Distal tubular disorders Flashcards
What are the sodium wasting disorders?
- Bartter
2. Gitelman
What is the hypertension related to disorders of sodium transport?
Liddle
What is the disorder of water handling?
Nephrogenic diabetes insipidus
What is the disorder of ammoniagenesis and urinary acidification?
Distal renal tubule acidosis
Where is sodium reabsorbed alon the tubule?
- Proximal tubule (60%)
- TALH 20-30%
- Distal tubule 7%
- Collecting duct 2%
What is neonatal Bartter syndrome?
Autosomal recessive disorder
What are the clinical signs of neonata Bartter’s syndrome?
- Polyhydramnios
- Preterm delivery
- Episode of fever and dehydration in infancy
Where are the defects in neonatal Bartter’s syndrome?
- Na-K-2CL co transporter
2. The luminal potassium channel ROMK in the TALH
What is Classic Bartter’s syndrome?
Autosomal recessive disorder presents later in infancy by failure to thrive polydypsia salt cravin episodes of dehydration
Where are the defects in Classic Bartter’s?
1.mUTATIOS in the luminal chloride channel in distal tubule
2.
What is Gitelman’s syndrome?
An autosomal recessive disorder usually presenting with dehydration and tetany
How are patients with Gitelman’s sometime disgnosed?
Incidentally on routine blood draws
What are the symptoms of Gitelmann’s which distinguish it from Bartter’s?
- Hypomagnemia
- Elevated urine Magnesium
- Low Calcium excretion
Where are the defects in Gitelman’s?
In Giltelman’s the defects are associated with mutations in the Thiazide-sensitive cotransporter on the luminal side of the distal convoluted tubule
What is Liddle?
- Autosomal Dominant
- Liddle syndrome results from the GAIN of function mutation in the beta or Gamma subunit of the epithelial sodium channel (ENaC)
What is the consequence of the mutation in Liddle?
Hyperabsorption of sodium with hypertension and hypokalemic metabolic alkalosis
How is Liddle treated?
Low sodium diet and Potassium sparing diuretics
What portion of the tubule is impermeable to water?
TALH
What controls the permeability of the Aquaporins in the collecting duct to water?
AVP through AVP receptor 2 and a G protein linked receptor
What is nephrogenic diabetes?
Characterized by the inability to concentrate despite normal levels of antidiuretic hormone AVP
What is the defect in Nephrogenic diabete insipidus?
Failure of the final pathway to insert into the luminal membrane of the collecting duct vasopressin-sensitive water channels Aquaporin 2
What are the causes of this defect?
- Defective arginine vasopressin receptor which fails to stimulate vessicles containing the water channels to insert in the plasma membrane
- Defective water channels themselves
Where is the AVPRz gene located?
X chromosome
Where is the Aquaporin 2 gene located?
Chromosome 12q13
What is reaponsible for the majority of cases of NDI?
deletions and point mutations in the gene for the receptor
what is the urine like in patients with NDI?
Large volune hypotonic <50-100mOsm
What is the transporter responsible for 80-90% of HCO3 reabsorption in the Prox tubule
Apical membrane Na+/H+ antiporter
Where does distal acidification of the urine occur?
Collecting Duct
What is RTA?
Hyperchloremic metabolic acidosis with a normal plasma anion gap (6-10)
What are the common causes of High Anion Gap?
- Inborn errors of metabolism such as organic acidemias
- Ketoacidosis
- Lactic Acidosis
What defines TYPE II RTA?
Results from proximal tubular defects leading to a decreased threshold for Bi-Carb reabsorbtion
What is Type II RTA usually associated with?
Fanconi’s syndrome
What is Tpie I (Classic distal) RTA
Rare disorder characterized by the inability of the collecting duct to decrease the urinary pH 5.5 even in sytemic acidosis
What characterizes TYPE I RTA?
Impaired ammonium excrtion and impaired excretion of titrable acid
How do patients present with Type I RTA?
Hyperchloremic, hypokalemic metabolic acidosis
Polyuria
Polydipsia
Short stature
What is the treatment for TYPE I RTA?
Potassium and Bicarb supplements (Polycitra)
What charaterizes type IV RTA?
Characterized by hyperchloremic metabolic acidosis and hyperkalemia
What is the cause of Type IV RTA?
- Deficiency of Aldossterone
2. Inability to respond to Aldosterone action
What are some of the etiologies?
Addison disease
Adrenal damage
21hydroxylase deficiency
Pseudohypoaldosteronis types I & II
What characterizes Pseudohypoaldosteronism?
Hypertension with Hyperkalemia
What are the defects in PHA Type II?
WNK1 and WNK4
What is the result of the mutations in WNK1 and WNK4
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
What is the treatment for Gordon’s syndrome aka Type II RTA?
Thiazide diuretics
