Session 3 Part 2

Question 1

Aspect of renal medicine related to pH control

Answer 1

Bicarbonate reabsorption by proximal tubule

Question 2

Aspect of renal medicine related to hypertension

Answer 2

Na+ reuptake by the kidney

Question 3

Kidney tubules transport of Na+ and bicarbonate

Answer 3

Reuptake by kidney proximal tubule cells

Question 4

Na+ resorption by proximal tubule mechanism

Answer 4

NHE brings Na+ into proximal tubule cell from lumen, Na+ goes into capillary by Na+-K+-ATPase

Question 5

Bicarbonate resorption by proximal tubule mechanism

Answer 5

Anion exchanger brings HCO3- into capillary and Cl- out

Question 6

Normal circumstances function of the kidney

Answer 6

Reabsorbs all the bicarbonate filtered into the proximal tubule into the blood to retain a base for pH buffers

Question 7

First line treatment for mild hypertension

Answer 7

Renal control of circulating Na+ concentration

Question 8

What does Amiloride do

Answer 8

Inhibits Na+ reuptake by the proximal tubule from the lumen via NHE

Less Na+ goes into capillary so Na+ excreted, water follows, reduces water uptake and blood volume hence bp

Question 9

Amiloride in turn inhibits

Answer 9

Bicarbonate reuptake by proximal tubule

Question 10

What do loop diuretics do

Answer 10

stop Na+-K+-2Cl- transporters bringing Na+ back into capillary in the thick ascending limb

Question 11

what do thiazides do

Answer 11

Inhibits Na+ reuptake by kidney in distal convoluted tubule by the Na+-Cl- transporter

Question 12

What is spironolactone

Answer 12

Mineralocorticoid receptor antagonist- disencourage uptake of water and sodium

Question 13

What does aldosterone do

Answer 13

Enhance sodium uptake

Question 14

What does ADH do

Answer 14

Increase aquaporin expression and encourage uptake of water

Question 15

What are OATs

Answer 15

Organic anion transporters (negatively charged_

Question 16

Renal OAT mechanism

Answer 16

Dicarboxylate transporter- secondary active transporter, brings dicarboxylate out of capillary (driven by Na+ into capillary by Na+-K+-ATPase)

Dicarboxylate then brought back into capillary by OAT1/2/3, tertiary active transport

organic anions (negative) flow out

Reduces therapeutic conc in blood

Question 17

OAT roles

Answer 17

Interorgan communication, interorganismal communication, complex whole organism homeostasis (regulate key metabolites and signalling molecules)

Question 18

What are OCT

Answer 18

Poly-specific cationic (positively charged) substrate transporters e.g. dopamine, serotonin, histamine

Question 19

OCT family members

Answer 19

OCT1-3
MATE 1-2 (multi drug and toxin extrusion)
PMAT (plasma mambrane monoamine transporter)

Question 20

Renal OCT mechanism

Answer 20

OC+ out of capillary by OCT2 (electrochemical gradient/negative membrane potential)

H+ into proximal tubule cell by MATE 1 and 2, drives OC+ out of proximal tubule cell (driven by pH gradient)

Question 21

How do OCTs affect metformin

Answer 21

• Anti diabetic drug for type 2 diabetes
• Decreases hepatic glucose production
• Polymorphism for OCT 1 = reduced activity
• Hepatic uptake of metformin reduced
• Anti-diabetic effects reduced, circulating glucose levels remain raised

Question 22

OCTs and cisplatin

Answer 22

Cisplatin taken up by OCT2 into proximal tubule cell from blood (excellent substrate)

Poor substrate for MATE1/2, reduces renal excretion, toxic build up, damages kidney cells, cause cell death in cancer