Glomerular filtration barriers.
In the kidneys, before the plasma ultrafiltrate can enter the lumen of the nephron Bowmanís capsule (i.e., Bowmanís space), it must go through four different physical barriers. These blood-to-urine barriers are collectively referred to as the glomerular filtration barrier, and they form the cellular and molecular basis for the selectivity of the permeation process. The filtration process is commonly referred to as glomerular permselectivity because it is characterized by more than simple filtration of plasma, and selects for various molecules based on molecular size, charge, and shape. As plasma and its contents move from the lumen of the glomerular capillary out and into the Bowmanís space, the four barriers they encounter are:
(1) Glycocalyx is a layer of negatively charged proteoglycans and glycosaminoglycans, which coat the luminal surface of endothelial cells. This layer is approximately 300 nm thick (i.e., extends 300 nm from the luminal surface of the endothelial cell into the lumen of the glomerular capillary). This layer appears to also cover the opening of the fenestrae of endothelial cells (which forms the next layer of physical barrier).
(2) Fenestrae (plural; singular form is fenestra) are pores that allow the passage of water and small molecules through the endothelial cells of capillaries including the glomerular capillaries. Due to extensive fenestration, the permeability in the glomerular capillaries is very high; 100-400 times more permeable than capillaries elsewhere in the body. The diameter of the fenestrae is about 70 nm. Fenestrae, therefore, allow the passage of water, ions, small molecules, and even some small proteins. However, they restrict the movement of large proteins, platelets, and cells.
(3) Endothelial cell basement membrane. This layer is a porous matrix of extracellular proteins such as type IV collagen, laminin, fibronectin, and other negatively charged glycoproteins. Typically referred to as the glormerular basement membrane, this layer is also an important physiological barrier to filtration.
(4) Filtration slits. The epithelial layer which forms the inner wall of the Bowmanís capsule is composed of cells referred to as podocytes. Podocytes have finger-like projections (i.e., foot processes) which interdigitate with similar structures from adjacent podocytes. The physical contact between the foot processes does not form a perfect seal. Rather, pores remain in-between the foot processes. These pores are referred to as filtration slits. This epithelial layer (containing podocytes, foot processes, and filtration slits) completely wraps around the endothelial cells of the glomerular capillary and its associated basement membrane. Thus, water and any other solutes that exit the glomerular capillary and pass through the matrix of the basement membrane must also pass through the filtration slits before entering the Bowmanís space. A thin porous structure exists at the mouth of the filtration slits facing the glomerular basement membrane. This porous filter structure is called the slit diaphragm, and is composed of a network of extracellular filaments. The pore molecular dimensions within the slit diaphragm appear to be 4 nm × 14 nm.