Metabolic Alkalosis

Question 1

Metabolic Alkalosis - Liddle’s Syndrome

Answer 1

Liddle’s syndrome

Liddle’s syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.

Treatment is with either amiloride or triamterene

Example Question:

A 32 year-old man is referred by his GP after collapsing while at work. He does not remember the episode but witnesses say that there was no incontinence or fitting and the patient does not have a sore mouth or tongue. This is the first time this has happened and the patient does not have any other past medical history of note and takes no regular medication.

Examination reveals a blood pressure of 162/95 mmHg, a pulse of 74 beats per minute, a respiratory rate of 16 and a temperature of 37.4ºC. Heart sounds 1 and 2 are present with no added sounds, the lung fields are clear and his abdomen is soft and non-tender.

Blood tests performed and reveal:

Na+ 143 mmol/l 
K+ 3.0 mmol/l 
Urea 5.6 mmol/l 
Creatinine 76 µmol/l 
Bicarbonate 31 mmol/l 
Renin low 
Aldosterone low 

Which of the following is the best treatment?

 > Amiloride 
 Bumetanide 
 Spironolactone 
 ACE inhibitor 
 Angiotensin II receptor blocker 

This man has Liddle’s syndrome, an autosomal dominant disorder characterised by hypertension associated with hypokalaemic metabolic alkalosis, low plasma renin activity, and suppressed aldosterone secretion. Amiloride is the best treatment for the hypertension and hypokalaemia as it acts on the sodium channels directly, as opposed to spironolactone, which acts on mineralocorticoid receptors.

Question 2

Metabolic Alkalosis - Causes

Answer 2

= LOSS OF [H+] OR GAIN OF [HCO3-]

May be caused by loss of Hydrogen ions or a gain of bicarbonate

Mainly due to problems of kidney or GI tract

Causes:

• vomiting/aspiration (eg peptic ulcer leading to pyloric stenosis, nasogastric suction)
• diuretics
• liquorice
• carbenoxolone
• hypokalaemia
• primary hyperaldosteronism
• cushing’s syndrome
• bartter’s syndrome
• gitelman’s syndrome
• liddle’s syndrome
• congenital adrenal hyperplasia

Question 3

Mechanism of Metabolic Alkalosis

Answer 3

Activation of RAAS = KEY

Aldosterone - causes reabsorption of Na+ in exchange for H+ in DCT

ECF (extracellular fluid) depletion eg in vomiting/diuresis > Na+ and Cl- loss > Activation of RAAS
> Increased aldosterone levels

In Hypokalaemia, K+ shift from cells > ECF
Alkalosis is caused by shift of H+ into cells to maintain neutrality