Renal- glomerular filtration

Question 1

Describe renal blood flow

Answer 1

Among the major organs, the kidneys have the highest blood flow per unit mass.
 Renal blood flow is 1200 ml/min which is 25% of the cardiac output, in comparison to the two kidneys only making up <0.5%
of the total body weight.
o 90% of blood flow goes to the cortex, 10% of medulla.
o The high blood flow is not required for the kidneys’ O2 demands, but for the filtration of 180 L of fluid per day. The
kidneys do have a high O2
(second to the heart), but because the blood flow is so high, the kidneys have the lowest
arteriovenous O2 difference of any organ.

Question 2

Describe the glomerulus

Answer 2

The glomerular capillaries are between the afferent arteriole and efferent arteriole. They are 0.95 mm long, and their total
estimated length is 19 km. Total surface area is 1 m2
for filtration.
 Starling forces enable fluid to pass from the glomerular capillaries into the Bowman’s capsule.
 Minimal protein passes through into the Bowman’s capsule due to the filtration barrier. All other molecules and ions are at
roughly the same concentration as in the plasma.

Question 3

What are podocytes in the filtration barrier

Answer 3

Podocytes are cells in the Bowman’s capsule that wrap around capillaries of the
glomerulus.
 Large primary processes wrap around the glomerular capillaries which branch
into secondary processes (or foot processes).
 Between the primary processes is the filtration slit (40 nm) and is breached by
the diaphragm which spans the filtration slit with the protein
nephrin. In congenital nephrotic syndrome, there is a mutation
in nephrin leading to high levels of proteinuria (protein in urea).

Question 4

What are the structural elements of the filtration barrier

Answer 4

The filtration barrier consists of:
o Endothelial pores: fenestrae (60-80 nm in diameter)
are plugged with glycocalyx which prevents large
proteins (i.e. platelets and erythrocytes) from passing
through. Fenestrae allow the endothelial layer to be
more permeable to water than other capillaries.
o Glycocalyx of endothelial cells
o Basement membrane: connects the endothelial cells and podocytes.
o Filtration slits connected by slit diaphragm.

Question 5

What are the factors that determine glomerular filterability

Answer 5

1. Electrical charge
    The glomerular filtration barrier has a negative charge (glycoproteins):
   endothelium and glycocalyx, basement membrane and epithelium
   (podocytes). This repels negatively charged solutes and attracts positively
   charged solutes.
    For small solutes (Na
   +, K
   +, Cl
   −,HCO3
   −), the charge doesn’t matter.
    For large solutes (plasma proteins) with a negative charge, they are
   repelled.
2. Molecular weight
    Filterability of plasma constituents vs water:
    Small molecules like urea and glucose don’t have a charge, and
   can freely pass through the filtration barrier.
    Myoglobin is much larger, but can still fairly freely pass through the filtration barrier.
   Haemoglobin and albumin are roughly the same size, and are affected by their negative charge (albumin) or lack of charge
   (haemoglobin) so poorly pass through the filtration barrier.

Question 6

What can get through the glomerular filter

Answer 6

As molecular diameter increases, up to about 3 nm for anions, filterability is at 100%, then it decreases suddenly.
 For neutral molecules, filterability decreases after about 4 nm.

Question 7

What causes glomerular filtration

Answer 7

 Hydrostatic pressure of the
glomerular capillary along
with the oncotic pressure of
the higher protein
concentration in the
glomerular capillary
compared drives filtration.
 Net ultrafiltration pressure = Net hydrostatic pressure −
Net oncotic pressure
 PUF = (PGC − PBS)− πGC

Question 8

Explain the Starling pressure values

Answer 8

Oncotic pressure within the glomerular capillary increases the most at the efferent end and influences the filtration rate.
This means that the further into the capillary, the force of filtration decreases.
Dynamics of glomerular filtration
 [Green line] Hydrostatic pressure in the capillary.
 [Purple line] Hydrostatic pressure in the Bowman’s
space.
What can alter the rate of glomerular filtration?
 Decrease in PGC (hydrostatic pressure in glomerular
capillaries) causes a reduction in ultrafiltration.
 Increase in PBS (hydrostatic pressure in the Bowman’s
space) causes a reduction in ultrafiltration.
 Increase in πGC (oncotic pressure in the glomerular
capillary) causes a reduction in ultrafiltration.
Renal plasma flow influences filtration rate
 In general, if capillary plasma flow increases, filtration rate increases. This can saturate transporters for reabsorption of
nutrients, so more nutrients could be excreted.
 Selective changes in resistance of the afferent or efferent arteriole influence renal blood flow and glomerular filtration rate.
 Afferent arteriolar constriction: decreases hydrostatic pressure and renal blood flow, so decreases glomerular filtration
rate.
o Example: adenosine does this.
Afferent end
(mmHg)
Starling pressure Efferent end
(mmHg)
45 PGC
(hydrostatic pressure in glomerular capillary, generated by systolic blood pressure) 44
10 PBS
(hydrostatic pressure in Bowman’s space) 10
25
πGC
(oncotic pressure within the glomerular capillary, it is an osmotic pressure because of
the plasma proteins in the capillary)
>25
10 PUF �

Question 9

Describe the dynamics of glomerular filitration

Answer 9

[Green line] Hydrostatic pressure in the capillary.
 [Purple line] Hydrostatic pressure in the Bowman’s
space.

Question 10

What can alter the rate of glomerular filtration

Answer 10

Decrease in PGC (hydrostatic pressure in glomerular
capillaries) causes a reduction in ultrafiltration.
 Increase in PBS (hydrostatic pressure in the Bowman’s
space) causes a reduction in ultrafiltration.
 Increase in πGC (oncotic pressure in the glomerular
capillary) causes a reduction in ultrafiltration.

Question 11

How does renal plasma flow influence filtration rate

Answer 11

In general, if capillary plasma flow increases, filtration rate increases. This can saturate transporters for reabsorption of
nutrients, so more nutrients could be excreted.
 Selective changes in resistance of the afferent or efferent arteriole influence renal blood flow and glomerular filtration rate.
 Afferent arteriolar constriction: decreases hydrostatic pressure and renal blood flow, so decreases glomerular filtration
rate.
o Example: adenosine does this.

Efferent arteriolar constriction:
increases hydrostatic pressure (within
the glomerular capillary) and decreases
renal blood flow, so increases
glomerular filtration rate.
o Example: angiotensin II does
this.
 Efferent arteriolar dilation: decreases
hydrostatic pressure and increases
renal blood flow to decreases
glomerular filtration rate.
o Example: blocking
angiotensin II receptors does
this.
 Afferent arteriolar dilation: increases hydrostatic pressure and increases renal blood flow so increases glomerular filtration
rate.
o Example: prostaglandins and NO does this.

Question 12

How is glomerular filtration rate measured

Answer 12

Total glomerular filtration rate = ∑ Filtration rate of all nephrons
 If the total number of functioning nephrons is reduced, this leads to chronic renal failure as a result of decreased GFR.
 Measurement of GFR is the single best means of quantitatively assessing kidney function.
1. How to measure GFR
 Needs a substance with special properties:
o Freely filtered: concentration in Bowman’s capsule is the same as the concentration in the plasma.
o Not reabsorbed
o Not secreted: from peritubular capillaries.
 Very few substances therefore meet this criteria.
2. Inulin clearance (= GFR)
 Polysaccharide of fructose
 Molecular weight is 5 kDa: freely passes through the filtration barrier.
 Inulin is used in vivo for experiments, but not used for laboratory investigations.
 Clinical measurement of GFR uses creatinine. However, some creatinine is secreted into the tubules. Creatinine is generated
in the body. Therefore, using creatinine for investigation is an estimate.
 Amount of inulin/creatinine secreted per minute = Amount of insulin/creatinine filtered per minute
 GFR =
Urine [inulin or creatinine]×Flow rate
Plasma [inulin or creatinine]

Question 13

Describe renal plasma flow, GFR and filtration fraction

Answer 13

Typical value for renal blood flow: 1200 ml/min.
 Typical value for renal plasma flow: 650 ml/min.
 Typical value for GFR: 120 ml/min.
 Filtration fraction =
GFR
RPF
=
120
650
≈ 19%
o 20% is under normal conditions

Question 14

Describe autoregulation of renal blood flow

Answer 14

Normally, renal blood flow changes very little between 90-180
mmHg (autoregulatory range).
 During autoregulation, as blood pressure increases, so does
vascular resistance.
 The afferent arteriole responds to a change in blood pressure, so
the pressure change is not transmitted to the glomerulus. If the
arterial pressure increases, the afferent arteriole vasoconstricts.

1. Mechanism: myogenic (rapid)
    In the afferent arteriole: ↑ blood pressure  ↑ afferent arteriole
   stretch  non-specific cation channels open within the arteriole  depolarisation  Ca
   2+ channels open  afferent
   arteriole contracts.
   o Decreases hydrostatic pressure and renal blood flow, so decreases glomerular filtration rate.
    Responds quickly to changes in systemic blood pressure.
2. Mechanism: tubuloglomerular feedback (long-term)
    Occurs in the juxtaglomerular apparatus.
    Afferent arteriole is in contact with the distal tubule which is connected to the Bowman’s capsule.
   o Increase in blood pressure increases filtration rate in the glomerulus.
   o This delivers high amounts of NaCl and water to the distal tubule.
   o Macula densa cell in the distal tubule senses NaCl and then causes the release of adenosine which leads to
   vasoconstriction of afferent arterioles.
   o Feedback mechanism (paracrine) reduces renal blood flow and pressure.
   o This mechanism is responsible for the constant rate of filtration and prevents loss of fluid in urine.
3. GFR is not always under autoregulation
    Autoregulation is not perfect.
    Autoregulation does not operate below 90 mmHg or above 180-200 mmHg.
    Can be overridden by extrinsic factors (nerves, hormones).
4. External factors can over-ride autoregulation
    Sympathetic nerves: cause afferent and efferent arteriolar constriction. Under normal conditions, this does not play a role
   in controlling renal blood flow. However, during haemorrhage, the sympathetic nervous system diverts blood flow away
   from the kidneys to more vital organs.
    Adrenaline: ↑ sympathetic activity  afferent arteriolar constriction  ↓ GFR.