Renal blood flow and glomerular filtration Flashcards
(43 cards)
The 2 kidneys which represent about 0.5% of body weight receive nearly a quarter of the resting cardiac output, which is an exceptionally high flow for organs their size.
Why?
This large blood flow is clearly not related to the metabolic needs of the kidney but is a function of the major role that the kidney plays in the regulation of ECF and blood volume regulation and rapid waste disposal.
Main functions of the kidney are: (5)
- Control volume & composition of body fluids
- To get rid of waste material from the body
- Acid-Base balance
- As an endocrine organ – EPO, Renin & Vit D activation
5) gluconeogenesis
Functional unit of kidney is nephron
what are the 2 elements?
how many in a kidney?
can kidney regenerate new ones?
- Average nephron ~4cm long
- Nephron has 2 elements – Bowmans capsule and tubule
- 1 million nephrons per kidney
- The kidney CAN NOT regenerate new nephrons.
- Therefore, you can still be able to function with one kidney or even a reduced function kidney
nephron is unusual in that it has 2 sets of capillaries
what is unusual about the glomerulus blood network?
what does it form afterwards?
Within the Bowman’s Capsule is a tuft of blood vessels known as the glomerulus, which has an unusual arrangement in that it enters as an artery (afferent arteriole) and also leaves as an artery (efferent arteriole), before forming the peritubular capillaries around to the tubule.
Blood and the tubule again meet up along the peritubular capillaries.
Hence nephron is unusual in that it has 2 sets of capillaries = glomerular & peritubular.
Urine Formation
2 stages
what happens to most of the fluid that is filtered out?
what urine output is considered renal failure?
- Glomeruli produce the liquid
- Tubules modifies its volume & composition
Nearly all of the fluid (and everything dissolved in it) are filtered through the glomerulus is reabsorbed back from the tubule into the blood, with the remainder being excreted as urine at a rate of 1ml/min (equivalent to ~1440ml/day or ~1.5L/day).
However, if your urine output is <5ml/day then this equates to renal failure.
Stage 1: Glomerular Filtration
how is it formed?
Glomerular fluid is formed by passive ultrafiltration of plasma across the glomerular membrane, as described by Starling’s principle of capillary fluid filtration.
Stage 1: Glomerular Filtration
Why such a huge filtration rate, namely 180 litre/day?
what is the gfr value typically?
• A high rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low.
• Example; a human produces 36 g urea per day:
o Yet normal plasma urea is only 0.2 g/litre.
o To wash 36 g urea into the urine, 180litre of plasma have to be filtered per day (because 180L x 0.2 g/L = 36g).
o This is a glomerular filtration rate (GFR) of 120 ml/min
The glomerular filtration rate (GFR) is set by (2)
o Autoregulation
o Renal sympathetic vasomotor nerve activity
The glomerulus consists
3 layers?
The glomerulus consists of a clump of capillaries & Bowman’s capsule
The glomerulus is also completely enclosed by epithelium of the Bowman’s Capsule, they are specialised to form podocytes.
Mechanism of Glomerular Fluid Formation
what is glomerular fluid?
what passes through completely?
what doesnt? clinical importance of this?
what drives the filtration?
Glomerular fluid is a passive ultrafiltrate of plasma.
The key features of glomerular filtration are:
• 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.
(Suggests that there is some sort of sieve that strains out larger molecules.)
Proteinuria
Proteinuria is a sign of renal/urinary tract disease.
An imbalance of starlings forces drives glomerular fluid formation (filtration)
what is unique about capillary pressure in the kidneys?
what 2 components act backwards on the driving force?
what is the net effect?
what happens to pressure from afferent to efferent end? and what happens to the plasma? does this change anything?
In the kidney the capillary pressure is highest compared to other arterioles in the body, hence have a pressure of ~50mmHg.
This results in an outward force i.e. pushing fluid out of the blood vessel.
There are 2 components of pressure acting in the opposite direction to this:
1. Colloid osmotic pressure exerted by proteins in the blood (25mmHg)
2. The other is the pressure in the Bowman’s space (10mmHg).
Hence the net effect is an outward force of approximately 15mmHg that drives fluid out of the capillary into the Bowman’s Capsule.
As the blood flows through the capillary there is a slight drop in pressure from the afferent end to the efferent end.
The plasma also gets more concentrated as the blood flows along due to fluid loss, an unusual effect observed just in the kidneys compared to other capillaries.
However, the net filtration force is always more than the net absorptive force resulting in a glomerular filtration rate of 20% which is colossal compared to 1% elsewhere in the body.
filtration fraction equation
value?
filtration fraction =
GFR/plasma flow = 120/600 = 20%
Starling force balancr is reversed (absorption) in peritubular capilaries
what happens at afferent end? result of this?
what happens at the efferent end? what drops and what rises? what effect does this have?
The blood pressure in the afferent arteriole is higher than the colloid osmotic pressure (COP) as you enter the glomerulus, resulting in a net filtration pressure out of the capillaries into the tubule.
As fluid travels out of the glomerulus into the efferent arteriole, the pressure begins to drop, and the COP rises because fluid is lost from capillaries, hence the protein is getting more concentrated thereby exerting a greater force driving fluid back from the tubule into the capillary i.e. Fluid is being absorbed back into the surrounding tissue and peritubular capillary where it comes into contact with the tubule wall.
Glomerular Membrane
what 3 layers are there?
what does a molecule have to be smaller than to be found in filtrate?
where can albumin pass? when do you find albumin in urine?
Fenestrated endothelium end of capilarry
Basement membrane
Foot processes of podocytes with filtration slits
Therefore, in a normal situation you would not expect to have blood in your urine. However, anything smaller than the fenestrae can enter the capillaries and then through the filtration slits into the urine.
Albumin can pass through the fenestrae but cannot pass through the filtration slits hence we would not expect albumin in the urine. However, if you have a lack of nephrin and podocin it will lead to the presence of albumin in the urine.
Ultra-high magnification of filtration slits
what does it look like?
what is it made up of?
defiency of these - what is that called?
Central spine with lateral rungs
subdivides filtration slit into pores 4nm wide
made of proteins nephrin and podocin
deficiency of these proteins causes nephrotic syndrome
Which layer is the molecular sieve?
what reacts with ferritin to produce a black precipitate?
where does this freely pass and where does it line up?
what is the primary filtration barrier for albumin?
describe the 3 sieves
what happens if last layer is broken down? (condition)
• Ferritin has and iron (Fe) core so each black dot is an individual molecule held up at the basement membrane because of its size.
Myeloperoxidase produces a black precipitate in a positive reaction
Glomerular filtration after iv administration of myeloperoxidase (MPO) with a MW of 160,000-180,000 showed that it readily traverses the endothelial fenestrations and crosses the basement membrane.
It then piles up beneath the surface of overlying pedicels and at the slit junctions of adjacent pedicels.
This suggests that the primary filtration barrier to molecules of the size of albumin is the slit pore.
Therefore, the glomerular membrane is 3 sieves in series, of increasing fineness. If the filtration slits breakdown then albumin gets through = nephrotic syndrome
Molecules that make it through to what point of sieve layers
all the way?
filtration slits?
basement membrame?
fenestrated endothelium?
water, glcuose, urea, creatinine, na, k all the way through
albumin stopped at filtration slits
fibrinogen stopped at the basement membrane
red cell stopped at fenestrated endothelium
Control of GFR Intrinsic control (intra-renal)
what rate is it held at constant at? why is this important?
what holds GFR constant?
what are chnages in urine production due to?
- GFR is in the main held constant (120ml/min)
- Important for capacity of tubules to reabsorb filtrate not be overwhelmed by 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 done by ADH.
In the normal range of renal arterial pressure even if BP changes up or down, GFR remains constant = autoregulation. (80 -180/200 bp)
If there was no autoregulation, 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.
Control of GFR
Autoregulation
2 mechanisms
name and describe the 2 mechanisms
what is their primary role?
what do they both do?
how do they respond differently to BP?
• When kidney subject to acute increases in BP, the renal plasma flow (RPF) and GFR remain relatively constant. Termed intrinsic because even if you denervated the kidney and isolate the kidney the GFR would remain relatively the same.
• 2 mechanisms acting together are responsible for this:
o Bayliss myogenic response:
- Direct vasoconstriction of afferent arteriole which is done by an increase in perfusion pressure
o Tubuloglomerular feedback (TGF):
- Flow-dependent signal detected in macula densa, that alters tone of afferent arteriole.
The current view is that these two mechanisms act in concert and that their primary role is to stabilise renal function by preventing pressure-induced fluctuations in RBF, GFR and the delivery of filtrate to the distal tubule. Both alter the tone of afferent arteriole
• The myogenic response can prevent changes in RBO in response to BP fluctuations that occur in intervals greater than 3-4 secs, whereas the TGF responds to slower BP fluctuations, over intervals of 20sec or longer.
Bayliss Myogenic Response
blood flow equation
how can you maintain flow and keep pressure down?
The relation between blood flow (F), the pressure difference that drives the blood from artery to vein (∆P) and resistance (R) is given by the equation F = ∆P/R.
- If the resistance was to remain constant i.e. the calibre of the vessels was not to change – a 50% increase in pressure would cause a 50% increase in flow.
- However, in the kidney and within a range of 80-180mmHg, a 50% increase in pressure only causes a 6-8% increase in flow.
• Resistance, therefore, increases with increasing pressure and this increase in resistance is localised entirely in the afferent arterioles.
Bayliss Myogenic Response
Blood pressure increase and blood flow
what happens when there is an increase in perfusion pressure?
what detects change?
effect?
how long till flow returns back to control?
Increase in perfusion 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 & increase in resistance -> flow returns to control value in 30s
Therefore, if you paralyse smooth muscle via drugs it would stop autoregulation.
Bayliss Myogenic Response
Blood pressure increase and bowman’s capsule pressure
what happens if BP rise? why?
what is maintained in parallel? so what happens if systemic pressure rises?
what also increases to balance rise in pressure?
If the blood pressure increases, then the vessels just upstream of the Glomerular capillaries contract resulting in a drop of pressure and keeping the pressure in the Bowman’s capsule (Pgc) still in the same range (constant at ~50mmHg).
Since the GFR and RPF are maintained in parallel, autoregulation must be mediated in part by changes in afferent arteriolar resistance.
As systemic pressure rises, for example, an increase in afferent arteriolar tone prevents the elevation in pressure from being transmitted to the glomerulus, allowing Pgc and GFR to remain unchanged.
The enhanced arteriolar resistance also increases total renal vascular resistance and this increase in vascular tone balances the rise in pressure and minimizes any change in RPF.
Bayliss Myogenic Response
Drop in pressure
what will happen?
when does the ability to maintain renal haemodynamics becoome impaired? what happens then?
Conversely, as blood pressure decreases, afferent arteriolar dilation will initially protect both GFR and RPF. However, the ability to maintain renal Haemodynamics becomes impaired at mean arterial pressures below 70.
In this setting, GFR and RPF fall in proportion to the drop-in blood pressure and the GFR ceases when the systemic pressure reaches 40 to 50 mmHg.
