Unit 7 - Filtration and Clearance

Question 1

what is glomerular filtration? its components? what causes it?

Answer 1

process by which plasma is filtered across glomerular capillaries to form a protein-free ultrafiltrate in Bowman’s space

• Starling forces across capillaries drive net efflux of ultrafiltrate from plasma
• with exception of plasma protein, organic and inorganic anionic and cationic solutes are freely filtered across glomerular capillaries and exist in same concentration in plasma and ultrafiltrate

Question 2

what is the daily GFR? how does this compare to other capillaries? to ECF?

Answer 2

125 ml/min = 180 L/day

• only 3-4 L of plasma are filtered daily to form interstitial fluid
• ECF is only 14 L, meaning the entire ECF is filtered every 2 hours
• -maintains ECF volume and solute composition within narrow limits

Question 3

how does hydrostatic pressure inside the glomerular capillary decrease by only a small amount (45-50 –> 41-57) from beginning to end?

Answer 3

post capillary efferent arteriole constriction uniquely specific to glomerular (not systemic) capillaries
-happens despite decrease of plasma volume

Question 4

how does Kf of glomerular capillaries compare to systemic? what does it account for?

Answer 4

filtration coefficient is more than 200x greater, accounting for large disparity in plasma filtration

Question 5

why does oncotic pressure increase from beginning to end (25 –> 35) of glomerular capillary? why does Bowman’s space oncotic pressure increase significantly in nephrotic syndrome?

Answer 5

plasma filtration and concentration of plasma protein

-increased Bowman’s space oncotic pressure causes edema due to increased filtration of plasma PRO

Question 6

what are the 3 components of the glomerular barrier to filtration? how do they help filter?

Answer 6

1. endothelial cells of glomerular capillaries restrict passage of cellular elements into Bowman’s space
   - fenestrations are ~70 nm
2. capillary basement membrane restricts filtration of solutes > 1 kDa
   - has anionic charge (due to proteoglycans), to favor filtration of cations and restrict filtration of anionic PRO
3. podocytes of visceral epithelial layer of Bowman’s capsule have foot processes covering outer glomerular capillaries
   - contiguous foot processes are separated by filtration slits connected by thin slit diaphragm with pores 4-14 nm
   - glycoPRO with negative charge cover podocytes, filtration slits, and slit diaphragms favoring filtration of small cationic solutes

Question 7

what size solutes are freely filtered?

Answer 7

those below 4 nm (most effective are s only reabsorbed

Question 8

equation of filterability

Answer 8

solute concentration in Bowman’s space / solute concentration in plasma
-a solute freely filtered exists at same concentration in plasma and filtrate (ratio of 1)

Question 9

how is solute filtration dependent on solute charge? what happens if this “barrier” is gone?

Answer 9

negative charge on basement membrane and foot processes impedes passage of negatively charged solutes (PRO) while allowing neutral and positively charged solutes

• removing the negative charge from the barrier will increase passage of anions
• -serum nerphritis has increased filtration of plasma PRO

Question 10

what are the renal hemodynamics and how do they relate to each other?

Answer 10

cardiac output = HR x SV = 5-6 L/min = 7200-8640 L/day
renal blood flow (RBF) = 1-1.2 L/min = 1440-1728 L/day
renal plasma flow (RPF) = 600-720 mL/min = 860-1040 L/day (55% of RBF)
GFR = 125 mL/min = 180 L/day (20% of RPF)

Question 11

what is the filtration fraction? what is it usually?

Answer 11

GFR/RPF = fraction of RPF filtered at the glomeruli

-125 mL/min / 600 mL/min = 0.2

Question 12

how is urine flow affected if chronic/acute renal failure reduces blood flow to zero? how should drugs be changed?

Answer 12

there is no urine output

-drugs should be reduced to allow less toxicity

Question 13

what happens to RPF and GFR if…

1. afferent arteriolar constriction
2. efferent arteriolar constriction
3. both afferent and efferent arteriolar constriction
4. increased plasma PRO
5. decreased plasma PRO
6. ureter obstruction

Answer 13

1. decreased glomerular hydrostatic pressure causes decreased RPF and GFR
2. increased glomerular hydrostatic pressure causes decreased RPF and increased GFR
3. no change in glomerular hydrostatic pressure causes very low RPF, but no change in GFR (since starling force are constant)
4. increased glomerular oncotic pressure causes no change in RPF, but decreased GFR
5. decreased glomerular oncotic pressure causes no change in RPF, but increased GFR
6. increased Bowman’s hydrostatic pressure causes no change in RPF, but decreased GFR

Question 14

what do Starling forces do in post-glomerular peritubular capillaries?

Answer 14

drive fluid reabsorption from interstitial space

-oncotic pressure difference > hydrostatic pressure difference

Question 15

what is the direction of filtration from tubular fluid in lumen to peritubular capillary?

Answer 15

tubular fluid in lumen –> tubular cell –> interstitial fluid –> peritubular capillary

Question 16

when does renal failure begin?

Answer 16

when GFR decreases to below 20 mL/min (loss of founction of 85% of nephrons)

Question 17

when can the renal clearance of a solute be used to measure GFR?

Answer 17

if renal handling of the solute is:

• freely filtered at the glomerulus (100%)
• not reabsorbed in any segment of the nephron (0%)
• not secreted in any segment of the nephron (0%)
• not synthesized by the kidney (0%)
• not metabolized (or otherwise chemically changed) by the kidney (0%)

if the above properties are matched, the amount of solute filtered should equal the amount excreted

Question 18

what are solutes used to measure GFR? why?

Answer 18

exogenous inulin (fructose polymer)

• IV infusion to maintain constant plasma concentration
• measured very accurately in plasma and urine even if low concentration

endogenous creatinine (from creatine phosphate metabolism in skeletal muscle)
-if no strenous exercise or disease, there should be a constant amount of creatinine/time diffusion from skeletal muscle to plasma

these 2 are used because both are filtered 100% from glomeruli

Question 19

if creatinine production is constant, what does increased plasma creatinine concentration indicate?

Answer 19

decreased clearance of creatinine from plasma

-indicates decreased GFR due to decreased number of functional nephrons

Question 20

if kidneys are recovering from acute renal disease, what should happen to plasma creatinine levels?

Answer 20

they should decrease, indicating an increase in creatinine clearance and increased GFR

Question 21

what is the equation for clearance of a solute?

Answer 21

Cs = Us x V / Ps

Question 22

how does “renal handling” of a solute differ within nephron?

Answer 22

may be only reabsorption, only secretion, or both, in same or different segments of a nephron
-if both occur, the difference in solute reabsorption and secretion determines either net solute reabsorption (Cs/Cin < 1) or net solute secretion (Cs/Cin > 1)

Question 23

fractional excretion of water

Answer 23

FEwater = V / GFR
fraction of glomerular filtrate not reabsorbed from tubular fluid along nephron, and thus appears as urine
-ratio of urine flow rate to GFR

Question 24

how is FE of water measured?

Answer 24

draw blood and collect urine specimen to measure plasma and urine [creatinine] without having to time flow

Question 25

fractional excretion of solute

Answer 25

FEs = Cs/Ccreatinine

-estimated as ratio of Cs to GFR

Question 26

what is fractional reabsorption?

Answer 26

fraction of filtered water or solute that is reabsorbed thus not in urine
-usually quantified as 1 - FE

Question 27

when water and Na are in balance, how much of filtered water and Na appears in urine? in negative water balance (dehydration)? in positive water balance? what about fractional reabsorption?

Answer 27

usually, FEwater = FEsodium = 1%, so fractional reabsorption is 99%

• negative balance: FEwater < 1%
• positive balance: FEwater > 5%

FEsodium constant at 1%

Question 28

what is autoregulation of RBF due to?

Answer 28

• myogenic response of renal vasculature to pressure changes
• tubuloglomerular feedback at macula densa cells, sensing an increase/decrease in GFR to cause increased/decreased resistance (constriction) of afferent arteriole to return GFR to normal

Question 29

how is autoregulation of RBF maintained?

Answer 29

it is intrinsic to kidney, and occurs in absence of autonomic innervation of kidney