Acid-Base Physiology

Case 31: A man with hypokalaemic paralysis

added 05Sep2015 (This case report is from Sunder et al - see reference below)

Clinical Details

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.

Arterial Blood Gases

pH 7.20

pCO2 31 mmHg

pO2 104 mmHg

HCO3 12.5 mmol/l


First: Initial clinical assessment

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.

Second: The acid-base diagnosis

Proceeding systematically:

  1. pH: The acidaemia indicates an acidosis
  2. Pattern: The combination of a low bicarbonate and a low pCO2 (in the presence of a known acidosis) indicates metabolic acidosis.
  3. Clues: Anion gap = 143 - 120 - 12.5 = 10.5 (i.e. normal). The delta ratio is (10.5 - 12)/(24 - 12.5) = -0.13 (i.e. <0.4) indicating a 'pure' NAGMA (i.e. no co-existent high anion gap metabolic acidosis.) There is no evidence of renal failure. Significant hyperchloraemia is present, as expected with a significant NAGMA. The UAG is useful to distinguish the location of the cause of a NAGMA: it is negative with GIT causes (such as diarrhoea), and positive with renal causes. The positive UAG result (+30) here indicates renal pathology, as does the significant proteinuria. Significant proteinuria will decrease the plasma albumin level, and decrease the normal value of the anion gap; this would explain the negative value of the delta ratio, as the standard AG value of 12 is used in the delta ratio formula.
  4. Compensation: For a metabolic acidosis, (rule 5) is used: The expected pCO2 is [(1.5 x 12.5)] + 8) = 27 mmHg. The actual pCO2 is 32 mmHg; this slightly higher than expected level indicates a mild respiratory acidosis. (The proviso is that "sufficient time" (12-24 hours) has elapsed for respiratory compensation to reach its maximum value).
  5. Formulation: A hyperchloraemic or normal anion gap metabolic acidosis (NAGMA) with a mild respiratory acidosis.
  6. Confirmation: Further investigations are required to find the renal cause of the NAGMA. Urine pH would have been useful.

Finally: the Clinical Diagnosis

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.)

1. A normal anion gap metabolic acidosis with hypokalaemia, high urine pH (>5.5) and a positive UAG occurs with distal renal tubular acidosis
2. The fractional excretion of bicarbonate following a bicarbonate infusion (to raise towards normal) is used to distinguish between proximal RTA and distal RTA
3. Urinalysis for glucose, ketones, protein and pH should be done in all patients with suspected acid-base disorders


  1. Sunder S et al. A rare case of type 1 renal tubular acidosis with membranous nephropathy presenting as hypokalaemic paralysis