A 49 year old woman was admitted to a medical ward because of severe vomiting and marked muscle weakness. She had been unwell for two weeks following a fall. Four days before presentation, she had developed abdominal discomfort with vomiting. The vomiting was severe and oral intake was poor. She said she had lost a significant amount of weight. She felt very weak, was anorexic and lethargic and had a dry mouth. She did not have diarrhoea or urinary symptoms. There was no significant past medical illness and she was on no medication. There was no family history of inherited inborn errors of metabolism.
She was afebrile but looked ill. BP 110/60 (sitting). Pulse 84/min and regular. Respiratory rate 18/min. Chest was clear. Heart sounds were normal. Slight abdominal tenderness on deep palpation was present in the right iliac fossa. Deep tendon reflexes were 1+ and muscle power was graded as 4/5. Sensation was normal.
Initial pathology: Na+ 128, K+ 1.6, Cl- 103, HCO3- 12.5, Glucose 9.9, urea 9.2, creatinine 0.12 mmol/l and total protein was 89 g/l. Anion gap 12. Amylase was within the normal range.
When pathology results became available, she was transferred to ICU for fluid and K+ replacement under ECG monitoring. On admission, it was noted that she was unable to lift her legs from the bed and her grip was weak. She was awake and alert.
The most glaring result is the serious hypokalaemia which is responsible for the severe muscle weakness. Correction of this problem is the highest priority and should be commenced without delay.
The history suggests the possibility of several disorders which should be considered: metabolic alkalosis due to vomiting (esp as vomiting severe and of four days duration), lactic acidosis due to poor perfusion related to dehydration with resp compensation (resp rate of 18/min), respiratory acidosis due to respiratory muscle weakness (but less likely due to high resp rate and good air entry), muscle weakness due to hypokalaemia from the metabolic alkalosis, and metabolic acidosis due to dehydration with pre-renal renal failure.
A normal anion gap acidosis can result from 2 major sites: the bowel or the kidneys. There is no diarrhoea or other bowel abnormality that would suggest a bowel source for the acidosis. This leaves a default site of the kidneys which means a default diagnosis of renal tubular acidosis. The normal urea & creatinine, and the normal anion gap exclude renal failure as a cause for the acidosis. We need to confirm the diagnosis and to search for a cause.
Type 4 RTA is associated with hyperkalaemia and is caused by low aldosterone levels. The hypokalaemia excludes this type here.
Type 2 is proximal RTA. This is usually associated with multiple proximal tubular defects and there is no evidence of these other defects at present. Once established the urine pH is below 5.5 and plasma bicarbonate is usually between 15 and 20 mmol/l
Type 1 is distal RTA. The major causes can be grouped as hereditary defects, autoimmune disorders, some drugs, obstructive uropathy and disorders which cause nephrocalcinosis. There was no evidence of any of these at this initial presentation. In there is no obvious cause, a autoimmune disorder should always be sought using appropriate laboratory investigations. Treatment is with oral NaHCO3 (1-4 mmol/kg/day) to correct the Na+ deficit and restore the extracellular fluid volume. The aldosterone levels then fall and the hypokalaemia will correct. K+ supplements are usually then not required but sodium or potassium citrate solutions can be useful if hypokalaemia is present. Also, the citrate will bind Ca++ in the urine and this assists in preventing renal stones which can be a problem.
Finally, a normal anion gap acidosis can result in two other ways:
Subsequent investigation in this patient confirmed a diagnosis of distal renal tubular acidosis (type 1 RTA). The patient subsequently developed Sjogren’s syndrome, an autoimmune disorder which is a known cause of distal RTA. In this patient, the RTA was the first evidence of the condition which was not diagnosed until some months after this initial presentation.