Glomerular capillary wall

These studies led to the realization that proteinuria— the abnormal appearance of protein in the urine— could result not only from the enlargement of submicroscopic holes in the glomerular capillary wall, but also from the loss or neutralization of its negatively charged components. This finding has provided a new direction for research on the molecular basis for the nephrotic syndrome, a group of kidney diseases all characterized by massive proteinuria. 

Like the walls of other capillaries, the glomerular capillary wall consists of a single layer of endothelial cells. However, these cells are specialized in that they are fenestrated. The presence of large pores in these capillaries makes them 100 times more permeable than the typical capillary. These pores are too small, however, to permit the passage of blood cells through them. 

Proteinuria (including albuminuria indicative of increases in the permeability of the glomerular capillary wall fi-2 microglobulin indicative of an impairment in tubular reabsorption)... 

Several factors, including molecular size, charge, and shape, influence the glomerular filtration of large molecules. The restricted passage of macromolecules can be thought of as a consequence of the presence of a glomerular capillary wall barrier with uniform pores. 

The glomerular capillary wall has a very high hydraulic permeability and the glomerular basement membrane and the slit diaphragm probably contribute approximately 50% each to the total hydraulic resistance of the capillary wall (D8). Foot process effacement found both in experimental models of nephrotic syndrome and in human glomerulopathies dramatically reduces the hydraulic permeability of the glomerular capillary wall (Gil). 

The endothelial cell barrier normally restricts the passage of formed elements (e.g., red cells) through the glomerular capillary wall, but it presents no restriction to the passage of different macromolecules. 

Contractile elements of the podocyte foot processes, which may influence the hydraulic permeability of the glomerular capillary wall, may be regulated via vasoactive hormones. Receptors for some vasoactive hormones, for example, en-dothelin (R4), atrial natriuretic peptide (S9), nitric oxide (K22), and angiotensin n (Yl), have been described on the podocyte surface. 

Idiopathic membranous nephropathy is the commonest form of nephrotic syndrome in middle-aged and elderly patients. The glomerular capillary wall is thickened due to immune deposits (containing mosty immunoglobulin G, IgG)... 

Heavy proteinuria is caused by increased permeability of the glomerular capillary wall for macromolecules. Mainly the size, the charge, and the shape influence the passage of macromolecules through the glomerular capillary wall. The glomerular basement membrane and the slit diaphragm represent the main barriers for the filtration of macromolecules. 

The glomerular capillary is believed to restrict (mainly due to the electrical charge) the filtration of molecules with molecular weights higher than 10 kDa, and molecules with of more than 40-50 kDa (i.e., approximately like albumin) almost do not pass through the glomerular capillary wall. 

Plasma Factors That May Increase Permeability of the Glomerular Capillary Wall... 

Nephrotic syndrome is a clinical and laboratory syndrome caused by the increased permeability of the glomerular capillary wall for macromolecules. Nephrotic syndrome is a potentially life-threatening state and persistent nephrotic syndrome has a poor prognosis with a high risk of progression to end-stage renal failure and a high risk of cardiovascular complications due to severe hyperlipidemia. 

Couser et al. (1978) studied the development of immune deposits on the subepithelial surface of the glomerular capillary wall in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen. 

Alcorn D and Ryan GB. Distribution of anionic groups in the glomerular capillary wall in rat nephrotoxic nephritis and amino-nucleoside nephrosis. Pathology 13 37-50,1981. 

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