Renal Blood Flow and Glomerular Filtration Flashcards
What does the renal corpuscle consist of?
The renal corpuscle consists of a clump of capillaries and bowman’s capsule
What is the mechanism of glomerular fluid formation?
Ludwig (1844) realised that glomerular fluid is a passive ultrafiltrate of plasma i.e. plasma from which the proteins have been filtered out
The key features of glomerular filtrate 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
How does an imbalance in starling forces drive glomerular fluid formation?
The principle force driving the passage of fluid from the capillary into the Bowman’s space is capillary blood pressure
There are pressures opposing this, the plasma colloid osmotic pressure
This is a pressure created by the protein that do not pass across the membrane, mainly albumin
So because the proteins cant cross it end up concentrating around the edge of the glomerular capillary such that there is a concentration gradient of albumin creating an osmotic force back into the capillary (opposing capillary blood pressure)
The third force is the pressure exerted by the fluid in the Bowman’s space which is a lot less
The sum of these two forces pushing into the capillary is a lot less than that of the force of the blood pushing fluid into the Bowman’s space
As the fluid crosses the membrane we get a decrease in volume which has a concentrating effect on the proteins that cannot cross, albumin mostly, such that as we move from the afferent end to the efferent end of the capillary we get a gradual drop in the capillary blood pressure and a corresponding rise in the plasma colloid osmotic pressure
Pc = capillary blood pressure, around 50 mmHg
pp= plasma colloid osmotic pressure (25 mmHg)
Pu= pressure in Bowman’s space (10 mmHg)
Net filtration force= Pc –(pp + Pu)
Filtered fraction= GFR/plasma flow (so you can end up with a percentage)
When are starling forces reversed?
Blood pressure profile in kidney; starling force balance is reversed (absorption) in peritubular capillaries
We can compare blood pressure changes to changes in the colloid osmotic pressure; an increase
In order to get enough force for fluid to return later on in the tubule, we need the net forces to go in the other direction
This happens in the efferent arteriole where the blood pressure drops beyond this force pushing inwards so we get absorption driven by a decrease in blood pressure within the efferent arteriole (the plasma colloid osmotic pressure also drops)
What are the filtration slits like?
Central spine with lateral rungs
Subdivides filtration slit into pores 4 nm wide.
Made of proteins; nephrin & podocin
The deficiency of these proteins causes nephrotic syndrome
Which layer is the molecular sieve?
It depends on the molecule
E.g. ferritin is of an 11nm radius
Ferritin freely permeates through the fenestral apertures but is stopped by the basement membrane into the lamina densa
Myeloperoxidase, an albumin-size protein, is held up at the filtration slits
Penetrates through basal lamina but piles up at filtration slits
None penetrates into urinary space
What is the glomerular membrane like?
The glomerular membrane is 3 sieves in series, each of increasing fineness
They are arranged in series to keep things out
Small molecules such as water and glucose, urea etc. can pass freely across
Big things such as red blood cells are kept out by the fenestrated capillary
Large molecules such as fibrinogen are kept out by the basement membrane
Albumin sized molecules will pass through the basement membrane but are stopped by the filtration slits of podocytes
What is the Bayliss myogenic response?
Increase in perfusion pressure (arterial blood 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 and increase in resistance -> flow returns to control value in 30s
F=DP/R
F= blood flow
DP= change in pressure
R= resistance
What is involves in the tubuloglomerular feedback?
JG cells- modifies smooth muscle cells in walls of afferent arteriole proximal to glomerulus- store inactive pro-renin
Macula densa- specialised epithelial cells within the DCT on the juxta-glomerular side
What is tubuloglomerular feedback?
The first thing that would happen is the GFR would increase from elevated blood flow
This increases the flow of fluid through the tubule which increases the flow of fluid past the macula densa
If you increase the flow of fluid you increase the concentration of sodium chloride ions in the lumen of the tubule thus increasing the luminal osmolality
This increased sodium chloride concentration means that more sodium chloride is taken up by the epithelial cells (particularly the macula densa ones); causing the macula densa cells to release paracrine signals that diffuse to the afferent arterioles
The afferent arteriole constricts offering more resistance and thus reducing the hydrostatic pressure in the glomerulus
So the GFR decreases to a safe amount
What does more tubular flow mean?
NaCl elicits ATP release from macula densa cells triggering to contraction of the afferent arteriole
More tubular flow means:
More [NaCl]
More ATP released
How is the GFR controlled extrinsically?
Renal sympathetic nerves (vasoconstriction, noradrenergic) 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
Sympathetic nerves reset GFR autoregulation to a lower level (a different effect than Bayliss myogenic but same result- constriction)
What are two major clinical disorders of the GFR?
- Glomeruli too leaky to plasma protein:
Nephrotic syndrome (e.g. filtration slit disordered by nephrin deficiency- nephrin which forms the filtration slit between podocytes)
Consequences:
-Proteinuria- proteins in urine
-Hypoproteinaemia- not enough proteins in the blood
-Oedema- fluid retention within the body (2 theories on why)
All of the above three respond well to steroids- GFR too low (more common)
Chronic glomerulonephritis -> non-functioning glomeruli
When GFR <30 ml/min, this is chronic renal failure
- GFR too low (more common)
