PATHOLOGY - 17 - Urological Pathology.pdf

diseases of the urinary system

1. Ephraim Imhotep Zulu, BSc BMS, MSc Path
University of ZambiaSchool of Health Sciences,Dept. of Biomedical Sciences,
Pathology
Lecture #17
Urological Pathology


| Version 01 | April 2017

Procedural document:
Rare disease nomenclature in English


www.orpha.net www.orphadata.org

2. Lecture Outline
•Congenital anomalies
•Glomerular Diseases
•Nephrosclerosis
•Diseases Affecting Tubules & Interstitium
•Urinary Outflow Obstruction
•Renal failure
•Renal tumours
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3. Learning Objectives:
At the end of this lecture, the student is expected to
•Know and understand the aetiology, pathogenesis/pathophysiology
and complications of common diseases of the urinary tract
•Appreciate the risk factors associated with common diseases of the
urinary tract
•Know the descritipon of congenital anomalies of the urinary track
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4. Learning Objectives:
•Differentiate/Compare and Contrast the following pairs of terms:
•Nephritic syndrome vs. Nephrotic syndrome
• Acute Pyelonephritis vs. Chronic Pyelonephritis
•Chronic Glomerulonephritis vs. Chronic Pyelonephritis
•Benign nephrosclerosis vs. Malignant nephrosclerosis
•Acute renal failure vs. Chronic renal failure
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5. Congenital Anomalies of the Urinary System
Renal Hypoplasia
•Failure of the kidneys to develop to a
normal size.
•May result in renal failure
•A truly hypoplastic kidney shows no
scars and has a reduced number of
renal lobes and pyramids, usually six or
fewer.
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8. Renal Hypoplasia
•Failure of the kidneys to
develop to a normal size.
•May result in renal failure
•A truly hypoplastic kidney
shows no scars and has a
reduced number of renal
lobes and pyramids, usually
six or fewer.
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9. Ectopic Kidneys
•May occur in ectopic foci,
usually at abnormally low levels.
•Are usually normal or slightly
small in size but otherwise are
not remarkable.
•Because of their abnormal
position, kinking or tortuosity of
the ureters may cause sonic
obstruction to urinary flow,
which predisposes to bacterial
infections.
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10. Horseshoe Kidney
•Fusion of the upper or
lower poles of the kidneys
•Produces a horseshoe-
shaped structure that is
continuous across the
midline anterior to the
great vessels
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12. Pancake kidney
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Cake kidney. Similar to horseshoe kidney,
but the fusion is more diffuse, rather than
being localized to the inferior poles

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16. Cystic Diseases of the Kidney
•Are a heterogeneous group
comprising hereditary,
developmental but nonhereditary,
and acquired disorders.
•Some forms, such as adult
polycystic disease, are major
causes of chronic renal failure
•They can occasionally be confused
with malignant tumors.
•Radiographic studies show that, in
contrast to renal tumors, renal
cysts have smooth contours, are
almost always avascular, and give
fluid rather than solid tissue
signals on ultrasonography.
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18. Bladder Exstrophy
•The presence of a developmental failure in the anterior wall of the abdomen
and in the bladder, so that the bladder either communicates directly through
a large defect with the surface of the body or lies as an opened sac.
•Are amenable to surgical correction, and long-term survival is possible.
•The exposed bladder mucosa may undergo colonic glandular metaplasia and
is subject to the development of infections.
•There is an increased tendency toward the development of carcinoma later
in life, mostly adenocarcinoma of the colon.’
•Patients also have an increased risk of adenocarcinoma arising from the
bladder remnant.
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19. Bladder Exstrophy.,
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20. Glomerular Diseases
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Spectrum of
glomerular diseases.
(FSGS = focal and
segmental
glomerulosclerosis;
MCGN =
mesangiocapillary
glomerulonephritis)
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24. The Nephrotic Syndrome
•Is a glomerular syndrome characterized by heavy proteinuria, hypoalbuminemia,
severe edema, hyperlipidemia, and lipiduria (lipid in the urine).
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Inflammatory cells in
capillary lumens
haematuria
Injure capillary wall
Reninin /
aldosterone
Hemodynamic changes,
decreased GFR
Oliguria, Azotemia
Sodium & water
retension, increased
plasma volume
Hypertension, Mild
edema
Acute Nephritic Syndrome
•Acute Nephritic syndrome is a glomerular syndrome
characterized by inflammatory rupture of the glomerular
capillaries, with resultant hematuria, oliguria and
azotemia and hypertension. It is the classic presentation
of acute poststreptococcal glomerulonephritis.

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662
SECTION III
Systemic Pathology
adolescents and has many diverse causes such as diseases
of the glomerulus, renal interstitium, calyceal system, ureter,
bladder, prostate, urethra, and underlying bleeding disorder,
congenital abnormalities of the kidneys or neoplasia.
Glomerular haematuria is indicated by the presence of red
blood cells, red cell casts and haemoglobin in the urine.
Glomerular haematuria is frequently associated with
asymptomatic proteinuria.
PATHOGENESIS OF GLOMERULAR INJURY
Most forms of primary GN and many of the secondary
glomerular diseases in human beings have immunologic
pathogenesis. This view is largely based on immuno-
fluorescence studies of GN in humans which have revealed
glomerular deposits of immunoglobulins and complement
in patterns that closely resemble those of experimental
models. The consequences of injury at different sites within
the glomerulus in various glomerular diseases can be
assessed when compared with the normal physiologic role
of the main cells involved i.e. endothelial, mesangial, visceral
epithelial, and parietal epithelial cells as well as of the GBM as
summed up in Table 22.8.
Immunologic mechanisms underlying glomerular
injury are primarily antibody-mediated (immune-complex
disease). There is evidence to suggest that cell-mediated
immune reactions in the form of delayed type hypersensiti-
vity can also cause glomerular injury in some situations.
In addition, a few secondary mechanisms and some non-
immunologic mechanisms are involved in the pathogene-
sis of some forms of glomerular diseases in human beings
(Table 22.9).
I.IMMUNOLOGIC MECHANISMS
Experimental studies and observations in humans have
revealed that immunologic mechanisms, most importantly
antigen-antibody complexes, underlie most forms of
glomerular injury. The general principles of these
mechanisms in different forms of glomerular diseases are
discussed below, while specific features pertaining to
individual types of GN are described separately later.
A.Antibody-Mediated Glomerular Injury
1.IMMUNE COMPLEX DISEASE. Majority of cases of
glomerular disease result from deposits of immune
complexes (antigen-antibody complexes). The immune
complexes are represented by irregular or granular glomer-
ular deposits of immunoglobulins (IgG, IgM and IgA) and
complement (mainly C3). Based on the experimental models
and studies in human beings, the following 3 patterns of
glomerular deposits of immune complexes in various
glomerular diseases have been observed as illustrated in
Fig. 22.10:
i)Exclusive mesangial deposits are characterised by very mild
form of glomerular disease.
ii)Extensive subendothelial deposits along the GBM are
accompanied by severe hypercellular sclerosing glomerular
lesions.
??TABLE 22.7: Contrasting Features of Acute Nephritic and Nephrotic Syndromes.
Feature Acute Nephritic Syndrome Nephrotic Syndrome
1. Proteinuria Mild (< 3 gm per 24 hrs) Heavy (> 3 gm per 24 hrs)
2. Hypoalbuminaemia Uncommon Present
3.Oedema Mild, in loose tissue Marked, generalised peripheral
4. Mechanism of Oedema Na
+
and water retention !!!!! plasma osmotic pressure, Na
+
and
water retention
5. Haematuria Present, microscopic Absent
6. Hypertension Present Present in advanced disease
7. Hyperlipidaemia Absent Present
8. Lipiduria Absent Present
9. Oliguria Present Present in advanced disease
10. Hypercoagulability Absent Present
??TABLE 22.8: Relationship of Physiologic Role of Glomerular Components with Consequences in Glomerular Injury.
Component Physiologic Function Consequence of Injury Related Glomerular Disease
1. Endothelial cells i)Maintain glomerular perfusion Vasoconstriction Acute renal failure
ii) Prevent leucocyte adhesion Leucocyte infiltration Focal/diffuse proliferative GN
iii) Prevent platelet aggregation Intravascular microthrombi Thrombotic microangiopathies
2. Mesangial cells Control glomerular filtration Proliferation and increased matrix Membranoproliferative GN
3. Visceral epithelial cellsPrevent plasma protein filtration Proteinuria Minimal change disease, FSGS
4. GBM Prevents plasma protein filtration Proteinuria Membranous GN, ? MPGN
5. Parietal epithelial cellsMaintain Bowman’s space Crescent formation RPGN

27. Chronic Glomerulonephritis
•Is the final stage of many forms of glomerular disease and
is characterized by progressive renal failure, uremia, and
ultimately death
•Clinical features: Anemia, anorexia, and malaise,
Proteinuria, hypertension, and azotemia
•Gross: small, shrunken kidneys
•Urinalysis shows broad waxy casts
•Treatment: dialysis and renal transplantation
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28. Chronic Glomerulonephritis.,
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Primary glomerular diseases leading to chronic
glomerulonephritis (GN). The thickness of the arrows
reflects the approximate proportion of patients in each
group who progress to chronic GN: poststreptococcal (1% to
2%); rapidly progressive (crescentic) (90%), membranous
(30% to 50%), focal segmental glomerulosclerosis (50% to
80%), Membranoproliferative GN (50%), IgA nephropathy
(IgAN, 30% to 50%).

29. Diseases Affecting Tubules & Interstitium
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30. Acute Pyelonephritis
•Pyelonephritis (from pyelo, "pelvis") is the inflammation
of the renal pelvis
•Is caused by bacterial infection.
•An important manifestation of urinary tract infection
(UTI), which implies involvement of the lower (cystitis,
prostatitis, urethritis) or upper (pyelonephritis) urinary
tract, or both.
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268 GENITOURINARY PATHOLOGY
involvement, neutrophils and, rarely, bacteria can be
seen within tubules and collecting ducts of the cortex
and medulla. Soon the suppurative inflammation spills
into the interstitium. Glomeruli may be spared initially,
but with increasing severity generalized parenchymal
destruction occurs, resulting in abscess formation that
may extend into the perinephric tissues. In emphyse-
matous pyelonephritis, empty spaces lacking epithelial
cell linings form, distorting the parenchyma. Adjacent
areas show vascular thrombosis, ischemic necrosis,
suppurative inflammation, and abscesses (Figs. 5-60
and 5-61).
ACUTE PYELONEPHRITIS—FACT SHEET
Definition
!Acute bacterial infection of the kidney
Incidence and Location
!Common
!Cortex and medulla
Morbidity and Mortality
!Renal insufficiency if bilateral
Gender, Race, and Age Distribution
!Ascending form: males > females in children, females > males in
adults
!Hematogenous form: sepsis and infective endocarditis
Clinical Features
!Fever
!Leukocytosis; white blood cells and white blood cell casts in urine
Prognosis and Treatment
!Antibiotic treatment or surgical resection
FIGURE 5-58
In hematogenous acute pyelonephritis, there is a miliary pattern of small
cortical abscesses.
begins with bacterial cystitis followed by vesicoureteral
reflux. Vesicoureteral reflux may be a congenital, often
hereditary, abnormality in the anatomy of the uretero-
vesical junction. Alternatively, reflux may develop in
nonrefluxing systems with severe cystitis or if there is
distal obstruction or a neurogenic bladder. The kidney
is infected when intrarenal reflux occurs. The archi-
tecture of the renal pyramids influences their sus-
ceptibility to intrarenal reflux (see later discussion).
The infection extends up the medullary rays before
generalized cortical spread occurs. Hematogenous
pyelonephritis is the second route of infection. It usu-
ally complicates prolonged sepsis or infectious endo-
carditis. The organisms responsible are more often
gram-positive bacteria or fungi.
Several complications can result from prolonged
infections.
Pyonephrosisrefers to the near-total destruction of an
obstructed kidney by acute pyelonephritis.
Perinephric abscessis the accumulation of infectious
material and neutrophils within perinephric fat. It
usually originates from rupture of a renal abscess or
from pyonephrosis.
Emphysematous pyelonephritisis an uncommon but
life-threatening complication. Gas bubbles develop
within the renal parenchyma and may extend into
perinephric and even retroperitoneal sites. Approxi-
mately 90% of patients have diabetes mellitus, and
urinary tract obstruction is present in approximately
40%. E. coliis responsible in 68% of cases and
Klebsiellain 9% of cases; a mixed infection occurs in
19% of cases.
CLINICALFEATURES
Patients present with fever, leukocytosis, and flank
tenderness and may have a variety of complications.
Pyuria and urinary white blood cell casts are present.
PATHOLOGICFEATURES
GROSSFINDINGS
In ascending acute pyelonephritis, yellow-white
suppurative foci or overt abscesses develop in the
pyramids and may extend into the cortex. In hemato-
genous forms, the kidneys are peppered with abscesses,
which are more numerous in the cortex than in the
medulla. The kidney in emphysematous pyelonephritis
shows widespread abscesses with papillary necrosis and
cortical infarcts (Fig. 5-58) and may appear cystic due to
gas bubbles.
MICROSCOPICFINDINGS
There is an intense neutrophilic response within the
tubules and interstitium (Fig. 5-59). In sites of early

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33. Acute Pyelonephritis.,
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CHAPTER ONE: Non-neoplastic diseases of the kidney
46
infi ltrate is also present, even in forms associated with
infection.
Infection-related tubulointerstitial nephritis
Acute pyelonephritis
Acute pyelonephritis is a bacterial infection of the kidney.
240

Patients present with fever, leukocytosis, and fl ank tender-
ness, and may suffer a variety of complications (Table 1-27).
Pyuria and urinary white blood cell casts usually are present.
The kidneys may be seeded by organisms via two major
pathways: ascending infection and hematogenously.
The most common avenue of infection is ascent from a
lower urinary tract infection. Escherichia coli is the most fre-
quent organism, followed by other enteric organisms such
as Proteus, Klebsiella, and Enterobacter. In most individuals
with bacterial cystitis the infection remains localized to
the bladder. In susceptible individuals vesicoureteral refl ux
occurs, permitting colonization of the upper tracts.
240–244

This most often occurs in children with primary vesicoure-
teral refl ux, a congenital (often hereditary) abnormality in
the anatomy of the ureterovesical junction.
245
Refl ux can also
develop in non-refl uxing systems if the cystitis is severe, or
if there is distal obstruction or a neurogenic bladder.
Even with an upper tract infection, parenchymal infection
is not inevitable. The organisms must fi rst gain access to the
papillary collecting ducts, a process known as intrarenal
refl ux.
241–247
The architecture of the renal pyramids infl u-
ences their susceptibility to intrarenal refl ux (see Refl ux
Nephropathy, later in this chapter). Following initial infec-
tion of the pyramids, the infection extends up the medullary
rays prior to more generalized cortical spread.
Acute pyelonephritis in surgical and autopsy specimens
represents the most severe example. The collecting system is
thickened, and yellow-white suppurative foci or overt
abscesses are present in both pyramids and cortex (Fig.
1-88). Microscopically, there is mucosal ulceration and an
intense neutrophilic response within the tubules and inter-
stitium (Fig. 1-89). Occasionally, in sites of early involve-
ment, bacteria or neutrophils can be seen in the collecting
ducts of the cortex and medulla (Fig. 1-90). Glomeruli may
be spared initially, but with increasing severity generalized
parenchymal destruction occurs that may liquefy, resulting
in abscess formation.
Hematogenous pyelonephritis usually complicates pro-
longed sepsis or infectious endocarditis. The kidneys are
usually peppered with abscesses that are more numerous in
the cortex than the medulla (Figs 1-91, 1-92). The organisms
responsible are more often Gram-positive bacteria or fungi.
Pyonephrosis
Pyonephrosis is the near total destruction of an obstructed
kidney by acute pyelonephritis. The parenchyma is replaced
by suppurative infl ammation, transforming the kidney into
a large abscess. The patient is typically septic. Urine cultures
may be negative because of the urinary tract obstruction.
Perinephric abscess
Perinephric abscess is the accumulation of infectious mate-
rial and neutrophils within perinephric fat (Fig. 1-93). It
usually originates from rupture of a renal abscess or from
pyonephrosis, but can develop following a surgical proce-
dure such as renal transplantation or surgery for calculi.
Rarely, it may originate from an infected nidus extrinsic to
Table 1-27 Complications of acute pyelonephritis
Renal abscess
Pyonephrosis
Perinephric abscess
Emphysematous pyelonephritis
Sepsis
Fig. 1-88 Ascending acute pyelonephritis complicated by abscess
formation most severely affecting the lower pole (left).
Fig. 1-89 Acute pyelonephritis showing numerous neutrophils within renal
tubules (destined to form urinary white blood cell casts).

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The cortical surface is
studded with focal
pale abscesses,
Between the
abscesses there is
dark congestion of
the renal surface.

35. Acute Pyelonephritis.,
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When obstruction is prominent, the pus may be unable to drain and thus fills the renal pelvis,
calyces, and ureter, producing pyonephrosis.

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40 2 Kidney
Fig. 2.45 Emphysematous pyelonephritis. This term is applied to gas
bubble formation in the renal parenchyma or perirenal tissues; it is often
accompanied by abscess and cortical infarcts. This is a kidney from a
teenaged diabetic female who died of urosepsis. Tiny gas bubbles are
visible within the purulent infiltrates in the renal cortex (see MacLennan
GT, Resnick MI, Bostwick DG, 2003. With permission)
Fig. 2.44 Acute pyelonephritis. Numerous neutrophils are present in
the interstitium and within renal tubules
Fig. 2.43 Acute pyelonephritis. The affected kidney appears swollen
and pale. Microabscesses may be visible in the papillae and the renal
cortex. The kidney shown in this image was from a patient who died of
urosepsis after a gynecologic surgical procedure during which the ure-
ter was inadvertently ligated
Fig. 2.42 Perirenal abscess, fungal. Fungal organisms consistent with
Aspergillus species were readily visible within the abscess cavity shown
in Fig. 2.40

37. Chronic Pyelonephritis
•A morphologic entity in which predominantly interstitial
inflammation and scarring of the renal parenchyma is associated
with grossly visible scarring and deformity of the pelvicalyceal
system.
•Aetiology: chronic urinary tract obstruction and repeated bouts of
acute inflammation.
•Complications: renal hypertension and end-stage renal disease
•Morphology: The hallmark of chronic pyelonephritis is scarring
involving the pelvis or calyces, or both, leading to papillary blunting
and marked calyceal deformities .
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38. Chronic Pyelonephritis.,
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.idney and 8rinary %ladder
.LGQe\ aQG 8rLQar\ %OaGGer

property as in prostatic ?uid and urethral trauma during sexual intercourse). There is
presence of fever with chills, dysuria (painful micturition), increased frequency and urgency
along with costovertebral angle tenderness.
Urinalysis reveals presence of leukocytes particularly neutrophils (pyuria) and WBC
casts
Q
suggestive of renal involvement (because casts are formed only in tubules).
Complications include papillary necrosis (usually bilateral), pyonephrosis and
perinephric abscess.
Concept of Sterile Pyuria: Causes
• 5ecently treated 87,
• 7%, Iungal inIection
• 3erinephric abscess
• &hronic prostatitis
• $cute interstitial nephritis
• &hronic interstitial nephritis including analgesic nephropathy
• &hronic pyelonephritis
Di!erences between Chronic glomerulonephritis and Chronic pyelonephritis
7raLWs &KrRQLc JORPerXORQeSKrLWLs&KrRQLc S\eORQeSKrLWLs
&auses 9arious glomerulonephritis5e?u[ nephropathy or chronic obstructive
pyelonephritis
3athogenesis (nd stage glomerular disease
due to speci?c glomerulone-
phritis
&hronic tubulointerstitial in?ammation and
scarring associated with renal disorder
*ross appearance oI
surIace
'iIIusely, granular, cortical sur-
faces
'epressed area on dilated and blunted
caly[
6car )ine and 6ymmetrical&oarse and $symmetrical
*lomeruli5educed in number with oblit-
eration
1ormal may show periglomerular ?brosis
7ubules $trophied $trophy in some and hypertrophy in others
?lled with colloid casts thyroidisation
5enal pelvis and caly[1ormal 'ilated
,nterstitial and periglo-
merular ?brosis
0ild 0ore marked
&linical Ieatures ,nsidious in onset
3roteinuria, a]otemia, hyper-
tension, edema
0ay be asymptomatic or present with back
pain, Iever, polyuria, nocturia, pyuria, bac-
teriuria with gradual onset oI hypertension
and renal insuI?ciency
Xanthogranulomatous pyelonephritis (XPN)
8nusual variant of chronic pyelonephritis. 0ost cases occur in the setting oI obstruction due to inIected
renal stones.
*rRssO\
• Yellow, lobulated masses diIIusely replace the renal architecture.
0LcrRscRSLcaOO\
• 7here is massive destruction oI the kidney due to granulomatous tissue containing lipidladen
macrophages the appearance may be confused with renal malignancy.
&OLQLcaO feaWXres
• ,t most oIten occurs in middleaged women with a history oI recurrent urinary tract inIections.
• 7ypical presenting symptoms include ?ank pain, Iever, malaise, anore[ia and weight loss.
• $ unilateral renal mass can usually be palpated on physical e[amination.
6WerLOe S\XrLa Ls de?ned as
?white cells in the urine in the
absence oI signi?cant bacterial
growth?.
,n cKrRQLc JORPerXORQeSKrLWLs
kidneys are diffusely and sym-
PeWrLcaOO\ scarreG whereas
in cKrRQLc S\eORQeSKrLWLs
the kidneys are irregularly and
as\PPeWrLcaOO\ scarreG.
?8rLQar\ freTXeQc\ is oIten the
earOLesW symptom and may be
the RQO\ PaQLfesWaWLRQ Rf reQaO
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40. Analgesic Nephropathy
•Individuals who consume large quantities of analgesics may develop chronic
interstitial nephritis, often associated with renal papillary necrosis.
•Aspirin and acetaminophen are the major culprits.
•Common clinical features include chronic renal failure, hypertension, and
anemia. The anemia results in part from damage to red cells by phenacetin
metabolites.
•Cessation of analgesic intake may stabilize or even improve renal function.
•A complication of analgesic abuse is the increased incidence of transitional-
cell carcinoma of the renal pelvis or bladder in persons who survive the renal
failure.
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41. Analgesic Nephropathy.,
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The necrotic papillae
appear yellowish brown, as
a result of the accumulation
of breakdown products of
phenacetin and other
lipofuscin-like pigments.
Later on, the papillae may
shrivel, be sloughed off, and
drop into the pelvis.

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Acute Tubular Necrosis
CHAPTER 5 Non-neoplastic Diseases of the Kidney 263
ACUTE TUBULAR NECROSIS—FACT SHEET
Definition
!Acute renal failure produced by acute tubular cell injury
Incidence and Location
!The most common cause of acute renal failure
Morbidity and Mortality
!Related to the underlying responsible conditions
Clinical Features
!Decreased urine output, muddy brown casts, azotemia
!Edema, dyspnea
Prognosis and Treatment
!Potentially reversible in ischemic causes
!Often irreversible in toxic causes
FIGURE 5-52
In this kidney with acute tubular necrosis, there is marked hyperemia of
the outer strip of the outer medulla.
ACUTE TUBULAR NECROSIS—PATHOLOGIC FEATURES
Gross Findings
!Elevated renal weight, cortical pallor, hyperemia of
corticomedullary junction
Microscopic Findings
!Coagulation necrosis of tubules
!Tubular cell attenuation with interstitial edema
!Crystals, pigmented casts, tubular vacuolization
Differential Diagnosis
!Autolysis
!Distinguish ischemic from toxic cause
develop. The urine usually contains renal epithelial cells
and muddy brown casts. The urine sodium level may be
elevated because of loss of sodium conservation.
PATHOLOGICFEATURES
GROSSFINDINGS
The kidneys may appear normal but more often
are enlarged and swollen, with increased renal weight
(usually >200 g) due to interstitial edema. The cortex
is pale, with hyperemia (Fig. 5-52) at the cortico-
medullary junction.
MICROSCOPICFINDINGS
There is cortical interstitial expansion due to edema
without significant inflammation. A mononuclear cell
infiltrate may be seen at the corticomedullary junction,
or within the vessels in the vasa recta of the outer
medulla. The tubules can show two patterns of injury.
The first is coagulation necrosis of tubular cells, which
is most commonly seen at autopsy (Fig. 5-53). The
nuclei disappear, the cell membranes become indistinct,
and cell debris may slough into the lumen. The proxi-
mal tubules are affected more than the distal tubules.
The second pattern is more subtle, resulting from single
cell necrosis and sloughing. It is characterized by
attenuation or flattening of the tubular epithelium with
widely spaced nuclei (Figs. 5-54 and 5-55). The remain-
ing cells lose their brush border and spread out to cover
the basement membrane. There may be short segments
of denuded tubular basement membranes. Mitotic
figures are present but usually infrequent. Distal tubules
and collecting ducts contain granular casts of sloughed
cells.
Most toxic causes of acute tubular necrosis produce
no specific morphologic clues and appear identical to
ischemia-related causes, although coexistent interstitial
fibrosis may be present. There are a few that have diag-
nostically useful features. Isometric tubular vacuolization
is seen in cases associated with intravenous immuno-
globulin G (IgG). Numerous birefringent oxalate crys-
tals are present in renal tubular oxalosis (Fig. 5-56).
Pigmented casts are present in rhabdomyolysis-
associated cases. Tubular intranuclear inclusions may
be detected in lesions associated with heavy metal
exposure. Chemotherapy-related causes may result in
marked nuclear atypia.
DIFFERENTIALDIAGNOSIS
Acute tubular necrosis must be distinguished from
autolysis, especially in autopsy material. Autolysis is
recognized when epithelial cells having intact cell
membranes and preserved nuclei separate from tubular
basement membranes and from each other. The renal
weight is not increased in autolysis as it is in acute

43. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY43

44. Acute Tubular Necrosis.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY44

45. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY45
Nephrosclerosis
CHAPTER 5 Non-neoplastic Diseases of the Kidney 245
BENIGN NEPHROSLCEROSIS—FACT SHEET
Definition
!Renal scarring resulting from essential hypertension
Incidence and Location
!Approximately 24% of Americans have hypertension
Morbidity and Mortality
!Mild renal insufficiency in many
!Renal failure in a small percentage
Gender, Race, and Age Distribution
!Hypertension appears at age 45-55 years
!African Americans have highest incidence
Clinical Features
!Usually asymptomatic
!Gradual rise in serum creatinine
!Proteinuria
Prognosis and Treatment
!Preventable with treatment of hypertension
!Second leading cause of end-stage renal disease
FIGURE 5-26
In arterial nephrosclerosis (left)secondary to a long history of essential
hypertension, there is a diffuse, coarsely granular subcapsular surface. The
normal kidney (right)has a smooth surface.
BENIGN NEPHROSLCEROSIS—PATHOLOGIC FEATURES
Gross Findings
!Small contracted kidneys, 60-100 g, finely granular surface
Microscopic Findings
!Subcapsular scars: glomerular obsolescence, arteriolar thickening,
tubular atrophy
!Arteries: myointimal thickening and elastica duplication
Differential Diagnosis
!Small remote infarcts
!Chronic glomerulonephritis
myointimal thickening with duplication of the elastic
lamina. Lipid and calcification are not usually present.
DIFFERENTIALDIAGNOSIS
Small remote infarcts also produce subcapsular scars,
and chronic glomerulonephritis results in a granular
surface. Remote infarcts are usually larger. They are
single or, more often, multiple. If multiple, they do not
affect the entire kidney in a uniform manner; rather,
they are irregularly distributed and vary in size.
Microscopically, a periodic acid-Schiff (PAS) stain can
distinguish the ischemic obsolescent glomerulus of
benign nephrosclerosis from an infarcted glomerulus. In
an infarcted glomerulus, the PAS stain shows a con-
densed, collapsed glomerular tuft without the collagenous
tissue in Bowman’s space that is observed in benign
nephrosclerosis (Fig. 5-29). Chronic glomerulonephritis
to develop and is manifested by a slowly rising serum
creatinine concentration. Low-grade proteinuria is
common, but nephrotic-range proteinuria may occa-
sionally develop.
PATHOLOGICFEATURES
GROSSFINDINGS
The kidneys are symmetrically reduced and weigh
between 60 and 120 g. They have a uniform granular
subcapsular surface and a thin cortex (Fig. 5-26). The
magnitude of these changes is influenced by the severity
and duration of the hypertension.
MICROSCOPICFINDINGS
The subcapsular granularity corresponds to shallow
scars that contain sclerotic glomeruli, atrophic tubules,
and thick-walled arterioles (Figs. 5-27 and 5-28). The
characteristic vascular lesion affects arterioles, which
show either medial hyperplasia or, more often, hyali-
nosis with eosinophilic material expanding the intima
and media and resultant luminal compromise. Glomeruli
initially exhibit capillary loop wrinkling, with collage-
nous tissue filling Bowman’s space (Fig. 5-29), begin-
ning at the vascular pole, and progressing to global
sclerosis. Arteries of interlobular size or greater show

46. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY46
CHAPTER 5 Non-neoplastic Diseases of the Kidney 247
FIGURE 5-29
The ischemic glomerulus in benign
nephrosclerosis has a uniformly col-
lapsed tuft with collagenous tissue
filling Bowman’s space. (Periodic
acid-Schiff stain.)
MALIGNANT NEPHROSCLEROSIS—FACT SHEET
Definition
!Renal damage produced by malignant hypertension
Incidence
!1-2 cases/100,000 per year
Morbidity and Mortality
!Renal failure, stroke, myocardial infarction
Gender, Race, and Age Distribution
!Males > females
!African Americans > other races
Clinical Features
!Diastolic pressure 120-140 mm Hg, headache, ocular findings
!Hematuria, proteinuria, microangiopathic hemolytic anemia
Prognosis and Treatment
!Renal failure is usually irreversible
MICROSCOPICFINDINGS
A range of lesions is encountered, reflecting the
sequence of injury and repair. Fibrinoid necrosis
characterizes the acute lesion in untreated cases (also
referred to in nephropathology as acute thrombotic
microangiopathy). Glomeruli show capillary loop
thrombosis (Fig. 5-30) and mesangiolysis resulting from
necrosis of endothelial and mesangial cells. The
renal failure in most patients, hypertension is suffi-
ciently prevalent to account for 15% to 30% of end-
stage renal disease.
MALIGNANT NEPHROSCLEROSIS
Malignant nephrosclerosis develops as a consequence of
malignant hypertension. It may arise in a patient with
benign hypertension, or it may develop de novo.
CLINICALFEATURES
Patients present with renal failure, headache, dizziness,
and impaired vision, and their diastolic blood pres-
sure exceeds 120 to 140 mm Hg. Retinal hemorrhages,
exudates, and papilledema are present. Hematuria,
proteinuria, and a microangiopathic hemolytic anemia
develop.
PATHOLOGICFEATURES
GROSSFINDINGS
The kidney in untreated malignant nephrosclerosis
may have a normal or increased weight to 400 g.
Petechial subcapsular hemorrhages are characteristic.
The cortex may also be mottled red and yellow if
infarcts develop.

47. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY47

48. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY48
.idney and 8rinary %ladder
.LGQe\ aQG 8rLQar\ %OaGGer

There is also presence of hyalinizing arteriolar sclerosis (affects characteristically both
Q

afferent and efferent arterioles), pyelonephritis and papillary necrosis.
Clinical features: The increased GFR is associated with microalbuminuria.It is very
important clinical predictor of development of diabetic nephropathy later on. The protein
excretion then reaches subnephrotic proteinuria followed by nephrotic proteinuria. Patients
of type I diabetes may also have hypertension which further aggravates the renal disease.
Di!erences between Benign nephrosclerosis and Malignant nephrosclerosis
)eaWXres %eQLJQ QeSKrRscOerRsLs0aOLJQaQW QeSKrRscOerRsLs
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caused by thickening and hyalini]ation oI
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. )ibroelastic hyperplasia oI arteries and
arterioles
i +yperplastic arteriolitis onion
skinning due to proliIeration and
elongation oI smooth muscle cells.
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neutrophils in?ltration and
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iii )ibrinoid necrosis oI arterioles
iv 1ecroti]ing arteriolitis
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$bsent 3resent such as retinopathy
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TUBULAR DISEASES
Acute Tubular Necrosis (ATN)/Acute Kidney Injury (AKI)
• It is a disorder characterized by destruction of tubular epithelial cells resulting in
loss of renal function.
• It is the most common cause of acute renal failure (ARF). ARF is de?ned as rapid and
reversible deterioration of renal function leading to reduction of urine out?ow to
less than 400 ml per day within 24 hours.
ATN
Ischemic ATN 1eSKrRWR[Lc $71
? 0ost common cause oI $71
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.
? 'ue to decreased blood ?ow in shock,
hemorrhage, hypotension or dehydration.
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oI loop oI +enle
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.
? 'ue to drugs gentamicin, methicillin, radio
contrast agents, organic solvents, ethylene
glycol, phenol, pesticides, myoglobin.
? Diffuse necrosis oI proximal convoluted
tubular segments and ascending +enle?s
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Q
occur.
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(thylene glycol%allooning and vacuolar degeneration oI 3&7, &alcium oxalate crystals in
tubular lumen
Q
3roteinuria in most adults with
glomerular disease is non
selective, containing albumin
and a mixture oI other serum
proteins while in children with
minimal change disease protein-
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composed oI albumin.
Concept
$cute .idney ,nMury is the most
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Iailure $5).

49. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY49
Urinary
Outflow
Obstruction

50. Urolithiasis (Renal Stones)
•Is calculus (stone) formation at any level in the urinary
collecting system, but most often the calculi arise in the
kidney.
•Symptomatic urolithiasis is more common in men than in
women.
•A familial tendency is also recognized.
•Urolithiasis may also result from the lack of substances
that normally inhibit mineral precipitation in the urine.
Thursday, August 29, 202450Ephraim Zulu - PATHOLOGY

51. Renal Stones.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY51

52. Renal Stones.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY52

53. Renal Stones.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY53

54. Renal Stones.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY54

55. Hydronephrosis
Refers to dilation of the renal
pelvis and calyces, with
accompanying atrophy of the
parenchyma, caused by
obstruction to the outflow of
urine.
Thursday, August 29, 202455
Hydronephrosis of the kidney, with
marked dilation of the pelvis and calyces
and thinning of renal parenchyma.
Ephraim Zulu - PATHOLOGY

56. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY56

57. Hydronephrosis.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY57

58. Renal (Kidney) Failure
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY58
ischemic injury; ischemic, toxic, or obstructive tubular
injury; and obstruction of urinary tract outflow. The
causes of ARF commonly are categorized as prerenal,
intrinsic, and postrenal
1–6
(Fig. 26-1). Collectively, pre-
renal and intrinsic causes account for 80% to 95% of
ARF cases.
3
Causes of renal failure within these cate-
gories are summarized in Chart 26-1.
Prerenal Failure
Prerenal failure, the most common form of ARF, is
characterized by a marked decrease in renal blood flow.
It is reversible if the cause of the decreased renal blood
flow can be identified and corrected before kidney dam-
age occurs.
Normally, the kidneys receive 22% of the cardiac out-
put.
9
This large blood supply is required to remove meta-
bolic wastes and regulate body fluids and electrolytes.
Fortunately, the normal kidney can tolerate relatively large
reductions in blood flow before renal damage occurs. As
renal blood flow falls, the GFR decreases, the amount of
sodium and other substances that are filtered by the
glomeruli is reduced, and the blood flow needed for the
energy-dependent mechanisms that reabsorb these sub-
stances is reduced (see Chapter 24). As the GFR and urine
output approach zero, oxygen consumption by the kidney
approximates that required to keep renal tubular cells
alive. When blood flow falls below this level, which is
about 25% of normal, ischemic changes occur.
9
Because
of their high metabolic rate, the tubular epithelial cells are
most vulnerable to ischemic injury. Improperly treated,
prolonged renal hypoperfusion can lead to ischemic tubu-
lar necrosis with significant morbidity and mortality.
Causes of prerenal failure include profound depletion
of vascular volume (e.g., hemorrhage, loss of extracellu-
lar fluid volume), impaired perfusion due to heart fail-
ure and cardiogenic shock, and decreased vascular filling
because of increased vascular capacity (e.g., anaphylaxis
or sepsis). Elderly persons are particularly at risk because
of their predisposition to hypovolemia and their high
prevalence of renal vascular disorders.
Some vasoactive mediators, drugs, and diagnostic
agents stimulate intense intrarenal vasoconstriction and
can induce glomerular hypoperfusion and prerenal failure.
Examples include endotoxins, radiocontrast agents such as
those used for cardiac catheterization, cyclosporine (an
immunosuppressant drug that is used to prevent transplant
642 UNIT 7 Kidney and Urinary Tract Function
!Acute renal failure is caused by conditions that
produce an acute shutdown in renal function.
!It can result from decreased blood flow to the
kidney (prerenal failure), disorders that disrupt
the structures in the kidney (intrinsic or
intrarenal failure), or disorders that interfere with
the elimination of urine from the kidney (postre-
nal failure).
!Acute renal failure, although it causes an accu-
mulation of products normally cleared by the
kidney, is a potentially reversible process if the
factors causing the condition can be corrected.
Acute Renal Failure
Postrenal
(obstruction of
urine outflow
from the kidney)
Prerenal
(marked decrease
in renal blood flow)
Intrinsic
(damage to
structures
within the
kidney)
FIGURE 26-1.Types of acute renal failure.
Prerenal
Hypovolemia
Hemorrhage
Dehydration
Excessive loss of gastrointestinal tract fluids
Excessive loss of fluid due to burn injury
Decreased vascular filling
Anaphylactic shock
Septic shock
Heart failure and cardiogenic shock
Decreased renal perfusion due to sepsis, vasoactive
mediators, drugs, diagnostic agents
Intrinsic or intrarenal
Acute tubular necrosis
Prolonged renal ischemia
Exposure to nephrotoxic drugs, heavy metals, and
organic solvents
Intratubular obstruction resulting from
hemoglobinuria, myoglobinuria, myeloma light
chains, or uric acid casts
Acute renal disease (acute glomerulonephritis,
pyelonephritis)
Postrenal
Bilateral ureteral obstruction
Bladder outlet obstruction
CHART 26-1Causes of Acute Renal Failure
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59. Acute Renal failure - Aetiology
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY59
ischemic injury; ischemic, toxic, or obstructive tubular
injury; and obstruction of urinary tract outflow. The
causes of ARF commonly are categorized as prerenal,
intrinsic, and postrenal
1–6
(Fig. 26-1). Collectively, pre-
renal and intrinsic causes account for 80% to 95% of
ARF cases.
3
Causes of renal failure within these cate-
gories are summarized in Chart 26-1.
Prerenal Failure
Prerenal failure, the most common form of ARF, is
characterized by a marked decrease in renal blood flow.
It is reversible if the cause of the decreased renal blood
flow can be identified and corrected before kidney dam-
age occurs.
Normally, the kidneys receive 22% of the cardiac out-
put.
9
This large blood supply is required to remove meta-
bolic wastes and regulate body fluids and electrolytes.
Fortunately, the normal kidney can tolerate relatively large
reductions in blood flow before renal damage occurs. As
renal blood flow falls, the GFR decreases, the amount of
sodium and other substances that are filtered by the
glomeruli is reduced, and the blood flow needed for the
energy-dependent mechanisms that reabsorb these sub-
stances is reduced (see Chapter 24). As the GFR and urine
output approach zero, oxygen consumption by the kidney
approximates that required to keep renal tubular cells
alive. When blood flow falls below this level, which is
about 25% of normal, ischemic changes occur.
9
Because
of their high metabolic rate, the tubular epithelial cells are
most vulnerable to ischemic injury. Improperly treated,
prolonged renal hypoperfusion can lead to ischemic tubu-
lar necrosis with significant morbidity and mortality.
Causes of prerenal failure include profound depletion
of vascular volume (e.g., hemorrhage, loss of extracellu-
lar fluid volume), impaired perfusion due to heart fail-
ure and cardiogenic shock, and decreased vascular filling
because of increased vascular capacity (e.g., anaphylaxis
or sepsis). Elderly persons are particularly at risk because
of their predisposition to hypovolemia and their high
prevalence of renal vascular disorders.
Some vasoactive mediators, drugs, and diagnostic
agents stimulate intense intrarenal vasoconstriction and
can induce glomerular hypoperfusion and prerenal failure.
Examples include endotoxins, radiocontrast agents such as
those used for cardiac catheterization, cyclosporine (an
immunosuppressant drug that is used to prevent transplant
642 UNIT 7 Kidney and Urinary Tract Function
!Acute renal failure is caused by conditions that
produce an acute shutdown in renal function.
!It can result from decreased blood flow to the
kidney (prerenal failure), disorders that disrupt
the structures in the kidney (intrinsic or
intrarenal failure), or disorders that interfere with
the elimination of urine from the kidney (postre-
nal failure).
!Acute renal failure, although it causes an accu-
mulation of products normally cleared by the
kidney, is a potentially reversible process if the
factors causing the condition can be corrected.
Acute Renal Failure
Postrenal
(obstruction of
urine outflow
from the kidney)
Prerenal
(marked decrease
in renal blood flow)
Intrinsic
(damage to
structures
within the
kidney)
FIGURE 26-1.Types of acute renal failure.
Prerenal
Hypovolemia
Hemorrhage
Dehydration
Excessive loss of gastrointestinal tract fluids
Excessive loss of fluid due to burn injury
Decreased vascular filling
Anaphylactic shock
Septic shock
Heart failure and cardiogenic shock
Decreased renal perfusion due to sepsis, vasoactive
mediators, drugs, diagnostic agents
Intrinsic or intrarenal
Acute tubular necrosis
Prolonged renal ischemia
Exposure to nephrotoxic drugs, heavy metals, and
organic solvents
Intratubular obstruction resulting from
hemoglobinuria, myoglobinuria, myeloma light
chains, or uric acid casts
Acute renal disease (acute glomerulonephritis,
pyelonephritis)
Postrenal
Bilateral ureteral obstruction
Bladder outlet obstruction
CHART 26-1Causes of Acute Renal Failure
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60. Acute Renal failure - Pathophysiology
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61. Acute Renal failure – Laboratory Findings
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY61
PRERENAL AZOTEMIA
Basic description:Source of azotemia originates proximal to
the kidney.
Causes:Low-volume stimulus caused by hypovolemia, heart
failure, sepsis, and renal vascular pathology (e.g., atherosclero-
sis, fibromuscular dysplasia).
Important point regarding prerenal azotemia:In prerenal
azotemia, the kidney functions normally and responds to a per-
ceived low-volume stimulus by reabsorption of sodium (FENa
!1%), water, and urea. Because creatinine is filtered and
secreted by the tubules, and urea is filtered and reabsorbed, the
low-volume stimulus in prerenal azotemia causes a rise in
serum BUN out of proportion to the rise in serum creatinine.
Therefore, in the absence of other causes of alterations in BUN
and creatinine (e.g., gastrointestinal bleed, rhabdomyolysis),
the BUN/Cr ratio is usually "20.
INTRINSIC AZOTEMIA
Basic description:Source of azotemia originates within the
kidney.
Causes:Acute tubular necrosis (toxic or ischemic type),
glomerular disease, acute interstitial nephritis.
Important point:Intrinsic azotemia implies dysfunction of the
kidney itself. In the setting of a normal kidney, oliguria would
be expected to be accompanied by avid sodium retention.
Intrinsic azotemia, however, is characterized by FENa "1%
due to impaired tubular function. The BUN/Cr ratio is !20
because of normal hemodynamics.
POSTRENAL AZOTEMIA
Basic description:Azotemia due to obstruction of the urinary
tract. The source of renal failure originates distal to the kidney.
Causes:Urethral, bladder, or prostatic obstruction; kidney
stones.
Important points:Urinary obstruction may be accompanied by
complete anuria, oliguria, or normal urinary output. Tubular
dysfunction in the setting of partial obstruction may even cause
polyuria. Renal ultrasound is the diagnostic test of choice in
postrenal azotemia and can identify hydronephrosis and most
stones.
Complications of acute renal failure
!Electrolyte disturbances:Hyponatremia, hyperkalemia,
hyperphosphatemia, and hypocalcemia. Hypocalcemia is a
result of the high phosphate level.
!Metabolic acidosis.
!Gastrointestinal hemorrhage, sepsis, and heart failure, which
represent many of the causes of death due to acute renal
failure.
Clinical presentation of acute renal failure (Table 16-1)
!Signs and symptoms:Oliguria (!400 mL of urine per day),
lethargy, fatigue, and nausea.
284 CHAPTER 16 Pathology of the Kidney and Bladder
TABLE 16-1.Laboratory Diagnosis of Acute Renal Failure
Prerenal Acute Intrinsic Renal
Laboratory Test Renal Failure Failure
FEN
a !1% "1%
BUN/Cr ratio "20:1 !20:1
Urine sodium !20 mEq/L "20 mEq/L
Urine osmolality"500 mOsm/kg !400 mOsm/kg
Specific gravity"1.020 !1.010
FEN
a, fractional excretion of sodium; BUN, blood urea nitrogen; Cr, creatinine.

62. Chronic Renal Failure
•Basic description: Symptoms of acute renal failure with longer duration. The
term uremia indicates the presence of clinical symptoms in the background of
chronic renal failure.
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY62

progression of renal disease
375
being treated by dialysis or who have a functioning kidney
transplant are said to be on ‘renal replacement therapy’.
Chronic kidney disease is common, being present in as
many as 10% of the population and the incidence increases
with increasing age. The commonest cause of CKD, particu-
larly in the elderly, is ischaemic nephropathy due to hyper-
tension or vascular disease. It is important to identify
because even in its milder stages it is associated with an
increased risk of cardiovascular death. As renal function
deteriorates further the toxicity of nitrogenous waste prod-
ucts, the loss of homeostasis of fluid, electrolyte and
acid–base balance and disturbances in the endocrine func-
tions of the kidney all result in important effects. There are
many diseases which may lead to chronic renal failure
(Table 13.2) and their pathological characteristics are
described in the appropriate sections. The biochemical,
clinical and morphological changes which accompany
chronic renal failure irrespective of the underlying primary
renal disease are described below.
leading to hypertension and peripheral and pulmonary
oedema. Less commonly but particularly where the primary
renal disorder is tubular or interstitial (e.g. calculus disease)
sodium and fluid depletion will occur unless a high salt and
fluid intake is maintained. Loss of concentrating function
due to tubular damage combined with the osmotic diuretic
effect of high concentrations of nitrogenous waste products
such as urea probably explain the relatively fixed output of
dilute urine occurring in chronic renal failure.
Acid–Base Balance and Electrolyte Disturbance
To conserve acid–base balance the kidneys must excrete
40–60 mmol of acid (H
!
) daily. In chronic renal failure total
ammonia production and secretion into the tubules is
reduced and there is also some loss of urinary bicarbonate,
which is normally completely reabsorbed. As a result of
these changes the patient with chronic renal failure is prone
to develop acidosis. In renal failure, chronic acidosis may
cause tissue catabolism which results in a deterioration in
nutritional status and may also aggravate renal bone disease.
Excessive potassium and phosphate generated by
dietary intake or protein breakdown is normally excreted
by the kidney. In chronic renal failure potassium retention
may occur and be exacerbated by acidosis which results in
the exchange of intracellular potassium for hydrogen ions.
Hyperkalaemia may cause muscle stiffness and abdominal
pain but is often asymptomatic until potentially fatal car-
diac arrhythmias develop. Hyperphosphataemia occurs in
later renal failure resulting in calcium phosphate depos-
ition (metastatic calcification) in the soft tissues particularly
in the arterial wall, the periarticular tissues, and the con-
junctivae. Pruritus is a frequent symptom in patients with
advanced renal failure and calcium phosphate deposition in
the skin is thought to contribute to this. These abnormal-
ities in calcium phosphate balance are compounded by
impaired activation of 25-hydroxy vitamin D in the kidney
(see below) and lead to secondary hyperparathyroidism.
Endocrine Disturbances
The principal endocrine functions of the kidney concern
bone metabolism, erythropoiesis and blood pressure con-
trol. Renal bone disease or renal osteodystrophy describes
the various bone changes occurring in renal failure as
a result of impaired activation of vitamin D, altered cal-
cium phosphate balance and secondary hyperparathy-
roidism.These include osteitis fibrosis cystica, osteomalacia
and osteoporosis (see Chapter 12). Anaemia is a common
feature of chronic renal failure and occurs principally due to
a lack of adequate production of erythropoietin from peri-
tubular cells of the renal cortex. This secondary anaemia
contributes to the symptoms of tiredness and poor exercise
tolerance in renal failure and can be corrected by subcuta-
neous or intravenous recombinant erythropoietin treatment.
In chronic renal failure the renin – angiotensin–aldosterone
system is inappropriately activated resulting in hypertension.
The renal changes resulting from hypertension cause further
TABLE13.2Causes of chronic renal failure
Glomerulonephritis
Reflux nephropathy
Renal calculi
Obstructive uropathy
Diabetes
Renovascular disease/hypertension
Polycystic kidney disease
Systemic vasculitis (e.g. systemic lupus erythematosus,
Henoch–Schönlein purpura)
Myeloma
Amyloidosis
Other diseases
Nitrogenous Waste Products
The clinical features of waste product retention are those
of chronic poisoning and become more pronounced as
renal function declines. Patients with CKD 4 and 5 com-
plain of non-specific symptoms such as tiredness, lethargy
and anorexia. Platelet function is abnormal, leading to easy
bruising and bleeding from the gastrointestinal tract and
disturbances of the immune system predispose to infec-
tion. In advanced renal failure fibrinous pericarditis and
pneumonitis, consisting of a serofibrinous exudate in the
alveolar spaces, may be present. The pulmonary changes
resemble those of neonatal hyaline membrane disease but
there is often partial organization of the exudate. The
effects on the nervous system include peripheral neuropathy,
poor concentration, sleep disturbance and ultimately coma
but there are few obvious pathological changes in the brain.
Sodium and Water
In chronic renal failure the kidney’s inability to control salt
and water balance can lead to both overhydration and
dehydration. In most cases sodium and fluid retention occur

63. Chronic Renal failure - Pathophysiology
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY63

64. Renal failure – Clinical Features
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY64

65. Urological Tumors
Renal Cell Carcinoma
•The most common malignant tumor of the kidney
•The three most common renal cell tumours are clear
cell (70-80%), papillary (10-15%) and Chromophobe
(5%) carcinomas,
•Hematuria is the most frequent presenting abnormality.
Thursday, August 29, 202465Ephraim Zulu - PATHOLOGY

66. Renal Cell Carcinoma
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY66
Renal cell carcinoma: typical
cross-section of yellowish,
spherical neoplasm in one
pole of the kidney. Note the
tumor in the dilated,
thrombosed renal vein.

67. Renal Cell Carcinoma – risk factors
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY67

68. Wilms Tumor
•AKA Nephroblastoma
•Occurs infrequently in adults
•3rd most common organ cancer in children
younger than the age of 10 years.
•may arise sporadically or be familial, with the
susceptibility to tumorigenesis inherited as an
autosomal dominant trait.
Thursday, August 29, 202468Ephraim Zulu - PATHOLOGY

69. Wilms Tumor.,
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY69

70. Bladder Neoplasms
Thursday, August 29, 202470Ephraim Zulu - PATHOLOGY

71. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY71

72. References & Credits
Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY
•Barone J, Castro M.A. (2016), USMLE Step 1 Pathology Lecture Notes, Published by Kaplan
Medical, a division of Kaplan, Inc. 750 Third Avenue, New York, NY 10017: ISBN: 978-1-
5062-0772-8
•BostwickD.G,Liang Cheng L, Urologic Surgical Pathology, 2nd Edition,(2008) morsby-
elsevier
•Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee brothers medical
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73. Thursday, August 29, 2024Ephraim Zulu - PATHOLOGY
End of Lecture
Ephraim Imhotep Zulu
Pathology
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