Renal Excretory Function

Question 1

What are the three layers of the filtratrion membrane of glomerulus? [3]

Answer 1

Fenestrated capillary endothelium [1]
Basement membrane [1]
Podocyte foot processes [1]

Question 2

Name 4 factors that determine filtrate that goes into glomerulus

Answer 2

• Net filtration pressure
• Podocyte slit pores
• Size of molecule (urea / creatinine can make it through)
• Charge of molecule: (albumin is negatively charged and so is BM - creates repulsion)

Question 3

Which molecules are filtered through the glomerulus? [3]

Answer 3

Small molecules:
* Water
* Electrolytes eg Na, K, Cl, phosphate, glucose
* Urea, small amino acids

Large molecules such as albumin have a too big molecular weight to do pass through

Question 4

What is the most important parameter of kidney function?

Answer 4

GFR

Question 5

Define GFR

Answer 5

GFR = Clearance of substance

Total amount of fluid that is filtered through the glomerulus

Question 6

What molecule do you use to measure GFR in specialised clinic? [1]

What molecule do you use to measure GFR in normal clinic? [1]

Answer 6

What molecule do you use to measure GFR in specialised clinic? [1]
Inulin

What molecule do you use to measure GFR in normal clinic? [1]
Creatinine

Question 7

What is creatinine a breakdown product of? [1]

Answer 7

creatine phosphate: found in muscle

Found at a steady-state concentration in the blood

Question 8

What are 4 disadvantages of using creatinine to eGFR? [3]

Answer 8

using creatinine to estimate GFR underestiamtes GFR by 10-20%

underestimated in black ethnicities

malnourished patients have low muscle mass so overestimates eGFR

muscular individuals have raised muscle mass so underestimates GFR

Question 9

How is creatinine clearance measured?

Answer 9

Cr Clearance = ( [U] / [P] ) x Volume

(Urine conc / plasma conc) x volume of urine

Question 10

How do you measure eGFR using the 4 variable MDRD equation?

Answer 10

Need:
Cretinine
Age
Gender
Ethnicity

Question 11

What is the function of the PCT? [3]

Answer 11

Reabsorption of:

Solutes: up to 80%
Water – up to 65%
Amino acids, low molecular weight proteins – up to 100%

Question 12

Explain the MoA of Kidney absorption

Answer 12

Reduce volume of water and solutes within urine but without changing the concentration: make a hypertonic medulla

MoA:

At thin descending loop
* Water pumped out via aquaporins due to increased osmolality produced by thick ascending limb pumping out Na+

At thick ascending limb
* Na is actively pumped into medullary space via Na/K channel
* Paracellular transport of Na, Ca and Mg down a electrochemical gradient
* This wall is impermeable to water.

At distal convoluted tubule:
* Aldosterone works to increase Na absorption

At collecting duct:

• ADH opens aquaporins to reabsorb more water
• Fluid passes down from here to ureter and ladders

Question 13

In th kidney, osmotic gradient is maintained by the countercurrent exchange by the which structures?

Answer 13

Osmotic gradient is maintained by the countercurrent exchange by the vasa recta

Question 14

Which parts of LoH action are active transport and which a passive transport?

Answer 14

Blue: passive
Red: AT

Question 15

Which parts of LoH action are active transport and which a passive transport?

Answer 15

Blue: passive
Red: AT

Question 16

Which transporter do loop diuretics (such as Furosemide) inhibit? [1]

Where is this transporter located? [1]

Answer 16

Loop diuretics inhibit NaKCl2 on the thick ascending limb

Results in Na & water remaining in tubular lumen and being excreted in urine:

Question 17

Which transporter do thiazide diuretics inhibit? [1]
​
Where is this transporter located? [1]

Answer 17

Block Na+/Cl− cotransporter at distal convoluted tubules

Question 18

Explain MoA of Spironolactone

Answer 18

Binds to mineralocorticoid receptor: an aldosterone antagonist

Question 19

The concentration/osmolality of the urine is determined by []

Answer 19

The concentration/osmolality of the urine is determined by Anti diuretic hormone (ADH, Vasopressin)

Question 20

ADH acts via which receptor to cause aquaporin insertion? [1]

Answer 20

ADH acts via V2 receptor to cause aquaporin 2 insertion and fluid movement from collecting duct to intersitium down osmotic gradient.

Question 21

Explain what the renal threshold of a substance is?

What happens when renal threshold of a substance is exceeded?

Answer 21

Renal threshold is the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine

When the renal threshold of a substance is exceeded, reabsorption of the substance by the proximal renal tubule is incomplete and some of the substance remains in the urine.

Question 22

The most common reason for the glucose renal threshold ever being exceeded is [].

Answer 22

The most common reason for the glucose renal threshold ever being exceeded is diabetes.

Question 23

What plasma concentration of glucose exceeds renal threshold, so glycosuria occurs / glucose threshold?

Answer 23

At a plasma glucose level of about 10 mmol/L

Question 24

The rate of glucose reabsorption reaches a constant maximal value called the []

Answer 24

The rate of glucose reabsorption reaches a constant maximal value called the transport maximum for glucose (TmG)

Question 25

A low GFR leads to an [] glucose threshold:

filtering rate []
[] in glucose load \ [] glucose reabsorbed.

Answer 25

A low GFR leads to an elevated threshold:
filtering rate reduced
decrease in glucose load \ more glucose reabsorbed.

Question 26

Explain why glycosuria leads to thirst sensation?

Answer 26

• Glucose in urine induces osmotic diuresis: excess solute present in tubular fluid, this will attract water and increases urine volume
• This leads to increased plasma osmolality and causes thirst

Question 27

`Label the class of drugs found at A, B & C [3]

Answer 27

A: Carbonic anhydrase inhibitors

B: Loop diuretics

C: Thiazides

Question 28

Name and explain which transport protein in the thick ascending loop of Henle assists NaKCl2 transporter

Answer 28

Renal Outer Medullary potassium channel or ROMK

• K is AT pumped into the tubular lumen / urine to generate positive voltage within the cell (because less K+ in)
• This creates an overall voltage gradient of +80mV; from +10mV in the tubular lumen to -70mV in the tubular cell
• This voltage difference drives Na into the tubular cell via NaKCl2 transporter