SM 189-190: GFR

Question 1

Differences between the two types of nephrons: Location in kidney, abundancy, length of LoH

Answer 1

1. Cortical Nephron: located all around cortex of kidney, most abundant, short LoH
2. Juxtamedullary Nephron: located near junction of cortex and medulla, less abundant, longer LoH - more responsible for medullary interstitial conc. gradient

Question 2

What are the 4 basic mechanisms for renal excretion?

Answer 2

Excretion = Filtration - Reabsorption + Secretion

Question 3

Three components to the Glomerular Filtration Barrier

Answer 3

1. Fenestrated Capillary Endothelium (filters size) - coated in glycocalyx (filters charge)
2. GBM - meshwork of negatively charged polyanions (filters charge and size)
3. Podocyte foot processes coated with negatively charged glycoprotein (filters charge and size) - molecules pass through slit diaphragms - regular spacing via these cell adhesion molecules

Question 4

What is the equation for determinants of GFR?
What do the variables mean?
What is a normal GFR?
Do pregnant women have a higher or lower GFR?

Answer 4

GFR = (Lp)(S)(deltaP - deltaPi)
Lp = Glomerular-Capillary Wall Permeability: intrinsic, normally constant
S = Total Glomerular Capillary Surface Area (modulated in some disease processes)
deltaP = hydrostatic pressure gradient = KEY filtration Driver, favors filtration because Pgc > Pbs always
deltaPi = oncotic pressure gradient = KEY filtration Opposer, fights filtration
Pi,bs almost always zero (no proteins in ultrafiltrate)
Normal GFR = 125mL/min (180L/day filtered)

Over course of glom, Pbs rises to meet Pgc; Pi,gc increases as fluid leaves during filtration - reaches equilibrium point where filtration stops

Question 5

What factors modulate (Lp*S) in GFR?

Answer 5

Mesangial Cell Contraction: reduces S - lowers GFR

Question 6

What factors modulate Pgc

Answer 6

Minor - Renal Artery Pressure (Systemic BP changes should not cause drastic GFR changes)

1. AA Tone
   1a. Intrinsic Myogenic Reflex: high GFR = high stretch = AA VC = lower GFR - buffer for BP Changes
   1b. Vasoconstrictors: Adenosine/ATP, catecholamines, PGF-2alpha
   1c. Vasodilators: NO, Prostaglandin, bradykinin
2. EA Tone
   2a. Vasoconstrictors: AngII, catecholamines
   2b. Vasodilators: adenosine

Question 7

How does GFR change in response to EA/AA VC/VD?

Answer 7

EA VC: GFR up
EA VD: GFR down
AA VC: GFR down
AA VD: GFR up

Question 8

Tubuloglomerular Feedback
When is it useful?
What parts of the nephron take action?
What is the signaling mechanism?

Answer 8

Operates in HIGH renal pressure to REDUCE GFR
involves Macula Densa - communicates to AA via adenosine
High GFR 2/2 high Pgc = High NaCl detected in macula densa = release of ATP/adenosine to AA = AA VC = GFR drops to normal

Macula densa releases ATP, gets converted to adenosine, which binds A1R on AA SMC surface GPCR to cause AA VC (EA has different adenosine receptor to cause EA VD, but unaffected in TGF)

Question 9

RAAS in GFR regulation
When is it useful?
What is the mechanism to secrete renin?

Answer 9

Operates in LOW renal pressure to RAISE GFR
Low GFR = low NaCl detected in macula densa = activates COX-2 = formation of PGE2 = binds EP4 on granular cells in wall of AA = degranulation and renin secretion!
Cl more of a trigger than the cation

Question 10

What 4 things stimulate renin release?

Answer 10

1. low Cl delivery to the macula densa
2. beta1-adrenergic stimulation (SNS)
3. catecholamines, PTH, glucagon, Prostaglandins, histamine
4. Cellularly: high cAMP and low Ca

Question 11

What inhibits renin release?

Answer 11

1. High Cl delivery to the macula densa
2. AngII (negative feedback)
3. ANP, ADH, adenosine, NO
4. Cellularly: low cAMP and high Ca

Question 12

What is the effect of AngII?

What are the effects of beta blockers, ACE-i, and ARBs on RAAS ability to modulate GFR?

Answer 12

EA VC = raise GFR (and systemic increase in BP)
beta blockers = decrease adrenergic tone = EA VD (lower GFR)
ACE-i = less AngII formation = EA VD
ARB = less AngII binding = EA VD
These meds make it difficult for GFR autoregulation - health consequences if GFR dips too low

Question 13

What is the clearance equation?

Answer 13

Clearance = [Urine Conc x Urine Flow Rate]/[Plasma Conc]

Note: Urine Conc x Urine Flow Rate = Excretion Rate

Question 14

What substance is the BEST approx of GFR?
What makes it the best?
What is it?
What are its limitations?

Answer 14

Inulin: Freely filtered by glom, not reabsorbed/secreted, not metabolized/excreted extra-renally, is measurable in urine/plasma
Inulin - poly fructose molecule (from Jerusalem Artichoke)
Limits: it is exogenous source, needs steady state IV infusion

Question 15

What substance is the most WIDELY used GFR surrogate?

From what sources does this substance arise?

Answer 15

Creatinine: metabolic byproduct of creatine used in muscle tissue to hold onto phosphate groups

Sources: Protein Metabolism, Muscle Breakdown, Dietary Supplements

Question 16

What are the limitations to using creatinine as approximating GFR?

How can you predict Cr Clearance with expected production of Cr?

Answer 16

Renal Function must be steady-state, no recent vigorous activity/protein loading
Some Cr is secreted; only low P,Cr is useful to approx GFR

Cr Clearance = (20-25 mg Cr/kg) x (Body Weight) for males; (15-20 mg Cr/kg) x (Body Weight) for females