*Renal PhysiologyZulkhah Noor

*THE URINARY SYSTEMKidneysBlood supply: Renal arteries and veinsUreterUrinary bladderUrethra

*Anatomi fisiologis ginjal2 ginjal : kanan & kiri, dinding posterior abdomen, di luar rongga peritoneumBerat 1 ginjal : 150 gr, seukuran kepalan tanganSuplai darah : arteri renalis masuk melalui hilum, lalu bercabang menjadi arteri interlobaris a. arkuata a. interlobularis arteriol aferen menuju kapiler glomerulusDarah yang menuju kedua ginjal sebesar : 1200 ml/menit (21% curah jantung)

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*Unit fungsional ginjalUnit fungsional ginjal : nefronTiap ginjal terdiri atas 1 juta nefronTiap nefron dapat membentuk urinGinjal tidak dapat membentuk nefronKomponen utama nefron :Glomerulus dilapisi sel epitel & dibungkus kapsula bowmanTubulus saluran panjang yang mengubah cairan filtrasi glomerulus menjadi urin

*THE NEPHRON IS THE FUNCTIONAL UNIT OF THE KIDNEY

*FUNCTIONS OF THE KIDNEYPengaturan keseimbangan air dan elektrolitPengaturan konsentrasi osmolalitas cairan tubuh dan konsentrasi elektrolitPengaturan keseimbangan asam basaEkskresi produk sisa metabolik (urea, asam urat, metabolit hormon) dan bahan kimia asingPengaturan tekanan arteri (sekresi renin)Sekresi hormon (eritropoetin)Glukoneogenesis (sintesis glukosa)Pengaturan produksi vitamin D3 (bentuk aktif)

*THREE BASIC RENAL PROCESSESGlomerular Filtration: Filtering of blood into tubule forming the primitive urineTubular Reabsorption: Absorption of substances needed by body from tubule to bloodTubular Secretion: Secretion of substances to be eliminated from the body/from the blood into the tubule

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BASIC RENAL PROCESSESGFTRTAUrine ExcretedEfferent ArterioleAfferentArterioleGlomerulusKidneyTubulePeritubular Capillary

*Glomerular FiltrationFirst step in urine formation180 liters/day filteredEntire plasma volume filtered 65 times/dayProteins not filtered: negatively charge large molecules are filtered less easily than pos charge mol of equal mol size.Filterability of substances : decreases with increasing molecular weight

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Forces Involved inGlomerular Filtration

Glomerular CapillaryBlood Pressure : arterial pressureAfferent arteriolar pressureEfferent arteriolar resistance+60Plasma Colloid Osmotic Pressure-321810Bowmans CapsuleHydrostatic Pressure -Net Filtration Pressure+

*Factors that can decrease the GFR and phathophysiologic causes Glom. Capilary Filtration Coef. (Kf) : Renal desease, DM, hypertentioncapilar desease) Bowmans Capsule Hydrostatic Pressure : Urinary tract obstruction (kidney stone) Glom.capilary plasma prot: renal blood flow, plasma protein Systemic arterial pressure : arterial pressure (only small effect)Efferent arteriolar resistance : angiotensin II (drugs that block angiotensin II formation) afferent arteriolar resistance : sympathetic activity, vasoconstrictor hormones (NE, endothelin)

*Autoregulation of GFR and Renal Blood Flow in preventing extreme change in renal excretionProximalNaCl reabsorbtion Arterial pressure Glom.hydrostatic pressure GFRMacula densa NaClreninangiotensin IIefferent arteriolar resistanceafferent arteriolar resistance

*Tubular ReabsorptionBy passive diffusion: water (osmosis)

By primary active transport: Sodium, Potassium,calcium, hydrogen, chloride, a few other ions

By secondary active transport: Sugars and Amino Acids

*Tubular Reabsorption is a Function of the Epithelial Cells Making up the TubuleLumenPlasmaCells

*Sodium ReabsorptionLumenPlasmaCellsPUMP: Na/K ATPaseSodiumPotassiumChlorideWater

*Transport Maximum: maximum rate of substance can be reabsorbed from the tubules

SubstanceTransport maximumGlucose320 mg/minPhosphate0.10 mM/minSulfate0.06 mM/minAmino acids1.5 mM/minUrate15 mg/minLactate75 mg/minPlasma protein30 mg/min

*Reabsorption in Proximal Tubule (Summary) Glucose and Amino Acids67% of Filtered SodiumOther Electrolytes65% of Filtered Water50% of Filtered UreaAll Filtered Potassium

*Glucose and Amino Acids are reabsorbed by secondary active transportThey are actively transported across the apical cell membranes of the epithelial cellsTheir active transport depends on the sodium gradient across this membraneAll other steps are passive

*GLUCOSE REABSORPTION HAS A TUBULAR MAXIMUMRenal threshold (300mg/100 ml)Plasma Concentration of GlucoseGlucoseReabsorbedmg/minFiltered ExcretedReabsorbed

*Tubular SecretionProtons (acid/base balance)

Potassium

Organic ions

*Potassium SecretionLumenPlasmaCellsPUMP: Na/K ATPaseSodiumPotassiumChlorideWater

*Secretion in Proximal Tubule (Summary)Variable Proton secretion for acid/base regulation

Organic Ion secretion

*Filtration, Reabsorbtion, and Excretion Rates different substaces

AmountfilteredAmount AbsorbedAmountexcreted% of filtered Load Reabs.Glu (g/day)1801800100HCO3 (mEq/day4.3204.318299.9Sodium (mEq/day)25.56025.41015099.4Chloride(mEq/day)19.44019.26018099.1Potassium (mEq/day)7566649287.8Urea (mEq/day)46.823.423.450Creatinine (g/day)1.801.80

*REGULATION OF URINE CONCENTRATIONMedullary countercurrent system

Vasopressin

*Medullary countercurrent systemOsmotic gradient established by long loops of Henle

Descending limb

Ascending limb

*Descending limbHighly permeable to water

No active sodium transport

*Ascending limbActively pumps sodium out of tubule to surrounding interstitial fluid

Impermeable to water

*COUNTERCURRENT MAKESTHE OSMOTIC GRADIENT30045060075090010501200 1200From ProximalTubuleTo DistalTubuleCortexMedulla

300450600750900105012001200

10025040055070085010001000ActiveSodiumTransportPassiveWaterTransportLong Loopof Henle

*Secretion in Distal Tubule (Summary)Variable Proton for acid/base regulation

Variable Potassium controlled by aldosterone

*Reabsorption in Distal Tubule (Summary)Variable Sodium controlled by Aldosterone

Chloride follows passively

Variable water controlled by vasopressin

*Rennin-Angiotensin-Aldosterone SystemStimulates Sodium Reabsorption in distal and collecting tubulesNaturetic peptide inhibitsIn absence of Aldosterone, 20mg of sodium/day may be excretedAldosterone can cause 99.5% retention

*Rennin-Angiotensin-Aldosterone SystemFall in NaCl, extracellular fluid volume, arterial blood pressureJuxtaglomerularApparatusReninLiverAngiotensinogen+Angiotensin IAngiotensin IIAldosteroneLungsConvertingEnzymeAdrenalCortexIncreasedSodiumReabsorptionHelpsCorrect

*DUAL CONTROL OF ALDOSTERONE SECRETIONFall in sodiumECF VolumeBlood PressureIncreased PlasmaPotassiumIncreased Aldosterone secretionIncreased TubularPotassium SecretionIncreased UrinaryPotassium SecretionIncreased TubularSodium ReabsorptionFall in UrinarySodium Excretion

*Collecting Duct (Summary)Variable water reabsorption controlled by vasopressin

Variable Proton secretion for acid/base balance

*WHEN VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS ABSENT A DILUTE URINE IS PRODUCEFrom DistalTubuleCortexMedulla

300450600750900105012001200

100100100100100100100100Interstitial FluidCollectingDuctPoresClosedNo Water FlowOut of Duct

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THE OSMOTIC GRADIENT CONCENTRATES THE URINE WHEN VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS PRESENTFrom DistalTubuleCortexMedulla

300450600750900105012001200

300400550700850100011001200Interstitial FluidCollectingDuctPoresOpenPassive Water Flow

*DIURETICSACE Inhibitors (Angiotensin Converting Enzyme): Cause loss of salt---> water followsAtrial Naturetic Peptide (ANP) also inhibits sodium reabsorptionOsmotic diuretics: Are not reabsorbed

*Renal FailureAcute: Sudden onset, rapid reduction in urine output - usually reversible

Chronic: Progressive, not reversible

Up to 75% function can be lost before it is noticeable

*Penyakit penyakit ginjalPenyakit ginjal dikelompokkan :Gagal ginjal akut seluruh atau hampir semua kerja ginjal berhenti tapi membaik mendekati normal lagi Gagal ginjal kronis ginjal secara lambat kehilangan fungsi nefronnya satu per satu yang menurunkan seluruh fungsi ginjalSalah satu penyebab kematian dan cacat tubuh yang penting di seluruh dunia

*Gagal ginjal akutPenyebabnya dibagi 3 :Akibat penurunan suplai darah ke ginjal (gagal ginjal akut prerenal)Gagal ginjal akut intrarenal akibat kelainan di dalam ginjal itu sendiriGagal ginjal akut post renal ada sumbatan pada sistem pengumpul urin dimana saja mulai kaliks sampai keluar kandung kemihEfek pada tubuh : penumpukan air dan garam berlebih, hiperkalemia, asidosis metabolik

*Gagal ginjal kronisDisebabkan hilangnya sejumlah besar nefron secara progresif dan ireversibelPenyebab penting gagal ginjal kronis :Gaqngguan imunologis : glomerulonefritis, lupusGangguan metabolik : diabetes melitusGangguan pembuluh darah ginjal : arterosklerosisInfeksiGangguan tubulus primer (obat, toksin)Obstruksi kronisKelainan kongenital

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*Hemodialisa Prinsip dasar dialisa mengalirkan darah melalui membran tipis yang terdapat cairan dialisa untuk membuang zat yang tidak diinginkanPada gagal ginjal akut dapat digunakan untuk membantu pasien melewati masa kritisPada gagal ginjal kronik dilakukan hemodialisa sepanjang hidup

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*THE URINARY BLADDER STORES THE URINEGravity and peristaltic contractions propel the urine along the ureterParasympathetic stimulation contracts the bladder and micturition results if the sphincters (internal and external urethral sphincters) relaxThe external sphincter is under voluntary control

*Reflex and Voluntary Control of MicturitionBladder filling reflexively contracts the bladderInternal Sphincter mechanically opensStretch receptors in bladder send inhibitory impulses to external sphincterVoluntary signals from cortex can override the reflex or allow it to take place