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+ concentrationi.e. the higher the pH, the lower the H + concentration.Pure water is neutral: pH of 7Thus, 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. Sren Peder Lauritz Srensen used the term to refer to the negative log of the hydrogen ion concentration, hence the H.He decided to call it WasserstoffionenexponentTo this day, there is debate as to what the p in pH actually means looks like Dr Sorensens electrodes were arbitrarily named p and q

Srensen, S. P. L. (1909). Enzymstudien. II: Mitteilung. ber die Messung und die Bedeutung der Wasserstoffionenkoncentration bei enzymatischen Prozessen; Biochemische Zeitschrift 21: 131304.Nrby 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 alkalosisan 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 alkalosisa 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

PhysiologyKidneys are responsible for maintaining a stable bicarbonate concentrationToo 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 initiatedGain of alkaliFrom the outside, eg. infusion of sodium bicarbFrom the inside, eg. metabolism of ketoanions to produce bicarbonate like lactate in Hartmanns, acetate in Plasmalyte, citrate in transfused bloodLoss of acidThrough the kidneys, eg. use of diureticThrough 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 depletionPotassium depletionReduced glomerular filtration rateExtracellular volume depletion

Chloride depletion alkalosisThe most common form: 90% of clinical casesChloride 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 adenomaDiuretic use, eg. frusemide infusionThese patients lose chloride in excess of bicarbonate , because loop diuretics increase sodium (and thus chloride) excretionThose 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 alkalosisBicarbonate resorption in the proximal and distal tubule is increased in the presence of potassium depletionPotassium depletion also decreases aldosterone release by the adrenal cortexExamples:Primary or secondary hyperaldosteronism increased aldosterone causes increased K+ and H+ losses Cushings syndrome, or COPD on IV hydrocortisone corticosteroids have some mineralocorticoid effectPotassium-depleting diuretics eg. frusemideAlso 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 alkalosisHypovolemia increased Na+ and fluid reabsorptionChloride and bicarbonate should be reabsorbed together with the sodium, but bicarbonate is absorbed in preference to chlorideIn this situation, chloride depletion is the single most significant causeCorrecting volume without correcting chloride deficit will not correct the alkalosisTHUS: 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/LLoss of hydrogen ions, eg. vomitingLoss of bicarbonate-poor water, (concentration of bicarbonate, contraction alkalosis)Chloride resistant alkalosis - > 20mEq/LRetention of bicarbonateShift of hydrogen ions into the intracellular space (eg. in hypokalemia)Administration of alkalotic agents, eg. bicarbonate

Urinary classification of metabolic alkalosisWhy is is this useful?If urinary chloride is low,The alkalosis is likely due to volume depletion and/or gastric losseswill respond to saline infusionIf urinary chloride is high,Likely the alkalosis is due to hypokalemia or aldosterone excessWill not respond to saline infusion'Acid-base pHysiology' by Kerry Brandis

Common causes of metabolic alkalosis in the INTENSIVE CARE UNITFrusemide infusion, use of thiazidesHigh volume NG aspirates DiarrhoeaSevere hypokalemia (eg. insulin infusion)Corticosteroid therapyOvercorrection of chronic respiratory acidosisRecovery 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 alkalosisIn critically ill patients, = significant increase in morbidity and mortalityDecreased myocardial contractiityArrhythmiasDecreased cerebral blood flow (vasoconstriction)Neuromuscular excitability tetany difficult ventilationImpaired 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, seizuresHypoventilation, thus atelectasisIncreased 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 alkalosisThe normal response is hypoventilationThe key is to compensate by increasing pCO2How much pCO2 is enough? Expected pCO2 = 0.7 [HCO3] + 20 mmHg (range: +/- 5)

Clinical features of metabolic alkalosisHypoventilation, even hypoxiaOther changes are similar to those of hypercalcemia: confusion, obtundation, seizuresparaesthesiaMuscle 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 ICUSUSPICION: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 UnitIts 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 UnitBasic management:GIVE OXYGEN: the tissues are not getting enoughUnless the patient is a CO2 retainer with severe compensatory hypercapneaGIVE CHLORIDE: in chloride-responsive alkalosis this will reverse the alkalosis give chloride means give salineGIVE 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 UnitMore basic management:REPLACE POTASSIUM / OTHER ELECTROLYTESAVOID HYPERVENTILATION

Management of metabolic alkalosis in the Intensive Care UnitAdvanced management strategies:Hydrochloric acid infusionVia a central line; just make sure it doesnt extravasateThe H+ will consume HCO3 then its all about blowing off enough of the created CO2AcetazolamideCarbonic 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

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