Renal 3 Flashcards
is a hereditary disorder characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyma and cause renal failure.
AUTOSOMAL DOMINANT (ADULT) POLYCYSTIC KIDNEY DISEASE
Inheritance pattern ADKPD
autosomal dominant
with high penetrance
ADKPD bilateral or unilateral?
Bilateral
PKD1 gene is located on
chromosome 16p13.3
Encodes an integral membrane protein named
polycystin-1.
PKD1 gene
Polycystin-1 is expressed in tubular epithelial cells,
particularly those of the
distal nephron
Located on chromosome 4q21.
PKD2 gene
PKD2 gene Encodes an integral membrane protein named _______
polycystin-2.
polycystic disease pathogenesis
ciliacentrosome complex
Act as mechanosensor to monitor changes
in fluid flow and shear stress.
single non-motile primary cilium.
Regulate ion flux and cellular behavior,
including cell polarity and proliferation
single non-motile primary cilium.
Gross polycystic kidney disease
● Kidneys are bilaterally and large
- External: mass of cysts with no intervening parenchyma
Microscopic polycystic disease
- The cysts may be filled with a clear, serous fluid or
with turbid, red to brown, sometimes hemorrhagic fluid.
-The cysts arise from the tubules throughout the
nephron and therefore have variable lining
epithelia
clinical features polycystic disease
- asymptomatic (many patients)
- renal colic
- dragging sensation
- insidious onset of hematuria
- proteinuria, polyuria, hypertension
- PKD2: older age, later devt of renal failure
- tend to have extrarenal congenital anomalies.
- azotemia- no symp
- Uremia- w/ symp
most common ARPKD
Perinatal, neonatal
ARPKD is mostly caused by mutations in the
PKHD1 Gene
PKHDA1 gene is located at
chromosome region 6p21-p23
PKHDA1 encodes for
fibrocystin
Gross ARPKD
- kidneys are enlarged and have a smooth external appearance
- sponge-like appearance
microscopic ARPKD
-Cylindrical or less commonly saccular dilation of all
collecting tubules
-The cysts have a uniform lining of cuboidal
cells, reflecting their origin from the collecting ducts.
-In almost all cases, the liver has cysts associated
with portal fibrosis and proliferation of portal bile
ducts.
CLINICAL FEATURES ARPKD
-peculiar hepatic injury characterized by bland periportal fibrosis and
proliferation of well-differentiated biliary ductules, now termed congenital hepatic fibrosis
-older children: portal hypertension with splenomegaly
T or F
Congenital hepatic fibrosis sometimes occurs in the
absence of polycystic kidneys or has been reported
in the presence of adult polycystic kidney disease.
T
2 categories of CYSTIC DISEASES OF RENAL MEDULLA
- Medullary Sponge Kidney
2. Nephronophthisis
medullary sponge kidney is restricted to multiple cystic dilatations of the
collecting ducts in the medulla
MEDULLARY SPONGE KIDNEY
On gross inspections, the papillary ducts in the medulla are
dilated, and small cysts may be
present.
Medullary sponge kidney
-Cysts are lined by
cuboidal epithelium or occasionally by transitional epithelium
This group of progressive renal disorders is
characterized by a variable number of cysts in the
medulla, usually concentrated at the
corticomedullary junction.
NEPHRONOPHTHISIS
is the cause of
the eventual renal insufficiency
cortical tubulointerstitial damage
Three Variants of Nephronophthisis disease complex
are recognized:
- Sporadic, non-familial
- Familial juvenile nephronophthisis (most common)
- Renal-Retinal dysplasia (15%)
NEPHRONOPHTHISIS familial forms
autosomal recessive traits
most common genetic cause of ESRD in
children and young adults.
As a group, nephronophthisis complex
CLINICAL FEATURES OF NEPHRONOPTHISIS
- Polyuria and polydipsia, which reflect a marked defect in the concentrating ability of renal tubules.
- Sodium wasting and tubular acidosis
- Some syndromic variants
syndromic variants nephronophthisis
Ocular motor abnormalities, retinal dystrophy, liver fibrosis and cerebellar abnormalities.
Nephronophthisis Expected course is ____
progression to ESRD in 5 to 10 years
mutated in the juvenile forms of nephronophthisis
, NPHP1 to
NPHP11, JBTS2, JBTS3, JBTS9, JBTS11
encode proteins in nephrocystins
NPHP1 to NPHP11
Kidneys are small, have contracted granular
surfaces, and show cysts in the medulla, most
prominently at the corticomedullary junction
-small cysts in the cortex
nephronophthisis
T or F
In nephronophthisis, glomerular structure is preserved
T
T or F
Multicystic renal dysplasia can be unilateral or bilateral. The kidney is usually enlarged, extremely irregular, multicystic
T
Cardinal feature of Multicystic renal dysplasia
presence of islands of undifferentiated
mesenchyme, often with cartilage, and
immature collecting ducts.
Unilateral renal dysplasia
may mimic and lead to surgical exploration and nephrectomy
bilateral multicystic renal dysplasia
renal failure may ultimately result
in acquired cystic disease, the cyts are lined by ______
either hyperplastic or flattened tubular epithelium, and often contain calcium oxalate crystals.
simple cysts
translucent, line by a gray, glistening, smooth membrane, and filled with clear fluid
Simple cysts micro
single layer of cuboidal or flattened cuboidal epithelium (no clinical significance)
T or F
Obstructive lesions of the urinary tract increase susceptibility to infection and to stone formation
T
T or F
Unrelieved obstruction almost always lead to permanent renal atrophy, termed hydronephrosis or obstructive uropathy
T
Dilatation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the
outflow of urine
Hydropnephrosis
when the obstruction is sudden and complete, it leads to
mild dilation of the pelvis and calyces and sometimes to atrophy of the renal parenchyma
When the obstruction is subtotal or intermittent,
progressive dilation ensues, giving rise to hydropnephrosis
chronic cases of urinary obstruction
cortical tubular atrophy with marked diffuse interstitial fibrosis
calculi lodged in the ureters may give rise to
renal colic
is a useful noninvasive technique of obstructive uropathy
Ultrasonography
earliest manifestation of bilateral partial obstruction
inability to concentrate urine reflected by polyuria and nocturia
complete bilateral obstruction of rapid onset:
Results in oliguria or anuria and is incompatible with survival unless the obstruction is relieved.
T or F
In urolithiasis, men are affected more than women, and the peak age at onset is between 20 and 30 years
T
characterized by excessive production and excretion of stone-forming substances
inborn errors of metabolism such as cystinuria and primary hyperoxaluria
4 main types of calculi
- calcium stones
- Triple stone/ struvite stone
- Uric acid stones
- Cystine
composed largely of calcium oxalate or calcium oxalate mixed with calcium phosphate
calcium stones
-most common
composed of magnesium ammonium phosphate
Triple stone or struvite stone
most important determinant (stones)
increased urinary concentration of the stones’ constituents
The mechanism of stone formation in this setting involves
‘nucleation’ of calcium
oxalate by uric acid crystals in the
collecting ducts.
Formed largely after infections by urea-splitting
bacteria (e.g., Proteus and some Staphylococci)
that converts urea to ammonia
MAGNESIUM AMMONIUM PHOSPHATE STONES
occupying the large
portions of the renal pelvis are frequently a
consequence of infection.
staghorn calculi
Common in individuals with hyperuricemia, such
as patients with gout, and diseases involving rapid
cell turnover, such as the leukemias and patients
undergoing chemotherapy
uric acid stones
urine of pH below ___ may predispose to uric
acid stones
5.5
T or F
uric acid stones are radiolucent
T
Caused by genetic effects in the renal
reabsorption of amino acids, including cystine,
leading to cystinuria
cystine stones
urolithiasis most favored sites
Renal calyces and pelvis and in the bladder
most common malignant tumor is
__________ followed by _______
renal cell carcinoma; Wilms tumor
Small, discrete adenomas arising from the renal
tubular epithelium
renal papillary adenoma
Benign neoplasms
A. Renal Papillary adenoma
B. Angiomyolipoma
C. Oncocytoma
Malignant neoplasms
A. Renal cell carcinoma
B. Urothelial carcinoma of the renal pelvis
● These small tumors are less than 1.5 cm in diameter
● They are present invariably within the cortex and
appear grossly as pale yellow-gray, discrete, and
well-circumscribed nodules
Renal papillary adenoma
microscopic appearance of renal papillary adenoma
cells are cuboidal to polygonal in shape and have regular, small central nuclei, scanty cytoplasm, and no atypia
Consists of vessels, smooth muscle, and fat originating from perivascular epithelioid cells
Angiomyolipoma
● The clinical importance of angiomyolipoma is due
largely to their susceptibility to
spontaneous hemorrhage
disease caused by loss-of-function
mutations in the TSC1 or TSC2 tumor suppressor
genes.
tuberous sclerosis
● Epithelial neoplasm composed of large eosinophilic
cells having small, round, benign-appearing nuclei
that have large nucleoli.
Oncocytoma
Oncocytoma thought to arise from the
intercalated cells of collecting ducts
Oncocytoma gross appearance
Tumors are tan or mahogany brown, relatively
homogenous, and usually well encapsulated with a central scar in one-third of causes.
T or F
Most renal cancer is sporadic, but unusual forms
of autosomal dominant familial cancers occur,
usually in younger individuals.
T
CLASSIFICATION OF RENAL CELL CARCINOMA:
- Clear cell carcinoma
- Papillary carcinoma
- Chromophobe carcinoma
- Xp11 Translocation carcinoma
- Collecting duct (bellini duct) carcinoma
most common type of renal cell carcinoma
-made up of cells with clear or granular cytoplasm and are non papillary.
Clear cell carcinoma
most: sporadic but can be familial
associated with VHL syndrome, there is loss of sequences on the short arm of chromosome 3
Clear cell carcinoma
characterized by a papillary growth
pattern
Papillary carcinoma
most common cytogenic abnormalities in papillary carcinoma are
Trisomies 7 and 17 and loss of Y in male patients in the sporadic form, and trisomy 7 in the familial form.
T or F
Unlike clear cell carcinomas, papillary
carcinomas are frequently multifocal in
origin
T
composed of cells with prominent cell
membranes and pale eosinophilic
cytoplasm, usually with a halo around
the nucleus.
Chromophobe carcinoma
● genetically distinct (uncommon) subtype of
renal cell carcinoma.
● It often occurs in young patients
Xp11 Translocation carcinoma
defined by translocations of the TFE3 gene
Xp11 translocation carcinoma
How do we differentiate it with papillary CA?
In contrast with the cytoplasm of papillary CA, Xp11 translocation CA has a clear cytoplasm.
Histologically these tumors are
characterized by malignant cells forming
glands enmeshed within a prominent
fibrotic stroma, typically in a medullary
location.
Collecting duct (bellini duct) carcinoma
most reliable clinical feature of renal cell carcinoma
hematuria
