Renal physiology

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  • Ram, just scanning through your presentation proved its relevance to me. I am not an MD, but a patient of the renal system. I am familiar with the PSA analysis and that it should not exceed 4 (some say 3). So, I am going to go through your slide deck with its excellent illustrations carefully.
    Timely sharing on a personal level. Thanks for taking the time to write such an informative show.
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  • 1. Renal phys iologyDr R ma n M med A . a da oha hmed. Esl m.a a nes@yahoo.com
  • 2. C hief Func tions of Renal S ys tem• Regulation of water & electrolyte balance• Regulation of ac id & bas e balance• E xc retion of was te products of protein metabolis m, e.g., Urea from protein breakdown Uric ac id from nucleic acid breakdown C reatinine from mus cle creatine breakdown E nd produc ts of hemoglobin breakdown• E xc retion of foreign chemic als , e.g., drugs , food additives , pes tic ides , …etc .• E ndocrine func tion: erythropoietin, renin, 1,25-dihydoxy- vitamin D. 2
  • 3. FUNC TIONA L A NA TOMY OF KIDNE YS & URINA RY TRA C T • The kidneys lie high on the pos terior abdominal wall below the diaphragm & on either s ide of the vertebral column. • In adults eac h kidney is the s ize of a clenched fis t & weighs ~ 150 g. • Urine produced by the kidneys is delivered to the urinary bladder by 2 ureters . • The bladder continuous ly acc umulates urine and periodically empties its c ontents via urethra under the control of an external urethral s phincter – a proces s known as micturition. 3
  • 4. FUNC TIONA L A NA TOMY: kid• E ac h kidney is formed of 2 dis tinct parts :A n outer cortexA n inner medulla.• The medulla c ontains 5-10 renal pyramids . Their tips projec t into the renal pelv is & the dilated upper part of the ureter.• The nephron is the func tional unit of the kidney. E ac h kidney contains ~ 1 million nephrons .• The nephron is c ompos ed of 2 main components : A . The renal corpus cle 4 B . The renal tubule
  • 5. The Nephron5
  • 6. THE NE PHRONA . Renal C orpus cle: (S ite of filtration of blood)1. The G lomerulus :- It is pres ent in the cortex. - E ac h glomerulus is formed of a tuft of capillaries that are invaginated into the B owman’s caps ule. - B lood enters the capillaries through the afferent arteriole and leaves through the s lightly narrower efferent arteriole. - G lomerular capillaries are unique in that they are interpos ed between 2 arterioles . This arrangement s erves to maintain a high hydros tatic pres s ure in the c apillaries , whic h is nec es s ary for filtration. - The capillaries in the glomerulus have large pores c alled 6 fenes trae,
  • 7. THE NE PHRONA . Renal C orpus cle: 2. The B owman’s C aps ule:It is the proximal expanded portion of the renal tubule forming a double-walled c up:a. The inner layer (vis ceral layer) is formed of s pec ialized epithelium made up of podocytes :  Thes e cells have an oc topus -like s tructure.  They have foot proces s es that interdigitate and s urround the glomerular capillaries .  The foot proces s es do not form a continuous layer, but leave gaps that provide filtration s lits .b. The outer layer (parietal layer) is c ontinuous with the 7 epithelium of
  • 8. The RenalC orpus cle 8
  • 9. THE GLOME RULA R ME MB RA NE • It s eparates the plas ma in glomerular capillaries from the fluid in B owman’s c aps ule. It is formed of 3 layers : 1. E ndothelium of c apillary with large fenes trae. 2. B as ement membrane: It contains large s paces , allowing the filtration of large amounts of water & s mall s olutes . Yet, the bas ement membrane is formed of negatively charged glyc oproteins &, thus , oppos es the filtration of the negatively charged plas ma proteins . 3. Foot proc es s es of podocytes with large filtration s lits . • Due to its s pecial s tructure, the glomerular membrane filters s everal hundred times as much water & s olutes as a us ual c apillary membrane. • The filtrate is called an ultrafiltrate as it is formed of plas ma minus plas ma proteins . 9
  • 10. Glomerular MembraneThus , the filtrability of s olutes is determined by:1. The s ize of molecules : The filtrability is invers ely related to the molec ular s ize of s olute. ⇒ E lec trolytes (as Na+) & s mall organic s olutes (as glucos e) pas s freely, while large molecules (as proteins ) do not pas s through the membrane pores .2. C harges of molec ules : Negatively c harged large 10 molecules are les s filterable than pos itively charged
  • 11. THE NE PHRONB . Renal Tubule: 1. Proximal convoluted tubule (PC T) 2. Loop of Henle: It is further s ubdivided into: ► Thin des c ending limb ► Thin as cending limb ► Thic k as cending limb 3. Dis tal c onvoluted tubule (DC T)- Many DC Ts open into a collecting duc t (C D). C Ds pas s from the c ortex (c ortic al C D) to the medulla (medullary C D) and finally drain urine into the renal pelvis .- PC T & DC T are pres ent in the c ortex, while the des cending 11 limb of
  • 12. THE NE PHRONJ uxtaglomerular A pparatus : E ach DC T pas s es between the afferent & efferent arterioles of its own nephron. A t this point there is a patch of c ells with crowded nuc lei in the wall of the DC T c alled the macula dens a. They s ens e the conc entration of NaC l in this portion of the tubule. The wall of the afferent arteriole oppos ite the macula dens a contains s pecialized cells known as the juxtag lomerular cells (J G cells ). They s ec rete renin.Together, the mac ula dens a & J G cells are called the juxtag lomerular 12apparatus (J GA).
  • 13. Juxtaglomerular apparatus* It is a structure formed when the distal convolutedtubule bends around to contact the afferent arterioleat the place where it enters the glomerulus.* It is composed of specialized tubular epithelial cellsof distal convoluted tubule and the granular cells ofthe adjacent of the afferent arteriolar wall.* The granular cells secrete an enzyme called renin.This enzyme is responsible for the production ofangiotensins, of which angiotensin II.Angiotensin II stimulates the secretion of aldosteronehormone.
  • 14. The J uxta-glomerularA pparatus 15
  • 15. THE NE PHRON (cont.) N.B .- There are 2 types of nephrons in the kidney: 1. C ortical Nephrons : (80% of nephrons )  Their glomeruli lie in the outer layers of the cortex.  Their tubular s ys tem is relatively s hort.  Their loops of Henle penetrate only for a s hort dis tanc e into the outer portion of renal medulla. 2. J uxtamedullary Nephrons : (20% of nephrons )  Their glomeruli lie at the boundary between cortex & medulla.  They have long loops of Henle, whic h dip deeply down into the medulla toward the tips of the pyramids . 16  They play a major role in the proc es s of urine conc entration.
  • 16. Types of nephrons I tem s Cor ti ca l n eph r on s J u x ta m ed u l l a r y n eph r on s % Of total 85 % 15% Glomeruli Out part of cortex Inner part of cortex . Loop of Hnle Short i.e. dips to the junction Long i.e. dips deeply into the between inner and outer medullary pyramids to the medulla. inner medulla Blood supply Peritubular capillaries Vasa recta and peritubular No Vasa Recta capillaries Special function Na reabsorption Urine concentrationAfferent arteriole Thick muscular wall Thin muscular wall Very sensitive to symp Less sensitive to symp Stimulation. Stimulation. Have JG apparatus Have no JG apparatus Exhibit autoregulation Do not exhibit autoreg Low resistance to blood flow at High resistance to blood flow at rest restEfferent arteriole Thin muscular wall Thick muscular wall Less sensitive to symp Very sensitive to symp Stimulation & vasopressin. Stimulation & vasopressin. Tone decreased by Prostaglandins (PGs). JG apparatus Present Absent Autoregulation Present Absent
  • 17. Renal corpuscle Renal corpuscle ProximalNephrons convoluted tubule Afferent arteriole Efferent arterioleThey are thestructural & Distal convoluted tubule Peritubular functional capillaries units of the Renal arteriole kidney There are 2 structural classes of nephrons which are: 1- Cortical nephrons: representing 85% of nephrons where almost all the length of which lies within the renal cortex. 2- Juxtamedullary nephrons: representing 15% where their loops of Henle dip deeply into the renal medulla.
  • 18. Juxtamedullary Nephron Cortical NephronThe efferent vessels of juxtamedullary glomeruli form long looped vessels,called vasa recta which is important for urine concentration.
  • 19. S o,why is the loop of Henleus eful?• T l he ongert l t mor concent aed he oop, he e rt t filr t a t medulayIFbecome he t ae nd he lr• Impora t colect t e r t nce: he l ing ubul uns t ough t hyper ic medula hr he osmot l mor a it t r bsor H2O e bil y o ea b Desert animals have long nephron Loop  More H2O is reabsorbed
  • 20. B LOOD VE S S E LS in the NE PHRONS• E ach kidney receives its blood s upply from a renal artery, which aris es directly from the abdominal aorta.• In the kidney, the renal artery progres s ively s ubdivides into s maller branc hes until they form afferent arterioles , whic h break up into a tuft of capillaries , the g lomerulus . Then the c apillaries form the efferent arteriole.• The efferent arteriole again s ubdivides to form peritubular capillaries , whic h s urround the various s egments of the renal tubules . N.B . There are 2 s ets of c apillaries & 2 s ets of arterioles !!• The efferent arterioles of juxtamedullary nephrons form a s pecial type of peritubular capillaries c alled v as a recta.  They are s traight & long c apillaries that form hairpin loops along s ide the loops of Henle. 22  They play an important role in the proces s of urine c onc entration.
  • 21. B lood s upply of the kidney
  • 22. B LOOD S UPPLY• Renal artery fr a t ; ent s hil div om ora er um; ides• Interlobar arteries – r lcol div ena umn; ide• A rcuate arteries – a boundayofcorex &medula div t r t l ; ide• Interlobular arteries – int corex; div int sev a o t ide o er l• A fferent arterioles : suppl one nephr end in cl erofca l r – y on; ust pilaies G LOME RULUS (ca l r filr t pilay taion)–• Dr ined by a• E fferent arterioles – w for pl – PE RITUB ULA R hich m exus C A PILLA RIE S - suround r lt e r ena ubul• Fom ca l r bl fl s r pilaies ood ow• Interlobular veins• A rcuate veins• Interlobar veins• Renal vein• Infer v ca a ior ena v• Nephr w h t deep in medula– E entat iol giv r t VA S A RE C TA ons it ubes l ffer rer es e ise o (ca l r pilaies).
  • 23. Portal system (capillary beds in series), paralleling the nephronRenal ==> afferent ==> glomerular ==> efferent ==> peritubulararteries ==> arterioles ==> capillaries ==> arterioles ==> capillaries.
  • 24. Major renal capillariesGlomerular capillary Peritubular capillary bed bed1. Receives bl from afferent Receives bl from efferent art. art. 2. High presure bed 55 Low pressure bed 13 mmHg mmHg3.Represents arterial end of Represents venous end of cap. cap. 4. allows fluid filtration. Allows fluid reabsorption.
  • 25. B lood S upplyof C ortical &J uxtamedullary Nephrons 27
  • 26. RENAL BLOOD FLOW (RBF)Renal blood flow is about 20% of the cardiac outputThis is a very large flow relative to the weight of the kidneys(≈350 g)RBF determines GFRRBF also modifies solute and water reabsorption and deliversnutrients to nephron cells.Renal blood flow is autoregulated between 70 and 170 mmHg by varying renal vascular resistance (RVR).i.e. the resistances of the interlobular artery, afferent arterioleand efferent arteriole
  • 27. Factors affecting RB F1) Autoreg ulation: – RBF is kept relatively cons tant between A B P; 70-170 mmHg, It is pres ent in denervated, is olated kidney, this proving that this property is intrins ic property.2) S ympathetic s timulation: – VC of afferent arteriole of cortical nephrons → dec reas ed cortical blood flow. – Les s effect on juxtamedullary nephrons → remains well perfus ed. – VC of vas a recta → decreas e medullary blood flow → more urine concentration.
  • 28. A utoregulation of RB F & GFR• Note: A utoregulation is important to prevent large changes in G FR that would greatly affect urinary output.
  • 29. A utoregulation (Myogenicmechanis m)• Response t cha in pr e w hin t nephr v scul r o nges essur it he on’s a a component• At iol conta inher l in r rer es r ct enty esponse t t stet o he r ch accompa ↑ pr e. V a omaical const ict w nying essur essel ut t ly r s, hich hel l bl fl int gl ul despit incr sed syst ps imit ood ow o omer us e ea emic pr e essur• Opposit r ct occur w smoot muscl sense adr in e ea ion s hen h es op pr e essur
  • 30. AUTOREGULATION AUTOREGULATORY 1.5 RANGERBF (L/min) 1.0 0.5 40 80 120 160 200 240 BP (mmHg)
  • 31. EFFECT OF ARTERIAL PRESSURE CHANGES ON GFR, RBF AND URINE OUTPUTRBF or GRF (% of normal) 150 RBF 100 GFR Urine Output 50 50 100 150 200 Arterial Pressure (mmHg)
  • 32. Tubuloglomerular feedback• J a omer a a r t uxt gl ul r ppaaus – t combinaion oft a a v scul rcels w e t t e pa t ough he t ubul r nd a a l her he ubul sses hr t a e for byt a enta effer at iol a t j t he ngl med he ffer nd ent rer es s hey oin he gl ul omer us• Smoot muscl cels w hin t a entat iol for gr nul rcels h e l it he ffer rer e m a a l• Speciaized t a cels in t r know a ma adensa sense l ubul r l his egion n s cul - cha in satl eloft a fl nges l ev ubul r uid
  • 33. • M cul Densa a a ↓ Arterial pressure ↑ Arterial pressure ↑ Fluid reabsorption ↑ GFR↓ GFR in proximal tubule ↑ Tubular flow rate ↓ Tubular flow rate ↑ Na+ and Cl- delivery ↓ Na+ and Cl- delivery to Macula Densa to Macula Densa ↑ Na+ and Cl- reabsortion ↓ Na+ and Cl- reabsorption in Macula Densa in Macula Densa ↑ Renin release ↓ Renin release
  • 34. A utoregulation of High FiltrationPres s ure
  • 35. Importance of Autoreg ulation• T myogenic a t ogl ul rfeedba mecha w k he nd ubul omer a ck nisms or in t ndem t a or ae G Rw hin aM Pr nge of8 - 0 a o ut egul t F it A a 018 mmHg• A or aion gr tybl s t dir effectt tcha in ut egul t eal unt he ect ha nges at ia pr e mightot w ha e on G Ra pr v rer l essur her ise v F nd eser es w t a sol e homeost sis a al s w st excr ion t aer nd ut a nd low a e et o car on a usua ry s l
  • 36. Impact of autoregulation• A utoregulation: – G FR=180L/day and tubular reabs orption=178.5L/day – Res ults in 1.5L/day in urine• Without autoregulation: – S mall ↑ in BP 100 to 125mm Hg, ↑ GFR by 25% (180 to 225L/day) – If tubular reabs orption cons tant, urine flow of 46.5 L/day• What would happen to plas ma volume?
  • 37. ME A S URE ME NT OF RE NA L B LOOD FLOW • Renal blood flow (RB F) is determined by meas uring firs t the renal plas ma flow (RPF) and then c alculating the RB F. • We meas ure RPF us ing paraaminohippuric ac id (PA H) . • PA H is a s ubs tanc e that is :  freely filtered by the glomeruli, s ecreted in the tubules , but not reabs orbed. If PA H is given by intravenous (IV) infus ion s o that its conc entration is kept low in plas ma (e.g., 2 mg%), it is almos t c ompletely removed with a s ingle c irculation of plas ma in the kidneys . 10% of PA H remain in blood, bec aus e 10% of the blood that goes to 40 the kidneys does not reach the nephrons , but s upplies other renal
  • 38. ME A S URE ME NT OF RE NA L B LOOD FLOW• If we apply Fic k’s principle, we can c alculate RPF: Amount of PAH Amount of PAH = filtered & secreted/min excreted in urine/min• A mount of PA H filtered & s ec reted = P x E RPF• A mount of PA H exc reted in urine/min. = U x V w e, P = conc. ofPA in pl sma her H a E RPF = effect e R (90 ofpl smaonl i.e., t king int a iv PF % a y, a o ccount t t10 ha % bypa t nephr sses he ons). U = conc. ofPA in ur H ine V = v ume ofur min. ol ine/ P x E RPF = U x V UxV E RPF 41 = P
  • 39. ME A S URE ME NT OF RE NA L BLOODFLOWE xample: In a patient, if PA H is infus ed s o that its conc . in plas ma (P) is2 mg% (= 0.02 mg/ml) and the urine vol. (V) is 1.3 ml/min. & PA Hc onc . in urine (U) is l0 mg/ml, then E RPF = 10 mg/ml x 1.3 ml/min. / 0.02 mg/ml = 650 ml/min.S ince E PRF is 90% of actual RPF, RPF = 650 x 100 / 90 = 720 ml/min.If the hematocrit value is 45%, then plas ma cons titutes 55% RB F = 720 x 100 / 55 = 1300 ml/min.S ince c ardiac output is 5 L/min, RB F (1300 / 5000 x100) is
  • 40. Urine formation
  • 41. Ur F maion ine or t• Glomerular Filtration • substances move from blood to glomerular capsule• Tubular Reabsorption • substances move from renal tubules into blood of peritubular capillaries • glucose, water, urea, proteins, creatine • amino, lactic, citric, and uric acids • phosphate, sulfate, calcium, potassium, and sodium ions• Tubular Secretion • substances move from blood of peritubular capillaries into renal tubules • drugs and ions
  • 42. Overall fluid mov ement in the kidneys
  • 43. Glomerular filtration.It takes place between glomerular capillaries endothelium(characterized by the presence of numerous small pores (fenestrations)and Bowman’s capsule (characterized by the presence of podocytes).Podocytes are modified squamous epithelial cells with numerouselongated branches called foot processes which are separated by narrowgaps called filtration slits (slit pores).Fluid and small solutes dissolved in the plasma such as glucose, aminoacids, Na, K, Cl, HCO3- , other salts, and urea pass through themembrane and become part of the filtrate.The glomerular membrane hold back blood cells, platelets and mostplasma proteins.The filtrate is about 10% of the plasma.The volume of fluid filtered per unite time is called the glomerularfiltration rate (GFR). The GFR is about 180 L/day (=125 ml/min.).
  • 44. C OMPOS ITION OF GFRa- Contents: -w t aer-ions: Na , K+ , Cl + --fr yfiler subst nces e.g. gl eel t ed a ucose, a a mino cids.-0 3 abumin (mol a w 690 ). .0 % l ecul r eight 0b - O sm olality: 3 0mosmolL isot (sa osmol l ya pl sma 0 /, onic me ait s a ).C- Sp ecific gravity: 10 10D - p H : dr t 6in ur due t a ops o ine o cidificaion byt kidney. t he
  • 45. GFR–In an av erag e man: 125 ml/minute. Inwomen  10% les s . :–High r lbl fl (2025% ofcadia out )needed forhigh G R ena ood ow - r c put F.–GF R equals about 180 L/day so pl smav ume (3 ) a ol Lfiler a 60t da y, M e t n 99% ofG Ris nor ly t ed bout imes il or ha F malr bsor ea bed.–Nor lvolume of urine is a 1.5 litre/day. ma bout
  • 46. Filtration fractionIt is the fraction of the renal plasma flow(RPF) that becomes glomerular filtrate. theaverage filtration fraction about 16-20%.It is calculated as (GFR/RPF X100).
  • 47. Glomerular membrane Capillary endothelium; It has small holes (70-90 nm). It does not act as a barrier against plasma protein filtration. Basement membrane; (BM) filamentous layer attached to glomerular endothelium & podocytes, carry strong-ve charges which prevent the filtration of plasma proteins, but filters large amount of H2O and solutes. Podocytes;Epithelial cells that line the outer surface of the glomeruli.They have numerous foot processes that attach to the BM, forming filtration slits (25 nm wide).
  • 48. Layers of Glomerular Membrane
  • 49. Permeability of the glomerularmembraneS ize of the molecules• S ubs tanc es having diameters les s than 4 millmicrons (molecular weight 5500) are freely filtered while thos e having diameters more than 8 millimicrons (molecular weight more than 7000) are not filtered.C harges of the molecules• -ve charged molecules are filtered Les s eas ily than neutral molecules of equal s ize. (pos s ibly due to neg ative charg es in the bas ement membrane).
  • 50. Filterability of the Membrane• Filterability is a term us ed to des cribe membrane s electivity bas ed on the molecular s ize and charge• Pore s ize would favor plas ma protein (albumin) pas s age, but negative charge on protein is repelled by the (-) charged bas ement membrane (proteoglyc an filaments & podocytes )• Los s of this (-) charge caus es proteinuria condition called minimal chang e nephropathy
  • 51. What Drives Filtration?Howdoes fl mov fr t pl smaa oss t gl ul r uid e om he a cr he omer a membr ne int Bow n’s ca e? a o ma psul• No a iv ta tmecha ct e r nspor nisms• No l lener expendit e oca gy urSimpl pa e physica for a e ssiv l ces ccompl filr t ish taion-F taion occur t oughoutt l h oft ca l r ilr t s hr he engt he pilaies
  • 52. F orces involved in F iltration• Gomer a ca l r bl pr e (fa or filr t l ul r pilay ood essur v s t aion)• Pl smacoloid osmot pr e (opposes filr t a - l ic essur t aion)• Bow n’s ca e hydr aic pr e (opposes filr t ma psul ost t essur taion)
  • 53. Forces affecting the GFR:A) Forces helping filtration:1- Hydrostatic pressure of the blood inside glomerular capillaries (HPG) (= 50 mmHg)due to:i- The afferent arteriole is 3 times wider than the efferent arterioleii- The diameter of the renal artery is large in relation to the relelatively small size ofthe kidney.iii- The renal artery comes directly from the aorta.2- Colloidal osmotic pressure of the fluid inside the Bowman’s capsule (COPBC).Where the filtrate is free of proteins, so this force normally equals to zero mmHg.B) Forces opposing filtration:1- Colloidal osmotic pressure of the glomerular capillary blood (COPG).This pressure is due to plasma proteins and equals 30 mmHg.2- 1- Hydrostatic pressure of the fluid inside the Bowman’s capsule (HPBC) (= 10mmHg). Accordingly, The net filtering force= The forces helping filtration - The forces opposing filtration = (HPG + COPBC) - (COPG + HPBC) = (50 + 0) - (30 + 10) = 10 mmHg.
  • 54. Forces affec ting filtrationFavoring Filtration Opposing Filtration Glomerular hydrostatic Glomerular capillary colloid osmotic pressure pressure 60 mm Hg 32 mm HgBowman’s capsule colloid Bowman’s capsule hydrostatic osmotic pressure pressure 0 mm Hg 18 mm Hg Net = +10 mm Hg
  • 55. Determinants of GFR GFR=Kf x Net filtration pressure Kf = Capillary filtration coeficient
  • 56. F iltration coefficient (Kf)• It is the GFR / mmHg of net filtration pres s ure, it is normally 12.5ml/min/mmHg. It is cons tant (normally).• Glomerular filtration rate = Net filtration pres s ure X Filtration coefficient• GFR = NFP (l0) X Kf (12.5) = 125ml/min.-Kf is determined by 2 factors :1-T per bil yoft ca l r bed. he mea it he pilay2-T sur ce aeaoft ca l r bed. he fa r he pilay
  • 57. Glomerular Filtration Rate• Depends on – T netfilr t pr e he t aion essur – Howmuch gl ul rsur ce aeais a a a e forpenet aion omer a fa r v il bl rt – Howper bl t gl ul rmembr ne is mea e he omer a a GFR = K f x net filtration pres s ure W e (Kf)= filr t coefficient(apr oft a e t o her t aion oduct he bov w gl ul rpr t omer a operies) -Roug hly 125 ml/min in males
  • 58. Regulation of Filtration(1) Chang es in g lomerular hydros tatic pres s ure. (1) Diameter of the afferent arterioles . – VD of afferent arterioles → ++ Hydros tatic pr. in glomerular capillary → ++ GFR. – VC of afferent arterioles e.g ++ s ympathetic activity → -- Hydros tatic pr. in glomerular capillary (HPGC ) → -- GFR. (2) Diameter of the efferent arterioles . – Moderate VC → ++ HPG C → s light ++ of G FR. – S evere VC → -- RB F → -- G FR. (3) ABP; B etween 70 & 170 mmHg: GFR and RB F are kept relatively cons tant by autoreg ulatory mechanis ms . (4) Renal blood flow: direct relation (5) S ympathetic s timulation: VC of aff. A rteriole.
  • 59. C hanges in GFR by cons triction or dilation ofafferent (A A ) or efferent (E A ) arterioles 65
  • 60. Regulation of Filtration(2) Chang es in Bowman’s Caps ule hydros tatic pres s ure + + Hydr aicprin Bow n’s ca e e.g. st in ost t ma psul one ur er→ - G R. et -F(4) Chang e in g lomerular colloidal os motic pres s ure Incr sed Coloida osmot pr e in gl ul rca l r ea l l ic essur omer a pilay • e.g in dehydr t → decr sed G R aion ea F . Decr sed Coloida osmot pr e in gl ul rca l r ea l l ic essur omer a pilay • e.g in hypopr einemia→ incr sed G R ot ea F .• F unctioning kidney mas s• Glomerular s urface areaa ding t t st t ofmesa lcels. ccor o he ae ngia lContracted: A &a II. DH ngRelaxed: A NP.
  • 61. Lis t fiv e conditions in which g lomerularfiltration rate (GF R) decreas es .1- g lomerular hydros tatic pres s ure is reduced (i.e. hypotens ive s hock)2-Bowmans s pace hydros tatic pres s ure are increas e ureteric obs truction.3- plas ma oncotic pres s ure ris es to unus ually hig h lev els in dehydration.4- decreas ed rates of renal blood and plas ma flow (e.g . heart failure).5- Reduced permeability and / or total filtering s urface area.
  • 62. review autoregulation
  • 63. Meas urement of GFR:(1) Inulin c learance; Inulin has the following characteris tics :• F eel filer i.e. pl smaconc.= filr t concent aion. r y t ed a tae rt – notr bsor orsecr ed byr lt es i.e. a ea bed et ena ubul mountfiler permin.= a t ed mountexcr ed in ur min. et ine/ – Notmet bol a ized. – Notst ed in t kidney. or he – Does nota filr t r t &it conc. is ea ymea ed. ffect taion ae s sil sur(2) C reatinine clearance• F eel filer r y t ed• Notr bsor ea bed• pat lysecr ed byr lt es. rial et ena ubul• E ndogenous so used ea ybutina ae. sil ccur t
  • 64. Renal C learanceDefinition: Volume of the plas ma cleared from the s ubs tance per minute. R = UVP C / R = r lcl r nce r t C ena eaa ae U = concentaion (mg/ )oft subst nce in ur rt ml he a ine V= fl r t ofur for t (mlmin) ow ae ine maion / P= concentaion oft sa subst nce in pl sma rt he me a a
  • 65. Inulin clearance
  • 66. Free Water C learance (C H20)Qua ifies r aiv l orga ofw t in t ur nt el t e oss in aer he ine• Cl r nce ofosmol (Cosm)is t v ume ofw t necessayt secr e t osmot eaa es he ol aer r o et he ic l d in aur isot w h pl sma oa ine onic it a – Differ bet een ur fl a t cl r nce ofosmol (Cosm) ence w ine ow nd he eaa es• CH20 = Ṽ – UosmṼ Posm – Negaiv w ur concentaed (hyperonic) t e hen ine rt t – Posit e w ur dil e (hypot iv hen ine ut onic)
  • 67. TUB ULA R FUNC TION• T glomerular filtrate he is for a ar t of125 ml/ med t ae min. or 180 L/day. It pa t t r lt es. sses o he ena ubul• In t t es, t tubular he ubul he fluid is subj ed t t 2 ma ect o he in t a funct ubul r ions, reabs orption & s ecretion.• Itis final excr ed a urine a a ly et s t r t ofa 1-2 ml/min. or ae bout c a. 1.5 L/day. 78
  • 68. TUB ULA R RE A B S ORPTION• R lt es ta tsubst nces a oss t membr nes t int st ia fl a t t ough t ena ubul r nspor a cr heir a o er it l uid nd hen hr he per ubul rca l r membr ne ba t bl it a pilay a ck o ood.• Subst nces ca be ta t by: a n r nspored1. Trans cellular Route: -Subst nces pa t ough t cel membr nes: a ss hr he l a–crossing t l lmembr ne &t t ba aer lmembr ne. he umina a hen he sol t a a -T ta tbyt r e ma be ac tive bymea ofapr ein he r nspor his out y ns ot car orpas s ive bydiffusion. rier2. Parac ellular Route: -Subst nces pa a oss t j ions bet een t a cels. a ss cr ight unct w ubul r l -Ta tbyt r e occur pas s ively bydiffusion. r nspor his out s 79
  • 69. Tubular Reabs orption is a Function of the E pithelial C ells Making up the TubuleLumen Cells Plasma
  • 70. Tubular Reabs orptionA) Active transport; against electrochemical gradient. (1) Primary active transport Requires energy directly from ATP. ►Example; Na+ reabsorption in PCT (2) Secondary active transport -It does not require energy direct from ATP. a) Co-transport two substances bind to a specific carrier are cotransported in one direction. b) Counter-transport two substances bind to a specific carrier are transported in two directions.B) Passive reabsorption; (1) Simple diffusion Passive reabsorption of chloride & Osmosis of water (2) Facilitated diffusion Need carrier.C) Pinocytosis It is an active transport mechanism for reabsorption of proteins and peptides in the proximal convoluted tubules.
  • 71. Primary ac tive trans port of s odium through the tubular epithelial c ell 82
  • 72. Proximal C onvoluted Tubule• 65% of t nephr funct occur in he on ion s PCT .• T PCT ha a singl l yer of cuboida he s ea l cels w h milions ofmicr ili. l it l ov l– Incr sed sur ce aeaforr bsor ion. ea fa r ea pt• PCT ma funct is r bsor ion. s in ion ea pt• T PCTis ful ofmit he l ochondria
  • 73. Reabs orption in Proximal Tubule• 10 % Gucose, pr ein a A A 0 l ot nd mino cids• 60 Sodium, Cl a H2O. % , nd• 8 % PH, HCO3 K. 0 ,• 60 Ca % .• 50 ofF t ed Ur . % iler ea
  • 74. Nar bsor ion ea pt A ba aer lside oft t a epit ia cel t e is a ext e Na - + APa syst (= t sol t a he ubul r hel l l her n ensiv + K T se em Na - + pump). + K  Itpumps 3Na a iv youtoft cel int t int st ium, a a t sa t car 2 K+ + ct el he l o he er it nd t he me ime ries int t cel. o he l  ButK+ w ldiffuse immediael ba int t int st ium due t il t y ck o he er it o: (1)high concentaion gr dient& rt a (2)high per bil yofepit ia cels t K+ . mea it hel l l o  A ar toft t e is: s esul his her -↓ inta l a Na concentaion r celul r + rt -↑ inta l a negaiv y(- mV r celul r t it 70 ) A l lmembr ne t e w lt efor be pa e diffusion ofNa int t cel aongbot t umina a her il her e ssiv + o he l l h concentaion a el r gr dient cr t byt Na - + APa pump. T diffusion is r t nd ectic a s eaed he + K T se his fa it t byapr ein car . cil aed ot rier
  • 75. Nar bsor ion ea pt
  • 76. Water Reabsorption
  • 77. G lucose reab sorp tion• The trans porter for glucos e on the bas olateral membrane has a limited capacity to carry glucos e bac k into the blood. If blood glucos e ris es above 180 mg/dl, s ome of the glucos e fails to be reabs orbed and remains in the urine  glucos uria.
  • 78. Glucos e reabs orption
  • 79. Tubular maximum for glucos e (TmG):• The maximum amount of glucos e (in mg ) that can be reabs orbed per min.• It equals the s um of TmG of all nephrons .• TmG not the s ame in all nephrons• It is an indication of the reabs orptive capacity of the kidney.• It is determined by the number of glucos e carriers in PC T.• The maximum reabs orption rate is reached when all the carriers are fully s aturated s o they can not handle any additional amounts at that time.• Value; 300 mg/min in ♀ , 375 mg/ min in ♂.
  • 80. Renal Thres hold for Glucos e• Is a oximael 18 mg/ ppr t y 0 dl• Ifpl smagl a ucose is gr t t n 18 mg/ : eaer ha 0 dl – T oft a cels is exceeded m ubul r l – gl a r in ur ucose ppeas ine
  • 81. GLUC OS E RE A B S ORPTION HA S ATUB ULA R MA XIMUMGlucose Filtered ExcretedReabsorbedmg/min Reabsorbed Plasma Concentration of Glucose
  • 82. Glucos uria pres ence of glucos e in urine 1. Diabetes mellitus –blood gluc os e level > renal thres hold. 2. Renal g lucos uria –It is c aus ed by the defect in the glucos e trans portmec hanis m. 3. Phlorhizin –A plant gluc os ide whic h c ompetes with gluc os e for thec arrier and res ults in gluc os uria (phloridzin diabetes ). 4 Preg nancy . –due to altered gluc os e handling in dis tal nephrons . 17-59
  • 83. B icarbonate reabs orption
  • 84. S ecretion in Proximal Tubule• Hydr secr ion fora ba r aion. ogen et cid/ se egul t• Ammoniasecr ion fora ba r aion. et cid/ se egul t• PA H.• Cr t eainine.• Ur a ic cid.• Penicilin. l
  • 85. Reabs orption: Loop of Henle
  • 86. S PE C IFIC FUNC TIONS OF DIFFE RE NTTUB ULA R S E GME NTS (cont.)II. Loop of Henle:• T l ofHenl w h it 3segment (t tdifferstuct al &funct ly)contibut t cr t agr dual incr sing he oop e it s s ha r ur ly ional r es o eaing a ly ea hyper ait (3 0→120 mosmolL)in t r lmedulayint st ium. osmol l y 0 0 / he ena l r er itA . Thin des cending limb: - highly permeable to w t . 20% ofH2Ois r bsor her aer ea bed e. -onl moder t yper bl t sol es. y ael mea e o ut⇒ Osmol l yoft a fl ↑ gr dual a l dips deep int t medulaypyr mid (r ches 120 mosmol ait ubul r uid a ly s oop o he l r a ea 0 ).B. Thin as cending limb: -impermeable to w t aer -l a pt e pow forsol es. ow bsor iv er utC . Thick as cending limb: -impermeable to w t aer -high r bsor iv pow forsol es: Ita iv yr bsor 25% offiler ea pt e er ut ct el ea bs t ed + + - + - + Na , K , &Cl (by1 Na , 2 Cl, 1 K cota t t medulayint st ium. r nspor) o l r er it⇒ Osmol l yoft a fl ↓ gr dual a itr ches DCT(becomes hypoosmot Itis cal t diluting s egment. ait ubul r uid a ly s ea ic). led he 97
  • 87. SPE F IONSOFDIF . T A SE M NT C. UNCT F UBUL R G E SIII. Dis tal C onvoluted Tubule (DC T) & C ollecting Duct (C D):A . E arly DC T: T patoft r lt es is in effecta ext his r he ena ubul n ension oft t a he hick scending l ofl ofHenl imb oop e: - Itis impermeable to w t . aer -T e is cont r a ofNa , K+ , Cl &ot ions w houtH2O. her inued emov l + - her it⇒ T e is furherdil ion oft a fl a it osmol l y↓ ev mor (10 mosmol her t ut ubul r uid nd s ait en e 0 ).⇒ T patis cal t cortical diluting s egment. his r led heB. Late DC T & C ortical C D: T ae impermeable to ur . hey r ea T ha e 2 cel t hey v l ypes: (1) Principal C ells : a. T a iv yr bsor Na in excha forK+ secr ion. T a ion is incr sed byaldos terone. hey ct el ea b + nge et his ct ea b. A ntidiuretic hormone (A DH) ca t inserion ofH2Ocha s (aquaporins ) in l l uses he t nnel umina membr ne oft cels → al s r bs. ofH2O. a hese l low ea In t a he bsence ofA t pr lcels ae imper bl t H2O. DH, he incipa l r mea e o 99
  • 88. DC T and C D
  • 89. SPE ICF IONSOFDIF E E T A SE M NT (cont CIF UNCT F R NT UBUL R G E S .)B . Late DC T & C ortical C D: (cont.) (2) α-Intercalated C ells : -T cels secr e H+ byH+ - T se independentofNa hese l et APa + r bsor ion. T a ion is incr sed byaldos terone. ea pt his ct eaC . Medullary C D:• In t l stporion oft nephr t e is final adjus tment of volume & concentration of his a t he on her urine.  T per bil y oft segmentt w t , sa a t toft l t DCT&corica CD, is v r bl &depends on t l el he mea it his o aer me s ha he ae t l aia e he ev ofcir aingA (= facultative water reabs orption). cul t DH  W h high bl l el ofA t e is ↑ r bsor ion ofH2O byosmosis, a t a fl in CD is subj ed t it ood ev s DH, her ea pt s ubul r uid ect o gr dual incr sing hyper ait oft medulayint st ium. a ly ea osmol l y he l r er it  T patis aso permeable t ur , t tdiffuses int t int st ium w it concentaion in t a fl ↑ due his r l o ea ha o he er it hen s rt ubul r uid t H2Or bsor ion. o ea pt T ur contibut t t hyper ait ofmedulayint st ium. hus, ea r es o he osmol l y l r er it⇒ In t pr he esence ofA ur excr ed is concentaed &smalin v ume. DH: ine et rt l ol⇒ In t a he bsence ofA ur excr ed is dil e ur &l r in v ume. DH: ine et ut ine age ol 101
  • 90. Medullary C ollecting Duct• r bsor < 10 offiler Na a w t ea bs % t ed + nd aer• fina sit forpr l e ocessingofurinefunctional characteris tics :5. per bil yt w t is contoled byA l el mea it o aer rl DH ev -↑A DH ↑ w t r bsor ion aer ea pt2. per bl t ur mea e o ea-ur is r bsor int t medulay ea ea bed o he lr int st ium w e ithel incr se t er it her p ea he osmol l yoft int st ium a t efor hel t concentae ur ait he er it nd her e p o r t ine.
  • 91. S ummary For Tubular Functions
  • 92. S ummary of c hanges in os molality of tubular fluidin various parts of the nephron
  • 93. RE GULA TION OF TUB ULA R RE A B S ORPTION
  • 94. 1. Glomerulotubular B alance• intinsic a it oft t es t incr se t r bsor ion r t in r bil y he ubul o ea heir ea pt ae response t a incr se in gl ul rfilr t o n ea omer a taion• cha in G Rinduces apr t lcha in t a r bsor ion nges F oporiona nge ubul r ea pt• t a r t ofr bsor ion incr ses a filer l d incr ses butt ot l ae ea pt ea s t ed oa ea he per a ofG Rr bsor r ins r aiv yconst nt cent ge F ea bed ema el t el a• second l ofdefense forpr ent cha in r l hemodyna ine ev ing nges ena mics fr ca l r cha in sodium orfl excr ion om using age nges uid et• bl s sodium excr ion r unt et esponse t cha in G Rinduced bycha in o nges F nges at ia pr e rer l essur
  • 95. 2. Peritubular C apillary andRenal Inters titial Fluid S tarling’sForcesA . Peritubular C apillary Hydros tatic Pres s ure: ↑ PPC ↓ r bsor ion ea ptSyst at ia pr e (PA): emic rer l essur ↑ PA ↑ PPC ↓ r bsor ion ea ptB. PTC Os motic Pres s ure (Π PC ): ↑ ΠPC ↑ r bsor ion ea ptC . Renal inters itial fluid hydros tatic pres s ure:-Decr sed r bsor ion in t per ubul rca l r w lr tin: ea ea pt he it a pilaies il esul 1. ↑ PIF due t a o ccumul t offl in t int st ia compat aion uid he er it l rment 2. ↓ ΠIF due t dil ion ofint st ia fl pr eins o ut er it l uid ot
  • 96. 3. A rterial Pres s ure• smalincr ses in at ia pr e oft ca maked incr ses l ea rer l essur en use r ea in ur r excr ion ofw t a sodium (pr e diur a inay et aer nd essur esis nd pr e nar esis) essur tiurmec hanis m:1. sl incr se in G R ight ea F.2. incr sed PPC ↓ r bsor ion fr int st ia spa ea ea pt om er it l ce ↑ PIF ↓ r bsor ion ofw t a ea pt aer nd sodium fr t a l om ubul r umen3 decr sed A ensin II . ea ngiot ↓ Na r bs + ea
  • 97. 4. Hormonal C ontrolHormone Site of Action EffectsAldosterone Collecting tubule and duct ↑ NaCl, H2O reabsorption, ↑K+ secretionAngiotensin II Proximal tubule, thick ↑ NaCl, H2O ascending loop of reabsorption, ↑H+ Henle/distal tubule, secretion collecting tubuleAntidiuretic Distal tubule/ collecting ↑ H2O reabsorptionhormone tubule and ductAtrial natriuretic Distal tubule/ collecting ↓ NaCl reabsorptionpeptide tubule and ductParathyroid Proximal tubule, thick ↓ PO4--- reabsorption, ↑hormone ascending loop of Ca- reabsorption Hental/distal tubule
  • 98. 5. S ympathetic S timulation• w ldecr se sodium a w t excr ion (incr se sodium a w t il ea nd aer et ea nd aer r bsor ion)bythe following mechanis ms : ea pt1. v soconstict ofbot a enta effer a r ion h ffer nd ent at iol t ebydecr singG R rer e her ea F .2. incr se sodium r bsor ion in t pr l ea ea pt he oxima t ea t a ubul nd hick scendingl imb.3 incr se r r ea . ea enin el se incr sed A IIea ng incr sed sodium ea r bsor ion. ea pt
  • 99. Hormones ac ting on the kidney1. A ldos terone:• S timulus for its s ecretion: ↓ Bl v ume (v r a ent syst ood ol ia enin- ngiot in em).• A ctions & their s ite: Itst aes Na r bsor ion in DC T & cortical C D t ough: imul t + ea pt hr 1) In principal cells : ↑ Na r bsor ion in excha w h K+ . + ea pt nge it 2) In α -intercalated cells : ↑ Na r bsor ion in excha w h H+ . + ea pt nge it2. A ngiotens in II: Itis t mostpow fulNa r a hor he er + et ining mone.• S timulus for its s ecretion: ↓ at ia bl pr e &bl v ume, e.g., hemorha (v r rer l . essur ood ol r ge ia enin).• A ctions & their s ite: 1. It↑ Na r bsor ion bysev a mecha + ea pt er l nisms: a Byst aing adost one secr ion. . imul t l er et b. In PC T: -Bydir l st aing Na - + APa a ba aer lbor . ecty imul t + K T se t sol t a der -Bydir l st aing Na - + count ta a l lbor . ecty imul t + H err nsp. t umina der 2. Itconstict effer at iol r s ent rer es. 112
  • 100. Hormones acting on the kidney3. A trial Natriuretic Peptide (A NP): Itfa it t Na &H2Oexcr ion. cil aes Cl et• S timulus for its s ec retion: ↑ Ar lpr e (r ea fr specific ar lfiber w bl v ume is ↑) tia essur el sed om tia s hen ood ol• A c tions & their s ite:1. It↑ G byV ofa ent&V ofeffer at iol FR D ffer C ent rer e.2. It↓ Na r bsor ion from DC T & cortical C D . + ea pt4. A DH:• S timulus for its s ecretion: ↑ Pl smaosmol r y&↓ bl v ume. a ait ood ol• A ctions & their s ite: ↑ w t r bsor ion in late DC T, cortical & medullary C D: byinseringa por w t aer ea pt t qua in aer cha s int t l lmembr nes. nnel o heir umina a5. Parathormone (PTH):• S timulus for its s ecretion: ↓ Pl smaCa concentaion. a 2+ rt• A ctions & their s ite: 114 1. ↑ Ca r bsor ion from DC T. 2+ ea pt 2. ↓ Phosphae r bsor ion from PC T. t ea pt
  • 101. H A N D L IN G O F C E R T A IN IM P O R T A N T S O L U TE S B Y RENAL TU B U L E S 116
  • 102. I. GLUC OS E :A nor lbl gl l el (~10 mg%), gl is fr yfiler a ar t of125 mg/ (= pl smaconc. XG R t ma ood ucose ev s 0 ucose eel t ed t ae min. a F= 10 mg% x 125 mlmin.). 0 / +T a he mountfiler is compl el r bsor fr t upperhafofPCTbyNa - ucose cota t(mecha see t ed et y ea bed om he l gl r nspor nism:before). +T e is, how er al ed numberofNa - ucose car s: her ev , imit gl riera- A t a blood glucos e level of les s than 180 mg%, alt filer gl l he t ed ucose ca be nr bsor beca pl yofcar s ae a a a e. ea bed use ent rier r v il blb- A t a blood glucos e level of 180 mg%, gl st rs t a rin ur ucose at o ppea ine. T l elofbl gl is cal t renal thres hold forgl his ev ood ucose led he ucose. It coresponds t arenal r otubular load of 220 mg/min.c- A t a renal tubular load of glucos e of 320 mg/min, alt car s ae saur t l he rier r t aed,i.e., t trans port maximum forgl he ucose, T G, is r ched. m eaA furher↑ in filer gl ny t t ed ucose is notr bsor &is117et in ur ea bed excr ed ine.
  • 103. Glucos e reabs orption
  • 104. G luc os e Titration C urves 119
  • 105. I. GLUC OS E : (cont.)I. G LUC OS E : (cont.)S play:-Itis t r ofgl cur es bet een r lt eshol &T G. he egion ucose v w ena hr d m-Itoccur bet een r lt a gl l ds of220 - 320 mg/min.. s w ena ubul r ucose oa-Itr esent t excr ion ofgl in ur befor ful saur t of epr s he et ucose ine e l t aion t gl car s forr bsor ion (T G)is a ed. he ucose rier ea pt m chiev-Itis expl ined byt het ogeneit ofnephr a he er y ons: Notalnephr ha e exa l t sa T G. Some nephr l ons v cty he me m ons r ch saur t a l erpl smaconcentaions t n ot s, a ea t aion t ow a r t ha her nd gl w lbe excr ed in ur befor t a er ge T G is r ched. ucose il et ine e he v a m ea 120
  • 106. GLUC OS URIA :• Definition: Itis t pr he esence ofgl in ur Itis usual a ucose ine. ly ccompa bypol iadue t osmot diur nied yur o ic esis.• C aus es :1. Diabetes Mellitus : -T bl gl l elis high, exceeding t nor lr lgl he ood ucose ev he ma ena ucose t eshol of18 mg%. hr d 0 -In t condit t pl smacl r nce ofgl is a e zer &t mor a a t condit of his ion, he a eaa ucose bov o, he e dv nced he ion dia es, t highert gl cl r nce. bet he he ucose eaa2. Renal G lucos uria: -In t condit t bl gl l elis nor l his ion he ood ucose ev ma. -T defectl in t r lt es t he ies he ena ubul hemsel es. T e is adecr sed r lgl t eshol bel it v her ea ena ucose hr d ow s nor lv l due t acongenit ldefectin t gl ta tmecha so t tt e is l ofgl ma aue o a he ucose r nspor nism, ha her oss ucose in ur a nor lbl gl l el ine t ma ood ucose ev s. 121
  • 107. S odium Handling- + is fr y filer a oss gl ul rca l r T it concentaion in gl ul rfilr t equas t tin Na eel t ed cr omer a pilaies. hus, s rt omer a tae l hapl sma a . +- ofNa ae r bsor aong alsegment oft r lt e, exceptt t descending l oft l 99% r ea bed l l s he ena ubul he hin imb he oopofHenle.Na+ reabs orption along the nephron:1. Proximal c onvoluted tubule: ea bs 3 t ed + R bsor 2/ (67%)offiler Na &H2O. T pr is isoosmot his ocess ic.a. E arly PC T: + -Na is r bsor bycota tw h gl ea bed r nspor it ucose, a a phosphae &l ct t mino cids, t a ae. -Na is aso r bsor bycount ta tv Na - + excha + l ea bed err nspor ia + H nge.b. Late PC T: Na is r bsor (1 ry a iv ta t w h Cl (pa e diffusion). + ea bed ct e r nspor) it - ssiv 122
  • 108. S odium Handling2. Thic k as cending limb of loop of Henle: R bsor 25% offiler Na byt Na - + - - cota t in t l l ea bs t ed + he + K 2Cl r nsporer he umina membr ne. a3. Dis tal convoluted tubule & collecting duct: oget hey ea b % he t ed + T hert r bsor 8 oft filer Na . a. E arly DC T: Cont ins aNa - + - - cot a t in l lmembr ne simil rt a + K 2Cl r nsporer umina a ao t tin t a ha hick scending l ofl ofHenl imb oop e. b. Late DC T & C D: (T effectis incr sed byaldos terone). his ea i. Principal cells : r bsor Na in excha forK+ . ea b + nge ii. α -Intercalated cells : r bsor Na in excha forH+ . ea b + nge 123
  • 109. Na+ handling along the nephron 124
  • 110. Factors affecting Na+reabs orption:1. Rate of tubular flow: Sl r t offl ↑ r bsor ion ofNa in l ofHenl e.g., in ↓ G R ow ae ow ea pt + oop e, F.2. Glomerulotubular balanc e in PC T: - Itr esent t a it oft PCTt r bsor aconst ntfr ct (2/ or67%)oft filer epr s he bil y he o ea b a a ion 3 he t ed + l d ofNa &w t . oa aer- IfG R↑ fora r son, t filer l d ofNa aso ↑. T w ll d t a incr se in t F ny ea he t ed oa + l his il ea o n ea he + + amountofNa r bsor in PCT so t tt a ea bed , ha he mountofNa excr ed incr ses onl sl l et ea y ighty.- Imporat nce: Itis a intinsic mecha t tca be seen in dener aed kidneys. Ithel pr entov l ding n r nism ha n vt ps ev eroa ofdist lt a segment w G R↑. a ubul r s hen F 125
  • 111. Factors affecting Na+reabs orption2. G lomerulotubular balanc e in PC T: - M nism: echa Gomer ot a baa is ba on l ul ubul r l nce sed St ring for in per ubul rca l r al ces it a pilaies, hich ler + w at Na &H2Or bsor ion: ea pt ↑ in G Rr t in ↑ in pr ein conc. & F esuls ot oncot pr e (πC), a w la a↓ hydr ic essur s el s o- st t pr e (PC)ofper ubul rca l r aic essur it a pilaies. T in t n, ca a ↑ in w t r bsor ion fr PCT his, ur uses n aer ea pt om . + Since w t r bsor ion is a aer ea pt ccompa byNa r bsor ion, t e is maching filr t &r bsor ion, nied ea pt her t taion ea pt orgl ul ubul rbaa omer ot a l nce.3. Hormones : (s ee before) 126 1. A ldos terone, 2. A ngiotens in II, 3. A NP
  • 112. Potas s ium Handling1. G lomerular c apillaries : F t aion ofK+ occur fr ya oss t gl ul rca l r ilr t s eel cr he omer a pilaies.2. PC T: Itr bsor 67% oft filer K+ aong w h Na &w t . ea bs he t ed l it + aer3. Thick as c ending limb of loop of Henle & early DC T: Itr bsor 20 oft filer K+ byt Na - + - - cota t in t l lmembr ne. ea bs % he t ed he + K 2Cl r nsporer he umina a4. Late DC T & c ollec ting duc t: T eit r bsor orsecr e K+ . hey her ea b et a. Reabs orption of K +: - It occur onl in K+ depl ion (= l K+ diet Under t condit K+ excr ion ca be a l a 1% of s y et ow ). hese ions et n s ow s + filer l d beca t kidney conser es a much K a possibl t ed oa use he v s s e. -Itinv v aK+ - + excha a l lmembr ne ofα- er l t cels. ol es H nge t umina a int caaed l b. S ec retion of K +: -Itoccur in pr lcels byNa - + excha s incipa l + K nge. -Itis v r bl Itdepends on diet r K+ , adost one &a ba st t aia e. ay l er cid- se aus. 127
  • 113. K + handling along the nephron 128
  • 114. Mechanis m of dis tal K + s ecretion in principal cells- A t bas olateral membrane: K+ is a iv yta t int t cel byt Na - ct el r nspored o he l he + K+ APa → T mecha ma a ahigh I.C. K+ conc. T se his nism int ins - A t luminal membrane: K+ is pa el secr ed int t l t ough K+ ssiv y et o he umen hr cha s. nnel he mount of t pa e secr ion is det mined by t concentaion gr dient a ing on K+T a his ssiv et er he rt a ct a oss t l lmembr ne: cr he umina aIn condit t t↑ I.C. K+ conc. or↓ t l lK+ conc. ions ha he umina → ↑ t dr ingfor forsecr ion. he iv ce etIn condit t t↓ I.C. K+ conc. or↑ t l lK+ conc. ions ha he umina → ↓ t dr ingfor forsecr ion. he iv ce et 129
  • 115. Mechanis m of K + s ecretion in the principal cell of the DC T 2 1 3 130
  • 116. HA NDLING OF C E RTA IN IMPORTA NT S OLUTE S B Y RE NA L TUB ULE SFac tors affecting dis tal K + s ec retion:1. Dietary K +: High K+ diet→ ↑ I.C. K+ → ↑ dr ing for → ↑ K+ secr ion. iv ce et LowK+ diet → ↓ I.C. K+ → ↓ dr ing for → ↓ K+ secr ion. iv ce et2. A ldos terone: -A t ba aer lmembr ne: Itst aes Na - + APa → ↑ K+ t he sol t a a imul t + K T se upt ke bypr lcels → ↑ I.C. K+ concentaion → ↑ dr ing for for a incipa l rt iv ce K+ secr ion. et -A t l lmembr ne: It↑ t numberofK+ cha s. t he umina a he nnel3. A c id-bas e s tatus :A Na ions ae r bsor in excha fort secr ion ofK+ orH+ ions, t e is compet ion forNa ions in t s + r ea bed nge he et her it + he t a fl ubul r uid: In a cidosis: M e H+ t n K+ ent s t a epit ia cel a oss t ba aer lmembr ne → ↓ I.C. K+ → ↓ or ha er ubul r hel l l cr he sol t a a dr ingfor forK+ secr ion. iv ce et In akaosis: L H+ t n K+ ent s t a epit ia cel a oss t ba aer lmembr ne → ↑ I.C. K+ → ↑ l l ess ha er ubul r hel l l cr he sol t a a dr ingfor forK+ secr ion. iv ce et 131
  • 117. HA NDLING OF C E RTA IN IMPORTA NT S OLUTE S B Y RE NA L TUB ULE SV. Phos phate: 5% t ed t ea bed r nspor it + nd he est - 8 offiler phosphae is r bsor in PCTbycota tw h Na a t r is excr ed in et urine.- Paahyr hor (PT inhibit phosphae r bsor ion in PCT&ca phos phaturia. r t oid mone H) s t ea pt uses- Phosphae is aur r bufferforH+ . t inay 132
  • 118. HA NDLING OF C E RTA IN IMPORTA NT S OLUTE S B Y RE NA L TUB ULE SVI. C alc ium:- Nor ly, 99% offiler cacium ae r bsor byr lt es. mal t ed l r ea bed ena ubul- Itshoul be not how er t tonl 50 ofpl smacacium, w is ionized cacium, is filer a oss d ed, ev , ha y % a l hich l t ed cr t gl ul rca l r w e t ot 50 ofpl smacacium ae bound t pl smapr eins a he omer a pilaies, hil he her % a l r o a ot nd ca be filer nnot t ed.  67% ae r bsor in PCT r ea bed .  25- 0 ae r bsor in t l ofHenl 3 %% r ea bed he oop e.  5- % ae r bsor in DCT&CD. PT st aes Ca r bsor t fr DCT 10 r ea bed H imul t 2+ ea p-ion om .
  • 119. Urea Handling(1) PC T A bout 50% of the filtered urea is pas s ively reabs orbed The wall of PC T is partially permeable to urea but highly permeable to water s o water reabs orption from PC T → increas es urea concentration in tubular lumen. This creates concentration gradient → Urea reabs orption.(2) Thick as cending limb of loop of Henle, DC T and cortical collecting tubules A ll are relatively impermeable to urea. H2O reabs orbed in DC T and cortical collecting tubule (in pres ence of A DH) → increas ed urea concentration in tubular fluid.(3) Inner medullary portion of the collecting duct Urea diffus es into the medullary inters titium to increas e its os molality. Diffus ion of urea is facilitated by A DH. 40 - 60% of the tubular load of urea is exc reted in urine.► Urea cycle • Urea moves from the medullary inters titium into the thin loop of • the Henle and back down into the medullary collecting • duct and again to medullary inters titium • s everal times before urea is excreted.
  • 120. Urea recycling
  • 121. Handling of Hydrog en 1. PC T 85% 2. Thic k as cending loop of Henle 10% 3. DC T and collec ting tubule 5%.Mechanis m of H+ s ecretionA) In PCT, LH and initial part of DCT: M ofH+ is secr ed bys econdary active trans port. ost et Itis Na dependent. A ipor car a l lbor bind Naa H. nt t rier t umina der ndB) In late part of DCT and CD: Hydr is secr ed byprimary activ e trans port ByInterc alated cells , ogen et hydr secr ion is st aed byadost one a bot ogen et imul t l er nd h hydr a pot ssium compet forsecr ion. ogen nd a e et
  • 122. B icarbonate Handling Plas ma HCO3 plays an important role in the reg ulation of pH of plas ma.Mos t of the filtered bicarbonate (99 % or more) is reabs orbed. 1) A bout 80 to 90 % of the bicarbonate reabs orption occurs in the PC T. 2) In the thick as cending loop of Henle, 10 % of the filtered bicarbonate is reabs orbed, 3) the remainder of the reabs orption takes place in
  • 123. Bicarbonate Handling
  • 124. A mino acid handling• S econdary active trans port coupled with s odium
  • 125. Subs Description Proximal tubule Loop of Henle Distal tubule Collecting duct If glucose is not reabsorbed by reabsorption (almost the kidney, it appears in the 100%) viaglucose urine, in a condition known as sodium-glucose transport proteins- - - glucosuria. This is associated (apical) with diabetes mellitus.. and GLUT(basolateral ).amino acids Almost completely conserved. Reabsorption (active) - - - urea Regulation of osmolality. Varies reabsorption (50%) via secretion - reabsorption in with ADH passive transport medullary ducts reabsorption reabsorption reabsorption (5%, Uses Na-H antiport, Na-glucose reabsorption (65%, (25%, thick (5%, principal cells),sodium symport, sodium ion channels isosmotic) ascending, sodium-chloride symporter by stimulated Na-K-2Cl symporter ) aldosterone ) Usually follows sodium. Active reabsorption reabsorptionchloride (transcellular) and passive ( reabsorption (thin ascending, (sodium- - paracellular) thick ascending, chlorid symp Na-K-2Cl reabsorption water Uses aquaporin. - reabsorption - (with ADH, via (descending) vasopressin recepto ) Helps maintain acid-base reabsorption (80-90%) reabsorption reabsorption HCO3 balance. [8] [9] (thick ascending) - (intercalated [10] cells, secretion H Uses [[vacuolar H+ATPase]] - - - (intercalated cells) reabsorption (20%, thick secretion increased by K Varies upon dietary needs. reabsorption (80%) ascending, aldosterone) Na-K-2Cl symporter ) reabsorption (thick reabsorptioncalcium reabsorption ascending) via stimulated - passive transport by PTH reabsorption (80%) phosp Excreted as titratable acid. Inhibited by - - - parathyroid hormone.
  • 126. Table 41-3 NaCl transport along the nephron Segment Percentage filtered Mechanism of Na+ Major regulatory reabsorbed entry across the hormones apical membraneProximal tubule 67% Na+-H+exchange, Angiotensin II Na+-cotransport with amino acids and Norepinephrine organic solutes, Na+/ H+-Cl-/anion Epinephrine exchange Dopamine ParacellularLoop of Henle 25% 1 Na+-1K+-2Cl- Aldosterone symportDistal tubule ~4% NaCl symport AldosteroneLate distal tubule ~3% Na+ channels Aldosteroneand collecting duct Atrial natriuretic peptide Urodilatin
  • 127. Table 41-4 Water transport along the nephron Segment Percentage of Mechanism of Hormones filtered load water that regulate reabsorbed reabsorption water permeabilityProximal tubule 67% Passive NoneLoop of Henle 15% DTL only; None passiveDistal tubule 0% No water None reabsorptionLate distal ~8%-17% Passive ADH, ANPtubule and
  • 128. URINEC ONC E NTRA TION
  • 129. Mechanis ms to C oncentrateUrine creation of• Countercurrent Multiplication-- osmot gr dient ic a – L ofHenl oop e – G aes aur t tis concentaed a high a 60 mosm/ ener t ine ha rt s s 0 L• Urea recycling – M l r Colect Duct edulay l ing – Needed t incr se t osmol rgr dientfr 60 t 120 mosm/ o ea he a a om 0 o 0 L – Kidneys use ur t do osmot w k w in st t ofa idiur ea o ic or hen ae nt esis• Countercurrent exchang e-- asarectam aintains the v medulayinst st ia osmot gr dientsetup byt count curentmulipl l r er it l ic a he er r t ier
  • 130. PRODUC TION OF C ONC E NTRA TE D URINE• Concentaed ur is aso cal hyperos motic urine (ur osmol r y> bl osmol r y). r t ine l led ine ait ood ait• T kidneyexcr es excess sol es, butdoes notexcr e excess a s ofw t . he et ut et mount aer• The bas ic requirements for forming a c onc entrated urine are:1. a high level of A DH, e.g., in w t depr aion orhemorha aer iv t r ge → ↑ per bil yofl t DCT&CDs t w t , al ing t segment mea it ae o aer low hese s t r bsor al r a o ea b age mountofw t . aer2. a high os molarity of the renal medullary inters titial fluid → pr ides t osmot gr dientnecessayforw t r bsor ion t ov he ic a r aer ea pt o occurin t pr he esence ofhigh l el ofA ev s DH.• A erpa t t int st ium, w t is car byt v sar aba int t bl ft ssing o he er it aer ried he a ect ck o he ood. 146
  • 131. PRODUC TION OF C ONC E NTRA TE D URINEReabs orption of Water in Pres ence of ADH:In PC T, loop of Henle & early DC T: -Sa a in for t ofdil e ur (see befor me s maion ut ine e). -T t a fl r ching t l t DCTis hyposmot (10 mOsm/). he ubul r uid ea he ae ic 0 LLate DC T: -A ↑ t w t per bil yoft pr lcels oft l t DCT DH he aer mea it he incipa l he ae . ⇒ Wt is r bsor unt t osmol r yoft DCTequas t tofsurounding int st ia fl in r l aer ea bed il he ait he l ha r er it l uid ena corex (3 0mOsm/). t 0 LC Ds : -A ↑ t w t per bil yofpr lcels ofCDs. DH he aer mea it incipa l -A t t a fl fl s t ough t CDs, itpa t ough r s he ubul r uid ow hr he sses hr egions ofincr sing hyper ait t ad ea osmol r y ow r t innermedula he l. -Wt is r bsor fr t CDs unt t osmol r yoft t a fl equas t toft surounding aer ea bed om he il he ait he ubul r uid l ha he r int st ia fl er it l uid. ⇒ T osmol r yoft fina ur r ches 120 mOsm/. he ait he l ine ea 0 147 L
  • 132. II. PRODUC TION OF C ONC E NTRA TE D URINE (cont.) 148
  • 133. II. PRODUC TION OF C ONC E NTRA TE D URINE (cont.) 149
  • 134. The C ounterc urrent S ys tem• T count curentsyst is r he er r em esponsibl fort cr t &ma ena ofagr dual incr sing e he eaion int nce a ly ea hyper ait in t r lmedulayint st ium, w is essent lforena ing t kidneyt osmol r y he ena l r er it hich ia bl he o concentae ur in t pr r t ine he esence ofenough cir aing A cul t DH.• T osmot gr dientis due t a his ic a o ccumul t ofsol es (pr r yNa &ur )in gr texcess ofw t in aion ut imail Cl ea ea aer t medulayint st ium. he l r er it• Once t high sol e concentaion in medulaha been a ed, itis ma a byabaa out owof he ut rt l s chiev int ined l nced fl sol es &w t in t medula ut aer he l.• T osmot gr dientis his ic a 1. est bl byt l ofHenl w a s a ac ounterc urrent multiplier. a ished he oop e, hich ct s 2. pot iaed byt colect duct w al s urea recycling t occur ent t he l ing , hich low o . 3 ma a byt v sar a w a a counterc urrent exchangers . . int ined he a ect , hich ct s 150
  • 135. THE C OUNTE RC URRE NT S YS TE MLoop of Henle A cting as C ounter C urrent Multiplier How does the renal medulla become hyperos motic?1. Befor t osmot gr dientoft medulais est bl e he ic a he l a ished, t osmol r yis t sa t oughoutt he ait he me hr he nephr (3 0mOsm/). on 0 L2. T a iv pumping ofNa outoft thick as c ending limb occur w houtconcomit nt he ct e Cl he s it a movementofw t → ↓ in osmol r yoft a fl inside a aer ait ubul r uid scending l (20 mOsm/)&↑ in imb 0 L osmol r yofmedulayint st ia fl (4 0mOsm/). ait l r er it l uid 0 L3 A fl pa dow t des c ending limb, itr ches osmot equil ium w h medulay . s uid sses n he ea ic ibr it lr int st ium due t osmosis ofw t outofdescending l [Int st ia osmol r yis ma a a 4 0 er it o aer imb. er it l ait int ined t 0 mOsm/ due t cont ta tofions outoft a L o inued r nspor imb.] T t e is agr dua ↑ in hick scending l hus, her a l t a fl osmol r ya itfl s t ads t ha pin bend. ubul r uid ait s ow ow r he ir4 A mor fl ent s descending l fr PCT hyper ic fl pr iousl pr in descending . s e uid er imb om , osmot uid ev y esent l nowfl s int t a imb ow o hick scending l imb. 151
  • 136. THE C OUNTE RC URRE NT S YS TE M Loop of Henle A cting as C ounter C urrent Multiplier5. M e Na is pumped fr t a or Cl om hick scending l int int st ium, but w t r ins in t e. T imb o er it aer ema ubul his cont unt a20 mOsm/ osmot gr dientis est bl inues il 0 L ic a a ished. Nowosmol r yin medulayint st ium ha ait l r er it s r furhert 50 mOsm/. isen t o 0 L6. Once a in t fl in descending l equil aes w h hyper ic medulay int st ia fl now ga he uid imb ibr t it osmot l r er it l uid, r ching 50 mOsm/ a t t ea 0 L t he ip.7. T st ae r t ov & ov , a hese eps r epeaed er er dding mor & mor sol e t t medulain excess ofw t . T e e ut o he l aer his pr ocess gr dual ta sol es in t medula ev ual r ising t int st ia osmol r y t 120 a ly r ps ut he l , ent ly a he er it l ait o 0 mOsm/. L• Ov al t pr essiv ta t of Na fr t t a fl int t int st ium r t in t er l, he ogr e r nspor Cl om he ubul r uid o he er it esuls he est bl a ishmentofal udina osmot gr dientin t medula ongit l ic a he l.⇒ Thus , the countercurrent arrangement of the loop of Henle multiplies a relatively s mall trans epithelial os motic gradient into a large longitudinal gradient. 152
  • 137. C OUNTE RC URRE NT MULTIPLIE R S YS TE M IN LOOP OF HE NLE 153
  • 138. Role of DC T & C Ds in Urine C oncentration• T a fl fl ing fr l ofHenl int DCTis dil e. ubul r uid ow om oop e o ut• T eal DCTfurherdil es t fl beca t segment l t a he ry t ut he uid, use his , ike he scending l ofl ofHenl imb oop e, a iv yta t Na outoft e, butis imper bl t w t . ct el r nspors Cl ubul mea e o aer• W h high A concentaions, l t DCT&corica CD become highl per bl t w t → large it DH r t ae t l y mea e o aer amounts of water are reabs orbed from the tubule into the c ortical inters titium, w e itis sw a a byt per ubul rca l r her ept w y he it a pilaies.• W h high A l el t e is furherw t r bsor ion fr medulayCDs t int st ium. How er t it DH ev s, her t aer ea pt om lr o er it ev , he amountofw t is r aiv ysmalcompaed w h t ta t t corica int st ium. R bsor w t aer el t el l r it ha dded o he t l er it ea bed aer is quickl car a a byv sar aint v y ried w y a ect o enous bl ood.N.B . T fa t tl r a s ofw t ae r bsor int t corex, r t t n int t medula hel he ct ha age mount aer r ea bed o he t aher ha o he l , ps t pr v t high medulayint st ia fl osmol r y. o eser e he l r er it l uid ait• T in t pr hus, he esence ofA t fl a t end ofCDs ha t sa osmol r ya t medulay DH, he uid t he s he me ait s he lr int st ium (120 mOsm/). er it 0 L⇒ Byr bsor a much w t a possibl t kidneys for ahighl concentaed ur w e a ea bing s aer s e, he m y r t ine hil dding w t ba t E &compensaing fordeficitofbodyw t . aer ck o CF t aer 154
  • 139. Urea Rec ycling• he esence ofA urea c ontibutes 40% t t medulayint st ia osmol r y(= In t pr DH, o he l r er it l ait 50 mOsm/)bypa e ur r bsor ion fr t innermedulayCDs int t int st ium. 0 L ssiv ea ea pt om he lr o he er itMec hanis m: -Ascending l ofl ofHenl DCT corica CDs &out medulayCDs ae imper bl t ur . imb oop e, , t l er lr r mea e o ea -A w t is r bsor fr l t DCT corica &out medulayCDs, ur concent aion ↑ r pidl s aer ea bed om ae , t l er lr ea rt a y. -In innermedulayCDs, furherw t r bsor ion t kes pl ce, so t tur concentaion r ev mor lr t aer ea pt a a ha ea r t ises en e. T ur diffuses outoft t e int r lint st ium beca t segmentis highl per bl t hus, ea he ubul o ena er it use his y mea e o ur , a A incr ses t per bil yev mor ea nd DH ea his mea it en e. -Amoder t shae oft ur t tmov int medulayint st ium diffuses int t descending l of ae r he ea ha es o l r er it o hin imb l ofHenl so t titpa a in in t a fl Itr cul t sev a t befor itis excr ed. oop e, ha sses ga ubul r uid. ecir aes er l imes e et E ch t aound itcontibut t ahigherconcentaion ofur in int st ium. a ime r r es o rt ea er it⇒ Ur r cul t pr ides a a iona mecha forfor ahyper icmedula ea ecir aion ov n ddit l nism ming osmot l. 155
  • 140. URE A RE C YC LING 156
  • 141. THE C OUNTE RC URRE NT S YS TE MVas a Recta as C ountercurrent E xchanger• Bl mustbe pr ided t r lmedulat suppl it met bol needs, butw houtaspecia bl fl syst ood ov o ena l o y s a ic it l ood ow em, sol es pumped int t medulabycount curentmulipl w d r pidl getl . ut o he l er r t ier oul a y ost• T e ae 2 specia feaur in medulay bl fl t t contibut t t pr v t of t high sol e her r l t es l r ood ow ha r e o he eser aion he ut concentaions: rt1. The medullary blood flow is low (onl 1- of t a R → sufficient for met bol y 2% ot l BF) a ic needs oftissues, butminimizes sol e l ut oss.2. The vas a rec ta s erve as countercurrent exchangers .C ountercurrent E xchange Mechanis m:• A bl des c ends into medulla, itbecomes mor &mor concentaed, byga sat&l s ood e e rt ining l osing w t . A t t ofv sar abl ha aconcentaion of1200 mOs m/L. aer t he ips a ect ood s rt• A bl a s ood scends ba t ad corex, t r er sequence occur a bl l v v sar ais onl sl l ck ow r t he ev se s, nd ood ea ing a ect y ighty hyperos motic to normal plas ma.⇒ Dur it pa ge t ough medula bl ha r ed t excess sat& w t t tha e been a by t ing s ssa hr l , ood s emov he l aer ha v dded he ta tpr r nspor ocesses occuring in t deeperr r he egions oft medula he l.⇒ T t U- pe ofv sar amaintains the concentration of s olutes est bl hus, he sha a ect a ished bycount curentsyst er r em. 157
  • 142. Vas a Rec ta as C ounterc urrent E xc hanger 158
  • 143. Diures is and diuretics Diures is is an increas e in the rate of urine output.(A ) H2O diures isIncreas e H2O intake → decreas e Os motic. Pr → decreas e A DH → decreas e facultative H2O reabs orption i.e. Urine large volume and hypotonic.(B ) Os motic diures isUnreabs orbable s olute in PC T→ decreas e obligatory H2O reabs orption → decreas e Na+ concentration in tubular fluid → decreas e os molarity of medullary inters titium → decreas e facultative H2O reabs orption.-Urine: large volume and is otonic or hypertonic.(C ) Pres s ure diures isIncreas e in arterial blood pres s ure leads to:• ↑G FR.• Inhibition of rennin angiotens in s ys tem → ↓ renin and angiotens in II production.
  • 144. (4) Diuretic drugs (A)Thiazides : inhibitNar bsor ion in DCT ea pt . (B) Aldos terone inhibitors : (Potas s ium-s paring diuretics ) e.g. alldactone: inhibitNaKexcha in DCTa colect t es → decr se ser - nge nd l ing ubul ea um Naa incr se ser K+ . nd ea um (C) Carbonic anhydras e inhibitors e.g. acetazolamide (Diamox). Itinhibit cabonic a a enzyme → decr se Hsecr ion → decr se Na s r nhydr se ea et ea a HCO3-r bsor ion in PCTa incr se Ksecr ion in DCT nd ea pt nd ea et → incr se Na HCO3 &Kexcr ion in ur ea , et ine. M yl d t acidos is . a ea o (D) Loop diuretics e.g. frus emide (las ix): inhibitNaK- cota t s in t t a - 2Cl r nsporer he hick scending l imb ofl ofHenl oop e.
  • 145. The act ofMicturition
  • 146. Micturition Reflex• A s bladder fills s ens ory s tretch receptors s end s ignals via pelvic nerves to s acral s egments of s pinal c ord.• Paras ympathetic s timulation of the bladder s mooth mus cle via the s ame pelvic nerves occurs .• It is “ s elf-regenerative” , s ubs ides , then re- generates again until the external s phincter is relaxed and urination can
  • 147. InnervationParasympathetic Pre-glanglionic  S2, S3, S4 unite to form Pelvic nerves Post-ganglionic  onto detrusor muscle & internal sphincter Sympathetic Pre-ganglionic  L1, L2, L3 Post-ganglionic  onto trigone, neck, & internal sphincter Little to do with bladder contraction o--------- o------------------------------------------ Ach NE
  • 148. Innervation con’t…Afferents (sensory nerves) Pelvic nerve: impulses due to bladder fullness; micturition reflex; pain impulses Hypogastric nerve: pain impulses Pudendal nerve: sensory impulses from urethraSomatic Efferent (Pudendal nerve) Impulses originate in S1 and S2; innervate external sphincter Mediate voluntary control of micturition
  • 149. Anatomy of Micturition
  • 150. • Internal s phincter-det usormuscl in t bl dderneck w t nor lykeeps t r e he a hose one mal he bl dderneck a post ior a nd erur hr empt ofur a t efor pr ent et a y ine nd her e ev sempt oft bl dderunt t pr e in t ma patoft ying he a il he essur he in r he bl dderexceeds acr ica l el a it l ev• E xternal s phincter-l yerofv unt r skel a muscl w surounds t ur hr a it a ol ay et l e hich r he et a s pa t ough t ur a dia a sses hr he ogenit l phr gm-underv unt r cont ola ca conciousl pr entur t ev w ol ay r nd n y ev inaion en hen inv unt r cont ol ae at ing t empt t bl dder ol ay r s r tempt o y he a
  • 151. Bladder Filling and MicturitionBladder Filling:1. Empty bladder: 0 pressure2. 30 - 50 mls of urine  5 - 10 cm H2O3. 50 - 300 ml little pressure change4. With filling, increased activity of external sphincter (maintains continence, or control of excretory functions)5. > 300 - 400 ml  discomfort; leads to urgency Start of Micturition: 1. As bladder fills, micturition (bladder) contractions begin to appear a. Last from a few seconds to more than a minute b. Pressure peaks (micturition waves) may rise a few cm H2O to more than 100 cm H2O c. Caused by micturition reflex
  • 152. Micturition Con’t…2. Micturition reflex (does not need the brain) a. Filling stimulates sensory stretch receptors b. Afferent impulses in Pelvic nerve c. Signal reflexively sent back to bladder via efferent parasympathetic fibers in the Pelvic nerve d. Detrusor muscle contracts, then relaxes 2. Micturition reflex - continued e. As bladder fills, micturition reflex occurs more frequently, with greater contraction of bladder wall (positive feedback loop) • Micturition powerful enough then another signal is sent through Pudendal nerve to inhibit external sphincter (internal relaxes passively when pressure is 20 - 40 cm H2O) • Voluntary relaxation of external sphincter allows for urination • Flow thru urethra stimulates parasympathic system, sustaining bladder contraction
  • 153. Micturition Reflex• stet r ex init t byfiling oft bl dderw h ur w r t in bl dder r ch efl iaed l he a it ine hich esuls a w l cont a ion al r ct• mediaed bysensor stet r or in t bl dderw l,special byr or in t y r ch ecept s he a al ly ecept s t post iorur hr he er et a BLADDER Detrusor muscle Sensory stretch receptor PELVIC NERVE PELVIC NERVE (Parasympathetic (Sensory Fibers) Motor Fibers) SPINAL CORD (sacral segments)
  • 154. Voluntary Control of Micturition1. Micturition reflex can be inhibited by: a. Pons b. Cerebral cortex2. Voluntary contraction of external bladder sphincter means emptying can be delayed even if a micturition reflex occurs (can go and stop voluntarily)3. Voluntary emptying: a. Contraction of abdominal muscles causes ↑ pressure in bladder  micturition reflex and inhibition of external sphincter b. Voluntary relaxation of external sphincter Problems: Atonic Bladder - destruction of sensory fibers Traumatic spinal cord injury Overflow incontinence. Automatic Bladder - spinal cord injury above sacral region Micturition reflex is intact but uncontrolled
  • 155. Micturition A bnormalities• A tonic B ladder - des truc tion of s ens ory fibers – Traumatic s pinal c ord injury – Overflow inc ontinenc e.• A utomatic B ladder - s pinal cord injury above s ac ral region – Mic turition reflex is intact but unc ontrolled
  • 156. E valuation of Kidney function
  • 157. The kidney function tes ts are grouped into:• Tes ting renal blood flow. • Tes ting glomerular filtration. • Tes ting tubular activity.
  • 158. A s s es s ment of Renal B loodFlowThe volume by PAH clearance• PA H is freely filtered and s ecreted but not reabs orbed.• The extraction ratio of PA H is 90% i.e. only 90% of PA H in renal arterial blood is removed in a s ingle circulation. This is becaus e only 90% of RPF go to the nephrons . RPF = about 625 mL/min.• A derivative of PA H, radioactive iodine PAH may be us ed. The concentration of this s ubs tance in blood and urine is es timated by determination of its radioactivity.The dis tribution
  • 159. As s es s ment of Glomerular F iltration1. Inulin c learanc e.2. C reatinine clearanc e.3. Urea c learanc e.4. B lood urea and s erum c reatinine blood urea; normal 20-40 mg/dL. (nons pecific tes t) Plas ma creatinine; normal 0.6 – 1.5 mg/dL. (more ac c urate).
  • 160. Inulin• Pol chaide mol e w h M = 520 yssa r ecul it W 0• Notpr oduced in t body he• R es IVinfusion equir• F eel filer r y t ed• Notr bsor orsecr ed ea bed et• Used t det mine G R~ r dioa iv iot l mae a o er F a ct e haa t nd cr t eainine
  • 161. Inulin• G aizaions: ener l t2. F t ed a notr bsor orsecr ed – cl r nce r t ofa iler nd ea bed et eaa ae subst nce equas t tofinul a l ha in3. R bsor -cl r nce r t ofasubst nce is l t n t tof ea bed eaa ae a ess ha ha inulin4. Secr ed -cl r nce r t ofasubst nce is gr t t n t t et eaa ae a eaer ha ha ofinul in
  • 162. C reatinine• By- oductofmuscl met bol pr e a ism• Cl r amostent el bygl ul rfilr t eaed l ir y omer a t aion• Caaso be used t a G R l o ssess F• Er s: ror Asmalal mountis secr ed byt t es: excr ed cr t et he ubul et eainine exceeds amountfiler t ed Er in mea in pl smacr t ov est t ofpl sma ror sur a eainine: er imae a cr t ainine
  • 163. As s es s ment of TubularF unction(1) Tes ts of tubular ability to c onc entrate and dilute urine • S pec ific gravity of urine • Water c onc entration tes t • Water dilution tes t(2) Tes ts of tubular ability to abs orbe gluc os e and s ec rete PA H G luc os e tubular maximum (Tm G luc os e) Para-amino hippuric acid tubular maximum (Tm PA H)
  • 164. Tubular trans port maximum (Glucos e & PA H)
  • 165. PA HA tubular maximum (Tm PA HA )
  • 166. Use of Clearance to Quantify Kidney FunctionTerm Equation UnitsClearance rate (Cs) ml/minGlomerular filtration rate(GFR)Clearance ratio NoneEffective renal plasma flow ml/min(ERPF)
  • 167. Renal plasma flow ml/min(RPF)Renal blood flow (RBF) ml/minExcretion rate Excretion rate = Us x V mg/min, mmol/min, or mEq/minReabsorption rate Reabsorption rate = Filtered load – Excretion mg/min, rate mmol/min, or = (GFR x Ps) – (Us x V) mEq/minSecretion rate Secretion rate = Excretion rate – Filtered load mg/min, mmol/min, or mEq/min
  • 168. Substance Clearance rate (ml/min)Glucose 0Sodium 0.9Chloride 1.3Potassium 12.0Phosphate 25.0Inulin 125.0Creatinine 140.0
  • 169. Water andE lectrolyte B alance
  • 170. I. C ontrol of E C F volume (defens e of volume)Factors controlling E C F volumel) ADH When ECF volume decreas esA ca incr se in w t r bsor ion bydist lt es a colect duct oft kidney→ incr se E DH using ea aer ea pt a ubul nd l ing s he ea CF v ume. ol When ECF volume increas esItca inhibit ofA secr ion t tincr ses w t excr ion a decr ses E v ume. uses ion DH et ha ea aer et nd ea CF ol2) Role of the kidney When ECF volume decreas esst aion ofadost one secr ion. imul t l er etincr se in t a r bsor ion ofNa ea ubul r ea pt . When ECF v olume increas esinhibitr ea ofadost one w incr se ur r excr ion ofNa el se l er hich ea inay eta w t ca decr se ofE v ume. nd aer using ea CF ol
  • 171. I. C ontrol of E C F volume (defens e of volume)3) Renin-angiotens in-aldos terone s ys tem:W E v ume decr ses, decr se in bl pr e st aes r secr ion fr t hen CF ol ea ea ood essur imul t enin et om he j a umer a uxt gl ul ra r t oft kidney. ppaaus he
  • 172. I. C ontrol of E C F volume (defens e of volume)4) Thirs t mechanis m:W hen ECF volum e d ecrease: t st aes t st cent in hypot l mus his imul t hir er haa t tl ds t incr se in w t int ke. ha ea o ea aer a5) Volume receptors :Pr in t ar a gr tv nea t heat esent he t ia nd ea eins r he r.W E v ume decr ses, t send impul t t hypot l mus ca hen CF ol ea hey ses o he haa using r ex efl incr se in sympahet dischage w h a iv t ofr a ensin syst ea t ic r it ct aion enin- ngiot em.6) A trial natriuretic peptide (A NP):Incr se in E v ume ca r ea ofA w a s ea CF ol uses el se NP hich cton t kidneyt incr se Na a w t excr ion. he o ea + nd aer et
  • 173. II. C ontrol of E C F Os molarity (defens e of tonic ity)Fac tors controlling E C F os molarity 1) ADH os moreceptor mechanis m. 2) Thirs t mechanis m.When ECF os molarity increas e (hypertonicity)a) S timulate os moreceptors in hypothalamus : which increas e A DH s ecretion and increas e water reabs orption in kidney.b) S timulation of thirs t s ens ation: Hypertonicity s timulates thirs t center in the hypothalamus that increas e water intake. S timuli which increas e thirs t includeIncreas ed extracellular fluid os molarity.Decreas e in extracellular fluid volume.Decreas e in arterial pres s ure.A ngiotens in II.Drynes s of mouth.Conv ers ely when os molarity decreas e (hypotonicity)a- Inhibition of ADH s ecretion .b- Inhibition of thirs t center.
  • 174. II. C ontrol of E C F Os molarity (defens e of tonic ity)