Distal Renal Tubular Disorders - Ault Flashcards
What are the targets of the following drugs?
Acetazolamide
Furosemide, bumetanide, ethacrynic acid
Thiazide
Amiloride, tramterene
Spironolactone, eplerenone
Acetazolamide - carbonic anhydrase
Furosemide, bumetanide, ethacrynic acid - Na-K-2Cl
Thiazide - NaCl
Amiloride, tramterene - ENaC
Spironolactone, eplerenone - Mineralocorticoid receptor
What are the mutations present in Bartter syndrome?
N-K-2Cl
ROMK
Cl- channel (CLCNKA, CLCNKB)
Barttin (Cl channel)
What are the mutations present in Gitelman Syndrome?
Thiazide-sensitive NaCl channel
What are the mutations in Liddle Syndrome?
Gain of function in ENaC
What is TTKG and what is the equation?
Transtubular Potassium Gradient
TTKG = (UK * Posm) / (PK * Uosm)
What are expected values of the TTKG in hypokalemia and hyperkalemia?
Hypokalemia < 2
Hyperkalemia > 8
What is the effect of hyperaldosteronism on potassium?
Hypokalemia
What are causes of hyperaldosteronism?
Primary (tumors)
Dehydration (pyloric stenosis)
Sodium-wasting disorders (Bartter-Gitelman)
Glucocorticoid-remediable hyperaldosteronism (GRA)
Apparent mineralocorticoid excess (AME)
What is the cause of glucocorticoid-remediable hyperaldosteronism (GRA)?
Recombination protducing hybrid molecule that makes ldosterone in response to stress
What are the effects of glucocorticoid-remediable hyperaldosteronism (GRA)?
Low renin hypertension
Hypokalemia
What is the cause of apparent mineralocorticoid excess (AME)?
Increased renal cortisol
What are the effects of apparent mineralocorticoid excess (AME)?
What is the effect of hypoaldosteronism and pseudohypoaldosteronism on potassium?
Hyperkalemia
What are the causes of hypoaldosteronism?
Congenital adrenal hypoplasia
Congenital adrenal hyperplasia
Autoimmune
What are the causes of pseudohypoaldosteronism?
PHA Type I
PHA Type II
Tubular injury (obstructive uropathy)
What are symptoms of PHA Type I?
Hyperkalemia
Hyponatremia
Hypotension
What are the causes of PHA Type I?
Mutation in mineralocorticoid receptor
Loss of function of ENaC
What is the treatment of PHA Type I?
Sodium supplements
High fluid intake
K-binding resin
What are symptoms of PHA Type II?
Hyperkalemia
Hyperchloremic metabolic acidosis
Hypertension
“Gordon syndrome”
What are the causes of PHA Type II?
Mutations in NaCl cotransporter
What is the treatment of PHA Type II?
Thiazide diuretics
What should you check first in metabolic acidosis?
Plama anion gap
Na - (Cl + CO2)
What causes elevated anion gap acidosis?
Ketoacidosis
Lactic acidosis
Metabolic errors
Poisons (ethylene glycol)
What causes normal anion gap acidosis (hyperchloremic metabolic acidosis)?
GI losses of bicarbonate
Exogenous chloride
Renal tubular acidosis
What principle does TTKG measure?
Aldosterone response in hypo/hyper kalemia
What is the anion gap in RTA?
Normal anion gap acidosis
What are the types of RTA?
Type II (proximal) - associated with Fanconi
Type I (classical distal) - very rare
Type IV (hyperkalemic) - syndrome of aldosterone deficiency
What are the tests for RTA?
Fractional excretion of bicarbonate
Urine pH
Urine anion gap
U-B PCO2
What are the fractional excretions of bicarbonate in each type of RTA?
Type I (classical distal) - <5%
Type II (proximal) - >10-15%
Type IV (hyperkalemic) - <5-10%
What is the urine pH in each type of RTA?
Type I (classical distal) - >5.5
Type II (proximal) - <5.5
Type IV (hyperkalemic) - either
What is the equation for urine anion gap?
Na + K - Cl
What is the value of the urine anion gap in diarrhea?
Negative
What is the value of the urine anion gap in RTA?
Positive
What is the U-B PCO2?
Measure of secreted CO2 following a HCO3 load
What are the results of a U-B PCO2 in each type of RTA?
Type I (classical distal) - <10-15
Type II (proximal) - 10-15
Type IV (hyperkalemia) - <10-15
What is a distinguishing feature of Type II (proximal) RTA?
Fanconi syndrome
What is a distinguishing feature of Type IV (hyperkalemic) RTA?
High plasma K
What causes RTA type IV?
Mineralocorticoid deficiency / resistance
Renal tubular dysfunction
