electrolytes and ph disturbancies: clinical signs to make a correct diagnosis and an early treatment...
TRANSCRIPT
Electrolytes and pH disturbancies: clinical signs to make a correct diagnosis and
an early treatment
Alberto BettinelliDepartments of Pediatrics
Leopoldo Mandic Hospital, Merate (LC)Italy
Case 1
An Albanese child…
Clinical presentation
• Male. Age: 2 years and 3 months• Poor clinical condition with signs of dehydration
and chronic malnutrition (hypotrophia of muscles with abdominal protrusion, hypotonia, psychomotor retardation)
• Polypnea, 60/min• Weight Kg. 7.610, lenght cm. 75 (< 3° percentile)• Blood pressure 68/34 mmHg
Emergency measures
• - adequate periferal perfusion with administration of isotonic saline (20 ml/kg/h)
• - delivery of 02
First biochemical examinations
• venous pH 7.101
• plasma bicarbonates, 5.0 mmol/l
• pC02 16.2 mmHg
QUESTIONS ?
1) Is it a simple metabolic acidosis?
2) Is it a metabolic acidosis with normal plasmatic anion gap?
Is it a simple metabolic acidosis?
• Predicted metabolic and respiratory compensations to simple primary acid-base disturbances
• (Bianchetti MG and Bettinelli A in Comprehensive Pediatric Nephrology, Geary DF and Schaefer F Ed; Mosby Elsevier 2008:395-432)
• Metabolic Acidosis: Primary Change HCO3- • Compensatory response: pCO2 by 1.3∆ mm Hg
for 1.0 mmol/L* in HCO3-
• ∆ range approximately ± 3 mm Hg; * from 25 mmol/L; range approximately ± 2.0 mmol/L; from 40 mm Hg.
First biochemical examinations
• Venous ph 7.101; plasma bicarbonates 5.0 mmol/l; pC02 16.2 mmHg
• ∆bicarbonates: 25-5 = 20
• ∆pC02: 20 x 1.3 = 26.0
• 40-26.0 = 14.0 = expected pC02
• The respiratory compensation is appropriate = simple metabolic acidosis
After some hours
• Venous ph 7.150; plasma bicarbonate 8.7 mmol/l, pC02 26.9 mmHg
• Plasma Na 135, K 4.3, Cl 116 mmol/l
• Plasma anion gap:• (Nap + Kp) – (Clp + Bicarbonate) = 14.6 • (Ref values 8-18; If you do not include K = 4-14)
• Plasma anion gap is normal: the major cause of metabolic acidosis with normal anion gap was excluded (gastrointestinal loss di bicarbonates)
Metabolic acidosis with normal anion gap
• - Losses of bicarbonate HCO3-• - intestinal: diarrhea, surgical drainage of the intestinal tract, gastrointestinal fistulas
resulting in losses of fluid rich in HCO3-, patients whose ureters have been attached to the intestinal tract
• - urinary: carbonic anhydrase inhibitors (e.g.: acetazolamide), proximal renal tubular acidosis (= type 2)
• - Failure to replenish HCO3- stores depleted by the daily production of fixed acids
• - distal renal tubular acidosis (either classic, also called type 1 or type 4) • - diminished mineralocorticoid (or glucocorticoid) activity (adrenal insufficiency,
selective hypoaldosteronism, aldosterone resistance)• - administration of potassium sparing diuretics (spironolactone , eplerenone,
amiloride, triamterene)• - Exogenous infusions• - Amino acids like L-arginine and L-lysine (during parenteral nutrition)• - HCl or NH4Cl• - Rapid administration of normal saline (= NaCl 9 g/L) solution (= “dilutional”
metabolic acidosis)
Other questions
3) How is the urinary ammonium (urinary anion gap)?
4) Can you perform some simple investigations?
Response: question 3
3) How is the urinary ammonium (urinary anion gap) ?
• Urinary anion gap: in non renal metabolic acidosis urinary Cl>Na+K; this is because urinary ammonium accompanies Cl
• In this case: Cl 23; Na 20; K 11.4 mmol/l• Na + K – Cl = 31.4 -23 = + 8.4; a positive net
charge indicates an impaired ammonium secretion and, therefore, impaired distal acidification of renal tubule
Response to question 4)
4) Can you perform some simple investigations?
Other investigations
• Renal ecography demonstrated nephrocalcinosis
• Urinary pH; not very simple to detect with the usual methodology
• Our urinary pH (with a plasma venous pH between 7.101 and 7.150): 7.248-7.456
• Diagnosis of DISTAL RENAL TUBULAR ACIDOSIS (DRTA, type 2)
Administration of bicarbonate?
• - Possible benefits: metabolic advantage of faster glycolysis with better availability of adenosine triphosphate in vital organs, and improved cardiac action
• - Risks: extracellular fluid volume expansion, tendency towards hypernatremia and devolepement of hypokalemia and hypocalcemia
• - In this case a correction was started slowly:• Body weight x 0.5 (desired bicarbonate- current
bicarbonate): 7.6 x 0.5 (9-5) = 15.2 mmol in some hours in normal saline
Treatment
• Glucose 5% = 1.800 ml/mq/day• NaCl = 60 mEq/mq/day• KCl = 40 mEq/day• NaHC03- = 20 mEq/day
• - Than orally: NaHC03-, 1 gr/kg/day + potassium citrate 1 mEq/kg/die
• After 7 days: venous pH 7.310; plasma bicarbonates 21.3 mmol/l; pC02 43.6 mmHg
Audiometry evaluation
• The first investigation (the test tones were warble tones) was in the normal range.
• Further audiometry evaluations are required
Molecular diagnosis
• …the molecular diagnosis was of distal renal tubular acidosis due to an homozygous mutation in the ATP6V1B1 gene ( homozygous L81P mutation)
• This mutation is known to be associated with neurosensorial deafness
(Tasic V et al: Atypical presentation of DRTA in two siblings. Pediatr Nephrol 2008; 23:1177-81)
- Laboratory investigations revealed proximal tubular dysfunction that disappeared some months after the beginning of the treatment
Case 2
• The child was in apparent good health up to the age of 9 months when he was admitted to the Hospital for gastroenteritis
• In the urgency plasma Potassium was 1.7 mmol/l• He presented a cardiac arrest followed by immediate
reanimation. • After this episode he did not present any cardiac or
neurologic complications• When he left the Hospital, the child was in good clinical
conditions and his plasma K was between 2.9-3.0 mmol/l
Interpretation
• The severe hypokalemia was considered the cause of cardiac arrest (probably associated with cardiac arrhythmias)
• Rotavirus was identified as the pathogenetic factor of the severe gastroenteritis
At 10 years of age
• He was admitted to the Hospital for a suspicious of appendicitis. His plasma potassium was 2.3 mmol/l
• After surgery his plasma potassium levels persisted at low levels (2.5 e 3.0 mmol/l )
• In this case the origin of hypokalemia was investigated
• New hypothesis?? • It appeared as a chronic condition of
hypokalemia
How is blood pressure?
• His blood pressure was always normal: 90/60 mmHg = in the reference range
• We can exclude hypokalemia associated with high blood pressure (often linked with metabolic alkalosis; total K+ body content normal)
• - renin: primary aldosteronism (either hyperplasia or adenoma), apparent mineralocorticoid excess (= defect in 11--hydroxysteroid-dehydrogenase), Liddle syndrome (congenitally increased function of the collecting tubule sodium channels), dexamethasone-responsive aldosteronism (synthesis of aldosterone promoted not only by renin but also by adrenocorticotropin), congenital adrenal hyperplasia (11--hydroxylase or 17--hydroxylase deficiency), Cushing disease, exogenous mineralocorticoids, licorice-ingestion (= 11--hydroxysteroid-dehydrogenase blockade)
• - or renin: renal artery stenosis, malignant hypertension, renin producing tumor
Hypokalemia associated with normal-low blood pressure
True potassium depletion (= total K+ body content reduced)• Extrarenal “conditions”• - Prolonged poor potassium intake, protein-energy malnutrition• - Gastrointestinal conditions: gastric (associated with alkalosis), vomiting,
nasogastric suction; small bowel ; associated with acidosis: biliary drainage, intestinal fistula, malabsorption, diarrhea, congenital chloride diarrhea
• - Acid-base balance unpredictable: bowel cleansing agents, laxatives, clay ingestion, potassium binding resin ingestion
• - Sweating, full thickness burns•• Renal “conditions”• - Interstitial nephritis, post-obstructive diuresis, recovery from acute renal failure• - With metabolic acidosis: renal tubular acidosis (type I or II), carbonic
anhydrase inhibitors (e.g.: acetazolamide), amphotericin B, outdated tetracyclines
• - With metabolic alkalosis:• - Inherited conditions: Bartter syndromes, Gitelman syndrome, and
related syndromes• - Acquired conditions: normotensive primary aldosteronism, loop and thiazide
diuretics, high dose antibiotics (penicillin, naficillin, ampicillin, carbenicillin)
Main investigations
• The child was in good clinical conditions; his growth was between the 30-50° percentile
• Main biochemical data: • - plasma K, 2.5-2.9 mmol/l ↓; FeK 39-45% ↑• - plasma bicarbonates 28-35 mmol/l ↑• - plasma Na, 140-141 mmol/l; FeNa 1.4-1.8% ↑• - plasma Cl, 94-99 mmol/l; FeCl 2.5-2.7 ↑• - plasma Mg 0.5-0.6 mmol/l ↓; FeMg 4.7-5.4% ↑• - urinary calcium/creatinine 0.001 mg/mg ↓ ↓• - plasma renin activity, 11-15 ng/ml /h (ref. < 5) ↑• - plasma aldosterone, 75-143 pg/ml (ref. 50-300)
Main probable diagnosis
• GITELMAN SYNDROME:- hypokalemia with increased FeK and increased FeCl
• - metabolic alkalosis• - hypomagnesemia• - hypocalciuria• - hyper-reninemia associated with normal
blood pressure• - usually diagnosis during schoolife and
young adults• - some patients with growth failure
Differential diagnosis
• BARTTER SYNDROME TYPE III:- hypokalemia with increased FeK and increased FeCl
• - metabolic alkalosis• - NORMO-MAGNESIEMIA (sometimes
hypomagnesemia, 39% of cases*)• - VARIABLE CALCIURIA (sometimes hypocalciuria
8% of cases*)• - hyper-reninemia associated with normal blood
pressure• - usually diagnosis during early childhood• - half of the patients with growth failure*Konrad M et al; J Am Soc Nephrol 2000; 11:1449-59
Thiazide test(Colussi G, Bettinelli A, 2007)
• A wash out period of at least 7 days was allowed between withdrawal of any therapy and thiazide test; however, oral KCl and Mg salts, if already in use, were maintained and stopped the day before the test
• Thiazide test: after un overnight fast, the patients were invited to drink tap water (10 ml/kg b.w.) to facilitate spontaneous voiding
- 60 - 30 0 30 60 12090 150 180
Plasma Na, K, Cl and creatinine
Hydrochlorothiazide (HCT)1 mg/kg b.w.
Mean of the twourinary values
Maximum urinary value obtained after HCT
FECl
• maximal excretion of FECl at any time after HTC administration
• minus the mean of the two basal FECl
FECl: 0.60%
t test dataControlGit AGit CBartterPseudob0.1110100
ControlSubjects
BartterSyndrome
Gitelman Syndrome
Adults Children
10
1
2
5
20
0.5
0.2
∆ F
ract
iona
l Chl
orid
e E
xcre
tion,
%
Molecular evaluation
• The child presented two heterozigous mutations on the gene SLC12 A3
• Therapy consisted of oral KCl supplementation
• QTc was 0.44”
• No other cardiac complication was reported
Mutations in the SLC12A3 genefound in the Italian population
NH2
R
COOH
1 3 4 5 7 8 9 10 11 1262
Mutations demonstrated in patients subjected to HCT test
Severe syncope and sudden death in children with inborn salt-losing
hypokalaemic tuulopathies. Cortesi C, Bettinelli A, Bianchetti M.; Nephrol Dial
Transplant 2005; 20: 1981-3• - 249 children were evaluated with inborn salt-losing hypokalaemic tubulopathies
• - 19 European paediatric kidney disease specialists
• - Four patients died suddendly and 3 had severe syncope
• - These episodes occurred in the context of severe chronic hypokalemia (< 2.5 mmol/l) or were precipitated by acute diseases, which exacerbated hypokalemia (< 2.0 mmol/l)
Chronic treatment
• - KCl supplementation
• - Antialdosteronic drugs (Spironolactone, amiloride)
Final message
• In patients with inborn salt-losing tubulopathies, diarrhoea or vomiting may cause severe, hazardous hypokalemia (< 2.0 mmol/l)
• A prompt electrolyte and fluid repair is of paramount importance