Renal Blood Flow & Glomerular Filtration

Question 1

How is glomerular fluid formed

Answer 1

There is a movement of fluid from the glomerular capillaries into the Bowman’s space and into the proximal tubule

Question 2

Describe glomerular blood supply/structure

Answer 2

• The afferent arteriole brings blood into the glomerular capillaries and then passes into the efferent arteriole where it enters peritubular capillaries
• The epithelium of the Bowman’s capsule is invaginated to coat the outer surface of the capillaries (podocytes)

Question 3

Describe the key features of glomerular filtrate

Answer 3

• Small solutes such as NaCl, glucose and urea have the same concentration in the glomerular fluid as it is in the plasma
• For plasma proteins- concentration in the glomerular fluid is almost zero - urine is routinely tested on wards for proteins as proteinuria is a sign of renal / urinary tract disease
• There is a net pressure drop across the glomerular membrane drives the ultrafiltrate

Question 4

How can glomerular membrane sieves be investigated?

Answer 4

• Glomerular fluid can be collected by micropuncture by a pipette
• These studies showed that the smaller molecules are in higher concentrations in the glomerular filtrate compared to larger molecules

Question 5

Describe the starling forces acting on the glomerular capillaries

Answer 5

• The primary force pushing fluid across the glomerular membrane is capillary blood pressure
• There is another force called the plasma colloid osmotic pressure - as proteins cannot pass through there is a high concentration of proteins around the edges of the capillaries which creates a gradient of proteins trying to move back to the middle of the capillary which exerts this pressure opposing the capillary blood pressure
• Pressure in the bowman’s space exerts a pressure against the capillary opposing the capillary blood pressure

Question 6

Describe how these pressures change from the afferent to the efferent end

Answer 6

• Capillary blood pressure decreases slightly
• Plasma colloid osmotic pressure increases slightly
• Pressure in the bowman’s space is constant

Between the capillary blood pressure pushing fluid out of the capillary and the 2 forces keeping fluid within the capillary is the net filtration force

Question 7

How do you calculate net filtration force?

Answer 7

Net filtration force = capillary blood pressure - (plasma colloid osmotic pressure + pressure in the Bowman’s space)

Question 8

Describe how pressures change throughout the blood supply to the nephron and how this related to filtration and absorption

Answer 8

• From the afferent arteriole to the venules the blood pressure decreases continually
• The plasma colloid osmotic pressure increases in the glomerulus and efferent arteriole and then decreases again in the peritubular capillaries and venule
• Hence in the glomerulus the blood pressure is greater than the plasma colloid osmotic pressure so there is filtration
• In the peritubular capillaries the plasma colloid osmotic pressure is higher than the blood pressure so there is absorption of water

Question 9

Describe the 3 stages of filtration through the glomerulus

Answer 9

Podocytes are cells that surround the tubules that have cell bodies which then extend into pedicels/ feet that create filtration slits between them by indigitating

1. Fenestration- between the capillary endothelial cells of glomerulus
2. Through the thick, fused basement membrane of capillary endothelial cells and podocytes
3. Filtration slit membrane- between podocyte foot processes - slit is 30 nm wide

Question 10

Describe filtration slits in more detail

Answer 10

• Between 2 podocyte feet is a central spine with lateral rungs
• It subdivides the filtration slit into pores that are 4nm wide
• It is made of proteins nephrin and podocin
• Deficiency of these proteins causes nephrotic syndrome

Question 11

Describe studies that show what molecules are stopped by what level of filtration and some examples of molecules

Answer 11

• Ferritin is a protein bound naturally to Fe2+ - is electron dense so easy to pick up in electron microscopy
• Ferritin molecule are injected into plasma and each molecule can be seen to see where it goes e.g. ferritin can freely pass through the fenestrations but get stopped by the basement membrane
• Myeloperoxidase is an albumin sized protein which cannot pass through the filtration slits - it is an enzyme that can be injected into the enzyme and the reaction product shows as a black material - protein gets stuck at the feet of the filtration slits
• Red blood cells cannot get through the fenestrations while fibrinogen cannot get through the basement membrane and albumin cannot get through the filtration slits

Question 12

How is pressure in the glomerular capillaries controlled?

Answer 12

• Via autoregulation mechanisms within the kidney (bayliss myogenic response and tubuloglomerular feedback
• Via extrinsic mechanisms involving the PNS

Question 13

Describe the bayliss myogenic response

Answer 13

• There is an increase in perfusion pressure - immediate increase in the vessel radius so blood flow increases briefly
• Bayliss observed that this initial stretch of smooth muscle in afferent arteriole quickly results in contraction which reduces the diameter and increases resistance so flow returns to the control value
• As mean arterial blood pressure increases the glomerular filtration rate increases
• It is during the period where arterial pressure is increasing but glomerular filtration rate stays constant which is the autoregulation range
• If blood pressure is too low there is a lack of glomerular filtration as there is a failure of the autoregulation system during hypotension/ shock - oliguria

Question 14

What would happen without the bayliss myogenic response

Answer 14

• Without the response if the artery pressure was higher the arteriole and capillary pressure would increase in conjunction with this
• With the response even if the artery pressure increases a lot it protects the capillaries by minimising the increase in pressure

Question 15

Describe tubuloglomerular feedback

Answer 15

1. The glomerular filtration rate increases as renal blood flow increases
2. Flow through the tubule increases so there is more fluid going down and up the loop of Henle and there is a change in [NaCl]
3. The cells of the macula densa are able to sense the faster flow rate and respond by signalling to the juxtaglomerular cells by releasing ATP (paracrine vasoactive agent) to make them contract so afferent arteriole contracts
4. The resistance in the afferent arteriole increases so the hydrostatic pressure in glomerulus decreases and the glomerular filtration rate decreases

Question 16

How do the macula densa cells detect increased flow?

Answer 16

1. Mechanically via cell surface cilia
2. Chemically via increased [NaCl]
   - Macula densa cells will release ATP in response to more tubular flow and to more NaCl

Question 17

Describe how there is extrinsic control of glomerular filtration rate

Answer 17

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

Question 18

state and describe 2 clinical disorders of GFR

Answer 18

1. Glomeruli too leaky to plasma proteins - nephrotic syndrome e.g. when filtration slits are disordered by a nephrin deficiency - leads to proteinuria, hypoproteinaemia and oedema
2. GFR is too low - chronic glomerulonephritis - nonfunctioning glomeruli- when GFR is less than 30ml per min it is chronic renal failure