L25 - Proximal Tubular Function and Renal Clearance

Question 1

What is reabsorption in regards to the PCT?

Answer 1

Movement of useful substances from the tubule lumen into the blood (peritubular capillaries)

Question 2

What is secretion in regards to the PCT?

Answer 2

Movement of less useful substances from the blood into the tubule lumen.

Question 3

Why is the reabsorption and secretion that occurs at the PCT useful?

Answer 3

These processes aid in homeostasis.

Question 4

Describe the pathway for solutes which are either reabsorbed or secreted.

Answer 4

1) Blood enters glomerulus via the afferent arteriole.
2) Solutes are filtered across into the bowman’s capsule.
3) Some solutes are reabsorbed from the tubular fluid into the pertitubular capillaries (which extend from the efferent arterioles)
4) Some solutes are secreted into the tubular fluid from the PCT cells.

Question 5

Describe the structure of PCT cells (lining the PCT)

Answer 5

1) Apical Membrane: which comes into contact with the tubular fluid.
2) Basolateral Membrane: which contacts the interstitial fluid at the base and sides of the cell.

Question 6

What are the functions of the proximal convoluted tubule?

Answer 6

PCT - the main site for active and passive reabsorption. The return of most of the filtered water and many of the filtered solutes into the blood stream (pertitubular capillaries)

Question 7

What does most reabsorption/secretion at the PCT involves?

Answer 7

Na+ transporters (Na+ antiporter or symporter).

Question 8

What are the two reabsorption routes for solutes/water?

Answer 8

1) Paracellular Reabsorption – fluid (or solutes) can leak between the cells passively.
2) Transcellular Reabsorption – a substance passes from the fluid in the tubular lumen through the apical membrane of a tubule cell, across the cytosol and out into the interstitial fluid through the basolateral membrane.

Question 9

Give examples of some solutes which are reabsorbed into the peritubular capillaries.

Answer 9

Glucose, amino acids, Na+, K+ Ca2+, Cl-.

Question 10

What is the function of Na+ symporters?

Answer 10

Na+ Symporters: two or more solutes cross membrane in same direction (e.g Na+ and glucose symporters).

Question 11

What is the function of Na+ antiporters?

Answer 11

Na+ antiports:Two or more solutes cross membrane in opposite direction

Question 12

How is the energy derived in order for Na+ transporters (symporters and anti-porters) to perform their function?

Answer 12

Energy is derived indirectly from the ATP used in primary active transport (Na+/K+ pump).

Question 13

What type of active transport do the Na+ transporters use?

Answer 13

Na+ transporters use secondary active transport.

Question 14

What does the “transport maximum” mean for Na+ transporters?

Answer 14

The Na+ transports have an upper capacity limit.

The point at which they become saturated.

Question 15

What are the units for the transport maximum (Tm)?

Answer 15

Tm = measured in mg/min

Question 16

What is the significance of the transport maximum for diabetic patient?

Answer 16

When the Na-glucose transporter is at it’s transport maximum, the amount of glucose that can be transported

Question 17

What type of forces regulate reabsorption into the lumen of the peritubular capillaries?

Answer 17

Starling forces govern the movement of substances within a capillary.

Question 18

What is the formula for the starling forces that determine the capillary uptake?

Answer 18

Capillary uptake = forces favouring uptake - forces opposing uptake.
(πcap + P LIS) – (πLIS + P cap)
Capillary uptake = (capillary oncotic pressure + hydrostatic pressure in the tubular fluid) - (tubular fluid oncotic pressure + hydrostatic pressure in the capillary)

Question 19

How is a constant concentration gradient maintained between the tubular fluid and the peritubular blood?

Answer 19

Due to constant circulation of blood, anything that is taken up by the blood is constantly moved on in the blood and so there is a constant concentration gradient for capillary reabsorption.

Question 20

Give examples of some of the solutes that are reabsorbed using Na+ transporters.

Answer 20

1) 100% of organic substances e.g. glucose
2) 80-90% bicarbonate
3) 65% H2O, Na+ and K+
4) 50% Cl-
5) Ca2+, Mg2+ and phosphate

Question 21

Where are Na/K+ pumps located on PCT cells?

Answer 21

Na+/K+ pumps are located on the basolateral membrane of PCT cells

Question 22

What is the purpose of Na+/K+ pumps?

Answer 22

The Na/K+ uses active transport to pump Na+ out of the cell (and K+ into the PCT cell) and into the interstitial fluid –> this is primary active transport & uses ATP. This drives the secondary transport (antiport & symport mechanisms)

Question 23

Which solutes are reabsorbed using secondary active transport?

Answer 23

1) Glucose
2) Amino acids
3) Bicarbonate
4) Chloride

Question 24

How do Na+/K+ cells aid reabsorption?

Answer 24

They create the intracellular conditions to allow for the movement of Na+ into the cytosol of PCT (via symport or anti port Na+ channels)

Question 25

Describe how the reabsorption/transportation of Na+ aids the reabsorption or secretion of other solutes.

Answer 25

1) There is a high concentration of Na+ ions in the tubular fluid (due to the filtration of Na+ from the blood which passes into the glomerulus)
2) The Na+ ions diffuse into the interstitial fluid via the paracellular route –> this creates a high concentration of Na+ ions at interstitial fluid.
3) The Na+/K+ pump is present on the basolateral membrane of tubule cells. This means that the cells lining the tubular have a low Na+ concentration in their cytosol (using active transport –> uses ATP)
4) Thus, there is a Na+ concentration gradient between the tubule cells and the tubular fluid –> so Na+ diffuses into the cell via Na+ symport or antiport transport channels (this uses the transcellular route).
5) If Na+ moves into the cytosol of the PCT using a symport cell then it does so with another molecule (glucose). If it enters using an antiport, then another molecule is secreted from the PCT cell into the tubular fluid (e.g H+)

Question 26

How does solute reabsorption encourage H2O reabsorption?

Answer 26

• Solute reabsorption in proximal convoluted tubules promotes osmosis of water.
• Each reabsorbed solutes increases the osmolarity, first inside the tubule cell, then in the interstitial fluid and then in the blood.
• Therefore, water moves rapidly from the tubular fluid via both paracellular and transcellular routes, into the peritubular capillaries and restores osmotic balance.

Question 27

What type of water reabsorption occurs at the proximal convoluting tubule?

Answer 27

1) Proximal Tubule: water will always follow the solutes into capillaries via osmosis as the PCT is always permeable to water. (OBLIGATORY WATER REABSORPTION)

Question 28

What type of water reabsorption occurs at the collecting duct?

Answer 28

2) Collecting Ducts: (water reabsorption varies depending depending on body conditions e.g dehydration and excessive fluid). Facultative water reabsorption is regulated by anti-diuretic hormone and occurs mainly in the collecting ducts. (FACULTATIVE WATER REABSORPTION)

Question 29

How does the Na+-glucose symporter work?

Answer 29

a) Present on the apical membrane of cells.
b) Two Na+ and a molecule of glucose attach to the Na-Glucose symporter protein.
c) This carries them from the tubular fluid into the PCT cell.
d) The glucose molecules then exits the basolateral membrane of the PCT cell via facilitated diffusion and they diffuse into peritubular capillaries.
e) The Na+ molecules within the cytosol are removed from the cell via the Na+/K+ pump.

Question 30

How does the Na+-H+ antiporter work? How does it facilitate reabsorption of HCO3-?

Answer 30

1) Na+-H+ antiporter on apical membrane of PCT cell Na+ moves into the cell and H+ from the cell moves into the tubular fluid.
2) Carbon dioxide diffuses into the cell from the tubular fluid or the peritubular blood.
3) Using carbonic anhydrase, CO2 and H2O combine to form H2Co3 which then dissociates H+ and HCO3- (bicarbonate)  within the cell.
4) H+ secreted into the tubular fluid combines with HCO3- (in the filtered fluid) to form H2CO3  this dissociates into Co2 and H2O (within the tubular fluid)
5) CO2 diffuses into the cell –> combines with H2O in the cell to form H2CO3 –> which dissociates into H+ and HCO3-  (within the PCT cell)
6) HCO3- concentration increases in the cytosol –> it exits the cell via facilitated diffusion and is diffuses into the peritubular capillary (with the Na+ from the Na/K+ pump)  within the PCT cell.

Question 31

What are the characteristics of secreted substances?

Answer 31

1) Secreted substances are filtered

2) secreted substances are small.

Question 32

Which type of movement is required for secretion?

Answer 32

Active transport is required for secretion.

Question 33

Why is para-aminohippuric acid (PAH) used as an indicator of renal blood flow?

Answer 33

PAH is an indicator of renal blood flow as it is freely filtered, it gives you an indication of how much blood is flowing through the glomerulus.

Question 34

Is PAH reabsorbed?

Answer 34

No, it is not reabsorbed.

Question 35

What are the properties of PAH?

Answer 35

1) Freely filtered
2) Not reabsorbed
3) Tm limited secretion.
4) Indicator of renal blood flow

Question 36

What is renal clearance?

Answer 36

The volume of plasma cleared of a substance in a given time

Question 37

What is the formula for renal clearance?

Answer 37

Renal Clearance (ml/min) = Urine conc of a substance (mg/ml) x Urine flow (ml/min) / plasma concentration of a substance (mg/ml)

Cx = Ux V / Px

Question 38

What is Inulin made up of?

Answer 38

Inulin is a Polysaccharide

Question 39

What are the properties of Inulin?

Answer 39

Inulin is:

1) Freely filtered at the glomerulus
2) Not reabsorbed
3) Not secreted

Therefore, inulin clearance can be used to measure GFR

Question 40

Why is inulin clearance useful?

Answer 40

Inulin is freely filtered, not reabsorbed and is not secreted (so it’s full concentration remains in the tubular fluid –> urine) so INULIN CLEARANCE CAN BE USED TO MEASURE GFR.

Question 41

What is the equation of GFR using inulin clearance?

Answer 41

GFR = U(inulin) x V / P(inulin)

Question 42

What is the disadvantage of using inulin clearance to measure GFR?

Answer 42

Inulin has to be infused (it is not endogenous).

Question 43

What substance is used to measure GFR instead of inulin?

Answer 43

Creatinine

Question 44

Why is creatine clearance used to measure GFR rather than inulin clearance?

Answer 44

1) Creatinine is endogenous so no infusion is needed

2) Creatinine is also freely filtered.

Question 45

What is the disadvantage of using creatinine clearance to work out GFR?

Answer 45

A small amount of creatinine is secreted into the filtrate.

Question 46

Why is the fact that creatine can be secreted significant for measuring GFR using creatinine clearance?

Answer 46

1) OVER-ESTIMATING OF GFR: if there is creatinine secreted into the tubular fluid then the urine will contain the filtered creatinine and the secreted creatinine. Therefore, creatinine clearance will appear to be higher and so GFR will appear to be higher.

Question 47

What effect does muscle metabolism have on creatinine clearance?

Answer 47

1) Creatinine is a by-product of muscle metabolism.
2) So, GFR using creatinine clearance is more accurate when patients are at rest.
3) More muscle metabolism = higher creatinine in the blood = more creatinine present in the urine = higher GFR.

Question 48

How is renal clearance measured?

Answer 48

The urine produced by the patient can be measured to measure their renal clearance.