Metabolic Alkalosis

Definition: Ý pH due to Ý plasma [HCO₃-] associated with an Ý arterial pCO₂

Etiology:

(1) excessive loss of acid: extra-renal (GI tract) or renal
(2) excessive gain of [HCO₃-]

Compensatory Mechanisms

(1) Chemical buffering – buffers 33% of an alkali load.

Intracellular H⁺ + HCO₃^- Þ H2CO₃- Þ H₂O + CO₂

Ý lactate production

(2) Respiratory compensation – Recall, [H+] = PCO₂/[HCO₃-]

Hypoventilation Þ Ý in PCO₂ Þ brings [H+] toward normal range but NOT into normal range

Mechanism limited by hypoxemia pCO₂ usually does not exceed 60mmHG.

(3) Renal response – major regulatory mechanism protecting against metabolic alkalosis.

Excess HCO₃- generally promptly excreted.
Metabolic alkalosis persists only when renal HCO₃- excretion is impaired.

Renal HCO₃ reabsorption regulation

Plasma HCO₃- : 23-26 mEq/L

Physiology: ALL HCO₃^- filtered is reabsorbed in proximal (85%) and distal (15%) nephron.

If HCO₃^- filtration exceeds tubular maximum (Tm) for HCO₃- absorption than Excess HCO₃- is excreted in urine

Factors affecting renal HCO₃- reabsorption

Ý HCO₃- reabsorption:

Extra-cellular fluid (ECF) volume contraction: Volume depletion induces sympathetic activity Þ 3 effects:

(1) Angiontension II release: Because of ß blood volume Þ AgII release Þ Ý Na/H exchange (proximal tubule) Þ HCO₃- is concurrently reabsorbed as NaHCO₃-.

(2) Aldosterone release: 3 effects

(a) Ý Na+ reabsorption – Na/K exchange (distal tubule principal cell) to Ý H₂O retention Þ Ý ECF

(b) Ý K+ secretion – Na/K exchange (distal tubule principal cell) to Ý urine K+ Þ ß serum K+

(3) Urinary ß Cl- : Cl-/HCO₃- exchanger exists in prox tubule. HCO₃- absorption causes Cl- excretion into urine

When ECFV is depleted, the prox tubule will still reabsorb HCO₃- despite alkalosis. Contraction alkalosis

Angiotensin II also vasoconstricts Þ ß renal blood flow Þ ß in GFR

ß GFR Þ ß filtration of bicarbonate Þ ß HCO₃- in proximal lumen Þ stimulation of HCO₃- resorption

Hypokalemia

Hypercapnia Ý in PCO₂ Þ Ý proximal reabsorption

Ý mineralocorticoid (MC) secretion: Ý aldosterone directly stimulates H+ ATPase – see above

ß HCO₃- reabsorption:

Ý GFR or ECF volume

Hyperkalemia

Hypocapnia

ß MC secretion

Production of a metabolic alkalosis

Requirements:

Generate new HCO₃^-
Maintain increased HCO₃^- by reducing renal excretion

(1) GENERATION of a metabolic alkalosis

Loss of acid:

Extra-renal: Fluid loss will only CAUSE a Met alkalosis if fluid is HCO₃- free. Vomiting: direct loss of H+ via HCL

Renal: in the presence of:

MC excess: primary or secondary hyperaldosteronism: Aldosterone directly stimulates H+-ATPase Þ H+ loss Þ alkalosis

Distal Na+ delivery : Diuretics (thiazide or loop): inhibit Na resorption in loop of Henle and distal tubule Þ excess Na is reclaimed in collecting tubule (principal cells) because of aldosterone release (Ý by fluid loss). Reabsoprtion of cationic Na creates a lumen-negative electrical potential Þ favors the retention of H+ secreted into distal lumen by H+ATPase and K,H+ ATPase

Hypokalemia : transcellular cation shift: K+loss (extracellular) Þ diffusion of K+ out of cell Þ movement of extracellular H+ and Na+ into the cell (maintain electroneutrality) Þ intracellular acidosis, extracellular alkalosis Þ stimulate bicarbonate resorption and ammonium excretion Þ alkolosis

Gain of HCO₃^- : coupled with ß renal excretion.

Exogenous – administered HCO₃-
Endogenous – oxidation of ketone bodies or lactate

(2) MAINTENANCE of a metabolic alkalosis : Abnormal retention of HCO₃- by Kidney.

ß GFR (unable to excrete HCO₃-) or ß ECF volume : Na/H exchange is augmented Þ loss of H+

Hypokalemia

Hypercapnia

Ý MC secretion

Syndrome	Generation	Maintenance
MC excess, Vol Ý primary hyperaldosteronism, Cushing’s syndrome	Renal	ß K+, Ý MC
MC excess, Vol ß Vomiting, Diuretics	Gastric, Renal	ß ECF, ß K+
Alkali load	Alkali load	ß ECF or GFR
Edematous states	Renal	ß ECF ß K+

Clinical Features

Nonspecific

Volume depletion: weakness, postural dizziness

Hypokalemia: polyuria, polydipsia, muscle cramps

Diagnosis

very useful to measure Cl^- excretion

Key Question to ask: Why is the kidney abnormally retaining bicarbonate? How is the alkalosis being MAINTAINED?

Alkalosis maintained by:

(1) ß ECF volume : ß ECF vol results in avid Na⁺ retention Þ Cl^- absorbed with Na+ Þ Urinary CL- less than 10 mEq/L

Cl^- responsive (saline responsive): condition responsive to treatment of NaCl administration as 0.9% NaCl

(2) ß K+ or Ý M.C. : ECF normal or increased Þ No stimulus to Na+ retention Þ Urinary Cl- greater than 10 mEq/L

Cl^- is an indicator of volume status

Why not measure urinary Na?

Na not as stable indicator of volume status as Cl. If a patient is acutely vomiting, the excess HCO₃- will bind to Na+ and be dumped into urine. Patient will have a paradoxical Ý in urine Na instead of the expected ß urinary Na seen with volume depletion.

Differential diagnosis

Urine Cl- < 10 mEq/L - (Cl- responsive): ß ECF volume

GI acid losses: Vomiting, NasoGastric drainage

Diuretic therapy (remote > 48 hours) : Ý distal Na delivery

Urine Cl- > 10 mEq/L - (Cl- resistant)

MC excess (volume expansion):

Primary hyperaldosteronism

Cushing's Syndrome

Ectopic ACTH

Secondary hyperaldosteronism: Renovascular disease, malignant HTN, CHF (with diuretics), Cirrhosis

Severe hypokalemia : from any cause

Therapy – Volume status and urinary Cl- dictate appropriate therapy

Volume depletion ß Urine Cl- : Restore ECF volume with saline.

MC excess, ß K⁺; Ý urine Cl- :

(1) Correct K⁺ deficits
(2) Inhibition of MC action

Spironolactone - aldosterone antagonist
Surgery