Lecture 5 -clincial Review Of Tubulopathies

Question 1

What syndrome is common in the thick ascending limb?

Answer 1

Bartter syndrome

Question 2

What syndrome is common in the DCT?

Answer 2

Gitleman syndrome

Question 3

What syndrome is a mirror image of Gitleman syndrome?

Answer 3

Gordon Syndrome

Question 4

What syndrome is common in the collecting duct (CD)?

Answer 4

Liddle syndrome

Question 5

What is CONRs syndrome?

Answer 5

Hypertension and fluid overload, it is an Na+ handling disorder, the K+ goes low because you prioritise the salt reabsorption

Question 6

What is a syndrome that is caused by SGLT2/1 transporters?

Answer 6

Renal glycosuria - which is when too much glucose is removed

Question 7

What can happen if the heterodimer (SLC3A1 and SLC7A9) in the PCT for amino acid reabsorption doesn’t work?

Answer 7

Cystinuria which leads to cystine crystals and stone

Question 8

What does the heterodimer transporter in the PCT?

Answer 8

Cystine, lysine and arginine

Question 9

What happens when SCL5 proton exchanged goes wrong in albumin reabsorption in the PCT?

Answer 9

You get dense disease, leads to proximal tubular dysfunction and leads to hyperoxaluria and kidney stones

Question 10

What happens if you get mutations in CUNB and AMN which are mechanisms for albumin in the PCT?

Answer 10

Vitamins B12 deficiency which leads to anaemia and proteinuria

Question 11

What do mutations in the NKCC2 lead to in the TAL?

Answer 11

Bartter syndrome

Question 12

What do babies with bartter syndrome get?

Answer 12

They get polyuric and this can happen before birth in the mothers womb

Question 13

What are mothers who have polyuric babies in the womb treated with?

Answer 13

Polyhydraminos

Question 14

What do mothers who have polyuric babies in the womb look like?

Answer 14

They often look like they having twins when they aren’t this is due to extra fluid around the baby

Question 15

When the baby is born polyuric what are the risks factors?

Answer 15

Risk of hypertension and electrolytes, they are kept in the ICU first few months of their life until on the right medicines.

Question 16

How is Na+/Cl- absorbed in the TAL?

Answer 16

It is absorbed by K+ recirculating, k+ is controlling the whole mechanism. If you run out of K+ the system stops working.

Question 17

What receptor can control ca2+ and K+?

Answer 17

The calcium sensing receptor

Question 18

What is the most common mutation in bartter syndrome?

Answer 18

NKCC2

Question 19

What is the subunit of CLC-KB on the basolateral membrane of the TAL?

Answer 19

Barttin which is also expressed in the inner eat as well as the kidney. People with bartter syndrome also get deafness as well as bartter syndrome

Question 20

What is the gene for the anti-natal form of bartter syndrome?

Answer 20

SLC2A1 which is an embryonic player in salt retention

Question 21

What are the transporters in the TAL?

Answer 21

NKCC2, ROMK, CLC-KB and Na/K+ ATPase (3Na+ and 2K+)

Question 22

What is ROMK?

Answer 22

It is a ATP dependent k+ channel in the TAL - K+efflux from the apical membrane

Question 23

What is another name for the Na/Cl- co transporter?

Answer 23

A thiazide sensitive co transporter (thiazide= salt waste)

Question 24

What is gitelman syndrome in the DCT?

Answer 24

It is a mutation in the NCC (Na/Cl- transporter), it is much milder than bartter syndrome. Symptoms don’t present until childhood or adulthood

Question 25

What is the related syndrome from Gitleman syndrome?

Answer 25

EAST/SESAME syndrome

Question 26

How does East/sesame syndrome occur?

Answer 26

By a mutation on the KCNJ10 transporter on the basolateral membrane

Question 27

Where is the KCNJ10 also expressed as well as the kidney?

Answer 27

It is also expressed in the brain whereas the NCC is only expressed in the kidney

Question 28

What are the symptoms for East/sesame syndrome?

Answer 28

Can also get epilepsy, Ataxia, deafness, electrolyte imbalances because its expressed in the kidney and the brain

Question 29

What is the syndrome called that is the mirror image of Gitelman syndrome?

Answer 29

Gordon syndrome - where instead of the NCC not working it is working too much

Question 30

What are the 4 players that regulate insertion and retrieval for the NCC?

Answer 30

WNK4, WNK1, KELCH3 and CUL3

Question 31

What are the symptoms from Gordon’s syndrome?

Answer 31

Too much salt absorption so you get hypertension, metabolic acidosis and hypercalceamia

Question 32

What is Liddles syndrome?

Answer 32

It is a disease in the CD where ENAC is overactive

Question 33

What two subunits does Liddles syndrome occur in?

Answer 33

SCNN1b (beta) and SCNNG (gamma)

Question 34

What are the symptoms for Liddles syndrome?

Answer 34

Because you have an overactive ENAC it means extra salt reabsorption, so you get extra protons and k+ = hypertensive hypokalemia phenotype

Question 35

What does aldosterone do?

Answer 35

It helps the body when there is extra salt reabsorption - it works on the mineral corticoid receptor

Question 36

Where is aldosterone recruited from?

Answer 36

It is recruited from the adrenal glands and acts on the kidney directly

Question 37

What does cortisol do?

Answer 37

It stimulates the mineral corticoid receptors - not supposed to as it pretends to be aldosterone.

Question 38

What does the body to to stop cortisol from stimulating the MRC?

Answer 38

It gets broken down into cortisone - this happens by an enzyme called 11beta-hydroxy steroid dehydrogenase

Question 39

How can you inhibit 11beta-hydroxy steroid dehydrogenase?

Answer 39

By eating too much liquorice - can cause pseudohypoaldosteronism

Question 40

What is the gene for Pendrin?

Answer 40

SLC26A4