deck_5121162 Flashcards
Where is Na+ reabsorbed?
-65-70% in the PT-25% in the thick ascending limb-5% in the distal tubule-1-2% in the CD
What is Bartter syndrome?
a hypochloremic, hypokalemic metabolic alkalosis (figure out why) caused by by mutations of genes encoding proteins that transport ions across renal cells in the thick ascending limb of the nephron (can be a mutation in the NAKCl pump, NAK ATPase, or in Ca sensing)
What is the MOI of Bartter syndrome?
AR
What is Bartter syndrome associated with?
-secondary hyperaldosteronism (via hyperplasia of the juxtaglomerular apparatus) from volume depletion-elevated PGE2 to help perfuse the glomeruli-Failure to thrive -Hypercalciuria /nephrocalcinosis (in some)-enormous salt cravings
How is Bartter syndrome treated?
-K+ supplements, and Mg supplements if needed low K+ can cause renal cysts and failure
What things are associated with neonatal Bartter syndrome?
-polyhydramnios due to fetal polyuria (can cause the baby to need to be born premature)-salt wasting at birth-nephrocalcinosis /hypercalciuria
How would neonatal bartter syndrome present?
-massive polyhydramnios due to fetal polyuria -Amniotic fluid has elevated levels of PGE2 -Massive salt wasting at birth-Nephrocalcinosis /hypercalciuria
How is neonatal bartter syndrome treated?
Sometimes treated with cyclooxygenase inhibitors
What are some potential Bartter causing mutations?
Bumetanide-sensitive Na+-K+-Cl-cotransporter (NKCC2)Apical ATP-sensitive K+ channel (ROMK)BL Cl- channel A subunit (CLCNKA) BL Cl- channel B subunit (CLCNKB)Barttin (necessary for insertion of Cl- channel A and B subunits in BL membrane in kidney and inner ear-associated in deafness)
What is Gitelman Syndrome?
AR syndrome of hypochloremic metabolic alkalosis and hypokalemia, but patients present later and usually have normal growth because it affects a less important transporter milder
What causes Gitelman Syndrome?
Mutation in the thiazide-sensitive Na+-Cl-cotransporter of the distal convoluted tubule only
Symptoms of Gitelman Syndrome?
Hypomagnesemia, hypokalemia is common Hypocalciuria (rather than hypercalciuria)- thus, thiazides can be used for kidney stones
What is Liddle syndrome?
Results from a gain-of function in the β or γ subunit of the Enac channel (aldosterone-sensitive channel; “stuck open”)
What does Liddle syndrome result in/cause?
AD MOI cause of hypertension with low renin and low aldosterone, hypokalemia, and metabolic alkalosis
How is Liddle syndrome treated?
salt restriction and diureticsNOTE: Mirror image of pseudohypoaldosteronism type I
What are some causes of hypokalemia?
-Diuretics-Hyperaldosteronism (primary or 2ndary)
What are some causes of hyperkalemia?
-Hypoaldosteronism-Pseudohypoaldosteronism
What is a TTKG?
The transtubular potassium gradient (TTKG) is utilized to held determine whether the renal response to hyperkalemia or hypokalemia is appropriate. During hyperkalemia, the TTKG should be greater than 7; lower values suggest hypoaldosteronism. During hypokalemia, the TTKG should be less than 3; greater values suggest renal potassium wasting.
What are the requirements of a TTKG?
Assumes that the only thing that happens between the cortical collecting duct, where K+ is secreted, and the final urine is that water is reabsorbedRequires measured urine and plasma osmolalityUrine osmolality must be greater than plasma osmolalityUrine sodium must be > 25 mmol/L
Eqn for a TTKG?
([K]urine/[K]plasma)/(U/Posm)
What are some requirements of a TTKG?
-urine Na must be below 20mEq/L-Uosm must be less than 300mOsm/kg
What things can cause primary hyperaldosteronism?
adrenal tumors or genetic disorders such as GRA or AME
What things can cause secondary hyperaldosteronism?
-Dehydration (pyloric stenosis- increased with with erthyromycin)-Sodium-wasting disorders (Bartter-Gitelman)will see a little hypokalemia
What is GRA?
Glucococorticoid-remediable hyperaldosteronism that results from recombination of the homologous genes for 11-β-hydroxysteroid dehydrogenase (11βHSD) (involved in cortisol synthesis pathway) and aldosterone synthase resulting in a hybrid that hyper-activates aldosterone in times of stress (when cortisol would normally be made)
What does recombination of the homologous genes for 11-β-hydroxysteroid dehydrogenase (11βHSD) and aldosterone synthase cause?
Produces a hybrid molecule that makes aldosterone in response to stress causing low renin hypertension and hypokalemia
How is GRA treated?
physiologic doses of glucocorticoids
What is AME?
Apparent Mineralocorticoid Excess that results from mutations in the kidney isozyme of 11βHSD (involved in cortisol synthesis pathway) causing increased levels of cortisol in the kidney which cross-react and activate the mineralocorticoid receptor (like extra aldosterone) causing low renin HTN and hypokalemiatreated the same as GRA
One of the main causes of hyperkalemia is hypoaldosteronism. What things can cause hypoaldosteronism?
-Congenital adrenal hypoplasia-Congenital adrenal hyperplasia (block in cortisol synthesis in adrenal gland promotes formation of androgen)-Autoimmune mediated
The other major cause of hyperkalemia is pseudohypoaldosteronism (PHA). What can cause this?
-PHA Type I (single gene)-PHA Type II (single gene)-Tubular injury (obstructive uropathy)
How does PHA Type I present?
-Hyperkalemia-Hyponatremia-Prone to severe volume depletion, hypotension“Mirror image” of Liddle syndrome look like no aldosterone is present
What are the causes of PHA type I?
Mutations in mineralocorticoid receptor-Associated with “childhood” PHA (This is AD) ORLoss-of-function mutation in the ENaC (“stuck shut”)-Associated with defects in Na+ transport in other organs -This is AR
How is PHA type I treated?
Treated with sodium supplements, high fluid intake, and K+-binding resin (sodium polystyrene sulfonate, Kayexalate®)
How does PHA Type II (aka Gordon syndrome) present?
-Hyperkalemia, hyperchloremic metabolic acidosis-Hypertension-Low renin and aldosterone levels or “chloride shunt” syndrome
PHA Type II is a mirror image of what disease?
Gitelman syndrome
What causes PHA Type II?
mutations in WNK1 and WNK4, serine-threonine kinases that regulate NCCT, the thiazide-sensitive Na+-Cl- cotransporter
How is PHA type II treated?
Treated with thiazide diuretics
What is the eqn for the plasma anion gap?
Na+ – (Cl- + HCO3)
What is a normal plasma anion gap?
Normal is 8-20 at Le Bonheur; in adults normal range is 10-12When you are confronted with a patient with acidosis, always check the anion gap: Is it normal or elevated?
What are potential causes of elevated anion gap acidosis?
-Ketoacidosis-Lactic acidosis-Inborn errors of metabolism (methylmalonic acidemia, propionic acidemia, etc.)-Poisons: Methanol, ethylene glycol, salicylates, etc.)MUDPILES
What are the causes of normal anion gap acidosis (aka Hyperchloremic Metabolic Acidosis)?
-GI losses of bicarbonate (i.e., diarrhea)-Exogenous chloride (arginine HCl challenge, volume expansion with NaCl)-Renal tubular acidosis
T or F. RTA is a normal anion gap acidosis
T. If normal, check the UAGUAG= (Na+K)-Cl
Type II (proximal) RTA is almost always associated with what?
Fanconi syndrome
How does Type I RTA present?
very rare and presents with hypokalemia, hypercalciuria, nephrolithiasis, and failure to thrive
What is Type IV RTA (most common)?
Type IV (hyperkalemic) RTA is a syndrome of aldosterone deficiency or unresponsivenessRTA almost never presents with diarrhea because they present with low K+ which is constipating
How can you test for RTA?
-Fractional excretion of bicarbonate-Urine pH-Urine anion gap-U-B PCO2
What is the eqn for Fractional Excretion of Bicarbonate?How does it vary with different RTAs?
FEHCO3 = UHCO3- x (PCr/PHCO3-) x UCr> 10-15% in proximal RTA (which is a threshold problem) (type II)less than 5% in classical distal RTA (type I)less than 5-10% in hyperkalemic RTA (type IV)
Why is Bartter syndrome associated with hypo magnesia?
Potassium from the NAKCl pump in the thick ATL is able to diffuse back into the tubule lumen through apical potassium channels, returning a net positive charge to the lumen and establishing a positive voltage between the lumen and interstitial space. This charge gradient is obligatory for the paracellular reabsorption of both calcium and magnesium ions.
How is neonatal Bartter Syndrome treated?
cyclo-oxygenase inhibitors limit the amount of fluid output, thus limiting the amount of fluid needed for the babies
What diuretic could cause Pna to gradually increase after prolonged use?
Furosemide. Thiazides will lower it.
What other disease could thiazides be useful in?
DI nephrogenic
Why is urine pH not that helpful?
If you let urine sit, the Co2 evaporates and pH increases
What is the equation for UAG?
(UNa+ UK+) - UCl-these are the principal urianryc ions
When is a UAG helpful?
for metabolic acidosis with normal anion gap
Interpretation of UAG results.
If negative, normal distal acidification is occurring (e.g. diarrhea)If negative, tubular acidosis occurring (e.g. proximal, type I and hyperkalemic RTA)
What is U-B Co2?
Giben a biarcarbonate load of acetazolamide, causing bicarbonaturia. HCO3+ combines with H+ in the proximal tubule to form H2O and Co2 (using CA). Co2 is then excreted in urine
What is a normal U-B Co2?
greater than 10-15 mmHg
When is U-B Co2 low?
normal in proximal RTA (type II) but low in types I and IV
Which RTA has high plasma K+?
Type IV (I and II are both low)
