23522882-acidozele-tubulare-renale
TRANSCRIPT
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Acidozele tubulare renale
Dr. G. IsmailCentrul de Medicina Interna - Nefrologie, Institutul Clinic Fundeni
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Acidoza metabolica:
Este o tulburare acido-bazica initiata de o reducere a concentratiei plasmatice a bicarbonatului, fiind asociata cu o scadere a valorii pH-ului plasmatic si a pCO2.
Introducere
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Acidoza metabolica:
Hiatusul anionic = [Na+] – ([Cl-] + [HCO3-])= 8-16 mEq/l
Acidoze metabolice cu valori ridicate ale HA: - acidocetoza diabetica - uremie - ingestie de etilenglicol - ingestie de metanol - acidoza lactica
Introducere
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Acidoza metabolica:
Hiatusul anionic = [Na+] – ([Cl-] + [HCO3-])= 8-
16 mEq/l
Acidoze metabolice cu valori normale ale HA: - acidozele tubulare renale - pierderi de bicarbonat pe cale gastrointestinala
Introducere
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Definitie:
Sindroame biochimice caracterizate prin acidoza metabolica cu gaura anionica pozitiva, de origine tubulara renala, frecventa asociata cu perturbari ale nivelului seric al potasiului si care sunt datorate alterarii capacitatii rinichiului de a excreta incarcatura acida zilnica disproportionat fata de reducerea filtrarii glomerulare.
Introducere
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Acidoza metabolica:
Dieta zilnica genereaza 1-1.5 mmol H+/Kgc/zi
Patogenie
~ 100 mmoli H+ zilnic
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- reabsorbtia de HCO3- la nivelul TCP
- sinteza si excretia la nivelul TCP a NH4+
- secretia de H+ la nivelul TCD si TC
Patogenie
Mecanismele renale implicate in realizarea echilibrului acido-bazic
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- Tubul contort proximal:
- principala functie: reabsorbtia HCO3- filtrat
- productia si secretia de NH4+
Patogenie
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PARS CONVOLUTA
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PARS RECTA
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- Tubul contort proximal:
- principala functie: reabsorbtia HCO3- filtrat
Patogenie
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H2CO3 ATP
+-
CO2 H2O
AC II
Cl-
3 HCO3
3 Na+
K+
Na+Cl-
H2O
CO2H2O
AC IV
H2CO3
HCO3
Na+
H+
2 K+
Celula tub proximalLumen tubular Sange
Tubul contort proximal
Patogenie
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- Tubul contort proximal:
- principala functie: reabsorbtia HCO3- filtrat
- productia si secretia de NH4+
- reducerea pH-ului urinar de la 7.4 la 6.7
Patogenie
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Glutaminaza
+ -
NH4 Glutamina
Na+
K+
Na+Cl-
H2O
Na+
2 K+
Celula tub proximalLumen tubular Sange
Tubul contort proximal
Patogenie
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- Tubul contort proximal:
- reabsorbtia a 80% din HCO3- filtrat
- productia si secretia de NH4+
- reducerea pH-ului urinar de la 7.4 la 6.7
Patogenie
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- Tubul contort distal si colector:
- principala functie: secretia de H+
- reabsorbtia a 20% din HCO3- filtrat
Patogenie
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- tubul contort distal si colector
- celule principale: reabs. Na, H2O, secretia de K
- celule intercalate:- : secretia de H+ (ATP-aza H+ si ATP-aza H+/
K+)- : reabs. HCO3 la schimb cu Cl -
Patogenie
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Tubul contort distal si colector
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Tubul contort distal si colector
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Modelul schematic al secretiei de H+ in tubul colector cortical
H2CO3
ATP
+-
CO2 H2O
AC II
Na+
3 HCO3
3 Na+
K+NH4 -
NH3
H+
H+ - ATPaza
2 K+
Celule intercalate tip
Lumen Sange
Cl-
Cl-
K+
K+
ATP
ATPH+
H+/K+ ATPaza
Tubul contort distal si colector
Diferenta de potential: -5 - 30 mV
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- gazometria sangvina (permite stabilirea diagnosticului de tulburare acido-bazica si aprecierea caracterului metabolic sau ventilator prin masurarea pH-ului, pCO2 si concentratiei de HCO3 in sangele arterial)
- ionograma plasmatica aduce informatii privind diagnosticul etiologic al unei acidoze metabolice prin calculul “gaurii anionice”, precum si prezenta diselectrolitemiilor asociate (hipo- sau hiperpotasemie)
- determinarea produsilor de retentie azotata
- determinarea valorii pH-ul urinar (peste 5.5 in prezenta unei acidoze sistemice sustine diagnosticul de ATR distala Pacientii cu ATR proximala sau ATR distala tip IV netratati cu acidoza sistemica severa pot avea pH-ul urinar sub 5.5).
- determinarea excretiei urinare de amoniu
Diagnosticul paraclinic:
Acidoza tubulara tip I
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- determinarea gaurii anionice urinare (GAU). GAU se calculeaza din formula: UAG = UNa+ + UK+ – U Cl-, unde UNA+ . O GAU > 0 echivaleaza cu o concentratie urinara scazuta de amoniu si sugereaza originea tubulara a acidozei.
- citratul urinar: este normal in ATRp si in ATR tip IV dar este redusa in ATRd Valoarea normala a excretiei urinare de citrat este de 1,6 – 4,5 mmoli/24 ore.
- calciul urinar: hipercalciuria este intalnita la unii pacienti cu ATRd tip I posibil datorita unei cresteri a reabsorbtiei osoase sau a unei scaderi a reabsorbtiei tubulare a calciului secundar acidozei metabolice
- Glucoza urinara, aa. urinari, fosfatul urinar: ATRp tip II se asociaza cu disfunctie tubulara proximala
- testul de incarcare la bicarbonat: fractia de excretie a HCO3- > 15-20% la o valoare a HCO3- seric > 26mmol/L in cazul ATRp tip II, iar in cazul acidozelor distale valoarea fractiei de excretie a HCO3- < 5%.
Diagnosticul paraclinic:
Acidoza tubulara tip I
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Clasificare:
• Tipul I: Acidoza tubulara distala cu normo sau hipoK
• Tipul II: Acidoza tubulara proximala
• Tipul III: Forma mixta tip III
• Tipul IV: Acidoza tubulara distala cu hiperK
Introducere
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- d.p.v al mecanismelor moleculare 3 tipuri:
- secretor
- retrodifuziune
- voltaj-dependent
Patogenie
Acidoza tubulara distala tip I
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- d.p.v al mecanismelor moleculare 3 tipuri:
- secretor- cel mai frecvent- incapacitatea secretiei de H+
- disfunctia ATP-azei H+ si ATP-azei H+/ K+
Patogenie
Acidoza tubulara distala tip I
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- d.p.v al mecanismelor moleculare 3 tipuri: - retrodifuziune:
- capacitatea de secretie pastrata - gradientul nu poate fi mentinut datorita retrodifuziei
Patogenie
Acidoza tubulara distala tip I
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- d.p.v al mecanismelor moleculare 3 tipuri:
- voltaj-dependent- incapacitatea de a mentine un potential
electronegativ intraluminal- scaderea secretiei de H+ si K+
- se asociaza cu hiper kaliemie
Patogenie
Acidoza tubulara distala tip I
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- clasica (cu hipokaliemie) - primara:
- ereditara
- sporadica
- disproteinemii (hipergammaglobulinemii, crioglobulinemii, amiloidoza)
- boli autoimune (Sd. Sjogren, PAN, CBP, etc)
- boli genetice (b. Fabry, Wilson, Marfan, etc)
- boli renale (nefropatia balcanica, pielonefrita cronica, transplantul
renal, etc)
- medicamente/ toxine (amphotericina, Li, toluen, etc)
Introducere
Cauze de acidoza tubulara distala tip I
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A BFIGURE 2Light chain cast nephropathy LAMBDA LIGHT CHAINS
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- K seric scazut/ normal
- pH urinar > 5.5
- FEHCO3 <5%
- Ca urinar crescut
- Citratul urinar este crescut
- excretia urinara de NH4 scazuta
Tablou clinico-biologic:
Acidoza tubulara tip I
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- manifestari neurologice
- manifestari pulmonare
- manifestari cardiovasculare
- manifestari musculo-scheletale: rare
- manifestari genito-urinare: nefrocalcinoza,
urolitiaza
Tablou clinico-biologic:
Acidoza tubulara tip I
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- administrarea de bicarbonat 1-2 mEq/Kg/24h
pt. a putea mentine niv. Bicarbonatului seric >
22 mEq/l
- corectia potasemiei
Tratament:
Acidoza tubulara tip I
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- incapacitatea de a reabsorbi HCO3-:
- functionarea defectiva a pompelor de protoni
- inhibitie sau deficit de anhidraza carbonica
- asociat cu alte disfuctii ale TCP: - co-transport cu Na
- aa, glucoza , fosfati, etc
Patogenie
Acidoza tubulara proximala tip II
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- Izolata (fara sindr. Fanconi):
- primara:
- ereditara
- sporadica
- anhidraza carbonica - inhibitie (acetazolamida, sulfamide, etc) - deficit ( AC tip II)
Introducere
Cauze de acidoza tubulara proximala tip II
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- Generalizate (cu sindr. Fanconi): - primara:
- ereditara
- sporadica
- boli autoimune
- boli genetice (cistinoza, galactozemie, etc)
- metale (Pb,Cd, Me,etc)
- medicamente/ toxine: aminoglicozide, tetracicline, cumarinice, etc
Introducere
Cauze de acidoza tubulara proximala tip II
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MYELIN BODIES
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Lead inclusions
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BISMUTH INCLUSIONS
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- manifestari neurologice
- manifestari pulmonare
- manifestari cardiovasculare
- manifestari musculo-scheletale: frecvent
- manifestari genito-urinare: rar
Tablou clinico-biologic:
Acidoza tubulara tip II
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- K seric scazut/ normal
- HCO3 > 15 mEq/l
- FEHCO3 >15%
- pH < 5.5
- excretia urinara de NH4 normala
Tablou clinico-biologic:
Acidoza tubulara tip II
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- administrarea de bicarbonat 10-15
mEq/Kg/24h, oral
- tratamentul osteomalaciei/ rahitismului
Tratament:
Acidoza tubulara tip II
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- incapacitatea de a excreta H+ si K+ la niv. TC:
- deficit de aldosteron
- rezistenta la aldosteron
- absenta stimularii ATP-azei H+ si/sau
scaderii reabsorbtiei distale a Na+
Patogenie
Acidoza tubulara distala tip IV
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- deficit primar mineralocorticoid
- izolat:
- deficit familial de methyloxidaza
- deficit combinat - boala Addison - deficit de desmolaza - deficit de 21 hidroxilaza
Introducere
Cauze de acidoza tubulara distala tip IV
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- hipoaldosteronism hiporeninemic
- nefropatie diabetica
- nefropatie tubulo-interstitiala
- nefropatie obstructiva
- nefropatie lupica
- deficit Ag II : inhibitori de EC
- rezistenta la aldosteron:
- nefropatie indusa de Cy, spironolactona
- medicamente: amilorid, triamteren, heparina
Introducere
Cauze de acidoza tubulara distala tip IV
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- manifestari neurologice
- manifestari pulmonare
- manifestari cardiovasculare
- manifestari musculo-scheletale: rar
- manifestari genito-urinare: nefrocalcinoza,
urolitiaza
Tablou clinico-biologic:
Acidoza tubulara tip IV
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- K seric crescut
- pH urinar < 5.5
- FEHCO3 <15%
- Ca urinar normal
- excretia urinara de NH4 scazuta
Tablou clinico-biologic:
Acidoza tubulara tip IV
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- corectia deficitului mineralocorticoid
- restrictie de potasiu
- dieta hipersodata si diuretice de ansa
- alcalinizare moderata (bicarbonat 1-2
mEq/kg/24 ore)
Tratament:
Acidoza tubulara tip IV
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I. In acidoza metabolica (spontana sau dupa incarcare acida)
K+ plasmatic N sau N sau pH urinar <5,5 >5,5 >5,5
<5,5 Excretie NH4
+ N Excretie K+ fractionata N sau Excretie Ca N N sau
II. Echilibru acido-bazic normal (dupa incarcare cu alcaline)
Excretie HCO3- fractionata >10-15% <5% <5% >5-
10%
III. Alte defecte ale tubilor adesea absente absente absente
IV. Nefrocalcinoza/litiaza absent adesea adesea absenta
V. Afectare osoasa adesea rareori rareori absenta
ATR distala (tip1)
ATR proximala (tip 2)
ATR hiperkaliemica (tip 4)clasica hiperkaliemica
Diagnosticul diferential al ATR
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HCO3- se filtreaza 24 meq/L x 180 L- se elimina 16 mEq/L (pH 7,25 6,7)- se absoarbe:
tub proximal pars convuluta +ansa Henle: 50 – 70%tub distal: redus intrucat 5 – 7 mEq/L
- se secreta: tub distal si colector
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I. ATR proximala primara izolata
A. Ereditara (persistenta)1. Autozomal dominanta2. Autozomal recesiva asociata cu retard mental si anomalii oculare
B. Sporadica (tranzitorie in copilarie)
II. ATR proximala secundara
A. In contextul sindromului Fanconi (cistinoza, galactozemie, intoleranta la fructoza, tirozinemie, boala Wilson, sindrom Lowe, leucodistrofie metacromatica, mielom multiplu, boala lanturilor usoare)
B. Medicamente si toxice (acetazolamida, tetraciclina expirata, aminoglicozide, valproat, 6-mercaptopurina, streptozocin, ifosfamid, plumb, cadmiu, mercur)
C. Asociata altor entitati clinice (deficit de vit. D, hiperparatiroidism, hipocapnie cronica, sindrom Leigh, boala cardiaca congenitala cianotica, boala chistica medulara, sindrom Alport, sindrom nefrotic corticorezistent, transplant renal, amiloidoza, litiaza renala recurenta)
Acidoza tubulara renala tip II
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Introducere
Tubul contort proximal
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Introducere
Tubul contort proximal
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Tubul contort distal si colector
Patogenie
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Tubul contort distal si colector
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Acidoza metabolica:
Este o tulburare acido-bazica initiata de o reducere a concentratiei plasmatice a bicarbonatului, fiind asociata cu o reducere a pH-ului plasmatic si reducere a pCO2.
Introducere
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Acidoza metabolica:
Hiatusul anionic = [Na+] – ([Cl-] + [HCO3-])= 8-16 mEq/l
Acidoze metabolice cu valori ridicate ale HA: - acidocetoza diabetica - uremie - ingestie de etilenglicol - ingestie de metanol - acidoza lactica
Introducere
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Acidoza metabolica:
Hiatusul anionic = [Na+] – ([Cl-] + [HCO3-])= 8-16
mEq/l
Acidoze metabolice cu valori normale ale HA: - pierderi de bicarbonat pe cale renala - pierderi de bicarbonat pe cale gastrointestinala - ingestie de saruri de clor
Introducere