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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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