moving in the same direction (up or down) the primary disorder is metabolic. The pH is decreased so this is a metabolic acidosis. 

Step two


Is the compensation appropriate, or do we have a primary respiratory disorder as well as a metabolic acidosis? 
We use Winter’s Formula to get the predicted pCO2 based on the bicarbonate.
1.5 x bicarbonate + 8 = 
1.5 x 8 +8 = 20

His actual pCO2 is 22 which is close enough, so a pure metabolic acidosis with appropriate respiratory compensation.

Step three

If there is a metabolic acidosis is there an anion gap?
138 – (114 +8) = 16
Yes, this is an anion gap metabolic acidosis.

Step four

If there is an anion gap, is there an osmolar gap? I usually don’t bother to look for an posmolar gap uness the patient is particularly toxic with a large anion gap, neither of which describe Lance, but since the information includes the measured osmolality we should check this. You know, Chekhov’s gun and all.
2 x Na + Glucose / 18 + BUN / 2.8 + Ethanol / 4.6 = calculated osmolality
2 x 138 + 96 / 18 + 14 / 2.8 + 0 / 4.6 = 286
Osmolar gap = measured osm – calculated osm

Osmolar gap = 292 – 286 = 6

This is a normal osmolar gap. Poor foreshadowing by the question writer.

Step five

If there is an anion gap, what was the bicarbonate before the anion gap? To calculate the bicarbonate before, take the anion gap, subtract 12 and add that to the current bicarbonate:

Bicarbonate before the anion gap = Bicarbonate + (Anion gap -12)

Bicarbonate before the anion gap = 8 + (16 –12)
Bicarbonate before the anion gap = 12

So the bicarbonate before the anion gap was 12 indicating a large non-anion gap metabolic acidosis and a relatively mild anion gap metabolic acidosis.

Step six

If there is an NAGMA, what is the urinary anion gap? What does it mean? The patient has a NAGMA as discovered in step 4. The differential of NAGMA is:

  1. chloride intoxication
  2. GI losses
  3. RTA

The patient doesn’t seem to be suffering from chlorine gas intoxication or have an isotonic saline drip running so number one is not likely.

The low potassium could indicate GI losses as well as type 1 or 2 RTA. The urine anion gap in the face of severe metabolic acidosis will help here. In GI losses and chloride intoxication the urine amnion gap will be negative, in RTA it should be positive.

Urine anion gap = (Na + K) – Cl

Urine anion gap = (56 + 32) – 78

Urine anion gap = + 10

The positive anion gap indicates a lack of NH4+ in the urine. In diarrhea, the kidney will up ammonium excretion to get rid of the acid load. The increase cation load in the urine will be balanced by an increased in chloride in the urine. The increase Cl– will make the urine anion gap negative (in reality it is an unmeasured cation, or a positive cation gap, but by convention we use an anion gap). The positive urinary anion gap is the face of a severe acid load indicates a renal tubular acidosis.

Put it all together

This patient has a well compensated metabolic acidosis. The metabolic acidosis is partly anion gap and non-anion gap. The non-anion gap is a distal RTA. The AGMA may be a lactici acidosis from the neoplasm as these are not uncommon in metastatic neoplastic disease.

The chief complaint of kidney stones points to type 1 RTA. Patients with testicular cancer receive platinum-containing chemotherapy. Platinum can cause proximal or distal RTA. However, proximal RTA is not associated with kidney stones. So I suspect this  is classic distal RTA due to platinum.

Coal Miner

The set up

Picture by Nicolas Holzheu

Coal miner presents to the ED with fever and vomiting

pH 7.23
pCO2 67
pO2 88
Na 144
Cl 96
BUN 8
K 3.2
Bicarb 27
Creatinine 0.6
glucose 128

Step one: determine the primary disorder

the pH is down, the HCO3 and CO2 are up so this is a respiratory acidosis

Step two: check to see if the compensation is appropriate

The CO2 is 67, since his chief complaint is not respiratory and he is a coal miner we will assume black lung and chronic COPD. So we will use the estimate for chronic respiratory acidosis
67 is almost 30 above normal pCO2, and for every 10 the CO2 rises the HCO3 should go up 3 (1 is this was acute). So a pCO2 of 67 should have a HCO3 of 2.7 x 3 = 8.1 above a normal bicarb of 24 = 32.1.
His actual bicarb is 27 so he has an additional metabolic acidosis (bicarb lower than predicted means metabolic acidosis).

Step three: if there is a metabolic acidosis what is the anion gap

The patient has a metabolic acidosis, so the anion gap is relevant. We calculate it and it is 21.

Step four: if there is an anion gap, calculate the bicarbonate before

The patient has an anion gap so to calculate the bicarbonate before the anion gap we subtract 12 from the calculated anion gap and add the difference to the current bicarbonate:
21-12 = 9 add that to the bicarbonate of 27 to get a bicarbonate of 36. This is higher than the predicted compensated bicarbonate from step two (32.1) so the patient has an additional metabolic alkalosis.

Final step: put it all together

The patient has black lung and COPD. His largest acid-base disorder is chronic respiratory acidosis. He does have an acute illness. This illness is causing an anion gap metabolic acidosis. Sepsis and multi organ failure does this. Prior to developing the anion gap the vomiting caused a metabolic alkalosis.
Its a triple disorder!