Renal blood flow and glomerular filtration

Question 1

what is glomerular filtration and what is renal failure

Answer 1

The formation of an ultrafiltrate of plasma in the glomerulus of a kidney nephron
An abrupt fall in glomerular filtration is renal failure
Abnormalities in renal circulation lead to reduced glomerular filtration i.e. renal failure.

Question 2

What is a cardinal sign of renal failure?

Answer 2

Sharp drop in GFR

Question 3

What is the driving force for ultrafiltration?

Answer 3

Passive process: fluid is ‘driven’ through the semipermeable (fenestrated) walls of the glomerular capillaries into the Bowmans capsule space by the hydrostatic pressure of heart.

Question 4

What is the filtration barrier (fenestrated endothelium of capillaries and semipermeable Bowman’s capsule) highly permeable to and impermeable to?

Answer 4

• fluids
• small solutes (these are “freely filtered”: same concentration in filtrate and plasma).

But impermeable to:
cells
proteins
drugs etc carried bound to protein

Question 5

What does ‘freely filtered’ mean?

Answer 5

A substance that has the same concentration in the filtrate as in the plasma (e.g. small solutes)

Question 6

what is an ultrafiltrate?

Answer 6

A clear fluid (ultrafiltrate), completely free from blood and proteins, is produced containing electrolytes and small solutes = ‘primary urine’

Question 7

How to work out the amount excreted?

Answer 7

Amount excreted= Amount filtered + amount secreted - amount absorbed

Question 8

what is the driving force of glomerular filtration pressures?

Answer 8

Driving force = hydrostatic pressure in glomerular capillaries (due to blood pressure) (Pgc)

Question 9

What are the two forces opposing the hydrostatic pressure and what is the equation to work out the net ultra filtration pressure?

Answer 9

Driving force = hydrostatic pressure in glomerular capillaries (due to blood pressure) (Pgc)

Opposing pressures: hydrostatic pressure of tubule (Pt)
osmotic pressure of plasma proteins in glomerular capillaries (πgc)
Together these determine the net ultrafiltration pressure (Puf)

Puf = Pgc- Pt- πgc

Question 10

What is the net ultrafiltration pressure and give the UNITS?

Answer 10

Puf = 10 - 20 mm Hg

Question 11

Define Glomerular Filtration Rate.

Answer 11

The amount of fluid filtered from the glomerulus to the Bowman’s capsule per unit of time [minute (ml/min)]

Question 12

What is the equation for glomerular filtration rate?

Answer 12

GFR = Puf x Kf

Kf = ultrafiltration coefficient (membrane permeability and available for filtration)

Question 13

Explain, using the equation, how renal disease can cause a decrease in GFR and what can cause a dilation of glomerular arterioles.

Answer 13

You can lose nephrons hence you lose surface area –> decrease in Kf –> decrease in GFR.

Kidney diseases may reduce number of functioning glomeruli = reduced surface area = Kf
Dilation of glomerular arterioles by drugs/hormones will Kf

Question 14

What proportion of cardiac output goes to the kidneys?

Answer 14

20%

Renal blood flow (RBF) = approx (1/5 of cardiac output)

Question 15

What is filtration fraction? Give an approximate value.

Answer 15

The ratio between the renal plasma flow and the amount of filtrate filtered by the glomerulus (usually around 20%)

Question 16

State another equation for glomerular filtration rate using filtration fraction.

Answer 16

GFR = RPF x FF

Glomerular filtration rate (GFR) = RPF x FF and is approx (volume of filtrate formed in 1 minute) – is kept within a narrow range….

Question 17

State four factors that affect GFR?

Answer 17

• Glomerular capillary pressure (Pgc)
• Plasma oncotic pressure (πgc)
• Tubular pressure (Pt)
• Glomerular capillary surface area or permeability (Kf).

GFR is not a fixed value but is subject to physiological regulation. This is achieved by neural or hormonal input to the afferent/efferent arteriole resulting in changes in Puf.

Question 18

State the two mechanisms involved in autoregulation of GFR.

Answer 18

Myogenic Mechanism

Tubuloglomerular Feedback

Question 19

Describe the myogenic mechanism.

Answer 19

Vascular smooth muscle constricts when stretched.
Keeps GFR constant when blood pressure rises.

Arterial pressure rises → afferent arteriole stretches →
arteriole contracts → (vessel resistance increases)→ blood flow reduces and GFR remains constant:

Question 20

Describe the tubuloglomerular feedback mechanism.

Answer 20

NaCl concentration of the urine is detected by the macula densa. The macula densa sends signals to the afferent arterioles to change the resistance and hence change GFR.

Question 21

Describe the effect on GFR of these effects?

1. Severe heamorrhage
2. Obstruction in nephron tubule
3. Reduced plasma protein concentration
4. Small increase in blood pressure

Answer 21

1. Decrease
2. Decrease
3. Increase
4. No effect

Question 22

Describe how changes in the afferent and efferent arterioles can affect ultrafiltration.

Answer 22

They can be constricted or dilated to affect the net ultrafiltration. (e.g. vasodilating the efferent means that more blood moves away from the glomerular capillaries so the GFR decreases)

Question 23

What is the normal GFR?

Answer 23

120 ml/min

Question 24

Define clearance.

Answer 24

The number of litres of plasma that are cleared of a substance per minute.

As substances in the blood pass through the kidney they are filtered to different degrees. The extent to which they are removed from the blood is called clearance. Clearance is the number of litres of plasma that are completely cleared of the substance per unit time.

Question 25

State the equation for clearance.

Answer 25

C = V x U/P

U = concentration of substance in urine
P = concentration of substance in plasma
V = rate of urine production

e.g for Na, suppose P = 145mM, U = 290mM, V = 1ml/min.

Question 26

What are the properties of a substance used to measure GFR? Give an example.

Answer 26

Inulin - is freely filtered and is neither reabsorbed nor secreted.

Inulin:
- a plant polysaccharide
- freely filtered and neither reabsorbed nor secreted
- not toxic
- measureable in urine and plasma.
Gives a clearance value of which is GFR for average adult.

But not found in mammals so needs to be transfused therefore use an endogenous molecule with a similar clearance.

Question 27

What is used practically to measure GFR?

Answer 27

GFR in humans is normally estimated from creatinine clearance.

Creatinine:
a waste product from creatine in muscle metabolism
amount of creatinine released is fairly constant
if renal function stable, amount creatinine in urine is stable
low values of creatinine clearance may indicate renal failure
high plasma creatinine may indicate renal failure

Question 28

What is used to measure Renal Plasma Flow Rate?

Answer 28

PAH - para aminohippurate

Question 29

What properties does this substance have that makes it appropriate for measuring RPF?

Answer 29

It is totally cleared from the plasma when it passes through the kidneys. The normal glomerular filtration removes around 20% of the total PAH and then secretion from the blood into the tubules removes the rest of the PAH. There is no PAH in the renal vein.
RPF = V x Upah/Ppah

clearance = 625ml/min
Filtered and actively secreted in one pass of the kidney, thus can be used to measure RPF.

In other words the all of the PAH is removed from the plasma passing through the kidney so its clearance equals the renal plasma flow (look again at the definition of clearance).

Question 30

What change in creatinine concentration indicates renal disease?

Answer 30

Increase = the cretinine is building up because the kidneys are unable to remove it