Question 5

College Answer

1.  Compensated respiratory alkalosis, or else a respiratory alkalosis superimposed on

a normal anion gap metabolic acidosis.

2.  Most likely rhabdomyolysis secondary to severe hypokalaemia. We need to examine muscle compartments, and measure the plasma CK.

3.  The mild metabolic acidosis may just be compensatory for her respiratory alkalosis. However, it could be a primary process (with a separate superimposed respiratory alkalosis from anxiety for example) in which case it is more consistent with enteric potassium loss, or else a proximal (Type 2) renal tubular acidosis. However urinary potassium loss of 18 mmol / day is low, and close to the obligatory minimum. Therefore bowel loss is more likely, or else transcellular potassium shifts (periodic paralysis). The persistent hypokalaemia after 24 hours of aggressive replacement makes periodic paralysis unlikely, as is the fact that this is the first episode. Apart from that, the absence of metabolic alkalosis and urinary potassium wasting are against Cushing’s and Conn’s syndromes as well as diuretic abuse, and the absence of hypertension is also against Cushing’s and Conn’s syndrome. Therefore on balance and with the history of diarrhoea, bowel loss is the most likely.

Bowel loss (eg villous adenoma, aperient abuse)

Diuretic abuse

Conn’s syndrome

Cushing’s syndrome

Periodic paralysis.

Renal tubular acidosis

Discussion

Let us dissect these results systematically.

1. The A-a gradient cannot be calculated
2. There is no acidaemia
3. The PaCO₂ suggests a compensatory respiratory alkalosis
4. The SBE is -6, suggesting a metabolic acidosis
5. The respiratory compensation is excessive; the expected PaCO2(17 × 1.5) + 8 = 33.5mmHg, and thus there is definitely also a respiratory alkalosis
6. The anion gap is normal:
   (144) - (119 + 17) = 8, or 10.9 when calculated with potassium

The urinary potassium loss is also normal, suggesting that gastrointestinal potassium losses must account for this hypokalemia.

Thus: this is a normal anion gap metabolic acidosis with respiratory alkalosis.

Let us leave the respiratory alkalosis well alone for the moment.

There are several differentials  for NAGMA.

The college asks for an explanation of the raised enzyme levels. The LDH and AST are not exclusively hepatic enzymes; they can also leak from damaged muscle, and the lady has presented with weakness, which might suggest that she is suffering from hypokalemia-associated rhabdomyolysis (though unless I am grossly mistaken, damaged muscle should also leak potassium, resulting in hyperkalemia). Certainly a CK an urinary/serum myoglobin levels will set this matter straight.

Differential diagnosis of hypokalemia is discussed at lengths elsewhere.

Below is a table of differentials which is organised according to the findings of investigations.

Causes of Hypokalemia

Low urinary potassium Diarrhoea Laxative abuse Insulin therapy Bicarbonate therapy Periodic hypokalemic paralysis High urinary potassium with acidosis Distal tubular acidosis (Type 1) Proximal tubular acidosis (Type 2) Diabetic ketoacidosis

High urinary potassium with alkalosis Diuretics Gastrointestinal secretion losses (eg. vomiting, excessive NG suction, etc) Bartter syndrome Gitelman syndrome Derangement of renin-aldosterone axis Low renin, high aldosterone Primary hyperaldosteronism High renin, high aldosterone Cardiac failure Renal artery stenosis Renin-secreting tumours Low renin, low aldosterone Adrenal hyperplasia Cushing syndrome Exogenous corticosteroid excess Liddle syndrome Cushings disease Exogenous corticosteroid excess Adrenal hyperplasia

This lady falls into the "low urinary potassium" category, which suggests that the potassium losses are occurring though the gut. Familial hypokalemic periodic paralysis is not out of the question, but this tends to start in adolescence so its unlikely.

The absence of alkalosis and hypertension steers the candidate away from thinking about the derangements of the renin-angiotensin-aldosterone axis. There is a normal anion gap metabolic acidosis present, which could be contributing to the picture. Of the possibilities, one may focus most on Type 1 and Type 2  renal tubular acidosis, seeing as Type 4 renal tubular acidosis tends to cause hyperkalemia instead. Of course, in all forms of hypokalemic RTA, the renal potassium losses are significant, and one would not have such a tiny 24-hour urinary K⁺ level. And on top of that the hypokalemic forms of RTA tend to present with profound acidosis - the pH would be very abnormal and the HCO₃^- would be very low.

Singhal, P. C., et al. "Hypokalemia and rhabdomyolysis." Mineral and electrolyte metabolism 17.5 (1990): 335-339.

 

Assadi, Farahnak. "Diagnosis of hypokalemia: a problem-solving approach to clinical cases." Iranian journal of kidney diseases 2.3 (2008): 115-122.

 

Weiner, I. David, and Charles S. Wingo. "Hypokalemia--consequences, causes, and correction." Journal of the American Society of Nephrology 8.7 (1997): 1179-1188.

 

Links, Thera P., et al. "Familial hypokalemic periodic paralysis: clinical, diagnostic and therapeutic aspects." Journal of the neurological sciences 122.1 (1994): 33-43.

 

Gennari, F. John. "Hypokalemia." New England Journal of Medicine 339.7 (1998): 451-458.

 

Huang, Chou-Long, and Elizabeth Kuo. "Mechanism of hypokalemia in magnesium deficiency." Journal of the American Society of Nephrology 18.10 (2007): 2649-2652.