Renal Blood Flow and GFR

Question 0

What does (re)absorption refer to?

Answer 0

Movement of water and solutes from the lumen of tubules into the interstitial space/ blood.

Question 1

What’s ultrafiltration?

Answer 1

The fluids that gets across the glomerulus into Bowman’s space.
Very little protein, but lots of ions, glucose, etc.

Question 2

What does secretion refer to?

Answer 2

Direct movement from tubule basolateral membrane -> lumen. (without being filtered)

Question 3

What does excretion refer to?

Answer 3

Actual loss of water or solutes into the outside world.

Question 4

What does oncotic pressure refer to?

Answer 4

Osmotic pressure resulting from the presence of large macromolecules (esp. albumin).

Question 5

Review: Which nephrons have loops of Henle that go deep?

Answer 5

Juxtaglomerular nephrones.

Question 6

About what percentage of CO (at rest) goes to the kidneys?

Answer 6

20%

Question 7

Is renal blood flow (RBF) really what matters for filtration rate?

Answer 7

No, it’s really the acellular plasma blood flow (PBF) that counts.

Question 8

How is PBF derived from RBF?

Answer 8

PBF = RBF(1 - HCT)

Question 9

What are the typical units of glomerular filtration rate (GFR)?

Answer 9

ml/min

often normalized to body surface area

Question 10

What’s a normalish GFR for a young adult?

Answer 10

120-125ml/min

or 100ml/min/1.73 m^2

Question 11

Do blood and protein get into the filtrate?

Answer 11

Nope. Not much anyway, in normal kidneys.

Question 12

What ratio expresses how permeable the glomerulus is to a particular substance?

Answer 12

Ultra filtrate / plasma ratio (UF/P).

Na+, K+, glucose have UF/P = 1.
Albumin’s UF/P is close to 0.

Question 13

Okay, so actually there are 4 forces that affect glomerular filtration. What are they?

Answer 13

Glomerular capillary hydrostatic pressure.
Glomerular capillary oncotic pressure.
Bowman’s space hydrostatic pressure.
Bowman’s space oncotic pressure. (but this last one is normally close to 0)

Question 14

Which of the 4 forces affecting glomerular filtration varies along the length of the glomerular capillary bed?

Answer 14

Capillary oncotic pressure increases downstream. (Water has been removed from the serum, leaving a higher concentration of osmotically active macromolecules behind.)
Thus the driving force for filtration diminishes downstream.

Question 15

Where does “normal” sit on the graph of RPF (renal plasma flow) vs. GFR?

Answer 15

Right before the shoulder/plateau of the relationship - such that increase in RPF won’t change GFR much, but decrease in RPF leads to rapid decline of GFR.

Question 16

How is glomerular capillary pressure kept fairly constant despite changes in arterial pressure?

Answer 16

By regulation of constriction/dilation of the afferent and efferent arterioles.

Question 17

What is the filtration factor?

What does a higher one mean for capillary oncotic pressure?

Answer 17

GFR / RPF.

Higher filtration factor -> increased capillary oncotic pressure.

Question 18

The relationship between afferent/efferent arteriole constriction, capillary pressure, and GFR is pretty obvious.

Answer 18

Yep.
Constrict the afferent -> decreased capillary pressure -> decreased GFR.
Constrict the efferent -> increased capillary pressure -> increased GFR.

Question 19

What effect does angiotensin II have on GFR? How?

Answer 19

Angiotensin II increases GFR.
It constricts both afferent and efferent arterioles, but has a much greater effect on efferents -> net increase in capillary pressure.
(thus ACE inhibitors can decrease GFR)

Question 20

What effect do catecholamines (epi and NE) have on GFR? How?

Answer 20

Both decrease GFR by causing constriction of the afferent arteriole.

Question 21

What effect does endothelin have on GFR? How?

Answer 21

Endothelin reduces GFR because both afferent and efferent arterioles are constricted.

Question 22

Effect of PGE2 and prostacyclin on GFR? How?

Answer 22

Increases GFR by causing dilation of afferent arteriole.

Question 23

What does the intrinsic myogenic reflex refer to?

Answer 23

The afferent arteriole constricts or dilates in response to the pressure it experiences.

Question 24

Review: Where are the macula densa cells?

Answer 24

Macula densa cells are in the thick ascending limb

Question 25

Review: Where are the juxtaglomerular cells? What do they produce?

Answer 25

Juxtaglomerular cells are in the efferent arteriole.

These cells produce renin.

Question 26

What does the macula densa actually detect?

What molecule is key for this?

Answer 26

Effectively it assesses tubuloglomerular flow (TGF), but it actually senses the amount of Cl- that enters it.
Cl- enters via the NKCC2 symporter.

Question 27

What is the response to increased tubuloglomerular flow (TGF)?

Answer 27

Renin release -> A-II -> constriction of afferent arteriole to reduce flow.

Question 28

For a solute that is not synthesized or metabolized by the kidney… how do arterial input, venous output, and urinary output of the substance relate?

Answer 28

Arterial input = venous output + urinary output

Question 29

What is the expression for the filtration rate of a substance in the plasma that is freely filtered?
How does this relate to urine content of the substance (assuming no reabsorption or secretion)?

Answer 29

amount filtered (per unit time) = GFR * Px
Where Px is the plasma concentration of substance "x".

GFR * Px = Ux * V
(where Ux = [x] in urine, V = urine volume; assuming no reabsorption or secretion)

Question 30

What molecule is an “ideal” marker of GFR?

Answer 30

Inulin - freely filtered, not secreted or absorbed, non-toxic, not metabolized
Thus P(in) * GFR = U(in) * V ... or GFR = ( U(in)*V ) / P(in)

U(in) and V is measured by 24 hour urine collection.

Question 31

More generally, what does Ux*V / P represent?

Answer 31

Clearance

for inulin, clearance = GFR

Question 32

What endogenous substance has clearance almost equal to GFR (like inulin)?

Answer 32

Creatinine (though it’s not perfect)

Question 33

Is creatinine clearance equal to, greater than, or less than GFR?

Answer 33

It’s a little greater than GFR, due to tubular secretion of creatinine.
Additionally, the less GFR there is, the more tubular secretion of creatinine happens (masking effects of declines in GFR).

Question 34

Why might creatinine rise despite no change in GFR? 3 drugs that cause this?

Answer 34

Inhibition of creatinine secretion will cause increased plasma creatinine without reduced GFR.

• Cimetidine
• Trimethoprim
• Probenecid

Question 35

For clinical purposes, what can you measure to get a pretty good easy estimate of GFR?

Answer 35

Take the average of creatinine clearance (overestimate) and urea clearance (underestimate).

Question 36

Can creatinine clearance be estimated without a 24 hour urine collection?

Answer 36

Yes.. there are several equations that produce an estimate from serum creatine (based on age, race, sex, etc.)

Question 37

What substance present in the serum might be used to calculate GFR in the near future?

Answer 37

Cystatin
(it’s an endogenous protease that’s produced at constant rate, 100%ish absorbed in the proximal tubule, and 100%ish metabolized there. So plasma levels correlate pretty well with GFR)

Question 38

What is fractional excretion? What does it tell you?

Answer 38

FE = Clearance / GFR = UV/(PGFR)

A low FE tells you the body is avidly holding on to that substance (assuming it is freely filtered).

Question 39

In order for creatinine to be a good measure of GFR, creatinine must be a steady state. When wouldn’t this be true?

Answer 39

This might not be true in acute renal injury. The GFR will be low, but the creatinine will not have risen.