ACIDOSIS

TUBULAR
RENAL
 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
 Acidosis & anion gap
• =[Na] – [Cl + Hco3]
• < 12 = normal or absence of anion gap
as in bicarbonate loss in {diarhea ,RTA,carbonic
anhydrase inhibitor , ureterosigmoidostomy,
dilutional acidosis, pancreatic fistula}
• >20 =increased anion gap
as in{ lactic acidosis, DKA, inborn errors of
metabolism, uremia, poisoning with
(salicylate,methanol,ethanol)}
Normal Urinary Acidification
• Urinary acidification involves two processes: bicarbonate
reabsorption and hydrogen ion excretion .

• 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.

• 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
DEFINITION
• Renal tubular acidosis (RTA) refers to the
development of a metabolic acidosis due to a
defect at the level of the renal tubule.
• All forms of RTA are non-anion gap or
hyperchloremic metabolic acidosis resulting
from loss of bicarbonate (inability to reabsorb
HCO3) or retention of hydrogen ion (inability to
excrete).
• In addition to the hyperchloremic metabolic
acidosis, RTAs can also present with varying
degrees of renal insufficiency
TYPES OF RTAs
• Distal RTA (Type I): loss of hydrogen ion
secretion into urine due to defect in distal
tubule.
• Proximal RTA (Type II): loss of bicarbonate
reabsorption due to defect in the proximal
tubule
• Hypoaldosteronism or hyperkalemic (Type IV):
aldosterone deficiency or distal tubule resistance
to aldosterone leading to loss of potassium
excretion. Ensuing hyperkalemia leads to
suppression of ammonia excretion.
Proximal (Type II) Renal Tubular
Acidosis
• Pathogenesis
Proximal RTA results from impaired proximal tubule
bicarbonate reabsorption. Isolated forms of inherited or
acquired proximal RTA occur, although they are generally
rare. Isolated 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 syndrom .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.
 X
-
Causes l
Isolated i
• Sporadic n
• Hereditary k
Fanconi Syndrom e
Primary d
Sporadic n
Hereditary e
Cystinosis p
Lowe syndrome h
Galactosemia r
Tyrosenemia
o
Fructosemia
Fanconi-Bickel syndrome
l
Wilson disease i
Mitochondrial diseases t
secondary h
Heavy metals i
Outdated tetracycline a
Gentamicin s
Ifosfamide i
Cyclosporine s
)
Clinical Manifestations of Proximal
RTA and Fanconi Syndrome.
• 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. 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. In contrast, urinary indices in patients
with Fanconi syndrome demonstrate varying
degrees of phosphaturia, aminoaciduria,
glycosuria, uricosuria, and elevated urinary
sodium or potassium. Depending on the nature
of the underlying disorder, laboratory evidence
of chronic renal insufficiency, including elevated
serum creatinine, may be present
Distal (Type I) Renal Tubular
Acidosis
Pathogenesis
Distal RTA occurs as the result of impaired distal urinary
acidification (hydrogen ion secretion). Primary or
secondary causes can result in 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. 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.
 y

E•
Acidosis Tubular Renal Distal (Type I) h
l

Causas
e
SECUNDARIA r
Nefritis Intersticial s
PRIMARIA Uropatía Obstructiva -
Reflujo Vesicoureteral D
Esporádica Pielonefritis a
Rechazo a Trasplante n
Hereditaria Nefropatía de anemia falciforme l
Síndrome de Ehlers-Danlos o
Nefritis Lúpica s
Nefrocalcinosis s
Cirrosis hepática y
n
Toxines\medications d
Anfotericina B r
Litio o
Cisplatino m
e

L•
Distal (Type I) Renal Tubular
Acidosis
Manifestaciones Clinicas:
Patients with distal RTA share common features with
those of proximal RTA, including 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.
Hyperkalemic (Type IV) Renal
Tubular Acidosis
• Pathogenesis.
Type IV RTA occurs as the result of 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. 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). 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.
Hyperkalemic (Type IV) Renal
Tubular Acidosis
Causes
• primary
• Sporadic
• Hereditary
• secondary
Hypoaldosteronism
• Addison disease
• Congenital adrenal hyperplasia
• Prolonged heparinization
• Pseudohypoaldosteronism (type I or II)
• Obstructive uropathy
• Pyelonephritis
• Interstitial nephritis
• Diabetes mellitus
• Sickle cell nephropathy
• Trimethoprim/sulfamethoxazole
• Angiotensin-converting enzyme inhibitors
• Cyclosporine
Hyperkalemic (Type IV) Renal
Tubular Acidosis
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. 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.
 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
NOTE:
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.
Diagnosis of RTA
# the anion gap should be calculated using
the formula [Na+] - [Cl- + HCO3-]. Values of
less than 12 demonstrate the absence of
an anion gap.
# True hyperkalemic acidosis is consistent
with type IV RTA, whereas the finding of
normal or low potassium suggests type I or
II .
# urine pH may help distinguish distal from
proximal causes. A urine pH of less than 5.5
in the presence of acidosis suggests
proximal RTA, whereas patients with distal
RTA typically have a urine pH of more than
6.0.
# The urine anion gap ([Urine Na + Urine K] -
Urine Cl) is sometimes calculated to confirm
the diagnosis of distal RTA. A positive gap
suggests distal RTA. A negative gap is
consistent with proximal tubule bicarbonate
wasting (or gastrointestinal bicarbonate
wasting).
# acid loading test with use of ammonium
chloride with finding of further fall in serum
bicarbonate without decline of urine PH
below 6.0 without development of –ve urine
anion gap is proof of distal RTA
# 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 .
# Random or 24-hr urine calcium and
creatinine measurements will identify
hypercalciuria .
# A renal ultrasound should be obtained to
identify underlying structural abnormalities
such as obstructive uropathies as well as to
determine the presence of nephrocalcinosis
Ultrasound examination of a child with distal renal
tubular acidosis demonstrating medullary
nephrocalcinosis
Treatment of RTA
• 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 Fanconi syndrome generally require
phosphate supplementation .
• 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.
Treatment of RTA cont.
• Patients with type IV RTA may require chronic treatment
for hyperkalemia with sodium-potassium exchange resin
(Kayexalate®).
• 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. Vitamin D is needed to offset the
secondary hyperparathyroidism that complicates oral
phosphate therapy
• The mainstay of therapy in all forms of RTA is
bicarbonate replacement .