This document summarizes a seminar on renal tubular acidosis (RTA). It includes two case scenarios of children presenting with features of RTA like failure to thrive and metabolic acidosis. Investigation of the cases showed metabolic acidosis with normal anion gap, hypokalemia, and hyperchloremia, consistent with RTA. The seminar discusses normal acid-base homeostasis, types and causes of RTA, pathophysiology of proximal and distal RTA, and clinical features of different types of RTA. Diagnosis involves evaluation of urine pH, bicarbonate threshold, and distinguishing features of different subtypes.
4. Presented by –
Dr. Shahrina Afroze Tisha.
MD Resident,
Dept. of Pediatric Nephrology,
Bangladesh Institute of Child Health.
5. Case scenario 1
Abdullah, 1 year 2 months old boy,
presented with polyuria, polydipsia and
failure to thrive for 3 months. Mother also
complaints of persistent vomiting for last 2
months. For these, he was conservatively
treated but there was no significant
improvement. On examination,the child
was irritable, dehydrated. There was poor
weight gain(7 kg) and widening of wrists
and ankle.
7. Case Scenario 2
The child aged 2 years, presented with the
complaints of failure to thrive. His birth weight
was 2.7 kg. He did well in the first 3 months
and then had problems with persistent
vomiting. He had poor weight gain as well. He
was given conservative management for the
next 3-4 months. There was no major
improvement seen thereafter also.
8. EXAMINATION:
weight 6.9 kg, height 73 cm, BP 92/60 mm
of hg
The child was unable to walk yet and was
irritable all the time. He had poor appetite.
There was no hepatospleenomegaly, rash or
joint pains.
10. Discussion
Both cases the investigations clearly showed
metabolic acidosis with a normal anion gap
associated with hypokalamia and
hyperchloremia. These are the classical
features of Renal Tubular Acidosis.
11. Normal Acid base Homeostasis
Acid base homeostasis requires the integration
of at least 3 organ systems, including the liver,
the lungs and the kidneys.
The liver metabolizes protein that produces H+
ion.
The lungs remove CO2 and thereby H+
reflecting HCO3 ions role as an extracellular
buffer.
The kidney generate new HCO3 to replace the
HCO3 consumed during the buffering process.
12. Metabolic Acidosis
Definition:
Loss of Bicarbonate(HCO3) or gain of
Hydrogen(H+) is called Metabolic acidosis.
Signs and symptoms:
Symptoms are not specific. Patient may
present with nausea, vomiting, abdominal
pain, chest pain, palpitations, headache,
deep rapid breathing called kussmaul
respirations,
13. Muscle weakness, bone pain and joint pain.
Extreme acidemia may lead to neurological
like lethargy, stupor, coma, seizures and
cardiac, like arrythmia, hypotension
complications.
18. Anion Gap
Definition:
The anion gap is the difference in the
measured cations and the measured anions in
serum, plasma or urine. It represents anions
other than bicarbonate and chloride required
to balance sodium’s positive charge.
Normal Anion gap: 12 ± 2 mEq/l.
19. • It is calculated by subtracting the serum
concentration of chloride and bicarbonate
from the concentration of sodium and
potassium.
• Anion Gap=Serum (Na++K+) - (Cl- + HCO3).
20.
21. Anion Gap Increases:
• When the plasma concentration of
K+,Ca++,Mg+ is decreased.
• When the concentration of or the charge on
plasma is increased.
• When organic anions e.g Lactate or foreign
anions e.g ethylene glycol accumulates in the
blood.
• Ketoacidosis, Lactic acidosis.
Anion Gap Decreases:
When cataions are increased or when plasma
albumin decreased.
22. DD of MA
Loss of bicarbonate MA with normal AG Addition of acids MA with increased AG
GIT loss of bicarbonate Diarrhea, fistula or drainage,
surgery for NEC, ileal loop
conduit, use of anion
exchange resin.
Increased acid production Increased βhydroxybutyric
acid&acetoacetic acid
production,
Starvation or fasting,
Ethanol intoxication.
Renal loss of bicarbonate Renal tubular acidosis Increased lactic acid
production
Tissue hypoxia, muscular
exercise, ethanol ingestion,
systemic disease−leukemia,
diabetes, cirrhosis,
pancreatitis, inborn errors of
metabolism−CHO, urea cycle,
amino acid, organic acid.
Other causes Addition of HCL, NH4Cl,
Arginine, lysine.
Hyper alimentation.
Dilutionalacidisis.
Organic acidosis Methanol, ethylene glycol,
paraldehyde, salicylate,
NSAID,etc. intoxication,
methylmalonicaciduria,
Increased sulphuric acid Methionine administration
Decreased acid excretion AKF
CKD
23. Urinary Anion Gap
According to Principle of Electronutrility
• Sum of urinary cataions= sum of urinary anions
• Urinary Na+ + K+ + NH4+ =Cl- + HCO3-
• Urinary Anion Gap: (Na+ + K +)-Cl- = -NH4+
• Urinary Anion Gap gives us a fair estimation of
NH4+ excretion as NH4 combines with Cl- to form
NH4Cl and excreted through urine.
• Normal value of Urinary Anion Gap is 30 to 35
mEq/L.
24. POSITIVE UAG:
RTA (type i and iv).
Diabetic ketoacidsis.
Normal UAG or low –ve:
Diarrhoea.
RTA (type ii).
26. Presented by –
Dr. Kanta Halder.
MD Resident,
Dept. of Pediatric Nephrology,
Bangladesh Institute of Child Health.
27. Renal Tubular Acidosis
Renal tubular acidosis comprises a group of
transport defects characterized by inability to
acidify urine appropriately resulting in
metabolic acidosis.
28. Classification
Renal tubular acidosis can be classified into 4
types –
1. Type I: Distal RTA (dRTA) or Classic RTA.
2. Type II: Proximal RTA (pRTA).
3. Type IV: Hyperkalemic.
4. Type III: Mixed dRTA & pRTA.
35. HCO3 reabsorption in Proximal
Renal Tubule
• The Na-K-ATPase located in the basolateral
membrane generates and maintains the low
intracellular sodium concentration.
• Protons are excreted into the tubule lumen by
the sodium-proton exchanger (NHE3) where
they combine with bicarbonate to form
carbonic acid.
36. • In the presence of carbonic anhydrase IV
(CAIV) the carbonic acid is hydrolyzed to water
and carbon dioxide which enter the cell and
recombine to form carbonic acid by the action
of intracellular carbonic anhydrase II (CAII).
• The carbonic acid ionizes into a proton which
is then excreted into the lumen and
bicarbonate which is transported by the
sodium-bicarbonate symporter (NBC1) into
the blood stream.
37. Pathophysiology of pRTA
• Primary defect: Defective reabsorption of
HCO3 ⁻, less HCO3 ⁻ reabsorption in PT.
• HCO3 ⁻ binds mainly with Na+ .
• Increase Na+ delivery in DT.
• Aldosterone secretion is stimulated.
• Hypokalaemia & Metabolic acidosis.
38.
39. Acid sectetion in intercalated cell in
distal nephrons
• Protons are excreted into the tubule lumen
by the proton-ATPase and are buffered by
ammonia or titratable acid (mostly
phosphate).
• Inside the cell, carbonic anhydrase II (CAII)
provides the protons and bicarbonate
through the hydration of carbon dioxide to
form carbonic acid.
40. • Bicarbonate is excreted into the blood
stream by action of the chloride
bicarbonate exchanger (AE1) on the
basolateral membrane.
• Chloride homeostasis is maintained by the
potassium-chloride cotransporter (KCC4)
and the chloride channel (ClC-Kb).
41. Pathophysiology of dRTA
Reduced proton secretion in distal tubule:
• “weak pump”inability for H+ pump to
achieve a steep H+ ion gradient between
tubular cell and lumen resulting decreased
secretion of proton.
• “Leaky membrane” causes back diffusion of
H+( due to Amphotericin B).
• “Low pump activity” insufficient distal H+
pumping capacity due to tubular damage.
42. Pathophysiology of Type IV RTA
The underlying defect here is the impaired
cation exchange in the distal tubules with
reduced secretion of H⁺ and K⁺.
Pathophysiology:
• Aldosteron deficiency/ distal tubular
resistance to aldosteron→ impaired
Na⁺/K⁺−H⁺ exchange mechanism→ decrease
K⁺ & H⁺ secretion→ acidosis& hyperkalemia.
48. Rachitic manifestation
Head:
Box like square head.
Craniotabs.
Chest:
Pigeon chest deformity.
Rachitic rosary( at costochondral junction).
Harrison sulcus.
49. Extrimity:
Widening of wrist and ankle.
Anterior bowing of leg.
Limb deformities:
coxa vara.
genu valgum.
genu varum.
50.
51. Features of Fanconi Syndrome
Diffuse proximal tubular dysfunction leading to excess
urinary loss of –
Glucose : glucosuria with normal blood glucose level
Phosphate : hypophosphataemia, rickets,osteomalacia
Amino acid : no obvious clinical consequence
HCO3- : leading to p RTA
K+ : hypokalaemia
52. • Na+, CL- & water : polyuria & polydipsia
recurrent episodes of
dehydration .
Tubular proteinuria: loss of low molecular
weight protein including retinol binding
protein.
53. Clinical features of type-ii RTA
• Global dysfunction of PT→proximal
RTA→phosphaturia, glucosuria, aminoaciduria
→polyurea, polydipsia.
• Global dysfunction of PT →phosphaturia→rickets
& osteomalacia, →FTT & growth retardation→
recurrent dehydration.
• Global dysfunction of PT →hypokalemia→muscle
weakness.
54. Type iii RTA
C/F of both p RTA &
dRTA.
Osteopetrosis.
Cerebral calcification.
Mental retardation.
Type iv RTA
Growth retardation.
Polyuria & polydipsia.
S/S of Obstructive
uropathy.
Pyelonephritis.
Bone diseases are
generally absent.
57. Presented by –
Dr. Faria Ahmed Asha.
MD Resident,
Dept. of Pediatric Nephrology,
Bangladesh Institute of Child Health.
58. Lab diagnosis of RTA
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.
59. Urine pH
S. K+
NaHCO3 loading
Urine pH <5.5
S. K+ low/
Normal
U-B CO2
>20mmHg
FEHCO3 > 10-
15%
Urine pH >5.5
S. K+
low/Normal
U-B CO2
<20mmHg
FEHCO3 <5%
Urine pH >5.5
S. K+
high/Normal
U-B CO2
< / >20mmHg
FEHCO3 <5%
Urine pH <5.5
S. K+
high/Normal
U-B CO2
>20mmHg
FEHCO3 <5 -10%
Proximal
RTA
Classic
type 1
RTA
Hyperkale
mic type 1
RTA
Type 4
RTA
60. Functional evaluation of proximal
bicarbonate absorption
Fractional excretion of bicarbonate
• Urine ph monitoring during IV
administration of sodium bicarbonate (3-
5ml/kg).
• Levels of bicarbonate & creatinine are
measured in blood & random urine
specimen.
• FEHCO3 = (urine HCO3 × Plasma creatinine)
÷ (plasma HCO3 × urine creatinine) × 100.
63. Urine pH
• Urine pH is useful for assessing the
overall integrity of distal urinary
acidification.
• In humans, the minimum urine pH that can
be achieved is 4.5 to 5.0.
• Ideally urine ph should be measured in a
fresh morning urine sample.
• A low urine ph does not ensure normal
distal acidification and vice versa.
63
64. NH4CL loading test / urinary
acidification test
• Administration of NH4Cl induces a metabolic
acidosis to which the kidney responds with
maximum urinary acidification.
• Measure baseline urine pH & acid-base status
in a venous sample.
• Then give NH4Cl 0.1 – 0.15g/kg p/o over 30-
45min with fruit juice.
• The pH of each urine specimen is measured
over the next 6 hours.
66. Urine Anion Gap
• Urine AG = Urine (Na + K - Cl).
• The urine AG has a negative value in most
patients with a normal AG metabolic acidosis.
• Patients with renal failure, type 1 (distal) renal
tubular acidosis (RTA), or hypoaldosteronism
(type 4 RTA) are unable to excrete ammonium
normally. As a result, the urine AG will have a
positive value.
67. • There are, however, two settings in
which the urine AG cannot be used.
• When the patient is volume depleted
with a urine sodium concentration
below 25 meq/L.
• When there is increased excretion of
unmeasured anions
69. Urine osmolal gap
• When the urine AG is positive and it is unclear
whether increased excretion of unmeasured
anions is responsible, the urine ammonium
concentration can be estimated from
calculation of the urine osmolal gap.
• UOG is more useful than the UAG in
estimating urinary NH4+ excretion.
• UOG=Uosm - 2 x ([Na + K]) + [urea/6+
glucose/18].
• UOG of >100 represents intact NH4 secretion.
70. Urine PCO2
• Measure of distal acid secretion.
• In pRTA, unabsorbed HCO3 reacts with
secreted H+ ions to form H2CO3 that
dissociate slowly to form CO2 in
medullary CT.
72. TTKG ( Transtubular K gradient)
• TTKG is a concentration gradient between the
tubular fluid at the end of the cortical collecting
tubule and the plasma.
• TTKG = [Urine K ÷ (Urine osmolality / Plasma
osmolality)] ÷ Plasma K.
• Normal value is 8 and above.
• Value <7 in a hyperkalemic patient indicates
hypoaldosteronism.
• This formula is relatively accurate as long as the
urine osmolality exceeds that of the plasma
urine sodium concentration is above 25 meq/L
73. Urine citrate
• The proximal tubule reabsorbs most (70-90%)
of the filtered citrate.
• Acid-base status plays the most significant
role in citrate excretion.
• Alkalosis enhances citrate excretion, while
acidosis decreases it.
• Citrate excretion is impaired by acidosis,
hypokalemia,high–animal protein diet and
UTI.
74. Laboratory findings in different type
of RTA
Parameter Proximal
(type 2 ) RTA
Distal ( type 1
) RTA
Hyperkalemic
( type 4 ) RTA
UAG Negative positive Positive
Urine PH < 5.5 > 5.5 < 5.5
Urine NH4 low Low Low
Urine Ca++ Normal High Normal/ Low
Plasma K+ Low Low High
FEHCO3 > 10% < 5% 5 to 10%
PCO2 mmHg > 20 < 10 >20
78. Type- 1 RTA( Distal)
Correction of acidosis:
• Sodium bicarbonate: 5-10 mEq/kg/day.
• Citrate- sodium/potassium(polycitra).
• Shohl solution(1 mEq/ml).
Correction of hypokalemia:
• Hypokalemia should be treated before
correction of acidosis.
79. Cont…
With adequate correction of acidosis, renal
potassium losses are reduced but some
patients require prolonged potassium
supplements.
Vitamin- D: If there is rickets and osteopenia.
Thiazide diuretics: If hypercalciuria persist
after correction of acidosis.
82. Type- IV RTA.
Avoidance of potassium containing
food, fruits and drugs.
Mineralocorticoid suppliment.
Thiazide diuretics.
83. Cont..
Loop diuretics: May be used in
Aldosteron resistant cases.
Potassium exchange regins (Kayexalate)
may be required.
84. Fanconi syndrome.
Adequate hydration:Patient may need 0.9%
saline.
Correction of acidosis.
Suppliments of sodium, potassium,
bicarbonate and phosphate.
Administration of moderate doses of Vit- D.
85. Follow Up
Assesment of growth.
Blood level of:
Electrolytes.
pH.
HCO3.
USG screening for nephrocalcinosis in
distal RTA.
86. Prognosis
o Usually depends on nature of underlying
disease.
o Patients with treated isolated proximal or
distal RTA generally demonstrate
improvement in growth , provided S. HCO3
level maintained in the normal range.