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61 Cards in this Set
- Front
- Back
Alport's Syndrome
1) Inheritance 2) Gene product defect |
1) X- Linked
2) Alpha- 5 subunit of Type IV collagen There are also AD and AR forms that are the defect ins s and 4 subunits respectively |
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ADPKD
1) Inheritance 2) Gene product defect |
1) AD
2) Polycystin 1 and 2 |
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Fabry's
1) Inheritance 2) Gene product defect |
1) Xlinked
2)Alpha-galactosidase |
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Primary Hyperoxaluria
1) Inheritance 2) Gene product defect |
1) AR
2) Various |
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Tuberous Sclerosis
1) Inheritance 2) Gene product defect |
1) AD
2) Tuberin |
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Wilms tumor
1) Inheritance 2) Gene product defect |
1) AD
2) WT1, 2 |
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ADPKD is a ___1____ disorder caused by a mutation in ____2____
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1) systemic
2 Polycystin 1 or 2 |
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1) Prevalence of ADPKD in US
2) Family history is present in ___2___% of people at first diagnosis |
1) 1:500
2) 60% |
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Criteria for ADPKD diagnosis
1) under age 30 2) age 30-59 3) mode of diagnosis |
1) one cyst on each side
2) 2 cysts on each side 3) Ultrasound |
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ADPKD Genetic diagnosis
1) what is needed and what test is done 2) what can make this test a false positive or negative? |
1) sequencing, need only sample from affected person
2) insignificant mutations and mutations in unseen parts of the gene |
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Why do we care about evaluating for ADPKD in young people?
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Only whe the are being eval'd as kidney donors
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1-5) 5 renal symptoms of ADPKD
6-9) 4 extrarenal manifestations od ADPKD |
1) hematuria
2) cyst belleding 3) cyst infection 4) HTN 5) progressive CKD 6) Berry aneurysms 7) Liver/ovary/panc cysts cysts 8) Mitral valve proplase 9) Diverticulosis |
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What manifestation of ADPKD can mimic kidney stone?
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Cyst bleeding
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ADPKD cyst infection is more common in ____1____ because of ____2___
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1) women
2) ascending infection |
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In ADPKD do we see HTN or decreased GFR first?
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HTN
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I see a patient with a hemorrhagic stroke and hemturia, what should i think?
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ADPKD-- berry aneurysm!!
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What is the presentation of Liver/ovary/pancreas cysts in ADKD
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1) no organ dysfunction, may present with pain
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Does ADPKD affect men or women more?
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SAME
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During kidney development, polycystin 1 is localized in the____1___.
In the adult kidney it is found mainly in the ___2___. Her they function in cell-matrix interactions and as _____3____ . |
1) ureteric bud
2) cell-cell juctions 3) signal transducers |
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second hit hypothesis in ADPKD
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Polycystin genes inherited ss normal has a high rate of spontaneous mutation, giving the second hit needed for dysfunction. both alleles must be knocked out. AD means that one is KO in germline.
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Three psteps for cyst formation in ADPKD
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1) Abnormal cell proliferation
2) Fluid accumulation 3) abnormal ECM metabolism |
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How do ADPKD cysts damage kidneys?
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distotion of normal tubules and blood vessels
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Describe how ADPKD which causes cilia dysfunction leads to cyst formation?
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Normal cilia sense flud flow. Those with defective cilia never sense this flow, so they are always inducing "repair". This is seen as clonal prolieration of the epithelial cell, with fluid secretion. there is also breakdow of cell cycle regulation.
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How many abnormal polycystin alleles does it take to cause ADPKD
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Cysts arise by clonal proliferation of cells with two abnormal PKD1 genes
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Why would we investigate rapamycin as a drug to give in ADPKD?
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One of the genes upreglated in ADPKD mediated inappropriate "repair" (cyst formation" is mTOR.
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how does ADPKD cause HTN?
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Stretches nearby arterioles causing renin and AII release. Also stimulates sympathetic nervous system
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1) Average age of onset in ADPKD
2) age at which half will develop renal failure 3) poor prognosis is indicated by this co-morbidity 4) other markers of poor prognosis |
1)45
2) 70 3) HTN 4) black, sickle cell trait, male, large kidneys |
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Compare the outcomes of the PKD1 vs. PKD2 mutations in the course of ADPKD
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1) PKD2 present later (40% after 60)
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1)Mainstays of therapy for ADPKD induced CKD
2) A drug in trial is a ___2____ receptor antagonist. The rationale behind this is that it could reduce ___3___ and thus halt cystic cell proliferation |
1) dialysis and transplant
2) Vasopression (V2) 3) cAMP |
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Also on the DDx fo kindey cyst:
Simple cyst... describe |
common in aging, thin walled. one or several may be seen.
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Also on the DDx fo kindey cyst:
Acquired cystic kidney disease...describe |
multiple bilateral renal cysts in patients after prolonged dialysis. Increases risk of reneal tumor.
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Also on the DDx fo kindey cyst:
Medullary cystic kidney disease... describe |
Ad inheirtance
Presents with renal failure in teens or 20s. Cysts form at corticomedullary juntion. Salt wasting sometimes seen |
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Medullary cystic kiney disease
1) Inheritance 2) Gene defects 3) age range 4) location of renal cysts |
1) AD
2) MCKD-1 and 2 3) teens-20s 4) corticomedullary junction |
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1) Alports inheritnace
Renal manifestations of alports 2) in childhood 3) In 20-40s 4) Mid 40s |
1) X-linked
2) Hematuria in childhood or adolesence Bad proteinuria by 20-40 Advdnaced CKD in males requiring dialysis or transplatnt by 40s |
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1) Alports defect
Extrarenal manifestations of Alports 2) _____ develops in 90% of pts. by age 30 3) Two possible optical findings 4) Hematologic |
1) Type IV collagen missing due to mutant alpha-5 subunit
2) Sensorineural hearing loss 3) Cataracts or Anterior lenticonus 4) platelet defects |
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)three subunits in normal adult type IV collagen
2) three subunits in embryonic type 4 collagen in kidney GBM. 3) What is present ins alports? |
1) alpha 3,4,5
2) Alpha 1,2,2 3) Embryonic |
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What is the only physical finding that is pathognomonic for Alports?
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Anterior lenticonus (looks like an oil droplet)
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Can women get Alports?
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Some female trait carriers can develop kidney failure. much less common than males.
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A Pt presents with hematuria and ESRD with a family history of hearing loss. Dx?
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Alports
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Two ways to biospy for Alports:
1) kidney biopsy shows? 2) what other kind of biposy can we do and what will it show? |
1) splitting of the lamella densa of the GBM
2) SKin biopsy shows lack of alpha-5 chain |
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What will ALL females with the Alports trait (carrier) show?
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microscopic hematuria
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Type IV collage in 4 places...
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GBM
nephron tubule epidermis vestibulocochlear aparatu |
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Why does normal type IV collagen (alpha 3,4,5) hold up better than embryonic type Iv collagen (1,1,2) as is seen in Alport's?
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greater crosslinking
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What is the difference between the common X-linked form of alportsad the uncommon AR form?
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AR has mutant in alpha 3 or 4 subunit of type IV collagen
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1) All affected mles with Alports will develop...
2) Best Tx 3) What is a complication of this procedure? |
1) ESRD
2) transplant 3) donor type IV colagen is anovel antigen in this pt.-- causes anti-GBM autoimmunity |
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1) how my benign familial hematuria (THin basement membrane disease) and Alports related?
2) Inheritance? |
1) it may be the trait-carrier (heterozygous) manifestation of the mutant seen in AR (rare) form of alport where alpha 3 or 4 for subunit is mutant
2) AD (makes sense, think about it) |
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1) Why does fabry's get so much attention
2) inheritance? 3) General type of disease? |
1) because we have a good Tx!
2) X-linked 3) multi-system lysosomal storage |
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1) Enzyme lost in Fabry's
2) function of the enzyme is to remove the _____1_____ from the ____3____ called __4____. |
1) alpha-galactosidase-A
2) terminal galactose 3) glycosphingolipid 4) globotriosyl-ceramide |
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1) Renal manifestation of Fabry's disease
2) skin manifestation 3) Cardiac manifestations 4) Optic manifestation |
1) proteinuria and hematuria with CKD by 50
2) purple papules on lower trunk and genitalia (Angiokeratosis) 3) LVH, CAD, arrhythmias 4) Corneal opacity |
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Diagnosis of Fabrys
1) Alpha-galactosidase A level can be measured in what cells and found to be low?? 2) Is this finding seen in female carriers? 3) what may be found in the urine 4) What finding is pathognomionic for Fabry's? |
1) peripheral WBCs
2) they will be in the lower range of NORMAL 3) ceramide trihexoside and digalactoside 4) Zebra Lamellar bodies on biopsy. |
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1) Tx for Fabry's
2) how often |
IV alpha-galactosidase A every two weeks
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Why do we see renal manifestations of sickle cell anemia
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Becuse the renal medulla is hypoxic and hyprosmolar
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Inreased GFR
Urine concentration defect Acidification deect Hyperkalemia Hematuria Papillary necrosis Proteinuria CKD .... are all possible renal problems caused by... |
SCD (Hb-SS)
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SCD can cause _____kalemia
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hyper
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Does the increased RBF and GFR caused by SCD reduce with transfusion?
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NOPE
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1) What is the most common renal defect seen in SCD and how is it causes.
This is not seen in children under 10 2) Up to age 15 we can reverse this problem with.... |
1) renal concentration defect. Cannot concentrate above 400 mosm/L. This is due to loss of the vasa recta due to ischemia and infarction
2) Transfusion |
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Highest Uosm achievable by a 20 YO with SCD
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400 mosm/L
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SCD can cause a metabolic ____osis and _____kalemia to ischemia of the distal nephron
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1) acidosis
2) hyper |
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What is the Tx for SCD induced acidosis, hyperkalmeia, and hematuria?
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hydration, transfusion, and alklaninization of the urine.
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Painless, gross hematuria in patient with SCD suggests what process?
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Papillary necrosis (15-36%)
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What pathologic finding is associated with nephrotic range proteinuria in SCD?
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Focal, segmental, glomerulosclerosis.
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