Metabolic alkalosis - Nephkids

Metabolic alkalosis

Dr N C GowrishankarMD DCH DNB FIAP

Pediatric Pulmonologist &Head-Pediatrics:Clinical Operations &Quality

Mehta Multispeciality Hospitals India Pvt Ltd, Chennai

Scope

• Basics

• Causes

• Pathophysiology

• Clinical features

• Investigations

• Management algorithm

12/6/2020 2NCGS metabolic alkalosis

Basics

• Normal pH - 7.35 to 7.45• CO2 levels regulated – Lungs : HCO3 levels regulated –kidneys• Arterial blood gas – normal values :

– pH - 7.35 to 7.45– HCO3 - 21 to 27 mEq/L– PCO2 - 35 to 45 mmHg

• Alkalemia – An arterial pH above normal range (greater than 7.45)• Alkalosis – A process that tends to raise extracellular fluid pH-

elevation serum HCO3 concentration and/or fall in PCO2 - Alkalosis is not necessarily accompanied by alkalemia


Metabolic alkalosis

• A disorder -elevates serum HCO3 concentration and pH

• pH > 7.45• HCO3- > 28 mmol/l• Kidney normally respond -

rapidly excrete excess alkali • Only when additional factor

disrupts renal regulation of body alkali stores- Sustained metabolic alkalosis

3 months - 2011 March – CF


Systemic pH- Chemoreceptors

• Central (ventrolateral surface-medulla oblongata )-sensitive to pH

• Peripheral (carotid & aortic bodies) -detect variation -arterial PCO2 & as well as arterial PO2

• Chemoreceptors - lead to adjustments -both components of minute ventilation: tidal volume & respiratory cycle frequency (through central respiratory control centers in pons and medulla)

• Lung-mediated changes in arterial PCO2 -rapid alteration in systemic hydrogen ions (H+) - CO2 lipid soluble - readily cross cell membranes -allow tight control of arterial PCO2 near 40 mm Hg


Kidney role in acid base balance

• Reabsorbing filtered HCO3 & excreting daily acid load derived – metabolism – sulfur containing amino acids

• Filtered HCO3

– 90% - reabsorbed - proximal tubules –primarily by Na-H exchange

– Remaining 10% -reabsorbed - distal nephron - primarily via hydrogen secretion by proton pump (H-ATPase)

• Under normal conditions - no HCO3 present in final urine.


Cellular and luminal event – bicarbonate reabsorbtion-Proximal convoluted tubule

Na + K + ATPase – create steep electrochemical gradient for Na+

H + secreted into lumen in exchange for Na + by Na + H + exchanger


Cellular and luminal event – bicarbonate reabsorbtion-Proximal convoluted tubule

H+ entering lumen – combine with filtered HCO3-

form H2CO3- dissociated by carbonic anhydrase IV tethered to membrane- H2O & CO2- passively reabsorbed

Peritubularcapillary Proximal Tubular cell Tubular lumen

CO2 combines with OH- – form HCO3-

(carbonic anhydrase II) – enter peritubular capillary by Na+ 3HCO3- cotransporter

90% filtered HCO3 reclaimed


Kidney role in acid base balance

• Reabsorbing filtered HCO3 & excreting daily acid load derived – metabolism – sulfur containing amino acids

• Filtered HCO3

– 90% - reabsorbed - proximal tubules –primarily by Na-H exchange

– Remaining 10% -reabsorbed - distal nephron - primarily via hydrogen secretion by proton pump (H-ATPase)

• Under normal conditions - no HCO3 present in final urine.


Type A cell-Distal convoluted & collecting tubule

10% filtered HCO3- enter distal tubule-Combine with H+ form H2CO3-

Dissociate- H2O & CO2- passively reabsorbed into cell

H+ATPase pump- drive H+ secretion

cellular HCO3- moves into peritubular capillary in exchange for extracellular chloride by

Cl-HCO3- exchanger


H+K+ATPase – luminal membrane- promote H+ secretion & K+ absorbtion

Type A cell-Distal convoluted & collecting tubule

Excretion of daily H+ load - occur distal tubule -H+ must be bound to buffer to avoid excessive urine acidification Kidneys synthesize and excrete NH3 - which combines with H+ - form NH4 +


Metabolic alkalosis

• Elevation- plasma HCO3- Several mechanisms – Excessive hydrogen loss– Functional addition of new HCO3– Volume contraction around a relatively constant amount of

extracellular HCO3 - “contraction alkalosis”• Kidneys

– Extremely efficient in eliminating excess HCO3 in urine


Addition of HCO3

• Decreased renal excretion of HCO3(Renal failure )

• Posthypercapnic alkalosis

• Excessive intake / very large quantities of HCO3 administered acutely

• Administration - large quantities >8 units citrated blood product infusion / fresh frozen plasma (citrate converted to bicarbonate by liver)

Contraction alkalosis • IV loop diuretics – fluid loss without bicarbonate• Disorders – high Cl & low HCO3 solution lost– Sweat losses in cystic fibrosis– Loss of gastric secretions in achlorhydria– Fluid loss from frequent stools- congenital

chloridorrhea/ villous adenoma• BPD - chronic respiratory acidosis - receive diuretics – further ↓intravascular volume

• Posthypercapnic alkalosis Chronic respiratory acidosis – compensatory ↑H+ secretion & ensuing ↑ in HCO3 Reduce PCO2 gradually by mechanical ventilation – if PCO2 decreased rapidly -

ensuing metabolic alkalosis - slow to disappear


Kidneys promptly respond to metabolic alkalosis –

increasing base excretion

For generation of metabolic alkalosis- addition of

base/loss of acid to body required

For maintenance of metabolic alkalosis –

impairment - kidney's ability to excrete base required


Maintenance phase of metabolic alkalosis

normal renal response to metabolic alkalosis –

urinary loss of bicarbonate

Volume depletion interferes with urinary loss of bicarbonate -

3 mechanisms

Reduction in GFR, so less bicarbonate filtered

↑angiotensin II & ↑adrenergic stimulation of kidney -

Increased reabsorption – Na+ & HCO3- in PCT - limit HCO3 that

can be excreted in urine

↑aldosterone -increases HCO3-

reabsorption & H+ secretion in collecting duct

caused by volume depletion (“chloride depletion” from gastric loss of HCl)


12/6/2020 NCGS metabolic alkalosis 16

Chloride resistant

Normal Blood Pressure High Blood Pressure

Bartter syndromeGitelman syndrome Autosomal dominant

hypoparathyroidismEAST syndromeBase administration

Cushing syndromeAdrenal adenoma/

hyperplasiaGlucocorticoid-remediable

aldosteronismRenovascular diseaseRenin-secreting tumor17α-Hydroxylase deficiency11β-Hydroxylase deficiency11β-Hydroxysteroid dehydro

genase deficiency Licorice ingestionLiddle syndrome

Chloride responsive

Gastric lossesEmesisNasogastric suctionDiuretics (loop or thiazide)Cystic fibrosis Chloride-losing diarrhea Post hypercapniaLow chloride formula

Metabolic alkalosis - Classification – based on response to chloride

Bartter & Gitelman syndromes

• Metabolic alkalosis & hypokalemia• Genetic defect - transporters

• Gitelman syndrome : Na-Cl cotransporter – distal tubule -same location as those inhibited by thiazidediuretics

• Bartter syndrome: Na-K-2Cl cotransporter- loop of Henle- same location as those inhibited by loop diuretics


Consequences of Untreated Alkalosis

System Effects

Cerebral •Cerebral vasoconstriction with reduction of cerebral blood flow•Tetany, seizures, lethargy, delirium, stupor

Cardiovascular •Vasoconstriction - small arterioles, including coronary arteries •Decreased threshold for arrhythmias

Respiratory •Compensatory hypoventilation with possible subsequent hypoxemia & hypercarbia

Hematologic •Oxyhemoglobin dissociation curve shifts to left

Metabolic & Electrolyte Imbalances

•Stimulation of anaerobic glycolysis•Hypokalemia•Decreased plasma ionized calcium •Hypomagnesemia and hypophosphatemia


Clinical features

• Features directly related to metabolic alkalosis uncommon• Asymptomatic: alterations in blood HCO3 concentration –

slow → less pronounced change in intracellular pH & brain pH• Symptoms primarily related to

– Alkalemia– Underlying etiology of metabolic alkalosis– Accompanying electrolyte abnormalities


Clinical features• Alkalemia –

– ↓ ionised Ca+ - ↑binding of calcium to albumin - symptoms of tetany

– ↓decrease cardiac output – Shift K+ intracellularly - decrease in extracellular K+ -

hypokalemia - muscle weakness, cardiac arrhythmias• Metabolic alkalosis

– compensatory ↑ in PCO2 decreasing ventilation -if underlying lung disease -hypoxia.

– With normal lungs, severe metabolic alkalosis can cause hypoxia


Clinical features

• If metabolic alkalosis from vomiting – symptoms of severe volume contraction– signs of dehydration - tachycardia, dry mucous

membranes, decreased skin turgor, postural hypotension, poor peripheral perfusion, weight loss.

• Children with congenital chloride –watery diarrhea at birth, metabolic alkalosis, hypovolemia.

• Weight gain &hypertension - ↑mineralocorticoid state.


Diagnosis

• History

• Clinical exam – rarely gives clue to diagnosis

• Investigations

– Arterial blood gas

– Serum electrolytes

– Spot urine chloride measurements


Investigations

• ABG: elevated pH - high bicarbonate (HCO3) level - with compensation, PCO2 may be near reference range/ elevated.

• Serum electrolytes: hypokalemia, hypochloremia, hyponatremia

• Urine chloride – < 20 mEq/L - chloride-responsive metabolic alkalosis– > 20 mEq/L - chloride-resistant metabolic alkalosis


Appropriate Compensation

• Metabolic alkalosis - appropriate respiratory compensation - by decreasing ventilation

• Should raise PCO2 by approximately 0.7 mmHg for every 1 mEq/L elevation in serum HCO3 concentration

• PCO2 appropriately increased or not :easy to use

• PCO2 = HCO3 + 10

• If PCO2

– Lower than expected compensation- concurrent respiratory alkalosis

– Greater than expected compensation - concurrent respiratory acidosis

• Respiratory compensation never exceeds PCO2 of 55-60 mm Hg


Treatment

• Address underlying disease state

• Goal

– prevent life-threatening complications with least amount of correction -target pH & bicarbonate levels (correcting severe alkalemia)

• Hypovolemia

– Intravascular volume expansion - isotonic crystalloid solution(Isotonic saline) – under close monitoring

• Diuretics

– if change tolerated- dose reduced/ eliminated


Treatment – moderate/severe metabolic alkalosis

• Reducing H+ loss– Nasogastric suction –discontinue /Replace NG aspirate equivalent

promptly –avoid volume loss

– Proton pump inhibitor - ↓ gastric secretion –reduces loss of HCl

• Correcting K+ -Potassium– Adequate K+ supplementation as chloride salt - also help replenish

chloride losses partly

– K+ sparing diuretic use : decrease renal K+ loss


Treatment - moderate or severe metabolic alkalosis

• Increasing HCO3 excretion

– K+ sparing diuretic use - block action of aldosterone → decrease H+

secretion in distal nephron – facilitate ↑HCO3 excretion– Acetazolamide (carbonic anhydrase inhibitor)

• ↓ HCO3 − resorption in PCT - significant bicarbonate loss in urine• Produces major K+ losses - urine • ↑ fluid losses - necessitating dose reduction -other diuretics

• Arginine HCl - chloride-responsive metabolic acidosis if sodium or potassium salts are not appropriate - may raise serum K+ levels during administration


Treatment- chloride-responsive

• Most metabolic alkalosis → Cl responsive etiology

• Sufficient NaCl & KCl administration

– Correct volume deficit & potassium deficit

– Not an option if volume depletion due to diuretics as volume repletion may be contraindicated.

• With adequate intravascular volume & normal serum K + - kidney excretes excess bicarbonate within 2 days


Renovascular disease – surgical correction

17α hydroxylase deficiency/11β-hydroxylase deficiency - glucocorticoid

11β-hydroxysteroid dehydrogenase deficiency – spironolactone –decrease mineralocorticoid effect of cortisol

Bartter or Gitelman syndrome –oral Na+ & K+ supplementation +/- potassium-sparing diuretics

Gitelman syndrome –Mg supplementation

Adrenal adenomas –resection

Treatment- chloride-resistant


Metabolic alkalosis – Suggestive history/ABG/electrolytes

Urine chloride level > 20 mmol/L< 20 mmol/L




Recent diuretic therapyGastric lossPost hypercapnic stateVillous adenoma





BP normal BP high





BP normal BP high

Ongoing diureticsBartter syndromeGitelman syndromeHypokalemiaHypomagnesemia





BP normal BP high

Ongoing diureticsBartter syndromeGitelman syndromeHypokalemiaHypomagnesemia

High renin Low renin





BP normal BP high

Ongoing diureticsBarrter syndromeGitelman syndromeHypokalemiaHypomagnesemia


Ongoing diureticsRenal A stenosisRenin sec tumor





BP normal BP high




Aldosteronelevel





BP normal BP high




Aldosteronelevel

Low High





BP normal BP high




Aldosteronelevel

Low High

Cushing syndromeCS use17hydroxylase defLiddle syndrome12/6/2020 38NCGS metabolic alkalosis




BP normal BP high




Aldosteronelevel

Low High

Cushing syndromeCS use17hydroxylase defLiddle syndrome

HyperaldosteronismAdrenal adenomaAdrenal hyperplasia


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Metabolic alkalosis - Nephkids

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