A woman with vomiting & muscle weakness

Clinical Details

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.
Arterial Blood Gases
pH ------------ 7.31
pCO2 mmHg ---- 26 mmHg
pO2 mmHg ----- 87 mmHg
HCO3 mmol/l---- 13 mmol/l

Firstly, initial clinical assessment:

The most glaring result is the serious hypokalaemia which is responsible for the severe muscle weakness. Correction of this problem is the highest priority in the care of this patient and 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
  • metabolic acidosis due to dehydration with pre-renal renal failure.
Secondly, the acid-base diagnosis:

1. pH: The acidaemia indicates an acidosis is present

2. Pattern: The low bicarbonate & low pCO2 indicate a metabolic acidosis with respiratory compensation. A respiratory alkalosis is excluded by the acidaemia & because the bicarbonate is lower then the lower limit (18mmol/l) of compensation with this disorder.

3. Clues: The anion gap is normal. The delta ratio is zero. Both these indicate a normal anion gap acidosis. Hyponatraemia is present. There is no renal failure.

4. Compensation: The pCO2 expected at maximal compensation (by rule 5) for a metabolic acidosis is (1.5 x 13 + 8) = 27.5mmHg. The actual pCO2 is 26mmHg and sufficient time has passed so we conclude that maximal respiratory compensation is present & there is no evidence of a respiratory acid-base disorder. The absence of a respiratory acid-base disorder is consistent with the clinical evidence of adequate ventilation despite the peripheral muscle weakness.

5. Formulation: A normal anion gap acidosis is present but the chloride is within the normal range. As mentioned previously, the terms ‘normal anion gap acidosis’ and ‘hyperchloraemic acidosis’ are used as though they were synonomous but this is not strictly correct. In the presence of hyponatraemia (for example), a normal anion gap acidosis may occur without the chloride being elevated out of the usual reference range. In effect, the chloride can be considered to be elevated relative to the value which would be appropriate for a low [Na+]. The low [Na+] means that fewer Cl- are required to replace HCO3- to maintain electroneutrality.

6. Confirmation: The cause of the disorder has not been determined and further specific investigations will be required to confirm the diagnosis. For example, if urine pH is >5.5 despite the bicarbonate being <15mmol/l then the diagnosis of a type 1 RTA is established.

Finally, the Clinical Diagnosis:

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 & 20 mmol/l

Type 1 is distal RTA. The major causes can be grouped as hereditary defects, autoimmune disorders, some drugs, obstructive uropathy & 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:

infusion of mineral acid (eg HCl infusions, NaCl infusions where Cl- replaces a lost organic acid anion, use of acidifying salts such as NH4Cl)

in a less severe disorder which would ordinarily result in a high anion gap acidosis (eg lactic acidosis when the lactate level is not high enough to result in marked elevation of the anion gap)
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.