Y khoa, y dược - The urinary system: Part B

25 The Urinary System: Part BTubular ReabsorptionA selective transepithelial processAll organic nutrients are reabsorbedWater and ion reabsorption are hormonally regulatedIncludes active and passive processTwo routesTranscellularParacellularTubular ReabsorptionTranscellular routeLuminal membranes of tubule cellsCytosol of tubule cellsBasolateral membranes of tubule cellsEndothelium of peritubular capillariesTubular ReabsorptionParacellular routeBetween cellsLimited to water movement and reabsorption of Ca2+, Mg2+, K+, and some Na+ in the PCT where tight junctions are leakyFigure 25.13Activetransport Passivetransport Peri-tubularcapillary2443311243Filtratein tubulelumenTranscellularParacellularParacellularTight junctionLateral intercellular spaceCapillaryendothelialcellLuminalmembraneSolutesH2OTubule cellInterstitialfluidTranscellularBasolateralmembranes1 Transport across the luminal membrane.2 Diffusion through the cytosol.4 Movement through the interstitial fluid and into the capillary.3 Transport across the basolateral membrane. (Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces.)Movement via thetranscellular route involves:The paracellular routeinvolves: • Movement through leaky tight junctions, particularly in the PCT.Sodium ReabsorptionNa+ (most abundant cation in filtrate)Primary active transport out of the tubule cell by  Na+-K+ ATPase in the basolateral membrane Na+ passes in through the luminal membrane by secondary active transport or facilitated diffusion mechanismsSodium ReabsorptionLow hydrostatic pressure and high osmotic pressure in the peritubular capillariesPromotes bulk flow of water and solutes (including Na+)Reabsorption of Nutrients, Water, and IonsNa+ reabsorption provides the energy and the means for reabsorbing most other substancesOrganic nutrients are reabsorbed by secondary active transportTransport maximum (Tm) reflects the number of carriers in the renal tubules available When the carriers are saturated, excess of that substance is excretedReabsorption of Nutrients, Water, and IonsWater is reabsorbed by osmosis (obligatory water reabsorption), aided by water-filled pores called aquaporinsCations and fat-soluble substances follow by diffusionFigure 25.141 At the basolateral membrane, Na+ is pumped into the interstitial space by the Na+-K+ATPase. Active Na+ transport creates concentration gradients that drive:2 “Downhill” Na+ entry at theluminal membrane.4 Reabsorption of water byosmosis. Water reabsorptionincreases the concentration of the solutes that are left behind. These solutes can then be reabsorbed asthey move down their concentration gradients:3 Reabsorption of organic nutrients and certain ions by cotransport at the luminal membrane.5 Lipid-solublesubstances diffuse by the transcellular route.6 Cl– (and other anions), K+, and urea diffuse by the paracellular route.Filtratein tubulelumenGlucoseAmino acidsSome ionsVitaminsLipid-solublesubstancesNucleusTubule cellParacellularrouteInterstitialfluidPeri-tubularcapillaryTight junction Primary active transport Passive transport (diffusion) Secondary active transport Transport protein Ion channel or aquaporinCl–, Ca2+, K+and otherions, ureaCl–3Na+2K+3Na+2K+K+H2ONa+654321Reabsorptive Capabilities of Renal Tubules and Collecting DuctsPCTSite of most reabsorption65% of Na+ and waterAll nutrientsIonsSmall proteinsReabsorptive Capabilities of Renal Tubules and Collecting DuctsLoop of HenleDescending limb: H2O Ascending limb: Na+, K+, ClReabsorptive Capabilities of Renal Tubules and Collecting DuctsDCT and collecting ductReabsorption is hormonally regulatedCa2+ (PTH)Water (ADH)Na+ (aldosterone and ANP)Reabsorptive Capabilities of Renal Tubules and Collecting DuctsMechanism of aldosteroneTargets collecting ducts (principal cells) and distal DCTPromotes synthesis of luminal Na+ and K+ channelsPromotes synthesis of basolateral Na+-K+ ATPasesTubular SecretionReabsorption in reverse K+, H+, NH4+, creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrateDisposes of substances that are bound to plasma proteinsTubular SecretionEliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid)Rids the body of excess K+Controls blood pH by altering amounts of H+ or HCO3– in urineRegulation of Urine Concentration and VolumeOsmolalityNumber of solute particles in 1 kg of H2OReflects ability to cause osmosisRegulation of Urine Concentration and VolumeOsmolality of body fluidsExpressed in milliosmols (mOsm)The kidneys maintain osmolality of plasma at ~300 mOsm, using countercurrent mechanismsCountercurrent MechanismOccurs when fluid flows in opposite directions in two adjacent segments of the same tubeFiltrate flow in the loop of Henle (countercurrent multiplier)Blood flow in the vasa recta (countercurrent exchanger)Countercurrent MechanismRole of countercurrent mechanismsEstablish and maintain an osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through the medullaAllow the kidneys to vary urine concentrationFigure 25.15CortexMedullaCountercurrent Multiplier: Loop of HenleDescending limbFreely permeable to H2O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluidFiltrate osmolality increases to ~1200 mOsm Countercurrent Multiplier: Loop of HenleAscending limbImpermeable to H2OSelectively permeable to solutesNa+ and Cl– are passively reabsorbed in the thin segment, actively reabsorbed in the thick segmentFiltrate osmolality decreases to 100 mOsmFigure 25.16aLoop of HenleOsmolalityof interstitialfluid(mOsm)InnermedullaOutermedullaCortex Active transport Passive transportWater impermeable(a) Countercurrent multiplier. The long loops of Henle of the juxtamedullary nephrons create the medullary osmotic gradient.The ascending limb:• Impermeable to H2O• Permeable to NaClFiltrate becomes increasingly dilute as NaCl leaves, eventually becoming hypo-osmotic to blood at 100 mOsm in the cortex. NaCl leaving the ascending limb increases the osmolality of the medullary interstitial fluid.Filtrate entering the loop of Henle is isosmotic to both blood plasma and cortical interstitial fluid.The descending limb:• Permeable to H2O• Impermeable to NaClAs filtrate flows, it becomes increasingly concentrated as H2Oleaves the tubule by osmosis. The filtrate osmolality increases from 300 to 1200 mOsm. H2OH2OH2OH2OH2OH2OH2ONaCINaCINaCINaCINaCIUrea RecyclingUrea moves between the collecting ducts and the loop of HenleSecreted into filtrate by facilitated diffusion in the ascending thin segmentReabsorbed by facilitated diffusion in the collecting ducts deep in the medullaContributes to the high osmolality in the medullaCountercurrent Exchanger: Vasa RectaThe vasa rectaMaintain the osmotic gradientDeliver blood to the medullary tissuesProtect the medullary osmotic gradient by preventing rapid removal of salt, and by removing reabsorbed H2OFigure 25.16bNaCIH2ONaCIH2ONaCIH2ONaCIH2ONaCIH2ONaCIH2ONaCIH2ONaCIH2OVasa rectaTo veinOsmolalityof interstitialfluid(mOsm)Blood fromefferent arterioleInnermedullaOutermedullaCortex Passive transport(b) Countercurrent exchanger. The vasa recta preserve the medullary gradient while removing reabsorbed water and solutes.The vasa recta:• Highly permeable to H2O and solute• Nearly isosmotic to interstitial fluid due to sluggish blood flowBlood becomes more concentrated as it descends deeper into the medulla and less concentrated as it approaches the cortex.Formation of Dilute UrineFiltrate is diluted in the ascending loop of HenleIn the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urineNa+ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm Figure 25.17a Active transport Passive transport(a) Absence of ADH Large volumeof dilute urineCollecting ductCortexNaCINaCINaCIUreaOutermedullaInnermedullaDCTH2OH2ODescending limbof loop of HenleFormation of Concentrated UrineDepends on the medullary osmotic gradient and ADH ADH triggers reabsorption of H2O in the collecting ductsFacultative water reabsorption occurs in the presence of ADH so that 99% of H2O in filtrate is reabsorbed Figure 25.17b Active transport Passive transportSmall volume ofconcentrated urineCortexNaCINaCINaCIUreaUreaH2OH2OH2OH2OH2OH2OH2OOutermedullaInnermedulla(b) Maximal ADHDCTDescending limbof loop of HenleCollecting ductH2OH2ODiureticsChemicals that enhance the urinary outputOsmotic diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient)ADH inhibitors such as alcoholSubstances that inhibit Na+ reabsorption and obligatory H2O reabsorption such as caffeine and many drugsFigure 25.18aCortexOutermedullaInnermedulla(a)(b)(c)(e)(d)Na+ (65%)GlucoseAmino acidsH2O (65%) and many ions (e.g.Cl– and K+)300Milliosmols6001200Blood pH regulationH+,NH4+HCO3–SomedrugsActive transport(primary or secondary)Passive transport(a) Proximal convoluted tubule: • 65% of filtrate volume reabsorbed • Na+, glucose, amino acids, and other nutrients actively transported; H2O and many ions follow passively • H+ and NH4+ secretion and HCO3– reabsorption to maintain blood pH (see Chapter 26) • Some drugs are secretedFigure 25.18bH2O(b) Descending limb of loop of Henle • Freely permeable to H2O • Not permeable to NaCl • Filtrate becomes increasingly concentrated as H2O leaves by osmosis (a)(b)(c)(e)(d)CortexOutermedullaInnermedulla300Milliosmols6001200Active transport(primary or secondary)Passive transportFigure 25.18cNa+UreaCl–Na+Cl–K+(c) Ascending limb of loop of Henle • Impermeable to H2O • Permeable to NaCl • Filtrate becomes increasingly dilute as salt is reabsorbed(a)(b)(c)(e)(d)CortexOutermedullaInnermedulla300Milliosmols6001200Active transport(primary or secondary)Passive transportFigure 25.18dNa+; aldosterone-regulatedCa2+; PTH-regulatedCl–; follows Na+(d) Distal convoluted tubule • Na+ reabsorption regulated by aldosterone • Ca2+ reabsortion regulated by parathyroid hormone (PTH) • Cl– cotransported with Na+ (a)(b)(c)(e)(d)CortexOutermedullaInnermedulla300Milliosmols6001200Active transport(primary or secondary)Passive transportFigure 25.18eBlood pHregulationUrea;increasedby ADHNa+K+H+HCO3–NH4+H2O regulatedby ADHRegulated byaldosterone:(e) Collecting duct • H2O reabsorption through aquaporins regulated by ADH • Na+ reabsorption and K+ secretion regulated by aldosterone • H+ and HCO3– reabsorption or secretion to maintain blood pH (see Chapter 26) • Urea reabsorption increased by ADH(a)(b)(c)(e)(d)CortexOutermedullaInnermedulla300Milliosmols6001200Active transport(primary or secondary) Passive transportRenal ClearanceVolume of plasma cleared of a particular substance in a given time Renal clearance tests are used toDetermine GFRDetect glomerular damageFollow the progress of renal diseaseRenal ClearanceRC = UV/PRC = renal clearance rate (ml/min)U = concentration (mg/ml) of the substance in urineV = flow rate of urine formation (ml/min)P = concentration of the same substance in plasmaRenal ClearanceFor any substance freely filtered and neither reabsorbed nor secreted by the kidneys (e.g., insulin),RC = GFR = 125 ml/minIf RC 125 ml/min, the substance is secreted (most drug metabolites)Physical Characteristics of UrineColor and transparencyClear, pale to deep yellow (due to urochrome)Drugs, vitamin supplements, and diet can alter the colorCloudy urine may indicate a urinary tract infectionPhysical Characteristics of UrineOdorSlightly aromatic when freshDevelops ammonia odor upon standing May be altered by some drugs and vegetablesPhysical Characteristics of UrinepH Slightly acidic (~pH 6, with a range of 4.5 to 8.0)Diet, prolonged vomiting, or urinary tract infections may alter pHSpecific gravity1.001 to 1.035, dependent on solute concentrationChemical Composition of Urine95% water and 5% solutesNitrogenous wastes: urea, uric acid, and creatinineOther normal solutesNa+, K+, PO43–, and SO42–, Ca2+, Mg2+ and HCO3–Abnormally high concentrations of any constituent may indicate pathologyUretersConvey urine from kidneys to bladderRetroperitonealEnter the base of the bladder through the posterior wallAs bladder pressure increases, distal ends of the ureters close, preventing backflow of urine UretersThree layers of wall of ureterLining of transitional epitheliumSmooth muscle muscularisContracts in response to stretchOuter adventitia of fibrous connective tissue Figure 25.20LumenAdventitiaCircularlayerLongitudinallayerTransitionalepitheliumLaminapropriaRenal CalculiKidney stones form in renal pelvisCrystallized calcium, magnesium, or uric acid salts Larger stones block ureter, cause pressure and pain in kidneysMay be due to chronic bacterial infection, urine retention, Ca2+ in blood, pH of urineUrinary BladderMuscular sac for temporary storage of urineRetroperitoneal, on pelvic floor posterior to pubic symphysisMales—prostate gland surrounds the neck inferiorlyFemales—anterior to the vagina and uterusUrinary BladderTrigoneSmooth triangular area outlined by the openings for the ureters and the urethraInfections tend to persist in this regionUrinary BladderLayers of the bladder wall Transitional epithelial mucosaThick detrusor muscle (three layers of smooth muscle)Fibrous adventitia (peritoneum on superior surface only)Urinary BladderCollapses when empty; rugae appearExpands and rises superiorly during filling without significant rise in internal pressure Figure 25.21bUreterTrigonePeritoneumRugaeDetrusor muscleBladder neckInternal urethralsphincterExternal urethralsphincterUrogenital diaphragmUrethraExternal urethralorificeUreteric orifices(b) Female.UrethraMuscular tubeLining epitheliumMostly pseudostratified columnar epithelium, exceptTransitional epithelium near bladderStratified squamous epithelium near external urethral orificeUrethraSphinctersInternal urethral sphincterInvoluntary (smooth muscle) at bladder-urethra junctionContracts to openExternal urethral sphincterVoluntary (skeletal) muscle surrounding the urethra as it passes through the pelvic floor UrethraFemale urethra (3–4 cm):Tightly bound to the anterior vaginal wall External urethral orifice is anterior to the vaginal opening, posterior to the clitorisFigure 25.21bUreterTrigonePeritoneumRugaeDetrusor muscleBladder neckInternal urethralsphincterExternal urethralsphincterUrogenital diaphragmUrethraExternal urethralorificeUreteric orifices(b) Female.UrethraMale urethraCarries semen and urineThree named regionsProstatic urethra (2.5 cm)—within prostate glandMembranous urethra (2 cm)—passes through the urogenital diaphragmSpongy urethra (15 cm)—passes through the penis and opens via the external urethral orificeFigure 25.21aUreterTrigone of bladderProstateMembranous urethraProstatic urethraPeritoneumRugaeDetrusor muscleBladder neckInternal urethral sphincterExternal urethral sphincterUrogenital diaphragmSpongy urethraErectile tissue of penisUreteric orificesAdventitia(a) Male. The long male urethra has three regions: prostatic, membranous and spongy.External urethral orificeMicturitionUrination or voidingThree simultaneous eventsContraction of detrusor muscle by ANSOpening of internal urethral sphincter by ANSOpening of external urethral sphincter by somatic nervous systemMicturitionReflexive urination (urination in infants)Distension of bladder activates stretch receptorsExcitation of parasympathetic neurons in reflex center in sacral region of spinal cordContraction of the detrusor muscleContraction (opening) of internal sphincterInhibition of somatic pathways to external sphincter, allowing its relaxation (opening)MicturitionPontine control centers mature between ages 2 and 3Pontine storage center inhibits micturition:Inhibits parasympathetic pathwaysExcites sympathetic and somatic efferent pathwaysPontine micturition center promotes micturition: Excites parasympathetic pathwaysInhibits sympathetic and somatic efferent pathwaysFigure 25.22Somatic motornerve activityExternal urethralsphincter opensSympatheticactivityParasympatheticactivityUrinary bladderfilling stretchesbladder wallSpinalcordPromotes micturitionby acting on all threespinal efferentsInhibits micturitionby acting on all three spinal efferentsAllow or inhibit micturitionas appropriateBrainSimplespinalreflexSpinalcordInhibitsParasympathetic activitySympathetic activitySomatic motor nerve activityPontine micturitioncenterPontine storagecenterHigher braincentersDetrusor musclecontracts; internalurethral sphincteropensAfferent impulsesfrom stretchreceptorsMicturitionDevelopmental AspectsThree sets of embryonic kidneys forming successionPronephros degenerates but pronephric duct persists Mesonephros claims this duct and it becomes the mesonephric ductMetanephros develops by the fifth week, develops into adult kidneys and ascendsFigure 25.23aDegeneratingpronephrosUrogenitalridgeDevelopingdigestive tractMesonephrosDuct toyolk sacAllantoisHindgutUretericbud CloacaMesonephric duct(initially, pronephric duct)(a) Week 5Figure 25.23bDegeneratingpronephros(b) Week 6MesonephrosMesonephricductDuct to yolksac AllantoisBody stalkUrogenitalsinus RectumUreteric budMetanephrosDevelopmental AspectsMetanephros develops as ureteric buds that induce mesoderm of urogenital ridge to form nephronsDistal ends of ureteric buds form renal pelves, calyces, and collecting ducts Proximal ends become uretersKidneys excrete urine into amniotic fluid by the third monthCloaca subdivides into rectum, anal canal, and urogenital sinusFigure 25.23cUrogenitalsinus(developingurinarybladder)Metanephros(kidney)GonadRectum(c) Week 7Figure 25.23d(d) Week 8GonadKidneyUrinary bladderUrethraAnusUreterRectumDevelopmental AspectsFrequent micturition in infants due to small bladders and less-concentrated urine Incontinence is normal in infants: control of the voluntary urethral sphincter develops with the nervous systemE. coli bacteria account for 80% of all urinary tract infectionsStreptococcal infections may cause long-term renal damageSexually transmitted diseases can also inflame the urinary tract