622
U N I T 7
Kidney and Urinary Tract Function
The agents or events that trigger glomerular injury
include infectious microorganisms, immunologic mech-
anisms, drugs, and environmental agents.
4,5,10–13
Most
cases of primary and many cases of secondary glomerular
disease probably have an immune origin. Although many
glomerular diseases are driven by immunologic events,
a variety of metabolic (e.g., diabetes), hemodynamic
(e.g., hypertension), and toxic (e.g., drugs, chemicals)
stresses can induce glomerular injury, either alone or in
concert with immunologic mechanisms.
Two types of immune mechanisms have been impli-
cated in the development of glomerular disease: (1) injury
resulting from antibodies reacting with fixed glomerular
antigens or antigens planted within the glomerulus and
(2) injury resulting from circulating antigen–antibody
complexes that become trapped in the glomerular mem-
brane
4,5,12
(Fig. 25-5). Antigens responsible for develop-
ment of the immune response may be of endogenous
origin, such as autoantibodies to deoxyribonucleic acid
(DNA) in systemic lupus erythematosus (SLE), or they
may be of exogenous origin, such as streptococcal mem-
brane antigens in poststreptococcal glomerulonephritis.
Frequently, the source of the antigen is unknown.
Glomerular diseases have traditionally been named
according to tissue appearance (i.e., proliferative, mem-
branous, or sclerotic) rather than according to the under-
lying cause. Accordingly, the term
proliferative
is used to
describe a hypercellular inflammatory process with pro-
liferation of glomerular cells;
membranous,
an abnor-
mal thickening of the glomerular basement membrane;
and
sclerotic,
an increase in the amount of extracellular
material in the mesangial, subendothelial, or subepi-
thelial tissue of the glomerulus.
4,10
Glomerular changes
can be
diffuse,
involving all glomeruli and all parts of
the glomeruli;
focal,
in which only some glomeruli are
affected and others are essentially normal;
segmental,
involving only a certain segment of each glomerulus; or
mesangial,
affecting only mesangial cells. Figure 25-4B
illustrates the location of lesions associated with various
types of glomerular disease.
Dependent upon the structures involved and the
extent of their involvement, glomerular disorders can
manifest with hematuria (red cells in the urine), protein-
uria (protein in the urine), and the presence or absence
of hypertension; azotemia (elevation of blood urea nitro-
gen); or renal insufficiency. The
nephritic syndrome
is
due to glomerular disease that is usually of acute onset
and is accompanied by grossly visible hematuria, mild to
moderate proteinuria, and hypertension. The
nephrotic
syndrome
, also due to glomerular disease, is character-
ized by heavy proteinuria, hypoalbuminemia, and severe
edema.
A
Epithelial cell
with podocytes
Endothelial
cell
Basement
membrane
Mesangial
matrix
Mesangial
cell
B
Fusion of
epithelial cell
podocytes
Endothelial
cell swelling
Subendothelial
deposits
Subepithelial
deposits
Basement
membrane
Mesangial
deposit
White
blood cell
FIGURE 25-4.
(A)
Normal.
(B)
Localization of immune deposits
(mesangial, subendothelial, subepithelial) and changes in
glomerular architecture associated with injury.
Basement
membrane
Epithelial cell
Foot process
(podocytes)
Subendothelial
deposit
Circulating
antigen–antibody
complexes
Antigen
Antibody
Antiglomerular
membrane antibodies
Circulating
antigen–antibody
complex deposition
A
B
FIGURE 25-5.
Immune
mechanisms of glomerular
disease.
(A)
Antiglomerular
membrane antibodies leave
the circulation and interact
with antigens that are present
in the basement membrane of
the glomerulus.
(B)
Antigen–
antibody complexes circulating
in the blood become trapped
as they are filtered in the
glomerulus.
