3 - gordons hypertension syndrome Flashcards
genetic characteristics of gordon’s syndrome
monogenic
fully penetrant
other name for gordons syndrome
pseudohyperaldosteronism type II
prevalence of high blood pressure
affects 1.13 billion people globally
systolic value refers to
blood pressure at time of contraction
definition of high blood pressure
sustained elevation of blood pressure
- greater than 140/90 mm/Hg
environmental risk factors for gordons syndrome
smoking
diet
stress
genetic risk factors for gordons syndrome
mitochondrial genome (cell death) nuclear genome (kidney/RAAS)
pathological features of gordons syndrome
hypertension
hyperalkalemia
normal renal function
sensitive to thiazide diuretics
what is hyperkalemia
increased blood/serum K+ levels
consequences of hyperkalemia
metabolic acidosis
hyperchloremia
muscle weakness –> periodic paralysis
why is hyperkalemia dangerous
Potassium is critical for the normal functioning of the muscles, heart, and nerves.
controls smooth muscle (e.g. in digestive tract) and skeletal muscle as well as the muscles of the heart–> controls rhythm
also important for transmission of electrical signals throughout the nervous system
how does metabolic acidosis cause hyperkalemia
increase in H+ in cells can displace K+ out of cells, causing a rise of serum potassium levels
how is renal function measured
using glomerular filtrate rate
differences between gordons syndrome and gitelmans syndrome
gordons:
- gain of function in NCC
- high BP, high serum K+
- normal genomic sequence of NCC
gitelmans:
- loss of function in NCC
- low BP, low serum K+
- point mutations and c-terminal tr
why is gordons syndrome known as pseudo
it mimics low levels of aldosterone
how do you diagnose gordons hypertension
molecular genetic testing
looking for mutations in WNK1, WNK4, CUL3, KLHL3
why are there increased levels of blood K+
efflux of K+ is reduced
Na+ channels are responsible for the efflux
why do levels of H+ increase
increased CO2
what causes metabolic acidosis
Decreased H+ excretion
Na+ transfer into Collecting Duct increases, in exchange for potassium as well as an H+
decreased ammonia (NH4+) excretion leads to decreased acid excretion
Increased H+ reabsorption
normal blood pressure
120/80mm/Hg
which transporters do loop diuretics inhibit
phosphorylation of NKCC1 and NKCC2
normal pH value of arterial blood
7.35-7.45
normal pO2 and pCO2 for arterial blood
pO2 = 11-13kPa pCO2 = 4.5-6kPa
effect of pCO2 on pH of the blood
increased pCO2 —> decreased pH
origin of changes in pCO2 compared to HCO3
changes in pCO2 are normally respiratory in origin
changes in HCO3 are normally metabolic in origin
effect of increased HCO3 and base excess
increased pH
causes of acidosis
respiratory accumulation of CO2
metabolic accumulation of H+ or loss of HCO3 (bicarbonate)
causes of alkalosis
respiratory cause –> hyperventilation –> loss of CO2
metabolic cause –> loss of H+, excess HCO3
what do we mean by compensation in terms of acid base balance
A change in pH outside the normal range
causes the body to attempt to compensate
to return pH towards normal
common causes of respiratory acidosis
Chronic obstructive pulmonary disease, severe asthma pneumonia muscle weakness airway obstruction
common causes of metabolic acidosis
Severe shock (e.g. sepsis) hypovolaemia cardiogenic shock diabetic ketoacidosis renal failure
common causes of respiratory alkalosis
Anything causing hyperventilation
e.g. hypoxia from pneumonia or asthma,
pain, fear, anxiety, most asthma,
salicylate poisoning
common causes of metabolic alkalosis
prolonged and severe vomiting
normal base excess or deficit from arterial blood
+ or - 2 mmol
normal bicarbonate concentration of arterial blood
25 mmol/l HCO3-
normal lactate concentration of arterial blood
> 2 mmol/l
normal oxygen saturation of arterial blood
> 96%
