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RENAL IV

Jun 04, 2018

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    Renal Handling of Organic

    Substances Glucose

    Amino acids

    Ascorbic acids

    Uric acid / Urea

    Creatine / Creatinine

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    Renal Handling of Inorganic

    Substances Sodium : RAAS / other factors

    Potassium

    Magnesium

    Hydrogen

    Chloride Bicarbonate

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    NEPHRON

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    Parts of the Nephron

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    PROXIMAL TUBULE

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    RENAL THRESHOLD

    (Tm / GFR)

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    Ultrafiltration is used to transportsubstances from ic to blood utilizing

    osmotic or hydrostatic pressure

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    PASSIVE TRANSPORTDiffusionFacilitated diffusionOsmosisSolvent drag

    ACTIVE TRANSPORTPrimary activeSecondary active

    cotransportcountertransport

    Endocytosis

    EnergyCarrier

    Permeability of the membraneElectrochemical gradient

    Equilibrium

    Saturationenergycarrier

    RENAL THRESHOLD

    (Tm / GFR)

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    Glucose filtration rate = 100 mg/min (Pcx GFR) reabsorption rate = 100 mg/min

    site = early portion of the proximal tubule

    It is freely filtered, absorbed by secondary active transport co-

    transport, the energy is received by Na+s movement into thecell along the gradient. The gradient of sodium is low in the cellbecause of the Na+ K+ pump.

    secretion rate = 0 mg/min

    excretion rate = 0 mg / min

    Tm = 375 mg/min ideal renal threshold = 300 mg/dL (tm / GFR)

    actual renal threshold = 200 mg /dL (arterial)

    180 mg/dL (venous)

    splay

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    SGLT 2

    PHLORHIZIN

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    GLUCOSE

    100 % REABSORBED

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    Amino Acids

    filtration rate --- small amount

    reabsorption ---- 100 %

    site -- early portion of the proximal tubule

    secretion ---- 0

    excretion ----- 0

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    amino acids

    amino acids

    amino acids

    SIMPLE OR FACILITATED DIFFUSION

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    AMINO ACIDS

    100 % REABSORBED

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    Proteins

    peptide hormones, small proteins andsmall amount of albumin

    filtration rate = 7.2 g/day (GFR x proteinin the ultrafiltrate)

    reabsorption rate = 7.2 g/day

    site --- early portion of the proximal tubule secretion rate = 0

    excretion rate = 0

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    PROTEINS

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    PROTEINS

    100 % REABSORBED

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    Urea filtration rate = 870 mmol/day

    reabsorption rate = 460 mmol/day

    site -- mainly in the medullary collecting duct

    secretion rate = 0

    excretion rate = 410 mmol/day (53%)

    45/ reabsorbed by diffusion at PT

    Its not reabsorbed at thin des and asc LH but secreted

    Its is then reabsorbed back at collecting duct through urea transporter a1.

    Uta1 is enhanced by ADH

    This is called the urea cycle. Urea undergoes this cycle about 6 times before

    being excreted.

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    UREA

    UREA

    MAIN SITE OF UREA

    REABSORPTION

    DIFFUSION

    ADH

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    Uric acid

    filtration rate = 50 mmol/day

    reabsorption rate = 49 mmol/day (98%)

    secretion rate = 4 mmol/day

    excretion rate = 5 mmol/day

    Primarily reabsorbed at PT

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    Creatinine / Creatine

    filtration rate = 12 mmol/day

    reabsorption rate = 1 (0) mmol/day (98

    secretion rate = 1 (0) mmol/day

    excretion rate = 12 mmol/day

    Excretion = Filtration Tm = 16 mg/min

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    Ascorbic acid excretion rate is regulated by

    glomerular filtration

    tubular reabsorption

    proximal tubule

    tubular secretion

    distal tubule ( promoted by adrenal steroid and

    increased filtered load of sodium)

    Tm

    - 2 mg/min

    Primarily absorbed at PT co-transported with sodium.

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    Primarily secreted at PT are bile salts,

    catecholamines, urate, oxalate, drugs.

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    Potassium Major cation in the cell.

    Has to be highly regulated. Regulated by secretion

    ECF K+concentration (N = 3.5 - 5.5 meq/L)

    ICF - 98%, ECF - 2%

    excretion

    kidneys - 90 - 95% feces - 5 - 10%

    Hyperkalemiacardiac arrest during systole

    Hypokalemiaca during diastole

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    ICF K+concentration

    140 mEq/L X 28 L

    3920 mEq

    ECF K+

    concentration

    4.2 mEq/L

    X 14 L

    59 mEq

    K+intake

    100 mEq/day

    K+output

    Urine = 92 mEq/day

    Feces = 8 mEq/day

    NORMAL K+INTAKE, DISTRIBUTION OF K+IN THE BODY FLUIDS AND OUTPUT FROM THE BODY

    Guyton, Medical Physiology, 2006

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    filtration rate = 756 mEq/day

    reabsorption rate = 644 mEq/day (87.8%)

    site -- proximal tubule (65%) and thick ascendong loop of Henle (35%)

    Proximal tubule - absorbance by negative chrge

    Thick asc LH absorbs by co-transporter.

    Secreted at collecting duct and distal tubule in exchange with sodium

    by principle cell and reabsorbed in exchange with hydrogen by the

    intercalated cell which is stimulated by aldosterone

    Potassium sparing drug will inhibit p cell.

    secretion rate = 31 mEq/day

    excretion rate = 92 mEq/ day

    ASCENDING LOOP

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    Na+

    K+K+ K+

    Na+

    K+K+

    PROXIAML TUBULE

    DISTAL TUBULE

    COLLECTING DUCT

    LUMEN PRINCIPAL CELL INSTERTITIUM

    INTERCALATED CELL

    NaK+pump

    Electrochemical gradient

    Permeability of the membrane

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    65%

    POTASSIUM25 -30%

    4%

    12%

    Increased ECF potassium concentration

    Increased aldosterone

    Increased tubular flow rate

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    Calcium

    filtration rate = 540 mEq/day (50%)

    reabsorption rate = 530 mEq/day

    (98.2%)

    site -- proximal tubule

    secretion rate = 0 mEq/day

    excretion rate = 10 mEq/ day

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    65%

    CALCIUM25 -30%

    4 - 9% regulated by PTH

    12%

    PTH

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    CALCIUM or PHOSPHATE

    PTH VITAMIN D3

    ACTIVATION

    CALCIUM RELEASE

    FROM BONES

    RENAL CALCIUM

    REABSORPTION

    INTESTINAL

    CALCIUM ABSORPTION

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    Phosphate

    excretion is controlled primarily by an

    overflow mechanism

    Tm - 0.1 mM/min (renal threshold - 0.8

    mM/min) --- decreased by PTH

    GFR > Tm ------- excretion of excess PO4-

    GFR < Tm ------- complete reabsorption

    of PO4-

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    Magnesium

    involved in many biochemical processes,

    activation of enzymes

    Primarily reabsorbed at thick ascending

    LH

    stored in the bones

    99 % - ICF, 1% - ECF

    50% - bound to proteins

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    25%

    MAGNESIUM65%

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    Hydrogen

    secretion of hydrogen is necessary for

    both HCO3-reabsorption and formation

    of new HCO3-. involves in the regulation of acid - base

    balance

    Its never reabsorbed but only secreted.

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    Bicarbonate

    filtration rate = 4320 mEq/day

    reabsorption rate = 4318 mEq/day

    (99.9%)

    site -- proximal tubule, loop of Henle and

    distal tubules

    secretion rate = 0 mEq/day

    excretion rate = 2 mEq/ day

    REABSORPTION OF BICABONATE

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    PROXIMAL TUBULE REABSORPTION1.Active transport of Na+ creates

    an intracellular (-) allowing passive

    diffusion of Na+

    2. H+ is secreted into the lumen by

    the Na+ - H+ exchanger

    3. H+ combines with the filtered

    HCO3- to form H2CO3 and then

    CO2 and H2O

    4. CO2 diffuses into the cell to

    combine with H2O to form H2CO3

    then H+ + HCO3-

    5. HCO3- returns to the

    circulation by a Na+ - 3 HCO3-

    cotransporter

    REABSORPTION OF BICABONATE

    H+ SECRETION

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    EXCRETION OF URINARY BUFFERS

    H+ secreted combines withnonbicarbonate buffers in the

    lumen and is excreted.

    H+SECRETION

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    SECRETION OF H+ AT THE - INTERCALATED CELL

    AT THE CORTICAL COLLECTING DUCT

    1. Intracellular H20 and CO2 in the

    presence of carbonic anhydrase form

    H+ and HCO3-

    2. H+ is secreted into the lumen by

    an active H+ - ATPase pump.

    3. HCO3- returns to the circulation

    via a Cl- - HCO3- exchanger.

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    85%

    BICARBONATE10%

    4.9%

    1 %

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    FATES OF SECRETED H+

    1. 90% TITRATES FILTERED BICARBONATE

    IN A RECLAMATION PROCESS (H2CO3----- CO2+ H2O)

    2. 1% IS BUFFERED BY NH3TO FORM NH4+

    3. 1 % IS BUFFERED BY OTHER TUBULAR BUFFERS

    MOSTLY HPO4=TO FORM TITRATABLE ACIDITY

    4. A VERY MINUTE AMOUNT OF H+ REMAINS FREE

    IN THE FINAL URINE

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    Sodium

    filtration rate = 25,560 mEq/day

    reabsorption rate = 25,410 mEq/day

    (99.4%)

    site -- proximal tubule, loop of Henle, distal

    tubules and collecting duct.

    secretion rate = 0 mEq/day excretion rate = 150 mEq/ day

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    EARLY SEMENT OF PROXIMAL TUBULES

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    Overview of Sodium Chloride and WaterTransport: The Loop of Henle

    TAL reabsorbsapproximately 25% -30% of filtered NaCl, K,Ca++ and HCO3-

    Descending thin limbreabsorbs approx. 15%

    of filtered water

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    Volume regulation andOsmoregulation

    Osmoregulation is achieved by changesin water balance, volume regulationprimarily by changes in sodium balance.

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    Volume regulation andOsmoregulation In summary, regulation of plasma osmolality

    or osmoregulation is governed byosmoreceptors influencing the release of ADHand thirst.

    Changes in effective circulating volume issensed by multiple volume receptors whichactivate effectors such as aldosterone.

    ADH increases water reabsorption and

    therefore increases urine osmolality but doesnot affect Na+ transport.

    Aldosterone enhances Na+ reabsorption butnot directly that of water.

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    LATE SEGMENT

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    65%

    SODIUM25%

    9%

    1 %

    aldosterone

    5%

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    The proximal tubule

    The proximaltubule reabsorbsapproximately67% of the

    filtered water, Na,Cl, K and othersolutes.

    100% of the

    filtered glucose,amino acids

    Also secretesorganic cations

    and anions.

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