TY  - CHAP
M1  - Book, Section
TI  - Renal Tubular Acidosis
A1  - DuBose, Thomas D.
A1  - Alpern, Robert J.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Renal  tubular  acidosis  (RTA)  is  a  clinical  syndrome  characterized  by  hyperchloremic  metabolic  acidosis  secondary  to  an  abnormality  in  renal  acidification.  The  acidification  defect  may  be  manifested  by  an  inappropriately  high  urine  pH,  bicarbonaturia,  and,  by  definition,  reduced  net  acid  excretion.  Classical  distal  renal  tubular  acidosis  and  proximal  renal  tubular  acidosis  are  frequently  associated  with  hypokalemia.  Distal  renal  tubular  acidosis  can  also  result  from  a  generalized  dysfunction  of  the  distal  nephron,  in  which  case  it  is  usually  accompanied  by  hyperkalemia  and  may  be  associated  with  either  hypoaldosteronism  or  aldosterone  resistance.Proximal  renal  tubular  acidosis  may  result  from  an  isolated  defect  of  acidification  in  the  proximal  nephron.  The  isolated  defect  in  acidification  could  be  the  result  of  selective  dysfunction  of  the  Na+/H+  antiporter,  the  proximal  tubule  H+-ATPase  or  the  Na+/HCO3−/CO3=  symporter.More  commonly,  proximal  renal  tubular  acidosis  occurs  as  one  manifestation  of  a  generalized  defect  in  proximal  tubule  function.  Patients  with  this  generalized  abnormality,  the  Fanconi  syndrome,  usually  have  glycosuria,  aminoaciduria,  citraturia,  and  phosphaturia.  The  acidification  defect  associated  with  this  generalized  tubular  dysfunction  may  be  the  result  of  (a)  impairment  of  cellular  ATP  generation,  (b)  cellular  phosphate  depletion,  or  (c)  a  selective  abnormality  of  the  basolateral  Na+,  K+-ATPase.Vitamin  D  deficiency  is  associated  with  the  Fanconi  lesion.  The  transport  defect  may  be  due  to  a  combination  of  factors  including  reduction  in  1,25-dihydroxy  vitamin  D3  levels,  elevated  parathyroid  hormone  levels,  hypocalcemia,  and  intracellular  phosphate  depletion.The  diagnosis  of  proximal  renal  tubular  acidosis  is  based  on  the  demonstration  of  a  chronic  hyperchloremic  metabolic  acidosis  and  an  acid  urine  pH.  Correction  of  the  metabolic  acidosis  with  alkali  raises  the  plasma  bicarbonate  level  above  the  renal  threshold  and  results  in  prominent  bicarbonaturia  and  an  alkaline  urine  pH.  The  fractional  excretion  of  bicarbonate  may  exceed  15  percent  of  the  filtered  load  in  such  conditions,  and  hypokalemia  is  common.  Bone  disease,  which  commonly  accompanies  this  disorder,  is  expressed  as  rickets  in  children  and  osteopenia  in  adults.The  goal  of  therapy  in  proximal  renal  tubular  acidosis  is  to  maintain  a  near  normal  serum  bicarbonate  concentration  while  avoiding  potassium  deficiency.  Concomitant  administration  of  thiazide  diuretics  to  reduce  intravascular  volume,  and  secondarily  to  reduce  the  filtered  load  of  bicarbonate,  is  often  beneficial.The  mechanisms  underlying  hypokalemic  classical  distal  renal  tubular  acidosis  have  not  been  fully  elucidated.  Nevertheless,  important  advances  in  our  understanding  of  the  molecular  bases  of  this  disorder  have  been  made  recently.  Distal  RTA  may  be  inherited  or  acquired.  The  hypokalemia  that  is  particularly  prevalent  in  the  acquired  forms,  suggests  a  lesion  in  the  medullary  collecting  duct  or  a  selective  lesion  in  the  cortical  collecting  tubule.  Possible  mechanisms  include  an  abnormal  leak  pathway  or  “gradient”  lesion  or  a  “secretory”  defect.  An  example  of  a  leak  defect  is  that  induced  by  amphotericin  B  in  which  the  urine  minus  the  arterial  blood  PCO2  (U−B  PCO2)  is  normal.  Only  two  patients,  both  young  children,  have  been  reported  in  which  a  normal  U−B  PCO2  was  present  in  the  absence  of  exposure  to  amphotericin  B,  suggesting  a  nonamphotericin-acquired  “gradient”  lesion.  The  observed  low  U-?B  PCO2  gradient  in  most  patients  with  distal  renal  tubular  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/20
UR  - ommbid.mhmedical.com/content.aspx?aid=1181473338
ER  -