Tubular Secretion

Question 1

What are organic anion transporters?

Answer 1

Antiporters responsible for transporting organic anions with a-KG

OAT1-3 transport OAs across the BL membrane

OAT4 transports OAs across the apical membrane

Question 2

What is the role of Na-dicarboxylate transporter (NaDC)?

Answer 2

Symporter that uses the sodium concentration gradient to bring a-KG into the cell against its concentration gradient

a-KG is then used for OA transport via OATs

Question 3

What transporters are responsible for transporting OAs into the tubular lumen?

Answer 3

OAT4 and MRP2

Question 4

How do organic cations cross the basolateral membrane?

Answer 4

By either passive diffusion driven by the cell-negative potential difference (because it is against their concentration gradient)

Or by one of three uniporters (OCT1-3)

Question 5

How do organic cations cross the apical membrane into the tubular fluid?

Answer 5

Via one of two OC-H antiporters (OCTN1-2) that exchange OCs by bringing H into the cell

MDR1 facilitates their diffusion across the apical membrane as well

Question 6

Describe the specificity and transport rate for the active secretion mechanisms of organic anions and cations.

Answer 6

Both have relatively low specificity and a maximum transport rate

Question 7

What is para-aminohippurate (PAH)?

Answer 7

Organic anion that is used for the measurement of effective renal plasma flow

Is filtered, but does not get reabsorbed

Excreted load = filtered load + secreted load

Question 8

Why does PAH give a measurement of effective renal plasma flow instead of true RPF?

Answer 8

At low Ppah, the kidney removes only 90% of PAH from plasma because the other 10% goes to non-tubular renal tissue

Underestimates true RPF by about 10%

Question 9

What is the extraction ratio?

Answer 9

The fraction of a substance which is removed form the plasma by the kidneys

E=(A-V)/A

A - concentration of substance in renal arterial plasma

V - concentration of substance in renal venous plasma

Question 10

How can actual renal plasma flow be obtained?

Answer 10

By dividing the effective renal plasma flow by the extraction ratio

ERPF/Epah

Question 11

What is bi-directional transport and what compound undergoes this process?

Answer 11

There are a few proximally secreted organic anions that undergo both active reabsorption and active secretion

Urate (uric acid)

Question 12

How does the kidney handle urate?

Answer 12

Urate is freely filtered

90% is reabsorbed early in the PT

Active tubular secretion in late PT, followed by reabsorption again in the late PT

Net flux is primarily reabsorbtion

Question 13

What four factors play a role in the production of hyperuricemia in gout?

Answer 13

Decreased filtration rate with maintained rubular reabsorption of urate

Increased reabsorption of urate

Decreased secretion of urate

Increased production of urate

Question 14

How is potassium handled by the kidney?

Answer 14

Net reabsorption of filtered K, transport is bidirectional

87% of the filtered load is reabsorbed prior to the early distal tubule regardless of K in diet

The kidneys are the primary regulators of K balance

Question 15

Describe the secretory process for K

Answer 15

The principal cell, when stimulated with aldosterone, will secrete K

The process is homeostatically regulated

Question 16

How is K transported in the proximal tubule?

Answer 16

Both active and passive

Pump on the apical and BL membranes

Most K reabsorption in PT is normally passive

Question 17

What are the determinates of K secretion in the distal tubule?

Answer 17

K concentration gradient between the principal cell and tubule fluid

Flow rate of tubule fluid

Electrical gradient across the luminal membrane of K secreting cells

Aldosterone

Question 18

Describe how the K concentration gradient affects secretion in the principal cell

Answer 18

K secretion will increase when ICF [K] is high and/ore TF [K] is low

Question 19

Describe how the flow rate of tubule fluid affects K secretion

Answer 19

Increased TF flow means the TF [K] is kept low, leading to increased secretion

SO, diruetics stimulate K secretion

Question 20

How does the electrical gradient across the luminal membrane affect K secretion?

Answer 20

Na is positive, so its reabsorption causes the lumen to become more negative, driving K secretion

Poorly reabsorbed anions in the TF will maintain the lumen negative potential and promote K secretion

Question 21

How does aldosterone affect K secretion?

Answer 21

Stimulates the secretion of K and H, and the reabsorption of Na

Increases the luminal Na and K channels and Na-K ATPase activity

Question 22

What is the result of primary hypermineralocorticoidism?

Answer 22

Hypertension (increased Na reabsorption)

Hypokalemia (increased K secretion)

Metabolic alkalosis (increased K secretion)

Question 23

What compounds primarily undergo passive reabsorption of secretion?

Answer 23

Non ionized forms of weak acids and bases

pH dependent

Urine is usually acidic, so most weak bases are charged and excreted

Question 24

What happens to the secretion of organic anions in acidosis?

Answer 24

Urine becomes acidic, so weak acids are uncharged and move by diffusion i.e. are reabsorbed

Question 25

What happens to the secretion of organic anions in alkalosis?

Answer 25

Urine becomes more alkaline and weak acids ionize, so their anions become trapped in the urine due to a decrease in permeability

Clincial relevance - aspirin poisoning, can alkalize the urine to trap the ionized form of aspirin and increase its excretion