Thread by @SwastiThinks

Ever wondered what causes edema in nephrotic syndrome (NS)? #nephtwitter #medtwitter #nsmc #Tweetorial #NephroticSyndrome #edema #albumin😃

Edema in NS is secondary to?

2 major factors thought to contribute to edema in NS. 1. Underfill hypothesis: low s. albumin➡️low plasma oncotic pressure➡️imbalanced starling forces➡️fluid leak into interstitium➡️reduced effective circulating blood volume➡️activation of RAAS, SNS, AVP
researchgate.net/figure/The-Und…

2. Overfill hypothesis: suggests that edema is due to primary renal sodium retention

But before we dive deeper, here is recap of Starling forces to understand the next few slides! Let's revisit the 4 main Starling forces:
Hydrostatic pressures in capillaries
Hydrostatic pressure in interstitium
Oncotic pressure in capillaries
Oncotic pressure in interstitium

Underfill hypothesis cannot fully explain edema. In animal studies, a slow drop in serum albumin is accompanied by a parallel drop in interstitial albumin. Hence the net driving force or transcapillary oncotic pressure gradient is not changed. kidney-international.org/article/S0085-…

2 things used to explain this lack of transcapillary oncotic pressure gradient: 1. Washdown: dilution of interstitial protein concentration by fluid leakage from intravascular space.

2. Washout: removal of interstitial protein by increased lymphatic flow.
Washdown and wahshout maintain the plasma/ interstitial protein ratio close to normal and thus prevents edema. journals.physiology.org/doi/abs/10.115…

Another finding from studies is that blood volumes are not consistently reduced in all studies and may often be increased in NS patients

For example, in a study of 62 nephrotic patients, no correlation was found between blood volume and plasma albumin

And NO correlation was found between the blood volume and plasma renin activity sciencedirect.com/science/articl…

So could there be another explanation for edema in NS and could it be due to primary renal sodium absorption or “Overfill Theory”? And what causes primary sodium retention in NS?

One proposed mechanism of sodium retention in NS is that increased plasminogen is filtered by the nephrotic glomeruli.
ncbi.nlm.nih.gov/pubmed/19073825

Plasminogen converted to plasmin by serine protease in cortical collecting duct cells. Plasmin then cleaves the γ chain of epithelial sodium channel (ENaC)➡️activation of ENaC and sodium retention in NS.
Result=Plasminogen filtered ➡️Activation of ENaC kidney-international.org/article/S0085-…

Furthermore, volume retention in NS can be inhibited by treatment with the serine protease inhibitor aprotinin in experimental model of NS
kidney-international.org/article/S0085-…

To conclude, it is likely that both underfill and overfill contribute to NS edema.