formed from the fusion of the capillary and podocyte-produced basal
laminae.
256.The answer is d.(Kierszenbaum, pp 373–375. Junqueira, pp 373–374,
- Kumar, p 988.)The genetic mutation in COL4A5 leads to a defect in
theα-chains that comprise type IV collagen found in the lamina densa
labeledAon the electron micrograph of the basement membrane in the
accompanying electron micrograph of the basal lamina. The glomerular
basement membrane will therefore show abnormal splitting and thinning
in the lamina densa and overall thickening. The hematuria results from
breakdown of the basal lamina allowing the passage of red blood cells and
eventually protein (proteinuria). The patient suffers from Alport’s syn-
drome resulting from a mutation of the α5 chain of type IV collagen.
Remember that type IV collagen consists of three alpha chains forming a
triple helix. The noncollagenous C-terminal (NC1) and the 7S N-terminal
are particularly important for the cross-linking of type IV collagen. The
cross-linking forms the scaffolding of the basement membrane necessary
for the normal filtration properties of the basal lamina. Proliferation of
mesangial cells and increased production of mesangial matrix are typical of
later stages of Alport’s syndrome when glomerulonephritis is a prominent
feature of the disease.
The glomerular filtration barrier consists of the pedicel (A)of the
podocyte, the basal lamina (C= lamina rara, D= lamina densa)synthe-
sized by the podocyte, and the endothelial cell (E).The podocyte consists
of a “cell body” of cytoplasm with long processes that encircle the glomeru-
lar basement membrane. The filtration slits are labeled B.The filtration slits
are located between adjacent pedicels (foot processes of the podocytes).
The remainder of the filtration barrier is formed by the glomerular base-
ment membrane, which contains type IV collagen and heparan sulfate. At
high magnification there are three distinct layers within the glomerular
basement membrane: (1) an electron-dense lamina densa (type IV colla-
gen) in the center surrounded by (2) the lamina rara externa on the
glomerular side and by (3) the lamina rara interna on the capillary
endothelial side.
The glomerular filtration barrier is a physical and charge barrier that
exhibits selectivity based on molecular size and charge. The presence of
collagen type IV in the lamina densa of the basement membrane presents a
392 Anatomy, Histology, and Cell Biology