This document discusses renal tubular acidosis (RTA). It describes the different types of RTA (proximal, distal, and hyperkalemic) and explains their pathophysiology. For each type it covers the mechanisms of impaired acidification, clinical manifestations like acidosis and electrolyte abnormalities, and treatments involving bicarbonate replacement. Key points are that proximal RTA involves impaired bicarbonate reabsorption, distal RTA impaired hydrogen ion secretion, and hyperkalemic RTA impaired aldosterone effects. Diagnosis involves assessing the nature of the metabolic acidosis through blood and urine tests.

1. Dr. Sajid Sultan
Resident Nephrology
The Kidney Centre PGTI Karachi

2. TUBULAR FUNCTION
• 2/3 of glomerular ultra filtrate
is reabsorbed from the PT
• 60% of Na ia absorbed in the
PT & 25% in the ALH &15%
in the DT.
• All filterd K is reabsorbed in
PT & excretion occur in DT
and collecting ducts.
• H excretion occur in early
parts of PT and also DT.
• Ca reabsorption occur in
parallel with Na reabsorption
• Majority of PH is reabsorbed
in the PT.
• The process of K and H ion
excretion and Na
reabsorption iall stimulated
by aldosteron.
• 85% of bicarbonate is
reabsorbed in PT and the
remaining 15% reabsorbed in
the DT

4. Acidosis & anion gap
< 12 = normal or absence of anion gap
 RTA
 carbonic anhydrase inhibitor ,
 Ureterosigmoidostomy
 pancreatic fistula
 diarhea

5. Acidosis & anion gap
>16 =increased anion gap
• lactic acidosis
• DKA
• inborn errors of metabolism
• Uremia
• poisoning with (salicylate,methanol,ethanol)}

6. Normal Urinary Acidification
• Urinary acidification involves two processes:
• Bicarbonate reabsorption and
• Hydrogen ion excretion .

7. Normal Urinary Acidification
 In infants, bicarbonate reabsorption is less efficient,
and renal bicarbonate excretion may occur at serum
concentrations less than 22 mmol/L.
 The hydrogen ion in the tubular lumen binds with
bicarbonate and, under the influence of carbonic
anhydrase, is converted to carbon dioxide and water.

8. Normal Urinary Acidification
 Secretion of the daily acid load (approximately 1
mEq/kg/24 hr produced during normal cellular
processes) is accomplished by hydrogen ion secretion
 Approximately 85% of the filtered bicarbonate is
reabsorbed in the proximal tubule .
 The remaining 15% of bicarbonate is reabsorbed
distally

9. DEFINITION
• metabolic acidosis due to a defect at the
level of the renal tubule.
• non-anion gap or hyperchloremic
metabolic acidosis ------------ from loss of
bicarbonate
 inability to reabsorb HCO3 or
 retention of hydrogen ion (inability to excrete).

10. 2----1-----4
proximal 2, distal 1, collecting tubules 4

11. 214-------low,low,MORE

12. Find the ODD for caphstones

13. Odd is one and its different

14. The odd one has the stones as
well

15. TYPES OF RTAs
• Distal ------------------loss of hydrogen ion
secretion into urine
• Proximal ---------------- loss of bicarbonate
reabsorption
• Hypoaldosteronism or hyperkalemic (Type
IV): ----------- distal tubule resistance to
aldosterone ----------loss of potassium
excretion--------hyperkalemia ------------
suppression of ammonia excretion.

16. In general mechanisms

17. Proximal (Type II) Renal
Tubular Acidosis
• Pathogenesis
 Impaired proximal tubule bicarbonate reabsorption.
 Isolated forms of inherited or acquired proximal occur,
 Autosomal dominant forms,
 As well as an autosomal recessive form associated with ocular
abnormalities, have been reported.
 More typically, proximal rta occurs as a component of global proximal
tubule dysfunction or fanconi syndrome. Both autosomal dominant
and autosomal recessive forms of primary fanconi syndrome occur.
 In addition, secondary fanconi syndrome may occur as a component
of one of several inherited renal tubular disorders or in acquired
disease states.

18. Pathogenesis

19. Pathogenesis

21. Clinical Manifestations
• Patients with isolated, sporadic, or inherited
proximal RTA commonly present with growth
failure in the first year of life.
• Additional symptoms may include polyuria,
dehydration (due to sodium losses), anorexia,
vomiting, constipation, and hypotonia.

22. Clinical Manifestations
 Patients with PRIMARY FANCONI SYNDROME will have
additional symptoms secondary to phosphate wasting such as
rickets.
 Those with systemic diseases will present with additional signs
and symptoms specific to their underlying disease.
 A non-anion gap metabolic acidosis will be present.
 Urinalysis in patients with isolated proximal RTA is generally
unremarkable.
 The urine pH is acidic (<5.5), because distal acidification
mechanisms are intact in these patients.

23. Distal (Type I) Renal Tubular
Acidosis
Pathogenesis
 Impaired distal urinary acidification (hydrogen ion secretion).
 Damaged or impaired functioning of one or more transporters or proteins
involved in the acidification process, including the h+/atpase, the hco3-/cl-
anion exchangers or the components of the aldosterone pathway.
 Because of impaired hydrogen ion excretion, urine ph cannot be reduced
below 5.5, despite the presence of severe metabolic acidosis.
 Loss of sodium bicarbonate results in hyperchloremia and hypokalemia.

24. Pathogenesis
 Hypercalciuria is usually present and may lead to
nephrocalcinosis or nephrolithiasis.
 Chronic metabolic acidosis also impairs urinary citrate excretion.
 Hypocitraturia further increases the risk of calcium deposition in
the tubules.
 Bone disease is common, resulting from mobilization of organic
components from bone to serve as buffers to chronic acidosis.
 Both primary sporadic or inherited forms occur. As with
proximal RTA, distal RTA can also occur as a complication of either
inherited or acquired diseases of the distal tubules.

25. Toluene induced RTA 1
 Present in glue
 Inhibits proton secretion
 Produceshipuuirc and benxzopic acid
 Buffered by bicarbonate, resulting in acidosis.

27. Clinical Manifestations
Non-anion gap metabolic acidosis and growth
failure.
However, distinguishing features of distal RTA
include nephrocalcinosis and hypercalciuria.
The phosphate and massive bicarbonate
wasting characteristic of proximal RTA is
generally absent.

28. Hyperkalemic (Type IV) Renal
Tubular Acidosis
• Pathogenesis:
impaired aldosterone production (hypoaldosteronism) OR
impaired renal responsiveness to aldosterone ("pseudo" hypoaldosteronism).
Because aldosterone has a direct effect on the H+ ATPase responsible for hydrogen
secretion, acidosis results.
In addition, aldosterone is a potent stimulant for potassium secretion in the collecting
tubule.
Loss of aldosterone effect results in hyperkalemia.

29. Pathogenesis:
 This further affects acid-base status by inhibiting ammoniagenesis
and, thus, hydrogen ion excretion.
 Aldosterone deficiency typically occurs as a result of adrenal gland
disorders such as Addison disease or congenital adrenal hyperplasia
(CAH).

30. Pathogenesis:
 In children, aldosterone unresponsiveness is a more common cause
of type IV RTA.
 This may occur transiently, during an episode of acute
pyelonephritis or acute urinary obstruction, or chronically, particularly
in infants and children with a history of obstructive uropathy.
 The latter patients may have significant hyperkalemia, even in
instances when renal function is normal or only mildly impaired.
Rare examples of inherited forms of type IV RTA have been
identified.

32. Clinical Manifestations.
Patients with type IV RTA, like those with types I and II
RTA, may present with growth failure in the first few
years of life.
Polyuria and dehydration (from salt wasting) are
common. Rarely, patients (especially those with
pseudohypoaldosteronism type 1) will present with life-
threatening hyperkalemia.

33. Clinical Manifestations.
 Patients with obstructive uropathies may present
acutely with signs and symptoms of pyelonephritis,
such as fever, vomiting, and foul-smelling urine.
 Laboratory tests reveal a hyperkalemic non-anion gap
metabolic acidosis.
 Urine may be alkaline or acidic.
 Elevated urine sodium levels with inappropriately low
urine potassium levels reflect the absence of
aldosterone effect.

34. Diagnosis of RTA
• confirm the presence of and nature of the metabolic
acidosis.
• assess renal function.
• rule out other causes of metabolic acidosis, such as
diarrhea ( which is extremely common) .
• identify electrolyte abnormalities (K,Na,Cl)
• blood urea nitrogen, calcium, phosphorus, and creatinine
and pH
blood should be obtained by
venous puncture. Traumatic blood draws (such as heel stick specimens) or
prolonged specimen transport time can lead to falsely low bicarbonate
levels, often in association with an elevated serum potassium value.

35. Diagnosis of RTA
 True hyperkalemic acidosis is consistent with type IV RTA, whereas
the finding of normal or low potassium suggests type I or II.

36. Urine pH
 Urine pH may help distinguish distal from proximal causes.
A urine pH of less than 5.5in the presence of acidosis
suggests proximal RTA,
 whereas patients with distal RTA typically have a urine pH
of more than 5.5

39. URINALYSIS
 A urinalysis should also be obtained to determine the
presence of glycosuria, proteinuria, or hematuria
suggesting the possibility of more global tubular
damage or dysfunction .

42. Urine Calcium
 Random or 24-hr urine calcium and
creatinine measurements will identify
hypercalciuria .

43. Renal ultrasound
 A renal ultrasound should be obtained to identify
underlying structural abnormalities such as
obstructive uropathies as well as to determine
the presence of nephrocalcinosis.

44. Ultrasound examination of a child with distal renal
tubular acidosis demonstrating medullary
nephrocalcinosis

45. Treatment:
• Patients with proximal RTA often require large quantities
of bicarbonate, up to 20 mEq/kg/24 hr in the form of
sodium bicarbonate or sodium citrate solution (Bicitra or
Shohl's solution). Also we have( polycitra solution) which
same as bictra with adding of potassium citrate.
• The base requirement for distal RTAs is generally in the
range of 2-4 mEq/kg/24 hr, although patient
requirements may vary .
• Patients with distal RTA should be monitored for the
development of hypercalciuria. Those with symptomatic
hypercalciuria (e.g., recurrent episodes of gross
hematuria), nephrocalcinosis, or nephrolithiasis may
require thiazide diuretics to decrease urine calcium
excretion.

46. Treatment of RTA cont.
• Patients with type IV RTA may require chronic treatment
for hyperkalemia with sodium-potassium exchange resin
(Kayexalate).
• The mainstay of therapy in all forms of RTA is
bicarbonate replacement .

47. Save the bones:
 Rickets may be present in primary renal tubular acidosis (RTA),
particularly in type II or proximal RTA.
 Administration of sufficient bicarbonate to reverse acidosis stops bone
dissolution and the hypercalciuria that is common in distal RTA.
 Proximal RTA is treated with both bicarbonate and oral phosphate
supplements to heal bone disease.
 Doses of phosphate similar to those used in familial
hypophosphatemia or Fanconi syndrome should be used.
 Vitamin D is needed to offset the secondary hyperparathyroidism that
complicates oral phosphate therapy

48. Thanks……