Inherited Renal Diseases

Question 0

pdk1 patients vs pdk2 patients

Answer 0

pdk1 present younger and have a worse px

Question 1

genetic mutations in ADPKD

Answer 1

PD1- chrom 16–>produces polycstin (cell membrane protein that mediates cell-cell/cell-matrix interactins
PKD2- chrom 4- encodes polycstin 2–>role in Ca signaling

Question 2

extra renal manifestations of ADPCKD

Answer 2

seminal vesicle and/or epidymal cysts are found in 40% of men
htn
hepatic cysts, pancreatic cysts

Question 3

ADPKD does not develop cysts in

Answer 3

ovaries

Question 4

ADPKD also manigests as

Answer 4

CT abnormalities

-cardiac valce disease, aortic root dilation, cerebral aneurysms, colonic diverticula

Question 5

most common cardiac valve abnormality in APCKD

Answer 5

mitral valve prolpase

Question 6

maturation arrest hypothesis

Answer 6

in addition to first hit of bad genes, epithelial cells from renal cysts have been found to overexpress epithelial growth factor (EGF) receptors–>increase downstream signalt ransduction via MAPK and JAK-STAT pathways–>increased cystic proliferation

Question 7

CFTR

Answer 7

camp regulated Cl channel implicated in secretory fluid regulation in ADPKD

Question 8

primary cilium’s job

Answer 8

direct the three-d geometry of development- disruption of this may lead to abnormal morphology of tubules

Question 9

therapies

Answer 9

block EGFR, JAK-STAT, MAPK/ERK, MTOR
block CFTR and downstream cAMP signal
block vasopressin release/binding to R–>decrease intracell camp

*avoid caffeine–>increases camp

Question 10

APCKD is a ciliopathy

Answer 10

polycystin 1 and 2 are located on primary cilium, and ARPKD has a PKHD1 mutation–>fibrocystin–also found on primary cilium

Question 11

mutations in kif31 and ift88

Answer 11

also show issues with synthesis of primary cilia

Question 12

loss of heterozygosity

Answer 12

patients born with one good gene and are okay until seomething messes up the second normal gene

Question 13

TSC1 and TSC2

Answer 13

tumor suppressor genes critical for regulation progression through teh cell cycle via effects on mTOR and CDC25C

Question 14

how does tsc1 and tsc2 work

Answer 14

tsc 1 encodes–>hamartin tsc 2 encodes–>tuberin

hamartin and tuberin combine and downregualate mtor and plk1

Question 15

if mtor is inhivited

Answer 15

the cell will not progress throug cell cycle

Question 16

tuberous scleoriss mutatiosn

Answer 16

mutated genes ont sc1 on chrom 9 and tsc2 on chrom 16

Question 17

tuberous scleoris sresults in

Answer 17

tumors and voluminous cytoplasm in kidneys, skin, cns and heart

Question 18

renal TS has three forms

Answer 18

renal angiomyolipomas
renal cysts
renal cell carcinoma

Question 19

2-3% of patients with large genomic deletions of TSC2 will have

Answer 19

adjacent PKD type 1 gene affected leading to combined TS and APCKD

Question 20

VHL gene

Answer 20

tumor suppressor gene located on short arm of chrom 3

Question 21

lack of VHL

Answer 21

increase GF including VEGF, PDGF-B, TGFa–>lead to tumor growth

Question 22

H1F1A

Answer 22

usually these growth factors taht VHL lets happen happen with hypoxia via H1FA
without functional pVHL, H1f1s just produce a shit ton of factors

Question 23

VHL syndrome and missense mutatiosn

Answer 23

signficantly greater risks for developing pheos

Question 24

most common lesions of VHL

Answer 24

benign neoplasms called hemangioblastomas (HABs)

Question 25

HABs

Answer 25

usually present young and are recurrent-->delay surgery until tumor so big it is causing symptoms

Question 26

second most common VHL tumor

Answer 26

retinal capillary hemangioblastoma

Question 27

third most common VHL tumor

Answer 27

renal cysts adn clear cell renal cell carcinoma

Question 28

what do you do with an RCC

Answer 28

watch it carefully- want to preserve kidney fx so weigh surgery only when necessary transplants last resort because IS treatment makes tumors happy

Question 29

most common cause of death vhl patients

Answer 29

clear cell renal cell carcinma

Question 30

all VHL tumors

Answer 30

hemangioblastoma retinal capillary hemangioblastoa renal custs and RCC pheos

Question 31

all tumors of TS

Answer 31

``` brain lesions rhabdomyomas angiomyolipomas cysts rcc ```

Question 32

characterstic tumor of TS

Answer 32

SGCT--children present with hydrocephalus

Question 33

CV manifestations TS

Answer 33

coarction of aorta, constriction of major vessels, aneurysms

Question 34

angiomyolipoma

Answer 34

benihn yumot composed of blood vessels, smooth muscle, and fat

Question 35

symptoms of angios

Answer 35

usually asymptomatic unless rupture

Question 36

treatment of angios

Answer 36

surgery renal artery emboliation nephrectomy mtor inhibitors (rapamycin)

Question 37

patients with TSC may also develop

Answer 37

lympahngioleiomymatosis | cystic disease which affects pulmonary fx

Question 38

LAM usually presents with

Answer 38

dyspnea or pneumothroax

Question 39

TSC and derm

Answer 39

hypopihmented macules (ash leaf spots) angiofibromas in the malar region offace shagreen pathces over lower trunk fibrous plaques on forehead