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.
i. classic distal (type I) RTA
ii. proximal (type II) RTA
iii. combined proximal and distal (type III)
iv. hyperkalemia(type IV) RTA
3. Distal (Type I) Renal Tubular Acidosis
damaged or impaired functioning of transporters or proteins
involved in the acidification process, including the H+/ATPase,
Because of impaired hydrogen ion excretion, urine pH cannot be
reduced to <5.5, despite the presence of severe metabolic acidosis.
Inability to secrete H+ is compensated by increased K+ secretion
distally, leading to hypokalemia
Hypercalciuria nephrocalcinosis or nephrolithiasis.
Hypocitraturia ca+ deposition in the tubules.
Bone disease serve as buffers to chronic acidosis.
4. PATHOPHYSIOLOGY
There is an inability to excrete H+ while K+ cannot be
reabsorbed, leading to
acidemia (as H+ builds up in the body) and hypokalemia (as K+
cannot be reabsorbed).
renal excretion is the primary means of eliminating acid from the
body, there is consequently a tendency towards acidemia
it leads to an inability to acidify the urine to a pH <5.3
the substance of the kidney develops stones bilaterally
5.
6. CLINICAL MANIFESTATIONS
non–anion gap metabolic acidosis
growth failure
distinguishing features of distal RTA include
nephrocalcinosis and hypercalciuria.
phosphate and massive bicarbonate wasting characteristic
of pRTA is generally absent.
7. Defect of the proximal tubule in bicarbonate (HCO3) reabsorption.
HCO3 fully reabsorbed only when plasma HCO3 concentration <15–16
mEq/L (compared with normal threshold of 24 mEq/L). Urine pH <5.5
unless plasma HCO3 above reabsorptive threshold.
Type 2 proximal RTA
8. It is caused by a failure of the proximal tubular cells to
reabsorb filtered
bicarbonate from the urine, leading to urinary bicarbonate
wasting and subsequent acidemia.
The distal intercalated cells function normally, so the
acidemia is less severe
than dRTA and the urine can acidify to a pH <5.3.
it is usually associated with a generalized dysfunction of the
proximal tubular cells called Fanconi's syndrome.
Pathophysiology
9. Faconi’s syndrome
component of global proximal tubular dysfunction
Fanconi syndrome (low-molecular-weight proteinuria, glycosuria,
phosphaturia, aminoaciduria) proximal RTA, cystinosis and Lowe
syndrome .
phosphaturia, glycosuria, aminoaciduria, uricosuria, and
tubular proteinuria. The principal feature of Fanconi's syndrome is
bone demineralization due to phosphate wasting.
10. • Autosomal dominant form is rare.
• -Autosomal recessive form is associated with ophthalmologic
abnormalities and mental retardation. Occurs in Fanconi syndrome,
which is associated with several genetic diseases
11. Diseases associated with Fanconi syndrome
Sporadic
Multiple myeloma & other dysproteinemic
states
Amyloidosis
Heavy-metal poisoning
Medications:
Acetazolamide, sulfanilamide, ifosfamide, o
utdated tetracycline, topiramate
Autoimmune disease
Interstitial renal disease
Nephrotic syndrome
Congenital heart disease
Defects in calcium metabolism
12. Cystinosis
accumulation of cystine crystals in most (kidney, liver, eye,and brain).
3 clinical patterns.
• infantile or nephropathic cystinosis
severe tubular dysfunction and growth failure.
• Adolescents(mild)
less-severe tubular abnormalities and a slower progression to renal failure.
• benign adult form with no renal involvement also exists.
13. Patients with nephropathic cystinosis present with clinical manifestations reflecting their
pronounced tubular dysfunction and Fanconi syndrome
polyuria and polydipsia, growth failure, and rickets.
Fever, caused by dehydration or diminished sweat production, is common.
fair skinned and blond because of diminished pigmentation.
photophobia, retinopathy, and impaired visual acuity.
Patients also can develop hypothyroidism, hepatosplenomegaly.
The diagnosis of cystinosis is suggested by the detection of cystine crystals in the
cornea and confirmed by measurement of increased leukocyte cystine content.
Treatment of cystinosis is directed at correcting the metabolic abnormalities associated with
Fanconi syndrome or chronic renal
failure. cysteamine,
14. Extremely rare autosomal recessive syndrome with features of
both type I and type II(juvenile RTA).
Combined dRTA and pRTA is also observed as the result of
inherited carbonic anhydrase II deficiency. give rise to an
autosomal recessive syndrome of osteopetrosis, renal tubular
acidosis, cerebral calcification, and mental retardation.
Type 3 RTA-Combined proximal and distal RTA
15. Hyperkalemic (Type IV) Renal Tubular Acidosis
Pathogenesis
impaired aldosterone production (hypoaldosteronism)
impaired renal responsiveness to aldosterone (pseudohypoaldosteronism).
aldosterone
potassium secretion in the collecting tubule;
inhibiting ammonia genesis and, thus, H+ excretion.
Aldosterone deficiency (Addison disease or some forms of CAH).
aldosterone unresponsiveness can occur transiently
acute pyelonephritis or acute /chronic urinary obstruction.
16. Clinical Manifestations
growth failure in the 1st few years of life.
Polyuria and dehydration (from salt wasting) are common.
may present with lifethreatening Hyperkalemia (pseudohypoaldosteronism type
1).
Patients with obstructive uropathies can 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.
17. History collection
Often asymptomatic (particularly type IV)
Failure to thrive in children
Anorexia, nausea/vomiting
Weakness or polyuria (due to hypokalemia)
Rickets in children
Osteomalacia in adults
Constipation
Polydipsia
18. Diagnostic Approach to Renal Tubular Acidosis
The blood anion gap should be calculated using the formula [Na+ ] − [Cl− +
HCO3 − ].
Values of < 12 demonstrate the absence of an anion gap.
detailed history (growth and development, recent or recurrent diarrheal illnesses, a
family history of failure to thrive, endstage renal disease, infant deaths, or
miscarriages is essential)
urine anion gap ([urine Na+ + urine K+ ] −urine Cl− )
positive gap distal RTA.
negative gap proximal tubule bicarbonate wasting (or gastrointestinal
bicarbonate wasting).
UDR glycosuria, proteinuria, or hematuria, suggesting more global tubular
damage.
Renal U/S obstructive uropathies, nephrocalcinosis
19. protracted diarrhea can deplete their total-body bicarbonate stores and can have
persistent acidosis despite apparent restoration of volume status.
full evaluation for RTA should be delayed for several days
falsely low bicarbonate levels (small volumes adult-size tubes, prolonged
specimen transport time)
RTA should be suspected when metabolic acidosis is accompanied by
hyperchloremia and a normal plasma anion gap (Na+ - [Cl- + HCO3-] = 8 to 16
mmol/L) in a patient without evidence of gastrointestinal HCO3- losses and who is
not taking acetazolamide or ingesting exogenous acid
20. Treatment
bicarbonate replacement all forms of RTA .
• Patients with pRTA often require up to 20 mEq/kg/24 hr,( sodium
bicarbonate or sodium citrate solution (Bicitra or Shohlsolution).
• distal RTAs require 2-4mEq/kg/24 hr
• Fanconi syndrome usually require phosphate supplementation.
• type IV RTA require chronic treatment for hyper-K with sodium–
potassium exchange resin (i.e., sodium polystyrene sulfonate).
• distal RTA should be monitored for the development of hypercalciuria.
. symptomatic hypercalciuria (recurrent episodes of gross
hematuria),nephrocalcinosis, or nephrolithiasis can require thiazide
diuretics.
21. • Thiazide diuretic may be beneficial if large doses of alkali are ineffective or not
well tolerated.
Distal RTA
• generally be treated with 1 to 2 meq/kg of sodium citrate (Bicitra) or
bicarbonate.
• Potassium citrate, alone or with sodium citrate (Polycitra), is indicated
for persistent hypokalemia or for calcium stone disease.
• For patients with hyperkalemic distal RTA, high-sodium, low-
potassium diet plus a thiazide or loop diuretic if necessary.
22. Prognosis
• Patients with The prognosis of RTA depends to a large extent on the
nature of any existing underlying disease. Patients with treated
isolated proximal or distal RTA generally demonstrate improvement
in growth, provided serum bicarbonate levels can be maintained in
the normal range.
• Patients with systemic illness and Fanconi syndrome can have
ongoing morbidity with growth failure, rickets, and signs and
symptoms related to their underlying disease.
23. COMPLICATIONS
• Nephrocalcinosis, nephrolithiasis(type I)
• Hypercalciuria (type I)
• Hypokalemia (type I, type II if given bicarbonate)
• Hyperkalemia (type IV, some causes of type I)
• Osteomalacia (type II due to phosphate wasting)