Renal Blood Flow and Glomerular Filtration

Question 1

Why is there such a huge filtration rate (namely 180 litres a day)?

Answer 1

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

Question 2

Generally, how is glomerular fluid formed?

Answer 2

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

Question 3

What is the glomerular rate (GFR) set by?

Answer 3

• autoregulation
• renal sympathetic vasomotor nerve activity.

Question 4

What does the glomerulus consist of?

Answer 4

It consists of a clump of capillaries and the Bowman’s capsule.

Question 5

What are the key features of glomerular filtration?

Answer 5

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

Question 6

On what basis does the glomerular membrane sieve out solutes?

Answer 6

Glomerular membrane sieves out solutes from plasma by molecular size.

Question 7

What drives glomerular fluid formation? What are the three forces that contribute?

Answer 7

• An imbalance of Starling forces drives glomerular fluid formation (filtration).
• The three forces:
  
  • Pc is capillary blood pressure, which is around 50 mmHg.
  • πp is plasma colloid osmotic pressure (oncotic pressure), which is around 25 mmHg.
  • Pu is the pressure in the Bowman’s space, which is around 10 mmHg.

Question 8

What are podocytes?

Answer 8

Podocytes are cells in the Bowman’s capsule in the kidneys that wrap around the capillaries of the glomerulus.

Question 9

Describe the filtration slits in between the podocytes.

Answer 9

It is through the filtration slit that glomerular fluid emerges. The slit is about 30 nm wide. It has a central spine with lateral rungs; this subdivides the filtration slit into pores that are 4 nm wide. It’s made of the proteins nephrin and podocin. The deficiency of these proteins causes nephrotic syndrome.

Question 10

The glomerular membrane is 3 sieves in series of increasing fineness. Expand on that.

Answer 10

1. First, we have the fenestrated capillary, which will not allow big structures like a RBC through, but will allow smaller molecules through, such as albumin, fibrinogen, and water.
2. Next, we have the basement membrane. This structure will allow albumin and water through, but will block molecules like fibrinogen.
3. Lastly, we have the filtration slits of podocytes. These will only allow small molecules through, such as water, glucose, NaCl, urea, creatinine, etc.

Question 11

Describe the intrinsic control of GFR.

Answer 11

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

Question 12

What 2 mechanisms are responsible for the intrinsic control of GFR?

Answer 12

When the kidney is subject to acute increases in BP, the renal plasma flow (RPF) and the GFR remain relatively constant. Two mechanisms acting together are responsible for this: - BAYLISS MYOGENIC RESPONSE: direct vasoconstriction of afferent arterioles with an increase in perfusion pressure - TUBULOGLOMERULAR FEEDBACK (TGF): flow-dependant signal detected in macula densa that alters the tone of afferent arterioles

Question 13

Describe the Bayliss Myogenic Response.

Answer 13

• F=∆P/R

where

* F= blood flow,
* ∆P=change in pressure,
* R=resistance * An increase in the perfusion pressure leads to an immediate increase in vessel radius (for a few seconds), which means that blood flow goes up briefly. * Bayliss observed that the resulting stretch of smooth muscle in afferent arterioles quickly resulted in contractions, which lead to a reduction in diameter and an increase in resistance, with the flow returning to the control value in 30 seconds.

Question 14

How does the myogenic response affect autoregulation?

Answer 14

The ‘myogenic response’ of afferent arterioles to pressure is one cause of autoregulation. Changes in diameter of the afferent arteriole alters the resistance, maintaining autoregulation.

Question 15

Describe tubulo-glomerular feedback.

Answer 15

1. The GFR increases.
2. The flow through the tubule increases.
3. The change in flow is registered by the macula densa. {It identifies this change in flow as there is a change in the luminal [NaCl] and luminal osmolality}
4. The macula densa responds by causing the constriction of the affert arteriole.
5. The resistance in afferent arteriole increases.
6. The hydrostatic pressure in glomerulus decreases.
7. GFR decreases.

Question 16

Step-wise, describe how TGF controls the GRF and RBF.

Answer 16

• there is a change in the RBF/ GFR - there is then a change in the NaCl delivery to the DCT - the macula densa sense the change - via paracrine and vasoactive agents, they affect the afferent arterioles - the arterioles then change their diameter and resistance - this restores the RBF/ GFR

Question 17

Describe the extrinsic control of GFR.

Answer 17

• The extrinsic control of GFR is neurohormonal.
• The renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR by resetting the autoregulation to a lower level.
• This happens in 3 conditions:
  
  • standing upright (orthostasis)
  • heavy exercise
  • haemorrhage and other forms of clinical shock
• Its role is to conserve body fluid during physical stress.
• In shock, these sympathetic actions are aided by circulating vasoconstrictor hormones such as adrenaline, angiotensin and vasopressin.

Question 18

Describe the two major clinical disorders of the GFR.

Answer 18

1. The glomeruli are too leaky to plasma protein: Nephrotic Syndrome (eg. filtration slit disordered by nephrin deficiency)
   
   • ​​This can cause proteinuria, hypoproteinaemia and oedema.
   • However, these respond well to steroids.
2. GFR is too low (more common)
   
   • Chronic glomerulonephritis is when we have non-functioning glomeruli.
   • When the GFR gets to <30 ml/min, this is considered chronic renal failure.

Question 19

The 2 kidneys, which make up about 0.5% of the body weight, receive nearly a quater of the resting cardiac output. Why?

Answer 19

The kidneys get an exceptionally high flow for rgans their size. This large blood flow is clearly not related to the metabolic needs of the kidney, but it is a function of the major role that the kidneys play in the regulation of the ECF and blood volume regulation and rapid waste disposal.