Renal blood flow and Glomerular filtration

Question 1

List the main functions of the kidney.

Answer 1

• To control volume and composition of body fluids
• To get rid of waste material from the body
• Acid-base balance
• As an endocrine organ – EPO, renin, vitaminD

Question 2

Name and describe the functional unit of the kidney.

Answer 2

Nephron (approx. 4cm long), nephron has two elements to it, the glomerulus and a tubule.
The glomerulus (a tuft of blood vessels) is contained within the Bowmans capsule. The glomerulus is unusual in that is has an artery entering (afferent arteriole) and the vessel leaving is also an artery (efferent arteriole) before becoming the peritubular capillaries the surround/are adjacent to the tubule. Importantly, the blood and tubule meet again through the peritubular capillaries.

Question 3

How many nephrons are there in each kidney?

Answer 3

1 Million nephrons in each kidney.

**Nephrons cannot be regenerated.

Question 4

How do the Glomeruli contribute to urine formation?

Answer 4

Glomeruli produce the liquid. Blood flowing through the renal artery enters the afferent arteriole, goes into the ball shaped glomerular capillaries. Here fluid is filtered out (by ultrafiltration) into the tubule at a relatively fast rate of normally about 120ml/min. Blood leaves via the efferent arteriole and goes to the peritubular capillaries, which is where a lot of reabsorption occurs.

Question 5

How do the tubules contribute to urine formation?

Answer 5

Tubule modifies the volume and composition of the liquid. 120ml is filtered through and enters the tubule, most of it is reabsorbed into blood, around 119ml/min. So, what you’re left with in the tubule is about 1ml/min formation of urine, this equates to about 1.5L of urine a day. If you fall below 5ml/day then you’re considered to be in renal failure. We also reabsorb any useful things, such as glucose and AA, anything that isn’t useful we leave in the urine and it is excreted.

Question 6

How is the Glomerular Filtration Rate (GFR) determined?

Answer 6

1. Autoregulation

2. Renal sympathetic vasomotor nerve activity

Question 7

What encloses the Glomerulus?

Answer 7

Glomerulus is completely enclosed by epithelium of the Bowman’s capsule, though they are specialised to form podocytes (epithelium is ‘invaginated’ to coat the capillaries).

Question 8

What type of ultrafiltrate is Glomerular fluid?

Answer 8

Passive ultrafiltrate of plasma i.e. plasma from which the proteins have been filtered out (so has very similar composition, just without as many proteins).

Question 9

What key features must the Glomerular fluid have for it to be an ultrafiltrate?

Answer 9

• For small solutes, such as NaCl, glucose and urea the concentration of glomerular fluid should equal the concentration in the plasma.
• For plasma proteins, concentration in the glomerular fluid is almost zero. Hence urine is routinely tested on wards for protein (proteinuria). Proteinuria is a sign of renal/urinary tract disease.
• It is a net pressure drop across the glomerular membrane drives the ultrafiltration process.

Question 10

How do we know that we the glomerular membrane sieves out solutes by molecular size?

Answer 10

It was found the ratio of glomerular filtrate/plasma was 1 for urea and glucose (because they are equal). But albumin was below 0.01. So, it was concluded that the glomerular membrane sieves out solutes from plasma by molecular size.

Question 11

What is the main force trying to push fluid out of the Glomerular capillary? (Give a value if possible)

Answer 11

Capillary blood pressure (Pc), which is around 50mmHg.

*An imbalance of Starling Forces drives glomerular fluid formation (filtration).

Question 12

What are the forces trying to push fluid back into the capillary? (Give values if possible)

Answer 12

Plasma oncotic pressure (Pi-p) around 25mmHg due to plasma proteins in the blood and there is also pressure in the Bowman’s space trying to push fluid in (Pu), around 10mmHg.

Question 13

What is the equation for the net filtration force?

Answer 13

Capillary BP – (Plasma oncotic pressure (or COP) + Pressure in Bowmans space)

Question 14

How do we know we get fluid filtration throughout the whole Glomerular capillary?

Answer 14

Along the whole capillary, despite the oncotic pressure rising, it is always less than Pc.

Question 15

What is the ‘filtration fraction’?

Answer 15

Tells us the proportion of fluid that is being filtered from the volume of blood that is flowing through. The glomerulus has a filtration fraction of 20% (in most capillary beds it is only 1%). i.e. 20% of blood which flows through is filtered.

Question 16

What happens to the plasma oncotic pressure (AKA Colloid osmotic pressure - COP) in the efferent arteriole?

Answer 16

Pressure starts to drop and COP rises because fluid has been lost from capillaries and protein is getting more concentrated. Therefore, it is exerting a greater pulling force. Hence in the peritubular capillaries, the COP rises above the hydrostatic BP and so we get reabsorption of fluid back into the blood.

Question 17

Describe the barriers in place, which can be seen in a cross section of the Glomerular membrane.

Answer 17

In the capillary we have a fenestrated endothelium, sitting on a basement membrane.
There are then the pedicels of the podocytes attaching to the capillary, in between them being the gaps called filtration slits.

Question 18

What is the fenestrae in the glomerulus?

Answer 18

The fenestrae are areas where there are no membrane present, these cover about 30% of the surface and are about 50-100nm wide. The RBCs are too large to pass through, but any substance that is less than 50nm wide can pass through the fenestrae, through the basal lamina

Question 19

How wide is the filtration slit?

Answer 19

The filtration slit, through which the glomerular fluid emerges from, is only about 30nm wide.

Question 20

How come albumin doesn’t pass through? Even though an albumin molecule is approx. 4nm across

Answer 20

Because the filtration slits are further sub-divided into even smaller slits, in the formation of a central spine with lateral rungs sticking out.
This sub-division results in slits only 4nm wide. The sub-division is made of the proteins nephrin and podocin.

Question 21

What molecules are freely able to pass in glomerular filtration?
*What does it mean when protein is found in urine?

Answer 21

Substances like water, glucose, NaCl, urea, creatinine can freely move through.
*Proteins will leak out (proteinuria) if the filtration slits of basement membrane are damaged. Which is why it is important to test urine for protein.

Question 22

What happens to GFR when blood pressure increases?

Answer 22

Would increase GFR (normally 120ml/min), if this happened and the rate of reabsorption remained the same (as body only has certain capacity to reabsorb) then urine volume would increase. So, you would end up losing blood volume.

Question 23

Name the internal mechanism which keeps GFR constant.

Answer 23

The mechanism holding GFR constant is an internal one called ‘autoregulation’. This means
changes in urine production (diuresis, antidiuresis) are not usually due to changes in GFR but due to changes in tubular reabsorption. Auto regulation is an intrinsic property of the kidney.

Question 24

What would happen to the kidney if there was no autoregulation?

Answer 24

Then a relatively small increase in bp (from 100-125mmHg) would cause a similar 25% increase in GFR i.e. increasing from 180-225L/day. If tubular reabsorption remained constant then urine flow would increase by 30-fold (difference between GFR and tubular reabsorption), thereby depleting blood volume very quickly.

Question 25

Name the 2 mechanisms which are responsible for keeping the GFR and renal plasma flow relatively constant.

Answer 25

• The Bayliss myogenic response

* Tubuloglomerular feedback (TGF)

Question 26

What is the Bayliss Myogenic Response?

Answer 26

F=∆P/R
(flow = change in pressure/ resistance)
Bayliss noticed if we had a 50% increase in pressure we only got a very small increase in flow, the reason is due to the afferent arteriole.
We see that when there is an increase in perfusion pressure there is an immediate increase in the vessel radius for a few seconds and blood flow goes up briefly .Blood flow then quickly drops back to what it normally is and that is because of stretch of the smooth muscle in the afferent arteriole results in it then contracting to reduce the diameter and increase resistance. So the change in BP was not transmitted to change in GFR.

Question 27

What happens when the BP drops below the autoregulation range (e.g. in hypotension or shock)?

Answer 27

It will lead to oliguria (low urine output)

Question 28

What are macula dense?

Answer 28

Distal convoluted tubule comes back up and comes in close contact with the vascular pole of that particular nephron (glomerulus). That area of close contact develops specialised cells called macula densa, these specialised cells can sense any change that is occurring.

Question 29

How are the macula densa related to Tubulo-glomerular feedback (TGF)?

Answer 29

if GFR has increased for any reason, then flow through the tubule will increase (due to more fluid) and this will change the concentration of NaCl and the osmolality of the fluid. This will be picked up by the macula densa which will release certain substances (ATP signaled) that will lead to an increase in tone of the afferent arteriole (i.e. it will constrict). Leading to an increased resistance an increase pressure drop and decreased hydrostatic pressure in the glomerulus thus decreasing GFR.

Question 30

Whats the point of having the RAAS system superimposed onto the autoregultaion?

Answer 30

Start to also combat the effect of the increased filtration (e.g. by absorbing more).

Question 31

What is extrinsic control of the GFR?

Answer 31

The renal sympathetic nerves can affect the afferent/efferent arteriole and reduce GFR by re-setting the autoregulation to a lower level.

Question 32

Which 3 conditions can extrinsic control of GFR happen in?

Answer 32

1. Standing upright (orthostasis)
2. Heavy exercise
3. Haemorrhage and other forms of clinical shock

Question 33

Describe 2 major clinical disorders of the GFR.

Answer 33

• Glomeruli is too leaky to plasma protein, this is nephrotic syndrome (e.g. filtration slit disordered by nephrin deficiency). Responds to steroids.
• GFR too low (more common)

Question 34

What happens when the glomeruli are too leaky?

Answer 34

• Proteinuria
• Hypoproteinaemia (low protein in blood)
• Oedema (decreased oncotic pressure)

Question 35

What happens when GFR is too low?

Answer 35

• Chronic glomerulonephritis (non-functioning glomeruli)

- When GFR falls below 30ml/min this is chronic renal failure.