Metabolic Alkalosis

Abnormal ↑ in plasma bicarbonate. Sustained metabolic alkalosis requires both a process for:

A maintenance process is required because renal bicarbonate excretion is highly efficient, such that a transient alkali load (e.g. an IV bolus of bicarbonate) will result in a rapid ↑ in urinary bicarbonate excretion and restoration of normal plasma pH.

This is the therapeutic mechanism behind urinary alkalinisation.

• Initiation
  • Alkali gain
    • Exogenous
      e.g. Bicarbonate, citrate, RRT.
    • Endogenous
      e.g. Ketones.
  • Acid loss
    • Renal
      e.g. Diuretics.
    • Gut
      e.g. Vomiting.
• Maintenance
  • Hypochloraemia
    Results in ↑ bicarbonate reabsorption despite alkalosis, in order to maintain electroneutrality.
  • Hypokalaemia
    Less common and typically milder than chloride depletion.

Aetiology

Causes of Metabolic Alkalosis

Acid Loss	Alkali Gain
Urinary: Diuretics Loop and thiazide diuretics ↓ chloride reabsorption. Licorice (glycyrrhizin) Chloride loss “Contraction alkalosis” occurs due to loss of chloride rather than volume, as HCO3- secretion is inhibited by insufficient available Cl^- for anion exchange. Mineralocorticoid effects ↑ Na+ reabsorption in exchange for K+ and H+. Severe hypokalaemia Hypomagnesaemia Magnesium is reabsorbed in exchange for potassium, which prolongs ↓ K+. Corticosteroids Cushing’s syndrome Primary hyperaldosteronism Bartter’s syndrome Hyperplasia of the juxtaglomerular apparatus, ↑ renin and aldosterone secretion. Inhibits conversion of cortisol to cortisone, which has a mineralocorticoid effect. Gitelman syndrome Autosomal recessive disease causing renal potassium and magnesium wasting.	Exogenous: Iatrogenic Sodium bicarbonate β-lactams Sodium citrate Blood RRT anticoagulation High SID RRT Milk alkali syndrome Consumption of vast quantities of calcium and alkali, leading to alkalosis: Directly From the alkali. Indirectly From the calcium, as the ↑ UO secondary to hypercalcaemia leads to hypovolaemia, ↓ GFR, and ↓ bicarbonate clearance. Antacids
Enteric: Vomiting Pyloric stenosis NG suction Chloride loss Laxative abuse Diarrhoea causes substantial K+ loss; consequently renal K+ resorption is ↑ in exchange for NH4+. Villous adenoma

Mineralocorticoid excess also ↑ HCO₃^- loss equivalent to the ↑ H⁺ load.

Milk alkali syndrome is mostly a relic when of a bygone age, when milk and cream was cutting-edge therapy for peptic ulcers.

Pathophysiology

Adverse effects of metabolic acidosis include:

• B
  • Hypoventilation
    • Atelectasis
• C
  • Arrhythmias
  • ↓ Inotropy
• D
  • Vasospasm
  • Seizures
  • Confusion
  • Cramps
• F
  • Electrolyte derangements
• H
  • ↑ Hb oxygen affinity

Management

Specific therapy:

Normal saline has a number of mechanisms of action:

• Diluting ECF with a low SID fluid
  
• Reversing volume depletion
  ↓ Renal sodium reabsorption, which ↑ SID and causes contraction alkalosis.
• Provides chloride
  Reabsorbed in preference for bicarbonate, aiding renal bicarbonate elimination.

• Pharmacological:
  • Chloride volume resuscitation
  • Correct hypokalaemia
  • Correct hypoalbuminaemia
  • Acetazolamide
• Physical
  • RRT

Hydrochloric acid infusions are also described for metabolic alkalosis refractory to more pedestrian therapies.

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References

1. Brandis, K. Acid-base pHysilogy. 2015.
2. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
3. Medarov BI. Milk-Alkali Syndrome. Mayo Clinic Proceedings. 2009;84(3):261.
4. Luke RG, Galla JH. It Is Chloride Depletion Alkalosis, Not Contraction Alkalosis. J Am Soc Nephrol. 2012;23(2):204-207. doi:10.1681/ASN.2011070720