Normal Histology Of Glomerulus
The glomerular capillary wall is the filtering membrane and consists of the following structures:
- A thin layer of fenestrated ndothelial cells, each fenestrum being about 70 to 100 nm in diameter.
- A glomerular basement membrane (GBM) with a thick electron-dense central layer, the lamina densa, and thinner electron-lucent peripheral layers, the lamina rara interna and lamina rara externa. Q
- The GBM consists of collagen (mostly type IV), laminin, polyanionic proteoglycans (mostly heparan sulfate), fibronectin, entactin, and several other glycoproteins. Q
- Type IV collagen forms a network suprastructure to which other glycoproteins attach. The building block (monomer) of this network is a triple-helical molecule made up of three -chains, composed of one or more of six types of -chains (1 to 6 or COL4A1 to COL4A6), the most common consisting of 1, 2, 1. Each molecule consists of a 7S domain at the amino terminus, a triple-helical domain in the middle, and a globular noncollagenous domain (NC1) at the carboxyl terminus. The NC1 domain is important for helix formation and for assembly of collagen monomers into the basement membrane supra structure. Glycoproteins (laminin, entactin) and acidic proteoglycans (heparan sulfate, perlecan) attach to the collagenous supra structure. Q
- These biochemical determinants are critical to understanding glomerular diseases. For example, as we shall see, the antigens in the NC1 domain are the targets of antibodies in anti- GBM nephritis; genetic defects in the a-chains underlie some forms of hereditary nephritis; and the acidic porous nature of the GBM determines its permeability characteristics.
- The visceral epithelial cells (podocytes), are structurally complex cells that possess interdigitating processes embedded in and adherent to the lamina rara externa of the basement membrane. Adjacent foot processes (pedicels) are separated by 20- to 30-nm-wide filtration slits, which are bridged by a thin diaphragm. Q
- The entire glomerular tuft is supported by mesangial cells lying between the capillaries. Basement membrane-like mesangial matrix forms a meshwork through which the mesangial cells are centered. These cells, of mesenchymal origin, are contractile, phagocytic, and capable of proliferation, of laying down both matrix and collagen, and of secreting a number of biologically active mediators. Biologically, they are most akin to vascular smooth muscle cells and pericytes.
Figure: Schematic diagram of the proteins of the glomerular slit diaphragm. CD2AP, CD2-associated protein.