GLOMERULAR FILTRATION Glomerular Membrane (GBM) The barriers through which filtration has to take placeGlomerular endothelial cell layer: (Fenestrated capillary with a gap of 70-90 nm in between endothelium cells) Basement membrane: A gel-like acellular meshwork of glycoproteins and proteoglycans. Visceral epithelial layer of Bowman’s capsule:i) The visceral epithelial cell is called a podocyte. ii) Each podocyte has many foor processes, which interdigitate to form filtration slits. iii) The slits are approximately 25 nm wide and each is closed by an extremely thin processes called slit diaphragms which bridge the slits between the pedicels. iv) Slit diaphragms are widened versions of the tight junctions and adhering junctions. v) Slit diaphragm is composed of several proteins, including nephrin (NPHS1), NEPH-1, podocin (NPHS2), a-actinin 4 (ACT), and CD2-Ap. Glomerular Membrane Permeability Depends onSize of particle: Neutral substances which are < 4 nm are freely filtered; > 8 nm are not filtered. Between 4 nm and 8 nm, the permeability is inversely proportional to the diameter. Charge of the particle: Since the filtration membrane are negatively charged, filtration of positively charged particles is facilitated whereas negatively charged particles are repelled. Electron microscopy demonstrates presence of an-ionic sites (negative charge) in all three layers of GBMMeasuring GFR (mGFR): to detect early damageClearance of exogenous substances: Inulin, iohexol, 51 CR-EDTA, 125I-iothalamate, 99m Tc-diethylenetriaminepenta-acetic acid (DTPA)- Evaluation: Precise and accurate, but costly, time-consuming.Clearance of endogenous blood substances - Serum creatinine: Insufficiently sensitive for detection of chronic renal disease (CRD) - Creatinine clearance: No longer recommended due to errors in urine collection Exception: Patients with highly abnormal muscle mass or vegetarian diet - Serum cystatin C: More sensitive than serum creatinine for detection of GFR reduction in the range 70-40; better than creatinine in children.