Reabsorption and secretory function

Question 1

Describe the amount of fluid and solutes filtered and reabsorbed by the kidney per day

Answer 1

• The kidneys produce around 180L of filtrate a day = 125ml/min
• Filtrate is essentially protein-free plasma, so solute concentration in initial filtrate is the same as in the plasma
• The amount of solute filtered = the plasma concentration of the substrate (Px) x GFR
• The amount of water filtered = GFR (125ml/min)
• The amount of water and solute in the filtrate is heavily modified as filtrate passes through the nephron

Question 2

Describe how different substances may be handled by the kidney

Answer 2

Solutes that are freely filtered may be handled by the nephron in 3 different ways

• Filtered and left untouched (Clearance = Clearance of inulin)
• Filtered and reabsorbed (Cx < C inulin eg. glucose, AAs, Na)
• Filtered and secreted (Cx > inulin eg. PAH)

Question 3

How do we work out amount excreted?

Answer 3

Amount excreted = amount filtered - amount reabsorbed + amount secreted

Question 4

Define clearance

Answer 4

The volume of blood from which ALL solute X is removed, per unit time, to account for the amount of solute appearing in the unit per unit time

• How much blood would have to be cleared of solute to match the amount apearing in urine?

Question 5

What is the equation for GFR?

Answer 5

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

Question 6

How is inulin handled?

Answer 6

It is a test substance, that isnt endogenous

• It is freely filtered with no reabsorption or secretion
• Therefore the amount of inulin excreted = amount of inulin filtered
• Because of this, inulin clearance gives an estimate of GFR - any solute that is filtered and not absorbed or secreted will have the same clearance rate as inulin

Question 7

How is glucose handled?

Answer 7

• Glucose is freely filtered
• It is absorbed in the PCT, mediated by SGLT1 and SGLT2.
• These transporters are saturable
• Under normal physiology, the amount of glucose is negligible

Question 8

What is the Tmax?

Answer 8

The maximum amount of a substance the transporters can absorb per minute

Glucose = 375mg glucose/min

Question 9

What happens if the glucose delivery exceeds the Tmax?

Answer 9

If the delivery of Glucose to the PCT exceeds 375mg/min, then Tmax is exceeded and the remainder over the Tmax will not be absorbed, spilling into the urine.

Question 10

What is the Plasma Threshold of glucose?

Answer 10

Plasma threshold is the plasma concentration at which glucose first appears in the urine
- This is around 12mM glucose

Question 11

What is familial glycosuria?

Answer 11

Mutation of SGLT2, meaning that lots of glucose gets to the SGLT1 in the late PCT, overwhelming it-> glucose in the urine

Makes the person very thin, and is mainly found in women. They can eat lots and never put on weight. It makes them more prone to UTI due to the glucose in the bladder and the urethra.

Question 12

How is phosphate handled?

Answer 12

Phosphate is freely filtered

• The amount excreted is around 10% of the filtered load, but varies depending on phosphate balance
• 80% filtered load of phosphate is absorbed in PCT, 10% in DCT
• mediated by phosphate transport proteins NAPi2a and NAPi2c
• Transporter-mediated phosphate uptake is saturable
• absorption is tightly controlled by PTH, which alters Tmax

Question 13

What is the Tmax of phosphate transporters?

Answer 13

0.1mM/min

Question 14

What is the Plasma threshold of phosphate?

Answer 14

1.2mM

Question 15

How is Para-amino hippurate handled?

Answer 15

PAH is freely filtered

• The amount of PAH excreted is around 450% of the filtered load, as it is secreted into filtrate in the PCT
• PAH secretion is mediated by a complex mix of anionic transport proteins- these are saturable

Question 16

What is the Tmax of PAH transporters?

Answer 16

80mg/min

Question 17

Describe SGLT2

Answer 17

• Early PCT
• High capacity
• Low affinity (needs high glucose levels to work properly)

Question 18

Describe SGLT1

Answer 18

• Late PCT
• low capacity
• high affinity
• this picks out the remaining glucose in the tubule

Question 19

How much … is left at the end of the tubule?

Answer 19

Sodium = 30% (70% reabsorbed into blood)
Water = similar to sodium (water follows sodium)
Glucose = normally, there should be none left
Inulin = 100% (none is reabsorbed)
PAH = 450% (more at the end than was in there at the start due to secretion)

Question 20

What are the 3 main Sodium coupled transporters? And how do they work?

Answer 20

Na/Glucose = SGLT
Na/Phosphate = NaPi
Na/Amino acid = eg. EAAC-1

The second solute uses the energy from the sodium gradient to be symported

Question 21

What is Fanconi syndrome?

Answer 21

An inherited condition.Damage to the PCT means that there is less reabsorption, giving high levels of glucose, phosphate and AAs in the urine