Een wandeling langs het nefron / klinische beelden · Een wandeling langs het nefron / klinische...
Transcript of Een wandeling langs het nefron / klinische beelden · Een wandeling langs het nefron / klinische...
Een wandeling langs het nefron /
klinische beeldenCOIG-cursusdag Water & Zout
2019
Dr. Gerald VervoortDept. of Internal medicine and Nephrology
Proximal tubule
Loop of Henle
Distal tubule
Collecting duct
Glomerulus
Filtratie
Endothelial Surface Layer (glycocalyx)
Hypothesis how endothelial sodium permeability could contribute to sodium homeostasis in the human organism.
Slit diaphragm
Tryggvason et al.
Tubulaire resorptie en secretie
Proximal tubule
Reabsorbs isosmotically ±60-70% of the filtered NaCl and H2OReabsorbs 90% of the filtered HCO3
-
Major site of ammonia production in nephronReabsorbs almost all of filtered glucose and amino acidsReabsorbs K+, phosphate, calcium, magnesium, urea, uric acidSecretes organic anions (such as urate) and cations (such as creatinine); this pathway is also used for excretion of PB-drugs and toxins
- +
basolateral (peritubular)apical (luminal)
Proximal Tubule
2K+
3Na+
ATP
ADP
Na+
Aquaporine-1H2O
- - ++
NHE3
H+
H+
Acetazolamide
H2O
HCO3-H+
CarboAnhydrase II
CO2
Na+
3HCO3-
SGLT(1)2
GlucosePhosphateAminoacidsHCO3
-
-- --
(.)gliflozine
H2O (Na+, Ca++ , Cl-, HCO3
-)Paracellular transport
- +basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
H+
Organic cation(kreatinine)
H+
Organic cation
OCT
Proximal Tubule
CimetidineTrimethoprimQuinine
-
Cimetidine Improves the Accuracy of Creatinine Clearance as an Indicator for Glomerular Filtration RateKi Chul Choi et al; 1993
GFR
- +basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
Organic anion**
Organic anion
ATP
ADP
OAT
MRP’s*
Proximal Tubule
*Multidrug resistance-associated protein** PAH, penicillins, diuretics
Probenicide
-
NaDC1
DC2-
OAT
DC2-
Proximal Tubule
*Alfa-1-MGBeta-2-MG
Imerslund-Gräsbeck syndrome
Loop of Henle
Reabsorbs 25-35% of filtered NaCl but almost no H2O
Countercurrent multiplier as NaCl reabsorbed in excess of H2O
Major site of active regulation of Mg+ excretionLoop of Henle
Tubulaire resorptie en secretie
+-
basolateralapical
2K+
3Na+
ATP
ADP
H2O
Na+
2Cl-
lisdiuretica
Cl-
ROMK
K+
K+
Na+,Ca2+, Mg2+
TALNKCC2
Loop of Henle
Defects causing Bartter’s syndrome(hypokalemia, metabolic alkalosis, hypercalciuria)
TAL
Na+,Ca2+, Mg2+
Ca2+
Ca2+
K+Na+
2Cl-
K+
Cl-
2K+
3Na+
ATP
ADP
NKCC2
ROMK CLCKB
Furosemide
K+Ba2+
+ -10 mV
basolateralapical
Barttin
CaSR
ADH, PTH?
-
-
WNK3SPAKSORLA
Countercurrent mechanism
H2O
Thiazide-diuretica(beïnvloeding verdunnend vermogen)
Lis-diuretica(beïnvloeding concentrerend vermogen)
Loop of Henle
Loop of Henle
Distal tubule Reabsorbs about 5% of filtered NaCl but almost no water
Major site, with connecting segment, of active regulation of Ca++ excretion
Tubulaire resorptie en secretie
DCT
- +Vitamin DPTHFGF23/klotho basolateralapical
2K+
3Na+
ATP
ADP
H2O
Na+
Cl-
Thiazide-diuretica
Cl-
NCCT
Ca++
Mg++
Ca++
3Na+
Ca-BP
TRPV5
ROMKK+
CLCKB
Barttin
TRPM6
Mg++?
Distale tubule
Ca++
DCT
- +
Vitamin DPTHFGF23/klotho basolateralapical
2K+
3Na+
ATP
ADP
H2O
Na+
Cl-
Thiazide
Cl-
NCCT
Ca++
Mg++
Ca++
3Na+
Ca-BP
K+
Mg++?
Defects causing Gitelman’s syndrome(hypokalemia, hypomagnesemia, hypocalciuria)
??
-
Ca++
Gain of function NCCT = Gordon’s syndrome(hypertension, hyperkalemia, metabolic acidosis) [=FHHt of pseudohypoaldosteronism type II]
- +Vitamin DPTH
basolateralapical
2K+
3Na+
ATP
ADP
H2O
Na+
Cl-
Thiazide
NCCT
Ca++
Mg++
Ca++
3Na+
Ca-BP
K+
Mg++?
Cl-
DCT
* Familiaire Hyperkalemische Hypertensie
Loop of Henle
Connecting segmentsand collecting tubule
Principle cells reabsorb Na+ and Cl - and secrete K + underinfluence of aldosteron
Intercalated cells secrete H +, reabsorb K +, and, in metabolicalkalosis, secrete HCO3
-
Reabsorb H2O in presence of antidiuretic hormone
Secrete H+ and NH3; urine pH can be reduced to as low as 4.5-5.0
Tubulaire resorptie en secretie
- +basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
AmilorideTriamterene
Aldosteron
+
SpironolactonEplerenon
ENaC
MR*
ANP-R
ANP
-
DigoxineCsA/tacrolimus
Heparin
Collecting tubule (principal cells)- -
* mineralocorticoidreceptor
- +basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
AmilorideTriamterene
Aldosteron
+
ENaC
MR*
-
Collecting tubule (principal cells)
* Mineralocorticoidreceptor** 11β-hydroxy-steroid dehydrogenase 2
Cortisol
+
11β-HSD2**
glycyrrhetinezuur
-
Liddle’s syndrome(hypertension, hypokalemia, metabolic alkalosis)
- +basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
Aldosteron
+
ENaC
MR
ANP-R
ANP
Pseudohypoaldosteronisme type 1(sodium wasting, hypovolemia, hyperkalemia)
+basolateralapical
2K+
3Na+
ATP
ADP
Na+
K+
Aldosteron
+
Spironolacton
ENaC
Aldo-R
ANP-R
ANP
-
- +
basolateralapical
vasopressine
Aquaporine 2Aquaporine 3(and -4)
V2-R
“vaptans”
Collecting tubules and ducts
-
- +
basolateralapical
Cl-
HCO3-
H+
H+
K+
ATP
ADP
ATP
ADP
H+
H2O + CO2
NH3
NH4+
Collecting tubule (intercalated cells type α)
- +
basolateralapical
Cl-
H+
HCO3
-
H2O + CO2
ATP
ADP
Collecting tubule (intercalated cells type β)
EJ Hoorn et al; JASN 2011
Aldosteron paradox
Magnesium
Calcium
PhosphateUrea cycle
Uric acid
Dr. Gerald VervoortRadboudumc Nijmegen
Thank you for your attention