History: A 20 year old man presented with sudden onset of muscle weakness in arms and legs. Only other recent history was of intermittent swelling of both legs over the previous 2 months. There were no other neurological abnormalities, in particular his level of conscioussness was normal, there was no fitting, bowel or bladder symptoms, or sensory abnormalities.
Examination: Muscle weakness was confirmed: power was 1/5 in legs, and 2/5 in arms, with decreased tendon reflexes. There were no cranial nerve or sensory abnormalities.
Investigations: Biochemistry on admission: Na+ 143, K + 2.0, Cl- 120, glucose 4.89, and creatinine 0.11 (all results in mmol/l). Serum albumin was low (21 g/l). Urinalysis: 3+ protein, 0 glucose. Urine anion gap = 70+25-65 = 30. Hb was 108 g/l. Arterial blood gases were collected on arrival.
The degree of muscle weakness is consistent with the severe hypokalaemia. This requires urgent correction with KCl supplements in a supervised hospital setting. Respiratory muscle weakness can cause respiratory acidosis due to decreased alveolar ventilation.
This man has a NAGMA due to a renal cause. Hypokalaemia is the cause of the paralysis and requires urgent correction.
This man had membranous nephropathy (diagnosed on renal biopsy) causing nephrotic syndrome, hypokalaemia and distal (or type 1) renal tubular acidosis. Distal RTA occurs when the kidneys are unable to maximally acidify the urine. Typically with distal RTA, urine pH is inappropriately high (> 5.5) despite severe acidaemia ([HCO3] < 15 mmol/l). As a generalisation, significant glomerular disease is associated with a low GFR and a high anion gap acidosis; and significant tubular disease is associated with a normal GFR and a normal anion gap acidosis. This interstitium in this patient was reported as showing "mild mononuclear cell infiltrate and fibrosis with tubular involvement" so tubular/interstitial pathology was indeed present. There was no azotaemia so a high anion gap from a renal cause is not present.
In this patient following IV infusion of bicarbonate, the fractional excretion of bicarbonate was 2% This test distinguishes between proximal RTA (>15% expected) and distal RTA (<5% expected). On ultrasound, this patient had normal sized kidneys with medullary nephrocalcinosis further indicating distal RTA. (Nephrocalcinosis is not present with proximal RTA.)
The causes of hypokalaemic paralysis are generally divided into 2 groups: hypokalaemic periodic paralysis (causing shift of K+ into cells), or secondary hypokalaemic paralysis (typically due to excessive K+ loss via bowel or kidneys.)