Week 3

Question 1

Loop of Henle

Answer 1

2 key functionally distinct components:
- descending limb
-thick ascending limb

The key function is for the thick ascending limb to create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct

Question 2

Descending limb

Answer 2

Permeable to water, which leaves the filtrate because of osmotic force
Paracellular and transcellular

Question 3

Thick ascending limb

Answer 3

Can sustain an osmotic gradient of about 200 mOsm.kg-1
Uses the Na+/K+/2Cl- cotransporter to move ions out of the filtrate. Common abbreviation: NKCC2; systematic name of the gene:SLC12A1. This is a member of the SLC12 family of ‘cation coupled chloride transporters’
K+ recycling through the apical membrane is necessary in order to ensure that the transporter can maintain its role of transporting large quantities of Na+ and Cl-
Na+/K+ ATPase drives sodium out cell to maintain electrochemical gradient

Question 4

Furosemide

Answer 4

Acts in the ascending limb of loop of Henle
Blocks Na+/K+/2Cl- co transporter
Allows up to 20% of filter Na+ to be excreted, causing enormous natriuresis and diuresis
Uses: cardiac failure, renal failure
Side effects: K+ loss (and subsequent hypokalaemia) leading to cardiac dysrhythmias (particularly when administered with digoxin)
Other side effects:
-hypovolaemia (assessed by acute weight changes)
-mild metabolic alkalosis (distal Na+/K+ exchange)
Loss of Mg2+ and Ca2+ (loss of filtrate +ve charge)

Question 5

Countercurrent multiplier

Answer 5

Involves the opposite flow of fluid in the 2 limbs of the loop of Henle
Is analogous to the retention of peripheral heat loss

Question 6

Tubules

Answer 6

If you’re reabsorbing fluid from the lumen into the intestinal space the change in composition of the interstitial space will affect the movement of other substances from nearby tubules
Ie the tubules dont exist in isolation they interact

Question 7

Loop of Henle

Answer 7

Consists of 2 functionally distinct components:
-descending limb
-thick ascending limb
The key function is of the thick ascending limb to create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct (reabsorbed back into body)

Question 8

Descending limb

Answer 8

Connected to the proximal tubule is the descending limb of the loop of Henle
It heads from cortex down into medulla
The descending limb is permeable to water- water leaves the filtrate because of osmotic force via a paracellular route (between cells)

Question 9

Thick ascending limb

Answer 9

Left side is lumen of the tubule contains filtrate
Right side is the interstitial space
The thick ascending limb is impermeable to water there are lots of tight junctions between epithelial cells
This means it can sustain an osmotic gradient of about 200mOsm.kg-1
The epithelial cells that make up thick ascending limb have Na+/K+/2Cl- cotransporters NKCC2 on their apical surface:
-systematic name of the gene: SLC12A1 this is a member of the SLC12 family of cation coupled chloride transporters
They take Na, K+ and 2Cl- out of the filtrate across the apical membrane
K and Cl- can be then reabsorbed across the basolateral membrane using ion channels
To get Na+ across you need a pump (Na/K ATPase) as Na+ are going against their electrochemical gradient
There is also a leak K+ channel located on the apical membrane transporting K+ back into filtrate
This is because theres more Na+ in plasma so more sodium in filtrate:
- so if only have a 1:1 transport of Na and K+ via NKCC2 transporter you’ll eventually run out of K before Na+
-therefore need to replenish K+ via the leak K+ channel to prevent the cotransporter from stopping
So in the thick ascending limb-slats are reabsorbed but water is not

Question 10

Furosemide

Answer 10

Furosemide is a diuretic that acts in the ascending limb of the loop of Henle
It’s concentration dependent
The vast majority of diuretics work by inhibiting the absorption of ions particularly Na+
This keeps Na+ in urine which in turn keeps water in the urine due to the osmotic pressure increased volume of urine produced
Mechanism of action:
-blocks Na+/K+/2Cl- co transporters
-this means up to 20% of filtered Na+ will be excreted causing enormous natriuresis (loss of Na+ in urine) and diuresis
Uses: when you have volume overload eg in cardiac failure, renal failure
Side effects:
-K+ loss in urine (and subsequent hypokalaemia), leading to cardiac dysrhythmias (particularly when administered with digoxin) as K+ is important in maintaining membrane potentials
-so people usually have to have K+ supplements when on this drug
Other minor side effects:
-hypovolaemia (assessed by acute weight changes)
-mild metabolic alkalosis (distal Na+/H+ exchange)
-loss of Mg2+ and Ca2+ (loss of filtrate +ve charge)

Question 11

Countercurrent multiplier

Answer 11

A countercurrent multiplier involves the opposite flow of fluid in the 2 limbs of the loop of Henle
In the kidney there is a countercurrent multiplier mechanism for Osmolality
The descending limb of the loop of Henle is in close contact of ascending limb of loop of Henle
The ascending limb is pumping Na+ out of the filtrate into the interstitial space which creates an osmotic gradient to help water movement out of the descending limb
The interaction of these 2 vessels is important for renal function

Question 12

No Osmolality coupling

Answer 12

Consider a hypothetical tubule without Osmolality coupling in a tubule with an Osmolality pump (ie just thick ascending limb)
We have filtrate flowing in from the proximal tubule
The Osmolality is 285mosmoles/kg
Na+ is being pumped out in order to maintain an osmotic gradient of 200mosmoles/kg
Na+ will flow out until we get osmolality down to 85 osmoles/kg then the pumping stops when we have reached 200osmotic pressure difference
Under these conditions then for each 1L of fluid entering the tubule, 200mOsm/kg 70% of ions could be removed (reabsorbed) whilst 85mosm/kg 30% would pass onto the next part of the tubule
This is not enough

Question 13

Osmolality coupling

Answer 13

Now consider a hypothetical tubule with an Osmolality countercurrent and an Osmolality pump
Solution flows into the descending limb starting off as 285mosmoles/kg
As the filtrate flows deep down into medulla water moves out of the tubule and is reabsorbed
This is because there is lots of salt (Na+ and Cl-) in medulla as it is being pumped out by the thick ascending limb
At each point the Osmolality gradient is never greater than 200mOsmoles/kg but much more Na can be reabsorbed:
-in the descending limb there is no Na being reabsorbed it is water thats moving
However there is lots of Na being reabsorbed via a transporter system in the ascending limb 1200 to 85mosmoles/kg
This means we are absorbing about 93% of our ions despite only have osmotic gradient of 200 mosmoles/kg: for each 1L entering containing 285mosm ions, we can now reabsorb 264mosm, allowing only 7% to pass onwards

Question 14

How do we get to Osmolality coupling

Answer 14

We are going to set up the loop of Henle with the descending limb ands ascending limb all having Osmolality of 300mosm/kg
Sodium leaves the ascending limb either via passive diffusion or by NKCC2 cotransporter
Because the thick ascending limb is impermeable to water the water stays behind and osmolarity of the ascending fluid decreases
Sodium however is being added to the interstitial fluid increasing its osmolality
This creates an osmolarity difference between the interstitial fluid and thick ascending limb
Water diffuses out of thin descending limb until fluid equilibrates with interstitial fluid
Once this occurs fluid from the proximal tubule enters pushing higher osmolarity fluid below it down loop of Henle
The osmolarity of fluid in descending limb and interstitium are again mismatched causing water to leave the descending limb until fluids have reequilibrated
These 2 steps are repeated with each cycle enhancing the gradient
At its maximum the Osmolality of inner medulla is 4x cortex

Question 15

Dialysis filter

Answer 15

In hemodialysis blood is pumped through the filter
Within the filter there is a semipermeable membrane
On other side of membrane theres dialysis solution
Blood is in contact with the dialysis solution which flows in opposite direction
So we have countercurrent exchange between blood and dialysis fluid leads to more efficient removal of solutes from blood

Question 16

Na+ absorption in the distal tubule

Answer 16

In the rest of the distal tubule we have other mechanisms for sodium Reabsorption
This is in cortex of kidney
In the distal tubule on the apical surface of the epithelial cells one of key transporters is the sodium chloride cotransporter
It transports both Na+ and Cl- ions into the epithelial cell
Equilibrium is established on basolateral membrane by K/Cl co transporter
Na crosses basolateral membrane against concentration gradient using Na pump
Theres a large class of diuretics which act by inhibiting the apical reabsorption of Na and chloride called Thiazides

Question 17

Thiazides

Answer 17

Eg Bendroflumethiazide, hydrochlorothiazide, and thiazide-like (eg indapamide) drugs
Act in the distal tubule
Block Na/Cl cotransporters
Stop na and Cl reabsorption
So Na and Cl stay in filtrate so water stays in filtrate due to osmotic pressure so lose more urine
Moderately effective diuretics
Uses: antihypertensive, as a diuretic in conjunction with furosemide (reduced amount of furosemide you need to give less side effects)
Other side effects:
-increased Uric acid
-hyperglycaemia
-hyponatraemia

Question 18

Na+, K+ and water transport in the collecting ducts

Answer 18

The collecting ducts are the last part of the nephron system before urine flows into the renal pelvis
Through much of the tubule system, Na+ electrochemical gradient has been used to drive the reabsorption of others substances across apical membrane
Now just as urine is about to be formed we need to separately regulate Na
On the apical surface of the epithelial cells that make up the collecting duct we have Na channels
These allow for the direct Reabsorption of sodium via ion channels
On the basolateral surface we have Na/K ATPase
On apical surface we also have another K+ channel- the collecting duct is quite important location for the secretion of potassium
The [Na]>[K] in plasma
However the intake of Na and K is similar
This creates problem for the kidney as they see a high concentration of Na and low concentration of K
This means relatively speaking the kidney has to reabsorb more of the sodium and secrete more potassium to maintain whole body homeostasis
Distal tubule is therefore an important site of Na reabsorption
The main hormonal regulation for this pathway is aldosterone
It increases expression of ENaC channel (epithelial sodium channel) and also Na/K ATPase so drives this process more strongly

Question 19

Water transport in collecting ducts

Answer 19

AQP2- aquaporin 2 allows for water reabsorption from the collecting ducts
under control of ADH

Question 20

Spironolactone

Answer 20

Acts in collecting tubules and ducts
Blocks the effect of aldosterone by inhibiting aldosterone receptor
So indirectly inhibits Na reabsorption causes diuresis
Also reduces amount of K secretion more K in body
Moderately effective diuretics
Uses: heart failure (K+ sparing diuretic)
Furosemide causes K loss, spironolactone causes K retention so by giving both you can get larger diuresis and balance K concentration
Other side effects:
-spironolactone are steroid receptor inhibitor so by inhibiting these receptors they cause feminising actions in men and menstrual disorder in women eg:
-gynaecomastia, menstrual disorders, testicular atrophy, hyperkalaemia
Eplerenone is a newer,more specific Mineralocorticoid inhibitor; currently however its much more expensive

Question 21

Urea countercurrent multiplication

Answer 21

In the late distal tubule and cortical collecting duct (urea impermeable) as water is removed the urea concentration rises.
In the medullary collecting duct the urea diffuses out of this urea-permeable tubule
Urea permeability is increased by ADH by increasing the expression of UT-A1 (urea transporter A1)
The urea now in medullary interstitial space contributes significantly to the high osmotic pressure in the medulla which further aids water Reabsorption in the medulla
The urea can then renter the filtrate by entering via UT-A2 into loop of Henle which further aids water reabsorption in medulla. Urea countercurrent
Ultimately some urea may return to body some also enters through different urea transporters back into filtrate
So in the kidney we have a cycle of urea from collecting duct back into descending limbs of the loop of Henle
So closely interacting tubules within the medulla allows the exchange of substances in order to allow more efficient water reabsorption

Question 22

Osmolality in the nephron (mOsm.kg-1)

Answer 22

Initially osmolality of filtrate is 285mosm/kg it doesn’t change much along length of proximal tubule
As water is reabsorbed in the descending limb the filtrate becomes more concentrated-> 1200mosm/kg (varies depending on expression of hormones). By the time you get to the end of the thick ascending limb much of salt has been reabsorbed so osmolality is quite low
Over the rest of the tubular system we get more water reabsorption eventually leading to urine osmolality which can vary 60-1400
Urine usually has osmolality higher than plasma this is because we tend to not excrete as much water as salt and toxins so our urine tends to be more concentrated than plasma

Question 23

Flow rate in the nephron (ml.min-1)

Answer 23

More than half of the water in the filtrate is reabsorbed in proximal tubule: flow rate -125-> 45ml/min
By the time you get to the end of the loop of Henle we still have significant flow of 25ml/min
We then get a drop in urine flow rates as we head along distal tubule and into collecting duct
However Reabsorption of water is only possible due to action in loop of Henle to absorb salts and generate high osmotic pressure in medulla allowing osmotic pressure gradient for reabsorption of water
Urine outflow is very variable 0.1-17 avg. 1.25ml/min

Question 24

Regulation of urine osmolality and flow

Answer 24

Primarily determined by ADH (vasopressin)

Question 25

ADH

Answer 25

Synthesised in hypothalamus
Also known as arginine vasopressin (AVP) or just vasopressin
Released from terminals of the hypothalamic neurones found within posterior pituitary
Acts in the distal tubule and collecting duct to increase water permeability by increasing AQP2

Question 26

Recalls: water transport in collecting tubule

Answer 26

On the apical membrane and basolateral membrane of the epithelial cells that make up the collecting tube there are aquaporins
AQP3 is present most of the time (basolateral membrane)
AQP2 expression on apical membrane is variable (under influence of ADH)
ADH increases expression of AQP2 on apical membrane
If we had no AQP2 there would be no net pathway for water
More AQP2-more water reabsorption

Question 27

Cellular pathways regulating AQP2 on the apical membrane

Answer 27

The receptor for ADH is a GPCR called V2 receptor
It’s located on the basolateral membrane as hormone travels via blood
ADH binds to receptor, this causes GS to stimulate Adenylyl cyclase which leads to the production of cAMP
cAMP in epithelial cells has 2 pathways:
-it causes the insertion of AQP2 channels AQP2 are performed in vesicles
-cAMP activates PKA which phosphorylates some of synaptic vesicle associated proteins and encourages their insertion into membrane and hence AQP2 ends up in membrane
Drives synthesis of new AQP2 proteins (replace those inserted)
Protein production takes time so if you did not have them pre synthesised it would take a lot of time to regulate water excretion

Question 28

Osmolality (mOsm/kg) in the nephron: no ADH

Answer 28

In the absence of ADH we get little water reabsorption
When theres no ADH present there is relatively little water Reabsorption (Osmolality in distal tubule usually 90-constant) 90->60 (reabsorption of Na) and therefore urine remains dilute (low osmolality)
This is because under these conditions the distal tubule and collecting duct are impermeable to water and so the urine remains dilute

Question 29

Flow rate in the nephron (ml/min) no ADH

Answer 29

Flow rate at end of distal tubule also reminds constant-> 25ml.min
However in the absence of ADH theres little water reabsorption over the length of the distal tubule and collecting duct so the urine flow rate remains quite high

Question 30

Osmolality (mOsm/kg) in the nephron maximum ADH

Answer 30

If we have maximum ADH the distal tubule and collecting duct become permeable to water-allow water Reabsorption
Now urine becomes more concentrated as water leaves the tubule system

Question 31

Flow in the nephron (ml/min) maximum ADH

Answer 31

If we have maximum ADH both sodium and water is reabsorbed so the flow rate drops down to a low value
We aren’t producing much urine

Question 32

Urea

Answer 32

Has a role in maintaining osmolality in the renal medulla
Urea helps to make concentrated urine
In the presence of selective protein starvation urea production is low and so the kidney has a lower capacity to concentrate urine
The urea transporter UT-A1 is also regulated by ADH in a similar way as for AQP2

Question 33

Cellular pathways regulating UT-A1 on the apical membrane

Answer 33

The same signalling pathway that causes insertion of AQP2 also causes the insertion of urea transporters into apical membrane allowing for urea absorption
This Reabsorption of urea is important for urine concentration

Question 34

Osmolality (mOsm/kg) in the nephron maximum ADH urea

Answer 34

In the presence of high ADH we have a high Reabsorption of urea as well as water
It’s this high reabsorption of urea which allows urea to accumulate in the medulla which contributes to generating high Osmolality
High osmolality in loop of Henle 1400

Question 35

Osmolality in the nephron no ADH urea

Answer 35

If we have no ADH we have got no urea reabsorption
This means urea cant contribute to medullary Osmolality which means that the medulla is more dilute than it would be otherwise be
This in turn means less water can be reabsorbed so theres low Osmolality in the loop of Henle 600

Question 36

Cell survival in the medulla

Answer 36

If cells in the medulla routinely see 1200mOsm/kg how do they survive- a normal cell would shrink as the high osmotic pressure would draw water out of the cells
One key adaptation is the accumulation of a range of organic osmolytes within the cells. These include sorbitol, inositol, glycerophosphorylcholine and betaine
This keep osmolality high which helps to keep water in the cell

Question 37

Diabetes insipidus

Answer 37

Associated with a loss of ADH secretion (central diabetes insipidus) or a loss in sensitivity of the kidney to ADH often because of a problem with the V2 receptors (nephrogenic diabetes insipidus)
This means they are unable to produce concentrated urine leading to polyuria (with low osmolality) (high dilute urine output), dehydration, hypovolaemia. This then causes polydipsia (drinking too much)
If fluid intake is inadequate they become hypernatraemic
Easy to be confused with DM due to similar symptoms

Question 38

Central diabetes insipidus

Answer 38

Lack of ADH secretion
Originates in the brain
Causes: head injury, tumours in pituitary fossa, infection (especially at base of brain)
Management:
-give desmopressin (ADH analogue with a longer half life) to replace missing ADH
-paradoxical use of thiazide diuretics, suggested mechanisms of action include: protection against hypernatraemia (they inhibit Na reabsoprtion), encouragement of proximal tubule water Reabsorption, and/or an increase in aquaporin expression (not linked to its action on the NCC cotransporters)

Question 39

Nephrogenic diabetes insipidus

Answer 39

Where kidney loses sensitivity to ADH
Causes:
-toxicity (eg lithium)
-hypercalcaemia
-genetic due to mutations in either V2 or AQP2
Treatment:
-not with desmopressin
-thiazide diuretic
-low salt diet- fix hypernatraemia

Question 40

SIADH

Answer 40

Syndromes in inappropriate ADH (SIADH)
Symptoms are related to inappropriately high ADH, commonly caused by head injury (and many other interesting rarer causes)
Produce concentrated urine- kidney retains water so does not pass out into urine
Become hyponatraemic- all water is retained so dilutes sodium concentration becomes low
Treatments include:
-fluid restriction fixes volume overload
-give urea in high concentrations (not in UK, acts as an osmotic diuretic to stop body retaining water )

Question 41

Aquaretic drugs- Vaptans

Answer 41

Cause water loss without salt loss no solute excretion
-diuretics cause volume loss (loss of solute and water)
They are V2 receptor antagonists (Vaptans; eg tolvaptan) are now being used to treat chronic hyponatraemia
Act on the late portion of distal tubule and the collecting duct to block action of AVP(ADH)
Particularly used in the treatment of SIADH (or hyponatraemia more broadly) pure water loss in urine so Na concentration increases if you have excess ADH you can treat it by block V2 receptor using antagonist

Question 42

Vasa recta

Answer 42

The vasa recta of the kidney branch off the efferent arterioles from the glomeruli, run into portal vessels which then plunge from cortex deep into medulla. they enter medulla forming hair pin loop surrounding loop of Henle
They take water and solvents from the interstitial space after absorption by the tubules
They also supply substances into the interstitial spaces where they can then be actively secreted by tubules
They also supply oxygen and glucose deep down into medulla
As the capillaries are permeable (excluding proteins) the osmotic pressure in the vasa recta changes with the local interstitial osmolality diluting the interstitum on the descending limb but concentrating it on the ascending limb

Question 43

Countercurrent in the vasa recta

Answer 43

The Osmolality of plasma flowing in vasa recta in its descending portion will initially be similar to that of systemic plasma 285mosm/kg
As these blood vessels descend down deep into medulla they start to be exposed to a more concentrated extracellular space (higher osmolality)
That means as the fluid descends there will be loss of water from the descending limb
This is compensated in the ascending portion of vasa recta with water Reabsorption
There is a net movement of water inwards because of the low hydrostatic pressure in the capillaries, high oncotic pressure in the capillaries and relatively high hydrostatic pressure in the turgid interstitial space
Sodium moves into the vasa recta in the descending portion down its concentration gradient

Question 44

Countercurrent in vasa recta- flow rate

Answer 44

Flow rate into vasa recta= RPF-GFR= 600-125=475
Flow rate in the descending limb must decline as water leaves
Flow rate in the ascending limb must increase as water arrives
RPF- rate of urine production (1.25) =600-1.25=approx 600
So the net effect of this system must be the reabsorption of water 475->600

Question 45

Auto regulation of renal blood flow

Answer 45

2 mechanisms are key:
-myogenic responses (regulating total renal blood flow)
-tubuloglomerular reflex (regulating single nephron GFR but affecting renal blood flow if many single nephrons are affected)
Such auto-regulation is present when the kidney is ex vivo so it cannot depend on central neuronal input (eg it cannot require a spinal cord reflex pathway)

Question 46

Hypothetical renal blood flow with no auto regulation

Answer 46

Imagine afferent arteriole is a rigid tube
If you were to increase blood pressure on the arteriole end the flow rate would also increase
This is a linear relationship-> double pressure= double flow rate
However if you try this with the kidney and change perfusion pressure you do not see this relationship

Question 47

Hypothetical renal blood flow: assuming elastic arteries

Answer 47

Instead of a rigid tube we now allow blood vessel to dilate
As the pressure goes up you might expect the diameter would also increase
With a dilating vessel you have lower resistance to flow so flow rate should increase at an ever-increasing rate
Curved line graph
This relationship doesn’t happen either

Question 48

Actual renal auto regulation

Answer 48

Perfusion pressure (BP) plotted against renal blood flow (promotional to renal plasma flow)
At around normal blood pressure, increases blood pressure does not significantly increase renal plasma flow rate graph plateauing
This is contrary to what we would expect in stretchy vessel- should be exponential curve
This suggests blood pressure is increasing renal afferent arterioles are not dilating but instead contracting in response to increased pressure
Protecting glomerulus downstream so glomerular capillaries dont see the high BP
At low BP an increase increase RBP linearly
And at very high BP RBF increases

Question 49

Myogenic response

Answer 49

The basis of this phenomenon is that when the afferent arterioles are stretched they contract. Hence an increase in the perfusion pressure causes a vasoconstriction which narrows the vessels increases resistance and hence reduces the flow rate so flow rate remains relatively constant
Recall Poiseuille’s law:
Flow_rate= pi(change in)PR^4/ 8(viscosity)length of vessel
So as change in P we might expect flow rate to increase but if radius reduces even slightly flow rate change can be minimised
The myogenic response exists in an isolated kidneys and BV
Doesn’t require nerves
Usually dependent on endothelial cells

Question 50

Myogenic response: quantitative

Answer 50

Suppose that the arterial blood pressure increased by 10%; to completely correct for the change in driving pressure the change in the R^4 much be to fall by 10% which means R needs to fall by 2.5% to balance increase in pressure
The implication of this is that only a small change in afferent arteriole diameter are necessary in order to correct change in pressure
This response is unlikely to be completed in part because as soon as the vessels narrow the pressure in them will begin to fall

Question 51

Cellular mechanism of myogenic response

Answer 51

Response generated by stretch activated cation channels depolarising the smooth muscle cells, as vessles stretch Channels open up, hence increasing Ca2+ influx (opening of voltage gated ca2+ channels) and subsequently causing contraction
This type of myogenic effects which can occur in many arterioles is traditionally known as the Bayliss effect

Question 52

Why have the myogenic response

Answer 52

Traditionally the idea is that the main useful feature is to maintain GFR regardless of the mean atrial pressure, allowing independent regulation of volume and pressure
However some have argued (Loutzenhiser et al., 2002)
That the main effect is to reduced the impact of high systolic pressures as the reflex is more sensitive to the peak than to the mean pressure

Question 53

Tubuloglomerular feedback

Answer 53

Longer pathway involved in regulation of blood flow
This is the key way in which each nephron can regulate its GFR
High Na+ in distal tubule is sensed by macula densa
(Na-K-2Cl cotransporter NKCC2- dependent)
Cells of the macula densa release ATP that is broken down to adenosine
Adenosine causes vasoconstriction of afferent arterioles, leading to a fall in glomerular hydrostatic pressure and a fall in GFR
This mechanism is hence a negative feedback system
The distal tubule runs very close to the glomerulus here the specialised cells in the macula densa mediate tubuloglomerular feedback
This is handy as the rate of sodium or water flow in distant tubule can help to regulate the amount of blood flow coming into glomerulus

Question 54

Hypothetical situation

Answer 54

A single nephron has very high GFR
With high GFR lots of water enter filtrate
So lots sodium entering filtrate
However previously mentioned mechanisms about loop of Henle means that a relatively fixed amount of sodium is being reabsorbed which means if you have high GFR and high amount of sodium being filtered you will have high sodium delivery into distal tubule
Some of sodium is transported by NKCC2
This leads to release of ATP from macula densa cells
ATP broken down into adenosine which caused constriction of afferent arteriole which causes a fall in glomerular hydrostatic pressure and hence a fall in single nephron GFR

Question 55

Factors opposing renal auto regulation of blood flow

Answer 55

There are 2 intrinsic factors that keep GFR constant:
-myogenic response
-tubuloglomerular feedback system
While the usefulness of auto regulation via the above mechanisms is clear in isolated tissues (in vivo) the renal blood flow is also influenced by:
-renal innervation
-circulating hormones
These factors help to match the needs of the body against the wants of the kidneys

Question 56

Renal innervation

Answer 56

Theres a dense plexus of nerves innervating and regulating the renal vasculature
Most of the efferent nerves are sympathetic releasing noradrenaline and causing vasoconstriction via alpha 1 adrenoreceptors
A key stimulus is hypotension causing a decrease in RBF in an attempt to retain volume and shunt blood flow to muscle for short term needs
Vasoconstriction is also useful as a mechanism for trying to retain water if you have a situation where systemically you are losing BP then at least afferent arteriole vasoconstriction are particularly important for retaining water
There are also many sensory (afferent) neurones NB: afferent and efferent in this sense are with respect to CNS

Question 57

Method for measuring renal plasma flow

Answer 57

To measure renal flow measuring compound that is completely removed from the plasma (tubular secretion or filtration and tubular secretion) and then is lost in urine
P-aminohippurate PAH
I.e:
-if any of this substance enters in the renal artery it all ends up in urine none comes out in renal vein
So PAH is freely filtered and also actively secreted into proximal tubule if it enters kidney all of it enters urine
So rate at which compound enters kidney= rate at which compound leaves kidney= rate at which it appears in urine
So we set the rate at which paraaminohippuric acid enters kidney to be equal to rate at which it enters urine
Then rearrange to make RPF subject
RPF= V dot *C(pah u)/ C(pah p)
Cpahp= concentration PAH in plasma, Cpah u= concentration PAH in urine
V dot is urine flow rate