8. Renal structure and function 1

Question 1

Describe the general structure of the kidney

Answer 1

Around the outside is the cortex
The inner part is the medulla - made up of pyramids of the medulla
Hilum is central - just inside the kidney
Ureter comes from hilum and carries urine from kidney to bladder - then carried out of bladder via urethra
Renal arteries pass through hilum and then branch
At the end of the arteries are glomeruli - whole vast of terminal arterioles end in this structure in the kidney cortex

Question 2

Describe the structure of the glomeruli

Answer 2

Each glomerulus is enclosed in a Bowman’s capsule

Urine is filtered out of the glomerulus into the Bowman’s capsule and then into the proximal convoluted tubule

Blood enters the glomerulus of each nephron via the AFFERENT ARTERIOLE and leaves via the EFFERENT ARTERIOLE

About 20% of blood plasma is filtered through here and enters into the proximal convoluted tubule

Question 3

Compare afferent arterioles to efferent arterioles and the implications of this

Answer 3

Blood enters the glomerulus via the afferent arteriole and leaves via the efferent arteriole

Afferent arterioles have larger diameters than efferent arterioles and so there is a considerable drop in pressure between the two - THIS IS BECAUSE the smaller diameter means there is an increased resistance and so a decreased flow and hence a reduced pressure through the efferent)

The increased resistance in the efferent results in an increased pressure in the glomerular cavity and this is known as the FILTRATION PRESSURE - this forces fluid through the endothelium of the capillaries into the capsular space

Question 4

Define filtration pressure in the kidney

Answer 4

The pressure exerted by fluid on the capillary walls of the glomerulus or the walls of the Bowman’s capsule

Question 5

How is filtration pressure regulated?

Answer 5

The pressure difference between the afferent and efferent arterioles
The pressure inside the glomerulus
The nature of the cells that do the filtering

Question 6

Describe the capillaries of the glomerulus and their basic structure

Answer 6

These are called PODOCYTES and cover the outside of the capillaries i.e. the capsule side

They have slits between them which form the filtration mechanism

These allow the passing of water and small molecules e.g. glucose, NA+, K+, HCO3- but prevent the loss of proteins

If these become inflamed (or enlarged in renal disease) then this enables more solutes i.e. proteins through into the urine - sign of renal infection

Question 7

Briefly describe the proximal convoluted tubule and it’s structure

Answer 7

Leads on immediately from the glomerulus/bowman’s capsule
Have many microvilli
From here, substances can either be reabsorbed or can go out into the urethra and be excreted

Question 8

Briefly describe the structure of the loop of Henle

Answer 8

Thin descending limb - low permeability to ions and urea but highly permeable to water

Thin and thick regions of ascending limb - thin is impermeable to water but permeable to ions and thick is where reabsorption of ions occurs

Question 9

Very briefly, give the movement of substances through the nephron

Answer 9

Fluid leaves the Bowman’s capsule and enters the proximal convoluted tubule
Then enters the loop of Henle
Goes into the distal convoluted tubule
Enters the collecting duct

From the collecting duct, fluid is drained down into the ureter and out to the bladder

Question 10

What is the ‘juxtoglomerular apparatus’?

Answer 10

Where the distal convoluted tubule folds back and meets the vessels entering the glomerulus i.e. the afferent and efferent arterioles

Question 11

Describe the flow of blood through the kidneys

Answer 11

Just under a quarter of systemic cardiac output flows through the kidney per minute

Cardiac output at rest is 5L/minute so about 1.2L/minute through the kidney - SO very high blood flow through the kidney

Question 12

Explain what is meant by ‘renal plasma flow’

Answer 12

The volume of blood plasma delivered to the kidneys per unit time
e.g. 1.25L/minute is the GFR (to both kidneys)
Haematocrit is 45% so blood plasma is only 55%
SO the RPF is 0.55 x 1.25 = 680ml/minute

Question 13

What is the ‘glomerular filtration rate’ (GFR)?

Answer 13

This is the total amount of general fluid through BOTH kidneys

It is about 120-125ml/minute

This is the best way to assess the health of the kidneys

Question 14

Describe the glomerular filtration rate and how it is maintained

Answer 14

This is auto-regulated via the constriction of afferent and efferent arterioles

The GFR does not change with changes in blood pressure so the dilation of the arterioles is generally adjusted to maintain pressure of 55mm/Hg in the glomerular capillaries

Question 15

How can you measure the glomerular filtration rate?

Answer 15

Measure by the ‘clearance’ of a selected material - clearance is measure in units of volume/time (litres/minute)

Question 16

What is ‘clearance’?

Answer 16

It is the effective volume of plasma completely cleared of a substance per minute

It’s units is volume/time e.g. litres/minute

Question 17

Explain the different possible values of clearance and what these mean

Answer 17

Clearance of glucose would be 0 because no blood would be cleared of glucose as it is all reabsorbed

If 100% of a substance is filtered through the glomerulus and NONE of it is reabsorbed then the clearance of this substance is the same as the GFR

NB. the portion of plasma which is not filtered and enters the efferent arteriole will still contain the normal concentration of this material - some will be present in the renal venous flow (as opposed to the urethra)

If 100% of the material is filtered out of the blood plasma into the efferent arteriole but then all of the material is SECRETED into the urine then the renal venous flow has NO material in it because all of the blood passing through the kidney will have been cleared of the material - in this case, the clearance will = renal plasma flow

SO clearance of a material can range from 0 to renal plasma flow

Question 18

Summarise the different possible measurements of clearance

Answer 18

Not removed at all by the kidneys: clearance = 0

Removed at the same rate as water passing through the glomeruli: clearance = GFR

Completely removed from the blood passing through the kidney: clearance = RPF

Question 19

What are the implications of the GFR and the RPF if the kidneys are damaged?

Answer 19

Damaged kidneys can result in a decreased GFR but the RPF may remain normal

Question 20

What is the formula to measure clearance?

Answer 20

Clearance = (urine concentration/plasma concentration) x urine flow

C = (U/P) x V

NB. as long as the concentration units are the same, it does not matter what they are

Question 21

What is required to be able to measure clearance (on paper/theoretically)?

Answer 21

Measure the concentration of the substance in the plasma

Collect urine for a fixed period of time to get the urine flow (ml/minute)

Measure the concentration of the substance in the collected urine

Question 22

What can be used to practically measure clearance in theory?

What are the problems with using this method?

Answer 22

Inulin can be used - polysaccharide that is completely filtered from the plasma and not reabsorbed

Not secreted or reabsorbed so the clearance of this is the GFR

BUT inulin does not occur naturally occur in plasma SO to measure the insulin clearance, have to infused inulin IV over a couple of hours to reach a steady plasma concentration - hence, this method of inulin clearance becomes impractical

Question 23

What is instead used to measure GFR in a clinical setting?

Answer 23

Creatinine is used

This is produced naturally in the body (breakdown product of creatine phosphate)

This is freely filtered by the glomerulus BUT IT IS ALSO actively secreted by the PERITUBULAR capillaries in small amounts - THIS MEANS that the CREATININE CLEARANCE OVERESTIMATES THE ACTUAL GFR BY ABOUT 10-20%

However, due to the ease of measuring creatinine clearance, this margin of error is accepted - creatinine is already at a stead-state concentration in the blood

Question 24

If the measurement of urinary excretion of creatinine is not possible, how can you measure the clearance?

Answer 24

Can use a formula method (look on notes for the formula)

Question 25

What is the regulatory response if there is a high filtration pressure and GFR?

Answer 25

The afferent arterioles relax and the efferent arterioles constrict

Question 26

What is the regulatory response if there is a low filtration pressure and GFR?

Answer 26

Afferent arterioles constrict and efferent arterioles relax

Question 27

How is the balance between the afferent and efferent arterioles controlled? Give the mechanism of the macula densa to maintain this

Answer 27

By the juxtaglomerular apparatus - structure where the distal tubule folds back and contacts with the glomerulus at the point where the afferent and efferent arterioles enter

Here, there are MACULA DENSA cells which line the distal tubule where it contacts the afferent and efferent arterioles

The macula densa sense the sodium concentration in the distal tubule:

• In the proximal convoluted tubule, Na+ is removed at a relatively constant rate
• If the flow in the proximal tubule is low (i.e. the pressure is low), then more Na+ is removed and the Na+ concentration goes down
• If the pressure is high, less Na+ is removed and the Na+ concentration increases
• SO if the Na+ at the macula densa is too low, this means that the GFR is too low
• When this occurs, chemical factors are released from the macula densa that selectively constricts the efferent arteriole (? NEED TO CHECK - SHOULD IT NOT RELAX TEH EFFERENT TO INCREASE THE PRESSURE?) to increase the GFR back to normal
• At the same time, Renin is released from the juxtaglomerular cells and this diffuses into the blood

Question 28

Describe the role of Renin within the blood and describe the mechanism that occurs

Answer 28

This is released into the blood and travels in the veins to the liver

At the liver, this cleaves the protein ANGIOTENSINOGEN to release the peptide ANGIOTENSIN 1

This travels to the lungs where it is converted to ANGIOTENSIN 2 by ANGIOTENSIN CONVERTING ENZYME (ACE)

This acts on the adrenal cortex to release ALDOSTERONE

Aldosterone increases the Na+ retention in the distal tubule

This renin-angiotenin-aldosterone system (RAAS) is a negative feedback mechanism to maintain the plasma volume of Na+, volume of blood and hence the blood pressure