Distal Renal Tubule Disorders Flashcards
1
Q
Where is renal sodium reabsorbed? Which diuretics act in each segment?
A
- 65-70% in proximal tubule (Acetazolamide)
- 25% reabsorbed in the thick ascending limb of the loop of Henle (Na+-K+-2Cl- cotransporter -> Loop Diuretics and ethacrenic acid)
- 5% reabsorbed in distal tubule by thiazide-sensitive co-transporter (Thiazides)
- 1-2% reabsorbed in collecting duct (epithelial Na+ channel -> Amiloride, Triamterene; Spironolactone, Eplerenone via aldosterone inhibition)
2
Q
Bartter Syndrome
A
- Hypochloremic metabolic alkalosis (failure to thrive)
- Hyperplasia of JG apparatus
- INC renin and aldosterone (due to Na wasting)
- Hypokalemia -> tx with potassium supplements
- Elevated PGE2 (dilates afferent arterioles)
- Hypercalciuria/nephrocalcinosis (in some)
- Hypomagnesemia (in some): Mg supplements, if needed
- Huge salt intake (pickle juice); autosomal recessive
3
Q
Neonatal Bartter
A
- Can present prenatally w/massive polyhydramnios due to fetal polyuria -> may need to tap pregnancy (or have premature birth)
- Amniotic fluid has elevated levels of PGE2
- Massive salt wasting at birth
- Nephrocalcinosis/hypercalciuria
- Low K: can’t concentrate urine appropriately, so have to pee a lot (polyuria)
- Sometimes treated w/COX inhibitors -> limits blood delivery to kidney, DEC amt of urine they give out, making it easier on them bc they don’t have to drink as much water and have more room for food
1. One of the reasons they fail to thrive
4
Q
What are the Bartter syndrome mutations?
A
- Bumetanide-sensitive NK2Cl cotransporter
- ATP-sensitive K+ channel (ROMK)
- Cl- channel A subunit (CLCNKA)
- Cl- channel B subunit (CLCNKB)
- Barttin (necessary for insertion of Cl- channel A and B subunits in cell membrane in kidney and inner ear)
- NOTE: tubule dumping all of this Na, so aldosterone on to try and maintain Na, but your tubules still won’t let you -> losing it faster than you can hold onto it
5
Q
Gitelman Syndrome
A
- Auto recessive hypochloremic metabolic alkalosis and hypokalemia, but patients present later and usually have normal growth
- Hypomagnesemia is common
- Hypocalciuria (rather than hypercalciuria)
- Mutation in the thiazide-sensitive Na+-Cl-cotransporter of the distal convoluted tubule
- These patients present later than Bartter’s because much less sodium loss (less reabsorption here)
6
Q
Liddle Syndrome
A
- GOF in the beta or gamma subunit of ENaC (aldosterone-sensitive channel -> “stuck open”)
- Auto dominant cause of HTN: low renin, low aldo, hypokalemia, and metabolic alkalosis
- Treatment: salt restriction and diuretics
- Consistent reabsorption of the 1-2% reabsorbed in the distal tubule, leading to volume overload
- Mirror image of pseudohypoaldosteronism type I
7
Q
What are the causes of hypokalemia and hyperkalemia?
A
-
Hypokalemia:
1. Diuretics
2. Hyperaldosteronism
a. Primary: tumors
b. Secondary: Bartter’s, Gitelman’s -
Hyperkalemia:
1. Hypoaldosteronism
2. Pseudohypoaldosteronism
8
Q
What is TTKG? What are the expected values and pitfalls?
A
- Index reflecting conservation of K in the CCD of the kidneys -> estimates ratio of K in the lumen of the CCD to that in the peritubular capillaries
-
Expected values:
1. Hypokalemia: <2 (low bc you are trying to hold onto K)
2. Hyperkalemia: >8 (high bc you are trying to get rid of K) -
Pitfalls:
1. Urine Na <20 mEq/L
2. Urine osmolality <300 mOsm/L
9
Q
What are the hyperaldosteronism causes of hypokalemia?
A
- Primary: adrenal tumors
-
Secondary:
1. Dehydration, pyloric stenosis (narrowing in the pylorus -> present with projectile vomiting)
2. Sodium-wasting disorders (Bartter-Gitelman) - Genetic disorders (low K w/HTN): glucocorticoid remediable hyperaldosteronism (GRA), apparent mineralocorticoid excess (AME)
10
Q
What is GRA?
A
- Glucocorticoid remediable hyperaldosteronism
- Recomb0 of homologous genes for 11-β-hydroxy-steroid dehydrogenase (11βHSD) and aldosterone synthase -> hybrid molecule that makes aldosterone in response to stress
- Causes low renin HTN and hypokalemia
- Treated with physiologic doses of glucocorticoids (i.e., hydrocortisone -> to keep body from making its own cortisol)
- Promoter that makes cortisol stuck on the gene that makes aldosterone, so the coding sequence makes aldosterone
11
Q
Apparent Mineralocorticoid Excess
A
- Mutations in kidney isozyme of 11βHSD
- Inactivating mut leads to elevated levels of cortisol in the kidney, which cross-react and activate the mineralocorticoid receptor -> kidney thinks it is more aldosterone (aldo-like effect)
- Causes low renin HTN, hypokalemia, hypernatremia
- Tx: physiologic doses of glucocorticoids
12
Q
What are the hyperkalemic disorders?
A
-
Hypoaldosteronism (hyperkalemia and acidosis)
1. Congenital adrenal hypoplasia: don’t have enough tissue to make what you need
2. Congenital adrenal hyperplasia: defect in synthesis pathway, so can’t get to aldosterone
3. Autoimmune -
Pseudohypoaldosteronism (PHA)
1. PHA Type I: hypotension (opposite of Liddle)
2. PHA Type II: hypertension (opposite of Gitelman)
3. Tubular injury (obstructive uropathy): babies born with urinary tract obstruction
13
Q
PHA Type I
A
- Hyperkalemia + hyponatremia -> prone to severe volume depletion, hypotension
1. Mutations in mineralocorticoid receptor: assoc w/childhood PHA; auto dom
2. LOF mut in ENaC (“stuck shut”): opposite of Liddle, assoc w/defects in Na+ transport in other organs, auto recessive - Tx: Na supplements, high fluid intake, and K+-binding resin (Na polystyrene sulfonate, Kayexalate®)
14
Q
PHA Type II
A
- Aka, Gordon or Cl shunt syndrome: hyperkalemia, hyperchloremic metabolic acidosis
- HTN (reabsorbing too much Na) w/low renin & ald
- Mirror image of Gitelman: muts in WNK1 and WNK4, serine-threonine kinases that regulate NCCT, the thiazide-sensitive Na+-Cl- cotransporter
- Treatment: thiazide diuretics
15
Q
Plasma Anion Gap
A
- Na+ – (Cl- + CO2) -> CO2 = HCO3 for our purposes
- Normal is 8-20 at Le Bonheur; in adults, normal range is 10-12
- When you are confronted with a patient with acidosis, always check the anion gap: is it normal or elevated? -> typically, elevated anion gap things are those that are really dangerous (can kill you)
24
Q
What are the distinguishing characteristics of the various RTA’s? Answer is a table.
A
