628
U N I T 7
Kidney and Urinary Tract Function
Tubular and Interstitial
Disorders
Several disorders cause histologic and functional altera-
tions that affect renal tubular structures, including the
proximal and distal tubules. Most of these disorders also
affect the interstitial tissue that surrounds the tubules.
Although these disorders, sometimes referred to as
tubu-
lointerstitial disorders
, may occur in the progression of
diseases that primarily affect the glomerulus or as sec-
ondary manifestations of other diseases such as diabetes
mellitus, they can also occur as a primary event. These
diseases have diverse causes and different pathogenic
mechanisms. They include acute tubular necrosis (dis-
cussed in Chapter 26), tubulointerstitial nephritis, acute
and chronic pyelonephritis, reflux nephropathy, and
nephropathy induced by drugs and toxins.
Tubulointerstitial Nephritis
Tubulointerstial nephritis represents acute or chronic
inflammation of the renal tubules and surrounding
interstitium. In chronic tubulointerstitial nephritis there
is infiltration with mononuclear leukocytes, interstitial
fibrosis, and widespread tubular atrophy.
The tubulointerstitial disorders are distinguished
clinically from glomerular diseases by the absence, in
the early stages, of such hallmarks of nephritis and
nephrosis as hematuria and proteinuria, and by the
presence of disorders in tubular function. These dis-
orders, which are often subtle, include the inability to
concentrate urine, as evidenced by polyuria and noctu-
ria; interference with acidification of urine, resulting in
metabolic acidosis; and diminished tubular reabsorp-
tion of sodium and other substances.
5
In their advanced
forms, however, they are difficult to distinguish from
other causes of renal insufficiency.
Pyelonephritis
Pyelonephritis is a renal disease affecting the tubules,
interstitium, and pelvis of the kidney. Acute pyelone-
phritis is caused by bacterial infection; whereas chronic
pyelonephritis is a more complex disorder involving not
only bacterial infection but other factors such as reflux.
Most infections of the kidney are ascending infections
that occur secondary to infections of the lower urinary
tract (discussed in Chapter 27).
Acute Pyelonephritis
Acute pyelonephritis is an acute suppurative inflamma-
tion of the kidney caused by bacterial infection.
4,5,21,22
Escherichia coli
is the causative agent in about 80%
of cases. Less common causative organisms include
Enterobacteriaceae
,
Pseudomonas
species, group B
Streptococcus, Staphylococcus,
and
enterococci.
21
There
are two forms of acute pyelonephritis: uncomplicated
and complicated. Uncomplicated acute pyelonephri-
tis most commonly occurs in healthy young women
without structural or urinary tract obstructions or
other contributing factors. Complicated acute pyelone-
phritis occurs in children or adults with structural or
functional urinary tract abnormalities or predisposing
medical conditions. Factors that contribute to the devel-
opment of complicated acute pyelonephritis are outflow
obstruction, catheterization and urinary instrumenta-
tion, vesicoureteral reflux, pregnancy, and neurogenic
bladder.
There are two routes by which bacteria can gain access
to the kidney: ascending infection from the lower uri-
nary tract and through the bloodstream (hematogenous
spread). Ascending infection from the lower urinary tract
is the most important and common route by which bac-
teria reach the kidney. The hematogenous route results
from seeding of the kidneys by bacteria from distant loci
in the course of septicemia or infective endocarditis.
5
It
is more likely to occur in debilitated, chronically ill per-
sons and those receiving immunosuppressive therapy,
and with nonenteric bacteria such as staphylococci and
certain fungi.
Although outflow obstruction is an important predis-
posing factor in the pathogenesis of ascending infection,
it is incompetence of the vesicoureteral orifice that allows
bacteria to ascend the ureter into the renal pelvis.
4,5
The
ureter normally inserts into the bladder at a steep angle
and in its most distal portion courses parallel to the blad-
der wall, forming a mucosal flap
4
(Fig. 25-11A). The flap
acts as a one-way valve: it is normally relaxed, allow-
ing urine to flow into the bladder, but is compressed
against the bladder wall during micturition, preventing
urine from being forced into the ureter. In persons with
vesicoureteral reflux, the ureter enters the bladder at an
approximate right angle such that urine is forced into
the ureter during micturition (Fig. 25-11B). It is seen
most commonly in children with urinary tract infections
■■
Glomerular disorders alter the permeability
of the glomerular capillary membrane to
plasma proteins and blood cells to produce
either a nephritic or nephrotic syndrome.
The nephritic syndromes, which evoke an
inflammatory response in the glomeruli and
a decrease in glomerular permeability, are
characterized by hematuria with red cell casts in
the urine, diminished GFR, azotemia, oliguria,
and hypertension.The nephrotic syndromes,
which increase glomerular capillary membrane
permeability, are characterized by massive
proteinuria, hypoalbuminemia, generalized
edema, lipiduria, and hyperlipidemia.
■■
Chronic glomerulonephritis represents the
chronic phase of a number of specific types of
glomerulonephritis.
SUMMARY CONCEPTS
(continued)
