Metabolic alkalosis

Metabolic Alkalosis:Metabolic Alkalosis:the Missing Puzzle the Missing Puzzle

PiecePiece

ByProf. Ashraf Abdel

BassetProfessor of Pediatrics

Case PresentationCase Presentation

History:History:

OA three-year old previously healthy female presented with recurrent episodes of quadriparesis.

Examination:Examination: Apparently healthy female. Her blood pressure was 90/60. Apart from generalized

hypotonia, her neurological examination was unremarkable.

She was followed in the pediatric neurology outpatient clinic as a case of periodic paralysis.

Few months later, she developed a similar attack of quadriparesis.

Laboratory Laboratory Investigations:Investigations:

Serum creatinine 0.5 mg/dl.PH 7.56, HCO3 37.Serum Na 138 mEq/L.Serum K 2.2 mEq/L.Serum Cl 93 mEq/L.Urinary Chloride 30 mEq/L.

So….So….

The main abnormality is “hypokalemic The main abnormality is “hypokalemic metabolic alkalosis with metabolic alkalosis with urine urine chloride”.chloride”.

Lumen

Ca2+, Mg2+, Na+, NH4+

Na+

2Cl-K+

K+

Lumen (+) voltage

Ca++

furosemide

TRPV4ROMKKCNJ1

ATP

Cl-

3Na+

2K+

ClC-Kb Barttin

Blood

Paracellin-1+8 mV

Cl-ClC-Ka

CaSR

NKCC2 SLC12A1

Thick ascending limb, Loop of HenleThick ascending limb, Loop of Henle

Distal convoluted tubuleDistal convoluted tubuleNa+

2Cl-K+

Classification of Metabolic Classification of Metabolic AlkalosisAlkalosis

Chloride responsive Chloride resistant(Urine chloride<15mEq/L) (Urine chloride>20mEq/L)

Metabolic alkalosis

• Vomiting• Low Chloride intake• Pyloric stenosis• Chloride losing

diarrhea• GI fistula• Cystic Fibrosis

With Hypertension•Hyperaldosteronism•Renal artery stenosis•Renin secreting tumor •Liddle syndrome •11β-HSD deficiency •11β-Hydroxylase deficiency•17α-OH/17,20-lyase deficiency • Licorice abuse

WithNormal Blood

PressureBartter syndrome Gitelman syndrome Diuretics therapyAlkali loading

Back to Our PatientBack to Our Patient

What is the most likely diagnosisWhat is the most likely diagnosis??

Chloride responsive Chloride resistant(Urine chloride<15mEq/L) (Urine chloride>20mEq/L)

Metabolic alkalosis



With Normal Blood

Pressure•Bartter syndrome •Gitelman syndrome •Diuretics therapy•Alkali loading


Urinary Chloride 30 Urinary Chloride 30 mEq/LmEq/L

Chloride responsive Chloride resistant(Urine chloride<15mEq/L) Urine chloride>20mEq/L

Metabolic alkalosis

• Post-diuretics therapy



With Normal Blood

Pressure•Bartter syndrome •Gitelman syndrome •Diuretics therapy•Alkali loading


Chloride Resistant Metabolic Alkalosis

Normal Blood PressureNormal Blood Pressure

Bartter Bartter SyndromeSyndrome

• Autosomal recessive renal tubular disorder Autosomal recessive renal tubular disorder characterized by hypokalemia, hypocholermia, characterized by hypokalemia, hypocholermia, metabolic alkalosis, hyperreninemia with normal blood metabolic alkalosis, hyperreninemia with normal blood pressure, decreased pressor responsiveness to pressure, decreased pressor responsiveness to infused angiotensin II, and hyperplasia of the infused angiotensin II, and hyperplasia of the juxtaglomerular complex.juxtaglomerular complex.

Bartter FC, Et al., Am J Med 33:811-828, 1962Bartter FC, Et al., Am J Med 33:811-828, 1962..

Bartter Syndrome Bartter Syndrome ClassificationClassification

ONeonatal Bartter Neonatal Bartter syndrome.syndrome.

OClassic Bartter syndrome.Classic Bartter syndrome.OGitelman syndrome.Gitelman syndrome.

Lumen

Ca2+, Mg2+, Na+, NH4+

Na+

2Cl-K+

K+

Lumen (+) voltage

Ca++

furosemide

TRPV4ROMKKCNJ1

ATP

Cl-

3Na+

2K+

ClC-Kb Barttin

Blood

Paracellin-1+8 mV

Cl-ClC-Ka

CaSR

NKCC2 SLC12A1

Thick ascending limb, Loop of Thick ascending limb, Loop of HenleHenle

ATP 3Na+

2K+

Na+

Cl-

Ca++

Na+

Ca++

ECaC1 TRPV5

Cl-

ClC-Kb Barttin

NCCT

thiazide NCX1

Ca++PMCA1B

Distal convoluted tubuleDistal convoluted tubuleLumen Blood

-10 mV

Mg++ TRPM6

PathophysiologyPathophysiology

Lumen

Ca2+, Mg2+, Na+, NH4+

Na+

2Cl-K+

K+

Lumen (+) voltage

Ca++

furosemide

TRPV4ROMKKCNJ1

ATP

Cl-

3Na+

2K+

ClC-Kb Barttin

Blood

Paracellin-1+8 mV

Cl-ClC-Ka ?

CaSR

NKCC2 SLC12A1

Thick ascending limb, Loop of Thick ascending limb, Loop of HenleHenle

Lumen

Ca2+, Mg2+, Na+, NH4+

Na+

2Cl-K+

K+

Lumen (+) voltage

Ca++

furosemide

TRPV4ROMKKCNJ1

ATP

Cl-

3Na+

2K+

ClC-Kb Barttin

Blood

Paracellin-1

+8 mV

Cl-ClC-Ka ?

CaSR

NKCC2 SLC12A1

Bartter syndromeBartter syndrome

type I

type II type III

type IV

type V

ATP 3Na+

2K+

Na+

Cl-

Ca++

Na+

Ca++

ECaC1 TRPV5

Cl-

ClC-Kb Barttin

NCCT

thiazide NCX1

Ca++PMCA1B

Gitelman syndromeGitelman syndromeLumen Blood

Mg++TRPM6

Bartter Syndrome Bartter Syndrome ClassificationClassification

ONeonatal Bartter syndrome.

OClassic Bartter syndrome.OGitelman syndrome.

Bartter Syndrome Genotype-Phenotype Correlations

Genetic Type Defective Gene Clinical Type

Bartter type INKCC2Neonatal

Bartter type IIROMKNeonatal

Bartter type IIICLCNKBClassic

Bartter type IVBSNDNeonatal with deafness

Bartter type VCLCNKB and CLCNKANeonatal with deafness

Gitelman syndromeNCCTGitelman syndrome

A) Hypokalemic metabolic

alkalosis.

B) Hypercalciuria.

C) Activated RAAS + Normal blood

pressure.

D) Diminished serum PGE2 level.

All the following are true of All the following are true of Bartter Syndrome EXCEPTBartter Syndrome EXCEPT

Na+

2Cl-K+

K, volume contraction & ANII entrarenal BGE2 vicious cercal growth retardation and hyperplasia, juxtaglomerular complex

Lumen

Ca2+, Mg2+, Na+, NH4

+

Na+

2Cl-

K+

K+

Lumen (+) voltage

Ca++

furosemide

TRPV4ROMKKCNJ1

ATP

Cl-

3Na+

2K+

ClC-Kb Barttin

Blood

Paracellin-1+8 mV

Cl-

ClC-Ka

?

CaSR

NKCC2 SLC12A1

The following Lab abnormalities are The following Lab abnormalities are present in patients with Gitelman present in patients with Gitelman syndrome:syndrome:

A) Hypercalciuria

B) Hypomagnesemia

C) Increased urinary

prostaglandins

D) Normal plasma renin activity

ATP3Na+

2K+

Na+

Cl-

Ca++

Na+

Ca++

ECaC1 TRPV5

Cl-

ClC-Kb Barttin

NCCT

thiazide

NCX1

Ca++

PMCA1B

Lumen Blood

-10 mV

Mg++ TRPM6

All the following are true about All the following are true about neonatal Bartter syndrome neonatal Bartter syndrome EXCEPTEXCEPT

A) Presents in neonatal period.

B) Associated with nephrocalcinosis.

C) Associated with oligohydraminos.

D) May be associated with deafness.

BS Type I BS Type III BS Type I BS Type III GSGS• Age at presentationAge at presentation Neonatal Neonatal ≤ 2 years old ≤ 2 years old

• Growth retardationGrowth retardation Severe Severe Mild-moderateMild-moderate

• PolyuriaPolyuria Present Present Present Present May May be presentbe present

• NephrocalcinosisNephrocalcinosis Present Present +/- +/-

• PolyhydramniosPolyhydramnios Present Present May be present May be present

• Chondrocalcinosis Chondrocalcinosis Absent Absent Absent Absent May May be presentbe present

• Carpal pedal spasmCarpal pedal spasm Absent Absent Absent Absent May be presentMay be present

• SN Hearing LossSN Hearing Loss May be present May be present Absent Absent AbsentAbsent

Clinical picture ….Clinical picture ….

Absent or mildAbsent or mild

AbsentAbsent

AbsentAbsent

Above 5 yearsAbove 5 years

BS Type I BS Type III BS Type I BS Type III GSGS• Hypokalemia Hypokalemia Present Present Present Present

PresentPresent

• Metabolic alkalosisMetabolic alkalosis Present Present Present Present PresentPresent

• Hyperreninemia Hyperreninemia Present Present Present Present PresentPresent

• HyperaldosteronemiaHyperaldosteronemia Present Present Present Present PresentPresent

• Urinary calciumUrinary calcium Very High Very High High High

• Hypomagnesemia Hypomagnesemia Absent or mild Absent or mild Absent or mild Absent or mild

• Urinary prostaglandinsUrinary prostaglandins High High High High

Biochemical markers ….Biochemical markers ….

LowLow

PresentPresent

NormalNormal

Back to Our PatientBack to Our Patient

Urinary Ca: 6 mg/kg/dSerum Mg: 2 mEq/ml

Neonatal Bartter Neonatal Bartter SyndromeSyndrome

Classic Bartter Classic Bartter SyndromeSyndrome

Gitelman Gitelman SyndromeSyndrome

BS Type I BS Type III GS

• Oral K supplements Usually required Usually required Usually

required

• K sparing diuretics Indicated Indicated Indicated

• NSAIDs Used with caution Indicated Not indicated

• NaCl Usually required Recommend Recommend

• ACE-inhibitors Indicated Indicated Indicated

• Oral Mg supplements Not required Not required Usually

required

• Growth Hormone May be beneficial May be beneficial May be

beneficial

Treatment ….

Hypokalemic metabolic Hypokalemic metabolic alkalosisalkalosis

CL, Mg, CL, Mg, Renin, Renin,

AldosteroAldosteronene

Ca

O Hypokalemic metabolic alkalosis is not an uncommon disorder among children.

O Patients are often asymptomatic but they may develop serious neurologic or respiratory symptoms.

O Do not forget to exclude hypokalemic metabolic alkalosis on dealing with a case of unexplained paresis or paralysis.

O The golden point during dealing with hypokalemia is not giving K supplementation, but knowing the cause to treat it.

ESPNT-14th Congress-Common Pitfalls in the Practice of Pediatric Nephrology

Education

Metabolic alkalosis