Distal Renal Tubular disorders Flashcards
% sodium reabsorbed in PT?
65-70%
% sodium reabsorbed in T.A.L.
25%
% sodium reabsorbed in DT
5%
Na transporter in TAL
NK2C co-transporter
Na transporter in DT
Thiazide-sensitive co-transporter Na/Cl
% sodium reabsorbed in CD
1-2% (by epithelial Na channel)
Acetazolamide target
carbonic anhydrase
Furosemide/bumetanide/ethacrynic acid target
NK2C cotransporter
Thiazides target
Na-Cl cotransporter
What targets epithelial sodium channels
amiloride and triamterene
What targets the mineral corticoid receptor
spironolactone and eplerenone
Hyperplasia of JG apparatus, elevated plasma renin and aldosterone
Bartter Syndrome
Presentation of Bartter Syndrome
1) acid base status
2) potassium
3) aldosterone
4) renin
5) 2 other features
1) Hypochloremic met alkalosis,
2) hypokalemia,
3) hyperaldosteronism,
4) hyperreninemia,
5) elevated PGE2, failure to thrive
Bartter treatment
potassium supplements, magnesium (also spironolactone)
What presents with prenatal massive polyhydramnios (due to fetal polyuria)
Neonatal Bartter (also has massive salt wasting at birth)
In neonatal Bartter, the amniotic fluid has elevated levels of
PGE2 (this is a target for treatment with COX inhibitors)
Bartter Mutations (5)
NKC2, ROMK, CLCNKA, CLCNKB, Barttin
What is barttin
Cl channel A/B inserter in kidney/inner ear
Presentation of Gitelman Syndrome
1) acid base status
2) potassium
3) magnesium
4) calcium (blood/urine)
5) other feature
1) hypochloremic met alkalosis,
2) hypokalemia,
3) hypomagnesemia,
4) Hypercalcemia / hypocalciuria
5) (presents later in life with Normal growth)
Gitelman mutation
Na-Cl co transporter of the DCT (thiazide sensitive)
Liddle syndrome presentation
1) [main feature]
2) renin
3) aldosterone
4) potassium
5) acid base status
1) hypertension,
2) low renin,
3) low aldosterone,
4) hypokalemia,
5) met alkalosis
Liddle syndrome closely resembles
Pseudohypoaldosteronism type 1
mutation in Liddle
gain of function in the Beta or gamma subunit of the epithelial sodium channel (aldosterone sensitive channel, stuck open)
Liddle treatment
salt restriction and diuretics
causes of Hypokalemia
diuretics and hyperaldosteronism
causes of hyperkalemia
hypoaldosteronism and pseudohypoaldosteronism
TTKG tests what?
aldosterone response in the DT
for TTKG, urine sodium must be?
greater than 25 mmol/L
TTKG formula
[urine potass over plasma potass] divided by [urine osm over plasma osm]
simplified TTKG formula
UK x Posm / PK x Uosm
Normal range for TTKG
2-8
Less than 2 on TTKG is?
hypokalemia
greater than 4 on TTKG is?
hyperkalemia
‘Pitfalls’ (what makes test invalid) of TTKG tests
1) urine Na less than 20 mEq/L
2) urine osm less than 300 mOsm/kg
Primary cause of hyperaldosteronism
adrenal tumor
secondary causes of hyperaldosteronism
dehydration (pyloric stenosis), sodium wasting (Barterr-Gitelman)
Genetic disorders that cause hyperaldosteronism
GRA, AME
GRA mutation
recombination of 11BHSD and aldosterone synthase (at promoter)
result/presentation of the GRA mutation
hypertension during stress
GRA causes
low renin HTN and hypokalemia
GRA treatment
glucocorticoids
GRA stands for
Glucocorticoid Remediable hyperaldosteronism
AME stands for
Apparent Mineralocorticoid Excess
AME mutation
11BHSD
AME results in
increase levels of cortisol (which activates the mineralocorticoid receptor), low renin HTN, hypokalemia
AME treatment
glucocorticoids
Hyperkalemic disorders
congenital adrenal hyperplasia/hypoplasia, autoimmune, PHA type 1 and 2, Tubular injury (obstructive uropathy)
PHA Type 1 lab findings
1) potassium
2) sodium
3) prone to what
4) mirror image of what
1) hyperkalemia,
2) hyponatremia,
3) prone to severe volume depletion (hypotension),
4) mirror image of liddle syndrom
Causes of PHA type 1
mutations in mineralocorticoid receptor and LOF mutation in the ENac (stuck shut)
which PHA type 1 cause is recessive
LOF in ENac
which PHA type 1 cause is auto dominant
mutations in M-C receptor
Liddle syndrome mode of inheritance
auto dominant
PHA type 1 treatment
sodium supplements, high fluid intake, K binding resin (kayexalate)
PHA Type 2 presentation/lab findings
1) potassium
2) acid base status
3) blood volume
4) renin/aldo
5) mirror image of what
1) hyperK,
2) hypercloremic met acidosis,
3) HTN,
4) low renin/aldosterone,
5) mirror image of Gitelman
PHA Type 2 also known as
Gordon syndrome or chloride shunt syndrome
treatment for PHA type 2
thiazide diuretics
PHA type 2 mutations
WNK1 and WNK4
function of WNK’s
serine-threonine kinases that regulate NCCT, the thiazide sensitive Na-Cl contransporter
Plasma Anion Gap formula
Na- (Cl + HCO3)
Normal range of plasma anion gap
8-20 at Le Bonheur, adults 10-12
Causes of Elevated anion gap acidosis
ketoacidosis, lactic acidosis, inborn errors of metab (methylmalonic acidemia, propionic acidemia) and poisons (methanol/ethylene glycol)
Causes of normal anion gap acidosis (hyperchlor met acid.) [according to Dr. Ault there are only 3]
1) G.I. losses of bicarbonate,
2) exogenous chloride (arginine HCl challenge, vol. expan. with NaCl),
3) renal tubular acidoses
RTA anion gap?
normal
which RTA is associated with Fanconi syndrome
type 2 (proximal)
which RTA is very rare and presents with hypoK, hypocalciuria, nephrolithiasis, and Failure 2 Thrive
Type 1 (classic distal)
which RTA is a syndrome of aldost. deficiency or unresponsiveness
Type 4
how often does RTA present with diarrhea
almost never
Tests for RTA
fractional excretion of bicarb, urine pH, urine anion gap, U-B pC02
Fract. Excr. >10-15% in which RTA
proximal RTA aka type 2
Fract. Excr.
classic distal RTA aka type 1
fract. excr.
hyperkalemic RTA aka type 4
Urine pH in classical distal RTA
greater than 5.5
Urine pH in proximal RTA (if HCO3 is below threshold)
less than 5.5
Urine anion gap
(UNa + Uk) - UCl
if UAG is negative….
NH4 is present and the CD can secrete H … also neg UAG during diarrhea
UAG in proximal, type 1, and hyperkalemic RTA
positive
can’t use UAG in what conditions
DKA, ketoacidosis
U-B pCO2 normal level
> 10-15 mmHg
U-B pCO2 is low in what type(s)
type 1 and 4
high plasma K, positive UAG, low U-B pCO2
type 4
low plasma K, pH >5.5, low U-B pCO2
type 1
low plasma K, pH
type 2
Type 4 RTA causes
primary M-C def., secondary M-C def. (diabetes, HIV), RT dysfunction (obstructive uropathy, Lupus nephritis), M-C resistance (pseudohypoaldosteronism)
Hey dipshit, what’s the anion gap in RTA?
it’s fucking normal, shit dude just remember it damn it to hell (easy killer, its too early for this shit)
