2. Introduction
• Lungs and Kidneys are responsible for Normal
acid base balance
• Alveolar ventillation removes CO2
• Kidneys reabsorb filtered Bicarbonate and
excrete a daily quantity of Hydrogen ion equal
to that produced by the metabolism of dietary
proteins
3. Introduction(contd)
• Normal renal response to Acidemia is to
reabsorb all of the filtered biacrbonate and to
increase hydrogen ion excretion primarily by
enhancing the excretion of ammonium ions in
the urine
4. RTA-Defination
• Renal tubular acidosis refers to the development of
metabolic acidosis because of a defect in the ability of
the renal tubules to perform these functions.
• All forms of RTA are characterised by--
• Metabolic acidosis,Normal anion gap, Hyperchloremia
• Usually results from ----
• Net retention of hydrogen chloride or its equivalent
( ammonium chloride)or
• Net loss of sodium bicarbonate or its equivalent
5. Classification/Subgroup
• Distal or Type 1 RTA
• Proximal or type 2 RTA
• Type 4 RTA( Hyperaldosternism)
• Type 3RTA??----features of both type 1 and
type 2RTA. RARE autosomal recessive
syndrome ( due to carbonic anhydrase II
deficiency).Other features include
Osteopetrosis,cerebral calcification and
mental retardation
6. Renal role in Acid-Base Balance
• To maintain acid –base balance
• Reabsorption of Filtered bicarbonate
• Excretion of Daily Acid load
7. Renal acid base balance
• Reabsorption of Bicarbonate
• Predominantly occurs in proximal Tubules
primarily by Na-H exchange
• Approximately 85-90% filtered load is
reabsorbed proximally.
• 10-15% is reabsorbed in Distal Nephron via H
ion secretion by a proton pump(H-ATPase)
• Under normal conditions, virtually no
bicarbonate is present in the final urine
8.
9. Acid excretion
• The excretion of daily H ion load is a function of distal tubules
• It requires sufficient buffering compounds to bind H ions , to
be excreted in urine
• The principal buffers in urine are Ammonia ( excreted as
ammonium) and phosphate ( ref to as titrable
acidity).Ammonium excretion requires the renal synthesis of
ammonia and the secretion of hydrogen ion by the collecting
duct cells into the tubular lumen which serves to trap the
ammonia in the urine as ammonium( ammonia diffuses freely
across cell memb while ammonium does not)
• Renal production of NH4 is stimulated by intracellular acidosis
• Hence when syst acid load is modestly increased , near normal
balnce occurs via increasing NH3 production and excretion
• Failure to excrete sufficient ammonium leads to retention of
net H ion and devpt of Metabolic acidosis
10. Acid excretion-consequences
• Impaired H ion secretion is the primary defect
in Distal RTA
• Impaired ammoniagenesis is the primary
defect in Type 4 RTA and renal failure.
• These disorders are associated with different
abnormalities of plasma potassium conc
• Distal RTA—hypokalemia
• RTA type 4 and renal failure in late stages
with hyperkalemia.
11. Acid excretion-consequences
• Degree of acidosis may be different in different types
of RTA
• Type 1-Plasm HCO3 may fall below 10
meQ/L(inability to excrete daily acid load leading to
progressive ion retention)
• Type 2Plasma HCO3 12—20 meQ/L(HCO3 wasting
only when plasma HCO3 above the reabsorptive
threshhold and the more disrtal seg have substantial
HCO3 reabsorptive capacity )
• Type 4RTA-Hyperkalemia is prominent .Plasma HCO3
usually above 17 meQ/L
12. Proximal RTA(type2)
• Occasionally present as Isolated defect
• More commonly associated with generalised
proximal dysfunction- Fanconi Syndrome—
bicarbonaturia,glucosuria,phosphaturia,uricosuria,a
minoaciduria and tubular proteinuria.
• Most common causes in Adults—Multiple
myeloma,carbonic anhydrase
inhibitor(acetazolamide),ifsofamide
• In children-several forms of genetically inherited
diseases are responsible,Cystinosis is most common
13. Proximal RTA type 2
• The diagnosis of proximal RTA is made by
measurement of urine pH and fractional
bicarbonate excretion during a bicarbonate
infusion. The hallmark is a urine pH above and
appearance of > 15 % of filtered bicarb in the
urine when a serum bicarb is raised to a
normal level.
14. Complications of type 2 RTA
• Poor growth in children
• Osteomalacia due to hypoPO4
• Treatment may be difficullt as large amount of alkali may be
required to correct acidosis which may increase
hypokalemia.Hence empirically determined fraction of alkali
given as potassium salt( usually K citrate)
• Thiazide diuretic( associated mild vol depletion depletion
enhances proximal Na reabsorption ans Secondarily HCO3
• Po4 and Vit D supllement
• Serial monitoring of Electrolytes
• Type 2 RTA is transient in some children
15. Distal RTA
• Distal type 1RTA is charcterised by an impaired capacity for H
ion and therefore NH3 secretion in the collecting tubules
• This manifest as an abnrmally high Urine pH (. 5.5 Normal
urine pH 4.5-5)during systemic acidosis
• Results from one of several defects in distal hydrogen ion
secretion---1) Decreased proton pump activity 2)Increased
luminal membrane permaebility with backleak of hydrogen
ions 3) Diminished distal tubular Na reabsorption which
reduces the electrical gradient for proton secretion
17. Distal RTA -Presentation
• Hyperchloremic acidosis with an appropriately high urine
pH( > 5.5 in p of acidosis)
• Hypercalciuria due to chronic acidosis on bone resorption and
renal tubular Reabsorption of Ca
• Nephrolithiasis and nephrocalcinosis
• Hypokalemia( due to K wasting due to proton pump defect) is
frequent –muscle weakness.
• Hyperkalemia can be seen esp. when RTA is associated with
obstructive uropathy or Sickle cell disease. Here the defect in
Na reabsorption interferes with both K and hydrogen ion
secretion
18. Treatment
• Correction of acidemia—with alkali therapy
• Advantages—minimize new stone
formation,nephrocalcinosis,diminished Ca losses and
hence osteopenia and help in correction of
hypokalemia
• Bicarb 1-2 meq/kg- sodabicarb/ or sodium
citrate.Children will require more
• Potassium citrate or Na citrate is indicated for
persistent Hypokalemia or Ca Stone disease
• High Na ,Low K diet with thiazide or loop diuretic in
pt with Hyperkalemic distal RTA
19. Type 4 RTA
• Due to either Aldosterone deficiency or tubular resistance to the action of
aldosterone.
• Major causes of Aldosterone deficiency
• Primary-1)Primary adrenal insufficiency 2)congenital hyperplasia(21
hydroxylase def),3)Isolated aldosterone synthase def ,4)Heparin and
LMWH
• Hyporeninemic hypoaldosteronism—1) renal disease-Diabetic
nephropathy, volume expansion as inGN,ACEI,NSAIDS,Cyclosporin,HIV
inf,some cases of obstructive uropathy
• Aldosterone Resistance—1)Drugs which close the collecting tubule Na
channel—
Amiloride,Spironolactone,triamterene,Trimethoprim,pentamidine,2)Tubul
ointerstitial disease ,3)Pseudohypoaldosteronism,4)Distal chloride shunt
20. Presentation RTA4
• Hyperkalemia (hypoaldosterone) associated with mild to
moderate acidosis( due to suppression of NH4 excretion)
• Appropriate urine acid pH below 5.3 in p of acidosis and
plasma HCO3 above 17 meq/L
• Diagnosis can be made by measuring plasma renin and
aldosterone level
• Many pts are treated empirically with low K diet, diuretics
and Ion excahange resins.
• Fludrocortisone ( 0.05-0.2mg/d)for pt with primary
aldosterone def.But often it is NOT used due to HTN, heart
failure and edema
