A L2.1 BP & Genetics Flashcards Preview

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Flashcards in A L2.1 BP & Genetics Deck (12)
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1

Relationship b/w populations & genes

  • Distribution remains similar
  • Small genetic effect, mainly env

2

3 sequence variances of genetic BP

  • Extremely rare  - major genetic diseases with big effect
  • Rare - (<1/2000) coding mutations (coding = proteins altered) with modest effect (<5mmHg)
  • Common (1/3) non-coding variant with small effect (<1mmHg)

3

What is the missing heritability?

  • All the BP loci discovered accounts for <5% of the heritability of BP

4

Renin-angiotensin system (RAS)

  • Renin (Kidneys) + Angiotensin (Liver) = Angiotensinogen I
  • ANG I → ANG II (By ACE from (lungs)
  • ANG II acts on → Adrenal → prod. Aldosterone (a mineralocorticoid - affects minerals i.e Na)
  • Aldosterone acts on principal cells → Mineralocorticoid R. → Nucleus → ↑Epitheial Na+ channels (ENaC) → ↑Na influx & retention

5

What is cortisol

  • a glucocorticoid (affects metabolism) 

6

v. rare genetic diseases

  • Liddle's syndrome (pseudoaldosteronism)
  • Apparent mineralocorticoid excess
  • Glucocorticoid suppressible hyperaldosteronism
  • Mineralocorticoid R. gene mutation
  • Gordon's syndrome
  • Hypertension with brachydactyly 

7

Liddle's syndrome

  • (pseudoaldosteronism)
  • Looks like aldosteronism (excess [aldosterone]), but [aldosterone] is low
  • Mutations in SCNN1B & SCNN1G genes → activates ENaC
    • ↑Na & ↓K+ (hypokalemia) & ↓H+ → ↑fluid retention → ↑BP

8

Apparent mineralocorticoid excess

  • Reduced 11β-HSD2 enzyme (responsible for deactivation cortisol → cortisome)
  • ↓ [aldosterone];
  • ↑[cortisol] 1000% → access to mineralocorticoid R. → ↑BP → further ↓[aldosterone] (action not needed)

9

Glucocorticoid suppressible hyperaldosteronism

  • ↑[aldosterone]
  • Chromosomal rearrangement → hybrid genes → create ACTH sensitive aldosterone synthase
    • No -ve feedback to turn it off
    • MC usually does not respond to ACTH (usually switched on by K+)
  • GC suppressible → GC suppresses ACTH → turns off excessive aldosterone

10

Mineralocorticoid R. gene mutation

  • Abnormal stimulation of MR by progesterone
    • Normally deaf to progesterone

11

Gordon's syndrome

  • Autosomal dominant
  • Hyperkalemia AND Hypertension with NORMAL renal function
  • WNK1 & WNK4 mutations (responsible for Na/K balance)
    • Disrupted normal control → Na & K retention

12

Hypertension with brachydactyly

  • Autosomal dominant
  • Normal RAS
  • Abnormal autonomic baroreceptor reflex function
    • Chromosome 12