Renal Physiology Lecture Notes PDF

NIER FISIOLOGIE (Figure: SEM of Renal Glomeruli and Blood Vessels: Silverthorne, 2019) Dr Shantal Windvogel [email protected] Division of Medical Physiology, 3042, Biomedical Research Institute (BMRI) Faculty of Medicine...

NIER FISIOLOGIE (Figure: SEM of Renal Glomeruli and Blood Vessels: Silverthorne, 2019) Dr Shantal Windvogel [email protected] Division of Medical Physiology, 3042, Biomedical Research Institute (BMRI) Faculty of Medicine and Health Sciences, Stellenbosch University 1  Nier Funksies Kidney Functions 1. Reguleer ekstrasellulêre volume 1. Regulates ECF volume and blood (ESV) en bloeddruk pressure 2. Reguleer osmolariteit 2. Regulates osmolarity 3. Ioon balans 3. Ion balance 4. pH-regulering 4. pH regulation 5. Hormoon produksie 5. Hormone production 6. Ekskresie 6. Excretion 7. Glukoneogenese 7. Gluconeogenesis Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings; Acknowledgements and references for slides in this pack: 1. Silverthorne D (2019). Human Physiology-An integrated approach. 8th ed. Pearson Benjamin Cummings; 2. Martini FH (2006). Fundamentals of Anatomy & Physiology. 7th ed. Pearson Benjamin Cummings; 3. Prof. J. Koeslag, Medical2 Physiology, Stellenbosch University Fig. 19.1 3 +/- 130-170g 4 Fig. 19.1  5 Fig. 19.1 6  80% * 20% 100% *FILTRATION FRACTION=GFR/RENAL PLASMA FLOW Fig. 19.2 7  Filtrasie Fraksie Filtration Fraction Fig. 19.4 8  Nierfunksie Renal Function Konsentreer die filtraat deur Concentrates the filtrate by glomerular glomerulêre filtrasie: filtration-failure → dehydration gebrek hieraan → dehidrasie Absorbeer en behou waardevolle Reabsorbs and retains useful materiaal vir gebruik deur ander substances that are used by other weefsels: suikers en aminosure tissues: sugars and amino acids Doel van urien produksie: Handhaaf Purpose of urine formation: Maintains homeostase deur die regulering van homeostasis by regulating the volume bloed volume en samestelling, en wat and composition of blood, which die ekskresie van metaboliese includes the excretion of metabolic afvalprodukte insluit wastes Niere vervaardig gewoonlik gekonsentreerde urien: 1200-1400 Kidneys usually produce concentrated mOsm/L urine: 1200-1400 mOsm/L 9  Filtration occurs in the renal corpuscle Renal filtrate= Plasma (iso- osmotic) minus blood cells and blood proteins  M.w. 7000 Da freely filtered  7000-70000 Da variable  Albumin 66000 Da 0.02% Proteinuria ‘protein in urine’ May result from: Prolonged (hypoxia) to cells of filtration membrane. Defective Fig. 19.5 /damaged filtration 10 apparatus. Watter faktore beïnvloed filtrasie druk en die spoed van filtraat produksie? Which factors influence filtration pressure and rate of filtrate formation? (SEM of Glomerular filtration apparatus showing podocyte foot processes around glomerular 11 capillary, Silverthorn D, 2014)  Faktore wat Glomerulêre Filtrasie Spoed (GFS) beinvloed Factors affecting Glomerular Filtration Rate (GFR) 1. Effektiewe filtrasie druk 1. Net filtration pressure Bepaal deur die bloeddruk en renale Determined by blood pressure and bloedvloei renal blood flow 2. Filtrasie koëffisiënt: 2. Filtration coefficient a) Glomerulêre oppervlak beskikbaar a) Glomerular surface area available for vir filtrasie filtration b) Deurlaatbaarheid van die b) Permeability of interface between koppelvlak tussen die kapillêre en capillary and Bowman’s capsule die Bowman kapsel 12  GFS en Netto Filtrasie Druk GFR and Net Filtration Pressure Blood pressure-main driving force for glomerular filtration Any factor that alters filtration pressure alters GFR, e.g. blockage of renal artery, etc. Hemorrhage, shock, dehydration can alter GFR and lead to acute renal failure Hidrouliese (hidrostatiese) druk in glomerulus (PH) Kolloïed osmotiese druk (π) in die glomerulus Hidrostatiese vloeistof (Pfluid/Pvloeistof) 13 druk in die kapsule Fig. 19.6  14 Fig.19.6 Renale Bloedvloei, Arteriole weerstand en GFS Renal Blood flow, Arteriolar resistance and GFR 15 Fig. 19.6  3 Vlakke van GFS Beheer 3 Levels of GFR Control 1. Outoregulering (plaaslike vlak) 1. Autoregulation (local level) Werksaamhede van die sel, weefsel, Activities of cell, tissue, organ, organ orgaan, orgaan-stelsel pas outomaties aan system automatically adjusts in response as gevolg van ʼn omgewingsverandering to an environmental change By changing diameters of afferent Deur die verandering van diameters van arterioles, efferent arterioles, and afferente arteriole, efferente arteriole, en glomerular capillaries glomerulêre kapillêre 2. Hormonale regulering (geïnisieer deur 2. Hormonal regulation (initiated by die niere) kidneys) 3. Outonomiese regulasie (deur 3. Autonomic regulation (by simpatiese afdeling van die ANS) sympathetic division of ANS) 16  Outoregulering: 2 Meganismes Autoregulation: 2 Mechanisms 1. Miogeniese teorie (outomatiese 1. Myogenic response (automatic reaksie van vaskulêre gladdespier tot response of vascular smooth druk veranderinge) muscle to pressure changes) 2. Tubuloglomerulêre terugvoer 2. Tubuloglomerular feedback (veranderinge in vloei in die distale (changes in flow in distal tubule kronkelbuis beïnvloed GFS) influences GFR) Verminderde bloedvloei en Reduced blood flow or glomerular glomerulêre bloeddruk ly tot : blood pressure triggers: - uitsetting van die afferente arteriole – dilation of afferent arteriole - uitsetting van glomerulêre kapillêre – dilation of glomerular capillaries - vernouing van efferente arteriole – constriction of efferent arterioles 17 Miogeniese respons Myogenic response ↑ renal blood pressure afferent arterioles stretch contraction smooth muscle cells constriction afferent arterioles ↓ glomerular blood flow (less effective response when renal blood pressure is low) 18 Tubuloglomerulêre Terugvoer Tubuloglomerular Feedback 19 Fig.19.7  Hormonale regulering van GFS Hormonal Regulation of GFR Deur hormone van die: By hormones of the: - renien-angiotensien-stelsel bv. – renin–angiotensin system Angiotensien II (vasokonstriktor) e.g. Angiotensin II (vasoconstrictor) - natriuretiese peptiede (ANP en BNP) – natriuretic peptides (ANP and BNP) Ander stowwe kan ook GFS reguleer bv. Prostaglandiene (vasodilator) – Other substances can also regulate GFR e.g. Prostaglandins (vasodilator) 20  Reaksie tot Verlaging in GFS Response to Reduction in GFR HOMEOSTASIS Normal GFR HOMEOSTASIS ↑ BP & BV DISTURBED ↓ GFR ANGIOTENSIN ACTIVATION RENIN 21 Hormonale en Outonome Regulering Hormonal and Autonomic Regulation Werk deur: Work by: a) Verandering in arteriole weerstand a) Changing arteriolar resistance ↑ deursnee= ↑ GFS ↑diameter= ↑GFR ↓ deursnee = ↓ GFS ↓diameter= ↓ GFR b) Verandering van filtrasie b) Changing filtration coefficient (By koëffisiënt (deur die grootte van changing size of filtration slits) filtrasie splete te verander) 22  Outonomiese Regulering van GFS Autonomic Regulation of GFR Bestaan meestal uit simpatiese Mostly sympathetic postganglionic postganglioniese vesels wat α-reseptore fibers innervating α-receptors innerveer Sympathetic activation:Adjusts rate of Simpatiese aktivering: Pas die tempo urine formation by changing blood flow van urienvorming aan deur bloedvloei and blood pressure at nephron en bloeddruk by die nefron te verander -vernou afferente arteriole – constricts afferent arterioles -verlaag GFS – decreases GFR -vertraag filtraat produksie – slows filtrate production Stimuleer die vrystelling van renien Stimulates release of renin Beperk water- en sout verliese in die urien deur herabsorpsie by die nefron te Restricts water and salt loss in urine by stimuleer stimulating reabsorption at nephron 23 Membraan Vervoer Membrane Transport  Membraan Vervoer Membrane Transport Sel membraan vorm ʼn skans wat Cell membrane forms a moet toelaat dat barrier but must allow for – Nutriënte binnegaan – Nutrients to enter – Produkte en afvalstowwe – Products and wastes toelaat om die sel te verlaat to leave Deurlatendheid bepaal wat in en uit ʼn sel beweeg, en ʼn membraan Permeability determines wat what moves in and out of Ondeurlaatbaar: niks kan a cell, and a membrane binnegaan of buitegaan that Vrylik deurlaatbaar: enigiets kan – Impermeable: nothing binnegaan of buitegaan can enter or leave Selektief deurlaatbaar: net sekere – freely permeable: stowwe kan binnegaan of anything can enter and buitegaan leave – selectively permeable: only certain substances can enter or leave 25  Impermeable membrane Freely permeable membrane Selectively permeable membrane 26  Membraan vervoer afhanklik van Membrane transport – Groote dependant on: – Elektriese lading -Size -Electrical charge – Molekulêre vorm -Molecular shape – Lipied oplosbaarheid -Lipid solubility Fig.5.5  Membraan Vervoer Membrane Transport Alle molekules is in konstante All molecules are constantly in beweging motion Molekules in oplossing beweeg Molecules in solution move ewekansig randomly Ewekansige beweging veroorsaak Random motion causes mixing vermenging Concentration is the amount of Konsentrasie is die hoeveelheid solute in a solvent soluut in ʼn oplosmiddel Concentration gradient Konsentrasie gradiënt – More solute in one part of a – Meer soluut in een gedeelte van solvent than another ʼn oplosmiddel as in ʼn ander 28  Diffusie Diffusion Funksie van Function of konsentrasie concentration gradiënt gradient Solute beweeg Solutes move langs konsentrasie down gradiënt concentration Molekules meng gradient ewekansig Molecules mix Soluut versprei randomly deur oplosmiddel Elimineer Solute spreads konsentrasie through solvent gradiënt Eliminates Fig. 5.6 Two dyes, equal concentration, concentration KI=166 daltons, Congo red=697 daltons. gradient 29  Faktore wat Diffusie Affekteer Factors Affecting Diffusion – Afstand wat partikel moet – Distance the particle has to beweeg move – Molekuul grote – Molecule size Kleiner=vinniger Smaller is faster – Temperatuur – Temperature Meer hitte, vinniger beweging More heat, faster motion – Gradiënt grote – Gradient size Verskil tussen hoë en lae konsentrasies The difference between high and low concentrations – Elektriese kragte Aantrekking van teenoorgestelde, – Electrical forces Afstoting van soortgelyke Opposites attract, like charges repel 30  Diffusie oor sel membrane Diffusion across cell membranes 1. Eenvoudige diffusie: 1. Simple diffusion: Materiale wat diffundeer Materials that diffuse – Lipied-oplosbare verbindings – Lipid-soluble compounds (alkohol, vetsure, en steroïede) (alcohols, fatty acids, and – Opgeloste gasse (O2 & CO2) steroids) – Dissolved gases (O2 & CO2) 2. Kanaal-bemiddelde diffusie: – (Via proteïenkanale) is water- 2. Channel-mediated diffusion: oplosbaar – (Via transmembrane proteins) – Is ione are water–soluble compounds – Are ions 31  Faktore in kanaal-bemiddelde diffusie Factors in channel-mediated diffusion Deurgang afhanklik van: Passage depends on: – grote – size – lading – charge – interaksie met die kanaal – interaction with the channel 32 33  Figure 5-10 MEMBRANE TRANSPORTERS Channel proteins create a water-filled pore Carrier proteins never form an open channel between the two sides of the membrane ECF Cell membrane ICF Carrier open Same carrier to ICF open to ECF can be classified can be classified Cotransporters Gated channels Open channels Uniport carriers Symport carriers Antiport carriers Open Closed 34  Osmose Osmosis Diffusie van water oor ʼn selmembraan Diffusion of water across the cell membrane Meer solute-laer konsentrasie van water molekules More solute molecules, lower concentration of water molecules Membraan moet vrylik deurlaatbaar tot water wees, selektief deurlaatbaar Membrane must be freely permeable tot solute to water, selectively permeable to solutes Water molekules diffundeer oor membraan in rigting van groter Water molecules diffuse across hoeveelheid solute membrane toward solution with more solutes Volume neem toe aan kant met meer solute Volume increases on the side with more solutes 35 Osmose Osmosis Fig. 5.2 36  Vergelyking van Osmolariteite Osmolariteit: Hoeveelheid partikels in oplossing Osmolarity: Number of particles in a solution Uitgedruk as osmol/L OF (OsM) Expressed as osmol/L OR (OsM) Gemiddelde osmolariteit in liggaam = 300 mOsM Average osmolarity in body = 300 mOsM Osmolaliteit: osmol van opgelosste stof/kg water Osmolality: osmoles of solute/kg of 37 water Isotonies (iso-= selfde, Isotonic (iso- = same, tonos = spanning) tonos = tension) ʼn Oplossing wat nie die A solution that does not osmotiese vloei van water cause osmotic flow of in en uit ʼn sel veroorsaak water into or out of a cell nie Martini FH, 2006 38  Hipotonies Hypotonic Hipotonies – Hypotonic (hypo- = (hipo- = onder) below) Het minder solute en verloor Has less solutes and water deur osmose loses water through osmosis ‘n Sel in ʼn hipotoniese oplossing: A cell in a hypotonic solution: - Kry water - Skeer (hemolise van rooi - Gains water bloed selle) - Ruptures (hemolysis of red blood cells) Martini FH, 2006 39  Hipertonies Hypertonic hiper = bo hyper = above Het meer solute en verwerf water deur Has more solutes and gains osmose water by osmosis ʼn Sel in ʼn hipertoniese A cell in a hypertonic oplossing: solution: - verloor water - krimp (krenering van rooi - loses water bloed selle) - shrinks (crenation of red blood cells) 40 Martini FH, 2006  Draer-gemedieerde Vervoer Carrier-Mediated Transport Gefasiliteerde vervoer Facilitated diffusion Aktiewe vervoer Active transport – Eienskappe – Characteristics Spesifisiteit: Specificity: – 1 oordrag proteïen, 1 stel substrate – one transport protein, one set of Versadigings limiete: substrates – Tempo afhangend van vervoer proteïen, nie substrate Saturation limits: – Rate depends on transport proteins, not substrate Regulering: Regulation: – Kofaktore, bv. hormone – Cofactors, e.g. hormones 41 Kompetisie Competition 42 Fig. 5.17  Kompetisie Competition Extracellular fluid Glucose Glucose Maltose GLUT transporter Intracellular fluid (a) The GLUT transporter (b) Maltose Fig. 5.17 43  Versadiging Saturation 44 Figure 5-17  Bemiddelde oordrag Carrier-Mediated Transport Kotransport Cotransport 2 stowwe beweeg in 2 substances move in dieselfde rigting op the same direction at dieselfde tyd the same time Uitruiling (Teenvervoer) Countertransport 1 stof beweeg terwyl die 1 substance moves in ander uit beweeg while another moves out 45 Bemiddelde Oordrag: Passief Facilitated Diffusion: Passive Draer proteïene dra Carrier proteins transport molecules too molekules wat te groot large to fit through channel proteins is om deur kanaal (glucose, amino acids): Carrier proteins transport molecules too large to fit proteïne te gaan (glukose, aminosure): through channel proteins (glucose, amino acids): reseptorsetel (specific) Martini FH, 2006 46 Draer-bemiddelde Oordrag Carrier-Mediated Transport Aktiewe vervoer Active transport Aktiewe vervoer proteïene: Active transport proteins: beweeg substrate teen konsentrasie – move substrates against gradiënt concentration gradient – Benodig energie, soos ATP – require energy, such as ATP – ioon pompe beweeg ione (Na+, K+, Ca2+, – ion pumps move ions (Na+, K+, Mg2+) Ca2+, Mg2+) – uitruilingspomp transport 2 ione in – exchange pump teenoorgestelde rigtings op dieselfde countertransports two ions at tyd the same time 47 – Aktiewe vervoer, draer bemiddeld: » Natrium ione (Na+) uit, kalium ione (K+) in N+-K+ - pomp » 1 ATP transport 3 Na+ en 2 K+ Ook: Ca2+ ATPase, H+- ATPase/proton pomp, H+- K+- ATPase – Active transport, carrier mediated: » Sodium ions (Na+) out, potassium ions (K+) in » 1 ATP moves 3 Na+ and 2 K+ » Also: Ca2+ ATPase, H+- ATPase/proton pomp, H+- K+- ATPase Martini FH, 2006 48 Figure 5–15 The Sodium–Potassium Exchange Pump 49 Sekondêr Aktiewe Vervoer Secondary Active Transport Na+ konsentrasie gradiënt dryf glukose transport ATP energie pomp Na+ terug uit Na+ concentration gradient drives glucose transport ATP energy pumps Na+ back out Fig. 5.16 Mechanism of the SGLT transporter 50 51  Vesikulêre Vervoer Vesicular Transport Materiale beweeg in of uit sel in vesikels Materials move into or out of cell in Endositose (endo- =binne) is aktiewe vesicles transport wat ATP gebruik: Endocytosis (endo- = inside) is active – reseptor medieerde transport using ATP: – Pinositose: Endosome “drink” – receptor mediated ekstrasellulêre vloeistof – Pinocytosis: Endosomes “drink” extracellular fluid Fagositose: Pseudopodia (pseudo- = Phagocytosis: Pseudopodia (pseudo- = false, pod- = foot) : Opneming van groot false, pod- = foot) engulf large objects in voorwerpe in fagosome phagosomes Eksositose (ekso- = buite): Korreltjies of Exocytosis (exo- = outside): Granules or druppeltjies wat vanaf die sel vrygestel droplets released from cell (reverse of is (teenoorgestelde van endositose) endocytosis) 52  Reseptormedieerde Endo- en Eksositose Reseptors (glikoproteïene) bind teken molekule (ligande) Omhulde vesikel (endosome) dra ligande en reseptore in die sel in 9 (klatrien) Fig. 5.19 53 Transsitose Transcytosis 54 Fig. 5.22 Fagositose Phagocytosis 55  56 Martini FH, 2006 57 1. Verduidelik deur middel van ʼn 1. Explain, by means of a flow diagram, the vloeidiagram, die basiese beginsels van basic principles of membrane transport membraanvervoer (oor enige (across any tissue membrane). weefselmembraan). 2. Define the concept “diffusion” and explain 2. Definieer die begrip “diffusie” en the difference between simple and verduidelik die verskil tussen eenvoudige facilitated diffusion with an example of en gefasiliteerde diffusie, met ʼn voorbeeld each. van elk. 3. Define the concepts “osmosis” and 3. Definieer die begrippe “osmose” en “osmotic pressure gradient”. “osmotiese drukgradiënt”. 4. Explain “osmolarity” and give the average 4. Verduidelik “osmolariteit” en gee die osmolarity of body fluids. gemiddelde osmolariteit van 5. Discuss the mechanism of action and give liggaamsvloeistowwe. examples of primary and secondary active 5. Beskryf die meganisme van aksie en gee transporters. voorbeelde van primêre en sekondêr 6. Describe diffusion across a membrane aktiewe transporters. using Fick’s Law. 6. Beskryf diffusie oor ʼn membraan met die 7. Discuss tonicity. gebruik van Fick se Wet. 8. Discuss transcytosis. 7. Beskryf tonisiteit. 9. Classify membrane transporters. 8. Beskryf transsitose. 10. Describe the characteristics of carrier 9. Klassifiseer membraan transporters. mediated transport. 10. Beskryf die eienskappe van draer- gemedieerde oordrag. 58  Produksie van urien: Gebeure in die nierbuisies: Herabsorpsie, Sekresie, Uitskeiding Production of urine: Events in the renal tubules: Reabsorption, secretion, excretion  Herabsorpsie En Sekresie Reabsorption and Secretion By die niere behels: At the kidneys involve: diffusie diffusion osmose osmosis kanaal-medieerde diffusie channel-mediated diffusion draer-bemiddelde vervoer carrier-mediated transport 180L vloeistof word filtreer by die 180L of fluid filtered at glomerulus glomerulus maar net 1.5L/dag word but 1.5L is excreted per day as urine. afgeskei as urien. Waarom? Why? 1. Laat snel opruiming van vreemde 1. Allows for rapid clearance of foreign stowwe toe. substances. 2. Regulering is vereenvoudig om 2. Regulation is simplified to enable herabsorpsie van water of ione, reabsorption of water of ions when wanneer benodig, toe te laat. required. 60  Vervoer Prosesse In Herabsorpsie Transport Processes In Reabsorption Epiteel: herabsorpsie oor apikale en Epithelial: reabsorption across apical basolaterale oppervlakte and basolateral surfaces Parasellulêr: transport tussen Paracellular: transport between aangrensende selle adjacent cells Roete word bepaal deur deurlatenheid en elektrochemiese gradiënte vir die Route determined by permeability opgeloste stof and electrochemical gradients for the solute 61 5 Funksies van die PKB 5 Functions of the PCT 1. Herabsorpsie 1. Reabsorption of van organiese organic nutrients voedingstowwe 2. Active 2. Aktiewe reabsorption of herabsorpsie ions van ione 3. Reabsorption of water 3. Herabsorpsie van water 4. Passive reabsorption of 4. Passiewe ions herabsorpsie van ione 5. Secretion 5. Sekresie ook lipiedoplosbare materiale, Cl- 62  1. Herabsorpsie van organiese voedingstowwe Reabsorption of organic nutrients >99% glukose, aminosure, ander organiese > 99% glucose, amino acids, other organic voedingstowwe word herabsorbeer. nutrients reabsorbed. Herabsorpsie van H20 en opgeloste stowwe H20 and solute reabsorption thus indirectly benodig dus indirek, aktiewe vervoer. requires active transport. Aktiewe vervoer skep elektrochemiese of Active transport creates electrochemical or konsentrasie gradiënte om toe te laat dat concentration gradients to allow substances to stowwe in die ESV beweeg. move into ECF. Fig. 19.8a Principle governing the tubular reabsorption of solutes and water 63  2. Aktiewe herabsorpsie van ione Active reabsorption of ions bv. natrium, kalium, magnesium, e.g. sodium, potassium, fosfaat, sulfaat magnesium, phosphate, sulfate Natrium ioon herabsorpsie is Sodium ion absorption is belangrik in baie PKB vervoer important in many PCT transport prosesse processes Ione dring buisie selle binne by: Ions enter tubular cells by: Diffusie deur proteïen ‘lek’ diffusion through leak kanale. channels Natrium-gekoppelde sodium-linked cotransport of kotransport van organiese organic solutes opgeloste stowwe countertransport for Teenvervoer vir waterstofione hydrogen ions 64 Fig. 19.8b Sekondére Aktiewe Oordrag: Natrium Gekoppelde Simport Secondary Active Transport: Sodium Linked Symport 1 + 2 2 1 3 3 KEY ATP = Active transporter = SGLT secondary active transporter Tubule lumen Proximal tubule cell Interstitial fluid 65 = GLUT facilitated diffusion carrier Fig. 19.8c  Plasma proteïne Plasma proteins Word gewoonweg agtergelaat en word Normally left behind and don’t become nie deel van die filtraat part of filtrate. Kleiner proteïne en hormone tree die Smaller proteins and hormones enter apikale membraan van buisie selle binne the apical membrane of tubule cells by deur endositose endocytosis. Word verteer en vrygestel as aminosure Are digested and released as amino acids. 66  Sekresie Secretion Aktiewe sekresie vind plaas by die PKB Active secretion occurs at PCT but also maar ook by die DKB at DCT. Sluit in K+, H+, dwelmmiddels bv. Include, K+, H+, drugs e.g. penicillin, penisillien, metaboliese produkte, ensv. metabolic products, etc. Vervoer oor die buisie epiteel is dmv. Transport across the tubule epithelium aktiewe vervoer is via active transport. 67 Fig. 19.12  Parallel Segmente van Henle-lus Parallel Segments of Loop of Henle Baie na aan mekaar, word net by die very close together, separated only peritubulêre vloeistof geskei by peritubular fluid. Deurlaatbaarheid verskil baie very different permeability characteristics. Dik Stygende Lus Die Dun Dalende Lus Relatief ondeurlaatbaar tot water en deurlaatbaar tot water oplosstowwe relatief ondeurdringbaar tot Aktiewe vervoer meganismes oplosstowwe pomp Na+ en Cl- vanaf buisievloeistof na peritubulêre vloeistof van Thin Descending Limb medulla permeable to water relatively impermeable to solutes Thick Ascending Limb relatively impermeable to water and solutes Active transport mechanisms pump Na+ and Cl— from tubular fluid into peritubular fluid of medulla 68  Natrium en chloried pompe: Laat Sodium and Chloride Pumps: Elevate osmotiese konsentrasie in peritubulêre osmotic concentration in peritubular fluid: vloeistof toeneem: – around thin descending limb – rondom dun dalende been Cause osmotic flow of water: Veroorsaak osmotiese vloei van water: – out of thin descending limb – Uit dun dalende been – into peritubular fluid – Tot in die peritubulêre vloeistof – increasing solute concentration in thin – Toenemende soluut konsentrasie in descending limb dun dalende been Concentrated Solution arrives in thick Gekonsentreerde oplossing ascending limb arriveer in dik stygende been Accelerates Na+ and Cl- transport into Versnel Na+ en Cl- vervoer na peritubulêre peritubular fluid of medulla vloeistof van medulla 69 pomp van solute by stygende been solute pumping at ascending limb ↑[ solute] in dalende been ↑[ solute] in descending limb ↑ pomping van solute in stygende been ↑ solute pumping in ascending limb Na+, Cl- vanaf buisie vloeistof in stygende been Na+, Cl- removed from tubular fluid in verwyder ascending limb ↑ [osmotiese] peritubulêre vloeistof rondom dun ↑ [osmotic] peritubular fluid around thin descending dalende been limb 70 Ioon herabsorpsie Ion reabsorption Aktiewe herabsorpsie van ione in die dik stygende lus lei tot die vervaardiging van ʼn verdunde filtraat in die lumen. Hoë osmolariteit van medullêre interstisium veroorsaak die vermoë van die niere om urien te konsentreer of verdun. Hierdie funksionaliteit word gedeeltelik deur die Henle-lus en Vasa recta gevestig. Active reabsorption of ions in the thick ascending limb creates a dilute filtrate in the lumen. High osmolarity of the medullary interstitium results in ability of kidneys to concentrate or dilute urine. Functionality established in part by the Loop of Henle and Vasa recta. Figure 20-7d  Teenstroom Uitruiling Fig. 20.7c Countercurrent exchange The Loop of Henle Die Henle-lus Reabsorbs ± ½ of water, 2/3 Herabsorbeer ± ½ of sodium and water, en 2/3 van chloride ions natrium en chloried remaining in ione wat in die buisie tubular fluid by vloeistof oorbly by countercurrent teenstroom uitruiling exchange Meer Na+ en Cl- word More Na+ and Cl- are in die medulla pumped into gepomp by die begin medulla: at start of van die stygende lus thick ascending limb as na aan die korteks than near cortex Streek verskille in Regional difference ioon vervoer tempo in ion transport rate veroorsaak causes concentration konsentrasie gradiënt gradient within binne die medulla medulla 72  73 Fig. 19.13  Osmolarity Changes through the Nephron Figure 20-4, steps 1–4 Konsentrasie gradiënt a.g.v. 2/3 (750 mosM) van Na+ Concentration gradient due to 2/3 (750 mosM) of en Cl- : word uit stygende been gepomp Na+ and Cl- : are pumped from ascending limb 450 mosM is van ureum 450 mosM is from urea Dalende Been van Henle-lus, versamelbuisies is Descending Leg of Henle loop, collecting tubules onlangs gevind om deurlaatbaar tot ureum te wees have recently been found to be permeable to urea (Na+-gekoppelde sekondêre aktiewe vervoer, (Na+ coupled secondary active transport, facilitated gefasiliteerde diffusie) diffusion)  Changes in Tubular Fluids Distal tubule Selective Only 15–20% of N K + reabsorption or initial filtrate volume H a + secretion, primarily + reaches DCT ATP along DCT, makes final adjustments in Concentrations of solute composition electrolytes and and volume of organic wastes in tubular fluid arriving tubular fluid no longer resemble Rate of K+ and H+ blood plasma secretion rises or falls: according to concentrations in peritubular fluid: higher concentration and higher secretion rate 75  Distale Buisie en H + Word genereer deur dissosiasie van koolsuur Distal tubule and H+ deur koolsuuraanhidrase Generated by dissociation of carbonic acid, by enzyme carbonic anhydrase Gewoonlik, in die proksimale buisie word sekresie verbonde met herabsorpsie van Normally, in the proximal tubule, Secretion natrium associated with sodium reabsorption Word sekreteer deur natrium-gekoppelde Secreted by sodium-linked teenvervoer: in ruil vir Na+ in buisie vloeistof countertransport: in exchange for Na+ in tubular fluid Hier word daar meer gebruik gemaak van ander tipe transporters Here, other transporters play a more predominant role Versuur buisie vloeistof (lei tot toename in bloed pH Secretion acidifies tubular fluid – Elevates blood pH Sekresie neem toe wanneer bloed pH afneem – Accelerates when blood pH falls Bikarbonaat ioone diffuundeer in bloedstroom: Bicarbonate ions diffuse into bloodstream: buffer veranderinge in plasma pH buffer changes in plasma pH *(As blood pH meer alkalies as normaal is, sal (*When blood pH is more alkaline than 76 waterstof ione herabsorbeer word) normal, hydrogen is reabsorbed) Reabsorption and Secretion along the Collecting System Regulation of Water and Solute Loss 1. Aldosterone: controls sodium ion pumps actions are opposed by natriuretic peptides 2. Antidiuretic Hormone (ADH): controls permeability to water is suppressed by natriuretic peptides Urea, Na+, bicarbonate Collecting ducts s H+ / bicarbonate (to help control body pH and is dependent on pH levels of the blood) 77 Reabsorption in Peritubular Capillaries Fig. 19.11 78 Nierfunksie: Maniere Om Nierfunksie In Die Laboratorium Te Bereken Kidney function: Ways to determine kidney function in the laboratory  Ekskresie verklaar nie hoe stowwe deur die nier behandel word nie. Ekskresie afhangend van 1) Filtrasie spoed, 2) Herabsorpsie, 3) Sekresie Fig. 19.3 80 ALGEMENE BEGINSEL GENERAL PRINCIPLE Fig. 19.4 120 ml/min IN 119 ml/min OUT 1 ml/min 81 ALGEMENE BEGINSEL GENERAL PRINCIPLE 120 ml/min IN 119 ml/min OUT ALMOST ENTIRELY A REABSORPTION PROCESS 82 ALGEMENE BEGINSEL GENERAL PRINCIPLE 120 ml/min IN 119 ml/min OUT K+, H+, HCO3-, NH3 ARE EXCEPTIONS 83 DRUGS AND DRUG METABOLITES FILTERED NOT REABSORBED SECRETED 84 DRUGS AND DRUG METABOLITES REMEMBER THAT THE DRUG CONCENTRATION FILTERED HERE IS THE SAME AS IN PLASMA EVERYWHERE IN THE BODY NOT REABSORBED SECRETED 85 DRUGS AND DRUG METABOLITES IF A DRUG IS AND THEN NOT FILTERED SECRETED OR REABSORBED THEN 120 ml OF PLASMA WILL BE “CLEARED” OF THE DRUG PER MINUTE 86 87 DIE PLASMA OPRUIMING THE PLASMA CLEARANCE RATE VAN ‘N DWELMMIDDEL OF ANDER STOF OF A DRUG (OR OTHER SUBSTANCE) Is die volume plasma per minute wat Is the volume of plasma that seems to heeltemal opgeruim word die niere be cleared entirely of that substance (by the kidneys)/minute As ʼn dwelmmiddel filtreer word en nie gesekreteer of herabsorbeer word van If a drug is filtered, and then neither die buisie vloeistof nie, is die secreted into, nor reabsorbed from, the opruimings spoed = Glomerulêre tubular fluid, then the clearance rate is Filtrasie Spoed equal to the Glomerular Filtration rate 88 INULIEN Inulin Is a fruktose-polimeer wat gefilter en, Is a poly-fructose which is filtered and dan nie in die buisie vloeistof sekreteer then neither secreted into, nor of uit die buisie vloeistof herabsorbeer reabsorbed out of the tubular fluid. word nie Dit word dus gebruik om glomerulêre It is therefore used to measure the filtrasie spoed (GFS) te bereken glomerular filtration rate (GFR) Kreatinien, wat dieselfde reageer, kom Creatinine, a naturally occurring vanaf kreatien in die spiere breakdown product of en kan gebruik word om die GFS van Creatine in the body behaves the same pasiënte te bereken way, and is used in the wards to measure the GFR of patients. 89 Om opruiming te bereken / To measure the clearance rate Hoef jy net die volgende te weet / All you need to know is: 1. Hoeveel van die stof in die urien per minuut voorkom/ how much of the drug appears in the urine per minute 2. Wat die stof se plasma konsentrasie/ what its concentration is in the plasma A patient excretes 20 mg penicillin in her urine/min The [penicillin]plasma = 100 mg/l (= 10 mg/100 ml) Clearance rate = excretion rate/[x]plasma Her penicillin plasma clearance rate Is therefore: 20mg/min/ 10mg/100ml = 20mg/min* 10ml/mg= 20mg/min* 10ml/mg = 200 ml/min 200 ml/min > GFR (120 ml/min), THEREFORE PENICILLIN IS BOTH FILTERED AND SECRETED INTO THE TUBULAR FLUID 90 PENICILLIN FILTERED NOT REABSORBED SECRETED 91  Inulin Inulin is freely filtered but neither reabsorbed nor secreted. [inulin]plasma=100mg/dl Excretion rate=125mg/min Clearance= 125mg/min/ 100mg/dl =125ml/min plasma 92  Kreatinien Creatinine Kliniese gebruik van inulien onprakties Clinical use of inulin impractical- want dit benodig konstante iv requires continuous IV administration. toediening Creatinine, a breakdown product of Kreatinien, produk van spier muscle metabolism is sometimes used metabolisme word soms gebruik om GFS to measure GFR. te meet [Kreatinien]plasma is relatief konstant [creatinine]plasma is relatively constant. Nadeel: klein hoeveelhede word in die Drawback: small amounts secreted urien gesekreteer into the urine. Geringe hoeveelheid, dus kan GFS gemeet word Neglible, therefore GFR can be measured. Daarom kan die hoeveelheid stof wat Therefore, amount of substance filtreer word bereken word filtered can be calculated. 93  Filtered load =[x]plasma x GFR Calculated by comparing filtration rate with excretion rate Hantering van solute deur die niere: Bereken deur die filtrasie snelheid met die ekskresie snelheid te vergelyk 94  Para-aminohippuursuur (PAH) Para-aminohypuric acid (PAH) Die opruiming van 'n stof heeltemal van die The clearance rate of a substance completely plasma verwyder, in teorie, is gelyk aan die cleared from the plasma, in theory, is equal to totale renal plasma vloei (hoeveelheid wat na the total renal plasma flow(amount to the niere gaan=hoeveelheid deur niere eksreet). kidneys =amount excreted by kidneys). Diagnostiese agent, I.V. toegedien, wat gebruik Diagnostic agent, administered I.V. and used to word om die spoed van bloedvloei deur die niere determine rate of blood flow through kidneys. te meet. No known substance is completely cleared but Geen stof bekend wat heeltemal opgeruim word PAH is 90% cleared (extraction ratio, EPAH=(PPAH- nie, maar PAH word 90% opgeruim (ekstraksie VPAH)/PPAH). verhouding, EPAH=(PPAH-VPAH)/PPAH). Renal blood flow can be estimated if [PAH] in Nier bloedvloei kan geskat word as [PAH] in arterial plasma and urine is known. arteriële plasma en urien bekend is. One can correct for PAH left in blood leaving the Mens kan aanpassings maak vir die PAH wat in kidneys. die bloed oorbly wat die niere verlaat. PPAH= PAH concentration in plasma PPAH= PAH konsentrasie in plasma VPAH= PAH concentration in venous blood leaving kidneys VPAH= PAH konsentrasie in veneuse bloed wat niere verlaat 95  PAH Clearance= PAHUXVu Urine production =1ml/min PPAH [PAH]u=5.9mg/ml Where PPAH=0.01mg/ml PAHU =[PAH] in urine VPAH=0.001mg/ml, so EPAH=0.01- Vu =volume of urine 0.001/0.01=0.9 PPAH=[PAH] in plasma Ht=45% (0.45) Total Renal plasma flow= Therefore, Clearance=[PAH]UXVU PAH clearance/EPAH [PAH]p *EPAH =extraction ratio for PAH = 5.9mg/mlx1ml/min 0.01mg/ml = 590ml/min (Effective renal plasma flow) Total renal plasma flow=590ml/min/0.9 =656ml/min RBF=RPF/(1-Ht)= 656/(1-0.45)=1193ml/min # # (If using the effective renal plasma flow in this calculation instead, the renal blood flow is underestimated by about 10%) 96  Effective renal plasma flow The blood plasma going to parts of the kidney associated with the nephron (90% of PAH) But 10% of blood goes to parts of kidney other than the nephron Thus blood leaving the kidney via the renal vein has some PAH in it 97  More simply… PAH in the plasma that flows to the kidneys is (almost) completely removed from it by the time the blood plasma leaves the kidneys. If 100mg/100ml =[PAH]plasma 20% of blood entering the glomerulus is filtered (FILTRATION FRACTION) Thus 20mg PAH and 20ml of blood plasma is filtered per min 80% leaves via efferent arteriole Thus 80mg PAH per 80ml of blood plasma there If this is all secreted, then 100mg was excreted and 100ml of plasma cleared of PAH, so 100ml/min of plasma entering the kidney was cleared and is the renal plasma flow 98 Transport maksimum (Tm) en Nier drempelwaarde Transport maximum (Tm) and Renal Threshold Tm= Vervoer snelheid by punt van saturasie Wanneer [voedingstowwe] > Tm, word die herabsorbering vermoë van die nefron oorskry en dit word in die urien uitgeskei Dit bepaal die nier drempelwaarde 99 Fig. 19.09  Nier drempelwaarde Renal Threshold Vir glukose: ±180 mg/dL For glucose ±180 mg/dL As [glukose] plasma >180 mg/dL When [glucose] plasma >180 mg/dL Tm van buisie selle word oorskry Tm of tubular cells is exceeded Glukose verskyn in die urien: Glucose appears in urine: Glukosurie – Glycosuria/glucosuria Vir aminosure: 65 mg/dL – For amino acids: 65 mg/dL Aminosure kom dikwels in die – Amino acids commonly appear in urien voor na ʼn proteïen-ryk urine after a protein-rich meal maaltyd. – Aminoaciduria Aminosuururie 100 Glucose Handling By the Nephron Fig. 19.10 101  Filtered Load= GFR X [Inulin]Plasma GFR= Filtered load/ [Inulin]Plasma BUT all inulin filtered is excreted, therefore filtered load=excretion rate So: GFR=Excretion Rate/ [Inulin]Plasma = = CLEARANCE Fig 19.13 102 Fig 19.13 103  104 Fig 19.13  105 Fig 19.13 Hantering van normale elektroliet- en waterbalans Regulation of normal electrolyte and water balance Hantering van Water in die Nier Water Management in the Kidney  Total Body Water 60%/bw 75%/bw 46-52%/bw 50%/bw 108 Vloeistof Kompartemente Fluid Compartments 109 Fig. 5.1  Vloeistof Kompartemente Fluid Compartments Fig. 5.1 66.7 % 33.3% Exchange among subdivisions of ECF occurs primarily across endothelial lining of capillaries From interstitial spaces to plasma 110 Through lymphatic vessels that drain into the venous system Water Balans in die Liggaam Water Balance in the Body 111 Fig. 20.2 Hoof onderafdelings van ESV Major Subdivisions of ECF Interstisiële vloeistof van perifere – Interstitial fluid of peripheral weefsels tissues Plasma van sirkulerende bloed – Plasma of circulating blood Kleiner onderafdelings van ESV Minor Subdivisions of ECF Limf, perilimf, endolimf – Lymph, perilymph, and Serebrospinale vloeistof (SSV) endolymph Sinoviale vloeistof – Cerebrospinal fluid (CSF) Sereuse vloeistowwe (pleuraal, perikardiaal, en peritoneaal) – Synovial fluid Waterige oogvog – Serous fluids (pleural, pericardial, and peritoneal) – Aqueous humor 112  ESV: Inhoud Van Opgeloste Stowwe ECF: Solute Content Tipe en hoeveelhede wissel Types and amounts vary regionally streeksgewys Electrolytes Elektroliete Proteins Proteïne Voedingstowwe Nutrients Afval stowwe Waste products 113 Die ESV & ISV The ECF and the ICF Word vloeistof kompartemente Are called fluid compartments genoem omdat hulle as afsonderlike because they behave as distinct entiteite reageer entities Word geskei deur plasma membrane Are separated by plasma membranes en aktiewe transport and active transport Katione en Anione Cations and Anions In ESV In ECF natrium, chloried, bikarbonaat sodium, chloride, and bicarbonate In ISV kalium, magnesium, en fosfaat-ione In ICF negatief belaaide proteïne potassium, magnesium, and phosphate ions negatively charged proteins 114 115 Membraan Funksies Membrane Functions Plasma membrane is selektief – Plasma membranes are selectively deurlaatbaar permeable Ione betree of verlaat via spesifieke – Ions enter or leave via specific membraan kanale membrane channels Draer meganismes beweeg spesifieke – Carrier mechanisms move specific ions ione in en uit die sel in or out of cell Osmotiese Konsentrasie Van Die ISV En Osmotic Concentration Of ICF And ECF ESV Is identies Is identical Osmose elimineer klein verskille in Osmosis eliminates minor differences in konsentrasie concentration Want plasma membrane is vir water Because plasma membranes are deurdringbaar permeable to water 116  Alle homeostatiese meganismes wat  All homeostatic mechanisms that liggaamsvloeistof inhoud monitor en monitor and adjust body fluid aanpas reageer tot veranderinge in die composition respond to changes in the ECV, nie die ICV nie ECF, not in the ICF  Geen reseptore monitor direk die  No receptors directly monitor fluid or vloeistof en elektroliet balans electrolyte balance  Selle kan nie water deur die gebruik  Cells cannot move water molecules by van aktiewe transport beweeg nie active transport  Die liggaam se water of elektroliet  The body’s water or electrolyte inhoud sal toeneem as content will rise if dietary gains exceed voedingsaanwins die environmental losses, and will decline omgewingsverlies oorskry, en sal if losses exceed gains afneem as verlies die aanwins oorskry 117  Ander Roetes Van Water Verlies Other Routes Of Water Loss Diarree Diarrhea Vloeistof volume ↓, dus ESV fluid volume ↓, thus ECF compartment, kompartement, kan bloeddruk ↓. can cause ↓ blood pressure. Indien nie aanvul, mag weefsels If not replenished, tissues may be onvoldoende perfuseer word. inadequately perfused. Oormatige sweting Excessive sweating As sweet hipotonies is ↑ESV osmolariteit. If sweat is hypotonic ECF osmolarity ↑. Water verlaat selle, affekteer sel Water moves out of cells, affects cell funksie. function. 118 Diurese Diuresis Verlies van ekses H20 in urien. Loss of excess H20 in urine. Diuretikums Diuretics Drugs that promote H20 loss in urine.(e.g. Dwelmmiddels wat H20 verlies in urien ethanol-inhibit. Vasopressin release); aanmoedig. (bv. etanol-inhibeer caffeine-Na+ reabsorption*; glucose- vasopressien vrystelling); (kafeïne- Na+ osmotic diuretic herabs.) Glukose-osmotiese diuretikum Antidiuretics Prevent excess loss of H20 in urine. (Eg. Antidiuretiese middels Desmopressin) Verhoed ekses water verlies in urien. (bv. Desmopressien) Diabetes Insipidus: Inadequate release of ADH from Diabetes Insipidus: posterior pituitary / Kidneys don’t Ongenoegsame vrystelling van ADH van respond to ADH neurohipofise / Niere regeer nie tot ADH Release of large amounts of dilute urine nie Stel groot hoeveelhede verdunde urien * loop diuretics vry 119 Integrated Responses to Changes in Blood Volume and Blood Pressure 120  Primêre Regulerende Hormone Primary Regulatory Hormones – Wat vloeistof en elektroliet – Affecting fluid and electrolyte balans handhaaf: balance: 1. Vasopressien (Antidiuretiese 1. Vasopressin (Antidiuretic hormoon) hormone) 2. Aldosteroon 2. Aldosterone 3. Natriuretiese peptiede 3. Natriuretic peptides 121  122 Fig. 20.6  123 Fig. 20.5 1) ↓ Na+ levels (10-20mEq/L) in blood reaching - adrenal cortex ↑ release. 2) ↑ECF osmolarity (e.g. in dehydration) directly inhibits secretion. 124 Fig. 20.9  Apical membrane has leak channels for: / Apikale membraan het lek kanale vir: Na+ (ENaC), K+ (ROMK). Early response and slow phases. / Vroeë respons en stadige fases. Reabsorbtion of water following sodium is dependant on presence of ADH. / Herabsorpsie van water wat natrium volg, is afhangend op die aanwesigheid van ADH. 125 Fig. 20.9  126 Fig. 20.11  Hoekom is elektroliet balans belangrik? Why is electrolyte balance important? Elektroliet konsentrasies affekteer water Electrolyte concentrations affect water balans balance Individuele elektroliet konsentrasies Individual electrolyte concentrations affekteer sel funksie affect cell function. Storinge in Natrium en Kalium-ione is Disturbances in Sodium and Potassium veral van belang ions particularly important. Hoekom? Why? [Na+] in ECF is high, [K+] in ICF is high [Na+] in ESV is hoog, [K+] in ISV is hoog Disturbances in these electrolytes can Storinge in hierdie elektroliete kan sel alter cell functioning. funksionering verander Sodium disturbances more common but Natrium steurings meer algemeen, maar potassium disturbances more dangerous (small changes in potassium have large kalium steurings is meer gevaarlik (klein effects on cells) veranderinge in kalium het groter effekte op selle) 127  Natrium Balans Sodium Balance Om balans te handhaaf, moet To maintain balance, Natrium-ioon absorpsie oor die Sodium ion uptake across digestive spysverteringsepiteel= natrium-ioon ekskresie in epithelium = Sodium ion excretion in urien en sweet urine and sweat + Na+ wins en verlies (-48-144mEq (1.1-3.3g)/dag Na gain and loss (48–144 mEq (1.1–3.3 Normale [Na+]plasma=135-145mOsm/L g)/ day) Normal [Na+]plasma=135-145mOsm/L Hipernatremie: [Na+] ESV >145 mEq/L Liggaamswater inhoud ↓ (dehidrasie) Hypernatremia: [Na+] ECF >145 mEq/L Body water content ↓ (dehydration) Hiponatremie: ESV Na+ konsentrasie loss ↑ Total ECF verlies inhoud content verlies > wins ↓ totale ESV Loss > gain ↓Total ECF inhoud content 128  Natrium Balans en ESF Volume Sodium Balance and ECF Volume Klein veranderinge in ESV Na+ inhoud: Small changes in ECF Na+ content: Verander nie konsentrasie nie Don’t change concentration Ooreenstemmende water aanwins of Corresponding water gain or loss keeps verlies hou die konsentrasie concentration constant onveranderlik – Na+ regulatory mechanism changes – Na+ regulatiewe meganisme verander ECF volume ESV volume Keeps concentration stable Hou konsentrasie stabiel – Wanneer Na+ verlies aanwins oortref – When Na+ losses exceed gains ↓ESV (↑ water verlies) ↓ ECF volume (↑water loss) Handhaaf osmotiese konsentrasie Maintaining osmotic concentration 129  Groot veranderinge in ESV volume Large Changes in ECF Volume Word gekorrigeer deur homeostatiese –Are corrected by homeostatic meganismes wat bloeddruk en bloed mechanisms that regulate blood volume volume reguleer and pressure As ESF volume ↑, gaan bloed volume –If ECF volume ↑, blood volume ↑ ↑ As ESF volume ↓, kom bloed volume ↓ –If ECF volume ↓, blood volume goes ↓ ESV volume word indirek gemonitor –ECF volume monitored indirectly by deur bloeddruk te monitor monitoring blood pressure Baroreseptore by die aortaboog en –Baroreceptors at carotid sinus, aortic karotissinus en regter- atrium sinus, and right atrium 130 Elektroliet Balans Electrolyte Balance Homeostasis N +] ECF=135-145mosm/L [Na ↑ [Na+]ECF Generalised regulation by osmoreceptors. Once blood volume, pressure is affected, pathways are much more ↑ Osmoreceptor activity complex. Reference: Silverthorne D (2010). Human Physiology-An integrated approach. 5th ed. Pearson Benjamin Cummings; 2. Martini FH (2006). Fundamentals of Anatomy & Physiology. 7th ed. Pearson Benjamin Cummings ADH ↑ thirst Water conserved ↑ Water intake ↓[Na+]ECF ↑ ECF volume 131 Elektroliet Balans Electrolyte Balance Homeostasis ↓ [Na+]ECF [Na+] ECF=135-145mosm/L ↓ Osmoreceptor activity ↓ ADH ↓ thirst ↑Water loss ↓ Water intake ↑ [Na+]ECF ↓ ECF volume 132 Homeostatic Responses to Salt Ingestion 133 Fig. 20.8  Juxtaglomerular Complex Jukstaglomerulêre Apparaat (JGA) –An endocrine structure that secretes Hormone erythropoietin (rbc production) Juxtaglomerular Apparatus (JGA) Enzyme renin (salt & water balance) JGA gevorm deur: Makula densa Fig. 19.7 Jukstaglomerulêre selle 134 Renin-Angiotensin-Aldosterone System‘RAA’ System/ Complex pathway that regulates blood pressure RAAS Triggers of Renin–Angiotensin System 1. ↓ in blood pressure at glomerulus: – due to ↓ in blood volume - ↓ in systemic pressures – blockage in renal artery or tributaries 2. Stimulation of juxtaglomerular cells by sympathetic innervation 3. ↓ in osmotic concentration of tubular fluid at macula densa 135 Fig. 20.10  Angiotensien II Angiotensin II Stimuleer sekresie van aldosteroon by Stimulates secretion of aldosterone by adrenal bynierkorteks cortex Vernou (effektief) die efferente arteriole van Constricts (effectively) efferent arterioles of nefron: nephron: help om glomerulêre druk en filtrasie snelhede te Helping to elevate glomerular pressures and handhaaf (deur NO, Prostaglandien, bradikinien filtration rates (Secretion of nitric oxide, sekresie en vaatverwyderende effek op afferente prostaglandin, bradykinin and vasodilatory affect arteriool) on afferent arteriole) Stimuleer herabsorpsie van natrium ione en water by die PKB Stimulates reabsorption of sodium ions and water Stimuleer dors at PCT Stimulates thirst Veroorsaak bevryding van antidiuretiese hormoon Triggers release of antidiuretic hormone (ADH): (ADH): stimuleer herabsorpsie van water in distale stimulates reabsorption of water in distal portion gedeelte van DKB en kollekteer buisie sisteem ↑ of DCT and collecting system simpatiese motoriese tonus: ↑ sympathetic activation: mobilizing the venous - mobiliseer die veneuse reserwe reserve - ↑ hartomset ↑ cardiac output - stimuleer perifere vasokonstriksie Veroorsaak kortstondige, kragtige stimulating peripheral vasoconstriction vasokonstriksie van arteriole en prekapillêre Causes brief, powerful vasoconstriction of sfinkters arterioles and precapillary sphincters ↑ arteriële druk deur die liggaam ↑ arterial pressures throughout body 136 Vloeistof en Elektroliete Fluid and Electrolytes  Kalium Potassium Normaalweg: 3.5 to 5 mequiv/L Normal range: 3.5 to 5 mequiv/L [K+]ESV representeer ʼn balans tussen [K+]ECF represents a balance between gain of aanwins van K+ by spysverteringstelsel en K+ at GIT and loss at kidneys verlies by die niere [K+] > in ICF than ECF [K+] > in ISV as ESV Energy expended to recover potassium ions Krag word bestee om kalium ione te herwin diffused from cytoplasm into ECF wat uit die sitoplasma na die ESV diffundeer Small changes in K+ has large effects on het excitable tissues Klein veranderinge in K+ het groot effekte regulated by activities of ion pumps op prikkelbare weefsel Along distal portions of nephron and Is gereguleer deur aktiwiteite van ioon collecting system pompe Langs distale gedeeltes van nefron en Na+ from tubular fluid is exchanged for K+ kollekteer sisteem in peritubular fluid Na+ van buisie vloeistof word verruil vir K+ in peritubulêre vloeistof Are limited to amount gained by Is gelimiteer tot hoeveelheid verkry deur absorption across digestive epithelium (± absorpsie oor die spysverterings epiteel (± 50–150 mEq/ 1.9–5.8 g/day) 138 50–150 mEq / 1.9–5.8 g/dag) Hipokalemie: lae K+ in plasma & ESV Hypokalemia: low K+ in plasma & ECF K+ verlaat selle en hiperpolariseer selle K+ leaves cells, hyperpolarising it Spier swakheid, verlamming Muscular weakness, paralysis Belang-respiratoriese verlamming, hart Concern-respiratory paralysis, cardiac versaking failure Hiperkalemie: Hoë K+ in plasma & ESV Hyperkalemia: High K+ in plasma & ECF K+ bly aan in selle: Selle depolariseer, K+ remains in cells: Cells depolarise, aanvanklik meer prikkelbaar initially more excitable Repolariseer nie volledig en word minder prikkelbaar Don’t repolarise fully and become less excitable Kardiale aritmieë Cardiac arrhythmias 139  + Factors Affecting Tubular Secretion Of K 1. [K+]ECF changes: Higher [K+]ECF increases secretion rate 2. pH changes: peritubular fluid pH lowered by low ECF pH Na+ exchanged for H+ instead of K+ in tubular fluid Rate of potassium secretion declines 3. Aldosterone levels: Affect K+ loss in urine High [K+ ]plasma stimulate aldosterone Na+ from filtrate reabsorbed by ion pumps in exchange for K+ from peritubular fluid 140 Faktore Wat Buisie Sekresie Van K+ Affekteer 1. [K+]ESF Verander: Hoër [K+]ESF ↑ sekresie snelheid 2. pH verander: pH van peritubulêre vloeistof word verlaag deur lae ESV pH Na+ verruil vir H+ in plaas van K+ in buisie vloeistof Snelheid van kalium sekresie verlaag 3. Aldosteroon vlakke: Affekteer K+ verlies in urien Hoë [K+ ]plasma stimuleer aldosteroon Na+ van filtraat herabsorbeer deur ioon-pompe in ruil vir K+ van peritubulêre vloeistof 141  Vloeistof en Elektroliete Fluid and Electrolytes Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings; Acknowledgements: 1. Silverthorne D (2010). Human Physiology-An integrated approach. 5th ed. Pearson Benjamin Cummings; 2. Martini FH (2006). Fundamentals of Anatomy & Physiology. 7th ed. Pearson Benjamin Cummings Gedrags Meganismes In Sout & Water Homeostase Behavioral Mechanisms In Salt & Water Homeostasis Neurale, endokrien, neuroendokrien  Neural, endocrine, neuroendocrine reflekse betrokke in sout & water reflexes involved in salt & water regulasie. regulation. As osmolariteit ↑, volume ↓, moet  Under ↑osmolarity, ↓ volume, fluids vloeistowwe verwang word. need to be replaced. Om balans te restoureer:  To restore balance: Vloeistowwe moet ingeneem word om ◦ Fluids must be ingested to restore volume te restoureer volume Sout moet ingeneem word om ◦ Salts must be ingested to ↑ [Na+]body [Na+]liggaam te ↑ as dit benodig word only if it is needed 143 Gedrags Meganismes In Sout & Water Homeostase Behavioral Mechanisms In Salt & Water Homeostasis  As Osmolariteit > 280mOsm  When Osmolarity > 280mOsm + + hipotalamiese osmoreseptore hypothalamic osmoreceptors + + dors thirst 144 Gedrags Meganismes In Sout & Water Homeostase Behavioral Mechanisms In Salt & Water Homeostasis Koue water Cold water Oropharynx receptors Orale farinks reseptore ↓thirst, ↓ADH ↓ dors, ↓ADH 145 Sout Lus Salt Appetite Sout aptyt sentrum na aan dors  Salt appetite centre close to thirst sentrum in hipotalamus geleë centre in hypothalamus Aldosteroon & angiotensien betrokke  Aldosterone & angiotensin involved Sout-soekende gedrag  Salt-seeking behaviors * Nog 'n meganisme van belang: Gedrag wat * Another mechanism of importance: vogverlies voorkom deur die hitte van die dag Avoidance behaviour in which we avoid te vermy. fluid loss by avoiding the heat of the day. 146 Geïntegreerde Kontrole Van Volume & Osmolariteit Integrated Control Of Volume & Osmolarity Osmolariteit & volume kan onafhanklik  Osmolarity & volume can change verander independently Om homeostase te handhaaf, moet  To maintain homeostasis, fluid loss vloeistof verlies gelyk aan vloeistof must equal fluid gain aanwins wees  Vloeistof kanverloor word deur:1)  Fluid can be lost by:1) diarrhea, 2) diarree, 2) buitensporige sweting, 3) excessive sweating, 3) vomiting, 4) braking, 4) bloedstorting, 5) dehidrasie hemorrhage, 5) dehydration  Vloeistof kanverkry word deur: te veel  Fluid can be gained by: drinking too water te drink-hier gebeur die much water-here the imbalance wanbalans wanneer die osmolariteit < occurs when osmolarity < acceptable aanvaarbare perke range 147 Stoornisse In Volume & Osmolariteit Disturbances In Volume & Osmolarity Fig. 20.12 148  Homeostatiese Reaksies Tot Dehidrasie Homeostatic Responses To Dehydration Kardiovaskulêre respons  Cardiovascular responses Renien-Angiotensien Aldosteroon  Renin-Angiotensin Aldosterone System Sisteem  Hypothalamic responses Hipotalamiese reaksie  Thirst Dors Dehidrasie Dehydration  ↓ blood pressure  ↓ bloeddruk  ↓ blood volume  ↓ bloed volume  ↑ plasma osmolarity  ↑ plasma osmolariteit 149 Homeostatic Compensation for Dehydration Fig. 20.13 150 Rol Van Die Nier In Suur-basis Balans The Role of the Kidney in Acid-Base Balance SUUR ACID Stel H+ vry in oplossing Liberate H+ in solution Sterk of swak (afhangend van die mate Strong or weak (degree to which H+ wat H+ ione geskenk word) ions are donated) H+ ione kan OH- bind [H+] >[OH-] H+ ions can bind OH- pH[OH-] pH7 [H+] < [OH-] pH>7 152  pH ‘Power of hydrogen’ Power of hydrogen Aanduidend van [H+] Indicative of [H+] 0-14 0-14 pH 7 –neutraal Normale liggaam pH = 7.38-7.4 (7.4) pH 7 –neutral Sure en basisse kan die pH van Normal body pH = 7.38-7.4 (7.4) liggaamsvloeistowwe verander Acids and bases can change the pH of pH = 6.1 + log [bicarbonate]/0.03 body fluids PCO2 (Henderson Hasselbach) pH = 6.1 + log [bicarbonate]/0.03 PCO2 (Henderson Hasselbach) Hoekom word pH noukeurig gereguleer? Why is pH tightly regulated? Any disruption can affect cell Enige ontwrigting kan sel membrane, membranes, proteins, enzymes. proteïne, ensieme affekteer. 3-dimensionele struktuur/vorm word 3-dimensional structure/shape is affekteer affected Regulasie hang af van sure basisse, Regulation depends on acids, bases, 153 soute salts  Asidose en Alkalose Acidosis and Alkalosis Alle sisteme is kosbaar, veral die senuwee All systems vulnerable, esp. nervous, stelsel en kardiovaskulêre stelsel cardiovascular systems Asidose en alkalose is gevaarlik Acidosis and alkalosis are dangerous Metaboliese prosesse genereer sure, dus is Metabolic processes generate acids, so asidose meer algemeen acidosis is more common Voedsel bronne is meestal sure Dietary sources are mainly acids Asidose Acidosis Fisiologiese toestand wat veroorsaak word Physiological state resulting from abnormally deur ʼn abnormale lae plasma pH (Oormatige low plasma pH (excess addition of H+ into body fluids) toevoeging van H + in liggaamsvloeistowwe) Asidemie: plasma pH < 7.35 Acidaemia: plasma pH < 7.35 Alkalose Alkalosis Fisiologiese toestand wat veroorsaak word Physiological state resulting from abnormally deur ʼn abnormale hoë plasma pH (Oormatige high plasma pH (excess removal of H+ from body verwydering van H + van liggaamsvloeistowwe) fluids) Akalaemia: plasma pH > 7.45 Akalaemia: plasma pH > 7.45 154  Regulasie van pH-meganismes Regulation of pH-mechanisms 1. Buffers 1. Buffers 2. Ventilasie 2. Ventilation 3. Regulering van H+ en HCO3- by die 3. Regulation of H+ and HCO3- at the niere kidneys HCO3- Is 600000 X more concentrated [H+]ECF= 0.00004mEq/L ; [HCO3-]=24mEq/L 155  Koolstofdioksied Carbon Dioxide – In oplossing in perifere weefsels – In solution in peripheral tissues Reageer met water om koolsuur te Interacts with water to form carbonic vorm acid – Koolsuur dissosieer en stel H+ en HCO3- – Carbonic acid dissociates to release vry Hydrogen ions Bicarbonate ions Koolsuuranhidrase (KA) CO2+H20 ⇔ H2CO3 ⇔ HCO3- + H+ Carbonic Anhydrase (CA) CO2+H20 ⇔ HCO3- + H+ (KA/CA) (KA) word in Found in - Sitoplasma van eritrosiete - Cytoplasm of red blood cells - Lewer en nier selle - Liver and kidney cells - Pariëtale selle van maag - Parietal cells of stomach - Ander selle, gevind - Other cells 156  CO2 & pH (Inverse relationship) 40-45mm Hg CO2, pH 7.38-7.42 40-45mm Hg CO2, pH 7.38-7.42 Meeste van die CO2 in oplossing word Most CO2 in solution converts to carbonic omgekeer na koolsuur acid - Die meeste koolsuur dissosieer - Most carbonic acid dissociates PCO is die mees belangrikste faktor wat pH 2 in liggaamsweefsels affekteer PCO is the most important factor affecting 2 - PCO en pH is in omgekeerde eweredigheid pH in body tissues 2 - As CO2 vlakke ↑ - PCO and pH are inversely related 2 Word H+ en HCO3- vrygestel When CO2 levels ↑ pH ↓ H+ and bicarbonate ions are released By die alveoli pH ↓ Diffundeer CO2 in die atmosfeer At alveoli ↓ H+ en HCO3- in alveolêre kapillêre neem af, CO2 diffuses into atmosphere Bloed pH ↑ H+ and bicarbonate ions in alveolar capillaries drop, Blood pH ↑ 157 Mechanisms of pH Control: geared to balance H+ gained and lost 158 Fig. 20.14  Bronne van Waterstof Sources of Hydrogen Dieet (vetsure, aminosure, suur vrugte) Diet (fatty acids, amino acids, acidic fruits) Metabolisme (CO2+H20, ketosure, melksuur) Metabolism (CO2+H20, ketoacids, lactic acid) Neutralisasie van H+ is belangrik om skade aan weefsels te vermy Neutralization of H+ is important to avoid Buffers in liggaamsvloeistowwe bied tydelike damage to tissues neutralisasie van metaboliese sure Buffers in body fluids provide temporary neutralization of metabolic acids. 159  Drie Hoof Buffer Stelsels Three Major Buffer Systems Proteïen buffer stelsel Protein buffer systems Help om pH in die ESV en ISV te reguleer Help regulate pH in ECF and ICF Reageer op ʼn groot skaal met ander buffer Interact extensively with other buffer stelsels systems Koolsuur–bikarbonaat buffer stelsel Mees belangrik in die ESV Carbonic aci