Cardiovasculair stelsel ademhaling nier en urinewegen (D001943)
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2023-2024 Fysiologie van de
nier-en water-
/ionenhuishouding
Cardiovasculair stelsel, ademhaling,
nier en urinewegen
Emma Degroote
2DE BACH GENEESKUNDE
,Algemene inleidende begrippen ..................................................................................................................... 4
Nierfunc)e .......................................................................................................................................................... 4
Eindproducten van het metabolisme............................................................................................................. 4
ConcentraAes in bloed en urine..................................................................................................................... 4
Opbouw van de nier ........................................................................................................................................... 5
Macroscopische opbouw van de nier ............................................................................................................ 5
Opbouw van het nefron ................................................................................................................................. 5
Opbouw van de glomerulus ........................................................................................................................... 6
Glomulaire filtra5e ......................................................................................................................................... 7
De glomerulo-capillaire membraan .................................................................................................................... 7
FiltraAekenmerken van glomerulo-capillaire membraan: basale lamina....................................................... 7
Neutrale moleculen .................................................................................................................................. 7
PosiAef geladen moleculen ....................................................................................................................... 7
NegaAef geladen moleculen ..................................................................................................................... 8
Stoornissen in de glomerulo-capillaire filtraAe .............................................................................................. 8
Stoornissen in size-selecAvity ................................................................................................................... 8
Stoornissen in charge-selecAvity............................................................................................................... 8
Stoornissen in serumeiwiSen ................................................................................................................... 8
De Starling-krachten ...................................................................................................................................... 9
Renale klaring ..................................................................................................................................................... 9
2 prototypische substanAes bij de bespreking van klaring ............................................................................ 9
Inuline voor GFR........................................................................................................................................ 9
Para-aminohippuurzuur (PAH) voor RPF ................................................................................................... 9
Regula)e van de nierdoorbloeding en de glomulaire filtra)e .......................................................................... 10
Renale autoregulaAe.................................................................................................................................... 10
Hormonale factoren..................................................................................................................................... 10
Angiotensine II ........................................................................................................................................ 10
Hypovolemische hormonen .................................................................................................................... 11
Hypervolemische hormonen................................................................................................................... 11
Andere hormonen ................................................................................................................................... 12
Tubulo-glomerulaire feedback ................................................................................................................ 12
Neurale factoren .......................................................................................................................................... 12
Tubulaire reabsorp5e en secre5e .................................................................................................................. 13
Tubulaire reabsorp)e ....................................................................................................................................... 13
De fracAonele reabsorpAe van water in de nier .......................................................................................... 13
De fracAonele reabsorpAe van Na+ en K+ .................................................................................................... 13
Tubulaire reabsorpAe van Na+ ..................................................................................................................... 13
Tubulaire reabsorpAe van zout en water: basisprincipes ........................................................................ 14
Na+-reabsorpAe ter hoogte van de PT..................................................................................................... 14
Na+-reabsorpAe ter hoogte van de thick ascending limb TAL ................................................................. 15
Na+-reabsorpAe ter hoogte van het distaal nefron ................................................................................. 15
WaterreabsorpAe door leaky Aght juncAons en aquaporine-kanalen .................................................... 15
KwanAtaAeve aspecten van tubulaire reabsorpAe en secreAe ............................................................... 16
KwalitaAeve aspecten van tubulaire reabsorpAe en secreAe-overzicht ................................................. 16
Overzicht en begrip van reabsorpAe in proximale tubulus .......................................................................... 16
TransporteiwiSen en maximumgrens reabsorpAe en secreAe .................................................................... 17
Tubulaire reabsorpAe van glucose .......................................................................................................... 17
Tubulaire secreAe van PAH ...................................................................................................................... 17
Glomerulo-tubulaire balans ......................................................................................................................... 17
Vasa recta..................................................................................................................................................... 17
Osmolariteit en toniciteit .............................................................................................................................. 18
1
, Algemeen.......................................................................................................................................................... 18
Osmolariteit vs toniciteit ............................................................................................................................. 18
Formule toniciteit en osmolariteit .......................................................................................................... 18
OsmoAsche samenstelling van de lichaamsvloeistoffen .............................................................................. 18
Berekening plasma-osmolariteit ............................................................................................................. 18
Normaalwaarden in het bloed ................................................................................................................ 19
Medullaire osmolaire gradiënt ......................................................................................................................... 19
Het countercurrent mulAplier-systeem in de lis van Henle ......................................................................... 19
Ontstaan van medullaire osmolaire gradiënt .......................................................................................... 20
Verloop van de osmolariteit van het tubulaire vocht.............................................................................. 21
Permeabiliteit in de tubulus .................................................................................................................... 21
Beïnvloeden van medullaire osmoAsche gradiënt .................................................................................. 21
Het countercurrent exchange-systeem in de vasa recta .............................................................................. 22
Concentra)e en dilu)e van urine ...................................................................................................................... 22
Diure)ca en hun aangrijpingspunten ............................................................................................................... 23
Aangrijpingspunten van diureAca ................................................................................................................ 23
Regula5e van de waterbalans ....................................................................................................................... 24
Volumeregula)e ............................................................................................................................................... 24
ADH-vrijstelling onder invloed van hypovolemie/daling MABP ................................................................... 24
Osmoregula)e .................................................................................................................................................. 24
Dorst en ADH-loslaAng onder invloed van plasma-osmolariteit .................................................................. 24
Stoornissen in de waterhuishouding ................................................................................................................. 25
Hypovolemie ................................................................................................................................................ 25
Verschillende vormen van dehydrataAe.................................................................................................. 25
ManifestaAes van hypovolemie .............................................................................................................. 26
Hypervolemie .............................................................................................................................................. 26
Vochtverschuiving voor hypervolemie .................................................................................................... 26
Oedeem ....................................................................................................................................................... 27
Oorzaken van oedeem ............................................................................................................................ 27
Pathofysiologie van oedeem ................................................................................................................... 27
VolumedepleAe versus daling effecAef circulerend volume ........................................................................ 28
Chronisch hargalen ................................................................................................................................. 28
HepaAsche cirrose................................................................................................................................... 28
Regula5e van de natrium-en kaliumbalans.................................................................................................... 29
Regula)e van Na+-balans ................................................................................................................................. 29
Hyponatriëmie ............................................................................................................................................. 29
Oorzaken hyponatriëmie......................................................................................................................... 29
Hypernatriëmie ............................................................................................................................................ 30
Oorzaken ................................................................................................................................................. 30
TherapeuAsche principes ........................................................................................................................ 30
Regula)e van de K+-balans ............................................................................................................................... 30
Hypokaliëmie ............................................................................................................................................... 30
Oorzaken van hypokaliëmie .................................................................................................................... 31
ManifestaAe van hypokaliëmie ............................................................................................................... 31
TherapeuAsch principes .......................................................................................................................... 32
Hyperkaliëmie .............................................................................................................................................. 32
Oorzaken van hyperkaliëmie ................................................................................................................... 32
ManifestaAe van hyperkaliëmie .............................................................................................................. 32
Behandeling hyperkaliëmie..................................................................................................................... 33
Gevolgen van een gedaalde glomerulaire filtra)e ........................................................................................... 33
2
, CreaAnine en ureum .................................................................................................................................... 33
GFR-daling en manifestaAes ................................................................................................................... 34
Natrium en chloor........................................................................................................................................ 34
Kalium, protonen, fosfaten, sulfaten en urinezuur ...................................................................................... 34
Zuur-base evenwichten en pH-regula5e ........................................................................................................ 35
Regula)e van de zuur-base-evenwicht ............................................................................................................. 35
Eerste defensie: pH-buffer ........................................................................................................................... 35
Chemische werking ................................................................................................................................. 35
Fysiologische werking ............................................................................................................................. 35
Bicarbonaat als fysiologische buffer........................................................................................................ 36
pH-buffers in het lichaam ........................................................................................................................ 36
Het Davenport-diagram .......................................................................................................................... 36
Enkele begrippen met betrekking tot pH-buffers.................................................................................... 37
Tweede defensie: respiratoire defensie ....................................................................................................... 37
Derde defensie: renale defensie .................................................................................................................. 38
Mechanismen van renale protonsecreAe en -excreAe............................................................................ 38
Metabole stoornissen van het zuur-base-evenwicht ........................................................................................ 38
Metabole acidose ........................................................................................................................................ 38
Opvangsystemen van een metabole acidose .......................................................................................... 39
ManifestaAes van een metabole acidose ................................................................................................ 39
TherapeuAsche principes ........................................................................................................................ 39
De anion gap ................................................................................................................................................ 40
De anion gap en oorzaken van metabole acidose ................................................................................... 40
Metabole alkalose........................................................................................................................................ 40
Oorzaken metabole alkalose ................................................................................................................... 40
Opvangsystemen van metabole alkalose ................................................................................................ 40
ManifestaAes en therapeuAsche principes ............................................................................................. 40
Metabole acidose en alkalose: overzicht .......................................................................................................... 41
, Algemene inleidende begrippen
Nierfunc)e
3 essen)ële func)es:
1. Verwijderen eindproducten van het metabolisme uit het lichaam
2. Bewaken evenwicht tussen inname en excre)e van water, ionen en andere moleculen
3. Endocrien orgaan: synthese en vrijstelling van hormonen
ñ Renine, angiotensine-II, erythropoë)ne
Concentra5es in bloed en urine
Concentra)e bloed > concentra)e urine: aYankelijk dagelijkse inname
- Hoeveelheid stoffen:
ñ Veel zout: meer Na+ in urine om Na+ in plasma gelijk te houden
- Hoeveelheid water:
ñ Veel water: dilu)e van urine => concentra)e ureum en andere substan)es
Belangrijke waarden in plasma:
- Na+ = 140 meq/L1
- Crea)nine = 1 mg/dL: nierfunc)e
ñ > 1 mg/dL wijst op daling nierfunc)e
1
mEq/l = concentraAe van een ion (ajankelijk van lading) in een oplossing: 1 mEq/l Na+ = 1 mmol/l maar
2mEq/l Ca2+ = 1 mmol/l
4
,Opbouw van de nier
Macroscopische opbouw van de nier
Doorbloeding van de nier:
- Schorszone = 90% renale bloed
- Mergzone = 10% renale bloed
Weg van urine afvoer:
- Proximale en distale tubulaire
structuren
- Verzamelkanalen --> kanalen van
Bellini
- Calyces minores --> majores
- Renale pelvis --> ureters
Opbouw van het nefron
Nefron = elementaire func)onele eenheid2
- Glomerulus: nierschors ontvangt bloed via afferente arteriole
ñ Filtert bloed => glomulaire filtraat => tubulaire stelsel
ñ Overblijvende bloed => efferente arteriolen
- Tubulaire stelsel:
ñ Proximale tubulus (PT):
˃ Complex gedraaid gedeelte (PCT)
˃ Recht gedeelte (pars recta)
ñ Lis van Henle:
˃ Afdalend dun gedeelte
˃ S)jgend dik gedeelte (TAL)
ñ Distale nefron: contact met afferente en
efferente arteriolen
˃ Complex gedraaid gedeelte (DCT)
˃ Verbindingstubulus (CT)
ñ Verzamelkanalen (CD) => kanalen van Bellini
2 soorten nefronen:
- Juxtamedullaire nefronen = 15% van nefronen
ñ Lange lissen van Henle: diep in merg
ñ Glomerulus: overgang cortex – medulla
- Korte nefronen: 85% van nefronen
ñ Lus van Henle: niveau buitenste gedeelte niermerg
De 3 belangrijkste basisprocessen in het nefron
1. Glomulaire filtra)e
2. Tubulaire secre)e
3. Tubulaire reabsorp)e
Permeabiliteit ook aYankelijk van vorm:
- Hemoglobine met MW van 68 kDa
ñ Verwacht = 20%
ñ Realiteit = 3%
- Draagt bij tot niet-lineair verloop filtra)ecurve
Posi0ef geladen moleculen
Curve is naar rechts verschoven: Kf > 5-100 kDa
- Ka)onen aangetrokken door basale lamina
- Solvent drag-effect: geassocieerde ka)onen met basale lamina door stroming
filtra)evloeistof meegetrokken door fric)e
7
, Nega0ef geladen moleculen
Curve naar links verschoven: Kf < 5-100 kDa
- Nega)ef geladen basale lamina stoot anionen af
- Albumine met MW van 69 kDa hees Kf van 1%
ñ Reabsorp)e ter hoogte van tubuli: zo min mogelijk verlies
ñ 20 mg albumine per dag in urine
Stoornissen in de glomerulo-capillaire filtra5e
figuur toont:
- Zeefcurves (sieving curve) van filtra)emembraan
ñ Volle lijn: neutrale moleculen
ñ S)ppellijn: nega)ef geladen moleculen
- Elektroforese plots van eiwiqen in serum (SPEP)
- Elektroforeseplots van eiwiqen in urine (UPEP)
ñ Piek bij albumine: normale beperkte lekkage
Moleculen gebruikt in figuur
- 𝛾-eiwiqen = gammaglobulines = immunoglobulines
- 𝛽-eiwiqen = transferrine
- 𝛼, -eiwiqen = circulerende an)trypsines
- 𝛼- -eiwiqen = macroglobulines en haptoglobulines
ñ Macroglobulines gestegen bij nefro)sch syndroom
ñ Haptoglobulines = levereiwiqen betrokken bij aUraak RBC
Stoornissen in size-selec0vity
Diameter van filtra)eopening in basale lamina verhoogd
- Grotere moleculen zoals 𝛾- en 𝛽-eiwiqen door filter in
urine
- Verandering in UPEP: [𝛾- en 𝛽-eiwiqen]
- Verandering sieving curve: grotere neutrale moleculen
kunnen erdoor
Stoornissen in charge-selec0vity
Nega)eve lading ter hoogte van basale lamina gedaald
- Lekkage nega)ef geladen albumine
- Verandering in UPEP: verhoogde piek albumine
- Verandering zeefcurve: verschuiving rechts ka)onen
Stoornissen in serumeiwi;en
Geen renaal probleem
- Verandering in SPEP: bijkomende piek
ñ Hypergammaglobulinemie in plasma
- Verandering in UPEP: bijkomende piek
ñ hoge serumconcentra)e --> grotere drijvende
kracht --> door filter
- Geen verandering sieving curve
8
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