Glomerular Filtration L04

Question 1

List the parts of a nephron.

Answer 1

1. afferent arteriole
2. efferent arteriole
3. glomerulus
4. Bowman’s capsule
5. Proximal tubule
6. Loop of Henle
7. Distal tubule
8. Collecting duct

Question 2

what is the renal plasma flow rate?

Answer 2

600ml/min

Question 3

define bulk flow.

Answer 3

movement of water and solutes together due to a pressure gradient.

*Glomerular filtration involves bulk flow as well as diffusion of molecules.

Question 4

which two ‘forces’ drive the flow of filtration across the glomerulus?

Answer 4

hydrostatic pressure - pressure generated by the heart, drives fluid out of capillaries.

osmotic/oncotic pressure - impedes flow, created by plasma proteins

Question 5

does the osmotic/oncotic force increase or decrease across the capillary?

Answer 5

increase - losing more water, increase in concentration of plasma proteins, greater oncotic/osmotic pressure (greater pressure to stop movement of water by osmosis)

technically osmotic force decreases as osmotic is opposing osmosis and water potential gradient decreases along capillary as solutions start to equilibrate but oncotic increases as more force from plasma proteins as more concentrated at end of capillary

Question 6

what effect will CONSTRICTION of the AFFERENT arteriole (proximal) have on glomerular hydrostatic pressure and flow of substances from capillary into glomerular space?

Answer 6

• decrease pressure in capillary

- decrease flow into glomerulus

Question 7

what effect will CONSTRICTION of the EFFERENT arteriole (distal) have on glomerular hydrostatic pressure and flow of substances from capillary into glomerular space?

Answer 7

• increase pressure in capillary

- increase flow into glomerulus

Question 8

what effect will DILATION of the AFFERENT arteriole (proximal) have on glomerular hydrostatic pressure and flow of substances from capillary into glomerular space?

Answer 8

• increase pressure in capillary

- increase flow into glomerulus

Question 9

what effect will DILATION of the EFFERENT arteriole (distal) have on glomerular hydrostatic pressure and flow of substances from capillary into glomerular space?

Answer 9

• decrease pressure in capillary

- decrease flow into glomerulus

Question 10

Why is filtration pressure along the glomerular capillary always outwards i.e. why is fluid always moving out of the capillary?

Answer 10

because the glomerular hydrostatic pressure is greater than the Bowman’s space hydrostatic pressure and the oncotic pressure. Therefore the net perfusion pressure is always out of the capillary (although this perfusion pressure decreases along the length of the capillary - pressure gradient decreases)

Question 11

Describe the course of the efferent arteriole once it has left the glomerulus.

Answer 11

> portal vein > second capillary bed surrounding loop of Henle (peritubular capillaries) > interlobular vein > arcuate vein > interlobar vein > renal vein

Question 12

How is the hydrostatic pressure in peritubular capillaries different to that of the glomerular capillaries?

Answer 12

much more similar to systemic capillary pressure *oncotic pressure is much higher

Question 13

What are the three layers separating the blood in capillary from the lumen of the Bowman’s capsule?

Answer 13

1. capillary endothelium
2. glomerular basement membrane
3. epithelial cells/podocytes of Bowman’s capsule

Question 14

What is special about the endothelial cells of the glomerular capillaries?

Answer 14

they have fenestrations

Question 15

Describe the structure of podocytes with regards to the filtration barrier.

Answer 15

podocytes have small foot processes (pedicles). pedicles interdigitate to form the barrier with filtration slits between them to allow the passage of substances.

Question 16

Apart from size of molecules, how else can the filtration barrier restrict the passage of molecules into the capsule?

Answer 16

Charge - basement membrane (collage) and endothelium (glyococalyx) are both negatively-charged.

This prevents the passage of negatively charged proteins into the filtrate but does allow the passage of positively charged molecules and generally neutral molecules too (but less).

Question 17

List the molecules which pass into the filtrate.

Answer 17

Na+, K+, Cl-, HCO3-, Mg2+/Ca2+, glucose, urea, water

Question 18

roughly, what is the glomerular filtration rate (GFR)?

Answer 18

120ml/min or 180L/day

Question 19

What is the filtration fraction?

Answer 19

the proportion of renal plasma flow which is filtered by the glomerulus

OR

GFR/ renal plasma flow
= 120/ 600
= 0.2

Question 20

Define GFR.

Answer 20

the amount of blood filtered in the glomerulus per unit time

Question 21

Why is creatinine used to measure GFR?

Answer 21

It is freely filtered into the filtrate but it is not secreted (adding more creatinine into filtrate) nor reabsorbed (losing creatinine) over the length of the tubules.
Therefore the concentration of creatinine in urine is same as concentration of creatinine in plasma.

• creatinine is a substance derived from creatine and creatine phosphate in muscle. It is produced by the body at a steady rate.
• can also use inulin (injected intravascularly) based on same concept

Question 22

How is the GFR measured using creatinine?

Answer 22

1. can calculate rate of excretion of creatinine:

creatinine excretion rate = (Ccr,u x V)/t = Ccr,u x V(dot)

where Ccr,u - urine creatinine concn
V - volume of urine produced
t - collection time
V(dot) - rate of production of urine

2. rate of creatinine excretion = rate of creatinine filtration (as freely filtered and not reabsorbed)
3. rate of creatinine filtration = GFR x Ccr,p

where Ccr,p = concentration of creatinine in plasma

4. Ccr,u x V(dot) = GFR x Ccr,p
5. rearrange to get FORMULA:

GFR = (Ccr,u x Vdot)/Ccr,p

Question 23

What is the formula for estimated GFR (eGFR)?

Answer 23

eGFR = k/Ccr,p

where k is a constant correlating with age, mass and sex.

*in Cockcroft-Gault formula:

eGFR = ((140-Age) x mass xC)/Ccr,p

where C=1.23 for men and 1.04 for women

Question 24

What does the eGFR formula tell you about the relationship between GFR and the rate of creatinine production/filtration?

Answer 24

they are inversely proportional.

Question 25

What happens to the GFR with age and why?

Answer 25

GFR falls as with age due to the progressive loss of nephrons as we age. *causes Ccr,p to rise as rate of production of creatinine remains high and GFR decreases.

Question 26

What is proteinuria?

Answer 26

protein in the urine

Question 27

What does proteinuria suggest pathologically?

Answer 27

Glomerular dysfunction which could indicate renal failure due to nephrotic syndrome.

Question 28

what is glomerulonephritis?

Answer 28

set of conditions where there is predominant dysfunction of glomerulus.

Question 29

What is congenital nephrotic syndrome and how does it affect glomerular filtration?

Answer 29

rare genetic disorder of either nephron or podocin (components of glomerular barrier between podocytes).

barrier is more permeable to plasma membranes –> proteinuria.