11 ) Polycystic Kidney Disease. Tumors of the kidneys Flashcards Preview

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1

what is the who classification for polycystic kidney disease ?

autosomal recessive
mutation on the 6th chromosome
age of onset from childhood

affects bilateral
equally sized cysts
OBLIGATE hepatic involvement

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autosomal dominant
mutation on the 16th chromosome
or some with alteration of polycystin 1 or 2
PC1 - earlier onset and more severe
PC2 -opposite

affects bilateral
cysts vary in size
multiple extraneal manifestations

age of onset is adulthood over 30 years old

2

what are the clinical manifestation of ARPKD?

frequent heamturea
protruding abdomen due to renal enlargmnet
hepatomegaly

extra renal
-maternal oligohydroaminos - leading to The classical triad of Potter sequence is craniofacial abnormalities (retrognathia , low set ears , flat nose) , clubbed feet, and pulmonary hypoplasia

liver - portal fibrosis - portal hypertension and progressive liver failure

hypertension - unknown cause - difficult to control = congestive heart faille

3

what are the clinical manifestation of ADPKD?

there is chronic renal failure - if there is sharp flank pain cyst rupture
abdominal pain

nephrolithiasis is common

extra renal :
multiple hepatic cysts - full abdominal pain in the right upper quadrant , bloating

also occur in pancreases , spleen , ovary , testicals

cardiovascular
arterial hyeperteniosn - moring headaches
left ventricular hypertrophyy
MITRAL valve prolapse common
colon diverticula - abdominal pain , inguinal hernias

cerebral berry aneurysm - due to hypertension
= anterior communicating artery = bitemporal loss of vision
posterioir - mydriasis , ptosis

polyurea
gross heamturea

4

diagnosis of PKD?

proteinurea
heamturea
urine concentrating ability is the early
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positive family history
genetic tests
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physical examination
palpable , bilateral abdominal masses that are not tender

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ultrasound
ARPKD
enlarged kidney with multiple cysts bilaterally , diffuse increased echogencity of the kidney despite anechoic zones
hepatic cysts and fibrosis of the liver can also be seen

ADPKD
enlarged kidney , multiple cysts with VARYING size
hepatic , pancreatic , splenic cysts also visible

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CT

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intravenous pyelgoran to evaluate obstruction to the renal pelvis and urinary tract

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renal biopsy

ARPKD
cystic dilation of the COLLECTING TUBULES - other nephron segments are not usually affected
and hepatic fibrosis can also be seen

ADPKD
progressive cystic dilation of the tubular system

5

WHAT IS THE TREATMNET OF pod ?

ACEI or ARB = prevent hypertension and porteinurea and ASRD

tolvaptan
rapidly progressive AUTOSOMAL DOMINANT , or mild chronic disease
it slows down the growth of the kidney cysts in ADPKD

early treatment of urinary tract infections

high fluid intake to prevent kidney stone formation

AVOID nephrotoxic substances such as nsaids , sulphonamides , ahminoglycosides
and vasopressin

in ESRD - severe
hemodilaysys
kidney transplantation - THE ONLY CURATIVE OPTION
portosystemic shunting or lover transplantation may be requires in ARPKD patients with severe hepatic involvement

6

renal cell carcinoma (RCC) arises from?

adenocarcinomas that usually arise from the epithelial cells of the proximal convoluted tubule

7

risk factors for RCC

Age of onset: 60–80 years
- earlier in hereditary


Acquired cystic kidney disease as a result of ESRD (unlikely in pkd)

Renal pelvic stones

Obesity / hypertension

hepc

Occupational exposure to cadmium, asbestos


Chronic analgesic use (especially acetaminophen, and aspirin)

8

causes for hereditary RCC?

4% of renal cell carcinomas are associated with hereditary factors. In both forms, sporadic and hereditary RCCs, structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene are commonly found.

Von Hippel-Lindau syndrome

Hereditary papillary renal cell carcinoma (HPRCC)

Tuberous sclerosis


Hereditary renal cell carcinomas are autosomal dominant and tend to affect patients at a younger age

9

Clinical features of rcc?

Renal cell carcinomas are asymptomatic in the early stages. Patients become symptomatic when the tumor has reached a large size (usually > 10 cm) and/or if metastases are present.

The classical triad of renal cell carcinoma:
Hematuria
Dragging/colicky flank pain
Potentially palpable renal mass

Anemia (common): pallor, lethargy

Constitutional symptoms: weight loss , fatigue, night sweats, fever

10

Paraneoplastic syndromes of rcc

Hypertension - renin

Hypercalcemia : PTHrP (parathyroid hormone-related protein) from the tumor

Polycythemia -erythropoietin secretion

leukemoid reaction - bone marrow stimulation,

Secondary hypercortisolism
ACTH release

Stauffer's syndrome: non-metastatic hepatic dysfunction characterized by elevated liver enzymes (esp. alkaline phosphatase) and clotting abnormalities

Symptoms of local spread
Varicocele
Budd-Chiari syndrome: lower limb edema, ascites, hepatic dysfunction

11

tnm classification of rcc?

T1
Tumor is limited to the kidney
Tumor size is ≤ 7 cm in greatest dimension

T2
Tumor is limited to the kidney
Tumor size is > 7 cm in greatest dimension

T3
Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland


T4 Tumor extends beyond the Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)

12

staging of rcc

AJCC stage
Stage I
T1; N0

Stage II
T2; N0

Stage III
T1 or T2; N1
T3; N0 or N1

Stage IV
T4; Any N; M0
Any T; Any N; M1

13

diagnosis of rcc?

Best initial test: abdominal CT scan with contrast
Distorted renal outline and stretched renal calyces

Renal lesion(s) with thickened irregular walls, variable enhancement, and calcification

Renal ultrasound : renal lesion(s) with variable echogenicity

Evaluation of metastatic disease

CT/MRI of the thorax: enlarged mediastinal lymph nodes


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Percutaneous renal biopsy is generally not recommended.

14

what are the types or RCC ?

Clear cell RCC
most abundant
Proximal convoluted tubule
mutation of vhl and chromosome 3p

histology :Polygonal cells with a clear, glycogen and/or lipid-filled cytoplasm that are arranged as cords or tubules

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Papillary (chromophilic) RCC
Proximal convoluted tubule

Cuboidal, low columnar cells that grow in papillary formations
Bilateral, multifocal growth may occur.
type 1
type 2 = papillary RCC: aggressive tumor with a poor prognosis

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Chromophobic RCC
Intercalated cells of the cortical collecting duct

histology : Large polygonal cells with a prominent cell membrane, eosinophilic cytoplasm, and a perinuclear halo

Excellent prognosis

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Oncocytic RCC
Originate from oncocytomas

Similar to chromophobic RCC except that there is no perinuclear halo and the cells occur as tumor nests

excellent prog

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Collecting duct carcinoma (Bellini duct carcinoma)

Medullary collecting duct

Malignant glandular cells that are arranged as irregular within a fibrous stroma (hobnail pattern)
Medullary duct carcinoma: a variant of a collecting duct carcinoma which is associated with sickle cell disease

v aggressive


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A sarcomatoid pattern (containing foci of high-grade spindle cells), which can occur in any type of RCC, is associated with a poor prognosis

15

what is the treatment of rcc?

Stage I: cryoablation, thermal ablation, partial nephrectomy , or simple nephrectomy

Stage II–IV: radical nephrectomy

Patients who are unfit for surgery should be monitored for tumor growth and may be treated palliatively with:
Arterial embolization

External beam radiotherapy

Immunomodulatory and/or targeted therapy
Interferon-α (immunotherapy)

Recombinant cytokines (e.g., interleukin-2)

Tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, pazopanib)

16

Chemotherapy is not used to treat RCC why?

RCC is highly resistant to chemotherapeutic agents. This occurs because tumor cells express MDR-1 (multidrug resistance protein-1).

17

when does wilms tumor affect children?

typically affecting children between 2 and 5 years of age

18

Etiology of wilms tumor

Associated with loss of function mutations of tumor supressor genes on chromosome 11

The WT1 (Wilms tumor 1) gene is the most important Wilms tumor gene

WT2 (Wilms tumor 2) gene

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Associated syndromes with mutation to WT1:

WAGR syndrome:
Wilms tumor
Aniridia
Genitourinary anomalies
Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
Early-onset nephrotic syndrome
Intellectual disability


Denys-Drash syndrome
Wilms tumor
Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
Early-onset nephrotic syndrome caused by diffuse mesangial sclerosis
a mild form of WAGR without aniridia or intellectual disability.


Beckwith-Wiedemann syndrome: mutations of the WT2 gene
affected infants are larger than normal. Other commonly associated features include macroglossia, abdominal wall defects (e.g., exomphalos), recurrent neonatal hypoglycemia

19

clinical features of WT

Palpable abdominal mass
Non-tender
Unilateral and large but not crossing midline
Smooth and firm

Abdominal pain

Hematuria

Hypertension

20

stages of WT

I
Unilateral
Limited to the kidney

II
Unilateral
Extends beyond kidney:
Renal capsule
Soft tissue of the renal sinus
Blood vessels beyond the renal parenchyma

III
Unilateral
Confined to the abdomen
Dissemination in abdomen (e.g., regional lymph nodes, peritoneal involvement)

IV
Unilateral
Hematogenous metastasis (e.g., lung, liver, bone, brain)
Distant lymph nodes involvement (outside of abdomen)

V
Bilateral
Both kidneys are affected

21

dagnosis of wt ?

Ultrasound (best initial test)
Hypervascular tumor
with hypoechoic areas of necrosis

Abdominal CT/MRI
To assess extent of involvement
Surgical planning

CT thorax/CXR

22

treatemnet of WT

stage 1
surgical- complete resection of tumor


stage 2
nephrectomy
dactinomycin and vincristine
epirubicin

stage 3
nephrectomy
dactinomycine and vincristine
epirubicin
radiation Based on size of lymph node involvement or residual tumor

stage 4
same

stage 5
renal parenchymal sparing resection
preoperative chemotherapy
post op
external beam radiation


WT has Good prognosis

23

histology of WT?

Classic type: consists of three cell types
Epithelial cells (i.e., glomeruli and tubules)
Stromal cells
Undifferentiated blastemal cells of metanephric origin

Anaplastic type = poorer prog
Contains multipolar polypoid mitotic figures
Marked hyperchromasia of nuclei