The Physiology of the Glomerular
Tuft
Structure
• The glomerulus consists of a capillary tuft that is
surrounded by Bowman's capsule, which passes the
filtered primary urine to the tubular system.
• It is a network held together by connective tissue and
composed of three distinct cell types: endothelial cells,
mesangial cells, and glomerular visceral epithelial cells
(podocytes).
• Glomerular filtration barrier is a trilaminar structure
composed of a fenestrated endothelium, the hydrated
meshwork of the glomerular basement membrane
(GBM), and the filtration slit formed by pedicel
interdigitation.
Mesangial Cells
• There are two distinct populations of
mesangial cells.
• The first population makes up about 85% to
95% of resident mesangial cells and has a
network of contractile elements, such as actin,
myosin, and tropomyosin.
• The second population exhibit features of
monocytes/macrophages and are derived
from bone marrow.
• The covering of the capillaries by the GBM is partial.
• Mesangial cells account for the completion of the capillary covering
by forming loops that completely encircle the capillaries.
• Those contacts establish a biomechanical unit, with the basement
membrane serving as the effector site and mesangial cells as the
contractile motor.
• These contacts permit the mesangial cells to support the
mesangium and regulate the capillary surface area and glomerular
volume, influencing glomerular hemodynamics.
• Therefore, mesangial cells can modulate GFR by changing the
capillary surface area and redistributing blood volume in glomerular
capillaries through the actions of mesangial loops.
• Contraction of a mesangial cell occurs in
response to hormones, vasoactive
compounds, and growth factors through G
protein–associated receptors that activate
phospholipase C.
• Hormones using the cyclic AMP and cyclic
GMP cascades relax mesangial cells through
direct effects or through antagonism of
contracting substances.
Glomerular Filter
• Endothelial Cell
– The glomerular endothelial fenestrae may be covered
by a diaphragm formed by a thick cell coat
(glycocalyx).
– This layer is a matrix-like gel composed of
proteoglycans, with negatively charged as well as
neutral glycosaminoglycans, glycoproteins, and
plasma proteins carrying a negative charge.
– Thus, the glycocalyx is an initial charge barrier in the
glomerular filter and function as a size-selective
barrier.
• Glomerular Basement Membrane
– The GBM is an especially thick membrane that lies
between the endothelial cells and the visceral
epithelium (podocytes).
– The main components of the GBM are triplehelical type IV collagen, proteoglycans, laminin,
and entactin.
• Glomerular Visceral Epithelial Cells
(Podocytes)
– Podocytes can be divided into three distinct
functional segments: cell body, primary processes,
and secondary processes, also known as foot
processes or pedicels.
– These cells are located at the external surfaces of
glomerular capillaries, which they cover with
pedicels.
– The covering of capillaries is achieved by
interdigitation of pedicels derived from adjacent
podocytes, forming between them filtration slits that
are bridged by a specialized cell junction, called slit
diaphragms, which represent the last filtration barrier
to proteins.
– The cell body and primary processes are mainly
constituted by microtubules and intermediate
filaments, whereas pedicels contain a dense network
of actin microfilament bundles associated with myosin
II, α-actin, talin, and vinculin, forming a complex
contractile apparatus.
– Podocytes have all the necessary elements to
generate tensile strength and stabilize glomerular
architecture by counteracting the hydrostatic
forces causing distentions of glomerular
capillaries.
– Podocytes also have receptors for several
contracting and relaxing factors.
– The slit diaphragm not only provides a structural
element, serving as a static molecular sieve, but also is
a dynamic multifunctional protein complex that
functions as a signalling platform for the podocyte.
– Podocytes seem to play a crucial role in the
development of the entire glomerular tuft, mainly
through production of angiogenic factors.
– During glomerular development, they express vascular
endothelial growth factor-A (VEGF-A), whereas the
endothelial and mesangial cells express the VEGF
receptors.