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47 Cards in this Set

  • Front
  • Back
Filtered Load Equation
(GFR) [P]x
Excretion Rate equation
(V)u [U]x
Filtered load in normal conditions is equal to
Excretion Rate
Reabsorption or Secretion Rate Equation
(Filtered Load-Excretion Rate)
+=reabsorptio
-=secretion of substance plus something being added
Some substances, like Ca2+ are not freely filtered why?
because they are bound to plasma proteins
Transcellular pathway
substances goes through luminal membrane..through epithelial cell, goes either to either basal membrane into interstitial space or into lateral space betwee epithelial cells
Paracellular
move in between lateral spaces by diffusion. Its regulated by type of tight junctions. Tight junction become more complicated as we move across the nephron, the most leaky ones are on the proximal tubule the tighter ones are on the collecting tubules
What regulates paracellular pathway?
Tight Junctions
Tight Junctions form zipper like structures by
membrane proteinswith extracellular domain :claddin and occludin. They also have connections to the cytoskelton.
Mutation in claudin-16 causes
A disease caused Hypomagnesemia-
Hypercalciuria Syndrome by affecting
paracellular transport of calcium
and magnesium in thick ascending limb
of the loop of Henle
Na sites of reabsorption
67% in proximal convoluted tubule
25% Thick ascending limb
5% Distal convoluted tubule
Site of Na reabsorption is site of action of
many diuretics like "loop diuretics" at thick ascending loop
Thiazide diuretics at the distal convoluted tubule
K sparing diuretics at the conducting tubule
Diuretics block
Na transport and as a consequence H2O is lost
Whats reabsorbed in the proximal tubule?
100% Glucose
100% Amino Acids
85% HCO3-
Most Pi, lactate, citrate
Large amounts of Na+
All of the transport mechanism on the proximal tubule dependent on
Na/K Atpase on basolateral membrane..Na out K in…low levels of K inside epithelia, great [] gradient from lumen into epithelia cell..so all transport are secondary active transport even though they don’t use the ATP they needed it to function
SGLT has two isoforoms in the proximal convoluted tubule
SGLT 1 and 2 on apical membrane
Once gluc inside the cell, it exits using
Glut 2
In the proximal tubule Carbonic Anhydrase converts HCO3 into CO2 and H+ and
it is pumped into lumen via Na/H, HCO3 is free and reabsorbed into blood in a facilitated diffusion.
Under normal conditions, SGLT takes care of all
glucose in proximal tubule
At concentrations less
than 200 mg/dL virtually
100% of glucose is
reabsorbed and excretion
is 0
Transport max (Tm) of glucose occurs
at about
350 mg/dL.
Glucose begins to be
excreted below
Tm (ie. at
threshold) because of the
phenomenon of splay
Mechanisms for splay
related to
to relatively low
affinity of SGLT for glucose
and because of nephron
heterogeneity with respect
to Tm
When saturation of SGLT occurs can lead to
diabetes mellitus
Transcellular reabsorption in late proximal tubule
Early PT absorbs primarily Na+/HCO3-

Late PT absorbs
Primarily Na+/Cl-
Paracellular Route in late proxima tubule
Cl- moves down a
concentration gradient
through tight junctions

Cl- movement establishes a postive
transluminal potential

Na+ follows an electrical gradient
The Na+ Concentration
in the lumen of the
nephron remains
relatively constant as
fluid moves along the
proximal tubule? why?
Water movement
must be balanced
so that the Na+
concentration
remains constant
Why does H2O follow Na?
Na moves AA and Gluc Phosphate across lumen, osmolality of interstitial fluid increases, so an osmotic gradient is built up and drives water in (paracellulary or transcellularly)
In the proximal tubule H2O is reabsobed via
AQP1 on apical membrane.
On basal membrane H2O exits through
QP3/4
is H2O readily regulated in the proximal tubule?
No, because it just follows Na, regulation occurs on distal parts.
Movement of water is also dependent on starling forces for reabsorption as blood moves through glomerulus (lots of filtration, no reabsorption) and enters paratubular capillaries lot of fluid loss, so
lots of proteins trapped in these capillaries leading to high oncotic pressure which favors fluid reabsorption from interstitial fluid into these capillaries
Glomerulotubular Balance refers to
ensuring a constant return of fraction of filtered load in proximal tubule
What if GFR was increased (doubled) what would happen to filtered load?
filtered load increases,leads to increase in oncotic pressure and decrease in capillary pressure hence reabsorption gradient from interstitum into capillary would increase and reabsorption would increase.Glomerulotubular balance ensures that 60% of this now higher filtered load would come back into the plasma
GGlomerulotubular balance when theres volume expansion
Volume is greater in plasma, this decreases oncotic pressure in capillaries and increases hydrostatic pressure, leadinf to decrease in reabsorption
Glomerulotubular balance when theres volume contraction
: proteins in peritubulular capillaries would be increased and oncotic pressure would go up, pressure goes down and reabsoprtion occurs
What would be the effect on reabsorption if during volume expansion, GFR is constant
less
reabsorption of Na+ and
water occurs
what happens to reabsorption if GFR is constant during volume contraction
more reabsorption of Na and water occurs
Protein reabsorption is returned as
returned as the ultrafiltrate
passes along the proximal tubule
All proteins that leaks in the nephron would be reabsorbed in proximal tubule. This relies on
endocytosis. Clathrin coated pits on apical membrane of proximal tubules. Cubulin and megalin and they bind any of the proteins found in tubule fluid and trigger endocytosis
Excessive Muscle cell breakdown could result in myoglobin found in plasma..why
it would saturate endocytotic processes and myoglobin would end up in blood
Why is secretion of organic anions and cations by proximal tubule important?
because organic compounds are bond to plasma protein (it wont be filtered) so they need to be secreted somehow
How are organic anions secreted?
tertiary active transport: Na/K Atpase (Na gradient used) gradient used by NaDicarboxylic acid transporter which transports along with Na, alpha ketogluterate across basolateral membrane into cell. Alpha ketogluterate is exchanged with organic anions OAT1,2,3
(no need to know names of transporters)
Organic Cations (creatine, epinephrine, NE) use
use electrical gradient to move passively into cell or they can exit luminal side by OC/H+ antiporter or MDR1
The thin descending loop
and thin ascending loop of
Henle are important in the
counter
current multiplication mechanism
and urine concentration and dilution
Thin Descending H2O and NaCl permeability
H2O=Permeable
NaCl=Permeable
Thin Ascending permeability to NaCl and H20
o
NaCl permeable
H2O impermeable