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Body Fluids
Distribution of Body Fluids:
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TOTAL BODY WATER: About 57%, in liters, of body weight in kilograms
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o EXTRACELLULAR: About 40% of total body water
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5% of extracellular water
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o INTRACELLULAR: About 60% of total body water
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INDICATOR DILUTION METHOD: Volume = Amount / Concentration
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We want to know the concentration that would have been measured, if the indicator had been distributed
instantaneously
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TOTAL BODY WATER?
o Tritiated Water
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 If you use 3H2O, it takes a long time get results
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It can also be
used to measure plasma volume
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o Mannitol is the best indicator we have for ECS, and was used in one of the problems
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TRANSCELLULAR WATER? These are special body compartments, separate from ICS, ECS, and plasma
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o This volume of fluid is small and is not normally considered in measurements, but should be kept in mind,
especially in cases of pathology
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o Radioiodinated Serum Albumin (RISA): RISA is also a large protein that stays in the bloodstream
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OSMOTIC PRESSURE: The amount of hydrostatic pressure necessary to exactly counter a concentration gradient
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PI = R T (Total Solute Concentration)
(mm Hg) = (19
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3) Delta(Solute Conc)
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Water flows from solution of low osmotic pressure to high osmotic pressure
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o ISOOSMOLAR: A 300 mOsm solution is the same as normal body osmolarity, both intracellularly and
extracellularly
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TONICITY: Refers specifically to the movement of water into or out of a cell
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o HYPOTONIC CELL: Having a lower osmolarity inside, such that water will leave the cell and the cell will
shrink
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o If you put a cell in a HYPOTONIC SOLUTION, water will come in and the cell will swell up
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Add a HYPOTONIC solution, and water will move into the intracellular spaces
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Principles:
o Over the whole body, water moves rapidly to equilibrate any osmolarity difference between extracellular
and intracellular spaces
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o Sodium and Chloride are confined to the extracellular space
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At equilibrium, pure water is distributed to body compartment according to the total solute content in each
compartment
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Then 50% of total volume after addition will be in each respective space after equilibrium
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5 mOsm -- pretty low

EQUIVALENTS: Moles of charge
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MEMBRANE PERMEABILITY:
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2

Small ions (Na+ and K+) have very limited permeability through the membrane directly, i
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through small, transient,
water-filled holes in the membrane
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DIFFUSION: Movement of a substance with its concentration gradient, due to random thermal motion over time
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o The flux is proportional to, and has the opposite sign of, the electrochemical gradient
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So, flux is proportional to the permeability of a substance through the membrane, and the concentration
gradient
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You can slow down glucose flux by adding galactose to the system (assuming galactose
can get through it)
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The Na gradient thus created, there is a Na/Glucose symport into the cell, to transport glucose into the cell, against
glucose's concentration gradient
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This allows patient to absorb water along with the
glucose and sodium
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Na/K ATPase PUMP MECHANISM:
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WITH PHOSPHATE BOUND (not ATP)
o The port is open to the outside
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o We have 3 low affinity Na-binding sites
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ATP BINDS to the inside
INNER GATE opens
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o The three Na binding sites are high affinity, so Na latches on
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INNER GATE closes, and we start over
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Ouabain is used to treat "cardiac insufficiency
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The Sodium pump makes sodium behave as though it were an impermeable solute, as it constantly restores any small
amounts of Na+ that leak into the cell
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Renal Physiology
Normal Values
Renal Blood Flow (RBF)

1000 - 1200 mL / min , 20%-25% of Cardiac Output

Maximum molecular weight that
is normally filtered in glomerulus

5000 Daltons

Autoregulatory Range of GFR
and RBF

80 - 180 mm Hg

Myogenic contraction and tubuloglomerular feedback will operate
within this range
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5 - 1
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6 mg / dL in children, 7 mg / dL in adults, which is close to solubility limit

Fractional Excretion from Water
Diuresis

8% - 11% of GFR
Water Diuresis never exceeds this level

Water diuresis acts only on distal
tubular mechanisms
ADH Basal Activity (DIURESIS)

280 mOSM / kg blood ------>

Low blood osmolarity

0
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0 pg / mL ADH ------>

Highly concentrated urine

1200 mOSM / kg urine, or 0
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24 mEq / L

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ANATOMY and PHYSIOLOGY
Renal Vasculature: Vessels are listed in order of blood flow
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Arcuate Arteries: They divide the kidney cortex from the medulla
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AFFERENT ARTERIOLES: Primary arterioles that provide incoming blood to the glomerulus
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GLOMERULAR CAPILLARIES: Filter blood into the glomerulus, and then unfiltered blood continues to
efferent arterioles
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o A major source of pressure drop in the kidney system
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They run parallel to the collecting tubules in juxtamedullary nephrons
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o Net Reabsorption: Oncotic Pressure > Hydrostatic Pressure
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Interlobular Veins
Arcuate Veins
Interlobar Veins
Renal Vein

GLOMERULUS: Initial filtration of blood
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o ENDOTHELIAL CELLS: Capillary endothelial cells are fenestrated
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 They extend interdigitating Foot Processes onto the capillary wall, which can separate from each
other when mesangial cells contract
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o FILTRATION SLITS: The spaces between the foot processes, through which blood and blood solutes
pass
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 MESANGIAL CELLS: They are interstitial cells in the glomerulus
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o GLOMERULAR BASEMENT MEMBRANE (GBM): The GBM is the primary barrier to filtration
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 Lamina Densa: Thick middle part
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 NEGATIVE CHARGE: The basement membrane has an overall negative charge due to
presence of Sialic Acid in the Glomerular membrane
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o BOWMAN'S SPACE: Contains the glomerular filtrate
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o Negative charges don't get through:
 Dextran: Neutral dextran has a fractional clearance of 0
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015
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Pathologies:
o GLOMERULONEPHRITIS: Immune reactions in kidneys ------> proteolytic enzymes destroy the
glomerular barrier, such that large blood proteins can get through
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GLOMERULAR FILTRATION PRESSURE: Pf = (Pgc - Pt - PIb)
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Variables:
o Pf = Glomerular Filtration Pressure
o Pgc = Glomerular Capillary Hydrostatic Pressure
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o Pt = Tubular Hydrostatic Pressure
o PIb = Glomerular Oncotic Pressure
As glomerular blood is filtered, the remaining blood increases in oncotic pressure (PIb), which allows for
reabsorption in the peritubular capillaries
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o You can calculate a value for Kf by measuring GFR and Pf
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o Lower Kf (less permeability) ------> lower GFR
 This is somewhat compensated by a slower rate of rise of oncotic pressure which is a direct
consequence of the lower GFR
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o ARTERIOLAR CHANGES:
 Efferent Arteriolar Vasoconstriction ------>
 LOWER RBF
 HIGHER GFR, because of higher Pgc
 Afferent Arteriolar Vasoconstriction ------>
 LOWER RBF
 LOWER GFR, because of lower RBF
 Afferent Arteriolar Vasodilation ------>
 HIGHER RBF
 HIGHER GFR, because of higher RBF
 COMBINED CHANGES: When two or more factors both change, RBF is generally affected more
than GFR
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o FACTORS AFFECTING ARTERIOLES:
 Resting tone in the arterioles, maintained by intrinsic myogenic activity
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 Epinephrine and Norepinephrine both cause vasoconstriction in the kidneys, because
alpha-Receptors greatly outnumber beta-Receptors
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 Large increase in sympathetics ------> stop glomerular filtration entirely
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This suggests that the kidneys respond to blood volume changes more than
to blood pressure changes
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 Drugs:
 Saralasin blocks the effects of Angiotensin II
 Captopril blocks ACE, thus preventing conversion to Angiotensin II
 Biosynthetic Pathway: JGA Cells secrete Renin in response to low tubular osmolarity
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ACE converts Angiotensin I ------> Angiotensin II in the lungs
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 PROSTAGLANDIN E2 (PGE2): Vasodilator
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It counteracts the actions of Angiotensin II
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 Because of the counteracting effects of Angiotensin II + PGE2, the net is to reduce RBF
while keeping GFR relatively constant
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 Smooth Muscle Myogenic Response: The smooth muscle response to pressure accounts for some
of this autoregulation
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 A higher arterial blood pressure will lead to higher tubular fluid flow: MABP ------>
Capillary Pressure ------> Tubular Flow ------> Macula Densa senses the higher tubular
flow ------> Resistance in Afferent Arteriole ------>Blood pressure
 This feedback is on a per-nephron basis
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 Macula Densa may sense Na+ or Cl- concentration
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o FNXN: The JGA ultimately regulates Glomerular Filtration Rate by regulating the vascular tone of the
Afferent and Efferent Arterioles, via Tubulo-glomerular Feedback
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 The Macula Densa cells form part of the wall of the DCT
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 GRANULAR (JGA) CELLS: Form the vascular part of the Juxtaglomerular Apparatus, in the
walls of the afferent and efferent arterioles
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 EXTRAGLOMERULAR MESANGIAL CELLS: Interstitial cells in the JGA
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 When they contract, they reduce glomerular capillary surface area available for
filtration, which ultimately can lead to lower glomerular filtration rate
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 NEURAL (Extrinsic Sympathetic)
 HUMORAL (Renin, Angiotensin, PGE2)
 ARTERIAL PRESSURE (Autoregulation)
 TUBULAR FLUID (Tubulo-glomerular Feedback)
GFR and DIURESIS: GFR has more pronounced effects on salt and water reabsorption when the GFR is high then
when it is low
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While
there may be a gradient driving the transport, the gradient does not normally present a barrier to transport
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o Back-diffusion of ions will occur simultaneously with the transport
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As long as enough
ATP is available, transport will move in the positive direction
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o Tight Junctions regulate movement
o Paracellular Spaces exist between cells
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PERMEABILITY:
o High permeability to water, due to presence of Aquaporin channels
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Lots of ions will move through the paracellular path in the
proximal tubule
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o SUMMARY: High Rate, Low Gradient Transport
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ORGANIC REABSORPTION: 60-70% of Na+, Cl-, HCO3-, and K+ occurs in proximal tubules
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o UREA: Proximal tubule is permeable to urea, but urea concentration still increases in this part because
more water is reabsorbed than urea
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It is both secreted and reabsorbed, but net reabsorption usually occurs
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o GLUCOSE: Na+-Glucose Cotransport
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e
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 Complete reabsorption occurs at concentrations lower than 250 mg / dL
 All transporters are filled at concentrations above 350 mg / dL
 D-Galactose and D-Fructose compete for the same transporters
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Almost complete reabsorption occurs at the proximal tubules
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o PROTEINS: Small protein-hormones (like ADH, PTH, Insulin) are reabsorbed by pinocytosis and then
broken down inside the cells, and then transported back into the blood
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 These anions weren't originally filtered because they were bound to plasma proteins
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 Prostaglandins are secreted in the proximal segment so that they can be delivered to the distal
tubule where they act
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o URIC ACID SECRETION occurs at high levels when blood levels of uric acid are high
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o DRUGS: Lots of drugs are secreted in the proximal tubule
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SALT REABSORPTION / ION CHANNELS: Salt reabsorption in the proximal tubule does not appreciably affect
the composition of blood plasma, but it can have a major effect on the volume of plasma
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The pump operates way below a saturated level
at a steady state, so more Na+ coming into the cell will increase the rate of pumping, thus maintaining the
gradient
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This is a minor contributor to
total Na+ transport
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This is a major contributor to
Na+ reabsorption
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The pH inside the cell is maintained by HCO3-/CO2 homeostasis
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+
 Na /GLUCOSE-SYMPORT: The channel is driven by Na+ gradient, and some Na+ is reabsorbed
by this path, dependent on how much glucose there is
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 IN FILTRATE: From Na/H Antiport, the secreted H+ reacts with HCO3- in the filtrate, to form
CO2 and H2O
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This HCO3- is
transported back into the blood via HCO3-/Na+ symport in a 3:1 ratio
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It speeds the process of
HCO3- reabsorption in both cases
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o Cl--REABSORPTION:
 Cl--BASE ANTIPORT: Cl- is reabsorbed into the cell, and base is kicked out into lumen
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 The base can be oxalate, OH+, HCO3-, or formate
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 PARACELLULAR reabsorption of Cl- occurs in later segments
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Cl- concentration rises early on because
reabsorption of other ions (Na+ and HCO3-) is occurring more readily
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o WATER REABSORPTION is driven by all of the above ion-transporters
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PROXIMAL TUBULE REABSORPTION: Na+ and water are always reabsorbed isosmotically
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PRIMARY INHIBITION of WATER REABSORPTION: The presence of poorly absorbed solute decreases
water reabsorption in the proximal tubule
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 As you proceed through the proximal segment, the concentration of impermeable solute in the
filtrate will relatively increase
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 UREA: Urea concentration in proximal segment relatively increases as you go forward ------>
water reabsorption is inhibited
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 MANNITOL is an osmotic diuretic for similar reasons
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 ACETAZOLAMIDE is a diuretic that works by blocking transport in the proximal tubule
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 MECH: GINHIBITORY ------> decrease levels of cAMP ------> disinhibition of channels
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

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PROXIMAL STRAIGHT TUBULE (PARS RECTA):
LOOP OF HENLE:
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THIN DESCENDING LIMB of LOOP of HENLE:
o TRANSPORT: No active transport occurs in the descending limb
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 In the Medulla, some NaCl and urea will move from the interstitium back into the tubular fluid
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THIN ASCENDING LIMB of LOOP of HENLE:
o PERMEABILITY: Low permeability to water starting in the thin ascending limb
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It
generates a hypotonic filtrate which it delivers to the distal tubule
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o TRANSPORT: Moderate Rate, Moderate Gradient
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NaCl is massively
reabsorbed through the TALH
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o Na / K / 2Cl SYMPORT: Electrically neutral secondary active transport of four ions at a time
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 LOOP DIURETICS: FUROSEMIDE, BUMETANIDE, inhibit this transporter
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DISTAL CONVOLUTED TUBULE (DCT): The distal tubule, in the kidney cortex
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TRANSPORT: Low Conductance, High Gradient
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o It has more Na/K-ATPase transporters than the proximal tubule, because it requires more energy to
maintain a strong enough gradient to keep driving Na+ out at this point
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 THIAZIDE is the diuretic that inhibits this port
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SUMMARY: Low Rate, High Gradient
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 ADH Present ------> open Aquaporin pores ------> High permeability ------> water reabsorption -----> filtrate becomes very hypertonic ------> concentrated urine
 ADH Absent ------> low permeability ------> water excretion ------> filtrate remains hypotonic -----> dilute urine
o Permeability to electrolytes is very low = low conductance
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TRANSPORT: Low Conductance, High Gradient, with gradient maintained by massive Na/K-ATPases
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 APICAL Na+ CHANNEL drives Na+ Reabsorption in the principle cell
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 Amiloride is a diuretic that will block this channel
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 ALDOSTERONE stimulates Na+ reabsorption and K+ secretion in these cells ------> more net
water reabsorption
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 K+-Secretion effect is not as well understood, but stimulation of Na/K-ATPase plays a
role
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ADH: Principle cells are sensitive to ADH
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 ADH is a short-term regulator
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o INTERCALATED CELLS: Intercalated cells are found only in the cortical segment
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 H+ and HCO3- Secretion
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+
 K Reabsorption and Secretion
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 This is true because increased flow rate ------> more Na+ is in the filtrate ------> reabsorption
gradient remains high for a longer period of time ------> more resorption
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Water increases because salt
increases
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The Na/Cl/K channel of the Thick Ascending Limb is the primary furnace for the counter-current multiplier
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o Ascending Limb: It is actively kicked back into the tubular fluid, on a gradient-limited basis
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o The highest gradient is created at the very bottom of the loop, in the deepest part of the medulla
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DISTAL / COLLECTING TUBULES:
o CORTICAL DISTAL CONV TUBULE: In the presence of ADH, it transports water into the cortical
interstitium, as it receives an extremely hypotonic filtrate
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It can
transport lots of water to create extremely hypertonic urine
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Salt leaks into the vasa recta
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o CORTEX: As the plasma goes into the cortex, it's hyperosmolarity allows it to reabsorb any water that was
transported from the Distal and Collecting Tubules
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 An equilibrium concentration of ISF salt is reached, where the rate of transport of salt into the
medulla (TALH channels) is equal and opposite to the rate of salt leakage out into the vasa recta
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 Most of the urea comes from the collecting tubule, inner medulla (very end of the nephron)
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 Sparing the detail, the countercurrent flow of the vasa recta help to keep the medulla high in urea
concentration
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FACTORS THE ALTER THE COUNTER-CURRENT MECHANISM:
o ANATOMIC: The longer (juxtamedullary) nephrons have a more powerful concentrating ability
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o ADH: Presence of ADH will cause reabsorption of water and a more concentrated urine
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o FLUID FLOW RATE: Maximum effectiveness occurs when the flow rate through the loop is high and
through the collecting tubule is low
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 A lower flow rate in the collecting tubules will tend to increase the effectiveness of the countercurrent multiplier
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UREA: Reduced supply of urea (via low dietary protein) can lessen the concentrating ability
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MEASUREMENT OF RENAL FUNCTION
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CLEARANCE: The Virtual Volume of plasma containing a substance that was excreted in the kidneys, per unit
time
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 This is based on the Dilution Principle:
 (Conc)(Volume) = (Conc)(Volume)
 Total Amount = Total Amount
GLOMERULAR FILTRATION RATE (GFR):
o GFR can be measured as the Clearance of Inulin, CIn
 Inulin is neither secreted nor reabsorbed
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INULIN is difficult to use because you must infuse the substance and then completely empty the bladder
both before and after the infusion, to ensure full recovery
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TUBULAR TRANSPORT: The difference between what is filtered and what is excreted
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o

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Amount Reabsorbed = Amount Filtered - Amount Excreted
= (GFR)(Plasma Conc) - (Urine flow)(Urine conc)
INCREASE PLASMA CONCENTRATION of a reabsorbed substance ------> channels get
saturated ------> relatively more is excreted ------> higher net clearance
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 Amount Secreted = Amount Excreted - Amount Filtered
 = (Urine flow)(Urine conc) - (GFR)(Plasma Conc)
 INCREASE PLASMA CONCENTRATION of a secreted substance ------> channels get saturated
------> relatively less is secreted ------> lower net clearance
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This ensures you have reached the maximum TM
RENAL PLASMA FLOW (RPF): The clearance of Para-Amino Hippurate (PAH), CPAH
o PAH is very effectively cleared by secretion in the proximal tubule
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Because virtually all PAH is cleared per volume of blood, PAH
clearance can be used as an estimate of RPF
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 Instead, inject a radioactive isotope into the plasma and watch it accumulate in the kidney
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RENAL BLOOD FLOW (RBF): It equals renal plasma flow + the flow of red blood cells
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•

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CREATININE CLEARANCE: Clinically Creatinine clearance is measured to estimate GFR, instead of Inulin
clearance
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o DENOMINATOR is falsely raised a little because of non-creatinine chromogens the react with the
creatinine testing reagent, in the blood
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o Falsely high GFR values may be obtained with people who have good blood flow (RPF) but poor
glomerular function (GFR)
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This is a
measure of reabsorption capacity
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Fractional Excretion of Water:

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All you have to do is measure Creatinine in the blood and in the urine and take the ratio
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A low fractional excretion indicates that
tubular reabsorption functions are working
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 Again, higher fractional excretion indicates impaired tubular function
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Anything higher than 3% indicates impaired tubular function
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o FRACTIONAL REABSORPTION RATE = (1 - Fractional Excretion) for any substance
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PLASMA CREATININE CURVE: High Plasma Creatinine means low creatinine clearance, which means trouble
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o If the reciprocal is decreasing rapidly over time, then the patients condition is worsening
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REGULATION of RENAL FUNCTION
UREA: It is freely filtered, and its reabsorption is dependent on urine flow rate
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Permeability to Urea occurs in two places:
o PROXIMAL TUBULE: Some urea reabsorption occurs, but more water reabsorption occurs so urea filtrate
concentration actually goes up
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Urea is reabsorbed and concentrated into the interstitial
medulla, where it plays an integral role in counter-current exchange
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However, urea is not as toxic as some other metabolites
that accumulate, so uremia toxicity usually isn't due to urea per se
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•

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Water Diuresis: Increased water excretion without corresponding increase in salt excretion
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o Increased water intake will cause plasma ADH levels to fall
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o Water diuresis only exerts its effects on the distal tubules
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 Thus water diuresis fractional excretion never exceeds 8% - 11% of GFR
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o Causes:
 Massive increase in salt present in the tubular fluid
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REGULATION OF PLASMA OSMOLARITY:
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ADH-SECRETION: Primary mechanism that respond to plasma osmolarity
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 Osmoreceptors in the hypothalamus sense an increase in plasma osmolarity
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 BASAL ACTIVITY: 280 mOsm / kg ------> 0
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 MAXIMAL SECRETION: 295 mOsm / kg ------> 4
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 Urea is not an effective stimulus
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In the
absence of insulin there is a small effect
...

o This effect is not enough to alter GFR
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ADH DISORDERS:
o DIABETES INSIPIDUS:
 Primary Insufficiency of ADH is the most common cause
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 Psychogenic Diabetes Insipidus is compulsive water-drinking (polydipsia)
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Excessive ADH secretion
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o STIMULATE Atrial Receptors ------> Fire Vagus Nerve ------> Multiple end-effects
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 Decreased Sympathetic Outflow ------> arteriolar vasodilation ------> higher capillary hydrostatic
pressure ------> edema (fluid moves out of vascular space and into interstitium)
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o ATRIAL NATRIURETIC FACTOR (ANF) is also released when the stretch receptors are stimulated
(but not via Vagus)
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 ANF will cause further arteriolar vasodilation ------> edema
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BARORECEPTORS: They will decrease sympathetic outflow ------> less Renin
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JUXTAGLOMERULAR APPARATUS:
o TWO STIMULI (INPUTS):
 Arterial Pressure Changes (Afferent Arteriole)
 Rate of flow of tubular fluid (i
...
rate of delivery of salt) in Macula Densa of the DCT
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\
SYMPATHETICS: An increase in sympathetics will result in more water retention, via peritubular capillaries, in
the kidney and will result in a higher filtration fraction
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 This is a direct JGA effect, as well as via Renin and Angiotensin (see below)
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o alpha-RECEPTORS:
 Vasoconstriction in the efferent arteriole
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o beta-RECEPTORS: beta-Receptors are on granule cells to promote renin release
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 SYMPATHETIC INPUT: Neural (NorE) and Humoral (Epi) input to the JGA stimulates rein
release
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 Atrial Stretch Receptors are believed to be the major sensors involved in this pathway -not the baroreceptors
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o ANGIOTENSIN II: Potent vasoconstrictor
 It stimulates release of Aldosterone
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 It preferentially constricts the efferent arteriole ------> capillary pressure and RPF ------> GFR /
RPF ratio (i
...
RPF decreases more than GFR)
...

ALDOSTERONE:
o Its release is stimulated by Angiotensin II and K+ in blood
...

ADH: ADH also responds to low blood volume (blood pressure) directly
...

ATRIAL NATRIURETIC FACTOR: It reduces blood volume by increasing the excretion of salt and water
(mechanism unknown)
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o

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SEVERE VOLUME DEPLETION: Summary of volume effects
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MAJOR STIMULI:
o Increased plasma osmolarity
o Decreased blood volume (atrial receptors)
o Decreased blood pressure (baroreceptors)
MAJOR OUTPUT
o SYMPATHETICS
o Increase in Renin / Angiotensin / Aldosterone system
KIDNEY: Reduced excretion of salt and water; increased retention
...

o Decreased Sympathetics
KIDNEY: Massive diuresis and dilute urine

ACID-BASE BALANCE: Usually, net secretion of acid occurs (we have an acidic diet)
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Na+/H+ ANTIPORT is stimulated by an acidic (less than 7
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 It is inhibited by a basic (greater than 7
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o HCO3- REABSORPTION occurs in the proximal tubule to the greatest extent (about 75%)
o However, because it is a low gradient system, it still does not affect the tubular fluid pH that much
...

o ACID PUMP: H+-ATPase secretes protons into the tubular fluid
...

 Transporters that balance the H+ pump:
 Cl-/HCO3- ANTIPORT gets rid of the excess HCO3- created by this proton pump
...

 Cl--Channel, finally, then recycles the Cl- back out into the blood as well
...

 ELECTROCHEMICAL GRADIENT: The H+ pump is limited by the electrochemical gradient
...

 The limit of H+-excretion by this pump is reached at a tubular pH of about 4
...

 beta-Intercalated Cells are the names of the cells that secrete base
...
The H+-ATPase pump is then put on the basolateral membrane
to counteract the HCO3- pump
...
However, the presence of any
HCO3- in this segment will lessen its ability to secrete acid as the non-bicarbonate buffers become weaker
...
All secreted protons must be buffered in the tubular fluid
...
This mechanism
predominates in the proximal tubule
...

 Inside the cell, the CO2 reacts with H2O and Carbonic Anhydrase to reform HCO3 HCO3- is then excreted into blood
...

 PLASMA HCO3- CONCENTRATION determines the filtrate HCO3- concentration, which
determines how much buffering capacity the filtrate will have
...

 Plasma [HCO3-] below 24 mEq/L: Almost all HCO3- will be reabsorbed to keep HCO3levels in blood higher
...
This mechanism
predominates in the distal tubules
...

 This is a non-bicarbonate buffer and is responsible for acid secretion
...

o AMMONIA NH3 : NH4+ BUFFER: Acid excreted in the form of NH4+
...

 As above, once NH3 accepts a proton to become NH4+, it is charged and lipid-insoluble, and thus it
must be excreted
...
The rate of acid-secretion
will be proportional to the strength of this buffer
...
It will yield ammonia + Glutamate, from Glutamine
...

 Both these rxns occurs in tubular cell mitochondria
...
brain101
...

ACID-EXCRETION: NON-BICARBONATE BUFFER CONCENTRATION ultimately determines the ability
of the kidney to excrete acid!
o Plasma HCO3- Concentration: High plasma HCO3- ------> High filtrate HCO3- concentration ------> the
HCO3- buffer becomes relatively stronger than the NH3 and HPO4- buffers in the tubular fluid ------> less
acid excretion
...

o SUMMARY: Low blood HCO3- and high blood PCO2 both lead to greater acid excretion
...

o ACETAZOLAMIDE inhibits Carbonic Anhydrase ------> less H+ secretion in proximal tubule (inhibit
Na+/H+ antiport) and less Na+ reabsorption ------> diuresis
...

 Continued use will cause secretion of an alkaline urine and will result in acidosis
...

•
•
•

HYPOVENTILATION ------> PCO2 ------> [HCO3-] ------> pH
The higher PCO2 in tubular cells stimulates the secretion of acid
...

OVERALL: Chronic Hypoventilation, as in COPD
...
35
o HCO3- extremely high 34-36 mEq/L
o PCO2 high (hypercapnia) 60 mm Hg

METABOLIC ALKALOSIS: As from chronic vomiting
...

KIDNEY RESPONSE: plasma [HCO3-] ------> HCO3- in filtrate ------> both excretion and reabsorption of HCO3increase, but excretion increases more ------> net alkaline urine is created
...

•

•

•

17

EXTRARENAL MECHANISMS:
o Insulin stimulates Na/K-ATPase in liver and muscle ------> K+ uptake
 This is a mode of absorbing dietary potassium, in the absorptive state
...

o Catecholamines (beta2) indirectly stimulate Na/K-ATPase
o Acidosis ------> blood K+ by shifting K+ to the ECF because of the shift in electrochemical gradient
...

 PROXIMAL TUBULE (65-70%): Mechanisms are not completely understood here; much
probably occurs via paracellular diffusion
...

o SECRETION: Basically all K+ in the urine came from secretion in the distal and collecting tubules
...

Factors affecting K+ Secretion:
o Plasma K+ concentration directly drives the Na/K-ATPase ------> more K+ into Principle cells ------>
more K+ secretion
...

 It is thought to do this by stimulating production of the Na/K-ATPase pumps
...

o ADH raises K+ permeability to stimulate secretion
...

o Alkalosis increases K+ membrane conductance in apical channels by increasing the pH of the tubular fluid
...
They potentially lead to hypokalemia which is an
unwanted side-effect of diuretics
...
brain101
...

Thiazide diuretics increase tubular fluid flow rate and thus K+ secretion
...


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