Ch.4/5 GFR,Prox,Henle Flashcards
Review: What are the 3 principle components of renal function?
GFR, Reabsorption, Secretion
What is PAH used to measure? Why?
Para-Amino-HippUric Acid is used to measure RPF..because it is freely filtered and avidly secreted for total excretion
What can you use to measure RPF?
PAH-freely filtered and fully secreted=total exctretion
What are examples of substances that are more reabsorbed then excreted?
Na+,Cl-, H2O
What are two examples of a substance that is filtered but then completely reabsorbed and NOTHING is excreted?
Glucose, Bicarb
What is the general trend of all the substances listed and their amount reabsorbed? (There was only one substance that didn’t fit in…what was it?)
Most of the substances were MOSTLY reabsorbed back into the body (H2O=99.2%, Na+=99.4%…) The only odd ball was Urea=50% reabsorption (thank God! were getting rid of it!)
What is transport from the Lumen of the Nephron to the Peritubular Capillary called? Which ends of the nephron participate?
Tubular Reabsorption…BOTH the Proximal and Distal ends of the Nephron participate in this.
What is transport from the peritubular capillaries to the Lumen of the Nephron? Which ends of the nephron participate?
Tubular Secretion…ONLY in the PROXIMAL tubules
What are the 2 ways transport can occur across the renal epithelial cells? Which one is the major way?
- Transcellular (majority) 2.Paracellular
What are the 3 trans-membrane transport systems at work?
1.Channel-Mediated diffusion (passive, uses [gradient])…2.Carrier Mediated diffusion (uniport, symport, anti port)…..3.Carrier-Mediated ‘active transport’ (ATP needed, against [gradient])
Absolute dependence on Na+-K+-ATPase located ONLY on the _______ membrane to maintain low intracellular ____ concentration.
basolateral…[Na+]
Where does Na+ enter the cell via luminal membrane Na+-selective channels?
The Cortical COLLECTING TUBULE
Where am I?(area of nephron and which membrane) Downhill” movement of Na+ across luminal membrane into the cell facilitates “uphill” movement of glucose
Proximal Tubule…Luminal Membrane
Where am I?(area of nephron and which membrane) … Glucose uniporter transports glucose out of the cell across the basolateral membrane
Proximal Tubule…Basolateral Membrane
What are the two Co-Transporters on the luminal membrane of the proximal tubule that transport Na+&Glucose?
SGLT-2 (high capacity-low affinity) & SGLT-1 (low capacity-high affinity)
What do type II DM patients use SGLT-2 inhibitors?
To keep Glucose out of the blood and excrete it into the urine. If they block these SGLT-2’s in the proximal tubule, they won’t reabsorb as much.
How do the 7 types of Na+ transporters of the Proximal tubule get categorized?
3 Amino Acid cotransporters, 2 phosphate co-transporters, 1 Na+-H+ exchanger and 1 Neutral/dibasic(cationic)/dicarboxylic(anionic)
For the 10% of protein that does sneak by and get filtered (OH and Vit-D as well)…What are the two binders and what is the area the protein is brought into the cell?
Megalin & Cubulin bind and then into membrane Clathrin-Coated Pits (CCP)
What happens to those sneaky filtered proteins once they’ve been endocytosed? (and Vit-D!)
Degraded to AA’s and released basolaterally..then randomly Vit-D gets activated
About how much glomerular filtrate is reabsorbed in the proximal tubule? What are the examples of H2O and Na+?
Approx 2/3…H2O 180L–>120L and 26,000mEq of Na+–>17,000mEq
Which solutes are COMPLETELY absorbed proximally?
Glucose, AA’s, HCO3-
What 2 things are unique about the reabsorption of Cl- in the proximal tube?
It happens much later then the other substances AND its absorbed paracellularly!
What is the 2 step process for the REST of absorption (after the initial 2/3 in the proximal tubule)?
1.Small osmotic gradient is made (tubular fluid osmolality < extracellular fluid) 2.Water moves from the lumen to the intersitium down its osmotic gradient
Complete reabsorption of this isotonic fluid from the proximal tubule is a two-phase process…What are they? What drives the second phase?
1.lumen —> interstitium 2.Interstitium—>peritubular capillaries DRIVEN by Starling Forces
Which two starling forces regulate peritubular capillary fluid uptake?
LOW Peritubular Capillary HYDROSTATIC pressure (downstream of the afferent/efferent resistance points) AND high oncotic pressure (high [protein])
The proximal tubule reabsorbs a constant percentage (~67%) of the filtered load: so-called _________.
GLOMERULOTUBULAR (GT) BALANCE
GT balance helps maintain a relatively constant delivery of fluid to the _______.
Distal nephron
If GFR is 100ml/min how much will make it to the Loop of Henle?
33ml/min = (100-(2/3x100)) 2/3 of GFR taken reabsorbed by this proximal tubule!
What happens to proximal tubule reabsorption when we increase efferent arteriolar resistance?
Increase in Efferent Arteriole Resistance = Increase in P in the GC = Increase in GFR = INCREASE in proximal reabsorption (WHA??)
What is the filtration fraction?
Filtration Fraction= (GFR/RPF)
When collecting samples via IN VIVO micropuncture, what areas can you access? What areas can’t you?
Can get the Proximal and Distal Tubules…Cannot get to juxtamedullary nor collecting tubule
If we use micro puncture in vivo, what do we use in vitro?
Microperfusion…cut out any portion of the Kidney you want to sample and run stuff through it.
What is the point where all transport proteins are saturated in the tubule??
Tubular Transport Maximum (Tm)
How do I find the amount of a material that is Reabsorbed?
Amount Reabsorbed=Amount Filtered- Amount Excreted
How do I find the amount filtered?
Amount Filtered = GFR x Particles of Glucose
How do I find amount excreted?
Amount excreted = Volume x Urine Glucose
“_____”- represents the slight variance in Tm between individual nephrons.
“Splay”–some nephrons have LOTS of SGLT-2s some have less..
“_______”- represents the plasma concentration (of glucose) at which Tm is exceeded.
“Threshold”
Why is there Glucose in the pee of DM Patients?
filtered load of glucose has become»_space;> than TubularTransportMaximum (Tm)
What is the primary site of secretion for organic anions and cations?
The proximal tubule!
What are the two Exogenous Anions used as “Loop Diuretics”? (they are not filtered well, but secreted)
Fur-os-em-ide & Bum-et-an-ide
What are the 3 transporters involved in Organic Anion(OA) transport across the Basolateral membrane? CAN YOU DRAW WHATS HAPPENING?
1.Organic Anion Transporters 1 & 3 (OAT-1 & OAT-3) 2.Na+-Dicarboxylate Cotransporter (NaDC) 3.Na+/K+ pump
Organic Anions are taken up across the ________ in exchange for_________ via Organic Anion Transporters 1 and 3 (OAT-1; OAT-3).
basolateral membrane…. α-ketoglutarate (αKG)
In organic anion transport in the Proximal tubule::: effluxed _______ is taken back into the cell via Na+-dicarboxylate cotransporter (NaDC).
α-ketoglutarate (αKG)
What are the two transporters that take Organic Anions across the Luminal Membrane? WOW! freaking lots of action to get these Organic Anions secreted into the Urine!!
OAT-4 and Multidrug Resistance-associated Protein-2 (MRP-2)
What atet the 4 pumps involved in the secretion of Organic Cations? (break them down by which membrane please)
Basolateral:Na+/K+ pump & OCT-1,2,3………Luminal:OC-H+ Antiporters (OCTN) and MDR1 (p-glycoprotein)
How do we use OAT’s non-selective behavior to our advantage during administration of penicillin?
Giving PAH with Penicillin keeps the OAT’s from secreting the Penicillin. (OATs will move either)
What are the two stipulations for a GFR marker?
1.Never Reabsorbed nor Secreted 2.Not produced or metabolized by the kidney
What are the two primary GFR markers? How will I find GFR if by knowing excretion?
Inulin and creatinine…Since Inulin and Creatinine are freely filtered and NOT reabsorbed nor secreted, GFR=excreterd GFR=Vol x Urine Inulin / Inulin in
For inulin or creatinine, ALL of the plasma filtered by the glomeruli is effectively “_______” .
“cleared”……Hence the clearance of inulin (CIN) or the clearance of creatinine (CCR) = GFR
Simultaneously measuring the clearance of substance X and the clearance of inulin or creatinine can provide an indication of how X is handled by the kidney: When CX
reabsorption
Simultaneously measuring the clearance of substance X and the clearance of inulin or creatinine can provide an indication of how X is handled by the kidney: When CX > CIN the substance must undergo net _______.
secretion
What substances have a clearance of 0?
Glucose, Bicarb (when things are working normally)
How are we to find RPF??
X amount in (renal artery) = X amount out (renal vein) + X amount out (urine)…1) RPF=Urine PAH x Vol / P PAH 2)
How do I find RBF??
RBF=RPF/(1-hematocrit)
Interstitial osmolarity progressively ________ from cortex / medulla border to papilla tip.
increases
Cortex interstitial osmolarity: _____ mOsm/L (isotonic)
ii. medulla interstitial osmolarity gradient in humans: ____—> _____ mOsm/L (cortical junction —> papilla tip).
300 mOsm/L….300—>1400mOsm/L
Hypertonicity created by deposition of ____ and ____ into medulla interstitial. This interstitial hypertonicity is essential for __________.
NaCl and urea….. urine concentration
Humans can excrete a urine with an osmolarity of ____ mOsm/L; rats, a urine of _____ mOsm/L)
1400 mOsm/L……3000mOsm/L
What are the two functions of the descending limb of Henle’s Loop?? (makes sense!)
- REABSORB H2O 2.NO SOLUTE REABSORPTION (especially NaCl!)…makes sense because we are gaining osmolality as we go down the loop
ThinDescendingLimb system capable of reabsorbing approx __ - ___ L H2O/day!
30-40L H2O/day!
What are the main 2 functions of the Ascending limb of Henle?
- AVID Reabsorption of NaCl (we have to get the osmolality of the surrounding area back down to 300) 2. NO reabsorption of H20 (same logic as above)
What is the nickname for the ascending loop of henle?
“the diluting segment”
What transporter is on the BasoLateral membrane of the thick ascending limb? (think of function!)
Na+/K+ pumps present on BL surface (we are AVIDLY reabsorbing NaCl) This will help us kick Na+ out
Which transporter is on the Luminal membrane of the thick ascending limb? (Think of overall function!)
We need to pull NaCl out of the Lumen for AVID reabsorption…so…An Na+-K+-2Cl- co-transporter is used here
Thick ascending limb: HOW IN THE WORLD do we get the necessary K+ out of the cell, into the luminal space, and then BACK into the cell to help other solutes out?
A K+ selective channel helps K+ go down its [gradient] out of the cell. This will then do 2 things. 1. Make a Positive Extra cellular environment for paracellular transport of cations…2.supplies our Na+-K+-2Cl- co-transporter
What transporter is blocked by LOOP DIURETICS?
Na+/K+/2Cl- transporter
What does ADH do to transportation in the thick ascending limb?
Increases transport (NaCl reabsorption)
What does Anti Natriuretic Peptide do to transportation in the thick ascending limb?
Inhibits transport
WHERE does Bartter’s syndrome have an effect?
The thick ascending limb
Where is K+ funky efflux happening?
Thick ascending limb
How would you describe the reabsorption of NaCl in the thin ascending limb?
Passive and limited…WEAK SAUCE
WHY is NaCl PASSIVELY absorbed along its gradient at the bottom of the L of H?
cause like the Tubular Fluid is 80% NaCl compared to the Interstital fluid of 50% NaCl (THANKS to 50% urea)
