Question 18.2

A 28-year-old female presented to the Emergency Department with general malaise. The following results are obtained from blood and urine respectively:

Parameter	Patient Value	Adult Normal Range
Blood Results:
FiO2	0.21
pH	7.29*	7.35 – 7.45
pO2	106 mmHg (14 kPa)
pCO2	26.0 mmHg (3.5 kPa)*	35.0 – 45.0 (4.6 – 6.0)
SpO2	97%
Bicarbonate	12.0 mmol/L*	22.0 – 26.0
Base Excess	-13.0 mmol/L*	-2.0 – +2.0
Sodium	137 mmol/L	135 – 145
Potassium	0.9 mmol/L*	3.5 – 5.0
Chloride	119 mmol/L*	95 – 105
Glucose	8.1 mmol/L*	3.5 – 6.0
Phosphate	0.3 mmol/L*	0.8 – 1.5
Urine Results:
pH	7.50
Sodium	36 mmol/L*	10 – 20
Potassium	37 mmol/L*	5 – 15
Chloride	22 mmol/L	20 – 40

Describe the acid base abnormality on the blood results. (10% marks)

Give three potential causes of these findings with a rationale for your answer.
(15% marks)

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College answer

a) There is a non-anion gap metabolic acidosis.

b)   Likely causes
1.   Type 1 or 2 Renal Tubular Acidosis (High urinary pH)
2.   Salt wasting nephropathies (high urinary Na)
3.   Diuretic use/abuse (High urinary Na and K, low K and Phos)
4.   Conns (High urinary Na and K, low plasma K)

Discussion

Let us dissect these results systematically:

1) The A-a gradient is essentially normal:
(0.21 x 713) - (26 x 1.25) - 106 = 11.23 mmHg

2) There is an acidaemia, which is mild.

3) The CO₂ is appropriately low

4) There is a metabolic acidosis (the SBE is -13)

5) The respiratory compensation is appropriate: (1.5 × 12) + 8 = 26 mmHg, or (40 - 13) = 27 mmHg, depending on which formula you use.

6) The anion gap is (137) - (119 + 12) = 6, or 6.9 when calculated using the absurdly low potassium value. To calculate the delta ratio would therefore be pointless.

7) The urinary anion gap is (36+37) - 22 = 51, i.e. it is a positive urinary anion gap. This suggests a renal cause of the acidosis. A negative (neGUTive) anion gap would suggest that gastrointestinal causes of NAGMA are in play, as the kidneys are doing their job. However, the combination of low urinary chloride and a urinary pH higher than the serum pH suggests that clearly they are not.

Additional findings include a low phosphate and a higher than expected glucose.

So, what are the possible renal-related reasons for a NAGMA?

Acetazolamide use (loop diuretic abuse would usually produce a metabolic alkalosis)
Normal saline intoxication (but this does not explain the potassium or the kidney's failure to excrete the chloride load)
Renal failure (but the phosphate and potassium would be higher)
Renal tubular acidosis Type 1 (distal) or Type 2 (proximal)
Ureteric diversion would explain the urinary electrolytes, but why would this young woman have this?

The inclusion of Conn's syndrome, or primary aldosteronism, is somewhat unexpected, as the excess of aldosterone (and therefore the increased activity of sodium-reabsorbing eNaC channels in the collecting duct) is actually expected to cause a decrease in the urinary sodium concentration. So much so in fact that the change in the ratio of serum to urinary sodium has been used as a cheap tool to screen for Conn's syndrome (Willenberg et al, 2009).

References

Willenberg, H. S., et al. "The serum sodium to urinary sodium to (serum potassium) 2 to urinary potassium (SUSPPUP) ratio in patients with primary aldosteronism." European journal of clinical investigation 39.1 (2009): 43-50.

Kraut, Jeffrey A., and Nicolaos E. Madias. "Metabolic acidosis: pathophysiology, diagnosis and management." Nature Reviews Nephrology 6.5 (2010): 274-285.

Fencl, Vladimir, et al. "Diagnosis of metabolic acid–base disturbances in critically ill patients." American journal of respiratory and critical care medicine162.6 (2000): 2246-2251.

Moviat, M. A. M., F. M. P. Van Haren, and J. G. Van Der Hoeven. "Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis." Critical Care 7.3 (2003): R41.

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