Flashcards in Distal Renal Tubular Disorders - Ault Deck (38)
What percentage of Na is absorbed in the distal tubule?
What transporter in the distal tubule is responsible for the Na reabsorption?
The Na-Cl co-transporter known as the thiazide-sensitive cotransporter (TSC)
How is neonatal bartter syndrome passed on?
Explain neonatal bartter syndrome?
polyhydraminos, preterm delivery and episodes of fever and dehydration in infancy. Failgure to thrive, hypercalciuria and nephrocalicnosis.
What are the two defective transporters in people with neonatal bartter syndrome?
Luminal Potassium Transporter ROMK in the TALH
How is classic bartter syndrome passed on?
Autosomal recessive (like neonatal bartter syndrome)
Explain classic bartter syndrome?
Presents later in infancy, failure to thrive, polydipsia, episodes of dehydration and salt craving. Hyper calciuria but not usually nephrocalcinosis.
What is the mutation in classic bartter syndrome?
Luminal chloride channel in distal tubule (ClC-Kb)
How is gitelman's syndrome passed on?
What do gitelman's affected individuals present with?
Less failure to thrive that bartters
Dehydration or tetany
What features of gitelman's distinguish it from the types of bartters syndrome?
hypomagnesemia, elevated urine magnesium, low urine calcium excretion.
What mutation is associated with gitelman syndrome?
mutation in the thiazide-sensitive cotransporter (TSC)
Both Bartters and Gitelmans Syndrome (hypochloremic metabolic alkalosis) have been associated with hyperplasia of the juxtaglomerular apparatus. Why
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?
Why are patients wth neonatal and classic bartter syndromes usually more serverly affected than patients with gitelman's syndrome?
hopefully the last time idk
What is liddle syndrome
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
If a parent had liddle syndrome, bartters or gitelmans syndrome, which must you be most concerned about passing on to your children?
liddles, because it is autosomal dominant
What is the g-protein coupled receptor that triggers the reabsorption of water from the collecting duct?
What characterizes nephrogenic diabetes insipidus?
an inability to concentrate the urine despite normal or elevated levels of ADH.
What is the final pathway malfunction in nephrogenic diabetes insipidus?
filure of the vaspressin-sensitive water channels (AQP2) to insert into the luminal membrane of the CD.
What are the two dysfunctions that can cause a lack of ADH responsitivity?
a mutation in the AVPR2 receptor
a mutation in the aquaporin itself
Of the two ways to disrupt the AQP2, what is the more common reason that leads to nephrogenic diabetes insipidus?
deletion or point mutation of the X chromosome XQ28, in 90% of cases.
What are the symptoms of nephrogenic diabetes insipidus?
polydipsia, polyuria, irritability, constipation, formula intolerance from vomiting, failure to thrive, hyperhtermia.
How does DDAVP work?
When DDAVP binds to AVPR2, it causes a release of Factor 8, to induce clotting factors.
How can you use DDAVP challenges to distinguish between a AVPR2 mutation versus an AQP2 mutation?
What can be severe problems associated with untreated nephrogenic diabetes insipidus?
the severe hypovolemia can lead to poor tissue perfusion leading to ischemia and tissue death, and mental retardation and renal damage.
What is RENAL Tubular Acidosis?
A hyperchloremic metabolic acidosis with a normal plasma anion gap
What is the normal plasma anion gap number?
What are causes of acidosis with an elevated anion gap?
inborn errors of metabolism, ketoacidosis, lactic acidosis secondary to hypoperfusion and tissue hypoxia, and exogenous poisons
What causes Type II Proximal RTA?
Proximal Tubular Defect leading to a decreased threshold for bicarbonate reabsorption
What is Type I RTA?
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
What is Type IV?
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.
What are the various causes of Type IV RTA?
Primary mineralocorticoid deficiency
Secondary mineralocorticoid deficiency
Renal Tubular Dysfunction
What is pseudohypoaldosteronism?
It's divided into two different phenotypes: PHA1 AND PHA2.
What is PHA1?
HTN, hyperkalemia with renal salt wasting. Treated with a high salt diet and fluid resuscitation with Na-containing fluid. May require K-binding resin
What is PHA2?
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.
How is urine pH used to diagnose RTA?
Can be normal in proximal RTA if serum HCO3 is below renal threshold.
Elevated in Type I RTA and variable in type IV