Renal Disease

Question 1

What sort of disease is Liddles syndrome?

Answer 1

Autosomal dominant

Question 2

Symptoms of Liddles syndrome

Answer 2

Sodium retention so fluid is retained so hypertension, hypokalaemia, metabolic alkalosis, low renin and aldosterone

Question 3

What happens in a principle cell?

Answer 3

Apical - ENaC, ROMK, AQP2

Basolateral- Sodium potassium pump, Kir2.3, AQP3+4

Question 4

What up regulates ENaC?

Answer 4

High renin and aldosterone

Question 5

Structure of ENaC?

Answer 5

a, B and Y subunits

Question 6

What are the mutation to ENaC in Liddles syndrome?

Answer 6

They are in COOH tail of B or Y subunits so leads to deletion of proline rich motifs which allow channels to be tagged by ubiquitin and removed from the membrane

Question 7

What experiments show the effect of ENaC mutation?

Answer 7

Rat mutant vs normal, cRNA aBY/ aBY mutant in Xenopus oocyte- both show smaller current with wildtype

Question 8

Why does Liddles syndrome cause metabolic alkalosis?

Answer 8

Causes H+ secretion further on in the a intercalated cell due Sodium reabsorption leaving a negative charge behind in the filtrate (transepithelial potential)

Question 9

What does an a intercalated cell do?

Answer 9

Apical- H pump (out), H out and K in

Basolateral - HCO3 (out) and Cl (in)

Question 10

What is used to treat Liddles syndrome?

Answer 10

Amiloride - blocks ENaC and raises renin and aldosterone

Question 11

What is not used to treat Liddles syndrome and why?

Answer 11

Spironolactone- MR recetor (on ENaC) anatagonist

Question 12

Prevelance of inherited diabetes insipidus

Answer 12

1:25000-30000

Question 13

How does vasopressin work?

Answer 13

Vasopressin receipt on basolateral membrane which binds Vasopressin and stimulates cAMp to PKA which leads to shuttling of AQP2 to the apical membrane

Question 14

Types of diabetes insipidus

Answer 14

Primary polydipsia, gestational diabetes, central, nephrogenic

Question 15

Primary polydipsia cause

Answer 15

Suppresion of AVP release

Question 16

Acquired central diabetes insidious cause

Answer 16

Infection, head trauma, surgery which damages posterior pituitary gland

Question 17

Congenital central diabetes insipidus cause

Answer 17

Neurophypophyseal D1, 67 mutation in AVP genes, many mutations in site for transport of AVP from hypothalamus to posterior pituitary

Question 18

Acquired nephrogenic diabetes insidious cause

Answer 18

Lithium for bipolar, antibiotics, antifungals, antineoplastic, hypokalaemia and hypocalciuria, acute and chronic renal failure

Question 19

When do symptoms appear of central diabetes insidious and what are they?

Answer 19

Infants- hypernatiric dehydration, poor feeding, skin dryness, depression anterior fontanel

Question 20

Treatment for central diabetes insipidus

Answer 20

Desmopressin- nasal spray, agonist at vasopressin receptor

Question 21

Possible treatments for nephrogenic diabetes insipidus

Answer 21

Modulator drugs- stops misfolded protein being degraded, heat shock protein 90, prostaglandins, station, pharmacological chaperones, cGMP and cAMP pathway agonists, cell permeable receptor agonists