RENAL RENAL TUBULAR TUBULAR ACIDOSISACIDOSIS

First described First described clinically in 1935clinically in 1935

Confirmed as a Confirmed as a renal tubular renal tubular disorder in 1946disorder in 1946

Designated as RTA Designated as RTA in 1951in 1951

Refers to disorders Refers to disorders affecting the overall affecting the overall ability of the renal ability of the renal tubules either to tubules either to secrete hydrogen secrete hydrogen

ions or to retain ions or to retain bicarbonate ionsbicarbonate ions

All types produce All types produce hyperchloremic hyperchloremic metabolic acidosis metabolic acidosis

with a normal anion with a normal anion gap.gap.

PROXIMAL RENAL PROXIMAL RENAL TUBULAR ACIDOSISTUBULAR ACIDOSIS

MAIN DEFECTMAIN DEFECT

Carbonic Anhydrase deficiencyCarbonic Anhydrase deficiency

Proximal RTA (Type Proximal RTA (Type 2)2)

Caused by an Caused by an impairment of impairment of HCO3- HCO3- reabsorption in the reabsorption in the proximal tubulesproximal tubules

Most cases occur in Most cases occur in the context of the context of Fanconi’s syndromeFanconi’s syndrome

Isolated proximal Isolated proximal RTA is rare.RTA is rare.

80% reabsorbed

15% reabsorbed

5% excreted

HCO3

HCO3

HCO3

HCO3

100%

Normal renal tubular function

60% reabsorbed

15% reabsorbed

HCO3

HCO3

HCO3

25% HCO3-

100%

K+

Proximal RTA or RTA type 2

Cl-Decreased proximal tubule efficiency

Proximal RTAProximal RTA

Massive loss of bicarbonate – Massive loss of bicarbonate – metabolic acidosismetabolic acidosis

Absorption of chloride - Absorption of chloride - hyperchloremiahyperchloremia

Loss of potassium – hypokalemiaLoss of potassium – hypokalemia Kidneys tries to compensate for the Kidneys tries to compensate for the

acidosis – urine ph is low - < 5.5acidosis – urine ph is low - < 5.5

Distal RTADistal RTA

Decreased excretion of titratable Decreased excretion of titratable acids = Acidification defectacids = Acidification defect

DISTAL RTADISTAL RTA Impairment of distal Impairment of distal

acidificationacidification Inability to lower urine Inability to lower urine

pH maximally below 6.0 pH maximally below 6.0 under acid loadunder acid load

Pathomechanism is Pathomechanism is inability to secrete H+ inability to secrete H+ adequately (secretory adequately (secretory defect or classic distal defect or classic distal RTA)RTA)

Gradient defectGradient defect Voltage dependent Voltage dependent

defectdefect In children mainly a In children mainly a

genetic defect of the H+ genetic defect of the H+ pumppump

excreted

HCO3-

Distal RTA or RTA type 1

Acidification defect

H+

K+

Cl-

Distal RTADistal RTA

Loss of bicarbonate less than type 2 Loss of bicarbonate less than type 2 – metabolic acidosis– metabolic acidosis

Absorption of chloride – Absorption of chloride – hyperchloremiahyperchloremia

Loss of potassium – hypokalemiaLoss of potassium – hypokalemia Decreased excretion of titratable Decreased excretion of titratable

acids – high urinary ph >5.5acids – high urinary ph >5.5

RTA Type IVRTA Type IV

Hypoaldosteronism or Deficiency of Hypoaldosteronism or Deficiency of aldosteronealdosterone

Pseudohypoaldosteronism or end Pseudohypoaldosteronism or end organ target failureorgan target failure

Adolsterone

Water

K+

Na

Na+

H+

Cl-RTA IV:

Hypoaldosteronism or pseudohypoaldosteronism

H20

RTA IVRTA IV

End organ target failure or low End organ target failure or low aldosterone:aldosterone: Lost of sodium – hyponatremiaLost of sodium – hyponatremia Retention or decreased excretion of Retention or decreased excretion of

potassium - hyperkalemiapotassium - hyperkalemia Absorption of chloride – hyperchloremiaAbsorption of chloride – hyperchloremia Decreased excretion of acids – Decreased excretion of acids –

metabolic acidosismetabolic acidosis Loss of fluid - dehydrationLoss of fluid - dehydration

Proximal Proximal RTARTA

Distal RTADistal RTA RTA IVRTA IV

Type of Type of AcidosisAcidosis

HyperchloreHyperchloremic mic metabolic metabolic acidosisacidosis

HyperchloreHyperchloremic mic metabolic metabolic acidosisacidosis

HyperchloreHyperchloremic mic metabolic metabolic acidosisacidosis

Serum Serum PotassiuPotassiumm

lowlow lowlow highhigh

Urine pHUrine pH < 5.5< 5.5 >5.5>5.5 < 5.5< 5.5

Urine Urine bicarbonbicarbonate lossate loss

Features of the RTA Features of the RTA SyndromesSyndromes

Feature Type 1 Type 2 Type 4

Nephro-lithiasis

present absent Absent

Nephro- calcinosis

present absent Absent

Osteo-malacia

present present Absent

Growth failure

+++ ++ +++

Hypokalemic muscle weakness

++ + -

Alkali therapy

Low dose (2 –4 meq/kg)

High dose ( 2-14 meq/kg)

Low dose ( 2-3 meq/kg)

Response to therapy

good fair fair

Features of the RTA Features of the RTA SyndromesSyndromes

Feature Type 1 Type 2 Type IV

Plasma HCO3

Variable, may be <10 meq/L

14- 18 meq/L

15-29 meq/L

Plasma Cl- increased Increased Increased

Plasma K+ Mildly to severely decreased

Mildly decreased

Mildly to severely decreased

Plasma anion gap

Normal Normal Normal

GFR Normal or slightly decreased

Normal of slightly decreased

Normal to moderately decreased

Fractional Excretion of HCO3

<5% > 15% <5%

Urine pH during acidosis

>6.0 </= 5.5 </= 5.5