Week 6: Renal clearance and Water Balance

Question 1

What is meant by clearance?

Answer 1

The rate at which a substances are removed from plasma

Question 2

What is meant by whole body clearance?

Answer 2

The total rate of removal of a substance from the body by all organs

Question 3

What is renal clearance?

Answer 3

The volume of plasma completely cleared of a substance by the kidneys per unit of time

Question 4

How do you calculate renal clearance?

Answer 4

C = [U]x X V̇
————-
[P]x

the concentration of a substance in the urine times the urine filtration rate

all divided by the concentration of the same substance in the plasma.

Question 5

What units are used for different values within the renal clearance equation?

Answer 5

Clearance - measured in mL/min
Urine and plasma concentration - mg/ml
Urine flow rate = ml/min

Question 6

What does the value of renal clearance indicate?

Answer 6

Value can vary from 0 upwards - getting up to greater than 600ml/min
Greater value indicates a higher level of clearance (more secretion in urine) - this indicates high levels of filtration and low levels or reabsoprtion.

Question 7

Why does albumin has a clearance value of 0?

Answer 7

Is not fitredted across the glomerular capillaries

Question 8

Why does glucose have a clearance value of 0?

Answer 8

Is filtered and then completely reabsorbed back into the bloodstream so is not excreted.

Question 9

Why does Na+, phosphate and other ions have a clearance rate greater than 0?

Answer 9

Are filtered, not all is reabsorbed, some is excreted in the urine.

Question 10

What is the use of inulin in measuring renal function?

Answer 10

Can be used as an indication of renal clearance
Is freely filtred across the glomerular capillaries but is not reabsorbed or secreted - so the value excreted is identical to the value filtered - its clearance is considered to be an estimated measurement of GFR.

Question 11

What molecules/substances are considered to have the highest clearance?

Answer 11

Organic acids such as PAh and organic bases such as morphine - they are both filtered and secreted - so a high level is excreted in the urine.

Question 11

What is the glomerular marker?

Answer 11

Inulin can be used as a reference point - considered a measurement of GFR as if only filtered not reabsrobed or secreted.
Clearance of other substances can be compared with clearance of inulin to be expressed as a clearance ratio.

Question 12

What does a clearance ratio value of less than one indicate?

Answer 12

The clearance of X is smaller than inulin
Hence X is either not filtered or is filtered then reabosrbed and not secreted
For example albumin, glucose and urea.

Question 12

How do you calculate a clearance rato?

Answer 12

The clearance of substance x

Divided by the clearance of inulin.

Question 13

What does a clearance value of one indicate?

Answer 13

Filtered but neither reabsorbed or secreted
Is a glomerular marker - the only example of this in inulin

Question 14

What does a clearance value of more than one indicate?

Answer 14

The clearance of X is greater than the clearance on inuulin
The substance is filtered and secreted, is not reabsorbed
For example organic bases and acids.

Question 15

What does the clearance ratio value indicate as a percentage?

Answer 15

The 1% of the filtered substance being excreted in the urine

Alternativly - 1-value - indicates the percentage being reabsorbed.

Question 16

What is the body’s response to water deprivation?

Answer 16

1. Deprived of water so plasma osmolarity increases
2. Stimulates osmoreceptors located in the anterior pituitary gland.
3. Increases thirst signals so drink more water
4. ADH secretion from the posterior pituitary gland increase.
5. Increases the permeability of the principle cells in the late distal tubule and the collecting duct to water
6. More water is reabsorbed into the interstitial fluid from the filtrate by osmosis
7. This leads to increased urine osmolarity and decreased urine volume
8. Altogether theis helps decrease plasma osmolarity back towards normal.
   This is an example of negative feedback.

Question 17

What is the bodys response to increased water intake?

Answer 17

1. Plasma osmolarity decreases
2. Inhibits osmoreceptors in the anterior hypothalamis
3. Decreased thirst signals so less drinking so less water volume is replaced
4. Decreased ADH secretion from the posterior pituitary gland
5. Late distal convulated tubule and the collecting ducts principle cells remains impermeable to water
6. Less water is reabosrbed from the filtrate into the interstitial fluid by osmosis
7. Body fluid decreases
8. Results in a large volume of dilute urine
   THis acts a negative feedback mechanism to increase plasma osmolarity back to homeostatic goal.

Question 18

What is meant by the corticopapillary osmotic gradient?
What does this value indicate?

Answer 18

The difference is osmolarity between the interstitial fluid of the renal cortex and the renal papilla.
Osmolarity tends to increase from the cortex to the papilla.
From 300mOsm/L to 1200mOsm/L in humans
The larger the greater the greater the ability to concentrate urine (typically very high in desert animals)

Question 19

What methods moving which solutes contribute to the corticopapillary osmotic gradient?

Answer 19

1. COunter current multiplication - in the Loop and Henle - the active transport of Na+ into the interstial fluid, deposits NaCl in the deeper regions of the kidney
2. Urea recycling - inner medullary collecting ducts which deposit urea.

Question 20

What is the mechanism of counter-current multiplication?

Answer 20

Descending limb - permeable to water
Ascending limb - impermeable to water - transport of NaCl

Filtrate enters the loop of Henle, in the ascending limb the single effect occurs
- this is when NKCC2 on the apical membrane, Cl- channels and the Na+ K+ pump on the basolateral membrane allow NaCl to be transported from the filtrate into the interstitial fluid - as impermeable to water, water can not follow the movement of sodium ions here - this leads to decreased filtrate osmolarity in thin decLOH and increased interstial osmolarity - two values will equilibrate

In the thin descending limb - is permeable to water, moves into intersitial fluid by osmosis down a water potential gradient - results in increased filtrate osmolarity

FLow od fluid - New fluid enters the LOH as travels down from the PCT - is the same osmolarity of the PCT (300mOsm/L). THis causes a corticopappilary gradient to start to develop

THe process repeats and the gradient increases (increase further in longer loops of henle)

Question 21

How does ADH affect the mechanism of counter current multiplication?

Answer 21

Acts to increase the activity of NKCC2 - enhances the single effect - more deposition of NaCl in the interstitial fluid - this increases the increase of osmolarity in interstial fluid and decrease in thick asloh
THis increased the corticopapillary gradient

Question 22

What are the two processes that contribute to counter current multiplication?

Answer 22

Single effect
Flow of fluid

Question 23

What is the mechanism of urea cycling?

Answer 23

Occurs when plasma osmolarity is high - activates baroreceptors and ADH secretion
1. In the cortex ADH increased permeability to water - increased water reabsoprtion
2. This increased the tubular filtrate concentration of urea found in the outer medulla
3. In the inner medullar ADH increases permeability to water and urea transport by increases UTI channels
4. THis allows the urea to diffuse from the tubular fluid into the interstitial fluid hence it is reabsorbed. - moves down concentration gradient established by step 1 and 2.
5. This prevents urea that would have been excreted from being excreted - leads to more water retention

Question 24

What are the effects of counter current exchange in vasa recta?

Answer 24

Helps maintain the corticopapillary gradient
Reliance on the passive properties of the blood vesssels/endothelial cells in the vesa recta (surrounding loop of henle)
They are freely permeable to water and small solutesand blood flow is slow through the,
This allows solutes and water to move in and out as appropriate to reach equilibrium hence efficient counter exchange maintains an osmolarity in the blood vessels equal to that in the interstitium.

Question 25

What is the mechanism of action of ADH as renal laste distal tubule and collecting ducts?

Answer 25

Delivered to the principle cells by the perirubular capillary.
Binds to V2 receptor - is a G stimulatory protein receptor
results in the activation of the second messenger adenylyl cyclase
This catalysed the conversion of ATP into cAMP
cAMP activates Protein Kinase A which causes phosphorylation
Result of signalling pathway is the fusion of vesicles containing AQP2 into the apical membrane to increase permeability to water.

Question 26

What is meant by intermembranous particles in relation to ADH action?

Answer 26

The insertion of AQP2 onto the membrane of principle cells in the late distal convoluted tubule and the collecting ducts.
These can be visualised using freex fracture elctron microscopy in clusters in the membrane known as intermembranous particles.
Greater number of clusters indicates greater permeability to water.

Question 27

What are the three action of ADH on the renal tubule?

Answer 27

1. Acts on the principle cells of the late DCT and the CD to insert aquaporints and increase permeability of the apical membrane to water
2. In the thick ascending limb of LOH increases the activity of the NKCC2 enhancing the countercurrent multiplication process increasing the corticopappilary gradient so greater potential to concentrate urine
3. Increase permeability in the inner medullary collecting ducts to urea recycling which further increases the corticopapillary concentration gradient.

Question 28

What are the basic causes of hyperosmotic urine?
What is meant by hyperosmotic urine?

Answer 28

Highly concentrated urine that has a concentration that is higher than blood osmolarity
Produced when circulating levels of ADH are high.
For example in water deprivation fo SIADH

Question 29

What is the maximum urine osmolarity concentration?

Answer 29

Equal to the concentration of the interstitial fluid at the bottom of the LOH in the renal papillae.

Question 30

What is the process by which the kidney produces hyperosmotic urine?

Answer 30

1. Requires high ADH levels - such as in water deprivation
   - increases activity of NKCC2 in thick ascendiing LOH - increase the counter current multiplication
   - increases urea recycling in the meduallry collecting ducts
   - increases permeability of the principle cells of the cortical DCT and the DT to water via the insertion of aquaporins.

Question 31

What is meant by hypoosmotic urine and what is the cause?

Answer 31

Diluted urine or urine that has a lower osmolarity than the blood omsolaroty
Is produced when circulating levels of ADH are law (water drinking or central diabetes insipidus) or when ADH is ineffective (nephrogenic diabetes inspipidus)

Question 32

What is the mechanism behind the formation of hypoosmotic urine?

Answer 32

Low levels or ineffective ADH
The thick ascending loop of Henle - NKCC2 is not enhanced by ADH so the counter current multiplication effect is reduced, the corticopappilary gradient is lower - less sodium in interstitium so less water reabsorbed from the thin descending limb
- the DCT and CD remains impermeable to water but are still reabsorbed NaCl to filtrate becomes more dilute
- lack of urea recycling in the medullary CT so reduced water potential gradient for the reabsoprtion of water (also CD is impermeable to water anyway)

Question 33

What is meant by free water in the nephron?

Answer 33

Distilled water that is free of solutes - found in the tubular lumen
Is generated in the diluting segments of the nephron (these segments remove solutes but water remains)
These are the impermeable segments - the thick ascending limb and the early distal convoluted tubule

Question 34

What are the diluting segments of the nephron?

Answer 34

The thick ascending limb and the early distal convoluted tubule.

Question 35

What is the importance of free water clearance to the function of the nephron?

Answer 35

CH20 - provides a method for assessing the ability of the kidneys to dilute or concentrate urine

High free water clearance - indicates low ADH - so less water reabsoprtion - hypoosmotic urine. (positive value of free water clearance)

Low free water clearance - indicates high ADH - so more water reabsoprtion - hyperosmotic urine (negative value of free water clearance)