3 - Clearance And Filtration

Question 1

What acts as the filter in the kidney?

Answer 1

The glomerulus.

Question 2

Where in each nephron is the glomerulus found?

Answer 2

Only in the cortex.

Question 3

Does the glomerulus filter all of the blood from the renal artery?

Answer 3

No. Only 20% of the blood from the afferent arteriole (which branches off from the renal arteries) can be filtered at any one time. The rest exits via the efferent arteriole.

Question 4

What are the types of nephron?

Answer 4

Cortical and juxtamedullary.

Question 5

Do the two types of nephrons differ in their levels of filtration?

Answer 5

No. Functionally they are exactly the same and have the same ability for filtration (20% of blood from renal artery). Structurally they differ.

Question 6

How do the two types of nephron differ structurally?

Answer 6

They have a different arrangement of peritubular capillaries.

Question 7

Is everything filtered at the glomerulus?

Answer 7

No. Cells and large proteins are not filtered. However, water, salts and small molecules pass through the glomerulus.

Question 8

What are the layers of the glomerulus?

Answer 8

1. Capillary endothelium permeable: will filter water, salts and glucose. Filtrate moves between cells.
2. Basement membrane: permeable to small proteins; acellular gelatinouws layer of collagen / glycoproteins - the latter repel protein movment due to their - charge.
3. Podocyte layer: pseudopodia interdigitate forms filtration slits.

Question 9

How are molecules filtered by the barrier?

Answer 9

Size: small molecular weight and radius <1.48nm

Charge: charged proteins will normally not be filtered. May be if -ve charge on the glycoprotein’s of the barrier is lost - leading to proteinuria.

Question 10

What are the three physical forces involved in filtering the plasma?

Answer 10

ENTERING the Bowman’s Capsule:
Hydrostatic pressure in the glomerular capillaries

EXITING the Bowman’s Capsule:
Hydrostatic pressure in the Bowman’s capsule
Osmotic pressure difference between the capillary and tubular lumen

Question 11

Once the plasma has been filtered, what is the fluid known as?

Answer 11

Ultrafiltrate.

Question 12

Which of the forces involved in filtering the plasma is regulated?

Answer 12

Hydrostatic pressure in the capillary (pushes fluid into the Bowman’s Capsule)

Question 13

What is the net filtration pressure (in mmHg)? Which direction does this go? Do you know the pressure of each of the forces involved in filtering plasma?

Answer 13

50mmHg - hydrostatic pressure in capillary (ENTERING)
MINUS
15mmHg - hydrostatic pressure in the tubule
25mmHg - osmotic pressure difference between capillary and tubular lumen (both EXITING)
EQUALS
10mmHg ENTERING the Bowman’s Capsule.

Question 14

What is GFR?

Answer 14

Glomerular filtration rate, is the rate at which plasma is filtered in the glomerulus. It is normally around 125ml/min.

Question 15

What is autoregulation?

Answer 15

Autoregulation keeps GFR within normal limits when blood pressure is within physiological limits (80-180mmHg).

Question 16

How does autoregulation work?

Answer 16

Through vasomodulation.

If blood pressure is high, there is afferent arteriole constriction.

If blood pressure is low, there is afferent arteriole dilatation.

If blood pressure is outside the physiological limit (80-180mmHg) then GFR will be compromised.

Question 17

What is TGF?

Answer 17

Tubular glomerular feedback, is the change in tubular flow as a result of changes in GFR. NaCl levels are important in this process.

Question 18

What will happen if arterial pressure exceeds its physiological limit?

Question 19

If GFR is high what will happen to the levels of NaCl in the nephron?

Answer 19

A raised GFR will decrease NaCl reabsorption. This will mean more NaCl reaches the distal convoluted tubule. This must be resolved.

Question 20

How does the nephron correct changes to NaCl levels in the distal convoluted tubule?

Answer 20

The macula densa cells (which are proximal to the glomerulus) are sensors of luminal [NaCl] (in the late thick ascending limb). They have a NaK2Cl transporter on their apical membrane which can adjust salt uptake, dependent on {NaCl].

If there is high {NaCl] then the macula densa cells will try to decrease GFR via vasoconstriction of afferent arteriole. Adenosine is released.

If there is low [NaCl} then the macula densa cells will try to increase GFR via vasoconstriction of afferent arteriole. Prostaglandins are released.

Question 21

Does tubular glomerular feedback apply in long term changes in GFR?

Answer 21

No. It is a response that only applies in acute changes.

Question 22

Describe the blood supply to the kidney.

Answer 22

Abdominal aorta –> Renal artery (L1-L2) –> Segmental arteries –> Interlobar arteries –> Arcuate arteries –> Interlobular arteries –> Afferent arterioles –> Glomerular capillaries –> Efferent arterioles –> Peritubular capillaries –> Interlobular veins –> Arcuate veins –> Interlobar veins –> Renal veins

Question 23

Are the renal arteries the same length?

Answer 23

No. The right renal artery is longer (the abdominal aorta is slightly to the left of the midline and the right renal artery must pass the IVC) and more inferior.

Question 24

What does the vasa recta do?

Answer 24

It is a group of capillaries that run parallel to the loop of Henle. They are a branch of the efferent arterioles in juxtamedullary nephrons. They are important in maintaining countercurrent exchange - which allows the kidney to produce concentrated urine.

Question 25

What is reabsorption?

Answer 25

Where solutes and water are removed from the tubular fluid and transported into the plasma.

(Can be transcellular, more common, or paracellular)

Question 26

What is reabsorption in the PCT driven by?

Answer 26

Na+ uptake. It is the main site of Na+ reabsorption. Other ions e.g. Cl- and HCO3- accompany Na+. Solutes move from tubular lumen to the intersticium and then into capillaries.

Question 27

What channel involved in Na+ reabsorption is present in the PCT?

Answer 27

SGLUT - 2 Na+, with 1 glucose molecule, move from the lumen of the tubule into the tubular cell.
Glucose is moving against its own concentration gradient. It then leaves the tubule cell by facilitated diffusion through the basolateral side.

Question 28

How much glucose is normally reabsorbed?

Answer 28

100%.

Question 29

Why might glucose reabsorption be impaired?

Answer 29

There is a transport maximum (Tm) - if plasma concentration exceeds this Tm the rest spills over into the urine.

Question 30

What is the renal threshold for glucose?

Answer 30

200mg/100ml

Question 31

If glucose has spilled over into the urine (glycosuria), what will normally follow?

Answer 31

Polyuria - water follows the glucose into the urine.

Question 32

How much H2O and Na+ have been filtered by the end of the PCT?

Answer 32

~2/3 of both - similar proportions of K+ and Cl- are reabsorbed. Majority of HCO3- is reabsorbed (80-90%) and all glucose is.

Question 33

What is tubular secretion?

Answer 33

Tubular secretion provides a 2nd route of entry for solutes that need to be secreted into the tubular fluid. Important since only 20% of the plasma is filtered each time blood passes the kidney.

Question 34

What substances can be secreted into the tubular fluid?

Answer 34

H+, K+ and organic anions/cations.

Question 35

What is a normal GFR for a male and a female?

Answer 35

115-125ml/min and 90-100ml/min respectively.

Question 36

How can you calculate GFR from renal blood flow?

Answer 36

Renal Blood Flow is 1.1L/min; Haematocrit (Erythrocyte Volume Fraction ~0.45) therefore ~0.55 = plasma

Renal Plasma Flow = 605ml/min

Filtration Fraction = 20%

GFR ~ 125ml/min

Question 37

How do we calculate GFR for a patient?

Answer 37

A compound such as inulin can be infused into the patient. Inulin is completely cleared from the plasma that is filtered i.e. 0% is reabsorbed. Therefore the rate it appears in urine is proportional to the GFR.

Question 38

What is the renal threshold for glucose?
What would be the filtered load at this threshold?
If Tm of glucose is 375mg/min and a patient had a plasma glucose concentration of 400mg/100ml, would glucose appear in the urine?

Answer 38

200mg/100ml

GFR: 125ml/min
Therefore 250mg of glucose can be filtered in a minute (250mg/min)

Therefore 500mg of glucose WOULD be filtered in a minute BUT Tm = 375mg/min so…
125mg/min of glucose will be lost in the urine.