Transcript Document

DISEASES OF KIDNEY AND
URINARY TRACT
Lecture on pathomorphology for
the 3-rd year students
by T. Filonenko
Syndromes of renal diseases
1.
2.
3.
4.
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8.
Acute nephritic syndrome
The nephrotic syndrome
Asymptomatic hematuria or proteinuria
Acute renal failure
Chronic renal failure
Renal tubular defects
Urinary tract infection
Nephrolitiasis
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Causes of the nephritic
syndrome:
all diffuse-proliferative glomerulonephritis
syndromes
– post-streptococcal glomerulonephritis
– bacterial endocarditis
– lupus
 mild / early RPGN syndromes
– anti-GBM (Goodpasture's, other)
– Wegener's
– polyarteritis
 bad IgA-family (Berger's, Henoch-Schonlein,
etc.)
 membranoproliferative glomerulonephritis
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Causes of the nephrotic
syndrome
amyloidosis
 diabetic glomerular disease
 foot process disease
– minimal change glomerulopathy
– focal-segmental glomerulosclerosis
 membranous glomerulopathy
 membranoproliferative glomerulonephritis
 birth defects
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Glomerular diseases
Named diseases (by service
pathologists):
- Diseases that primarily involve the
glomerulus (acute post-streptococcal
glomerulonephritis, etc.)
- Systemic disease in which there are
glomerular changes (systemic lupus,
amyloidosis, diabetes, Goodpasture's
syndrome, etc.)
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Principles of glomeluronephritis classification
 Gomerulonephritis may be primary or secondary.
 According to the etiology it may be bacterial, viral,
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unclear.
According to the pathogenesis there are 2 types of
glomeluronephritis: immuno- associated and nonimmunoassociated.
According to the course GN may be classified into acute,
sub-acute, chronic.
Histologic and ultrastructural appearance of injury (by light
and electron microscopists).
According to topography: inter- and extracapillary GN.
According to character of inflammation: nonsuppurative
exudative and proliferative.
According to propagation: diffuse and local.
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MECHANISMS OF GLOMERULAR
INJURY
Immune:
 In situ immune complex formation
 Circulating immune complex deposition
Nonimmune:
Metabolic glomerular injury (diabetic nephropathy)
Hemodynamic glomerular injury (systemic
hypertension)
Deposition diseases (cryoglobulinaemia, amyloidosis)
Infectious diseases (HBV, HCV, HIV)
Inherited glomerular diseases(Alport’'s syndrome).
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HISTOLOGIC ALTERATIONS IN
GLOMERULAR DISEASE
 Cellular proliferation (intra- and
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extracapilary)
Leukocyte infiltration
Visceral epithelial cell swelling and
detachment
Glomerular basement membrane
thickening
Hyalinosis
Mesangiolysis
Necrosis
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Acute poststreptococcal
glomerulonephritis
• This disease may follow several weeks after infection
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with certain strains of group A beta hemolytic
streptococci.
This produces the nephritic syndrome.
Patients typically have an elevated anti-streptolysin O
(ASO) titer and decreased C3 levels in the serum.
The cause is deposition of circulating immune
complexes which fix complement and attract PMN's
In occurs most frequently in children of six to ten years
of age, but adults of any age can be affected.
Duration of disease from 1.5 to 12 months.
Gross appearance: Kidney enlarged; cortex broad,
pale, without markings; medullary rays congested;
glomeruli just visible as grey avascular dots.
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The hypercellularity of poststreptococcal glomerulonephritis
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•Proliferation of
endothelial,
mesangial and
epithelial cells;
•Infiltration by
leukocytes; The
proliferation and
leukocytes
infiltration are
diffuse;
•Swelling of
endothelial cells;
•Obliteration the
capillary lumen
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Electron microscopy shows these granules to be large,
dense, hump-shaped deposits located subepithelially
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Crescentic glomerulonephritis
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Glomerulus, crescentic
glomerulonephritis, PAS stain
Large crescent
Notice the fibrin in the crescent that has escaped from the severely
damaged and broken glomerular basement membrane (GBM).
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Glomerulus, crescentic
glomerulonephritis
BM
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Glomerulus with crescents
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Glomerulus, IgA nephropathy,
PAS stain
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By electron microscopy in membranous glomerulonephritis, the darker
electron dense immune deposits are seen scattered within the thickened
basement membrane.
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Membranous glomerulonephritis
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Membranous glomerulonephritis,
silver stain
Capillary loops
Mesangial areas
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Minimal change disease (MCD)
(Lipoid nephrosis)
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Nephrotic syndrom in children can be often;
characterized by normal glomeruli on light
microscopy but uniform and diffuse effacement of
the foot processes of visceral epithelial cells on
electronic microscopy.
GBM isn’t changes.
Tubules are dilated; their epithelium is swelling,
containing hyaline and fatty droplets.
Fatty
degeneration,
necrobiosis,
atrophy,
desquamation in tubular epithelium take place.
Gross appearances (“big white kidneys”): kidneys
enlarged, flabby, yellow color.
Minimal change disease (MCD),
silver stain
Podocytes
CL
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Minimal change disease (MCD),
trichrome stain
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Tubular lipoid cells
Minimal change disease (MCD) (Lipoid
nephrosis)
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Focal segmental glomerulosclerosis (FSGS)
Hematoxylin and eosin
Trichrome stain
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Focal segmental glomerulosclerosis (FSGS)
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2
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1- segmental sclerosis
2- interstitial inflammation
3- Atrophic tubules
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Membranoproliferative
glomerulonephritis
Notice the lobular
pattern, the
hypercellularity, and the
collapse of the
capillaries.
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Membranoproliferative glomerulonephritis (MPGN),
later stage, silver stain
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At a later stage of MPGN, many of the capillary loops show a double
contour, or "tram-track," appearance
This electron micrograph demonstrates the dense
deposits in the basement membrane of MPGN.
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Chronic glomerulonephritis (CGN)
 CGN is the final stage of GN when sclerosis
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has eliminated many glomeruli and their
associated tubules.
 Light microscopy shows hyaline obliteration of
glomeruli, transforming them into acellular
hyaline masses made of mesangial matrix,
basement-membrane material, dense
collagen, and trapped plasma protein.
 Tubules are lost, vessel walls are thickened,
and ultimately the kidney is totally destroyed.
 Given the usual trans-stygian kidney, the
pathologist cannot even tell whether the
original disease was glomerular, interstitial, or
vascular.
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Gross appearance:
 The
kidneys
are
symmetrically
contracted and have diffusely granular,
cortical surfaces.
 Pieces of renal tissue adhere to
stripped capsule; capsule is adherent
and strips with difficult.
 Weight is 50 gm each.
 On section, the cortex is thinned and
irregular,pelvis dilated and they’re in an
increasing peripelvic fat.
 Such kidneys are called “secondary
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shrinkage kidneys”
This is nodular glomerulosclerosis. Nodules of pink
hyaline material form in regions of glomerular capillary
loops in the glomerulus.
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Kidney failure: loss of renal
function.
 Acute renal failure usually presents as
oliguria (less than 500 mL urine/day) plus
azotemia. Hyperkalemia is the main threat to
life during the oliguric phase.
 Chronic renal failure is the end result of
irreversible kidney damage from any cause.
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Acute renal failure and acute tubular necrosis.
Acute renal failure (ARF) is a syndrome associated with
acute suppression of renal function, often accompanied
by oliguria, and rarely anuria or polyuria.
ARF is caused by:
 Organic vascular obstruction.
 Severe glomerular disease.
 Acute tubulointerstitial nephritis
 Massive infection
 Disseminated
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intravascular
coagulation
 Urinary obstructions
 Acute tubular necrosis
renal
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Acute tubular necrosis (ATN).
 ANT is characterized by destruction of
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renal tubular epithelial cells either from
ischemia or nephrotoxins.
 Ischemic ATN is called tubulorrhectic
ATN or shock kidney, occurs due to
hypoperfusion of the kidneys resulting in
focal damage to the tubules.
 Nephrotoxic ATN occurs as a result of
direct damage to tubular cells by
ingestion, injection or inhalation of a
number of toxic agents.
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Acute tubular necrosis (ATN)
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The clinical course of ATN may be deviled into
stages:
1. The initiating stage (shock), lasting for
about 36 hours, is dominated by the
inciting medical, surgical, or obstetric
event in the ischemic form of ATN.
Macroscopically, kidneys are diffusely
swollen
and
edematous.
It
is
characterized by ischemic cortex and
congestion of pyramids. Acute renal
failure and oliguria, hyperkalemia and
fluid overload in patients develop.
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 2. The maintenance stage (Oliguric phase, 2-9
days) is characterized by sustained decreases
in urine output to between 40 to 400 ml per
day, with salt and water overload, rising blood
urea nitrogens, hyperkaliemia, metabolic
acidosis, and other manifestations of uremia
dominating this phase. There is blockage of
renal tubules by necrotic cells, and a
secondary reduction in glomerular blood flow
(caused by arteriolar constriction) reduces
glomerular filtration. It stage may be fatal.
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 3. The recovery stage (Polyuric phase, 10-21 days)
is ushered by a steady increase in urine volume
that may reach up to 3 liters per day. Regeneration
of renal tubular epithelium takes place, with
removal of dead material by phagocytic cells, as
well as in the form of casts in urine. As tubules open
up and glomerular blood flow increases, patients
develop polyuria. This is because the regenerated
tubular cells are undifferentiated and have not
developed the specializations necessary for
resorption of electrolytes and water. Replacement
of fluid and electrolytes is needed to compensate
for excessive loss from urine. Hypokalemia, rather
than hyperkalemia, becomes a clinical problem.
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Pyelonephritis (PN)
 PN is a renal disorder affecting tubules,
intrestitium, and renal pelvis and is one of the
most common diseases of the kidney. It
occurs in two forms:
1. Acute PN is acute pyogenic infection.
2. Chronic PN is a more complex disorder:
bacterial infection plays a dominant role, but
other
factors
(vesicoureteral
reflux,
obstruction) are involved in its pathogenesis.
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Etiopathogenesis of PN.
 The dominant etiologic agents are the gram-negative
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bacilli that are normal inhabitants of the intestinal
tract: E.coli (Proteus, Klebsiella and Enterobacter),
Str. fecalis etc.
In most patients with UTI, the infecting organisms are
derived from the patient’s own fecal flora. This is thus
a form of endogenous infection.
There are two routs by which bacteria can reach the
kidneys:
Through the bloodstream (hematogenous).
From the lower urinary tract (ascending infection).
Although obstruction is an important predisposing
factor in the pathogenesis of ascending infection, it is
incompetence of the vesicoureteral orifice that allows
bacteria to ascend the ureter into the pelvis.
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Morphology of Acute Pyelonephritis
 The hallmarks of acute PN are patchy interstitial
suppurative inflammation and tubular necrosis.
 Macroscopically, the kidneys show variable numbers of
small, yellowish white cortical abscesses, which are
usually spherical, under 2 mm in diameter, and are
sometimes surrounded by a zone of hyperemia; the
cortical abscesses are often most prominent on the
sub-capsular surface, after the capsule has been
stripped away. In the medulla the abscesses tend to be
in the form of yellowish white linear streaks that
converge on the papilla. The pelvical mucosa is
hyperemic or covered with a fibrinopurulent exudate.
 Histologically: the neutrophilic infiltration is limited to
the interstitial tissue. Some tubules destroyed:
abscesses formed; other tubules filled by puss cells.
Glomeruli usually unaffected.
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Acute pyelonephritis
Three complications of acute PN are
encountered in special circumstances.
1.
2.
3.
Papillary necrosis is seen mainly in
diabetics and in those with urinary tract
obstruction. Papillary necrosis is usually
bilateral, but may be unilateral.
Pyonephrosis is seen when there is total or
almost complete obstruction, particularly
when it is high in the urinary tract (pelvis
filled with puss).
Perinephric abscess implies extension of
suppurative inflammation through the renal
capsule into the perinephric tissue.
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Outcomes of Acute PN
 At the acute phase of PN, healing occurs.
 The pyelonephritic scar is almost always associated
with inflammation, fibrosis, and deformation of the
underlying calyx and pelvis.
 Uncomplicated acute PN usually follows a benign
course, and the symptoms disappear within a few
days after the institution of appropriate antibiotic
therapy. In the presence of unrelieved urinary
obstruction, diabetes mellitus acute PN may be more
serious, leading to repeated septicemic episodes.
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Morphology of Chronic PN
 Gross examination.
 The kidneys are usually small and contracted
(weighing less than 100 gm) showing unequal
reduction; if bilateral, the involvement is
asymmetric.
 The surface of the kidney is irregularly
scarred; the capsule can be stripped off with
difficulty due to adherence to scars.
 There is generally dilatation of pelvis and
blunted calyces.
 This
contrasts
with
chronic
glomerulonephritis, in which the kidneys are
diffusely and symmetrically scarred.
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The microscopic changes involve
predominantly tubules and interstitium.
 The
tubules show atrophy in some areas and
hypertrophy in others, or dilatation. Dilated tubules
may be filled with colloid crystals, producing
thyroidisation of tubules (thyroid-like).
 Interstitium. There is chronic interstitial inflammatory
reaction, chiefly composed of lymphocytes, plasma
cells and macrophages with pronounced interstitial
fibrosis. Pelvicalyceal system. The renal pelvis and
calyces are dilated. And show marked chronic
inflammation and fibrosis.
 Blood vessels. Blood vessels entrapped in the scarred
areas show obliterative endarteritis.
 Glomeruli. There is often periglomerular fibrosis. In
advanced cases, there may be hyalinisation of
glomeruli.
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“End stage kidney"
 In end stage renal disease,
the kidneys are small
bilaterally, as shown here.
This
condition
is
associated with chronic
renal failure, and the
patient's
BUN
and
creatinine are elevated.
Chronic renal failure can
be treated by dialysis or by
transplantation, as shown
here.
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The microscopic appearance of the "end stage kidney"
(appearance of "thyroidization“)
Nephrosclerosis is morphologic basis of chronic renal failure.
Uremia is final stage of chronic renal failure, which is characterised
by
1.
Hypernitrogenemia
2.
Metabolic acidosis (accumulation of sulphates, phosphates,
and organic acids).
3.
Hyperkaliemia, hypercalcemia.
4.
Anemia. This ia due largely to depression of the bone marrow,
due to deficient erythropoietin production by the kidney.
5.
Depression of immunological reaction. Infections are common
and will in turn affect renal function.
6.
Arterial hypertension.
7.
Hemorrhagic syndrome (petechias, hemorrhagic erosions and
ulcer in mucosa)
8.
Fibrinous inflammation:

a) Fibrinous pericarditis (“cor vilosum”).

b) “Uremic pneumonitis” with pleural exudates.

c) Uremic gastritis, enteritis, colitis.

d) Edema of lungs.
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Diabetic Glomerular Nephropathy (Kimmelstiel-Wilson Lesion)
Low power view showing sclerosis of para-glomerular arterioles in
kidney; another renal complication of diabetes. Glomerulosclerosis
and arteriosclerosis lead to tubular ischemia, and the kidney will
undergo tubular atrophy, interstitial fibrosis, and become nonfunctional.
Diabetic Glomerular Nephropathy (Kimmelstiel-Wilson Lesion)
High power view of diabetic glomerulopathy or Kimmelstiel-Wilson
disease. Note the ovoid, hyaline masses present within the
mesangium and surrounded by patent capillary loops. These nodules
contain lipids and fibrin. As these lesions progress they will close
down the capillaries and destroy the glomerulus.