1. What can go wrong? – Hereditary disorders of tubule function. Bartter's syndrome (Type 1) – impaired SLC12A2 TAL cells: Effects (choose one) a) Loss of Na +, K +, modest H 2 O, hypocalcuria b) Loss of Na + K +, H 2 O; hypercalcuria c) Na + loss, K + retention, high aldosterone d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ Just like a loop diuretic!

2. What can go wrong? – Hereditary disorders of tubule function. Gitelman's syndrome – impaired SLC12A3 Effects (choose one) a) Loss of Na +, K +, modest H 2 O b) Loss of Na + K +, H 2 O; hypercalcuria c) Na + loss, K + retention, high aldosterone d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ SLC12A3 Just like thiazide diuretics!

3. What can go wrong? – Hereditary disorders of tubule function. Liddle's syndrome – hyperactive ASC (=ENaC) Effects (choose one) a) Loss of Na +, K +, hypocalcuria b) Loss of Na + K +, H 2 O; hypercalcuria c) Na + loss, K + retention, high aldosterone d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ ASC (can treat with amiloride) (this is obviously not like any diuretic)

4. What can go wrong? – Hereditary disorders of tubule function. Pseudohyporaldosteronism – inactive ASC (=ENaC) Effects (choose one) a) Loss of Na +, K +, hypocalcuria b) Loss of Na + K +, H 2 O; hypercalcuria c) Na + loss, K + retention, high aldosterone d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ ASC Secondary to altered Na + flow Aldosterone is 'trying' to correct the problem, but can't with no working ASC: symptoms mimic lack of aldosterone Like amiloride diuretics

5. What can go wrong? – Hereditary disorders of tubule function. Inactivating Mutations of Aquaporins Effects (choose one) a) Loss of Na +, K +, hypocalcuria b) Loss of Na + K +, H 2 O; hypercalcuria c) Na + loss, K + retention, high aldosterone d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ AVP + This is "nephrogenic" diabetes insipidus (please remember that the word 'diabetes' refers to passing much water, and not to the glucose problems present in diabetes mellitus).

6. What can go wrong? – Problems outside the kidney Effects (choose one) a)Loss of Na+, hyperK+, hypovolaemia b)Loss of Na + K +, H 2 O; hypercalcuria c) Whole body hypo- osmolarity d) Diabetes insipidus (polyuria, polydipsia) e) Volume expansion (body), hypertension CLICKER QUIZ Addison's disease (destruction of adrenal glands) (JFK was a sufferer) Loss of adrenal tissue -> less aldosterone: same renal result as treatment with spironolactone

7. What can go wrong? – Problems outside the kidney Effects (choose one) a)Loss of Na +, K +, hypovolaemia b)Loss of Na + K +, H 2 O; hypercalcuria c) Whole body hypo- osmolarity CLICKER QUIZPsychogenic polydipsia (this is just a random image of someone drinking, not a patient) Kidneys can only filter so much…