Glomerular filtration barrier and podocyte injury in nephrotic syndrome
Core concept
- Three layers, each with a distinct job
- 1. Fenestrated endothelium (70-100 nm pores) + glycocalyx - excludes cells, contributes charge selectivity
- 2. Glomerular basement membrane - type IV collagen (alpha3/4/5), laminin, nidogen, heparan sulfate proteoglycans (agrin)
- Size and charge barrier (fixed negative charge repels albumin, itself anionic)
- 3. Podocyte foot processes and the slit diaphragm - the final and most important barrier to protein
- Nephrin (NPHS1) and podocin (NPHS2) form the slit diaphragm zipper, anchored by CD2AP, alpha-actinin-4, TRPC6
- Podocytes are terminally differentiated and cannot proliferate
- Injury -> foot process effacement -> proteinuria
- -> detachment and podocytopenia -> denuded GBM -> synechiae -> segmental sclerosis (FSGS)
- *Podocyte loss is the point of no return* - beyond ~20-40% loss, glomerulosclerosis is inevitable
3 more sections, plus exam facts
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