Chronic Renal Failure & Renal/LUT Carcinoma Flashcards
3 most common causes of chronic renal failure
diabetes mellitus,
hypertension,
glomerular disease
- Uremia
- Salt and water retention –> HTN
- Hyperkalemia w/ metabolic acidosis (anion gap)
- Anemia
- Hypocalcemia
- Renal osteodystrophy
chronic renal failure
Nausea, anorexia, pericarditis, platelet dysfunction, encepalopathy with asterixis, deposition of urea crystals in skin
Chronic renal failure –> increased nitrogenous waste products in blood (azotemia) –>
why do you get anemia in chronic renal failure?
Decreased epo production by renal peritubular interstitial cells
why do you get hypocalcemia in chronic renal failure?
- decreased I-alpha-hydroxylation of vitamin D by proximal renal tubule cells
- hyperphosphatemia
Why do patients with CRF get platelet dysfunction?
uremia –> impairs platelet aggregation and adhesion
Why do patients with CRF get renal osteodystrophy?
- secondary hyperparathyroidism –> osteitis fibrosa cystica
- osteomalacia (can’t mineralize osteoid made by osteoblasts)
- osteoporosis (leach calcium from bone due to metabolic acidosis)
treatment of CRF
dialysis or renal transplant
what develops in the shrunken end-stage kidneys during dialysis?
cysts
patients on dialysis for chronic renal failure have increased frisk for
renal cell carcinoma
hamartoma comprised of blood vessels, smooth muscle, and adipose tissue; associated with tuberous sclerosis
angiomyolipoma
triad of renal cell carcinoma
hematuria, palpable mass, flank pain
malignant epithelial tumor arising from kidney tubules
renal cell carcinoma
paraneoplastic syndromes associated with RCC
EPO, renin, PTHrP, ACTH
involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein
RCC –> left variocele
why do you not get right-side varicocele in RCC?
right spermatic vein drains directly into the IVC
Increased IGF-1 –>
promotes growth
Increased HIF transcription factor –>
increased VEGF and PDGF
pathogenesis of RCC
loss of VHL (3p) tumor suppressor gene –> increased IG-F and HIF transcription facot
on what chromosome is VHL
3p
major risk factor for sporadic RCC
cigarette smoke
sporadic tumors classically arise in adult males (average age is 60) as a single tumor where?
upper pole of kidney
what disease –> hereditary RCC (wh/ arises in younger adults and is often bilateral)?
Von Hippel Lindau disease
Besides RCC, VHL dz increases risk for?
Hemangioblastoma of the cerebellum
based on size and involvement of renal vein (occurs commonly and increases risk of hematogenous spread to lungs and bone)
T staging of RCC
spread to retroperitoneal lymph nodes
N staging of RCC
Malignant kidney tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal ce;;s
Wilms tumor
average age of onset of Wilms tumor
3
Large, unilateral flank mass with hematuria and HTN (due to renin secretion) in a 3 yo
Wilms tumor
WAGR syndome
Wilms tuomr
Aniridia
Genetial abnormalities
mental and motor Retardation
WAGR syndrome is associated with DELETION of what tumor suppressor gene?
WT1
Where is WT1 located?
11p13
Wilms tumor, progressive renal (glomerular) dz. male pseudohermaphroditism
Denys-Drash syndrome
What causes Denys-Drash syndrome?
MUTATION of WT1
deletion of WT1 –>
WAGR syndrome
mutation of WT1 –>
Denys-Drash
Wilms tumor,
neonatal hypoglycemia,
muscular hemihypertrophy,
organomegaly (including tongue)
Beckwith-Wiedmann
Beckwith-Wiedman is associated with mutations in what gene cluster?
WT2, particularly IGF-2
WT2 gene cluster = imprinted genes at ?
11p15.5
Types of lower urinary tract carcinoma
- urothelial (transitional cell) carcinoma
- squamous cell carcinoma
- adenocarcinoma
malignant tumor arising from the urothelial lining of the renal pelvis, ureter, bladder, or urethra
urothelial carcinoma
most common type of lower urinary tract cancer
urothelial carcinoma of bladder
major risk factors for urothelial carcinoma
cigarrettes (polycyclic aromatic hydrocarbons),
napthylamine (also in cigarrettes),
azo dyes (used for coloring - hairdressers) ,
long term cyclophosphamide or phenacetin use
two pathways by which urothelial carcinoma arises
flat
papillary
Painless hematuria
urothelial carcinoma
urothelial carcinoma that develops as a low-grade papillary tumor that progresses to high-grade papillary tumor and then invades
Papillary pathway
urothelial carcinoma that develops as a high grade flat tumor and then invades
flat pathway
flat pathway of urothelial carcinoma is associated with
p53 mutation
why are urothelial carcinomas often multifocal and recurrent
field defect - all urothelial cells are mutated
malignant proliferation of squamous cells, usually involving bladder, that arise in a background of metaplasia
squamous cell carcinoma
Risk factors of squamous cell carcinoma of LUT
chronic cystitis schistosoma hematobium (young middle eastern male) long-standing nephrolithiasis
malignant proliferation of glands usually involving bladder
adenocarcinoma
Do you normally have glandular epithelium lining the bladder?
No
LUT adenocarcinoma arises from
urachal remnant
cystitis glandularis
exstrophy
congenital failure to form the caudal portion of the anterior abdominal and bladder walls
exstrophy
when adenocarcinoma arises from urachal remnant, the tumor develops where?
at the dome of the bladder
What connects the fetal bladder to the yolk sac?
urachus (duct)
chronic inflammation of bladder –> columnar metaplasia
Cystitis glandularis