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47 Cards in this Set
- Front
- Back
Filtered Load Equation
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(GFR) [P]x
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Excretion Rate equation
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(V)u [U]x
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Filtered load in normal conditions is equal to
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Excretion Rate
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Reabsorption or Secretion Rate Equation
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(Filtered Load-Excretion Rate)
+=reabsorptio -=secretion of substance plus something being added |
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Some substances, like Ca2+ are not freely filtered why?
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because they are bound to plasma proteins
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Transcellular pathway
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substances goes through luminal membrane..through epithelial cell, goes either to either basal membrane into interstitial space or into lateral space betwee epithelial cells
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Paracellular
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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
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What regulates paracellular pathway?
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Tight Junctions
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Tight Junctions form zipper like structures by
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membrane proteinswith extracellular domain :claddin and occludin. They also have connections to the cytoskelton.
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Mutation in claudin-16 causes
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A disease caused Hypomagnesemia-
Hypercalciuria Syndrome by affecting paracellular transport of calcium and magnesium in thick ascending limb of the loop of Henle |
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Na sites of reabsorption
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67% in proximal convoluted tubule
25% Thick ascending limb 5% Distal convoluted tubule |
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Site of Na reabsorption is site of action of
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many diuretics like "loop diuretics" at thick ascending loop
Thiazide diuretics at the distal convoluted tubule K sparing diuretics at the conducting tubule |
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Diuretics block
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Na transport and as a consequence H2O is lost
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Whats reabsorbed in the proximal tubule?
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100% Glucose
100% Amino Acids 85% HCO3- Most Pi, lactate, citrate Large amounts of Na+ |
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All of the transport mechanism on the proximal tubule dependent on
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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
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SGLT has two isoforoms in the proximal convoluted tubule
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SGLT 1 and 2 on apical membrane
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Once gluc inside the cell, it exits using
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Glut 2
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In the proximal tubule Carbonic Anhydrase converts HCO3 into CO2 and H+ and
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it is pumped into lumen via Na/H, HCO3 is free and reabsorbed into blood in a facilitated diffusion.
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Under normal conditions, SGLT takes care of all
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glucose in proximal tubule
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At concentrations less
than 200 mg/dL virtually 100% of glucose is |
reabsorbed and excretion
is 0 |
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Transport max (Tm) of glucose occurs
at about |
350 mg/dL.
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Glucose begins to be
excreted below |
Tm (ie. at
threshold) because of the phenomenon of splay |
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Mechanisms for splay
related to |
to relatively low
affinity of SGLT for glucose and because of nephron heterogeneity with respect to Tm |
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When saturation of SGLT occurs can lead to
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diabetes mellitus
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Transcellular reabsorption in late proximal tubule
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Early PT absorbs primarily Na+/HCO3-
Late PT absorbs Primarily Na+/Cl- |
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Paracellular Route in late proxima tubule
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Cl- moves down a
concentration gradient through tight junctions Cl- movement establishes a postive transluminal potential Na+ follows an electrical gradient |
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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 |
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Why does H2O follow Na?
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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)
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In the proximal tubule H2O is reabsobed via
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AQP1 on apical membrane.
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On basal membrane H2O exits through
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QP3/4
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is H2O readily regulated in the proximal tubule?
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No, because it just follows Na, regulation occurs on distal parts.
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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
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lots of proteins trapped in these capillaries leading to high oncotic pressure which favors fluid reabsorption from interstitial fluid into these capillaries
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Glomerulotubular Balance refers to
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ensuring a constant return of fraction of filtered load in proximal tubule
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What if GFR was increased (doubled) what would happen to filtered load?
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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
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GGlomerulotubular balance when theres volume expansion
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Volume is greater in plasma, this decreases oncotic pressure in capillaries and increases hydrostatic pressure, leadinf to decrease in reabsorption
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Glomerulotubular balance when theres volume contraction
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: proteins in peritubulular capillaries would be increased and oncotic pressure would go up, pressure goes down and reabsoprtion occurs
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What would be the effect on reabsorption if during volume expansion, GFR is constant
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less
reabsorption of Na+ and water occurs |
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what happens to reabsorption if GFR is constant during volume contraction
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more reabsorption of Na and water occurs
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Protein reabsorption is returned as
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returned as the ultrafiltrate
passes along the proximal tubule |
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All proteins that leaks in the nephron would be reabsorbed in proximal tubule. This relies on
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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
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Excessive Muscle cell breakdown could result in myoglobin found in plasma..why
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it would saturate endocytotic processes and myoglobin would end up in blood
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Why is secretion of organic anions and cations by proximal tubule important?
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because organic compounds are bond to plasma protein (it wont be filtered) so they need to be secreted somehow
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How are organic anions secreted?
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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) |
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Organic Cations (creatine, epinephrine, NE) use
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use electrical gradient to move passively into cell or they can exit luminal side by OC/H+ antiporter or MDR1
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The thin descending loop
and thin ascending loop of Henle are important in the |
counter
current multiplication mechanism and urine concentration and dilution |
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Thin Descending H2O and NaCl permeability
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H2O=Permeable
NaCl=Permeable |
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Thin Ascending permeability to NaCl and H20
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NaCl permeable
H2O impermeable |