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Flashcards in Renal diseases Deck (20)
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What is Liddles syndrome

Autosomal dominant inheritance - Na and fluid retention - hypertension and hypokalemia
Low renin and aldosterone levels


Where is the problem found for Liddles syndrome

Principal cells of the collecting duct - ENaC - Liddles mutation in the carboxy terminus of beta and gamma subunits


How does the mutation in ENaC lead to hypertension

Deletion of proline rich motifs used for intracellular signalling - This is necessary for endocytosis from the principal cell - Can't reuptake ENaC at normal rate so there is excess Na and water reuptake


How does Liddles lead to hypokalemia

High Na reuptake means there is more K secretion via ROMK


How does Liddles lead to a transepithelial potential and therefore a metabolic alkalosis

In the alpha intercalated cells - Absorbing Na leaves behind a negative charge - this drives H secretion - Loss of H causes a metabolic alkalosis


What happens to levels of aldosterone and renin in response to increased BP

They drop - low aldosterone causes loss of ENaC from apical membrane of the principal cells - so reduced Na reabsorption so reduced fluid retention


How do Liddles sufferers renin and aldosterone behave

In increased BP low aldosterone and renin still occur but they are unable to remove ENaC from the apical membrane - so there is no reduction in reabsorption


What is used to treat liddles syndrome

Amiloride - blocks the function of ENaC


What is diabetes insipidus

AQP2 and AVP mutations


What is the normal action of vasopressin

Produced in the hypothalamus, released from the posterior pituitary gland - acts on V2 receptors on the basolateral membrane of the principal cells - causes adenylate cyclase action - cAMP - PKA phosphorylates aquaporins in vesicles which leads to their transport to the apical membrane - water reabsorption


What is type 1 diabetes insipidus

Primary polydipsia - suppressed AVP production - caused by excessive water intake


What is type 2 diabetes insipidus

Gestational - Decreased AVP levels - metabolized by placental enzymes - relieved after childbirth


What is type 3 diabetes insipidus

Central - Impaired AVP production - can be acquired or congenital


What is type 4 diabetes insipidus

Nephrogenic - impaired effect of AVP - can be acquired or congenital


What are causes of central diabetes insipidus which is acquired

Infection, trauma, surgery - damage to pituitary gland


What are the causes of central diabetes insipidus which is congenital

Neurohypophyseal diabetes insipidus - 67 mutations in AVP gene - many mutations in sites important for AVP transport of AVP to the posterior pituitary gland


What are the causes of nephrogenic diabetes insipidus which is acquired

More common - Lithium for bipolar treatment
Some antibiotics, antifungals, hypokalemia, hypercalciuria, acute and chronic renal failure


What are the causes of nephrogenic diabetes insipidus which is congenital

Mutations in AVPR2 or AQP2 genes
AVPR2 genes are x linked
AQP2 gene impacts on trafficking(dominant), or function of protein (recessive)
Symptoms appear in infants


What are treatments of central diabetes insipidus

Desmopressin - increases urine osmolality by stimulating V2 receptors


How are nephrogenic causes treated

Difficult - possibly:
Modulator drugs - protein misfolded but still functioning
Pharmacological chaperones
Cell permeable receptor agonists
cGMP and cAMP antagonists
Heat shock protein 90