diseases

Question 1

what is the role of renin/aldosterone

Answer 1

promote Na+ retention + cause vasoconstriction

Question 2

what is mutated in Liddle’s syndrome and how is it mutated?

Answer 2

ENaC
mutation in -COOH tail of beta or gamma subunits containing proline-rich PY motif - allows ENaC to interact with nedd4-2 ubiquitin ligase and be ubiquitinated = tag for endocytosis of EnAC
results in slower rate of endocytosis of ENaC

Question 3

How does Liddle’s syndrome lead to hypokalaemia

Answer 3

high number of Na+ channels on apical membrane
high Na+ reabsorption across principal cells
K+ secreted via ROMK on apical membrane
loss of K+ normally retained

Question 4

how does Liddle’s syndrome lead to metabolic alkalosis

Answer 4

Na+ reabsorption –> negative membrane potential
driving force for H+ secretion from alpha intercalated cell into tubular fluid –> H+ is removed from the body
METABOLIC ALKALOSIS

Question 5

describe the AVP-AQP2 system

Answer 5

1. AVP (vasopressin) binds vasopressin 2 receptor
2. activates PKA
3. PKA phosphorylates vesicles containing AQP2 -> causes vesicles to insert AQP2 into apical membrane
4. there is a driving force for water to move from the tubular fluid to the blood via AQ2 and constitutively expressed AQP3 and AQP4 on the basal membrane

Question 6

gestational diabetes insipidus

Answer 6

decrease in circulating AVP levels because of AVP metabolism by placental enzymes
increased urine flow rate

Question 7

what are the acquired causes of central diabetes insipidus

Answer 7

trauma resulting in damage to hypothalamus, posterior pituitary gland, pituitary stalk etc.
decrease in ability to respond to changes in plasma osmolality or decrease ability to produce or release AVP

Question 8

what is neurohypophyseal diabetes insipidus caused by?

Answer 8

67 mutations in AVP gene resulting in:

• impact on transport of AVP from hypothalamus to posterior pituitary gland
• no release of AVP from posterior pituitary
• AVP released but is inactive

Question 9

nephrogenic diabetes insipidus

Answer 9

AVP is produced but kidneys lose ability to respond to AVP

Question 10

what are the acquired causes of nephrogenic diabetes insipidus?

Answer 10

• lithium
• hypokalemia and hypercalciuria - reduces AQP2 levels
• antibiotics, antifungals and antineoplastic agents
• acute and chronic renal failure

Question 11

what are some congenital causes of nephrogenic diabetes insipidus?

Answer 11

mutations in AVPR2 and AQP2:
AVPR2 mutations = x linked so more common in males
AQP2 mutations affect trafficking (dominant mutation) or function (recessive mutation)

Question 12

what are some symptoms of nephrogenic diabetes insipidus?

Answer 12

• depressed anterior fontanel
• hypernatrimic dehydration = low plasma volume, high plasma Na+
• skin dryness
• poor feeding