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Samenvatting Nier 1

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​Fysiologie van de nier​

,​Normale​​histologie​​van​​het​​nefron​​(0)​​.......................................................................................​​5​
​Overzicht​​histologie​​.................................................................................................................​​5​
​1.​​Algemeen​​.............................................................................................................................​​5​
​2.​​Bloedvoorziening​​.................................................................................................................​​5​
​3.​​Nefron​​-​​Glomerulus​​............................................................................................................​​6​
​Nefron​​................................................................................................................................​​6​
​Podocyt​​..............................................................................................................................​​7​
​LM:​​“Glomerulaire​​basaalmembraan”​​................................................................................​​8​
​Globulaire​​filtratie​​...............................................................................................................​​8​
​Mesangium​​........................................................................................................................​​9​
​Twee​​types​​nefronen​​..........................................................................................................​​9​
​4.​​Nefron​​-​​Tubuli​​.....................................................................................................................​​9​
​Tubulus​​contortus​​primus​​=​​proximale​​tubulus​​................................................................​​10​
​Tubulus​​contortus​​secundus​​=​​distale​​tubulus​​.................................................................​​10​
​Lus​​van​​Henle​​..................................................................................................................​​10​
​Afvoerbuis​​=​​ductus​​colligens​​..........................................................................................​​11​
​5.​​Juxtaglomerulair​​apparaat​​.................................................................................................​​11​
​Functies​​van​​de​​nier​​(1)​​............................................................................................................​​12​
​1.​​Uitscheiding​​van​​afvalstoffen​​.............................................................................................​​12​
​2.​​Endocriene​​functie:​​productie​​hormonen​​...........................................................................​​12​
​R-A-A​​systeem​​en​​Erytropoëtine​​.....................................................................................​​12​
​Productie​​van​​calcitrol​​......................................................................................................​​13​
​3.​​Homeostase​​van​​de​​pH​​.....................................................................................................​​13​
​Zuurbase​​verstoring:​​keto-acidosis,​​lactic​​acidosis​​..........................................................​​13​
​Zuurbase​​verstoring:​​bv​​braken​​.......................................................................................​​13​
​4.​​Regulatie​​van​​de​​osmolariteit​​............................................................................................​​14​
​5.​​Regulatie​​extracellulair​​volume​​&​​bloeddruk​​......................................................................​​14​
​Toediening​​oplossing​​aan​​het​​extracellulaire​​volume​​......................................................​​15​
​6.​​Behoud​​van​​ionenbalans​​...................................................................................................​​15​
​Functionele​​eenheid​​van​​de​​nier:​​Nefron​​...............................................................................​​15​
​Reservecapaciteit​​van​​de​​nieren​​.....................................................................................​​15​
​Glomerulaire​​functie:​​Filtratie​​&​​urinevolume​​...................................................................​​16​
​Hoe​​werkt​​het​​nefron?​​......................................................................................................​​16​
​Urine​​excretie​​substantie-X​​..............................................................................................​​17​
​Glomerulaire​​filtratie​​(1)​​............................................................................................................​​18​
​Glomerulus​​............................................................................................................................​​18​
​Glomerular​​Filtration​​Rate​​(GFR)​​...........................................................................................​​18​
​GFR:​​capillary​​pressure​​(PH)​​drijft​​filtratie​​.......................................................................​​19​
​GFR:​​Autoregulatie​​..........................................................................................................​​19​
​Renale​​bloedflow,​​capillaire​​bloeddruk​​(PH)​​&​​GFR​​..............................................................​​20​
​Hormones​​&​​automatic​​neurons​​influence​​GFR​​..............................................................​​20​


​1​

, ​ egulatie​​GFR:​​Tubulo-glomerulaire​​feedback​​................................................................​​21​
R
​GFR​​.................................................................................................................................​​21​
​Glomerulaire​​hemodynamische​​autoregulatie​​.......................................................................​​22​
​Intrarenale​​mechanismen​​voor​​GFR​​autoregulatie​​................................................................​​22​
​Pathologie​​..............................................................................................................................​​22​
​Oefeningen​​............................................................................................................................​​22​
​Tubulaire​​reabsorptie,​​secretie​​en​​excretie​​(2a)​​.....................................................................​​22​
​Algemeen​​.........................................................................................................................​​23​
​Filtratie​​...................................................................................................................................​​23​
​Reabsorptie​​...........................................................................................................................​​24​
​Actief​​transport​​van​​natrium​​.............................................................................................​​24​
​Symport​​met​​Natrium​​.......................................................................................................​​24​
​Saturatie​​van​​gemedieerd​​transport​​................................................................................​​25​
​Reabsorptie​​in​​peritubulaire​​capillairen​​............................................................................​​26​
​Secretie​​..................................................................................................................................​​26​
​Excretie​​..................................................................................................................................​​27​
​Voorbeelden​​uit​​de​​klinische​​praktijk​​(2b)​​...............................................................................​​27​
​1.​​SGLT2​​inhibitoren​​........................................................................................................​​27​
​2.​​Penicillin​​en​​probenecid​​...............................................................................................​​28​
​Nierfunctiemeting​​(3a)​​...............................................................................................................​​29​
​Het​​begrip​​klaring​​...................................................................................................................​​29​
​Inulineklaring​​....................................................................................................................​​29​
​Glomerular​​filtration​​rate​​(GFR)​​.......................................................................................​​30​
​Voorbeeld:​​glucose​​..........................................................................................................​​30​
​Voorbeeld:​​ureum​​.............................................................................................................​​30​
​Voorbeeld:​​penicilline​​.......................................................................................................​​30​
​Formules​​................................................................................................................................​​31​
​Nierfunctiemeting​​oefeningen​​................................................................................................​​31​
​Waterbalans​​(4)​​..........................................................................................................................​​32​
​Total​​Body​​Water​​(TBW)​​........................................................................................................​​32​
​Waterbalans​​.....................................................................................................................​​32​
​Cel​​in​​andere​​osmolariteit​​................................................................................................​​32​
​Waterbalans​​...........................................................................................................................​​33​
​Antidiuretisch​​hormoon​​(ADH)​​...............................................................................................​​33​
​ADH​​effect​​nier​​.................................................................................................................​​34​
​Concentreren​​en​​dilueren​​van​​urine​​......................................................................................​​35​
​Countercurrent​​multiplication​​...........................................................................................​​36​
​Ureum​​recycling​​en​​vasa​​recta​​........................................................................................​​36​
​Terug​​naar​​ADH…​​.................................................................................................................​​37​
​Zoutbalans​​en​​extracellulair​​volume​​(5a)​​................................................................................​​38​
​Zoutbalans​​/​​behoud​​ECV​​......................................................................................................​​38​


​2​

, ​Tubuloglomerulaire​​feedback​​(JGA)​​......................................................................................​​38​
​Aldosteron​​........................................................................................................................​​39​
​Atriale​​Natriuretische​​Peptide​​(ANP)​​.....................................................................................​​41​
​Zoutbalans​​en​​waterbalans​​toepassingen​​en​​oefeningen​​.....................................................​​41​
​Kaliumbalans​​(6)​​........................................................................................................................​​42​
​Kaliumbalans​​.........................................................................................................................​​42​
​Kalium​​en​​de​​membraanpotentiaal​​........................................................................................​​42​
​Hypokaliëmie​​-​​symptomen​​..............................................................................................​​43​
​Hyperkaliëmie​​-​​symptomen​​............................................................................................​​43​
​Kaliumbalans​​.........................................................................................................................​​43​
​Intracellulaire​​[K]​​opname​​secundair​​aan​​[K]​​intake​​........................................................​​43​
​Verstoring​​kaliumbalans​​...................................................................................................​​44​
​Oorzaken​​...............................................................................................................................​​44​
​Behandeling​​hyperkaliëmie​​....................................................................................................​​45​
​Behandeling​​hypokaliëmie​​.....................................................................................................​​45​
​Zuur-base​​evenwicht:​​inleiding​​tot​​zelfstudie​​(7a)​​.................................................................​​46​
​Wat​​is​​pH?​​.............................................................................................................................​​46​
​Belang​​van​​pH​​regulatie​​..................................................................................................​​46​
​Zuren​​en​​basen​​komen​​in​​het​​lichaam​​...................................................................................​​47​
​Behoud​​zuur-base​​balans​​......................................................................................................​​47​
​pH​​homeostase​​behouden​​.....................................................................................................​​48​
​1e​​systeem:​​buffers​​..........................................................................................................​​48​
​2e​​systeem:​​ventilatie​​......................................................................................................​​49​
​3e​​systeem:​​nieren​​...........................................................................................................​​49​
​Mechanismen​​........................................................................................................................​​50​
​Henderson-Hasselbalch​​vergelijking​​...............................................................................​​51​
​Zelfstudie-opdracht​​................................................................................................................​​52​
​Zuur-base​​evenwicht:​​casussen​​(7b)​​.......................................................................................​​52​
​Compensatiemechanisme​​...............................................................................................​​52​
​Metabole​​acidose​​-​​anion​​gap​​................................................................................................​​53​
​Oorzaken​​high​​anion​​gap​​metabole​​acidose​​...................................................................​​53​
​Oorzaken​​normale​​anion​​gap​​metabole​​acidose​​.............................................................​​53​
​Casussen​​.........................................................................................................................​​53​
​Transport​​in​​de​​nier​​(8)​​..............................................................................................................​​54​
​Even​​opfrissen​​.................................................................................................................​​54​
​Natrium​​(Na+)​​........................................................................................................................​​55​
​Basolaterale​​Na+/K​​pomp​​................................................................................................​​56​
​Proximale​​tubulus​​............................................................................................................​​56​
​Dikke​​ascenderende​​deel​​Lus​​van​​Henle​​........................................................................​​57​
​Distale​​tubulus​​.................................................................................................................​​58​
​Distale​​tubulus​​thv​​de​​connecting​​tubule​​en​​de​​corticale​​ductus​​colligens​​......................​​58​


​3​

, ​Chloor​​....................................................................................................................................​​59​
​Proximale​​Tubulus​​...........................................................................................................​​59​
​Distale​​tubulus​​thv​​TAL​​en​​distal​​convoluted​​tubule​​.........................................................​​61​
​Distale​​tubulus​​thv​​TAL​​en​​distal​​convoluted​​tubule​​.........................................................​​61​
​Waterreabsorptie​​.............................................................................................................​​62​
​Kalium​​(K+)​​............................................................................................................................​​62​
​Even​​opfrissen​​.................................................................................................................​​62​
​Kaliumbalans​​invloeden​​...................................................................................................​​63​
​DUS​​.................................................................................................................................​​63​
​Proximale​​tubulus​​............................................................................................................​​64​
​TAL​​...................................................................................................................................​​65​
​Distale​​tubulus​​.................................................................................................................​​65​
​Kaliumbalans​​door​​veel​​factors​​gereguleerd​​...................................................................​​66​
​vaak​​meerdere​​factoren​​at​​play​​.......................................................................................​​69​
​Ureum​​....................................................................................................................................​​69​
​Glucose​​..................................................................................................................................​​70​
​Aminozuren​​............................................................................................................................​​71​
​Eiwitten​​..................................................................................................................................​​71​
​Urinezuur​​(niet​​kennen)​​.........................................................................................................​​71​
​Fosfaat​​...................................................................................................................................​​72​
​Calcium​​(Ca2+)​​......................................................................................................................​​72​
​Proximale​​tubulus​​............................................................................................................​​72​
​TAL​​...................................................................................................................................​​73​
​DCT​​..................................................................................................................................​​73​
​BL​​.....................................................................................................................................​​73​
​Apicaal​​passief​​.................................................................................................................​​73​
​Factors​​affecting​​Ca2+​​reabsorption​​along​​the​​nephron​​..................................................​​74​
​Magnesium​​(Mg2+)​​................................................................................................................​​74​
​PT​​....................................................................................................................................​​75​
​TAL​​...................................................................................................................................​​75​
​DCT​​..................................................................................................................................​​75​
​Samenvatting​​.........................................................................................................................​​76​
​ oelstellingen​​............................................................................................................................​​77​
D




​4​

,​Normale histologie van het nefron (0)​
​ belangrijke pathologie: vaak door hypertensie nefronen verliezen​

​=> nefropathie en nierinsufficiëntie​


​Overzicht histologie​
​ .​ A
1 ​ lgemene kenmerken​
​2.​ ​Bloedvoorziening​
​3.​ ​Nefron - Glomerulus​
​○​ ​Bouw​
​■​ ​Podocyt​
​■​ ​Glomerulaire basaalmembraan​
​■​ ​endotheel​
​○​ ​Filtratie​
​4.​ ​Nefron - Tubuli​
​○​ ​Verloop​
​○​ ​Microscopische kenmerken​
​5.​ ​Juxtaglomerulair apparaat​


​1. Algemeen​
​Nier = boonvormig orgaan​
​●​ ​Nierbekken​
​○​ ​Uitmonding calyces majores en minores​
​●​ ​Macroscopische doorsnede​
​○​ ​Merg​
​→ veel bloedvoorziening​
​○​ ​Schors​
​○​ ​Mergpiramiden​
​○​ ​Nierkapsel = dik fibreus kapsel = collageen BW​
​→ zorgt dat nier niet kan uitzetten​
​→ als wel willen door bv niersteen: verstopping tegen vergrote druk → tubuli​
​uitzetten → druksysteem zet zich verder tegen nefron => pijn​


​2. Bloedvoorziening​
​ sterk vasculair orgaan wnt HD door de nieren (enorme doorstroom)​

​→ lich kan HD goed regelen doorheen nier: autoregulatie arteriën:​
​A renalis​
​●​ ​Interlobaire arterieën​
​○​ ​Aa. arcuatae​
​■​ ​Aa. interlobulares (aa. radiate)​
​●​ ​Afferente​​arteriole​


​5​

, ​●​ G ​ lomerulaire vaatkluwen​
​= enige plaats waar vaatbed door arteriën aanvoer en afvoer heeft​
​→ individ glomeruli minder/meer bevloeien: filtratiedruk regelen​
​●​ ​Efferente​​arteriole​
​■​ ​Peritubulair capllaire plexus​
​■​ ​Vasa recta (juxtamedullaire efferente arteriolen)​
​= zeer lange rechte vaten die in merg lopen​
​→ geven aanleiding tot osmotische gradiënt​
​●​ ​Merg nauw contact tussen v. en a. rectae​
​●​ ​Osmotische gradiënt naar de papil toe​
​○​ ​Vv. stellatae​
​●​ ​Vv. arcuatae​
​V. renalis​


​3. Nefron - Glomerulus​
​ efron = functionele eenheid v nier bestaande uit 1 glomerulus en tubulus stelsel dat afvoerd in​
N
​verzamelbuis (ductus colligens)​
​→ afvoerende buis van een bepaalde glomerulus raakt op einde nog in contact met eigen​
​glomerulus → beschouwen als osmostaat = osmose van bijna finale urine meten en doorgeven​
​aan eigen glomerulus om onmiddellijke regeling te hebben van filtratiedruk​


​Nefron​
​(= nierlichaampje = lichaampje van Malpighi)​
​●​ ​Glomerulus​
​○​ ​1-2 miljoen/menselijke nier (krijgen bij gebooorte en niet bijgemaakt)​
​○​ ​Arteriolair vaatkluwen​
​○​ ​Filtratieruimte​​(​ruimte van Bowman​​= virtuele ruimte​​tussen kapsel en nier)​
​→ omgeven door​​kapsel van Bowman​​met​​visceraal en​​parietaal blad​
​→ bepaalde moleculen kunnen niet door omdat te groot: bv albumine*​
​○​ ​Productie van primaire urine​
​●​ ​Tubulussysteem​
​●​ ​Eindigt in ductus colligens (verzamelbuis)​

​Path albumine*: reden hypoalbumie​
​1.​ ​Aanmaak verminderd​
​→ bij ernstig leverlijden​
​2.​ ​Export vermeerderd (uitplassen of via huid bij bv brandwonden)​
​→ lek in glomeruli grootste oorzaak: filtratiemembraan kapot → kan door →​
​autoimmuunreactie OF lekken hebben thv membraan door lokale ontsteking​
​→ pt eruitzien als michelin manneke: helemaal opgeblazen wnt vocht sijpelt uit bloedb.​

​Indien RBC in urine: teken probleem filter nier​



​6​

,​L afbeelding zien:​
​-​ ​Pariëtale en viscerale blad van Kapsel van Bowman​
​-​ ​Bovenkant = vasculaire pool (met afferente en efferente arteriolen)​
​-​ ​Onderkant = urinaire pool​
​-​ ​Vasculaire kluwen = vasculaire lussen = verkleefd met elkaar door mesangiumcellen​
​-​ ​Rond glomerulus klassieke samenstelling basaalmembraan (bij globulaire BM specifiek)​

​ ij kapotgaan glomerulus: tubulus ook atrofiëren (1 systeem, hangt samen)​
B
​=> fibreuze gebieden krijgen = nierlittekening​
​=> allen hierdoor het onderscheid kunnen maken tussen de verschillende nefron systemen:​
​indien deeltje fibreus weefsel zien​




I​ndien EXACTE lokatie willen weten: metalen gebruiken die​
​neerslagen → Bv op foto: zilverneerslag zien​
​●​ ​Rode sterren = capillaire lumina​
​●​ ​Rode pijl = mesangiumcellen​
​●​ ​Gele pijl = endotheelcel​
​●​ ​Zwarte pijl = viscerale blad v kapsel v Bowman = podocyt​


​Podocyt​
​ cel met kleine voetjes die plaatsen op BM​
=
​→ veel grote en kleine uitlopers​
​→ bedekken volledig globulaire BM​

​Globulaire filtratie​​gevormd door:​
​1.​ ​Podocyten​
​2.​ ​Endotheel met fenestrae​
​3.​ ​Globulaire BM​



​7​

,​ lomerulus = filtratie apparaat onder druk​
G
​→ mechanisme moet tegen druk weerstand kunnen bieden​
​→ voetjes dienen om tegendruk te geven tegen globulaire BM​
​→ zal beschadiging glomeruli en verlies van eiwitten tegen gaan​


​LM: “Glomerulaire basaalmembraan”​
​●​ ​Endotheel​
​○​ ​Fenestrae (gaten; zeef)​
​■​ ​70-150 nm diameter​
​■​ ​Geen diafragma (=open venster)​
​→ filtratie: cellen tegenhouden maar opgeloste​
​stoffen door​
​Bv RBC niet door kunnen​
​●​ ​Basale membraan​
​○​ ​Negatief geladen (oa. heparaansulfaat)​
​○​ ​Op EM: drie lagen​
​1.​ ​Lamina rara interna​
​2.​ ​Lamina densa​
​3.​ ​Lamina rara externa​
​= lagen gevlochten matten als vezelplaten over elkaar die alleen kleine stoffen doorlaten​
​met de juiste lading (membraan neg geladen dus zal neg geladen deeltjes afstoten)​
​●​ ​Podocyten​
​○​ ​Viscerale blad van kapsel van Bowman​
​○​ ​Primaire uitlopers (trabekels)​
​○​ ​Secundaire uitlopers (pedikels)​
​○​ ​Filtratiespleten afgesloten met dun diafragma​
​» Vertraagt passage van moleculen​


​Globulaire filtratie​
​gevormd door:​
​1.​ ​Endotheliale fenestrae​
​●​ ​RBC​
​2.​ ​Basale membraan​
​●​ ​Negatief geladen deeltjes geblokkeerd door lading (heparaansulfaat!)​
​» Bvb albumine (60kDa): grootte nog net erdoor MAAR door neg lading toch niet​
​●​ ​Positief geladen deeltjes tegengehouden vanaf 70 kDa​
​3.​ ​Filtratiespleet podocyt​
​●​ ​Moleculen < 3,5nm met positieve of neutrale lading gemakkelijker dan negatief​
​geladen of grotere deeltjes (bvb. Albumine 3,6nm en negatief geladen)​
​●​ ​Indien neg geladen deeltjes niet door → vasthangen en lokale inflammatie​
​veroorzaken → lek veroorzaken → toch door​




​8​

, ​Mesangium​
​= manier waardoor de glomerulus wordt samengehouden​
​●​ ​Intraglomerulaire structuur​
​(→ er is ook een extraglomerullaire maar niet deze)​
​●​ ​Mesangium cellen​
​○​ ​= actieve cellen die receptoren hebben voor Ang 2​
​→ kunnen cytokines vrijstellen die influx van ontstekingscellen induceren​
​→ onstekingsreactie in capillair → capillair membraan kapot → lek in membraan​
​○​ ​Kunnen fagocyteren: resorberen​
​○​ ​Kunnen prolifereren​
​Bv delen tegen 1 vd stoffen die neerslagen in capillair membraan (door fenestrae​
​geraakt maar niet verder)​


​Twee types nefronen​
​1.​ ​Corticale nefronen​
​●​ ​Buitenste deel cortex​
​●​ ​Korte lus van Henle​
​→ komt niet tot in merg​
​●​ ​Efferente glomerulaire arteriole wordt peritubulair capillair netwerk​
​2.​ ​Juxtamedullaire nefronen​
​●​ ​Op grens cortex-merg​
​●​ ​Lange lus van Henle tot in merg​
​●​ ​Efferente glomerulaire arteriole daalt in merg als vasa recta (= recht bloedvat)​


​4. Nefron - Tubuli​


​Tubulus contortus primus​




​Tubulus contortus secundus​


​Ductus colligens​


​Lus van Henle​




​9​

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