Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Renal by Minnie > SM 216a - Genetic Cystic Disease > Flashcards

SM 216a - Genetic Cystic Disease Flashcards

1
Q

Why is adequate fluid intake important for the treatment of ADPKD?

A

The goal is to reduce ADH secretion - adequate fluid intake (>3L/day) prevents ADH secretion by keeping plasma Osm low

  • When ADH binds to its V2 receptor, it increases intracellular cAMP
  • In patients with ADPKD, this is bad because
  • *increased cAMP -> increased fluid secretion into cysts
  • > cyst growth**
  • Preventing ADH from binding to its receptor prevents this increase in cAMP, thus reducing fluid secretion into cysts and cyst growth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which polycystic kidney disease is characterized by kidneys that get progressively larger?

A

ADPKD

In ARPKD, cysts develop then stabilize

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is ADPKD diagnosed?

A

Count the cysts on ultrasound; you can predict teh number of cysts that a person with ADPKD would have at each age

More cysts = higher liklihood of ADPKD

If there is a family history, you know what to look for. If no family history, genetic testing may be useful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why is total kidney volume often reported in patients with ADPKD?

A

Total kidny volume is an accurate prognostic factor that predicts the rate of GFR decline

Larger size = predictive of GFR decline

Limiting kidney growht can protect against GFR decline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What mutation causes Autosomal-Dominant Polycystic Kidney Disease (ADPKD)?

A

Mutations in either PDK1 or PKD2

Encode fro proteins polycystin 1 or polycystin 2

These proteins are necessary for maintaining ciliary function, which contributes to normal intracellular Ca2+ and cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How are most cases of AKPKD diagnosed?

A

Ultrasound

Look for a certain number of cysts based on patient age (in patients with family history)

Genetic testing is availble, but not as widely used. Useful in patients without family history

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What causes autosomal recessive polycystic kidney disease (ARPKD)?

A

Genetic mutation in PKHD1

Encodes for fibrocystin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the inheritance pattern for ADPKD?

A

Autosomal dominant, but ~5% of cases are caused by de novo mutations

2nd hit hypothesis - Patients usually dont’ develop disease until later in life, when their functional copy of PDK1 or PDK2 is presumably compromised

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

A mutation in PDK1 or PKD2 leads to which genetic kidney disease?

A

Autosomal dominant polycystic kidney disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the clinical manifestation of a patient with ARPKD

A
  • Kidney dysfunction
    • Usually before age 10
  • Liver involvement (always)
    • Biliary dysgenesis
    • Congenital hepatic fibrosis -> portal hypertension
  • Risk for cholangitis (inflammation of the biliary duct)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

A mutation in UMOD will lead to which genetic kidney disease?

A

Medullary cycstic kidney disease

(UMOD encodes uromodulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the clinical presentation of ADPKD

A
  • Usually adult onset
  • Renal manifestations
    • Hypertension
    • Proteinuria
    • Hematuria
    • Abdominal/flant pain
    • Kiney stones
    • UTI/kidney infections
  • Extrarenal
    • Hepatic cysts
    • Intracranial aneurysm
    • Mitral valve prolapse
    • Aortic aneurysm
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What causes medullary cystic kidney disease?

A

Mutations in one of the following genes

  • MUC1 (encodes mucin 1)
  • UMOD (encodes uromodulin)
  • REN (Endodes renin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A mutation in REN will lead to which genetic kidney disease?

A

Medullary polycystic kidney disease

(REN encodes renin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the clinical manifestation of medullary cystic kidney disease

A
  • Commonly associated with hyperuricemia and gout
  • Progressive CKD
    • ESRD by the 3rd-6th decade
  • No extrarenal manifestations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the common extrarenal clinical manifestations of ADPKD?

A

Hepatic cysts

Intracranial aneurysms

Mitral valve prolapse

Aortic aneurysm

17
Q

Describe the histologic changes seen in ADPKD

A

Very little normal kidney tissue between cysts

Cysts are round

18
Q

What is medullary cystic kidney disease (MCKD)?

A

A kidney disease characterized by tubular fibrosis and interstitial fibrosis, but the clinical manifestation is not severe

19
Q

Describe the pathophysiology of Autosomal-Dominant Polycystic Kidney Disease (ADPKD)?

A

Mutations in either PKD1 or PDK2

  • -> Abnormal ciliary function
  • -> Decreased intracellular Ca2+, increased cAMP
  • -> Deranged cellular signaling
  • -> Cell proliferation & fluid secretion into the expanding cyst
    • Increased ADH casues cysts to grow faster
      • Binding of ADH to V2 receptors stimulates cAMP
      • -> Increased proliferation and fluid secretion
  • -> Cyst growth
    • Normal parenchyma is replaced by nonfunctional cysts
    • Compression and distortion of renal vasculature
    • Activation of RAAs
    • Obstruction, decreased tubular flow
20
Q

Describe the histologic changes seen in ARPKD

A

Cysts are longitudinal

Not much functional kidney in between cysts

21
Q

Describe the treatment approach to ADPKD

A
  • Blood pressure control
    • Goal = 130/80, maybe even lower
    • Use ACE inhibitro OR ARB
  • Low Na+ intake
  • Low caffeine intake
  • Avoid contact sports
  • Adequate water intake (at lease 3L/day)
    • Goal is to minimize ADH secretion
    • Increased ADH -> Increased cAMP -> Increased fluid secretion into cysts
  • Transplant
22
Q

Describe the pathophysiology of Autosomal Recessive PKD (ARPKD)

A

Genetic mutation in PKHD1 -> Abnormal fibrocystin

Normally, fibrocystin is found in primary cilia, tubular epithelial cells, and bile duct epithelial celsl

Mutation in PKHD1 -> Cystic kidney and liver

  • Oligohydramnios
  • -> Pulmonary hypoplasia
  • -> Limb defects
  • If the baby survives the neonatal period, the child will develop ESRD by age 10
23
Q

What proteins are encoded by PKD1 and PKD2?

What do they do?

A

Polycystin 1 and Polycistin 2

  • Co-localize to the primary cillum of kidny tubular epithelial cells
  • Important for maintaining normal ciliary function
    • Ciliary function is important for normal intracellular cAMP and Ca2+ levels
    • These are important for cellular signaling

Mutations = autosomal diminant polycystic kidney disease

24
Q

A mutation in MUC1 will lead to which genetic kidney disease?

A

Medullary cystic kidney disease (MCKD)

MUC1 encodes mucin 1

25
Q

What is the role of V2 receptor antagonists in treating ADPKD?

A

When ADH binds to its V2 receptor, it increases intracellular cAMP

In patients with ADPKD, this is bad because increased cAMP -> increased fluid secretion into cysts -> cyst growth

Preventing ADH from binding to its receptor prevents this increase in cAMP, thus reducing fluid secretion into cysts and cyst growth

26
Q

A mutation in PKHD1 causes which genetic kidney disease?

A

Autosomal recessive polycystic kidney disease (ARPKD)

Renal by Minnie (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions