The kidney

Bereket
Acute renal failure
- It implies a rapid & frequently reversible deterio-
ration of renal function

- Acute renal failure is dominated by oliguria or

anuria (reduced or no urine flow), with recent
onset of azotemia. It can result from glomerular,
interstitial or vascular injury or acute tubular
necrosis
Chronic renal failure
It characterized by prolonged symptoms &
signs of uremia, is the end result of all
chronic parenchymal diseases
Chronic renal failure progresses through
four stages that merge into one other
1. In diminished renal reserve , the GFR is
about 50% of normal. Serum BUN & crea-
tinine values are normal, & the patients
are asymptomatic.
2. In renal insufficiency, the GFR is 20% to
50% of normal. Azotemia appears, usually
associated with anemia & hypertension.
3. In renal failure , the GFR is less than 20%
to 25% of normal, the kidneys can not
regulate volume & solute composition &
patients develop edema, metabolic acido-
sis & hypocalcemia. Overt uremia may en-
sue.
4. In end-stage renal disease , the GFR is
less than 5% of normal; this is the terminal
stage of uremia
• Renal tubular defects are dominated by
polyuria (excessive urine formation), noc-
turia, & electrolyte disorders (eg metabolic
acidosis). They are the result of either dis-
eases that directly affect tubular structure
or defects in specific tubular functions.
• Urinary tract infection is characterized
by bacteriuria & pyuria (bacteria & leuko-
cytes in the urine). The infection may be
asymptomatic or symptomatic, & it may af-
fect the kidney (pyelonephritis) or the
bladder (cystitis).
• Nephrolithiasis (renal stone) is mani-
fested by renal colic, hematuria, & recur-
rent stone formation.
Congenital anomalies
- About 10% of all people are born with po-
tentially significant malformations of the
urinary system.
Agenesis of the kidney
- Total bilateral agenesis is incompatible
with life. But unilateral agenesis is un-
common anomaly but is compatible with
normal life . The opposite kidney is usually
enlarged as a result of compensatory hy-
pertrophy later leading to chronic renal
failure.
Hypoplasia
- It refers to failure of the kidneys to develop
into a normal size. It may occur bilaterally
but is more commonly unilateral. A truly
hypoplastic kidney shows no scars & has
a reduced number of renal lobes & pyra-
mids.
Ectopic kidneys
- Ectopic kidneys may be found at abnormally low
levels. The kidneys lie either just above the
pelvic brim or sometimes within the pelvis. They
are usually normal. B/c of their abnormal posi-
tion, kinking or tortuosity of the ureters may
cause some obstruction to urinary flow which
predisposes to bacterial infections.
Horseshoe Kidneys
- 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.
- The anomaly is common & is found in about 1 in
500 to 1000 autopsies.
- 90% of such kidneys are fused at the lower pole,
& 10% are fused at the upper pole.
Cystic Diseases of the Kidney
- Cystic disease of the kidney are heteroge-
nous group comprising hereditary, devel-
opmental & acquired disorders.
Cystic renal dysplasia
- This sporadic disorder is due to an abnormality in
metanephric differentiation characterized histo-
logicaly by the persistence in the kidney of ab-
normal structures – cartilage, undifferentiated
mesenchyma, & immature collecting ductules &
by abnormal lobar organization.

- Dysplasia can be unilateral or bilateral & is al-

most always cystic
• In gross appearance, the kidney is usually
enlarged & multicystic.
Autosomal-Dominant (adult) Polycystic Kidney Disease
- Inherited autosomal dominant trait
- Commonest form of congenital cystic disease
- The kidneys contain bilateral large number of cysts
which enlarge throughout life & destroy the renal
parenchyma(due to pressure atrophy) & cause renal fail-
ure.
- 50% of patients develop HTN(pressure atrophy’s effect
on the vessels) or uremia in fourth or fifth decade of life.
- In 90% of families, PKD1, the defective gene, is on the short arm of
chromosome 16. This gene encodes a large and complex cell
membrane-associated protein, called polycystin-1, that is mainly ex-
tracellular. The polycystin molecule has regions of homology to pro-
teins known to be involved in cell-cell or cell-matrix adhesion

- it is thought that the resultant defects in cell-matrix interactions may

lead to alterations in growth, differentiation, and matrix production
by tubular epithelial cells and to cyst formation.

- The PKD2 gene, implicated in 10% of all cases, resides on chromo-

some 4 and encodes polycystin-2, a 968-amino acid protein. Al-
though structurally distinct, polycystins 1 and 2 are believed to act
together by forming heterodimers. Thus, mutation in either gene
gives rise to the same phenotype
Morphology
- The kidneys may achieve enormous size, and weights of
up to 4 kg for each kidney. These very large kidneys are
readily palpable abdominally as masses extending into
the pelvis.
- On gross examination the kidney seems to be composed
solely of a mass of cysts of varying sizes up to 3 or 4 cm
in diameter with no intervening parenchyma.
- Microscopic examination reveals some normal
parenchyma dispersed among the cysts.
- Cysts may arise at any level of the nephron, from tubules
to collecting ducts.
Clinical Course
- Polycystic kidney disease in adults usually does not produce symp-
toms until the fourth decade, by which time the kidneys are quite
large.
- The most common complaint of the patient is flank pain or at least a
heavy, dragging sensation.
- Sometimes attention is first drawn to the lesion by palpation of an
abdominal mass.
- The most important complications, because of their deleterious effect
on already marginal renal function, are hypertension and urinary in-
fection. Hypertension of varying severity develops in about 75% of
patients.
- End-stage renal failure occurs at about age 50, but there is wide
variation in the course of this disorder. Those who develop renal
failure are treated by renal transplantation. Death usually results
from uremia or hypertensive complications.
Pateints tend to have extrarenal anomalies such as
o Polycytic liver disease -Asymptomatic liver cysts occur in
one third of patients

o Intraranial berry aneurysm- Saccular aneurysms of the

circle of Willis) are present in 10% to 30% of patients,
and these individuals have a high incidence of sub-
arachnoid hemorrhage.

o Mitral valve prolapse

Autosomal-Recessive (Childhood) Poly-
cystic Kidney Disease
• It is inherited in an autosomal recessive pattern, giving a
25% recurrence risk for parents having subsequent chil-
dren.
• The kidneys are affected bilaterally, so that in utero,
there is typically oligohydraminos because of poor renal
function and failure to form significant amounts of fetal
urine. The most significant result from oligohydramnios is
pulmonary hypoplasia, so that newborns do not have suf-
ficient lung capacity to survive, irrespective of any at-
tempt to treat renal failure.
• Grossly, the kidneys are markedly enlarged and tend to
fill the retroperitoneum and displace abdominal contents.
The kidneys tend to be symmetrically enlarged. The
cysts are quite small and uniform, perhaps 1 to 2 mm on
average.
• Microscopically, the characteristic finding in the later third
trimester is cystic change of collecting tubules with the
cysts elongated and radially arranged. The few remain-
ing glomeruli are not involved by the cysts.
• A helpful finding at autopsy is the presence of
congenital hepatic fibrosis, which accompanies
RPKD
Simple cysts
- These occur as multiple or single , usually
cortical cystic spaces that vary widely in
diameter. They are commonly 1 to 5cm in
diameter
- They are usually postmortem finding with-
out clinical significance
Malignant tumors
Renal cell carcinoma/hypernephroma
- Account for 85% or renal cancers in adults
- Common in sixth & seventh decade of life
Epidemiology
- Tobacco is the most important risk factor .

Other risks include

- obesity,
- HTN,
- unopposed estrogen therapy,
- exposure to asbesto

A genetic predisposition is indicated by a strong

association with von Hippel-Lindau disease.
Classification
Clear cell (nonpaippilary) carcinoma (70-
80%)
Papillary carcinoma(10-15%)
Chromophobe renal cancer
Morphology
- Most commonly affects poles
- They are spherical masses composed of bright
yellow-gray-white tissue. The yellow color is due
to accumulation of lipid
- As tumor enlarges it may bulge into calyces &
pelvis
- It has a tendency to invade the renal vein &
grow as a solid column of cells extends into the
inferior vena cava & rarely, into the right atrium.
Clinical features
The three diagnostic features
- Costovertebral angle pain
- Palpable mass
- Hematuria
- Constituitional symptomes such as fever, malaise, weak-
ness & weight loss occur
- Renal cell ca produces a number of paraneoplastic syn-
dromes – polycythemia, HTN, Cushing syndrome etc
- The tumor has tendency to metastasize widely before
giving rise to any local sign & symptom
- The 5 yr survival is about 45-70%
Nephroblastoma /wilm’s tumor
- Embryonic tumor derived from the renal
blastema with features of rapidly growing sar-
coma
- Most common in the first 3 yrs of life
- One of the commonest malignant tumors in
childhood
Lower Urinary Tract
Ureter
Congenital anomalies
 Double ureters
 Ureteropelvic junction obstruction
 Hydroureter – dilation & tortuosity of the ureter
Inflammation
- ureteritis may develop as one component of uri-
nary tract infection
Obstructive lesions
Different pathologies obstruct ureter & result in
hydroureter & hydronephrosis
Causes
 Intrinsic
urinary calculi
 Extrensic
tumors of rectum, prostate & bladder
Tumors
- Primary tumors of the ureter are usually
transitional cell carcinomas
Urinary bladder
Congenital anomalies
 Diverticula
- out pouching of the bladder mucosa
- It could be congenital or acquired from persis-
tent urethral obstruction
- The diverticula as they constituent sites of uri-
nary stasis , predispose to infection, formation of
bladder calculi & vesicouretral reflux.
 Exstrophy
- Presence of a developmental failure in the ante-
rior abdominal wall & bladder so that the bladder
either communicates directly through a large de-
fect with the surface of the body or lies as an
opened sac
- Infection & pyelonephritis with predisposition to
adenocarcinoma are important sequelae
 Persistent urachus
-The urachus may remain patent in part or in
whole
- When totally patent, Fistulous tract is created that
connects the bladder with umbilicus. Partial re-
tention results in a diverticulum arising from the
dome of the bladder. Or the central area may
persist & present as a cyst
- Adenocarcinoma develop in these urachal remi-
nant.
Inflammation
cystitis
- Cystitis is common in young women of reproductive age
& in older age groups of both sexes
- Common etiologic agents include E.coli, Proteus, Kleib-
siela, enterobacter
- Women are more likely to develop cystitis as a result of
their shorter urethras
- Other causes – tuberculous cystitis, candida albicans ,
schistosoma hematobium,
- Radiation & trauma due to instrumentation cause cystitis,
which is often sterile.
- Predisposing factors include bladder calculi, uri-
nary obstruction, diabetes mellitus , instrumen-
tation & immune deficiency
Morphology
- There is hypermia of the mucosa associ-
ated with exudate
Clinical features
- All cystitis are characterized by a triad of
symptoms
 Frequency
 Lower abdominal pain localized on supra-
pubic region
 Dysuria – pain or burning sensation during
micturation
- Cystitis is important as antecedents to
pyelonephritis
Neoplasms
Urothelial (transitional cell) tumors
- They account for 90% of all bladder tumors
- They range from small benign tumor to aggressive can-
cers
Pathogenesis
- 80% of patients are b/n age of 50-80 yrs
- Many factors are implicated in causation of transitional
cancer
 Cigarette smoking
 Industrial exposure to arylamines
 Long term use of cyclophosphamide
Morphology
Most bladder tumors are papillary (as opposed to
the predominant non papillary(clear cell type) in kid-
ney’s renal cell carcinoma.
Squamous cell carcinoma
- Arise from metaplastic squamous epithe-
lium. This change occurs most often in as-
sociation with calculi & schistosomaisis
Clinical features
- Bladder tumors classically produce pain-
less hematuria
- But frequency, dysuria & urgency occa-
sionally accompany the hematuria
- Characteristically urothelial tumors tend to
recur after excision
- Prognosis depend on stage & grade at di-
agnosis
Obstruction
- A great variety of intrinsic & extrinsic diseases of bladder can
cause partial or complete vesical obstruction

 Enlargment of prostate either due to hyperplasia or carci-

noma
 Urethral strictures

 Cystocele of the bladder

 Bladder tumor
 Mechanical obstruction by foreign bodies & calculi
 Neurogenic bladder
Urethra
Inflammations
- Urethritis is classically divided into gono-
coccal & non gonococcal urethritis
- Gonococcal urethritis is one of the earliest
manifestation of this venereal(STD) infection
- Non gonococcal urethritis is common & can
be caused by a variety of bacteria , among
which E.coli & other enteric organisms pre-
dominate