Electrolytes and pH Electrolytes and pH disturbances : clinical disturbances : clinical signs to make a correct signs to make a correct diagnosis and an early diagnosis and an early treatment treatment

G.S. ReuszG.S. ReuszFirst Department of PediatricsFirst Department of PediatricsSemmelweis UniversitySemmelweis UniversityBudapestBudapest

Case 1Case 1

Six weeks old boy, Six weeks old boy, Uncontrolled gestation. Delivery at Uncontrolled gestation. Delivery at

home. home. No postnatal screeningNo postnatal screening BW: 2200g actually: 1920g BW: 2200g actually: 1920g

Admitted beause of failure to thrive, Admitted beause of failure to thrive, vomitingvomiting

Case 1Case 1First inspection + laboratory First inspection + laboratory fidingsfidings Physical aspectPhysical aspect

– Signs of deydration Signs of deydration (fontanelles, dry tongue, (fontanelles, dry tongue, decreased turgor) decreased turgor)

Blood gasesBlood gases

pH:7.18pH:7.18; ; pCO2:2pCO2:26 mmHg;6 mmHg;

aHCO3aHCO3:: 9.79.7 mmol/l; mmol/l;

BE-17.5BE-17.5 mmol/l mmol/l

ElectrolytesElectrolytes

Na:1Na:1449 K:69 K:6,,3 Cl:3 Cl:109 109 mmol/lmmol/l

Differential Differential diagnosis?diagnosis?

Pylorus stenosis?Pylorus stenosis?– Alkalosis, hypokalemiaAlkalosis, hypokalemia

congenital adrenal congenital adrenal hyperplasia (CAH)hyperplasia (CAH) = = „pseudo-pylorus stenosis”„pseudo-pylorus stenosis”– Functional Functional

mineralocorticoid deficiency mineralocorticoid deficiency causes hyperkalemiacauses hyperkalemia

Diabetes insipidus?Diabetes insipidus?– Thirsty, polyuria, despite of Thirsty, polyuria, despite of

dehydration, high Na, dehydration, high Na, normal pH normal K, normal pH normal K,

RTARTA– low K low K

(could be – type IV?)(could be – type IV?) ARF-CRFARF-CRF

Laboratory data 2Laboratory data 2

RR: RR: 1126/70 26/70 Htk: 25% Htk: 25% Ca:1.72 P:2.Ca:1.72 P:2.6 6

mmol/lmmol/l CCrea:rea: 256 256

micromol/lmicromol/l

Differential Differential diagnosis?diagnosis?

ARF?ARF? CRF?CRF?

Physical exam. + USPhysical exam. + US Physical examinationPhysical examination

– Signs of deydration Signs of deydration (fontanelles, dry tongue, (fontanelles, dry tongue, decreased turgor) decreased turgor)

– Bilateral abdominal massesBilateral abdominal masses

USUS– Enlarged hyperechogenic Enlarged hyperechogenic

kidneyskidneys– No sign of obstructionNo sign of obstruction

Dg: Dg: – ARPKDARPKD– CRFCRF– DehydrationDehydration

Differential diagnosisDifferential diagnosis– Obstructive Obstructive

uropathy ? uropathy ? – ARPKD?ARPKD?– Other (Wilms tu, Other (Wilms tu,

neuroblastoma)neuroblastoma)

– Question of Question of dehydrationdehydration

Acute worsening of Acute worsening of underlying CRFunderlying CRF

Elevated creatnineElevated creatnine– Prerenal component Prerenal component

of azotemiaof azotemia– Decreased GFR ANDDecreased GFR ANDdehydrationdehydration

TreatmentTreatment

Directions of Directions of treatmenttreatment– Increase fluid Increase fluid

intakeintake– Treat Treat

AcidosisAcidosis HypernatremiaHypernatremia AnemiaAnemia Ca-P metabolismCa-P metabolism Blood pressureBlood pressure

Problems:Problems:

NaHCO3NaHCO3– Sodium loadSodium load– CNS?CNS?

HypernatremiaHypernatremia

Long term treatmentLong term treatment

NaHCO3NaHCO3: : 88 mmol/daymmol/day NaCl: 31.5NaCl: 31.5 mmol/day mmol/day Na total:Na total: 38.5 mmol=8.9 38.5 mmol=8.9

mmol/kg/daymmol/kg/day calcitriolcalcitriol, calcium-carbonate, calcium-carbonate Treatment if BP: amlodipineTreatment if BP: amlodipine ErythropoetinErythropoetin

Last control:Last control:

Blood gasesBlood gasespH:7.pH:7.35; 35; pCO2pCO2 mmHg mmHg:: 42; aHCO3: 24 42; aHCO3: 24

mmol/l; mmol/l; BEBE::-1.5-1.5 electrolyteselectrolytesNa:1Na:13535 K: K:3.8 mmol/l3.8 mmol/l Htk: Htk: 3434% % Ca:Ca:2.22.2 P: P:1.5 mmol/l1.5 mmol/l CCrea:rea: 130 micromol/l 130 micromol/l RR: RR: 105/66 mmHg105/66 mmHg

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Case 2Case 2 One month old boy admitted because of One month old boy admitted because of

failure to thrive, vomiting, weight loss in the failure to thrive, vomiting, weight loss in the last 2 weeks.last 2 weeks.

Uncomplicated gestation BW: 3300 gUncomplicated gestation BW: 3300 g

Family history: his brother died 3 years ago Family history: his brother died 3 years ago at the age of 6 month. He suffered from at the age of 6 month. He suffered from postnatal hypoxia, followed by „salt loosing postnatal hypoxia, followed by „salt loosing kidney” and electrolyte inbalancekidney” and electrolyte inbalance

Physical exam: severly dehidratedPhysical exam: severly dehidrated– Fontanelle, tongue, turgorFontanelle, tongue, turgor– Alert, reacts to painful stimulyAlert, reacts to painful stimuly

Laboratory dataLaboratory data pH: 7.pH: 7.5959, pCO2: 34 , pCO2: 34

NaHCO3NaHCO3: 36.7 : 36.7 mmol/lmmol/l BE: +12.9BE: +12.9 mmol/l mmol/l

Na: 102, K: 2.1, Cl: Na: 102, K: 2.1, Cl: 7474 mmol/l, mmol/l,

Ca: 2Ca: 2..6767, , P: 1.2P: 1.2 mmol/lmmol/l osmolaritosmolarityy:243 :243 mosmol/lmosmol/l

CCrea:48rea:48 micro micromol/l mol/l TPTP:55 alb:38g/l:55 alb:38g/l

The dehydrated The dehydrated child has child has metabolic metabolic alkalosisalkalosis with with

– hyponatraemihyponatraemiaa,,– HypochloraemiHypochloraemiaa– hypokalaemihypokalaemiaa

DifferenDifferenttiialal diagn diagnsissis

1. Pylorus stenosis1. Pylorus stenosis– Usually less severe; physical and US examinationUsually less severe; physical and US examination

2. 2. Salt loosing kidneySalt loosing kidney ( (ex: tubular dysfunction due ex: tubular dysfunction due to to hydronephrosis, hydronephrosis, ATN, metabolic diseaseATN, metabolic disease). ). – Alkalosis?Alkalosis?

3. 3. Salt loosing form of aSalt loosing form of adrenogenital sdrenogenital syndromeyndrome– But: Functional mineralocorticoid deficiency causes But: Functional mineralocorticoid deficiency causes

hyperkalemiahyperkalemia 4. 4. Hyponatremic, hypokalemic, hypochloremic Hyponatremic, hypokalemic, hypochloremic

alkalosisalkalosis:: – Bartter syndromBartter syndromeses

Ion transport Ion transport at the loop of at the loop of HenleHenle

Pathophysiology of Bartter Pathophysiology of Bartter syndromesyndrome

Decreased Na+Cl reabsorption at the ascending part of the loop of Henle

Na-reabsorption and - increased K and H secretion at the distal tubule Hypo-K, (hypo-Cl, alkalosis) renal PG E2 vascular PGI2 plasma bradykinine renin angiotensin II normal blood pressure aldosterone noradrenalin kallikrein JGA hypertrophy

depressor activity pressor activity.

pressor activity

TreatmentTreatment NaCl (10-15 mmol/kg/day)NaCl (10-15 mmol/kg/day) KClKCl (10mmol/kg/day)(10mmol/kg/day) IIndometndomethhacinacin (2 mg/kg/(2 mg/kg/dayday)) SpironolactonSpironolacton (5 mg/kg/(5 mg/kg/dayday)) His somatic and mental His somatic and mental

development is normaldevelopment is normal Repeated need of hospitalization due Repeated need of hospitalization due

to acute metabolic derailements to acute metabolic derailements following gastrointestinal and following gastrointestinal and respiratory tract infections. Transient respiratory tract infections. Transient need of parenteral supplementationneed of parenteral supplementation

CommentsComments

Case 3Case 3

8 month old boy8 month old boy Admitted because vomiting, Admitted because vomiting,

muscle weakness, lethargymuscle weakness, lethargy History of failure to thriveHistory of failure to thrive

Pysical aspect + labPysical aspect + lab Lethargic, severely dehidrated, Lethargic, severely dehidrated,

Kussmaul-type breathingKussmaul-type breathing

pH: 7.19, pCO2: 22 mmHg, pH: 7.19, pCO2: 22 mmHg, NaHCO3: 10 mmol/l; BE: -19 mmol/lNaHCO3: 10 mmol/l; BE: -19 mmol/l

Na: 136, K: 3.1 mmol/lNa: 136, K: 3.1 mmol/l Ca: 1.9, P: 0.7 mmol/lCa: 1.9, P: 0.7 mmol/l ALP: 1359 U/l, ALP: 1359 U/l, Crea: 46 micromol/lCrea: 46 micromol/l

First conclusionsFirst conclusions

AcidosisAcidosis Electrolyte imbalanceElectrolyte imbalance

– K, Ca, PK, Ca, P Normal creatinineNormal creatinine Elevated ALPElevated ALP

Next diagnostic steps?Next diagnostic steps?

UrineUrine

Urine: pH: 7.9 Protein:+, glucose:++Urine: pH: 7.9 Protein:+, glucose:++

Collected urine: FeNa: 3% TPR: 67% Collected urine: FeNa: 3% TPR: 67%

Acidosis, glycosuria, phosphate loss, Acidosis, glycosuria, phosphate loss, aminoaciduria, proteinuria, aminoaciduria, proteinuria, hypercalciuriahypercalciuria

Dg: Fanconi syndromeDg: Fanconi syndrome

1930-ies: de Toni, Debré and Faconi1930-ies: de Toni, Debré and Faconirenal renal rickets+glycosuria+hypophosphataemiarickets+glycosuria+hypophosphataemia

=proximal tubular defect==proximal tubular defect=aminoaciduriaaminoaciduriaglycosuriaglycosuriahyperphosphaturia-hypophosphataemiahyperphosphaturia-hypophosphataemiabicarbonate wastingbicarbonate wastinghypokalaemiahypokalaemiaproteinuriaproteinuria

Clinical signs:Clinical signs:polyuria, dehydration+disease-specific signspolyuria, dehydration+disease-specific signs

growth retardation, rickets, growth retardation, rickets,

Fanconi syndromFanconi syndromee

Fanconi syndromFanconi syndromee. . AetiolAetiolooggyy::

InheritedInherited cystinosiscystinosis galactosaemiagalactosaemia fructose intolerancfructose intolerancee tyrosinaemiatyrosinaemia WilsonWilson’s disease’s disease Lowe syLowe sy glycogenosisglycogenosis cytochrome-c cytochrome-c

oxidase def.oxidase def. idiopathiidiopathiicic

AcquiredAcquired Lead poisoningLead poisoning Solvent inhalationSolvent inhalation AzathioprinAzathioprinee GentamycinGentamycinee StreptozocinStreptozocinee myeloma multiplexmyeloma multiplex Sjögren sySjögren sy amyloidosisamyloidosis cysplatincysplatinee iphosphamidiphosphamidee transplantatiotransplantationn

Molecular mechanism Molecular mechanism of cystinosisof cystinosis

Depletion of cystin by cysteamineDepletion of cystin by cysteamine

a

b

c

A: healthy lysosomeA: healthy lysosomeB: cystinotic lysosomeB: cystinotic lysosomeC: treatment by cysteamineC: treatment by cysteamine

Clinical pictureClinical picture::

Usually blond children, with white skin. Usually blond children, with white skin. Latency of several month, then: Latency of several month, then:

polyuria, polydipsia, dehydratiopolyuria, polydipsia, dehydrationn, acidosis, , acidosis, no weight gainno weight gain

1-5g glycosuria, 1-5g glycosuria, phosphate diabetesphosphate diabetes, gen. , gen. aminoaciduria, tubular proteinuria, acidosis aminoaciduria, tubular proteinuria, acidosis seHCO3 12-15 mmol/lseHCO3 12-15 mmol/l

RicketsRickets leucocytleucocytee-cystin-cystinee measurementmeasurement

Clinical picture (cont)Clinical picture (cont) 3-6 3-6 yy: photophob: photophobyy (cornea-(cornea-cristalscristals+retina, +retina,

blindnessblindness))

7-8 7-8 yy: ESRD: ESRD 5-10 y hypothyreosis5-10 y hypothyreosis 12-40 y myopathy, swallowing difficulties12-40 y myopathy, swallowing difficulties 13-40 y retina degeneration, blindness13-40 y retina degeneration, blindness 18-40 y diabetes mellitus18-40 y diabetes mellitus 18-40 y male hypogonadism18-40 y male hypogonadism 21-40 y lung dysfunction21-40 y lung dysfunction 21-40 y CNS calcification21-40 y CNS calcification 21-40 y deterioration of CNS function21-40 y deterioration of CNS function

2 y

Cornea Cornea cristalscristals

RicketsRickets

TreatmentTreatment FluidFluid: : 3-3.5 l = cca. 250 ml/kg3-3.5 l = cca. 250 ml/kg K K 350 mmol/350 mmol/dayday = 25 mmol/kg = 25 mmol/kg HCO3HCO3 300 mmol/300 mmol/dayday = 21.5 mmol/kg = 21.5 mmol/kg Ca Ca 2x250 mg2x250 mg P SandozP Sandoz 4x500 mg 4x500 mg Alpha-D3Alpha-D3 50 mi50 miccrog/rog/dayday Amilorid Amilorid 1.25 mg1.25 mg HCTZHCTZ 12.5 mg12.5 mg L-ThyroxinL-Thyroxin 25 mi25 miccrogrog FolFolic acidic acid//ironiron supplement supplementationation CystagonCystagonee 5x250 mg5x250 mg Cysteamin Cysteamin eye dropseye drops 5x 5x /day/day

Effectivenes off Effectivenes off treatmenttreatment Kidney functionKidney function GrowthGrowth Organ damageOrgan damage

– eyeeye– thyroideathyroidea– Glucose metabolismGlucose metabolism– gonadgonadss– CNSCNS

Adequate treatment: Adequate treatment: n= 17n= 17

Partial treatment: n= Partial treatment: n= 32 without therapy: 32 without therapy: n=67n=67

  Markello: N Engl J Med, Markello: N Engl J Med, Volume 328: Volume 328: 1993.1157-11621993.1157-1162

GFR in function of age

Gahl: N Engl J Med, Volume 347(2).July 11, 2002.111-121

Cysteamin - Cysteamin +

Kidney function and age

Prognosis depends on Prognosis depends on early diagnosis and early early diagnosis and early treatmenttreatment Early cysteamin Early cysteamin treatment could prevent treatment could prevent

deterioration of kidney functiondeterioration of kidney function Prevent the development of multiorgan Prevent the development of multiorgan

damagedamage Prevent complications secondary to Fanconi Prevent complications secondary to Fanconi

syndromesyndrome Late introduction of cysteamine treatmentLate introduction of cysteamine treatment

can only slow down progresscan only slow down progressiion of on of established renal diseaseestablished renal disease

In CRFIn CRF: supportive treatment and : supportive treatment and transplantationtransplantation

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