Lecture 5 -clincial Review Of Tubulopathies Flashcards
What syndrome is common in the thick ascending limb?
Bartter syndrome
What syndrome is common in the DCT?
Gitleman syndrome
What syndrome is a mirror image of Gitleman syndrome?
Gordon Syndrome
What syndrome is common in the collecting duct (CD)?
Liddle syndrome
What is CONRs syndrome?
Hypertension and fluid overload, it is an Na+ handling disorder, the K+ goes low because you prioritise the salt reabsorption
What is a syndrome that is caused by SGLT2/1 transporters?
Renal glycosuria - which is when too much glucose is removed
What can happen if the heterodimer (SLC3A1 and SLC7A9) in the PCT for amino acid reabsorption doesn’t work?
Cystinuria which leads to cystine crystals and stone
What does the heterodimer transporter in the PCT?
Cystine, lysine and arginine
What happens when SCL5 proton exchanged goes wrong in albumin reabsorption in the PCT?
You get dense disease, leads to proximal tubular dysfunction and leads to hyperoxaluria and kidney stones
What happens if you get mutations in CUNB and AMN which are mechanisms for albumin in the PCT?
Vitamins B12 deficiency which leads to anaemia and proteinuria
What do mutations in the NKCC2 lead to in the TAL?
Bartter syndrome
What do babies with bartter syndrome get?
They get polyuric and this can happen before birth in the mothers womb
What are mothers who have polyuric babies in the womb treated with?
Polyhydraminos
What do mothers who have polyuric babies in the womb look like?
They often look like they having twins when they aren’t this is due to extra fluid around the baby
When the baby is born polyuric what are the risks factors?
Risk of hypertension and electrolytes, they are kept in the ICU first few months of their life until on the right medicines.
How is Na+/Cl- absorbed in the TAL?
It is absorbed by K+ recirculating, k+ is controlling the whole mechanism. If you run out of K+ the system stops working.
What receptor can control ca2+ and K+?
The calcium sensing receptor
What is the most common mutation in bartter syndrome?
NKCC2
What is the subunit of CLC-KB on the basolateral membrane of the TAL?
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
What is the gene for the anti-natal form of bartter syndrome?
SLC2A1 which is an embryonic player in salt retention
What are the transporters in the TAL?
NKCC2, ROMK, CLC-KB and Na/K+ ATPase (3Na+ and 2K+)
What is ROMK?
It is a ATP dependent k+ channel in the TAL - K+efflux from the apical membrane
What is another name for the Na/Cl- co transporter?
A thiazide sensitive co transporter (thiazide= salt waste)
What is gitelman syndrome in the DCT?
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
What is the related syndrome from Gitleman syndrome?
EAST/SESAME syndrome
How does East/sesame syndrome occur?
By a mutation on the KCNJ10 transporter on the basolateral membrane
Where is the KCNJ10 also expressed as well as the kidney?
It is also expressed in the brain whereas the NCC is only expressed in the kidney
What are the symptoms for East/sesame syndrome?
Can also get epilepsy, Ataxia, deafness, electrolyte imbalances because its expressed in the kidney and the brain
What is the syndrome called that is the mirror image of Gitelman syndrome?
Gordon syndrome - where instead of the NCC not working it is working too much
What are the 4 players that regulate insertion and retrieval for the NCC?
WNK4, WNK1, KELCH3 and CUL3
What are the symptoms from Gordon’s syndrome?
Too much salt absorption so you get hypertension, metabolic acidosis and hypercalceamia
What is Liddles syndrome?
It is a disease in the CD where ENAC is overactive
What two subunits does Liddles syndrome occur in?
SCNN1b (beta) and SCNNG (gamma)
What are the symptoms for Liddles syndrome?
Because you have an overactive ENAC it means extra salt reabsorption, so you get extra protons and k+ = hypertensive hypokalemia phenotype
What does aldosterone do?
It helps the body when there is extra salt reabsorption - it works on the mineral corticoid receptor
Where is aldosterone recruited from?
It is recruited from the adrenal glands and acts on the kidney directly
What does cortisol do?
It stimulates the mineral corticoid receptors - not supposed to as it pretends to be aldosterone.
What does the body to to stop cortisol from stimulating the MRC?
It gets broken down into cortisone - this happens by an enzyme called 11beta-hydroxy steroid dehydrogenase
How can you inhibit 11beta-hydroxy steroid dehydrogenase?
By eating too much liquorice - can cause pseudohypoaldosteronism
What is the gene for Pendrin?
SLC26A4
