Renal blood flow and glomerular filtration

Question 1

What percentage of cardiac output from the heart do the kidneys receive?

Answer 1

2 kidneys (0.5% body weight) receive ~20% of resting cardiac output.

Question 2

What are the 4 functions of the kidney?

Answer 2

1. Control volume & composition of body fluids
2. To get rid of waste material from body
3. Acid-Base balance
4. As an endocrine organ – EPO, Renin & Vit D

Question 3

What are the main 2 stages of urine production?

Answer 3

Urine is formed in 2 stages : glomeruli produce the liquid; tubules modifies its volume & composition

Refer to slides

Question 4

Why such a huge filtration rate, namely 180 litre/day?

Answer 4

Answer; a high rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low.

Example; a human produces 36 g urea per day:- yet normal plasma urea is only 0.2 g/litre.- To wash 36 g urea into the urine, 180litre of plasma have to be filtered per day (because 180L x 0.2 g/L = 36g).- This is a glomerular filtration rate (GFR) of 120 ml/min!

Question 5

HOW is glomerular fluid formed?

Answer 5

By passive ultrafiltration of plasma across the glomerular membrane, as described by Starling’s principle of capillary fluid filtration.

Question 6

What is the rate of glomerular filtration set by?

Answer 6

The glomerular filtration rate (GFR) is set by-

(i) autoregulation:
(ii) renal sympathetic vasomotor nerve activity

Question 7

Describe the structure and contents of the Bowsman capsule

Answer 7

On slide

Question 8

Describe the mechanisms for the glomerular fluid formation

What drives the ultrafiltration process?

Answer 8

The key features of glomerular filtration are therefore –

For small solutes, such as NaCl, glucose and urea, concentration in glomerular fluid = concentration in plasma.

For plasma proteins, concentration in glomerular fluid = almost zero. Hence, urine is routinely tested on wards for protein (proteinuria). Proteinuria is a sign of renal/urinary tract disease.

A net pressure drop across the glomerular membrane drives
the ultrafiltration process.

Question 9

Describe the mass, radius and filtrate or urea, glucose and albumin in GF

Answer 9

On slides

Question 10

What drives GF?

What pressures are in with GF?

Answer 10

An imbalance of starlings forces

Pc, capillary blood pressure, around 50 mmHg
PIp, plasma colloid osmotic pressure (25 mmHg)
Pu, pressure in Bowman’s space (10 mmHg)

Question 11

How do we calculate the filtration fraction?

Describe the graph of pressure against distance along the capillary

Answer 11

GFR/ Plasma flow

on slides

Question 12

Describe the Blood pressure profile in the kidney: Starling force balance is reversed (absorption) in peritubular capillaries.

Answer 12

On slides

Question 13

Describe the 3D structure of the glomerular membrane

Answer 13

On slides

Question 14

Describe the Electron micrograph of the glomerular barrier

Answer 14

On slides

Question 15

Describe the surface view of filtration slits between foot processes, seen from urinary space

Answer 15

On slides

Question 16

Look at the higher magnification of membrane slits

Answer 16

On slides

Central spine with lateral rungs
Subdivides filtration slit into pores 4 nm wide.
Made of proteins nephrin & podocin
Deficiency of these proteins causes nephrotic syndrome.

Question 17

Which layer is the molecular sieve?

Answer 17

On image

Question 18

What happens to Myeloperoxidase, an albumin-size protein, is held up at the filtration slits

Answer 18

1. Myeloperoxidase injected into plasma. The black material is enzyme, the reaction product
2. Penetrates through basal lamina but piles up at filtration slits.
3. None penetrates into urinary space

Question 19

—so, the glomerular membrane is 3 sieves in series, of increasing fineness

Answer 19

1. Fenestrated capillary
2. Basement membrane
3. Filtration slits of podocytes

Question 20

Describe the intrinsic control of GFR

What is the filtration rate?

How does the filtration rate aid reabsorption?

What mechanism maintains a constant GFR?

What are changes in urine production not cause and caused by?

Answer 20

[i] Intrinsic control (intra-renal)

1. GFR is in the main held constant (120ml/min)
2. Important for capacity of tubules to reabsorb filtrate not be overwhelmed by excessive GFR
3. The mechanism holding GFR constant is an internal one called ‘autoregulation’.
4. Changes in urine production (diuresis, antidiuresis) are not usually due to changes in GFR, but due to changes in tubular reabsorption.

Question 21

When there is an acute rise in blood pressure, the renal plasma flow and GFR main constant, what 2 mechanisms are responsible?

Answer 21

When kidney subject to acute increases in BP, the renal plasma flow (RPF) and GFR remain relatively constant

2 mechanisms acting together are responsible for this:

1. Bayliss myogenic response:
   direct vasoconstriction of afferent arteriole with increase in perfusion pressure
2. Tubuloglomerular feedback (TGF):
   flow-dependent signal detected in macula densa, that alters tone of afferent arteriole

Question 22

Describe the Bayliss Myogenic response

What is the equation for flow?

What does an increase in perfusion pressure cause?

What happens to contraction when smooth muscle is stretched?

Answer 22

F=∆P/R
where F= blood flow, ∆P=change in pressure, R=resistance

Increase in perfusion pressure → immediate increase in vessel radius (few seconds only) → blood flow goes up briefly

Bayliss observed that resulting stretch of smooth muscle in afferent arteriole quickly results in contraction → reduction in diameter & increase in resistance » flow returns to control value in 30s

Question 23

Does the contraction of arterioles protect the capillary?

Answer 23

Yes, increased precapillary resistance causes a bigger pressure drop

Question 24

How does Tubulo-glomerular feedback (TGF)is a second mechanism contributing to autoregulation?

Answer 24

Specifically the delivery of filtrate to the distal segment, which has a more limited capacity for reabsorption, needs to be precisely regulated.
Thus in the vast majority of mammalian nephrons, the early distal tubule makes direct contact with the vascular pole of it’s originating glomerulus. This TGF depends on the unique anatomical relationship between the early distal tubule (cells become specialised to form macula densa) and the vascular region of the glomerulus.

Question 25

How does NaCl contribute towards the maintenance of the GFR?

Answer 25

increase in [NaCl] and osmolality results in a release of ATP which leads to contraction of the afferent arteriole which contributes to the maintenance of pressure in the BC seen during autoregulation.

Question 26

Describe the intrinsic control of GFR

Answer 26

[I] Intrinsic control

Autoregulation of GFR by Bayliss myogenic response & TGF.

Question 27

How do Sympathetic nerves re-set GFR autoregulation to a lower level?

Answer 27

II] Extrinsic control (neurohumoral)
Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR, by re-setting autoregulation to a lower level.
This happens in 3 conditions-
standing upright (orthostasis)
heavy exercise
haemorrhage & other forms of clinical shock
The role is to conserve body fluid volume during physical stress.
In shock, these sympathetic actions are aided by circulating vasoconstrictor hormones such as adrenaline, angiotensin and vasopressin.

Question 28

What are the two major clinical disorders of the GFR?

Answer 28

Glomeruli too leaky to plasma protein: nephrotic syndrome (eg. Filtration slit disordered by nephrin deficiency)

1. Proteinuria
2. Hypoproteinaemia
3. Oedema

GFR too low (more common)

• Chronic glomerulonephritis  nonfunctioning glomeruli
• When GFR < 30 ml/min, this is chronic renal failure.

Question 29

Describe the histology of glomerular and Chronic glomerulonephritis

Answer 29

On image