Schematic diagram showing the relationship between the intra-glomerular mesangial cells and the glomerular capillaries. The mesangial cell and its surrounding matrix are enclosed by the basal lamina of the glomerular capillaries. Note that the mesangial cells are
The glomerular basement membrane acts as a physical barrier and an ion-selective filter
The GBM contains type IV collagen, sialoglycoproteins, and other noncollagenous glycoproteins (e.g., laminin, fi-bronectin, entactin), as well as proteoglycans and gly-cosaminoglycans, particularly heparan sulfate (Fig. 19.13). These components are localized in particular portions of the GBM:
• The lamina vara externa, adjacent to the podocyte processes. It is particularly rich in polyanions, such as heparan sulfate, that specifically impede the passage of negatively charged molecules.
• The lamina rara interna, adjacent to the capillary endothelium. Its molecular features are similar to those of the lamina rara externa.
• The lamina densa, the overlapping portion of the two basal laminae, sandwiched between the laminae rarae. It contains type IV collagen, which is organized into a net-
in the same compartment as the endothelium and that they can be intimately associated with the basal lamina as well as with the endothelial cells. (Modified from Sakai T, Kriz W. Anat Embryol 1987; 176:373-386.)
work that acts as a physical filter. The laminin and other proteins present in the lamina rara interna and externa are involved in the attachment of the endothelial cells and podocytes to the GBM.
The GBM restricts the movement of particles, usually proteins, larger than approximately 70,000 daltons or 3.6 nm radius, e.g., albumin or hemoglobin. Although albumin is not a usual constituent, it may sometimes be found in urine, indicating that the size of albumin is close to the effective pore size of the filtration barrier. The polyanionic gly-cosaminoglycans of the laminae rarae restrict the movement of anionic particles and molecules across the GBM, even those smaller than 70,000 daltons. Despite the ability of the filtration barrier to restrict protein, several grams of protein do pass through the barrier each day. This protein is reabsorbed by endocytosis in the proximal convoluted tubule. The presence of significant amounts of albumin or hemoglobin in the urine (albuminuria or hematuria) indicates physical or functional damage to the GBM. In such cases (e.g., di-
endothelial cell foot processes (pedicels) of podocytes endothelial cell basal lamina foot processes (pedicels) of podocytes
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