Gordon's Syndrome Flashcards
Define hypertension
It is sustained elevation of BP (high BP)
what is systolic blood pressure (SBP)?
when the heart beats and pumps blood out
systolic pressure > cuff pressure = can hear pulses
what is cuff pressure on blood flow?
when there is occlusion in blood flow, the cuff pressure blocks the flow of blood
what is diastolic blood pressure (DBP)?
when the heart relaxes b/w beats
systolic pressure > cuff pressure = cannot hear pulses
what are blood range for
- normal
- pre-hypertension
- stage 1 hypertension
- stage 2 hypertension
- normal - 120/80
- pre-hypertension - b/w 120/80 and 139/89
- stage 1 hypertension - b/w 140/90 and 159/99
- Stage 2 hypertension - 160/100
For people over 50years, SBP is more crucial for DBP as a CVD risk factor
A. True
B. False
A. True
at 115/75mmHg, CVD risks doubles with each increment of 20/10mmHg throughout the BP range
A. True
B. False
A. True
what are risk factors for hypertension?
- environmental
2. genetic
what are the environmental risk factors for hypertension?
- smoking
- diet
- stress
what are the other names for Gordon’s syndrome?
- PHA2- Pseudohypoaldosteronsim type II
2. FHHt ( familial H & H, Hyperkalaemia and Hypertension)
what is the genetic background of Gordon’s syndrome?
- rare familial form of hypertension: monogenic and fully penetrant
- sporadic cases reported as well
what is hyperkalaemia? what does it include in GS?
- it is high serum potassium, K+
- > 8 mmol/l
- metabolic acidosis/ hyperchloremia (Cl-)
- muscle weakness, even period paralysis
what are the organs involved in hypertension?
- heart
- myocardial infarction
- diastolic dysfunction
- heart failure with reduced ejection fraction
- obstructive cardiomyopathy - brain
- kidney
- reduced GFR
- chronic kidney disease
- end stage kidney failure
- albuminuria - eyes
what are the elements required for CUL3-KLHL3 E3 ligase complex and WNK-SPAK-NCC signalling?
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.
What is mechanism that contributes to the development of Gordon’s hypertension syndrome?
the mutations resulting in ubiquitin activity inhibition
Examples of genetic modification causing Gordon’s disease. Give a further explanation for each example.
- KLHL3 - R528H
- CUL3 - exon 9 deletion
- WNK4 - D561A
What is the established treatment option for PHA II? Are there any new treatment options for PHA II, what is the targeting molecular?
established - thiazide diuretics
new - STOCK1s-50669
what are its clinical characterstics?
- hyperkalemia
- hypertension (BP>140/90)
- hyperchloremia and increased Na+ reabsorption
- metabolic acidosis
- hypercalciuria (increased ca2+ in urine)
- suppressed plasma renin levels
- variable but usually low aldosterone levels (elevated serum K+ is a potent stimulus for aldosterone secretion)
- increased sensitivity to thiazides
why is GS called pseudohypoaldosterism when you get low aldosterone?
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.
what is the diagnosis of GS?
- 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.
despite hypercalciuria the serum calcium and parathyroid hormone levels are normal
A. True
B. False
A. True
what is the BP goal to achieve for patients with diabetes or renal disease?
from BP<140/90 to <130/80
what is the location and function of the following ?
- NKCC
- NKCC2
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
what is the role of electroneutral cation chloride cotransporters (CCC) in the kidney?
- defines the salt concentration in urine
- affects the BV and BP (arterial pressure)
- their effects can be inhibited by loop or thiazide type diuretics
