Barters, Liddle's etc

Question 1

Bartter’s Syndrome

Answer 1

Normotensive
Hypokalaemia, metabolic alkalosis
HYPERcalciuria
Often hypomagnesaemia
Increase in urine prostaglandin E (Important to diff from Gittleman’s)
High renin, high aldosterone to compensate for sodium loss

Autosomal recessive
Neonatal presentation or “Classical” in older children when calciuria not as bad and the people have polyuria and polydipsia

Question 2

Cause of Bartter’s syndrome (what is the defect)?

Answer 2

Neonatal: Na/K/2Cl or TAL K channel
Adults: Cl- channel TAL

Question 3

Treatment of Bartter’s?

Answer 3

Lots of salt and K in diet, spironolactone, NSAIDs, ACEi

Question 4

What are the causes of hypokalaemia, metabolic alkalosis, normal to low BP?

Answer 4

Bartter’s
Loop diuretics
Chronic vomiting (comp barters will have low urine chloride)

Question 5

How does tacrolimus cause low Mg in transplant patients?

Answer 5

Inhibits TRMP6 in DCT–>loss in urine

Question 6

Gitleman’s Syndrome

Answer 6

Normotensive, metabolic alkalosis
Hypokalaemia
Hypomagnesaemia
HYPOcalciuria 
Urine prostaglandin E NORMAL 
Increased renin and aldosterone. 

Autosomal recessive, more benign than Bartters
Dx in late childhood or adulthood
MSK presentation -cramps, weakness, fatigue.

Question 7

Gitleman’s mechanism?

Answer 7

Loss of function in gene coding for Na, CL cotransporter in DCT
Looks like thiazide effect

Question 8

Where does PTH act in the tubule?

Answer 8

blocks reabsorption of phosphate in the proximal tubule

promoting calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule.

Question 9

Liddle syndrome clinical features?

Answer 9

Early onset hypertension
Hypokalaemia metabolic alkalosis
Reduced plasma renin and aldosterone

Autosomal dominant on chromosome 6

Question 10

Mechanism of Liddle syndrome?

Answer 10

Increased number of sodium channels in collecting duct cells- unable to catabolise sodium channel

Present similar to liquorice abuse and apparent mineralocorticoid excess

Question 11

Treatment of Liddle syndrome

Answer 11

Amiloride or Triamterone NOT spironolactone- need something to bind directly to the channels and block

Question 12

Gordon’s syndrome AKA…

Answer 12

AKA pseudohypoaldosteronism type II

Question 13

Gordon’s syndrome clinical features

Answer 13

Hypertension second or third decade
Hyperkalaemia, normal anion gap metabolic acidosis 
Normal renal function
Low renin and aldosterone
Hypercalciuria

Autosomal dominant
Treat with thiazides

Question 14

Gordon’s syndrome mechanism?

Answer 14

Disruptions in WNK kinases which are proteins that localise to the distal nephron and affect the thiazide sensitive Ca-Cl cotransporter in the luminal membrane.

Defect leads to increased expression and activity of transporter. This leads to increased sodium and water reabsorption and hypertension, and diminished renin secretion. Reduced salt and water is delivered distally to the potassium and hydrogen secreting cells, so less secretion occurs.

A GAIN OF FUNCTION mechanism.