Disorders of the Distal Tubule Flashcards
Bartter’s syndrome pathogenesis
Defect in Cl- reabsorption in the NK2C cotransporter, or K+ channel ROMK, or Cl- channel, or Barttin (needed to insert Cl channels)
Bartter’s syndrome is similar in effect to which kind of diuretic?
Loop
In Bartter’s syndrome, which ions will be altered and how so?
Hypochloremia
Hypokalemia
Hyponatremia
What happens to levels of aldosterone and renin in Bartter syndrome?
Both up
What tissue changes occur in Bartter’s syndrome and why?
Hyperplasia of juxtaglomerular apparatus due to elevated prostaglandin activity
How is Bartter’s inherited?
AR
What are some S/S for neonatal Bartter syndrome?
Fetal polyuria causing polyhydramnios
Amniotic fluid - elevated PGE2
Salt wasting at birth
Calcium stones and hypercaliuria
Gitelman’s Syndrome is similar to which diuretic?
Thiazides
How is Gitelman’s inherited?
AR
Gitelman’s effects on ion levels
Hypomagnesemia
Hypokalemia
Hypocalciuria
What kind of acid-base disorder to Bartter’s syndrome patients usually have?
Hypochloremic metabolic alkalosis
Gitelman’s defect
Mutated Na/Cl cotransporter in DCT
What is the typical age of presentation for Bartter’s and for Gitelman’s?
Bartter’s is young
Gitelman’s is adults
Explain Gitelman’s pathogenesis
Defective Na/Cl symporter in DCT causes increased distal Na delivery, increasing K secretion and H secretion (leading to hypokelamia and alkalosis). The distal delivery increase also increases excreted sodium, leading to RAAS activation.
Gitelman’s S/S
Hypomagnesemia
Hypokalemia
Hypocalciuria
Hypochloremic metabolic alkalosis
Is Gitelman’s or Bartter’s more severe and why?
Bartter’s is more severe because more sodium wasting since earlier in tubule
Liddle syndrome defect
Gain of function of ENaC leading to constitutive activation
Liddle syndrome treatment
Salt restriction and diuretics
Liddle syndrome inheritance
AD
Liddle syndrome S/S
Hypertension Low renin Low aldosterone Hypokalemia Metabolic alkalosis
What are some causes of hypokalemia?
Diuretics Hyperaldosteronism (1 or 2ndary)
What are some causes of hyperkalemia?
Hypoaldosteronism
Pseudohypoaldosteronism
What does the TTKG measure?
estimates the ratio of potassium in the lumen of the CCD to that in the peritubular capillaries
What are the expected values for TTKG for hypo- and hyperkalemia?
Hypokalemia: 8
What is a primary cause of hyperaldosteronism?
Adrenal tumors
What are some secondary causes of hyperaldosteronism?
Dehydration
Bartter
Gitelman
What is the defect in glucocorticoid-remediable hyperaldosteronism?
Recombination of 11BHSD and aldosterone synthase
GRA pathogenesis
Fusion protein produces hybrid molecule that binds aldosterone receptors in times of stress, causing low renin hypertension and hypokalemia
GRA treatment
Glucocorticoids
Apparent mineralocorticoid excess pathogenesis
Mutant kidney enzyme 11BHSD causes increased cortisol in kidney which cross-reacts to activate aldosterone receptor.
Leads to low renin hypertension and hypokalemia, and treated with glucocorticoids
S/S of PHA Type I
Hyperkalemia
Hyponatremia
HYPOTENSION thru volume depletion
PHA Type I defects -2
AD mutant mineralocorticoid receptor
or
AR ENaC always off mutation
PHA Type I treatment
NA supplementation
Lots of fluids
K-binding resins
PHA Type II S/S
Hyperkalemia
Hyperchloremic metabolic acidosis
HYPERTENSION
Low RAAS
PHA Type II treatment
thiazide diuretics
PHA Type II defect
Mutated WNK1 and WNK4 which regulate Na/Cl cotransporter (thiazide target)
What are some types/causes of elevated anion gap acidosis?
Ketoacidosis
Lactic acidosis
Inborn metabolic errors
Poisons like methanol and ethylene glycol
What are some causes of normal gap acidosis?
GI loss of bicarb through diarrhea
Exogenous Cl?
**Renal tubular acidosis
Type II renal tubule acidosis
Associated with Fanconi syndrome
Proximal tubule damage
Type I renal tubule acidosis
Distal tubule
Very rare
Type IV renal tubule acidosis
Hyperkalemic
Aldosterone deficiency or unresponsiveness
What are some tests for RTA?
Fractional excretion of bicarbonate
Urine pH
Urine anion gap
Urine vs blood pCo2
What are the expected values of fractional bicarb excretion for the different types of RTA?
Proximal RTA (II): <5-10%
What are the expected values of urine pH for the different types of RTA?
Proximal RTA (II): 5.5 Hyperkalemic (IV): either
What is the formula for urine anion gap
Na + K - Cl
What would urine anion gap analysis show for the types of RTA?
All would show positive value (normal gap)
How is U-B pCO2 used to differentiate between types of RTA?
Proximal RTA: normal of >10
Type I and IV: abnormally low bicarb clearance
Low values mean lots of bicarb combined with the excess H and was turned into H20 + CO2
Explain a quick differential diagnosis for the types of RTA
Is there Fanconi? Type II
Is there hyperkalemia? Type IV
If neither one, then it is Type I
Defect in Type IV RTA
Mineralocorticoid deficiency Tubular dysfunction from obstruction or lupus Aldosterone resistance (pseudohypo...)
Does RTA have a negative or normal anion gap?
Normal anion gap acidosis
