Brainscape's Knowledge GenomeTM

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


See full index

TMS > Gordon's Syndrome > Flashcards

Gordon's Syndrome Flashcards

1
Q

Define hypertension

A

It is sustained elevation of BP (high BP)

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

what is systolic blood pressure (SBP)?

A

when the heart beats and pumps blood out

systolic pressure > cuff pressure = can hear pulses

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

what is cuff pressure on blood flow?

A

when there is occlusion in blood flow, the cuff pressure blocks the flow of blood

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

what is diastolic blood pressure (DBP)?

A

when the heart relaxes b/w beats

systolic pressure > cuff pressure = cannot hear pulses

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

what are blood range for

  1. normal
  2. pre-hypertension
  3. stage 1 hypertension
  4. stage 2 hypertension
A
  1. normal - 120/80
  2. pre-hypertension - b/w 120/80 and 139/89
  3. stage 1 hypertension - b/w 140/90 and 159/99
  4. Stage 2 hypertension - 160/100
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

For people over 50years, SBP is more crucial for DBP as a CVD risk factor
A. True
B. False

A

A. True

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

at 115/75mmHg, CVD risks doubles with each increment of 20/10mmHg throughout the BP range
A. True
B. False

A

A. True

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

what are risk factors for hypertension?

A
  1. environmental

2. genetic

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

what are the environmental risk factors for hypertension?

A
  1. smoking
  2. diet
  3. stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the other names for Gordon’s syndrome?

A
  1. PHA2- Pseudohypoaldosteronsim type II

2. FHHt ( familial H & H, Hyperkalaemia and Hypertension)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the genetic background of Gordon’s syndrome?

A
  1. rare familial form of hypertension: monogenic and fully penetrant
  2. sporadic cases reported as well
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is hyperkalaemia? what does it include in GS?

A
  • it is high serum potassium, K+
  • > 8 mmol/l
  • metabolic acidosis/ hyperchloremia (Cl-)
  • muscle weakness, even period paralysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the organs involved in hypertension?

A
  1. heart
    - myocardial infarction
    - diastolic dysfunction
    - heart failure with reduced ejection fraction
    - obstructive cardiomyopathy
  2. brain
  3. kidney
    - reduced GFR
    - chronic kidney disease
    - end stage kidney failure
    - albuminuria
  4. eyes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the elements required for CUL3-KLHL3 E3 ligase complex and WNK-SPAK-NCC signalling?

A 
1. ubiquitination
E1 ubiquitin activating enzyme
E2 ubiquitin conjugative enzyme 
E3 ubiquitin ligase
2. Wnk/SPAK signalling 
Cul3+KLHL3+WNK1/4;
WNK1/4 with ubiquitin train + E1+E2;
SPAK: Kinase domain+S-motif+CCT domain and MO25 alpha/beta;
NCC+NKCC2+NKCC1+KCC2/3;
And, present RFQV motif with WNK1/4 or N(K)CC.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is mechanism that contributes to the development of Gordon’s hypertension syndrome?

A

the mutations resulting in ubiquitin activity inhibition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Examples of genetic modification causing Gordon’s disease. Give a further explanation for each example.

A
  1. KLHL3 - R528H
  2. CUL3 - exon 9 deletion
  3. WNK4 - D561A
17
Q

What is the established treatment option for PHA II? Are there any new treatment options for PHA II, what is the targeting molecular?

A

established - thiazide diuretics

new - STOCK1s-50669

18
Q

what are its clinical characterstics?

A
  1. hyperkalemia
  2. hypertension (BP>140/90)
  3. hyperchloremia and increased Na+ reabsorption
  4. metabolic acidosis
  5. hypercalciuria (increased ca2+ in urine)
  6. suppressed plasma renin levels
  7. variable but usually low aldosterone levels (elevated serum K+ is a potent stimulus for aldosterone secretion)
  8. increased sensitivity to thiazides
19
Q

why is GS called pseudohypoaldosterism when you get low aldosterone?

A

Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels.

20
Q

what is the diagnosis of GS?

A
  • no formal diagnostic criteria for GS published
  • clinical characterstics (lab findings)
    and/or
  • identification of a heterozygous pathogenic variant in CUL3, WNK1, or WNK4 or a heterozygous pathogenic variant or biallelic pathogenic variants in KLHL3.
21
Q

despite hypercalciuria the serum calcium and parathyroid hormone levels are normal
A. True
B. False

A

A. True

22
Q

what is the BP goal to achieve for patients with diabetes or renal disease?

A

from BP<140/90 to <130/80

23
Q

what is the location and function of the following ?

  1. NKCC
  2. NKCC2
A 
1. NKCC 
Location - DCT 
Function - reabsorbs 5-10% of filtered Nacl 
2. NKCC2 
Location - TAL of loop of Henle
Function - reabsorbs 15-20% of filtered
24
Q

what is the role of electroneutral cation chloride cotransporters (CCC) in the kidney?

A
  1. defines the salt concentration in urine
  2. affects the BV and BP (arterial pressure)
  3. their effects can be inhibited by loop or thiazide type diuretics
25
Q

what is the role of nephrons in kidney?

A
  1. reabsorbs about 99% of salt

2. filters 20% of blood pumped from heart (180L per day)

26
Q

what is the role of NKCC in Cl- homeostasis?

A

it absorbs Cl-/ mediates Cl- influx

  • they are transmembrane membrane proteins
  • NCCs increase the sodium/chloride concentration inside the cell and decrease it from the serum
27
Q

What are the similarities b/w SPAK and OSR1?

A

they are 68% identical in sequence and possess a highly similar (90%) kinase catalytic domain

28
Q

Name few thiazide drugs

A
  1. chlorothiazide (diuril)
  2. hydrochlorothiazide (microzide)
  3. metolazone
  4. indapamide
  5. chlorthalidone
29
Q

what is the function of thiazide drugs?

A
  1. increases renal excretion of
    a. sodium
    b. potassium
    c. hydrogen ions (causing metabolic alkalosis)
  2. decreases renal excretion of calcium
30
Q

what are the new drug treatments for GS?

A

Stock1s-50699 is a WNK pathway inhibitor that blocks WNK-SPAK or SPAK-NCC binding.

31
Q

what goes wrong in Wnk/SPAK pathway to result in GS?

A

the ubiquitination is inhibited due to mutations in CUL3, KLH3 and Wnk1/4 which results in up regulation of wnk1/4 and therefore, increase in NKCC2/NCC activity which ultimately results in increased Na+ reabsorption

32
Q

what is ubiquitination?

A

Ubiquitination (or ubiquitylation) is an enzymatic post-translational modification in which a ubiquitin protein is attached to a substrate protein

TMS (10 decks)

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