Distal Tubular Disorders Flashcards Preview

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Flashcards in Distal Tubular Disorders Deck (44):

What are the Na disorders?

Bartters syndrome, Gittlemans, and Liddle


What is the etiology of Bartter's syndrome?

Mutation in Na, K, 2Cl in TALH

 Etiology: (Autosomal Recessive) -Na, K, 2Cl mutation
-ROMK (ATP-dependent) mutation -Cl- mutation


What is the etiology of neonatal Bartter’s Syndrome?

 Polyhydraminous; high PGE2, give COX-I

Volume depletion --> excess fetal urine --> failure to thrive


What are the clinical findings in Bartter's syndrome?

1. Sodium wasting disorder
2. Hypocalcemia, hypomagnesiumemia
3. Hyochloremia, hypokalemia ---- metabolic alkalosis
---Increased K+ and H+ secretion come from increased luminal negative transiepithelial potential downstream due to increased Na delivery and increased ENaC from aldosterone
3. High renin and aldosterone because constant volume depletion
4. Crave pickle juice


What is the treatment of Bartter's syndrome?

Treatment of Bartter’s Syndrome 1. Potassium supplements
2. Magnesium supplements
3. high salt intake


What causes Gittleman's syndrome?

Mutation in thiazide sensitive NCCT in DCT causes Gittleman's, which is an autosomal recessive sodium wasting disorder


Do patients have more normal growth in Bartter's or Gittleman's?

Patients have more normal growth compared to Bartter’s because less sodium is wasted with this mutation.


What are the clinical findings in Gittleman's syndrome?

1. Hypohcloremic, hypokalemia metabolic alkalosis; low magnesium; hypercalcemia (b/c PTH effect), and high renin, aldosterone


What is Liddle's syndrome?

ENaC channel is always open due to Beta/gamma mutations. It's autosomal dominant, gain of function mutation. 


What are the clinical findings in Liddle's syndrome?

1. Hypertension
2. Mirror image of Pseudohypoaldosternism Type I
• ↓Renin and ↓Aldosterone
• ↑Na will ↑Lumen Negative Transepithelial Charge --> ↓K+ retention -->↑Hypokalemia
• ↑K in lumen will provide substrate to alpha-intercalated K/H+ ATPase -->
↑H+ excretion --> Metabolic Alkalosis


How would you treat Liddles syndrome?

Treat with triamterene or amiloride (K+ Sparing ENaC inhibitors)


What causes hypokalemia?

Diuretics, Primary or Secondary Hyperaldosteronism


What causes primary hyperaldosteronism?

Adrenal tumors


What causes  Secondary Hyperaldosteronism?

 Dehydration, pyloric stenosis (barfer’s), Bartter’s/Gittelman


What are the findings in pyloric stenosis and dehydration?

Pyloric stenosis is common in first born males with ↑vomit --> dehydration -->↑aldosterone
↓Urinary chloride


What are the findings in Bartter’s/Gittelman?

↑Urinary chloride because this is a genetic defect in Cl- transport
This is important for differentiating between secondary causes for hyperaldosteronism


What is Glucocorticoid Remediable Aldosteronisum (GRA)?

Recombination of aldosterone synthase and 11-Beta-hydroxy-dehydrogenase --> ↑aldosterone in response to stress


What are the findings in GRA?

 ↓Renin -- aldosterone not created by RAAS
 ↑Na will ↑Lumen Negative Transepithelial Charge --> ↓K+ retention -->↑Hypokalemia
 ↑K in lumen will provide substrate to alpha-intercalated K/H+ ATPase -->↑H+ excretion --> Metabolic Alkalosis


How would you treat GRA?



What is apparent mineral corticoid excess (AME)?

↑Activation of Aldosterone Receptor --> ↑ENaC

• Enzyme 11-Beta-hydroxy-dehydrogenase 2 exists to prevent glucocorticoids from binding to aldosterone receptors
• Mutated 11BHD2
• In cases of excess glucocorticoids (Cushing’s Syndrome), 11-BHD2 is overwhelmed


What are the findings in AME?

↓Renin and ↓Aldosterone
 ↑Na will ↑Lumen Negative Transepithelial Charge --> ↓K+ retention -->↑Hypokalemia
 ↑K in lumen will provide substrate to alpha-intercalated K/H+ ATPase -->↑H+ excretion ----> Metabolic Alkalosis


How would you treat AME?



What are the hyperkalemic disorders?

Hypoaldosteronism, Pseudohypoaldosteronism Type I and Type II


What three diseases fall under the catagory of hypoaldosteronism?

 Congenital Adrenal Hypoplasia, Congenital Adrenal Hyperplasia and Autoimmune Disease


What is Congenital Adrenal Hypoplasia?

Addison’s Disease-no aldosterone


What is Congenital Adrenal Hyperplasia?

Disorder of steroid synthesis pathway (21 hydroxylase most common); also could create excess cortisol activation of aldosterone receptor as in Cushing’s syndrome


What autoimmune diseases can cause hypoaldosteronism?

IDD, Hypothyroidism, and Addison’s Disease


What are the findings of hypoaldosteronism?

↓Aldosterone and ↓activation of ENaC --> ↓Lumen Negative Transepithelial Charge --> ↑K+ retention, and
hyperkalemic metabolic acidosis


What is Pseudohypoaldosteronism Type I?

Tubular disorder: have aldosterone, but doesn’t work right. OR and AD mutation in mineralocorticoid receptor OR and AR ENaC mutation (loss of function -- stuck closed -- opp. of Liddle)


What are the findings in PHA type I?

• ↑Renin to ↑Na retention
• Hyperkalemia, hyponatremia (aldosterone dysfunction)
• Prone to volume depletion( Hypotensive)


What is Pseudohypoaldosteronism Type II?

“Gordon’s Syndrome” OR “Chloride Shunt Syndrome”
Mutation in WNK 4 (regulator of NCCT) or WNK 1 (regulator of WNK 4) of NCCT


What is the mechanism of PHA type II?

↑Na reabsorption in distal convoluted tubule.
 WIll have less delivery of sodium to the CD, so no extra
excretion of K+.  Hyperkalemia


What are the findings in PHA type II?

• ↓RAAS b/c increased Na reabsorption
• Hyperkalemic
• Hyperchloremic
• Metabolic acidosis
• Mirror image of Gittelman Syndrome


What is the treatment for PHA type II?

Thiazide diuretics


What is type 1 RTA (aka Classical Distal RTA)

Inability of distal tubule to secrete H+
• Associated with nephrolithiasis (stones) and amphotercin
• Failure to thrive
• Hypokalemia -- no H+ secretion, no K+ reabsorption


What is type 2 RTA?

Proximal tubular defect. Inability of PT to resorb HCO3-. It's associated with Faconi’s Syndrome. Also see hypokalemia and it occurs in rickets, multiple myeloma (bones)


What is Type 4 RTA?

It's secondary to hypoaldosteronism

↓Aldosterone --> ↓Na reabsorption --> ↑K+ retention --> hyperkalemia
• Considered a distal tubule issue, but actually has to do with NH3 secretion proximally
• Hyperkalemia --> ↑K+ movement intracellularly --> ↑H+ movement out of cell --> ↑pH intracellular --> ↓NH3 production to restore pH
• ↓NH3 --> ↓NH4 formation


Do all RTA types have normal plasma anion gap?



What four tests are used to determine between types I, II, and IV?

1. Fractional excretion of bicarb

2. Urine pH

3. Urine Anion Gap

4. U-B PCO2



How will you determine type II vs IV using the Fractional Excretion of Bicarb assay?

• ↑HCO3- excretion in Type 2 --- ↑FeHCO3 in Type 2
• Normal HCO3- excretion in Type 1, 4


How will the urine pH assay allow you to distinguish between the different types of RTA?

• pH < 5.5 --- Type 2 because defect is proximal before acidification
• pH > 5.5 --- Type 1, 4


How will the urine Anion Gap (UNa + UK+ - UCl-) assay help you determine if the patient has RTA?

Normally: ↑H+ secretion --> ↑NH4+
Because NH4+ is not measured in urine anion gap, an elevated NH4+ will require that Cl- increases to maintain neutrality, thus Cl > Na + K
In RTA: ↓H+ secretion ---> no NH4+
Therefore, Na + K > Cl = positive


How will the U-B PCO2 assay allow you to differentiate between the types of RTA?

Give HCO3- + Acetozolamide
HCO3- cannot be absorbed in PT
In DT/CD it will react with H+ --> H2O + CO2; measure the CO2 Normal in Type 2
Low in Type 1/4 because no H+ to react