Distal Renal Tubular Disorders - Ault

Question 1

What percentage of Na is absorbed in the distal tubule?

Answer 1

7%

Question 2

What transporter in the distal tubule is responsible for the Na reabsorption?

Answer 2

The Na-Cl co-transporter known as the thiazide-sensitive cotransporter (TSC)

Question 3

How is neonatal bartter syndrome passed on?

Answer 3

autosomal recessive

Question 4

Explain neonatal bartter syndrome?

Answer 4

polyhydraminos, preterm delivery and episodes of fever and dehydration in infancy. Failgure to thrive, hypercalciuria and nephrocalicnosis.

Question 5

What are the two defective transporters in people with neonatal bartter syndrome?

Answer 5

NaK2Cl co-transporter

Luminal Potassium Transporter ROMK in the TALH

Question 6

How is classic bartter syndrome passed on?

Answer 6

Autosomal recessive (like neonatal bartter syndrome)

Question 7

Explain classic bartter syndrome?

Answer 7

Presents later in infancy, failure to thrive, polydipsia, episodes of dehydration and salt craving. Hyper calciuria but not usually nephrocalcinosis.

Question 8

What is the mutation in classic bartter syndrome?

Answer 8

Luminal chloride channel in distal tubule (ClC-Kb)

Question 9

How is gitelman’s syndrome passed on?

Answer 9

autosomal recessive

Question 10

What do gitelman’s affected individuals present with?

Answer 10

Less failure to thrive that bartters

Dehydration or tetany

Question 11

What features of gitelman’s distinguish it from the types of bartters syndrome?

Answer 11

hypomagnesemia, elevated urine magnesium, low urine calcium excretion.

Question 12

What mutation is associated with gitelman syndrome?

Answer 12

mutation in the thiazide-sensitive cotransporter (TSC)

Question 13

Both Bartters and Gitelmans Syndrome (hypochloremic metabolic alkalosis) have been associated with hyperplasia of the juxtaglomerular apparatus. Why

Answer 13

idk

Question 14

How can you distinguish bartter and gitelman syndromes from other chronic hypochloremic metabolic alkalosis (ie chronic vomiting diuretic abuse congential chloride diarrhea, cystic fibrosis, ingestion of formula deficient in chloride?

Answer 14

idk again

Question 15

Why are patients wth neonatal and classic bartter syndromes usually more serverly affected than patients with gitelman’s syndrome?

Answer 15

hopefully the last time idk

Question 16

What is liddle syndrome

Answer 16

A gain of fxn mutation in the beta or gamma subunit of the epithelial sodium channel (enac). results in hyperabsorption of sodium with htn and hypokalemic metabolic alkalosis. it is treated with low na diet and potassium-sparing diuretics

Question 17

If a parent had liddle syndrome, bartters or gitelmans syndrome, which must you be most concerned about passing on to your children?

Answer 17

liddles, because it is autosomal dominant

Question 18

What is the g-protein coupled receptor that triggers the reabsorption of water from the collecting duct?

Answer 18

AVP/Vasopressin/ADH

Question 19

What characterizes nephrogenic diabetes insipidus?

Answer 19

an inability to concentrate the urine despite normal or elevated levels of ADH.

Question 20

What is the final pathway malfunction in nephrogenic diabetes insipidus?

Answer 20

filure of the vaspressin-sensitive water channels (AQP2) to insert into the luminal membrane of the CD.

Question 21

What are the two dysfunctions that can cause a lack of ADH responsitivity?

Answer 21

a mutation in the AVPR2 receptor

a mutation in the aquaporin itself

Question 22

Of the two ways to disrupt the AQP2, what is the more common reason that leads to nephrogenic diabetes insipidus?

Answer 22

deletion or point mutation of the X chromosome XQ28, in 90% of cases.

Question 23

What are the symptoms of nephrogenic diabetes insipidus?

Answer 23

polydipsia, polyuria, irritability, constipation, formula intolerance from vomiting, failure to thrive, hyperhtermia.

Question 24

How does DDAVP work?

Answer 24

When DDAVP binds to AVPR2, it causes a release of Factor 8, to induce clotting factors.

Question 25

How can you use DDAVP challenges to distinguish between a AVPR2 mutation versus an AQP2 mutation?

Answer 25

????

Question 26

What can be severe problems associated with untreated nephrogenic diabetes insipidus?

Answer 26

the severe hypovolemia can lead to poor tissue perfusion leading to ischemia and tissue death, and mental retardation and renal damage.

Question 27

What is RENAL Tubular Acidosis?

Answer 27

A hyperchloremic metabolic acidosis with a normal plasma anion gap

Question 28

What is the normal plasma anion gap number?

Answer 28

6-10

Question 29

What are causes of acidosis with an elevated anion gap?

Answer 29

inborn errors of metabolism, ketoacidosis, lactic acidosis secondary to hypoperfusion and tissue hypoxia, and exogenous poisons

Question 30

What causes Type II Proximal RTA?

Answer 30

Proximal Tubular Defect leading to a decreased threshold for bicarbonate reabsorption

Question 31

What is Type I RTA?

Answer 31

The inability of CD to decrease the urinary pH below 5.5 even with systemic acidosis. The person cannot excrete ammonium sufficiently and is:

hyperchloremic, hypokalemic metabolic acidosis, polyuria, dehydro, constipation, short stature, failure to thrive. Nephrocalcinosis

Question 32

What is Type IV?

Answer 32

Characterized by hyperchloremic metabolic acidosis and hyperkalemia. Results from deficiency of aldosterone or an inability to respond to aldoseterone action. Unlike Type I RTA, can have urine pH below 5.5.

Question 33

What are the various causes of Type IV RTA?

Answer 33

Primary mineralocorticoid deficiency
Secondary mineralocorticoid deficiency
Mineralocorticoid resistance
Renal Tubular Dysfunction

Question 34

What is pseudohypoaldosteronism?

Answer 34

It’s divided into two different phenotypes: PHA1 AND PHA2.

Question 35

What is PHA1?

Answer 35

HTN, hyperkalemia with renal salt wasting. Treated with a high salt diet and fluid resuscitation with Na-containing fluid. May require K-binding resin

Question 36

What is PHA2?

Answer 36

AKA gordon’s syndrome HTN with hyperkalemia. Genetic defect in wnk1 and wnk4. Abnormalities in these proteins lead to XS reabsorption of the electroneutral sodium chloride transporter in DCT. As such, XS Na and Cl to the CD, which limits potassium secretion, contributing to hyperkalemia.

Question 37

How is urine pH used to diagnose RTA?

Answer 37

Can be normal in proximal RTA if serum HCO3 is below renal threshold.

Elevated in Type I RTA and variable in type IV

Question 38

How can urine anion gap be used to diagnose RTA?

Answer 38

UAG is typically +10.

With a negative number, indicates presence of increased ammonium.

UAG is pos in proximal, I, IV RTA. Negative in presence of Bicarb loss and exogenous acid.