2.
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.
3.
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
7.
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.
8.
9.
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
11. 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 essential
Physical examination should determine
growth parameters
volume status
dysmorphic features suggesting an
underlying syndrome
12. •Urine pH should be assesed during state of
metabolic acidosis
•Urine and blood pCO2 difference is more than
20mmHg
13.
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)
14. Mutation in CTNS gene(17p)--encodes novel
protein:cystinosin(H+ driven cystine transporter)
Defect in metabolism of cystine
Accumulation of cystine crystals in major organs
Kidney, brain ,liver,eye,others
15. 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
17. Diagnosis:
1.Detection of cystine crystals in cornea
2.Increased leukocyte cystine content
3.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
18. Mutation in OCRL1 of X chromosome(XLR)
Encodes PIBPase in golgi network
Accumulation of PIBP
1.Changes in protein trafficking
2.Defective actin cyctosleleton polymerization
3.Altered cell signalling for endocytosis
20. 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
21. 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
22.
23.
24. •Urine and blood pCO2 difference is
<10mmHg provided urine pH >7.5 and
bicarbonate >23mEq/L
25.
26.
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
27. 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).
