Distal tubular disorders

Question 1

What are the sodium wasting disorders?

Answer 1

1. Bartter

2. Gitelman

Question 2

What is the hypertension related to disorders of sodium transport?

Answer 2

Liddle

Question 3

What is the disorder of water handling?

Answer 3

Nephrogenic diabetes insipidus

Question 4

What is the disorder of ammoniagenesis and urinary acidification?

Answer 4

Distal renal tubule acidosis

Question 5

Where is sodium reabsorbed alon the tubule?

Answer 5

1. Proximal tubule (60%)
2. TALH 20-30%
3. Distal tubule 7%
4. Collecting duct 2%

Question 6

What is neonatal Bartter syndrome?

Answer 6

Autosomal recessive disorder

Question 7

What are the clinical signs of neonata Bartter’s syndrome?

Answer 7

1. Polyhydramnios
2. Preterm delivery
3. Episode of fever and dehydration in infancy

Question 8

Where are the defects in neonatal Bartter’s syndrome?

Answer 8

1. Na-K-2CL co transporter

2. The luminal potassium channel ROMK in the TALH

Question 9

What is Classic Bartter’s syndrome?

Answer 9

Autosomal recessive disorder presents later in infancy by failure to thrive polydypsia salt cravin episodes of dehydration

Question 10

Where are the defects in Classic Bartter’s?

Answer 10

1.mUTATIOS in the luminal chloride channel in distal tubule

2.

Question 11

What is Gitelman’s syndrome?

Answer 11

An autosomal recessive disorder usually presenting with dehydration and tetany

Question 12

How are patients with Gitelman’s sometime disgnosed?

Answer 12

Incidentally on routine blood draws

Question 13

What are the symptoms of Gitelmann’s which distinguish it from Bartter’s?

Answer 13

1. Hypomagnemia
2. Elevated urine Magnesium
3. Low Calcium excretion

Question 14

Where are the defects in Gitelman’s?

Answer 14

In Giltelman’s the defects are associated with mutations in the Thiazide-sensitive cotransporter on the luminal side of the distal convoluted tubule

Question 15

What is Liddle?

Answer 15

1. Autosomal Dominant
2. Liddle syndrome results from the GAIN of function mutation in the beta or Gamma subunit of the epithelial sodium channel (ENaC)

Question 16

What is the consequence of the mutation in Liddle?

Answer 16

Hyperabsorption of sodium with hypertension and hypokalemic metabolic alkalosis

Question 17

How is Liddle treated?

Answer 17

Low sodium diet and Potassium sparing diuretics

Question 18

What portion of the tubule is impermeable to water?

Answer 18

TALH

Question 19

What controls the permeability of the Aquaporins in the collecting duct to water?

Answer 19

AVP through AVP receptor 2 and a G protein linked receptor

Question 20

What is nephrogenic diabetes?

Answer 20

Characterized by the inability to concentrate despite normal levels of antidiuretic hormone AVP

Question 21

What is the defect in Nephrogenic diabete insipidus?

Answer 21

Failure of the final pathway to insert into the luminal membrane of the collecting duct vasopressin-sensitive water channels Aquaporin 2

Question 22

What are the causes of this defect?

Answer 22

1. Defective arginine vasopressin receptor which fails to stimulate vessicles containing the water channels to insert in the plasma membrane
2. Defective water channels themselves

Question 23

Where is the AVPRz gene located?

Answer 23

X chromosome

Question 24

Where is the Aquaporin 2 gene located?

Answer 24

Chromosome 12q13

Question 25

What is reaponsible for the majority of cases of NDI?

Answer 25

deletions and point mutations in the gene for the receptor

Question 26

what is the urine like in patients with NDI?

Answer 26

Large volune hypotonic <50-100mOsm

Question 27

What is the transporter responsible for 80-90% of HCO3 reabsorption in the Prox tubule

Answer 27

Apical membrane Na+/H+ antiporter

Question 28

Where does distal acidification of the urine occur?

Answer 28

Collecting Duct

Question 29

What is RTA?

Answer 29

Hyperchloremic metabolic acidosis with a normal plasma anion gap (6-10)

Question 30

What are the common causes of High Anion Gap?

Answer 30

1. Inborn errors of metabolism such as organic acidemias
2. Ketoacidosis
3. Lactic Acidosis

Question 31

What defines TYPE II RTA?

Answer 31

Results from proximal tubular defects leading to a decreased threshold for Bi-Carb reabsorbtion

Question 32

What is Type II RTA usually associated with?

Answer 32

Fanconi’s syndrome

Question 33

What is Tpie I (Classic distal) RTA

Answer 33

Rare disorder characterized by the inability of the collecting duct to decrease the urinary pH 5.5 even in sytemic acidosis

Question 34

What characterizes TYPE I RTA?

Answer 34

Impaired ammonium excrtion and impaired excretion of titrable acid

Question 35

How do patients present with Type I RTA?

Answer 35

Hyperchloremic, hypokalemic metabolic acidosis
Polyuria
Polydipsia
Short stature

Question 36

What is the treatment for TYPE I RTA?

Answer 36

Potassium and Bicarb supplements (Polycitra)

Question 37

What charaterizes type IV RTA?

Answer 37

Characterized by hyperchloremic metabolic acidosis and hyperkalemia

Question 38

What is the cause of Type IV RTA?

Answer 38

1. Deficiency of Aldossterone

2. Inability to respond to Aldosterone action

Question 39

What are some of the etiologies?

Answer 39

Addison disease
Adrenal damage
21hydroxylase deficiency
Pseudohypoaldosteronis types I & II

Question 40

What characterizes Pseudohypoaldosteronism?

Answer 40

Hypertension with Hyperkalemia

Question 41

What are the defects in PHA Type II?

Answer 41

WNK1 and WNK4

Question 42

What is the result of the mutations in WNK1 and WNK4

Answer 42

Leads to excessive reabsorption of electroneutral sodium chloride transporter in the DCT resulting in excessive NaCl reabsorption and hypertension, reduced delivery of NaCl to the collecting duct leads to the secretion of K

Question 43

What is the treatment for Gordon’s syndrome aka Type II RTA?

Answer 43

Thiazide diuretics