metabolic acidosis develops because of defects in the ability of the renal tubules to perform the normal functions required to maintain acid-base balance.

1. RENAL SYSTEM
RENALTUBULAR ACIDOSIS

2. INTRODUCTION
 Lungs and Kidneys are responsible for Normal acid
base balance
 Alveolar ventilation removes CO2
 Kidneys reabsorb filtered Bicarbonate and excrete
a daily quantity of Hydrogen ion equal to that
produced by the metabolism of dietary proteins.
 Hydrogen ions are excreted primarily by
enhancing the excretion of ammonium ions in the
urine

3. DEFINITION
The term "renal tubular acidosis" (RTA)
refers to a group of disorders in
which, despite a relatively well-
preserved glomerular filtration
rate, metabolic acidosis develops
because of defects in the ability of the
renal tubules to perform the normal
functions required to maintain acid-
base balance.

5. INCIDENCE
 Predominant age: All ages
 Predominant sex: Male > Female (with
regard to type II RTA with isolated defect
in bicarbonate reabsorption)

6. TYPES
 Distal / type 1 RTA
 Proximal / type 2 RTA
 Hypoaldosteronism / type 4 RTA
 Type 3 / mixed RTA (not in use)

7. Type 1-Distal RTA
Distal RTA (dRTA) is the classical form
of RTA. Inability of the distal tubule to
acidify the urine. Due to impaired
hydrogen ion secretion, increased backleak
of secreted hydrogen ions, or impaired
sodium reabsorption (causing less negative
potential in the lumen and hence less
hydrogen/potassium secretion).
 Urine pH >5.5.

8. PATHOPHYSIOLOGY
 failure of acid secretion by the alpha
intercalated cells of the cortical collecting
duct of the distal nephron.
 it leads to an inability to acidify the urine to
a pH <5.3
 renal excretion is the primary means of
eliminating acid from the body, there is
consequently a tendency towards acidemia
 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).
 the substance of the kidney develops stones
bilaterally

9. RISK FACTORS
Genetics
Autosomal dominant or recessive. May
occur in association with other genetic
diseases (e.g., Ehlers-Danlos
syndrome, hereditary elliptocytosis, or
sickle cell nephropathy). The autosomal
recessive form is associated with
sensorineural deafness.

10. ETIOLOGY
• Genetic
• Sporadic
• Autoimmune diseases:
rheumatoid arthritis (RA), SLE
• Hematologic diseases:
Sickle cell disease, hereditary
elliptocytosis
• Medications:
Amphotericin B, lithium, K+-
sparing diuretics
• Toxins:
Toluene, glue
• Hypercalciuria, diseases
causing nephrocalcinosis
• Vitamin D intoxication
• Medullary cystic disease
• Glycogenosis type III
• Fabry disease
• Wilson disease
• Hypergammaglobulinemic
syndrome
• Obstructive uropathy
• Chronic pyelonephritis
• Chronic renal transplant
rejection
• Leprosy
• Hepatic cirrhosis
• Malnutrition

11. CLINICAL MANIFESTATIONS
 non-anion gap metabolic
acidosis
 growth failure
 nephrocalcinosis
 hypercalciuria

12. 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.

13.  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.

14. Clinical manifestations -
phosphaturia, glycosuria, amin
oaciduria, uricosuria, and
tubular proteinuria. The
principal feature of Fanconi's
syndrome is bone
demineralization due to
phosphate wasting.

15. -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

16.  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

17.  growth failure in the 1st year of life
 polyuria
 dehydration
 anorexia
 vomiting
 constipation
 hypotonia
 Patients with primary Fanconi
syndrome will have additional
symptoms
 Those with systemic diseases will
present with additional signs and
symptoms specific to their underlying
disease

18. Type 3 RTA-Combined
proximal and distal RTA
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. Mutations in the gene encoding this
enzyme give rise to an autosomal recessive
syndrome of osteopetrosis, renal tubular
acidosis, cerebral calcification, and mental
retardation.
•

19. Type 4 RTA
 Due to aldosterone resistance or deficiency
that results in hyperkalemia.
 It was included in the classification of renal
tubular acidoses as it is associated with a
mild (normal anion gap) metabolic acidosis
due to a physiological reduction in
proximal tubular ammonium excretion
(impaired ammoniagenesis), which is
secondary to hypoaldosteronism, and
results in a decrease in urine buffering
capacity.
 Urine pH <5.5.

20. RISK FACTORS
Some cases familial, such as
pseudohypoaldosteronism type
I (autosomal dominant)

21. ETIOLOGY
 Medications: Nonsteroidal anti-inflammatory
drugs, angiotensin-converting enzyme
inhibitors, angiotensin receptor
blockers, heparin/LMW heparin, calcineurin
inhibitors (tacrolimus, cyclosporine) (1)
 Diabetic nephropathy
 Obstructive nephropathy
 Nephrosclerosis due to hypertension
 Tubulointerstitial nephropathies
 Primary adrenal insufficiency
 Pseudohypoaldosteronism(end-organ
resistance to aldosterone)
 Gordon syndrome
 Sickle cell nephropathy

22. CLINICAL MANIFESTATIONS
 with growth failure in the first few years of
life
 Polyuria
 Dehydration
 Rarely, with life-threatening hyperkalemia
 Patients with obstructive uropathies may
present acutely with signs and symptoms of
pyelonephritis
 hyperkalemic non-anion gap metabolic
acidosis
 Alkaline or acidic urine
 Elevated urine sodium levels &
inappropriately low urine potassium levels
reflect the absence of aldosterone effect.

23. 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

24.  Electrolytes - hyperchloremic metabolic
acidosis.
 Plasma anion gap normal (anion gap = Na - [Cl +
HCO3])
 Hypokalemia or normokalemia
 Hyperkalemia
 Plasma HCO3 (in untreated RTA)
 Blood urea nitrogen and creatinine usually
normal (rules out renal failure as cause of
acidosis)
 Urine pH: Inappropriately alkaline (pH >5.5)
 Urine culture: Rule out UTI with urea-splitting
organism and chronic infection

25.  Urine anion gap: Reflects unmeasured urine
anions, so inversely related to urine NH4+ (or
acid) excretion. Positive urine anion gap in an
acidemic patient indicates impaired renal acid
excretion.
 Urine calcium:
 High in type I
 Typically normal in type II
 A renal ultrasound - to identify underlying
structural abnormalities such as obstructive
uropathies as well as to determine the presence
of nephrocalcinosis.

26.  correction of the acidemia with oral sodium
bicarbonate, sodium citrate or potassium citrate.
This will reverse bone demineralization
 Hypokalemia and urinary stone formation and
nephrocalcinosis can be treated with potassium
citrate tablets
 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

27.  The base requirement for distal RTAs is generally in
the range of 2-4 mEq/kg/24 hr.
 Patients with Fanconi syndrome generally require
phosphate supplementation .
 Patients with distal RTA should be monitored for the
development of hypercalciuria. Symptomatic
hypercalciuria, nephrocalcinosis, or nephrolithiasis
may require thiazide diuretics to decrease urine
calcium excretion.
 Patients with type IV RTA may require chronic
treatment for hyperkalemia with sodium-potassium
exchange resin

28.  Administration of sufficient bicarbonate to reverse
acidosis stops bone dissolution and the
hypercalciuria.
 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 .

29. PROGNOSIS
• Depends on associated
disease, otherwise good with therapy
• Transient forms of all types of RTA
may occur.

30. 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)