Metabolic Alkalosiscauses, clinical features, diagnosis, and

management.

Alex YartsevDerived largely from Brandis

The concept of pHpH = - log10 aH+

Where aH+ is the activity of the H+ ion at the glass electrode in the ABG machine

• “ a dimensionless representation of the H+ concentration”

• i.e. the higher the pH, the lower the H + concentration.

• Pure water is neutral: pH of 7• Thus, it has 0.0000001 moles of hydrogen ion

per litre

'Acid-base pHysiology' by Kerry Brandis - from http://www.anaesthesiaMCQ.com

What does pH mean anyway? • 1909, Dr. Søren Peder Lauritz

Sørensen– used the term to refer to the negative log of the hydrogen ion concentration, hence the H.

• He decided to call it “Wasserstoffionenexponent”

• To this day, there is debate as to what the “p” in pH actually means – looks like Dr Sorensen’s electrodes were arbitrarily named “p” and “q”

Sørensen, S. P. L. (1909). Enzymstudien. II: Mitteilung. Über die Messung und die Bedeutung der Wasserstoffionenkoncentration bei enzymatischen Prozessen; Biochemische Zeitschrift 21: 131–304.Nørby JG. (2000) The origin and meaning of the little p in pH. Trends in Biochemical Sciences 25: 36-37.

The physiological range of pH

7. 45

7.35

Above 7.45 = alkalosis

7.45 to 7.35 – normal range

Below 7.35 = acidosis

Definition of alkalosis• an abnormal process or condition which would raise arterial

pH if there were no secondary changes in response to the primary aetiological factor.

Definition of metabolic alkalosis• a primary acid-base disorder which causes the plasma

bicarbonate to rise to a level higher than expectedThe severity of a metabolic alkalosis is determined by the difference between the actual [HCO3] and the expected [HCO3].

Definitions from the findings of the Ad-Hoc Committee of the New York Academy of Sciences in 1965.Cited in 'Acid-base physiology' by Kerry Brandis

Physiology• Kidneys are responsible for maintaining a

stable bicarbonate concentration• Too much bicarb and it is rapidly excreted in

the urine (eg. when you inject sodium bicarb into a healthy person, the pH only rises very briefly)

• Too little bicarb, and all of it gets reabsorbed from the urine

• THUS: for alkalosis to persist, there needs to be an additional process which impairs renal bicarb regulation

How a metabolic alkalosis is initiated• Gain of alkali

– From the outside, eg. infusion of sodium bicarb– From the inside, eg. metabolism of ketoanions to

produce bicarbonate – like lactate in Hartmanns, acetate in Plasmalyte, citrate in transfused blood

• Loss of acid– Through the kidneys, eg. use of diuretic– Through the gut , eg. vomiting or NG suction

How a metabolic alkalosis is maintainedWhatever maintains the alkalosis has to cause a massive decrease

in the kidneys ability to handle bicarbonate and hydrogen ions.These causes can be divided into 4 groups:

• Chloride depletion• Potassium depletion• Reduced glomerular filtration rate• Extracellular volume depletion

Chloride depletion alkalosis• The most common form: 90% of clinical cases• Chloride and bicarb are the only anions present in any significant

quantity in the ECF: decrease in one leads to an increase in the other

• Gastric acid loss eg. due to NG suction or vomiting:– If the acid from the stomach is lost, pancreatic secretions are not stimulated, and

there is no loss of bicarbonate.

• Enteric chloride loss eg. due to villous adenoma

• Diuretic use, eg. frusemide infusion– These patients lose chloride in excess of bicarbonate , because loop diuretics

increase sodium (and thus chloride) excretion– Those patients who develop alkalosis from diuretic use are also volume depleted

and have reduced chloride intake.

• Administration of chloride is required to correct these disorders

Potassium depletion alkalosis• Bicarbonate resorption in the proximal and distal tubule is

increased in the presence of potassium depletion• Potassium depletion also decreases aldosterone release by the

adrenal cortex

• Examples:• Primary or secondary hyperaldosteronism – increased

aldosterone causes increased K+ and H+ losses • Cushings syndrome, or COPD on IV hydrocortisone –

corticosteroids have some mineralocorticoid effect• Potassium-depleting diuretics eg. frusemide• Also Bartter syndrome ( inherited juxtaglomerular

hyperplasia), licorice abuse (pseudohyperaldosteronism)• Severe potassium depletion alone

Iida R, Otsuka Y, Matsumoto K, Kuriyama S, and Hosoya T. Pseudoaldosteronism due to the concurrent use of two herbal medicines containing glycyrrhizin: interaction of glycyrrhizin with angiotensin-converting enzyme inhibitor. Clin Exp Nephrol 2006 Jun; 10(2) 131-5.'Acid-base pHysiology' by Kerry Brandis -from http://www.AnaesthesiaMCQ.com

Extracellular volume depletion and reduced GFR alkalosis

• Hypovolemia increased Na+ and fluid reabsorption• Chloride and bicarbonate should be reabsorbed

together with the sodium, but bicarbonate is absorbed in preference to chloride

• In this situation, chloride depletion is the single most significant cause

• Correcting volume without correcting chloride deficit will not correct the alkalosis

• THUS: these should be treated with normal saline infusion

Another classification of metabolic alkalosis:

• Urinary chloride classification: Based on measured urinary chloride concentration (which can be elevated

with diuretic infusion)

– Chloride responsive alkalosis - < 20mEq/L• Loss of hydrogen ions, eg. vomiting• Loss of bicarbonate-poor water, (concentration of

bicarbonate, “contraction alkalosis”)

– Chloride resistant alkalosis - > 20mEq/L• Retention of bicarbonate• Shift of hydrogen ions into the intracellular space (eg. in

hypokalemia)• Administration of alkalotic agents, eg. bicarbonate

Urinary classification of metabolic alkalosis

• Why is is this useful?– If urinary chloride is low,

• The alkalosis is likely due to volume depletion and/or gastric losses

• will respond to saline infusion- If urinary chloride is high,

- Likely the alkalosis is due to hypokalemia or aldosterone excess

- Will not respond to saline infusion

'Acid-base pHysiology' by Kerry Brandis

Common causes of metabolic alkalosis in the INTENSIVE CARE UNIT

• Frusemide infusion, use of thiazides• High volume NG aspirates • Diarrhoea• Severe hypokalemia (eg. insulin infusion)• Corticosteroid therapy• Overcorrection of chronic respiratory acidosis• Recovery phase post organic acidosis (excess

regeneration of HCO3)• Large doses of IV penicillin-based drugs

“ Acid Base Disorders “ - in Principles of Critical Care Medicine, Mc Graw Hill

Consequences of metabolic alkalosis• In critically ill patients, = significant increase in morbidity and

mortality– Decreased myocardial contractiity– Arrhythmias– Decreased cerebral blood flow (vasoconstriction)– Neuromuscular excitability tetany difficult ventilation– Impaired peripheral oxygen unloading (oxygen-hemoglobin

dissociation curve shifts to the left, thus hemoglobin is less inclined to part with oxygen in the tissues)

– Confusion, obtundation, seizures– Hypoventilation, thus atelectasis– Increased V/Q mismatch (alkalosis inhibits hypoxic pulmonary

vasoconstriction)Anderson LE, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J 1987;80:729-33

Compensation for metabolic alkalosis

• The normal response is hypoventilation• The key is to compensate by increasing pCO2• How much pCO2 is enough?

Expected pCO2 = 0.7 [HCO3] + 20 mmHg (range: +/- 5)

Clinical features of metabolic alkalosis• Hypoventilation, even hypoxia• Other changes are similar to those of

hypercalcemia:– confusion, obtundation, seizures– paraesthesia– Muscle cramps, tetany

DuBose, Jr. Thomas D, "Chapter 48. Acidosis and Alkalosis" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e:

Diagnosis of metabolic alkalosis in the ICU

• SUSPICION:– Is the patient vomiting, is the NG sucking?– Is the pt on frusemide? Whose week is it?– Has there recently been a massive transfusion?

• ABGS: routine and frequent

Management of metabolic alkalosis in the Intensive Care Unit

• Its usually something we did. • Stop doing that.• If it is a side-effect of a greater therapeutic

strategy, and cannot be avoided, then one can focus on managing the alkalosis and ameliorating its ill effects.

Management of metabolic alkalosis in the Intensive Care Unit

Basic management:• GIVE OXYGEN: the tissues are not getting enough

– Unless the patient is a CO2 retainer with severe compensatory hypercapnea

• GIVE CHLORIDE: in chloride-responsive alkalosis this will reverse the alkalosis – “give chloride” means “give saline”

• GIVE PROTON PUMP INHIBITOR: if you reduce the rate of H+ excretion by the gastric mucosa, the NG aspirates will cause less of a

Hixson R and Christmas D. Use of omeprazole in life-threatening metabolic alkalosis. Intensive Care Med 1999 Oct; 25(10) 1201.

Management of metabolic alkalosis in the Intensive Care Unit

More basic management:• REPLACE POTASSIUM / OTHER ELECTROLYTES• AVOID HYPERVENTILATION

Management of metabolic alkalosis in the Intensive Care Unit

Advanced management strategies:• Hydrochloric acid infusion

– Via a central line; just make sure it doesn’t extravasate– The H+ will consume HCO3 – then its all about blowing off enough of

the created CO2

• Acetazolamide– Carbonic anhydrase inhibitor: forces kidneys to excrete HCO3 and

H+ to enter the bloodstream together with CL-– Increases losses of Na+, K+, and water.

Buchanan IB, Campbell BT, Peck MD, and Cairns BA. Chest wall necrosis and death secondary to hydrochloric acid infusion for metabolic alkalosis. South Med J 2005 Aug; 98(8) 822-4. Worthley LI. Intravenous hydrochloric acid in patients with metabolic alkalosis and hypercapnia. Arch Surg 1986 Oct; 121(10) 1195-8. Marik PE, Kussman BD, Lipman J, and Kraus P. Acetazolamide in the treatment of metabolic alkalosis in critically ill patients. Heart Lung 1991 Sep; 20(5 Pt 1) 455-9

Questions?