Chapter 20: The Kidney - Congenital, Cystic Dz, Urinary Obstr. and Neoplasms Flashcards
1
Q
What occurs to the solitary kidney as a result of unilateral agenesis?
Some pts eventually develop what later in life?
A
- Solitary kidney enlarges = compensatory hypertrophy, therefore increased risk for HTN
- Some pts eventually develop progressive glomerular sclerosis —> CKD
2
Q
True renal hypoplasia is most often observed in?
Bilateral or unilateral?
May contribute to an increased lifetime risk for?
A
- Low birth weight infants
- May be bilateral but is more often unilateral
- Increased risk for CKD
3
Q
Where is the most common location of Ectopic Kidneys?
May lead to what issues?
A
- Just above the pelvic brim or within the pelvis
- Ureteral abnormalities may cause obstruction/infection
4
Q
What are the 3 major pathologic features of ADPKD?
Unilateral or bilateral?
A
- Large, mutlicystic kidneys, bilaterally
- Liver cysts
- Berry aneurysms
5
Q
Mutation in which gene and on which chromosome account for 85% of ADPKD cases?
A
PKD1 on chromosome 16
6
Q
Mutation in which gene and on which chromosome account for 15% of ADPKD cases?
A
PKD2 on chromosome 4
7
Q
How does the severity of disease and progression to complications differ between ADPKD pts with a PKD1 vs. PKD2 mutation?
A
- PKD1 = more severe, increased risk of earlier onset renal failure (95% by 70 yo)
- PKD2 = somewhat better prognosis; less risk of renal failure, at least earlier on.
8
Q
What are the cysts seen in ADPKD filled with, describe its morphology
A
Clear serous fluid or turbid red-brown, hemorrhagic fluid
9
Q
What is the typical clinical course of ADPKD and how does it typically present?
A
- Generally asymptomatic w/ insidious onset in 4th-6th decade w/ renal insufficiency (HTN, azotemia)
- Some exhibit abd. pain due to cyst enlargement and hemorrhage, thus hematuria may be manifestation
10
Q
There is a more aggressive (earlier onset, more severe) clinical course in which patients w/ ADPKD?
A
- Blacks (particularly those w/ sickle cell trait)
- M>F
- Those w/ concomitant HTN
11
Q
What are the clinically significant extra-renal manifestations of ADPKD?
A
- Hepatic cysts; less common in spleen, pancreas, and lung
- Berry aneurysms –> subarachnoid hemorrhage
- Mitral valve prolapse
- Many have diverticular dz of colon
12
Q
How is diagnosis of ADPKD made?
A
Radiologic imaging
13
Q
How do the majority of pts w/ ADPKD ultimately end up dying?
A
Coronary or hypertensive heart disease
14
Q
Most cases of ARPKD are due to mutation in which gene and on what chromosome?
A
- PKHD1 on chromosome 6
- Encodes fibrocystin
15
Q
What are the 2 most common clinical subtypes of ARPKD?
Type of hepatic fibrosis in each?
A
- Perinatal (most common) –> minimal hepatic fibrosis
- Neonatal –> mild hepatic fibrosis
16
Q
What is the gross morphology of the surface of the kidneys in ARPKD?
What does a cut section of the kidney show?
A
- Enlarged w/ SMOOTH surface (contast to cystic surface of ADPKD)
- Cut section shows numerous small cysts linearly arrayed in cortex ans medulla w/ spongelike appearance
17
Q
Where are the cysts seen in ARPKD derived from?
A
Dilated collecting ducts
18
Q
What is the typical clinical course of ARPKD?
A
- Perinatal form = most common; survival only a few hours; death due to pulmonary hypoplasia
- If survive infancy develop congenital hepatic fibrosis —> portal HTN and splenomegaly
19
Q
In almost all cases of ARPKD the liver contains what?
A
Cysts associated w/ portal fibrosis and proliferation of bile ducts
20
Q
What are the 3 major subtypes of medullary cystic disease?
A
- Medullary sponge kidney
- Nephronophthisis
- Adult-onset medullary cystic disease
21
Q
What is seen in Medullary Sponge Kidney?
Affected population?
Renal function?
A
- Mutliple cystic dilations of the collecting ducts and medulla
- Occurs in adults and is usally discovered radiographically
- Renal function is usually normal
22
Q
What are the disorders characterized as ciliopathies or abnormalities of the cilium-centrosome complex?
A
- Polycystic kidney diseases (both AD and AR)
- Medullary Cystic Kidney
- Nephronophtisis
23
Q
In Nephronophthisis-Medullary Cystic Disease where are the cysts localized?
Gross morphology of the kidneys and on microscopy of the cortex?
A
- Localized to corticomedullary junction and medulla
- Kidneys are small w/ contracted granular surfaces
- Cortex has diffuse atrophy and thickening of tubular BM w/ interstitial fibrosis
24
Q
What are the 3 clinically recognized variants of the Nephronopthisis-Disease complex?
Which is most common?
A
- Sporadic, non-familial
- Familial juvenile nephronophthisis (most common)
- Renal-retinal dysplasia
25
Although the medullary cysts in Nephronophthisis-Medullary Cystic Disease Complex are important, what is the cause of the eventual renal insufficiency?
Cortical tubulointerstitial damage
26
Inheritance pattern of familial juvenile nephronophthisis?
Autosomal **Recessive**
27
How do children w/ familial juvenile nephronophthisis typically present?
- First w/ **polyuria** and **polydipsia**
- **Sodium wasting** and **tubular acidosis** are also prominent
- Expected course is progresion to **ESRD** in **5-10 years**
28
What is the most common genetic cause of ESRD in children and young adults?
Nephronophthisis complex
29
What is the inheritance pattern of Adult-onset Medullary Cystic Disease?
Which genes mutated?
- Autosomal **Dominant**
- ***MCKD1** and **MCKD2***
30
How does Familial Juvenile Nephronophthisis differ from Adult-onset Nephronophthisis (medullary cystic disease)?
- **Juvenile** is marked by progressive renal failure beginning in **childhood**
- **Adult-onset** is marked by chronic renal failure beginning in adulthood
\*Both present w/ corticomedullary cysts, shrunken kindeys, salt wasting and polyuria
31
Since the medullary cysts associated w/ nephronophthisis are usually to small to visualize, this disease should be considered in children presenting how?
- Unexplained chronic renal failure
- A positive family hx
- Chronic tubulointerstitial nephritis on biopsy
32
How is Multicystic Renal Dysplasia acquired and what is it characterized by?
- **Sporadic** disorder; common mass in **perinatal** period
- Unilateral or b/l kidney(s) usually **enlarged, extremely irregular,** and **multicystic**
33
What is the characteristic histological finding of Multicystic Renal Dysplasia?
**ISLANDS** of **undifferentiated mesenchyme**, often with **CARTILAGE** and **immature collecting ducts**
34
Most cases of Multicystic Renal Dysplasia are associated what other renal/GU anomalies?
- Ureteropelvic obstruction
- **Ureteral agensis** or atresia
- Other lower GU anomalies
35
What is the significance of **unilateral** Multicystic Renal Dysplasia, especially in a child and its **prognosis**?
Bilateral?
- **Unilateral =** abd. mass in child may mimic a neoplasm. Surgically removed via **nephrectomy** = **excellent prognosis**
- **Bilateral** will eventually progress to **renal failure**
36
What type of cysts are associated with pts w/ ESRD who have undergone **prolonged dialysis** and sx's?
What is the significance of these cysts long-term?
- Numerous cortical and medullary cysts w/ **calcium oxalate** crystals
- Often asymptomatic, but may bleed = **hematuria**
- ↑↑↑ risk of **renal cell carcinoma**
37
What are Simple Cysts of the kidney?
Significance?
- **Single** or **multiple** cysts on renal surface (**cortex**)
- Generally filled w/ **clear fluid**
- Common postmortem finding
- May be a bizarre radiograph finding requiring differentiation by observer from a tumor
38
Dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine is known as?
Hydronephrosis
39
The initial functional alterations caused by obstruction are primarily manifested as what?
Eventually progresses to?
- **1st sign** = impaired concentrating ability
- **Later on** the GFR decreases
40
What are the early vs. late mophological features of Hydronephrosis?
- **Early** = simply dilation of the pelvis and calyces, may be significant interstitial inflammation
- **Later** = cortical tubular atrophy + marked diffuse interstitial fibrosis
41
In advanced cases of Hydronephrosis what morphological changes are seen in the kidney?
- Kidney = **thin-walled** cystic structure
- Striking **parenchymal atrophy**
- Total obliteration of **pyramids** + thinning of **cortex**
42
Which imaging technique is useful for diagnosis of obstructive uropathy?
Ultrasound
43
In hydronephrosis due to bilateral **partial** obstruction, what are the common signs/symptoms?
- Earliest = inability to concentrate, **polyuria** and **nocturia**
- Some pts develop **distal tubule acidosis, salt wasting, 2' renal calculi** and **chronic tubulointerstital nephritis**
- **HTN** is common
44
In hydronephrosis due to **complete** bilateral obstruction, what are the common signs/symptoms?
How must this be dealt with and what is commonly seen after treatment?
- **Rapid** onset of **oliguria** or **anuria** = **INCOMPATIBLE w/ survival** unless obstruction is relieved
- After removal there is **postobstructive diuresis** = massive amts of urine that is rich in NaCl
45
Is Nephrolithiasis (aka kidney stones) typicall bi- or unilateral?
Sex most often affected and at what age?
- **80%** are **unilateral**
- **M\>F**
- Peak age at onset = **20-30 yo**
46
Is there a familial or hereditary predisposition to developing nephrolithiasis?
Yes
47
What are the 4 main types of renal calculi?
1. Calcium stones (70%)
2. Struvite stone/Triple stone (magnesium-ammonia-phosphate)
3. Uric acid stones
4. Cystine
48
Magnesium ammonium phosphate stones are formed largely due to?
Size of stone and form what?
- Following **infection** by **urea-splitting** bacteria (i.e., ***Proteus*** and some **staphylococci**)
- Some of the **largest stones** form **staghorn calculi**
49
What is important to take into consideration about the development of Uric Acid stones?
- Common in ppl w/ gout, and diseases such as leukemia
- BUT, **more than 1/2** of pts have **neither** hyperuricemia **nor** increased excretion of uric acid
50
What are 4 factors that influence the development of calculi (stones) in the urinary tract?
1. **Increased concentration** of **stone constituents**
2. **Changes** in **urinary pH**
3. **Decreased urine volume**
4. **Presence of bacteria**
51
What is the favored sites within the urinary tract for the formation of stones?
- Renal **calyces** and **pelves**
- **Bladder**
52
What is the most common malignant tumor of the kidney in both adults and in children?
- **Adults** = Renal Cell Carcinoma (1st) and Urothelial Carcinomas of the Calyces and Pelvis (2nd)
- **Children** = Wilms Tumor
53
What is the most common benign neoplasm of the kidney?
Arise from what?
- Renal papillary adenomas
- Arise from **renal tubular epithelium**
54
Describe the morphology (i.e., size, shape, location, and color) of Renal Papillary Adenomas?
- **Small**, usually \<0.5 cm within **cortex**
- Discrete, cortical, **pale yellow-gray**, **well-circumscribed** nodules
- Branching, papillomatous structures w/ **cuboidal to polygonal** cells
55
Renal papillary adenomas share what similar cytogenetic features that are also present in low-grade RCC?
Trisomies **7** and **17**
56
Which feature of Renal Papillary Adenomas are related to its prognosis?
- Size
- **Benign = \<1.0 cm or less** in diameter
- Neoplasma \>1.0 cm w/ adenoma histomorph. = low grade RCC
57
Which benign neoplasm of the kidney is highly associated with Tuberous Sclerosis?
Angiomyolipomas
58
Angiomyolipomas usually present in which sex and when?
Associated with what genes?
- Adults, middle-aged, **F\>M**
- Loss of **TSC1** or **TSC2** tumor suppressor genes
59
What is the clinical significance of Angiomyolipomas as far as significant complications which may arise?
May spontaneously rupture w/ **massive hemorrhage**, initialy presentation may be **shock secondary** to **massive retroperitoneal** and/or **intra-abdominal hemorrhage**
60
Tuberous Sclerosis has what type of inheritance?
Manifests as a complex of what type of disorders?
- Autosomal Dominant
- Tumors or lesions of: **brain, skin, kidney, lungs**, and **eyes**
61
Renal Oncocytomas arise from where and what are their characterisitcs?
- Benign **epithelial** neoplasm w/ large **eosinophilic cells** that have **small, round, benign-appearing nuclei** w/ **large nucleoli**
- Arise from **intercalated cells** of collecting ducts
- Grossly, appear **tan** or **mahogany brown**, usually **well encapsulated** w/ a **central scar**
62
On EM, Renal Oncocytomas have eosinophilic cells packed with what?
Mitochondria
63
Whos is most often affected by RCC and when does it arise?
- **M \> F**
- Arise in **older adults**; **6th-8th decade**
64
What is the major risk factor and other risk factors for RCC?
- Major = **smoking**
- Obesity (particularly woman)
- HTN
- Estrogen therapy
- Asbestos, petroleum prods., and heavy metals
- Tuberous Sclerosis
65
Most RCC arises how?
Sporadic
66
The *VHL gene* is implicated in what types of RCC?
Both **familial** and **sporadic clear cell carcinomas**
67
Pts w/ Von Hippel-Lindau syndrome, most often develop what type of renal malignancies?
- **Hereditary clear cell carcinoma**
- **Hereditary papillary carcinoma**
\*Often **bilateral** and **multiple**
68
Hereditary leiomyomatosis and renal cells cancer syndrome is inherited how and due to what gene?
This disease is characterized by what?
- Autosomal **dominant** due to mutations in ***FH gene***
- Characterized by: **cutaneous** and **uterine leiomyomata** and an **aggressive type** of **papillary carcinoma** w/ ↑ propensity for metastasis
69
Hereditary papillary carcinoma has what type of inheritence and due to what gene?
Characterized by?
- Autosomal **dominant** w/ mutations in ***MET*** proto-oncogene
- **Multiple bilateral tumors** w/ **papillary** histology
70
What is the inheritance of Birt-Hogg-Dube syndrome?
Manifested by what?
- Autosomal **dominant** mutation ***BHD gene***
- **Skin** (fibrofolliculomas, trichodiscomas, and acrochordons), **pulmonary** (cysts or blebs), and **renal tumors**
71
What is the most common type of Renal Cell Carcinoma?
Describe its histological characteristics.
- Clear cell carcinoma
- **Non-papillary** cells w/ **clear cytoplasm** (some granular)
72
How do the majority of the clear cell type of renal cell carcinoma arise?
Majority contain which mutation and on what chromosome?
- **Sporadic (95%)**, but can be familial
- **Short arm** deletions/translocations of **c****hromosome 3**(harbors the***VHL*** tumor suppressor gene)
73
The loss of VHL in RCC causes the inappropriate expression of what genes?
- **HIF-1** induced genes
- **VEGF**
- **IGF-1** (stimulates growth)
- **PDGF**
74
Papillary carcinomas (10-15% of renal cancers) are associated w/ what cytogenetic abnormalities in both the sporadic and familial form?
- **Trisomies 7 and 17** and **loss of Y in males** **= Sporadic**
- **Trisomy 7** = **Familial**
75
Which gene located on chromosome 7 is associated with Renal Papillary Carcinoma?
Encodes what?
- ***MET*** a proto-oncogene
- Encodes **RTK** for **HGF = Scatter Factor**
76
Renal Chromophobe Carcinoma (5% of renal cancers) arise from where and are composed of what kind of cells?
i.e., describe their distinct morphology
- Arise from **intercalated cells** (difficult to distinguish from **oncocytoma**)
- **Pale eosinophilic** cells, with a **perinuclear halo**, arranged in **solid sheets** w/ large concentration around **blood vessels**
77
What is the prognosis of renal chromophobe carcinoma?
Excellent
78
Cytogenetic examination of which renal carcinoma shows mutliple chromosome losses and **extreme hypodiploidy?**
Chromophobe Carcinoma
79
Xp11 translocation carcinoma is a distinct subtype of RCC, why?
Defined by translocation of what gene?
- Often occurs in **young patients**
- Defined by translocations of the ***TFE3 gene*** w/ a number of partner genes
80
Collecting duct (Bellini duct) carcinoma is a rare and is defined by what histological characteristics?
- Malignant cells forming **glands** enmeshed within **prominent fibrotic stroma**
- Typically in **medullary location**
81
Medullary carcinoma is a rare tumor most often seen in whom?
Patients w/ **sickle-cell trait**
82
Renal clear cell carcinomas usually occurs as what type of lesion?
Often occuring where in kidney?
- Most commonly **upper pole**
- Occur as **solitary UNILATERAL** lesions that are **bright yellow-gray-white spherical masses**
83
Which renal tumor is this and how can you tell?
- RCC --\> Clear cell type
- Rounded or polygonal shaped cells w/ adundant clear or granular cytoplasm, containing glycogen and lipids
84
What are some of the most striking characterisitcs as far as growth and invasion go for RCC?
- Tendency to reach **large size** and have **widespread metastases** before local signs/sx's
- Tendency to **invade the renal vein** and can grow upwards to **IVC**, sometimes all the way to **right side of heart**
85
Papillary type of RCC arise from **where** in the kidney and commonly grows how, **unilateral or bilateral**?
What are the **major morphological characteristics** and **major cell types** found?
- Arise from **DCT** and can be **multifocal** and **BILATERAL**
- Typically **hemorrhagic** and **cystic**
- Contain **interstitial FOAM cells** and may also have **psammoma bodies**
86
What morphological change arises infrequently in all types of RCC and is an ominous feature?
**Sarcomatoid** changes --\> spindle cells simulating mesenchymal neoplasm
87
What is the classic triad of sx's for Renal Cell Carcinoma?
Which is the most reliable clue?
1. Costovertebral pain
2. Palpable mass
3. **Hematuria** = **most reliable clue**
88
Why is RCC considered one of the great mimics in medicine?
- Tends to produce diversity of systemic sx's **not** related to kidney
- Abnormal hormone prod, may cause: **polycythemia**, **hypercalcemia**, **HTN**, **hepatic dysf.**, **feminization** or **masculinization**, **Cushing's**, **eosinophilia**, **leukemoid rxns**, and **amyloidosis**
89
What is the most common mode of spread from RCC and where are the most common sites?
- **Hematogenous**
- **Lungs** and **bones --\> regional LN's, liver, adrenal**, and **brain**
90
Tx options of choice for RCC?
- Radical nephrectomy
- **VEGF inhibitors** and **various tyrosine kinases**
91
Urothelial Carcinoma of the Renal Pelvis usually becomes clinically apparent when?
Produce what signs/sx's?
- Clinically apparent in **relatively short time**
- Lie within pelvis and by fragmentation, produce **noticeable hematuria**
- **May block urinary outflow** and causes **palpable hydronephrosis** and **flank pain**
92
In 50% of urothelial carcinomas of the renal pelvis there exists a concomitant tumor where?
Bladder urothelial tumor
93
In which 2 disorders is there a higher incidence of Urothelial Carcinoma of the Renal Pelvis?
- Lynch syndrome (HNPCC)
- Analgesic nephropathy
94
What is the prognosis of Urothelial Carcinoma of the Renal Pelvis?
Are they infiltrative?
- Commonly **infiltrate** wall of renal pelvis and calyces
- **Poor prognosis**
