Diseases of Urinary System

I
Congenital dis. Of kidney
Agenesis
The absence of both kidneys is not compatible with life.
Absence of one kidney, the other kidney undergoes compensatory
hypertrophy to maintain normal renal function
Hypoplasia
failure of one kidney to reach adult size. , the other kidney undergoes
compensatory hypertrophy

Persistant faetal lobulation

Displacement or ectopic kidney
Horse shoe Kd. The 2 Kds. are fused at one Pole
Double ureter & pelvis
Aberrant renal a. abn, site of renal art.
Cong. Cysts of the kidney
Solitary cyst. Or Multiple Cysts

(The horseshoe kidney is a form of ectopic kidney in which the poles of the two kidneys
fuse in the pelvic cavity prior to ascending.
This leads to a large U-shaped kidney which is unable to ascend to the level of L1
because it is blocked by the inferior mesenteric artery at the aorta. )

CYSTIC DISEASES OF THE KIDNEY

ADULT POLYCYSTIC KIDNEY DISEASE
AUTOSOMAL DOMINANT PKD (ADPKD)
A very common form of PKD that does not manifest until mid-adulthood.
Formation of very large, disparate cysts.
Process can involve any part of the nephron.
Renal failure occurs late-onset (adult) when it occurs, but it only occurs in about 50% of
cases. The kidneys can withstand an incredible number of cysts before function is
compromised.
Etiology:
Genetic, autosomal dominant
A Genes located on the short arm of chromosome 16 (APKD1).
Pathogenesis:
• The basic pathologic process may be considered a proliferative /hyperplastic
abnormality of the tubular epithelium.

• In the early stages of cyst development, the cysts are connected to the tubules from
which they arise and the fluid content is glomerular filtrate.

• When the cyst diameter exceeds 2 mm, most detach from the patent tubule and the
fluid content is derived from secretions of the actual lining epithelium.

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 • With time, the cysts enlarge and cause progressive damage to adjacent functioning
nephrons.
• Cysts develop along the entire length of the nephron
Pathogenesis:
• The basic pathologic process may be considered a proliferative /hyperplastic
abnormality of the tubular epithelium.

• In the early stages of cyst development, the cysts are connected to the tubules from
which they arise and the fluid content is glomerular filtrate.

• When the cyst diameter exceeds 2 mm, most detach from the patent tubule and the
fluid content is derived from secretions of the actual lining epithelium.

• With time, the cysts enlarge and cause progressive damage to adjacent functioning
nephrons.

• Cysts develop along the entire length of the nephron

Epidemiology:
• Relatively common, occurring in one in 500 to 1000 individuals.

• Adult PKD is the third most common cause of end-stage renal disease.

General Gross Description:

• The disease is bilateral.

• The kidneys are enlarged (can be massive, up to 4 kg each).

• The kidneys overall remain reniform in shape but the parenchyma shows
innumerable cysts of varying sizes from barely visible to 4 to 5 cm.

• The fluid content may be clear to reddish brown.

• Cysts found in both cortical and medullary regions.

General Microscopic Description:

• Most of the cysts are lined by non-descript, flattened to cuboidal epithelial cells.

• Some cysts however show epithelia with features of proximal tubules, distal tubules
and collecting ducts.

• Tissues between the cysts may show unremarkable or atrophic nephron elements.

Clinical Correlations:
• usually present in the fourth to fifth decade of life with progressive renal
insufficiency and bilaterally enlarged cystic kidneys.
• Hypertension is a common complication

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Extrarenal manifestations include:
hepatic, pancreatic and splenic cysts;
intracranial and aortic aneurysms;
and cardiac valve abnormalities.

INFANTILE AUTOSOMAL RECESSIVE PKD (ARPKD)

The cysts uniformly arise in the collecting ducts, rather than the whole nephron.
As compared to ADPKD, the cysts are diffuse and evenly distributed.

Renal failure is virtually inevitable, usually occurring in childhood, but it can occur in
adulthood.

Associated with congenital Hepatic Fibrosis.

Etiology:
Genetic, autosomal recessive.
Pathogenesis:
• The pelvis, calyces, papillae as well as the nephrons are believed to develop normally in
the initial stages of renal genesis.
• The cystic development of the collecting ducts are believed to occur subsequently by a
hyperplastic process.
Epidemiology:
• Developmental disorder of the kidneys discovered in developing fetuses (by
ultrasound) or in the newborn period (enlarged kidneys).

General Gross Description:

• The kidneys are bilateral and symmetrically enlarged but retain a reniform shape.

• Cut surface of the kidneys shows elongate cylindrical spaces radially arranged from the
medulla into the cortex. This feature blurs the normal distinct cortico-medullary junction.

General Microscopic Description:

• On microscopic examination, the cysts are elongate and cylindrical and radiate from the
medulla to the cortex.
• The cysts are lined by a single layer of cuboidal epithelium similar to that of the
collecting ducts.

Clinical Correlations
• Cases are discovered antenatally if prenatal care includes utrasonographic studies.
• Most cases that go to term die shortly after birth from respiratory difficulties due to the
enlarged kidneys that have resulted in developmental pulmonary hypoplasia.
• This disease is not invariably fatal. Those cases that survive infancy may subsequently
develop hepatic portal fibrosis, portal hypertension and splenomegaly.

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ACQUIRED PKD
PATHOGENESIS: Happens with renal failure patients on dialysis.

CLINICAL ,COMPLICATIONS
Renal Cell Carcinoma is the most common complication..

SIMPLE RENAL CYSTS

•That's just what they are.

II
Glomerular Diseases

Glomerular Diseases
• Glomerular diseases are one of the MC causes of CRF

• Primary glomerulopathies – glomeruli are injured &

the kidney is the only or predominant organ involved

• Secondary glomerulopathies – glomeruli are injured

during the course of a systemic disease

•They are bilateral and mostly immunologically mediated

Glomerular Diseases
•diffuse – all glomeruli are involved
• focal – only a certain proportion of the glomeruli are involved

• global – entire glomerulus is involved

• segmental – only a portion of the glomerulus is involved

Primary Glomerulopathies
Acute diffuse proliferative glomerulonephritis
Poststreptococcal
Non-poststreptococcal
Rapidly progressive (crescentic) glomerulonephritis
Membranous glomerulopathy
Minimal change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis

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Systemic Diseases with Glomerular Involvement (Secondary)
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis

Hereditary Disorders
Alport syndrome
Thin basement membrane disease
Fabry disease

Glomerular Diseases – Pathogenesis

• immune mechanisms underlie most cases of 10 glomerulo-nephritis & many cases of 20
glomerulonephritis
• glomerular deposits of Ig’s &/or complement components are found in
> 70% of patient’s with glomerulonephritis

• 2 forms of antibody-associated injury have been established

• antibodies reacting in situ with Ag’s in the glomerulus
• insoluble fixed (intrinsic) glomerular Ag’s, or
• molecules planted within the glomerulus
• deposition of soluble circulating antigen-antibody complexes within the glomerulus

Immune Mechanisms of Glomerular Injury

Antibody-Mediated Injury
In Situ Immune Complex Deposition
Fixed intrinsic tissue antigens
 NC1 domain of collagen type IV antigen (anti-GBM nephritis)

 Heymann antigen (membranous glomerulopathy)

Mesangial antigens

Others

Planted antigens
Exogenous (infectious agents, drugs)

 Endogenous (DNA, nuclear proteins, immunoglobulins, immune complexes, IgA

Circulating Immune Complex Deposition

 Endogenous antigens (e.g., DNA, tumor antigens)

Exogenous antigens (e.g., infectious products)

Cytotoxic Antibodies

Cell-Mediated Immune Injury

 Activation of Alternative Complement Pathway

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HISTOLOGIC ALTERATIONS
Various types of glomerulonephritis are characterized by one or more of four
basic tissue reactions.

Hypercellularity.
Basement Membrane Thickening.
Hyalinization and Sclerosis.

Hypercellularity.
Some inflammatory diseases of the glomerulus are characterized by an increase in
the number of cells in the glomerular tufts.

This hypercellularity is characterized by one or more combinations of the

following:

 Cellular proliferation of mesangial or endothelial cells

 Leukocytic infiltration, consisting of neutrophils, monocytes ..

Formation of crescents. These are accumulations of cells composed of proliferating

parietal epithelial cells and infiltrating leukocytes.

Basement Membrane Thickening.

 By light microscopy, this change appears as thickening of the capillary walls, best
seen in sections stained with periodic acid-Schiff (PAS).

 By electron microscopy, such thickening can be resolved as one of two

alterations:
 deposition of amorphous electron-dense material, most often immune
complexes, on the endothelial or epithelial side of the basement membrane or
within the GBM itself. Fibrin, amyloid, cryoglobulins, and abnormal fibrillary
proteins may also deposit in the GBM; or
 thickening of the basement membrane proper, as occurs in diabetic
glomerulosclerosis

Hyalinization and Sclerosis.

By light microscopy ,the accumulation of homogeneous and eosinophilic material.
By electron microscopy, the hyalin is extracellular and consists of amorphous substance,
made up of plasma proteins that have exuded from circulating plasma into glomerular
structures.
 Hyalinosis is usually a consequence of capillary wall injury and typically is the
end result of various forms of glomerular damage.
 Additional alterations include intraglomerular thrombosis or accumulation of lipid
or other metabolic materials.

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Types of glomerulonephritis
The most common types with established pathological and clinical characteristics are:
Acute diffuse post-streptococcal proliferative glomerulonephritis
Rapidly progressive glomerulonephritis (crescentic glomerulonephritis).
Membranous glomerulonephritis.
Membranoproliferative glomerulonephritis
Minimal change glomerulonephritis (lipoid nephrosis
Focal glomerulosclerosis
Focal glomerulonephritis.
Chronic glomerulonephritis.

Clinical Manifestations of Glomerular Disease

asymptomatic proteinuria

Nephrotic syndrome

(proteinuria, hypoproteinemia, lyperlipidemia, edema)

asymptomatic hematuria

Glomerulonephritis (Nephritic Syndrome)

(hematuria, proteinuria, hypertension, renal failure)

acute glomerulonephritis

(neprhitis with short term renal failure)

crescentic glomerulonephritis

(nephritis with rapidly progressive renal failure)

chronic glomerulonephritis

(chronic progression of renal failure)

End Stage Renal Disease

(irreversible renal failure)

NEPHRITIC SYNDROME
A group of renal diseases with the following common clinical features
Hematuria
Oliguria (GFR↓, Cr↑, BUN↑)
Edema (salt and water retention)
Hypertension
Proteinuria
Hypoalbuminemia

NEPHROTIC SYNDROME
A group of renal diseases with the following common clinical features
Proteinuria (“nephrotic range” >3.5g/24h)
Hypoalbumimenia
Edema
Hyperlipidemia
Lipiduria

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 Acute Proliferative Glomerulonephritis
characterized histologically by diffuse proliferation of glomerular cells with an influx
of leukocytes

 Caused by deposition of immune complexes

 inciting Ag may be exogenous or endogenous

Prototypical exogenous pattern is postinfectious
glomerulo-nephritis
Prototypical endogenous pattern is SLE

Acute Post streptococcal Proliferative GN

Aetiology Develops 2 wks after upper resp.infection or skin infection

by β hemolytic strept.group A

Pathogenesis Immune complex disease

Naked Eye  Both kidneys are slightly enlarged equal ,slightly

pale
 With thin easily stripped capsule
 Smooth outer surface
 Cut section shows wide coreex &differentiated from
medulla
Light microscopy  All glomeruli are enlarged hypercellular due to
proliferation of endothelial and mesangeal cells
 Obliteration of capillary lumen and narrowing of
Bowman 's space
 PNL & monocytes infiltration
 Red cell cast in distal tubules
 Interstitial oedema

EM. Discrete subepith. Deposits (humps)

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 IF Granular flourescence of glom. cap. wall & mesangium.for
C & IgG

Clinical & lab.  Fever , malaise

Finding  Oedema of face
 Transient Mild hypertension
 ⇑Bl. Urea (mild)
 Oliguria
 Smoky urine(haematuria)
 Sp.gr. of urine high
 ⇑ESR , ⇑ Aso Low serum comp.
Prognosis • In children 95% recover
• In adults 60%
Complications
• Acute R.F.
• Rapidly prog.
• Ch. G.N.

Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN)

Deterioration of renal function over a period of days to weeks
Goodpasture Syndrome (Type I)
Type II (With Immune Complexes)
Type III (Without Immune Complexes)

RPGN is classified as follows

Type I – Anti GBM disease/Goodpasture syndrome

Type II – Immune complex mediated like

MPGN, Lupus nephritis, Ig A nephropathy

Type III – Pauci-immune ANCA associated Vasculitis like Wegner’s

granulomatosis, Microscopic Polyangiitis

Rapidly Progressive (Crescentic) Glomerulonephritis

• Not a specific etiologic form of glomerulonephritis

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•Characterized clinically by rapid & progressive loss of renal function with severe
oliguria

• Death from renal failure within weeks to months if untreated

•divided into 3 groups based on immunologic findings

Type I RPGN
• anti-GBM disease with linear deposits of Ig’s & C3
• in some patients the anti-GBM Ab’s cross-react with pulmonary alveolar BM
(Goodpasture syndrome)
• exposure to viruses, solvents, various drugs & cancers have been implicated in
triggering formation of the Ab’s

Type II RPGN
• immune complex-mediated disease
• can be a complication of any of the immune complex nephritides
• granular pattern of staining for Ig’s & C3

Type III RPGN

• pauci-immune type
• most of these patients have ANCA
• some cases are associated with a systemic vasculitis

Rapidly progressive glomerulonephritis

Aetiology IdiopathicMay follow acute

Pathogenesis Immune compex disease. orAntiglomerular b.m disease

Naked Eye As acute but the kidney is pale with petechaeal

hemorrhage in cortex
Light microscopy •Glom.enlarged hypercellular with proliferation of
endothelial,mesangial &capsular epithelium
•More than 50% of glom.show crescent formation due to
localized proliferation of capsular epith.
there may be segmental necrosis with hemorrhage into
Bowman's space.
•Blood vessels may show malignant hypertension
•Interst.oedema
•Red cell casts& protein in tubules

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 IF Granular or linear flour.
May be negative in pauci immune type
Fibrin is seen in the crescents.

EM. focal ruptures in the GBM

Clinical & lab. As acute but more sever

Finding

Prognosis Fatal in weeks to 1 year.Due to :

Acute R.F.
Hypertension.

Goodpasture’s syndrome
Definition:
A form of rapidly progressive glomerulonephritis (Bilateral pulmonary hemorrhage
+rapidly progressive GN)

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Progressive decrease in kidney function,
Accompanied by a cough with bloody sputum.
More in children especially ♂

The disorder is characterized by

deposits of antibodies in the basement membranes of both the kidney
glomerulus and the lung alveoli, causing both glomerulonephritis and
pulmonary (lung) bleeding.

NEPHROTIC SYNDROME
A group of renal diseases with the following common clinical features
Proteinuria (“nephrotic range” >3.5g/24h)
Hypoalbumimenia
Edema
Hyperlipidemia
Lipiduria

Important causes of N.S. :

1- Glomerulonephritis esp.
 Membranous G.N.

Membranoproliferative G.N

 Minimal lesion G.N.

2- SLE.
3- Diabetic glomerulosclerosis
4- Amyloidosis
5- Infections as syphilis. malaria , viral hepatitis B
6- Malignancy esp. lymphoma.
7- Drugs as NSAI.

•in children: 95% of cases are due to primary glomerular diseases

• in adults: 60% of cases are due to primary glomerular diseases
• MC 10 glomerular diseases causing nephrotic syndrome
• minimal change disease (mostly children)
• focal segmental glomerulosclerosis (all ages)
• membranous glomerulopathy (mostly adults)
• MC systemic diseases causing nephrotic syndrome
• diabetes mellitus (mostly adults)
• amyloidosis (mostly adults)
• systemic lupus erythematosus (mostly adults)

complications:
apart from chronic renal failure
•⇑ infections due to loss of Ig’s & complement
•0 ⇑ thrombosis due to loss of anticoagulant factors

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 Membranous Glomerulopathy
•MC cause of nephrotic syndrome in adults
• primary membranous GN (85% of cases)
• secondary membranous GN
• drugs (e.g., penicillamine, NSAIDs)
• malignancies (esp. carcinoma of lung & colon, melanoma)
• SLE
• infections (e.g. hepatitis B & C, syphilis)
• Hashimoto thyroiditis
•secondary membranous GN is caused by deposition of immune complexes
•primary membranous GN is caused by autoantibodies directed against an Ag on the
visceral epithelial cells

•proteinuria is probably caused by C5b-C9

• damage to visceral epithelial cell membrane (10 MGN)
• activation of epithelial & mesangial cells ⇒ release of
proteases & oxidants ⇒ capillary wall damage

morphology
• diffuse thickening of glomerular capillary wall
• EM reveals subepithelial deposits
• spikes can be seen (silver stains )
• granular deposits of Ig’s & complement on IF
• GBM becomes progressively thicker and compresses
the capillary lumens

Clinical Course
• usually present with nephrotic syndrome

• important to rule out secondary causes

• proteinuria is nonselective & does not usually respond well to corticosteroids

• course is variable but generally indolent

• only ~ 10% die or progress to CRF within 10

years

Course & prognosis

Remission & exacerbation then Ch. G.N.

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 Minimal Change Disease
Most common in children
Etiology:
Idiopathic
Drugs – NSAID
Toxins – Mercury, Lead
Infections – HIV, Mononucleosis
Tumors – Hodgkin disease
Patient usually normotensive, nephrotic sediment, normal renal function.
(Lipoid Nephrosis)
• peak incidence 2-6 years of age
• MC cause of nephrotic syndrome in children
• sometimes follows a respiratory infection or vaccination
• ⇑ incidence in patients with Hodgkin disease
• morphology
• glomeruli are normal by light microscopy
• epithelial cells exhibit diffuse loss of foot processes on EM
• proximal tubular cells are often laden with lipid
• no Ig or complement deposits detected by IF
etiology & pathogenesis
• evidence indicates an immune mechanism
•immune dysfunction ⇒ circulating cytokine ⇒ injures
visceral epithelial cells ⇒ proteinuria
• some cases are caused by mutations in genes that
encode slit diaphragm proteins
clinical course
• massive proteinuria, mostly albumin
• renal function remains good, usually no ⇑ BP or hematuria
• most children exhibit a dramatic response to cortico- steroid
• long-term prognosis is excellent

Membranoproliferative Glomerulonephritis
Membranoproliferative glomerulonephritis (MPGN) can
present with the nephrotic syndrome, nephritic syndrome,
or, most often, a mixture of the two.
The two most common variants of MPGN are
 Type I MPGN (also called mesangiocapillary GN)
Type II MPGN (also called dense deposit disease).

Type I is much more common than type II, which is a rare

Characterized by
alterations in the GBM,
proliferation of glomerular cells &
 leukocyte infiltration

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 MPGN accounts for 10-20% of cases of nephrotic syndrome in children & young
adults

Often present with a combined nephritc/nephrotic picture

 May be primary or secondary MPGN

 Primary MPGN is divided into types I & II

Pathogenesis
type I MPGN
• deposition of immune complexes with activation of both classical & alternative
complement pathways
• Ag’s involved in primary MPGN are unknown

type II MPGN
• ⇓ serum C3, factor B & properidin, but normal serum C1 & C4 ⇒ activation of
alternative complement pathway
• > 70% of patients have C3 nephritic factor (C3NeF)
•0 C3NeF stabilizes alternative pathway C3 convertase

Course : remissions & exacerbations finally end in chronic renal failure.

Morphology
 glomeruli are enlarged, hypercellular & lobulated
glomerular capillary wall has a “double contour” or “tram-track” appearance caused by
duplication of the GBM with mesangial & monocyte interposition

EM &IF
Type I MPGN
 subendothelial electron-dense deposits
 granular deposits of C3 and often IgG, C1q & C4

Type II MPGN
 lamina densa is extremely electron-dense (dense-deposit disease)
 C3 is present in the GBM & mesangium (mesangial rings)
IgG, C1q & C4 are usually absent Diseases of Urinary System 02

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 Diseases of the Tubules & Interstitium
• May occur secondary to :
1. glomerular disease
2. Vascular disease
3. Cystic disease
4. Metabolic :DM
• Primary interstitial Nephritis

Pyelonephritis
This means suppurative inflammation of the pelvicalyceal ayatem and the renal
parenchyma; it is usually bilateral.
affects the women more than men.
Most commonly, it occurs as a result of urinary tract infection.
Incidence
About 3 to 7 out of 10,000 people.
Predisposing factors
• Obstruction of the urinary tract with stasis of urine
• vesicoureteric reflux:
)Normally, the urine does not ascend along the ureters during micturition due to
the oblique course of the intravesical portion of the ureter, which provide a
sphincter-like effect during contraction of the bladder.) If this effect is disturbed
due to congenital or acquired reasons, the urine will ascend along the ureter and
may even reach the kidneys during bladder emptying.
• Bilharsisis.
• Instrumentation of the urinary tract.
• Diabetes mellitus due to ???
• Female more due to short urethra.
• Pregnancy due to hormonal relaxation of smooth muscle and pressure of the
gravid uterus.

Causative organism :
any pyogenic bacteria as E.coli, B. proteus, B pyocyaneus, Klebsiella and Strop .
foecalia.

Routes of infection:
1. Ascending infection from the lower urinary tract.
2. Lymphatic spread from the intestinal tracL
3. Blood borne infection complicating boils or carbuncles.

Pathology:
Acute pyelonephritis
Chronic pyelonephritis

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Acute pyelonephritis
Grossly:
The plevicalyceal system is acutely inflamed,
the renal parenchyma shows multiple foci of suppuration which appear as yellow streaks
radiating from the renal papillae, to expand into "abscesses" in the cortex.

Microscopically:
The pelvicalyceal system is acutely inflamed.
The renal parenchyma is congested and infiltrated by neutrophils which collect in
the interstitial tissue or within the tubular lumena to form abscesses.

Fate :
It may resolve,
kill by acute renal failure or
progress to chronic pyelonephritis

Chronic pyelonephritis
Chronic pyelonephritis results when the kidneys become increasingly damaged due to
repeated urinary infections. Or unresolved acute attack

Incidence
1 in 4 of the people who are diagnosed as having chronic kidney failure have chronic
pyelonephritis.

Grossly :
The kidneys are unequally shrunken with multiple irregular depressed scars
On cut section, these scars extend from deformed calyces towards the surface .
Thickened,opaque pelvicalyceal mucosa

Microscopically:
Periglomerular fibrosis.
Tubular atrophy .
In foci tubules are dilated and filled with hyaline casts giving an appearance reseinbling
thyroid follicles ( thyroidization).
Infiltration of interstitial tissue by chronic inflmmatory cells and neutrophils.

Tubulointerstitial nephritis caused by drugs

Drugs may produce renal injury by three mechanisms:
1. An immunologic (allergic, hypersensitivity) reaction leading to an
acute interstitial nephritis.
2. Direct nephrotoxicity leading to
acute tubular necrosis.
3. Slowly progressive damage to the tubules leading to a

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 chronic tubulointerstitial nephritis.

Acute drug induced tubulointerstitial nephritis

may be induced by
synthetic penicillins (methicillin, ampicillin),
sulfonamides, rifampin, diuretics (thiazides)
and non steroidal antin-flammatory drugs (phenyl butazone).
It is characterized clinically by
acute renal insufficiency that typically starts two weeks after the beginning of drug
administration.
Acute tubular necrosis, due to direct nephrotoxicity
may be induced by
antibiotics (gentamicin) and
antifungal agents (amphotericin B).
It leads to acute renal failure.

Chronic tubulointerstitial nephritis

may be induced by
heavy usage of analgesic , mainly those containing phenacetin (analgesic nephropathy).
It may end in chronic renal failure.

Acute tubular necrosis ATN

Ichemia and exposure to nephrotoxins that poison the kidney are the two main causative
agents of acute tubular necrosis
Two types
1. anoxic tubular necrosis (lower nephron nephrosis)
2. toxic tubular necrosis

Anoxic tubular necrosis may be caused by:

1. Mismatched blood transfusion.
2. Crush injuries.
3. Burns.
4. Shock.

Toxic tubular necrosis may be caused by:

1. Poisons eg mercuric chloride, phosphorous, carbon tetrachloride, insecticides.
2. Some drugs eg. gentamicin, amphotericin B.

VASCULAR DISEASES OF
THE KIDNEY

Renal Artery Stenosis

Unilateral renal artery stenosis accounts for 2% to 5% of renal hypertension, resulting
from excessive renin secretion by the involved kidney.

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70% of stenoses are caused by obstructive atheromatous plaques at the origin of the renal
artery
The remainder by fibromuscular dysplasia.
Fibro or fibromuscular thickening of intema,media or adventia (3 types:intimal,medial or
advential)
Ischaemic kidney
Small size due to ischemic atrophy
Arteries in ischemic kidney are protected from high pressure
Contra lateral non ischemic kidney
Arteries will show hyaline arteriolosclerosis
Bilateral cortical necrosis
very rare . ischaemic in origin, it appears probable that vascular spasm followed by
thrombosis.
Causes:
1. Toxaemia of pregnancy.
2. Severe infections: Such as pneumonia, diphtheria and scarlet fever.

Grossly:
cortex of both kidneys, with the exception of a very thin surface layer (supplied
by the capsular arteries), is bright yellow outlined with red.

Microscopically:
coagulative necrosis of the cortex of both kidneys.

Clinically:
There is oliguria or anuria with the development of acute renal failure.

Necrosis of the renal papillae

Papillary necrosis
It is a rare condition
there is necrosis of the papillae of both kidneys.
Sometimes it is accompanied by necrosis of the medulla
and in this case, the disease is called renal medullary necrosis.

It is an ischaemic necrosis
may be due to an accompanying pyelonephritis due to some predisposing factors such as
1. diabetes mellitus,
2. excess intake of phenacetine or
3. chronic alcoholism.

HYDRONEPHROSIS

It is the dilatation of the pelvis and calyces of the kidney leading to pressure atrophy of
the kidney tissue.

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It is due to gradual, incomplete or intermittent obstruction to the flow of urine.

Grossly: The kidney is enlarged in size, the outer surface

May be lobulated. The pelvis and calyces are dilated
with, atrophy and fibrosis of the renal tissue.

Microscopically:
There is atrophy of the tubules and the glomeruli with fibrosis.

Causes of hydronephrosis:

In the urethra: leading to bilateral hydroureter and hydronephrosis.

1.Nodular hyperplasia of the prostate and cancer prostate.
2.Stricture of the urethra wether congenital, traumatic or due to gonorrhea.

In the urinary bladder: If the cause is in the bladder neck it will cause bilateral
hydronephrosis, but elsewhere it will cause unilateral hydronephrosis.
1.Bilharzial stricture: Either in the ureteric orifice or causing bladder neck obstruction.
2.A large stone in the urinary bladder.
3.Tumours: As carcinoma or papilloma of the urinary bladder.

In the ureter: Leading to unilateral hydroureter and hydronephrosis:

1.Congenital causes as congenital stricture or aberrant renal artery pressing the ureter.
2.Stone in the ureter,
3.Bilharzial stricture.
4.Tuberculosis of the ureter. .
5.Endometriosis with pelvic lesions, followed by scarring.
6.Cancer cervix in females infiltrating the ureter.
7.Ectopic kidney leading to kinking of the ureter.
8. Retroperitoneal fibrosis: It is an idiopthic disease leading to the formation of dense
fibrous tissue extending from the lower part of the vertebral column and extends laterally
to involve the ureter.
Renal Stones
UROLITHIASIS
Renal calculi
Risk Factors
– Increased conc. of solutes
– change in urinary Ph
– decreased urinary volume
– infection

Types
1.Calcium oxalate(phosphate)stones 75%
)hypercalcinuria, hypercalcemia, excess)
2.Magnesium Ammonium phosphate stones10-15%
)alkaline urine due to infection(

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3.Uric acid stones 6%
) gout, leukemias, acidic urine)
4.Cystine stones 1-2%
Pathogenesis :
For calcium stones
↑ urine conc. of the stone constituent (supersaturation)
Hypercalcemia with hypercalcuria
hyperparathyroidism,
bone metastases,
↑ Ca++ absorption
↓ renal reabsorption
Hypercalcuria without hypercalcemia

For Magnesium Ammonium phosphate stones

Infection with urea splitting organism →alkaline urine →ppt.Mg Amm Phosphate

For uric acid stones

Gout & leukemia,lymphomas
50% form without hyperuricuria
unexplained tendency to excrete a persistantly acid urine pH 5.5 favouring stone
formation

For cystine stones

genetically determined defect in renal transport of amino acids

Effects &complications of renal stones

Renal colic
Hematuria
Obstruction
Infection
Stricture
Squamous metaplasia

TUMOURS OF THE KIDNEY

TUMOURS OF THE KIDNEY
Tumours of the kidney tissue
&
Tumours of the renal pelvis
Tumours of the kidney tissue:
Benign tumours
adenoma, fibroma, lipoma, angiomyolipoma and oncocytoma.
Malignant tumours:
i) Primary
- Renal cell carcinoma (Hypernephroma).
- Embryoma (Wilms tumour or Nephroblastoma)
ii) Secondaries from:

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- Carcinomas of the lung, breast and prostate.
- Sarcomas, like osteosarcoma.
- Malignant melanoma and choriocarcinoma.
Renal Cell Carcinoma
6th to 7th decade
Male predominance 3:1
Yellow round mass, 3 -15 cm
Often invade renal vein and extend into the inferior vena cava
Chromosome 13
General features
A tumour which arises from the epithelial cells of the renal tubules

Renal cell carcinoma is generally tumor of adults >55 to 60 y

The male to female ratio is about 2:1

One of the many peculiarities of renal cell carcinoma is its occasional regression in the
absence of all treatment, a phenomenon found also with gestational choriocarcinoma,
malignant melanoma, neuroblastoma,

Renal cell carcinoma is the most common "recipient" of the curious phenomenon of
metastasis of a cancer into another cancer. Lung carcinoma is the most common "donor,"
the resulting microscopic appearance leading to interesting problems of interpretation

Conditions that may be complicated by renal cellcarcinoma are the following:

Von HippelLindau (VHL) disease. Renal cell carcinoma occurs in about 40% to 50% of
individuals with this syndrome.

Acquired cystic disease.

Half of the patients on long term dialysis develop an acquired form of polycystic
renal disease, which in a few cases has been complicated by the appearance of renal cell
adenomas and carcinomas.

Adult form of polycystic kidney disease

Von Hippel-Lindau (VHL) syndrome

VHL
Hemangioblastomas of the cerebellum and retina.

Renal cysts.

Renal cell carcinomas (nearly all, if they live long enough) bilateral, often multiple.

Clinical features
Renal carcinoma usually presents with
Hematuria (59%)

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Flank pain (41%), or
Abdominal mass (45%).
Weight loss (28%),
Anemia (21%),
Fever (7%), and
Symptoms caused by a metastatic deposit (10%).

Grossly
most renal cell carcinomas are well delineated and centered on the cortex
In about 5% of the cases, multiple tumor nodules are seen scattered throughout the organ
In a typical case, the cut surface shows a solid golden yellow tumor sharply separated
from the surrounding tissues by a fibrous pseudocapsule
Hemorrhage, necrosis, calcification, and cystic change

Microscopically,
the tumor cells may be large with clear cytoplasm, resulting from the accumulation of
glycogen (clear cell type) or
may be smaller in size with granula cytoplasm (granular cell type), or
most often there is a mixture of clear and granular cells (mixed cell type).

The stroma of the tumour is scanty, very vascular with areas of haemorrhage and
necrosis.

Tubular, papillary, and cystic formations may be present.

Spread:
 Locally to adjacent renal tissue more to pelvis and late to capsule
 Hematogenous spread to-------- .
– Invasion of left testicular vein in males will cause left side varicocele
 Lymphatic

Paraneoplastic syndrome:
RCC is known for its hormonal & hormone like effect
e.g. it can produce parathyroid like hormone
hypercalcemia

Wilm ’s tumor
Also known as nephroblastoma (currently the preferred term), embryoma,
carcinosarcoma, adenosarcoma, and adenomyosarcoma.

Childhood tumor .Primarily in infants,

50% before the age of 3 years and 90% before the age of 6 years
Only exceptionally seen as a congenital neoplasm

No appreciable sex predilection.

There are 2 specific genetic loci predisposing to Wilms' tumor.

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 Chromosome 1 -loss of cancer suppression gene WT -1

Clinical features
The classic clinical presentation of Wilms'
an abdominal mass felt by the mother
Hypertension
Proteinuria
Hematuria and pain are rare.

Grossly
solitary, well circumscribed, rounded,
soft.
variable size
rapidly growing, destroying the kidney
infiltrating the renal capsule.
Infiltration of renal pelvis & ureter is rare & late
The cut section is solid and pale gray or tan
cystic change, necrosis, and hemorrhage

Microscopically
Most Wilms' tumors show a representation of three major components:
Undifferentiated blastema,
The blastematous areas are extremely cellular and composed of small round-to-oval
primitive cells;

Mesenchymal (stromal) tissue

The mesenchymal elements usually have a spindle-cell fibroblast-like configuration
smooth muscle and skeletal muscle.

Epithelial tissue.
formation of embryonic tubular (and sometimes glomerular) structures that closely
recapitulate the appearance of normal developing metanephric tubules (and glomeruli)

but the proportions vary widely. Some tumors are biphasic, and still
others are monophasic (monomorphous).

Spread and metastases

In advanced cases, local spread occurs in the perirenal soft tissues. From here, the tumor
may involve
the adrenal glands,
bowel, liver,
vertebrae, and paraspinal region;
Invasion of the renal vein is common,
but extension into the renal pelvis or ureter is a rare and late event.
Metastases in regional lymph nodes are found in 15% of the cases.

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The most common sites of distant metastases are
lungs, liver, and peritoneum.
bone metastases in only 1% of the cases

Tumours of the renal pelvis:

Benign such as
villous papilloma, haemangioma and fibroma.
(2) Malignant
i) Primary carcinoma such as transitional cell carcinoma, squamous cell carcinoma
sacroma (rare).
ii) Secondary (rare).

DISEASES OF THE URINARY BLADDER

Congenital anomalies

1. Ectopia vesica (exostrophy:

The anterior bladder wall and the overlying part of the anterior abdominal
wall are defective,
It may be complicated by
urinary tract infection,
squamous or glandular metaplasia of the urothelium and
carcinomas.

2. Epispadius:
The urethra opens on the dorsum of the penis.
3. Hypospadius:
The urethra opens on the ventral surface of the penis.
4. Patent urachus:
A fistulous tract between bladder & umbilicus, discharging urine
5. Valves (mucosal folds) in the posterior urethra:
Which may lead to obstruction.

CYSTITIS
Clinical Manifestations:
frequency, pain, dysuria
Causes:
1Infections: E. coli, Proteus, et al; TB, Candida, Chlamydia, Schistosomiasis,
Adenovirus
2 Radiation & chemotherapy
3 Prolonged catheterization.
Morphologic Types:
Acute: nonspecific, hemorrhagic, suppurative, or ulcerative
Chronic: nonspecific, cystitis follicularis & eosinophilic
cystitis

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Special Forms of Cystitis:
Interstitial Cystitis (Hunner’s ulcer)
painful chronic cystitis MC seen in women

Predisposing factors:
1. Bilharziasis
2. Stasis of urine: due to obstruction nodular hyperplasia of prostate, stricture of the
urethra and tumours of the urinary bladder.
3. Inflammation of nearby organs, such as kidneys, ureters, prostate, vulva, vagina,
cervix and urethra.
4. Trauma to the urinary bladder by stones or catheter.
5. General diseases, such as diabetes.
6. Females are more commonly affected due to short wide urethra
Grossly :
wall is thickened , oedematous, red and congested
and may be areas of haemorrhage,ulceration and necrosis.

Chronic non specific cystitis: may follow acute or may start as such
Grossly : The wall is thickened, congested with increased fibrosis granularity of the
mucosa reduction of the lumen of the urinary bladder.

In chronic cystitis one of the following lesions may be added t

Leukoplakia: whitish patches due to squamous metaplasia with keratinisation. occurs
usually due to irritation stones, or bilharzial ova.

Follicular cystitis: In which the mucosa of the trigone shows minute greyish nodules due
to the presence of lymphoid follicles even with germ centers, in the sub-epithelial
tissues.

Calcareous (encrusted) cystitis:

The trigone and surrounding parts show multiple, whitish, hard, granular elevated
patches due to precipitation of Ca salts in the mucosa. It is usually accompanied with
alkaline urine.

Emphysematous cystitis:
caused by gas-forming bacteria
associated with gas filled vesicles in the bladder wall.
About 50% of the patients are diabetic.

Malakoplakia:
rare condition associated with immune deficiency states.
The mucosa of trigone shows multiple nodular yellow soft thickenings 1-4 cm
Microscopically,
chronic inflammatory cells
foreign body giant cells containing calcified material known as Michaelis - Gutmann
bodies ( an end result of bacterial degradation.)

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 Tumours of the urinary bladder

Benign tumours
• Transitional cell papilloma:
commonly near the ureteric orifices and bladder neck.
It usually recurs after removal
considered potentially malignant.
It is considered by some authors as grade I carcinoma

Grossly: multiple delicate finger-like processes.

Microscopically: multiple delicate vascular connective tissue stroma, covered by layers

of transitional epithelial , regularly arranged , no criteria of malignancy.

• Inverted papilloma
a benign epithelial tumor, more in adult and elderly males,
mostly located in the trigone, bladder neck, or prostatic urethra.
It is usually solitary
presents with haematuria and obstruction.

• Others:
o Fibroma,
o Leiomyoma,
o Rhabdomyoma,
o Neurofibroma,
o Angioma and
o Myxoma

Malignant Tumors
Are common occurring more in males above the age of 40 years

Precancerous lesions:
a) Urinary bladder bilharziasis: It may be due to :
Mechanical irritation of the ova
Tryptophan metabolites as a carcinogenic agents which are usually present in high
concentration in the urine.
Metaplastic changes including cystic glandularis squamous metaplasia.
b) Transitional cell papilloma.
c) Aniline dyes used by dye workers.
d) Cigarette smoking.
e) Chronic irritation by stones, chronic cystitis.
f) Leucoplakia.
g) Congenital anomalies (ectopia vesica).

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Site:
The region of the trigone, as a consequence, partial or complete blockage of one
or both ureters is frequent.
Types :
Transitional cell carcinoma
Squamous cell carcinoma
Adenocarcinoma

TRANSITIONAL CELL TUMORS of the

URINARY BLADDER
comprise ~ 90% of all bladder tumors
~ 80% of patients with TCC are between 50 - 80 years old

Gross Morphology:
The better differentiated urothelial neoplasms commonly project into the lumen
and have a delicate papillary appearance.
In contrast poorly differentiated neoplasms are solid ulcerative lesions that
frequently show evidence of infiltration of the bladder wall.

Microscopic appearance:
Over 90% are transitional cell carcinoma.
Squamous or glandular differentiation commonly occur in transitional cell
carcinoma (especially in invasive types).
Grading :
The International World Health Organisation histologic grading system for
urothelial neoplasms recognize 4
histologic grades:
Grade I transitional cell carcinoma shows
• well formed papillary structures
• lined by epithelium that is cytologically normal but thicker than 7 layers.
• Invasion is uncommon.

Grade II transitional cell carcinoma shows

• well formed papillary and solid areas.
• mild to moderate cytologic atypia
• a greater degree of pleomorphism.
• Invasion may occur.

Grade III transitional cell carcinoma

• predominantly solid invasive growth pattern
• with or without a papillary structure
• shows cytologic anaplasia
• high mitotic rate.

Grade IV transitional cell carcinoma:

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 • Most of these lesions are sessile, cauliflower-like, necrotic and ulcerated.
• Microscopically papillary areas are absent,
• cellular atypia and pleomorphism are so marked that the transitional cell nature
may be obscured.
• Mitotic figures are frequent.

Prognosis:
depends on histologic grade & stage
papillomas & grade I tumors – 98% 10 yr. survival rate
grade III tumors – 40% 10 yr. survival rate

Squamous Cell Carcinoma of the

URINARY BLADDER
It is common where bilharziasis is common (squamous metaplasia).

Well differentiated keratinizing squamous cell carcinoma tends to form large bulky mass.
Since foci of squamous cell differentiation are common in high grade transitional
carcinoma, the term squamous cell carcinoma should be reserved for those tumours that
are squamous throughout.
Adenocarcinoma:
May arise from:
a) urachal remanents in the dome of the bladder.
2) areas of cystitis glandularis. (after metaplasia by bilharziasis).
Non epithelial neonlasms:
a) Paraganglioma (pheochromocytoma).
b) Mesenchymal neoplasms:
i) Leiomyoma and leiomyosarcoma.
ii) Embryonal rhabdomyosarcoma (sarcoma botroides) in young children.


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