Renal Disease Flashcards
What sort of disease is Liddles syndrome?
Autosomal dominant
Symptoms of Liddles syndrome
Sodium retention so fluid is retained so hypertension, hypokalaemia, metabolic alkalosis, low renin and aldosterone
What happens in a principle cell?
Apical - ENaC, ROMK, AQP2
Basolateral- Sodium potassium pump, Kir2.3, AQP3+4
What up regulates ENaC?
High renin and aldosterone
Structure of ENaC?
a, B and Y subunits
What are the mutation to ENaC in Liddles syndrome?
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
What experiments show the effect of ENaC mutation?
Rat mutant vs normal, cRNA aBY/ aBY mutant in Xenopus oocyte- both show smaller current with wildtype
Why does Liddles syndrome cause metabolic alkalosis?
Causes H+ secretion further on in the a intercalated cell due Sodium reabsorption leaving a negative charge behind in the filtrate (transepithelial potential)
What does an a intercalated cell do?
Apical- H pump (out), H out and K in
Basolateral - HCO3 (out) and Cl (in)
What is used to treat Liddles syndrome?
Amiloride - blocks ENaC and raises renin and aldosterone
What is not used to treat Liddles syndrome and why?
Spironolactone- MR recetor (on ENaC) anatagonist
Prevelance of inherited diabetes insipidus
1:25000-30000
How does vasopressin work?
Vasopressin receipt on basolateral membrane which binds Vasopressin and stimulates cAMp to PKA which leads to shuttling of AQP2 to the apical membrane
Types of diabetes insipidus
Primary polydipsia, gestational diabetes, central, nephrogenic
Primary polydipsia cause
Suppresion of AVP release
Acquired central diabetes insidious cause
Infection, head trauma, surgery which damages posterior pituitary gland
Congenital central diabetes insipidus cause
Neurophypophyseal D1, 67 mutation in AVP genes, many mutations in site for transport of AVP from hypothalamus to posterior pituitary
Acquired nephrogenic diabetes insidious cause
Lithium for bipolar, antibiotics, antifungals, antineoplastic, hypokalaemia and hypocalciuria, acute and chronic renal failure
When do symptoms appear of central diabetes insidious and what are they?
Infants- hypernatiric dehydration, poor feeding, skin dryness, depression anterior fontanel
Treatment for central diabetes insipidus
Desmopressin- nasal spray, agonist at vasopressin receptor
Possible treatments for nephrogenic diabetes insipidus
Modulator drugs- stops misfolded protein being degraded, heat shock protein 90, prostaglandins, station, pharmacological chaperones, cGMP and cAMP pathway agonists, cell permeable receptor agonists
