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    The Kidney Function

    ByM. Rasjad Indra

    Retty RatnawatiEndang SriwahyuniEdwin Widodo

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    Clinical Case:

    A 10 year boy has some symptoms: dark red urine andswollen/puffy face. This patient also complains about pain duringswallowing, high fever and respiratory tract inflammation. Now, all

    symptomps are relieved.

    From physical analysis: increased blood pressure and edema on face

    and foot.

    From blood analysis: increased creatinin and urea and reducedplasma albumin. Also foundproteinuria and gross hematuria.

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    Based on those anamneses and physical analysis, this patient is

    suspected to sufferglumerulonephritis, a disease of immune system

    with failure ofglumerulus. This disease is self-relieved, with loss

    of signs and symptomps. Some patients can have worse outcome,

    the diseases becomes persistent and develop as permanent renal

    failure.These signs and symptoms are the effect of glumerolus function

    failure leading to renal failure.

    Human kidney plays important roles on maintainingvolume and

    composition ofextracelluler fluid. This organ maintains internalbody environments. As a result, failure of structure and function of

    this organ will dysharmonize humanbody homeostasis.

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    Main function

    Excretion of metabolic waste products &foreign chemicals

    Regulation of: water & electrolyte balances.

    body fluid osmolarity & electrolyteconcentration.

    acid-base balance.

    arterial pressure.

    Secretion, metabolism, and excretion ofhormones

    Gluconeogenesis

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    Slide 6

    Blood Clearance

    Efective Efficient

    What and how

    much should beremoved

    Space

    Time

    EnergyFiltration

    Still needed

    Unsufficient

    Reabsorption Secretion

    Pore Pressure

    Na

    K

    Cl

    HydrogenGlucose

    Protein

    Creatinine

    Urea

    Glomerulus

    Tub. Proks.

    Ansa Henle

    Tub. distalis

    Peritubular I

    Vasa recta

    Peritubular II

    Difusion

    Osmosis

    Bioche

    mistry

    ExcretionSELESAI

    Slide 11

    Slide 16

    Slide 28

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    Renal Blood Flow (RBF)

    1200 ml/minute or 20-25% of cardiac out put

    Both kidney weigh: 300 gr or 0.5% b.w. Blood flow per grams of kidney tissue: 4 ml /

    minute => 1200 ml / 300 gr, why?

    Blood flow is highest in the renal cortex, why? RBF & GFR change relatively little if arterial blood

    pressure between 80 - 180 mmHg, why?

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    The nephron ~ Functional Unit

    Each kidney contains about 1 million nephrons

    The kidney cannot regenerate new nephrons.

    After age 49 the number usually decrease 10 %

    every 10 years.

    Regional differences in nephron structure:

    Cortical nephrons: they have short loops.

    Juxtamedullary nephrons: they have long loops. Urine formation results from: Glumerular filtration,

    tubular reabsorption, and tubular secretion.

    Urinary excretion rate = Filtration rate- Reabsorption rate + Secretion rate

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    Ke Counter Current

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    Two capillary beds: The glomerular & Peritubularcapillaries

    Are arranged in series

    Separated by the efferent arterioles

    Regulate the hydrostatic pressures in both sets of capillaries.

    Hydrostatic pressure: The glomerular (high ~ 60 mmHg) => for filtration.

    The peritubular (low ~ 13 mm Hg) => for reabsorption.

    By adjusting the resistances of afferent and efferent arterioles

    The kidneys regulate the hydrostatic pressure of the glomerular &

    peritubular capilaries.

    Changing the rate of filtration and / or tubular reabsorption.

    Response to body homeostatic demands.

    KEMBALI

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    Urine formation start with the filtration of plasma inthe glomeruli:

    Glomerular Filtration Rate (GFR) determined by: The balance of hydrostatic & colloid osmotic forces across the

    glomerular membrane

    The glomerular filtration coefficient (Kf)Net Filtr.Pressure= PG - PB - G+ B.

    GFR= Kfx Net Filtration Pressure

    Glomerular filtration is rather non selective: Protein are mostly retained in the plasma

    Low-molecular weight substance are freely filtered(excepts that are bound to the plasma protein).

    Negative charged large molecules are filtered less easilythan positively charged molecules of equal molecules size

    Glomerular Filtration

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    Macula densa

    Juxtaglomerular cells

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    Autoregulation of Glomerular Filtration Rate (GFR)& Renal Blood Flow (RBF)

    Sympathetic activation decrease RBF & GFR Hormonal & Autocoid:

    Norepinephrine, epinephrine & Endothelin decreasesRBF & GFR

    Angiotensin II : Constricts Efferent arteriolincreasesGFR

    Endothelial-derived Nitric Oxide (NO), Prostaglandin, &Bradykinin: increases RBF & GFR

    Role of Tubuloglomerular Feedback: Macula densa (Sodium Chloride level in Macula Densa)

    Renin-Angiotensin Efferent arteriolar resistance & Afferent arteriolar

    resistance

    Myogenic Autoregulation

    High protein intake & High blood sugar => increase RBF& GFR

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    Arterial Pressure

    Glomerular hydrostatic

    pressure

    Macula Densa

    Na Cl

    Proximal Na Cl

    reabsorption

    Efferent Arteriolar

    resistance

    Afferent Arteriolar

    resistance

    Angiotensin II

    Renin

    GFR

    KEMBALI

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    Reabsorption & Secretion Tubular reabsorption includes Passive & Active

    mechanism.1.Across the tubular epithelial cells into interstitiel

    2.Through the peritubular capillary membrane back intothe blood

    Active transport (against electrochemical gradient& requires energy.1.Primary active transport

    Expl: Sodium transport in luminal membrane prox. Tub.

    2.Secondary active reabsorption Expl.: Glucose & amino acid reabs.

    Secondary active Secretion: Expl: Hydrogen ion: Counter-transport with sodium

    reabsorption in luminal membrane

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    Glucose:All of the filtered are activelyreabsorbed and sodium dependent.

    Urea & Chloride arepassively reabsorb.

    Active absorb. of Na+

    --> the driving forcefor tubular reabsorb. of water, glucose,amino acids, chloride and phosphate.

    Some organic compounds are secreted

    from the blood into the tubular urine.

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    Transport Maximum

    Transport maximum for substances that are activelyreabsorbed:

    Glucose 320 mg/min.

    Phosphate 0.10 mM/min.

    Sulfate 0.06 mM/min.

    Amino acid 1.5 mM/min. Uric acid 15 mg/min.

    Lactate 75 mg/min

    Plasma protein 30 mg/min

    Transport maximum for substances that are actively

    secreted:

    Creatinin 16 ng/min

    Para-aminohipuric acid 80 ng/min

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    Constituent Filtered Reabsorbed Excreted

    Water 167.5 liters 166 liters 1.5 liters

    Sodium 24,000 mmoles 23,900 mmoles 100 mmoles

    Potasium 720 mmoles 630 mmoles 90 mmoles

    Chloride 19,500 mmoles 19,400 mmoles 100 mmoles

    Bicarbonate 4,500 mmoles 4,498 mmoles 2 mmolesPhosphate 6 g 5 g 1 g

    Glucose 150 g 150 g 0 g

    Urea 50 g 25 g 25 g

    Uric acid 8 g 7.2 g 0.8 g

    Creatinine** 1.5 g 0 g 1.8 g

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    Reabsorption of glucose

    Glucose is cotransport with sodiumacross the luminal cell membrane(uphill)

    the energy from:

    the sodium gradient, how?

    the electrical gradient

    Glucose leave the cell membrane to

    peritubular capillary blood byfacilitated difussion

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    Glucose Threshold

    The ability to reabsorb is limited

    At normal plasma glucose levels(65-90 mg/dl) => completely

    reabsorb.

    At 180-200 mg/dl => glucose firstappear in the urine (threshold).

    Tubular transport maximum (Tm)for glucose: the maximal rate ofglucose reabsorption.

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    Sodium (Na+):

    Most filtered sodium is reabsorbed. The proximal tubules: 70%.

    The loop of Henle: 20%

    The distal tub. and collecting duct: 9%

    The quantity of Na+ excreted =>importantrole in body sodium balance.

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    CountercurrentMechanism

    Loop of Henle (countercurrent multipliers)&Vasa recta (countercurrent ex-changers)

    Loops of Henle: establish an osmotic gradientin the medulla.

    The descending limb: water permeable

    The ascending limb:

    Active sodium transport

    Low water permeability The vasa recta: remove water from the

    medulla.

    Ke Slide 9

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    The collecting ducts:

    Final regul. of Na+

    excretion.Aldosterone andADH: increase Na+ and

    water reabs. by the collecting duct.

    Potasium (K+):

    Filtered, reabsorb and secreted

    The cortical collecting tubules:important site of K+ secretion.

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    Ke Slide 5

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    Clearance(CX)= UX x V (ml plasma/ minute) U: urine, V: Volume of urine

    PX P: Plasma, x: substance

    The Inulin clearance (CIN) = GFR .....Why ?

    Endogenous Creatinine Clearance also = GFR ..... Why ?

    Clearance Ratio = Cx

    CInulin

    PAH : para-amino hipuric acidPAH clearance (CPAH)=Effective Renal Plasma Flow (ERPF)

    Renal Plasma Flow (RPF) = CPAH EPAH =PPAH-VPAH (Extraction Ratio)

    EPAH PPAH

    Renal Blood Flow (RBF) = RPF1-Hematocrit

    Excretion Rate = Ux x V

    Reabsorption Rate = Filtered Load Excretion Rate

    = (GFR x Px) (Ux x V)

    Secretion Rate = Excretion Rate Filtered Load

    The Clearance Concept (CX) to Quantify Kidney Function

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    Inulin:

    Not be reabsorbed or secreted by the kidney

    Not be metabolized, synthesized, or stored

    Pass through the glomerular filtration

    barrier unhindered

    Nontoxic

    Be able to measure in plasma and urine

    Clearance Inulin ~ GFR (Glomerular Filtration rate)

    Para-amino hipuric acid (PAH) is avidly secreted by tubules

    that it is almost completely cleared from all of the plasma in

    one passage of blood through the kidneys

    Clearance PAH ~ ERPF (Effective Renal Plasma Flow)

    uteplasmaml

    plasmamlxmg

    uteurineXmlurinemlxmgCx min/)(

    )(/)(

    min/)()(/)(

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    Factor affecting urinaryconcentrating ability are:

    Anti Diuretic Hormone

    The length of Henles loop. Tubule fluid and blood flow

    Urea.

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    Urea Recirculation in RenalTubules

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    The two ureters are muscular tubesthat carry the urine from the

    kidneys to the bladder. The urinary blader functions as a

    reservoir for urine and is

    periodically emptied (micturition).

    MICTURITION

    A complex act involving autonomicand somatic nerves, spinal reflexes,and higher brain centers.

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    Ke slide 5

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    Kalium intake

    Increase

    [K+] plasmaEffect to

    adrenal cortex

    Increase

    [K+] intracell

    (including kidneyepithelial cell)

    Secretion of aldosteron

    Increase

    Plasma aldosteron

    Increase natrium pump / kalium in

    tubulus distalis and ductus kolektivus

    Increase

    Kalium secretion

    Increase

    Kalium excretion

    Normalkalium level

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    Reduce

    Effective

    Blood volume

    Kidney

    Angiotensinogen

    Renin

    Angiotensin I

    Liver

    Angiotensin II

    Pembuluh darah Korteks Adrenal Hipotalamus

    Vasokonstriksi Sekresi Aldosteron

    Reabsorbsi NatriumBlood pressure > Reabsorbsi H2O

    Sekresi ADH

    Volume darah arterial efektif normal

    Converting enzyme

    Paru

    Pusat Haus

    Minum

    Kembali ke 15

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    Based on this data :

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    Based on this data :

    Konsentrasi inulin plasma = 0,3 mg / ml

    Konsentrasi inulin urine = 6,0 mg / ml

    Konsentrasi glukosa plasma = 4,0 mg / ml

    Konsentrasi glukosa urine = 20,0 mg / ml

    Konsentrasi PAH plasma = 0,02 mg / ml

    Konsentrasi PAH urine = 2,4 mg / ml

    Aliran urine rata-rata = 5 ml / minute

    Hematokrit darah = 45 %

    Answer these following questions :

    Glomerular Filtration Rate (GFR) = ...........ml / minute

    Clearance PAH = ml plasma / minute

    Clearance glucose = ml plasma / minute

    Glucose reabsorbsi rate = ...........mg / minute

    Renal blood flow (RBF) = ..............l / minute