Step I FA 2012 Page 514: Type 2 RTA

[MedPR]

Advertisement - Members don't see this ad

Why is Type 2 (proximal) renal tubular acidosis associated with hypophosphatemic rickets? I know that acid will degrade bone, but I don't kow what hypophosphatemic has to do with it.

Also, why are type 1 and 2 renal tubular acidosis associated hypokalemia?

 

[Morsetlis]

The RTA is due to failure to excrete H+ (distal tubules) or failure to reabsorb HCO3- (proximal tubules).

If there is impairment of bicarbonate resorption (NHE3 failure), there is excess Na+ flow in the lumen by the time it gets to the distal tubules. This will activate the ENaC channels, which through 1 or 2 intermediary steps (I believe they involve protons) will activate K+ excretion, causing hypokalemia. Notice that the NHE3 mechanism reabsorbs HCO3- while recycling the same proton, thus alkalinizing the blood.

If there is impairment of H+ excretion in the distal tubules / collecting duct, the H+/K+ ATPase cannot reabsorb K+, leading to hypokalemia.

I... have no idea about phosphate, I hate phosphate, sorry 😛

Perhaps Type 2 RTA is secondary to hyperPTH, which inhibits phosphate reabsorption?

 

[VisionaryTics]

Type 2 RTA is most commonly associated with Fanconi syndrome, in which the kidneys suck at everything and piss out amino acids, bicarb, phosphate, etc.

It's the phosphate loss that causes rickets. The RTA has no direct effect on the rickets. Isolated type 2 RTA will not have rickets.

 

[CATrtb]

Isn't the proximal tubule where phosphate is reabsorbed? Seems like if you knock that out you would just excrete all your phosphate.

 

[VisionaryTics]

Isn't the proximal tubule where phosphate is reabsorbed? Seems like if you knock that out you would just excrete all your phosphate.

The proximal tubule is where everything is pretty much reabsorbed. So, yeah, that's why you often see phosphate loss and bicarb loss together (along with glucose loss, amino acid loss, etc). Hence, type 2 (proximal) RTA is usually part of Fanconi syndrome.

 

[MedPR]

Type 2 RTA is most commonly associated with Fanconi syndrome, in which the kidneys suck at everything and piss out amino acids, bicarb, phosphate, etc.

It's the phosphate loss that causes rickets. The RTA has no direct effect on the rickets. Isolated type 2 RTA will not have rickets.

But FA specifically says that inadequate bicarb reabsorption is associated with hypophosphatemic rickets. Is there some mechanism where bicarb reabsorption affects phosphate reabsorption?

 

[Morsetlis]

But FA specifically says that inadequate bicarb reabsorption is associated with hypophosphatemic rickets. Is there some mechanism where bicarb reabsorption affects phosphate reabsorption?

If there were no channelopathy, inadequate bicarb absorption would put a greater Na+ flow in the lumen and thus drive the gradient toward phosphate/Na+ cotransport back into the cells...

Acidemia would also lead to albumin-mediated release of more free Ca++ into the blood, inhibiting release of PTH, disinhibiting phosphate reabsorption.

So you need the Fanconi Syndrome for the paradox.