Renal tubular acidosis
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Transcript of Renal tubular acidosis
Renal Tubular Acidosis
Dr.Anurag FursuleDNB Resident II yr
JLNHRC,Bhilai
Renal tubular acidosis (RTA) is a disease state characterized by a normal anion gap (hyperchloremic) metabolic acidosis in the setting of normal or near-normal glomerular filtration rate.
Definition
Anion Gap = Serum(Na+ + K+ )-(Cl- + HCO3-) Purpose of using anion gap: metabolic
acidosis resulting from bicarbonate loss can be differentiated from accumulation of non volatile acis
Normal value : 14 – 18 mEq/L >20 is highly suggestive of presence of anion
gap For every mEq of bicarb loss there is equal
increase in serum chloride levels so anion gap remains within normal range
What is anion gap?
Mostly reabsorped in PCT 80-85% Remainder in initial part of distal tubule
Bicarbonate reabsorption
Normal Urinary Acidification
Proximal (type II ) RTA is characterized by impairment of PCT reabsorption of bicarbonate.
So at normal plasma HCO3 levels 15%(30% or mor in fanconi) or more HCO3 is excreted in urine and during sustained acidosis excessive HCO3 excretion is reduced and increased reabsorption of HCO3 from proximal tubule.
Distal acidification mechanisms are intact.
Proximal (type II ) RTA
Common Causes of TYPE I RTA
Primary isolated proximal RTA secondary to defective HCO3 reabsorption is rare,may occur as sporadic or inherited(AR).
In children RTA II is usually part of global proximal tubular dysfunction i.e Fanconi syndrome.
Proximal RTA is mc caused by sporadic Fanconi syndrome
Among inherited conditions cystinosis is commonly identified
Clinical Features
Hypophosphatemia,acidosis,low 1,25(OH)3 D3
A detailed history, with particular attention to growth and development recent or recurrent diarrheal illnesses family history of mental retardation failure to thrive end-stage renal disease infant deaths miscarriages is essentialPhysical examination should determine growth parameters volume status dysmorphic features suggesting an
underlying syndrome
Lab Findings
•Urine pH should be assesed during state of metabolic acidosis
•Urine and blood pCO2 difference is more than 20mmHg
Correction of acidosis: 5-20mEq/kg of alkali Prudent to give 5-8 mEq/kg bicarbonate
(shohl solution,polycitra) Part of alkali is given in form of potassium
citrate Dietary Na restriction Hydrochlorthiazide : contraction of ECF and
increased proximal HCO3 reabsorption Supplements of phosphate (neutral
phosphate , joulie solution)are necessary in Fanconi syndrome. Dose: 1-3gm/day
Small doses of vit D may enable healing of rickets(though rare)
Treatment
Mutation in CTNS gene(17p)--encodes novel protein:cystinosin(H+ driven cystine transporter)
Defect in metabolism of cystine
Accumulation of cystine crystals in major organsKidney, brain ,liver,eye,others
Cystinosis
1.Infantile /Nephropathic cystinosis-1st 2 years of life-severe tubular dysfuntion-if no t/t then ESRD till first decade 2.Adoloscents-mild-slower progression to ESRD 3.Benign adult form with no kidney
involvement
Forms
Diminished pigmentation: fair and blond Fanconi syndrome: polyuria, polydipsia Growth failure Rickets Fever: dehydration and decreased sweat production Ocular: photophobia, retinopathy, impaired visual
acuity Hepatosplenomegaly, delayed sexual maturation,
hypothyroidism Complications: CNS abnormalities, muscle weakness,
swallowing dysfunction, pancreatic insufficiency.
Clinical Features and Complications
Diagnosis:1.Detection of cystine crystals in cornea2.Increased leukocyte cystine content3.Prenatal diag by CVS,amniocentesis
Early initiation of therapy is important. correcting the metabolic abnormalities associated
with Fanconi syndrome or chronic renal failure. cysteamine,which binds to cystine and converts it
to cysteine: facilitates lysosomal transport and decreases tissue cystine.
cysteamine eyedrops is required growth hormone for growth failure
Diagnosis & Treatment
Mutation in OCRL1 of X chromosome(XLR)
Encodes PIBPase in golgi network
Accumulation of PIBP
1.Changes in protein trafficking2.Defective actin cyctosleleton polymerization
3.Altered cell signalling for endocytosis
Lowe Syndrome
Clinical Features
•Hypotonia with hyporeflexia•Severe psychomotor retardartion•Bilateral cong Cataract•Strabismus•Infantile onset Glaucoma•cheloids
•Frontal bossing•Deep set eyes•Chubby cheeks•Fair complexion
Rachitic rosary
Fanconi syndrome
Diagnosis is clinical,molecular testing for OCLR gene is available.
Prenatal Dx: slit lamp examination of mother(punctate white opacities)
Treatment is symptomatic-cataract extraction-glaucoma control-physical and speech therapy-drugs to address behavioral problem
Diagnosis & Treatment
Defects in one or more of following:-H+ ATPase-HCO3/Cl anion exchanger-Components of aldosterone pathway Due to impaired H+ excretion urine pH cannot be reduced to
<5.5 Inability to secrete H+ distally is compensated by secreting K+
leading to hypokalemia Lack of NaHCO3 distally, owing to lack of H+ to bind to tubuLar
lumen, leads to chloride absorption leading to hyperchloremia. Chronic metabolic acidosis: impairs citrate excretion leading
hypocitraturia Hypercalciuria:-Increased calcium release from bone to buffer systemic acidosis-Acidosis induced downregulation of renal Calcium transport
protein-Increased distal sodium delivery
Distal (Type I) RTA
Secretory defects causing Distal RTA
Clinical Features
•Urine and blood pCO2 difference is <10mmHg provided urine pH >7.5 and bicarbonate >23mEq/L
Radiology
Base requirement for distal RTA is generally 2-4mEq/kg/24hr.(requirement decreases after age of 5 yrs)
Patient should b monitored for development of hypercalciuria
Some patients may require K+ replacement Symptomatic hypercalciuria: gross
hematuria, nephrocalcinosis, nephrolithiasis — treated with thiazide diuretics
Vit D should be used in case of severe rickets
Treatment
aldosterone -direct effect on the H+/ATPase responsible for
hydrogen secretion-potent stimulant for potassium secretion in
the collecting tubule Type IV RTA occurs as the result of -impaired aldosterone production
(hypoaldosteronism)-impaired renal responsiveness to
aldosterone (pseudohypoaldosteronism).
Type IV RTA
Etiology
Type IV RTA
ACUTE CHRONIC
OBSTRUTIVE UROPATHY
•ACUTE PYELONEPHRITIS•ACUTE URINARY OBSTRUCTION
ALDOSTERONE UNRESPONSIVENESS
ACIDOSISHYPERKALEMIA
Growth failure Polyuria Dehydration with salt wasting Life threatning hyperkalemia
Clinical Features
PHA ISalt loss Hypotensionhyperkalemia PHA IIHypertensionAcidosisHyperkalemiaHyporeninemic hypoaldosteronism
hyperkalemic non–anion gap metabolic acidosis Urine may be alkaline or acidic Elevated urinary sodium levels with
inappropriately low urinary potassium levels reflect the absence of aldosterone effect.
require chronic treatment for hyperkalemia with sodium-potassium exchange resin (Kayexalate).
PHA I- Kayexelate PHA II-thiazides Addisons- fludrocortisone
Lab investigation and treatment
Approach to RTA
Nelson Textbook of Pediatrics 19th edition IAP Textbook of Pediatrics 5th edition Pediatric Nephrology by RN Srivastava,A
Bagga 5th edition
References