Ch 1, part 1 - Hyponatremia Flashcards
Hyponatremia effects on:
1) Bones
2) Heart
3) Lifespan
1) Bones -> increase risk for osteoporosis, gait instability, fall, fracture.
2) Heart –> Myocardial fibrosis (rats)
3) Lifespan –> early senescence ( rats).
Copeptin - describe metabolism
Pre-pro-AVP –cleaved–> ADH + Copeptin + neurophysin II
Copeptin is surrogate for what? Why is this measured?
Surrogate for ADH levels.
Measured b/c more STABLE compound than ADH.
Copeptin increased/decreased in what conditions?
Increased in CHF, SIADH, sepsis
Reduced in cDI.
T/F: Copeptin shown to be increased earlier than troponin in acute MI and suggested to be used as marker of early MI.
True
Why do we not check copeptin in US?
not commercially available in US yet.
What would it mean if there is loss of “pituitary bright spot” on MRI?
ADH may be seen as Pituitary “bright spot” on MRI
If Pit bright spot is absent on MRI, that is suggestive of central DI.
range of clinical presentation of hyponatremia?
Asymptomatic. Slowed mentation Lethargy, HA, n/v, disorientation, Muscle cramps, Reduced reflexes. Seizures
What is Pseudohyponatremia? Why does it happen?
Happens with old technique (Flame photometric assay) where lipids/proteins get in the way in vitro.
How can we avoid pseudohyponatremia?
Newer methods avoid this via Ion-specific electrodes, supra-cenrifugation of serum removes paraproteins/lipids prior to measuring sNa.
Hyperosmolar Hypernatremia causes and mechanism
Mechanism: shift of water from intra –> extracellular space
Causes:
- hyperglycemia
- hypertonic mannitol
- sucrose, maltose (eg, mixed in IVIG solutions)
Renal salt wasting mechanism of hypoNa
volume depletion –> appropriate ADH release –> hyponatremia
Renal salt wasting causes/situations
- Acute, recent diuretic use
- HypoAldosterone
- Cerebral salt wasting
- hypovolemic pt but Una > 20-30 and Uosm > 300
Cytoxan is a/w SIADH (T/F)
True
symptomatic HIV is a/w SIADH (T/F)
True
Mechanism of Hypothyroidism and hypoNa
severe (eg, myxedema), TSH > 50 mIU/ml —> reduced CO, PVR, renal perfusion –> increased ADH secretion.
Kidney failure usually has what Uosm?
isosthenuric Uosm 300 mOsm/L.
can’t dilute or concentrate urine when kidneys don’t work
Situations where Uosm < 100
Polydipsia –> appropriate dilution of urine
Low solute intake –> need solute in nephron to get rid of water (see card 21).
Hypotonic fluids –> appropriate dilution
Hypocortisolism and hypoNa - mechanism?
Increased synthesis of Corticotropin-releasing hormone (co-expressed w/ ADH) –> thus, higher ADH.
Pregnancy and hypoNa – mechanism?
Reduced threshold for ADH secretion + increased thirst
Tea and toast/beer potomania: explain.
Kidneys can’t excrete just pure water, they need at least 50-100mOsm of solute to excrete every 1L of water.
Low solute states –> less Na delivery –> less water excretion.
Irrigation fluids: eg, Transurethral resection, Hysteroscopy, nephrolithotomy
Explain the hyponatremia. Which fluid should not cause hyponatremia?
HYPO-osmotic 1.5% glycine = 200mOsm/kg.
Note:When > 1.5-2L of it is used, ADH can be stimulated directly.
- Hypo-osmotic 3% Sorbitol = 165mOsm/kg. Sorbitol becomes glc/fructose in liver, then CO2 + H2O.
- Isotonic 5% mannitol does not cause hyponatremia (275 mOsm/L).
SIADH vs. NSIAD
Long answer
SIADH is inappropriate ADH release –> kidney –> water reabsorption
NSIAD = Nephrogenic syndrome of inappropriate anti-diuresis = Constitutively activated ADH receptor w/o presence of ADH. == X-linked gain of function mutation of AVP 2 receptor. == Clinically, looks same as SIADH, but ADH levels low. == Confirmatory Diagnosis == Sequencing AVP2 receptor gene == carriers of mutation have abnormal response to water-loading test.
(similar conceptually to cDI vs. nDI)
SIADH vs. NSIAD
Short answer
SIADH –> too much ADH
NSIAD –> low ADH, but abnormal V2 receptor (always active)
Diuretics that can lead to hyponatremia
Most common -- thiazides, Less common: Indapamide (thiazide) Amiloride (eNaC blocker, K sparing) Lasix (if becomes hypovolemic)
2 ways drugs affect ADH
1) Increase hypothalamic ADH production
2) Potentiate ADH effect
Drugs that increase hypothalamic ADH
Anti-depressants
Anti-psychotics (thioridazine, trifluoperazine, haldol).
Anti-epileptics (Carbamezepine, Oxcarbazepine, Valproic acid),
ChemoTx (Vincristine, vinblastine, IV cytoxan, melphalan, ifosfamide, MTX, IFN alpha/gamma, levamisole, pentostatin, monoclonal antibodies),
Opiates.
ACEi – mechanism of hypoNa
Rare
AT 1 –> AT 2. ACEi blocks this in peripheral tissues, not in brain.
ACEi –> increased AT1 levels in periphery, AT1 then goes to brain –> makes more AT 2 in brain –> more thirst and ADH release –> hyponatremia.
Drugs that Potentiate ADH effect
Anti-epileptics (carbamezepine, lamotrigine)
IV Cytoxan
NSAIDs
How does IVIG cause hyponatremia
1) IVIG (w/ sucrose or maltose) –>
(i) PseudohypoNa if flame photometric assay used (lot of globulins);
(ii) hyper-osmolar (similar to hyperglycemia induced hyponatremia mechanism of water coming out to high sugar) - more likely to happen in renal insufficiency since there is reduced sugar excretion.
mechanism of Ecstasy and other amphetamines in hyponatremia
Increased hypothalamic ADH secretion + increased water intake due to hyperthermia.
T/F Less commonly associated w/ hyponatremia: Nicotine patch, Colchicine poisoning, Tacrolimus, PPIs, Hydroxyurea, Azithro, Glipizide, Heparin (unfractionated).
True
what is effect of hypoxemia in pt with hyponatremia
Hypoxemia can exacerbate hyponatremic encephalopathy
Oxygenation is therefore important.
As you correct the hypoNa, who is at risk of hypotonic polyuria the most?
Theme: loss or reduction of ADH = hypotonic polyuria
- post - pituitary infarction (loss of ADH)
- steroid replacement for cortisol deficiency (suppression of ADH release).
- d/c of DDAVP in pts using it chronically (eg, central DI)
- primary polydipsia
- volume depleted pt who gets rapid volume expansion
- recovery from acute resp failure
- d/c of thiazides
T/F
K+ supplementation will increase Na+ and correct it same amount.
True
Pt needs 200meq Na to raise Na to goal, but also needs 75mEq K. What can you do?
Give 125meq Na + 75meq K = 200meq.
You don’t need to give 275, otherwise you’ll overshoot.
K+ = Na+ in terms of correction of hypoNa.
what are the concurrent factors that increase ODS risk?
ODS can happen independent of rate of Na correction
Concurrent HYPO: K, Mg, Phos, Thiamine, or any combo of these.
Classic: ALCOHOLIC
what % of increase in Na should reduce cerebral edema significantly?
~5%
eg, Na 115 (5% = 5.75), so ~6meq/L to Na 121 should do it.
Who is at high risk for ODS?
- Na < 105
- Alcoholic
- Malnourished
- Advanced Liver disease
- Hypokalemia
How does ODS look in 1-2 days post over correction?
generalized encephalopathy
How does ODS look in 2-3 days post over correction?
behavioral changes, CN palsies, weakness, Quadriplegia (“locked in” syndrome), possible death
Is ODS reversible?
Partial to complete recovery of mild to moderate neurological complications possible.
DDAVP and hypotonic fluids to reverse overcorrection has been shown to be beneficial in rats and humans (case reports).
What is recommended correction rate for acute hyponatremia (< 48 hr)?
6-8 mEq/L per 24 h
What is recommended correction rate for chronic hyponatremia (> 48 hr)?
4-8meq/L per day
4-6meq/L per day for high risk ODS
Don’t exceed ___ in 48 hours of hypoNa correction
not more than 18mEq/L in 48 hrs
In whom to consider fluid restriction?
euvolemic/hypervolemic.
Anyone not hypovolemic basically.
does “fluid” in fluid restriction only refer to “free water” intake?
no!
all fluids
how much should pt fluid restrict by?
aim for 500ml BELOW pt’s average daily UOP.
pt w/ euvolemic hyponatremia, making ~1200 mL UOP per day. How much should they fluid restrict themselves?
aim for 500ml BELOW pt’s average daily UOP.
~700mL/day
who usually fails fluid restriction for hyponatremia tx?
- -> High Uosm > 500
- -> (Una + Uk) / SNa > 1 (high urine solutes)
- -> Baseline urine volume < 1500ml/day
when to use 0.9% saline in hyponatremia
hypovolemic (regardless of how high Uosm is).
what to do if pt w/ severe symptomatic hyponatremia (eg, seizures, severely depressed mental status)?
3% NS 100ml every 10 min to break seizures or total 3 boluses (whichever is first).
Other than in severe symptomatic hyponatremia, can we use hypertonic 3% saline in less symptomatic patients?
yes, could consider in SIADH pt w/ Na < 120 w/ very high Uosm»_space; 300.
(We know 2% would be king here, but what do they know?? hehehehe)
T/F
Any salt solution used should have higher osmolarity than the pt’s Uosm (in SIADH pts), otherwise may worsen hyponatremia.
True
If NS is used for SIADH w/ Uosm > 300, then desalination occurs and more water is retained than salt.
how many mEq of Na are in:
1) 1gm NaCl tab
2) 0.9% NS
3) 3% NS
1) 1gm NaCl –> 18 meq Na
2) 0.9% NS –>154 mEq of Na
3) 3% NS –> 513 mEq of Na
Give 3 ADH blockers
Demeclocycline
Tolvaptan
Conivaptan
Mechanism and issues with Demeclocycline
Inhibits ADH binding to receptor.
Contraindicated in pregnancy, kids due to bone/teeth development/staining.
Nephrotoxic, photosensitive rash.
this vaptan is given only PO
tOlvaptan (O for oral)
this vaptan is given only IV
conIVaptan (IV in the name!)
this vaptan blocks both V1a and V2 receptors
Conivaptan
this vaptan blocks only V2 receptor
Tolvaptan
why should conivaptan use be limited to 4 days
significant drug interactions w/ other agents metabolized by CYP3A4
T/F
Vaptan use has been shown to improve long term survival in hyponatremia
False, it has not improved long term outcomes.
(T/F)
If pt just came off 3% NS, it is highly recommended to start them on vaptan
False – can cause overcorrection
in which situation is a vaptan ineffective
in renal failure (sCr > 3mg/dl)
who is at risk of ODS on vaptan?
if they are also on diuretics and/or have little/no access to free water intake.
T/F
you should d/c fluid restriction if you are starting a vaptan. why or why not?
True
to avoid dehydrating pt and causing overcorrection of hyponatremia.
Has ODS been reported in overcorrection of hyponatremia with dialysis in ESRD patients?
Yes, therefore should follow same guidelines for non-uremic patients.
What should the Hemodialysis Rx be for hyponatremia pt?
1) Low Na bath (aim for lowest possible based on pt’s Na, usually lowest is 130)
2) Lowest BFR possible.
PROBLEM:
ESRD pt (female) with Na 120meq/L.
Weight 60kg
Goal Na is 126 mEq/L by end of iHD treatment.
If you will use Na bath 130mEq/L over 3 hours, what should be your BFR? Are there any other considerations re: the dialyzer?
every 1 L of blood w/ gain 10mEq Na
TBW = 30L
Total Na to add to pt = 6mEq/L x 30L = 180mEq Na
180mEq/10meq/L = 18 L that would need to pass through over 3 hours.
BFR = 18,000mL/180min = 100ml/min
Use pediatric mode on dialyzer.
T/F
for acute water intoxication, re-lowering Na is necessary to avoid ODS
False, it is not necessary.
What can you do to manage hyponatremia overcorrection?
1) d/c fluid restriction (ie, give PO water)
2) D5W IV to desired Na level.
3) DDAVP – 2-4mcg q8-12 hrs
in addition to D5W, DDAVP, what else can you consider in severe overcorrection of hypoNa?
high dose steroids (eg, Dexamethasone 4mg q6h for 24-48 h)
What are some long term strategies for a patient with primary polydipsia other than fluid restriction?
1) Behavioral therapy
2) Clozapine (anti-psychotic) has been reported to be useful in some cases.
PROBLEM:
CHF pt w/ volume overload and hypoNa.
mild to moderate symptoms
Whats a good treatment strategy?
1) fluid restrict 1L/day
2) add loop diuretic for v/o
3) consider Tolvaptan
PROBLEM:
CHF pt w/ severe sx hypoNa.
How to treat?
consider 3% NS + loop diuretics.
High risk for over-correction, need very close monitoring.
PROBLEM: NSIAD -- mild to moderate sx. Treatment? severe sx? what about Vaptans?
1) fluid restrict + increase solute intake (can consider Urea)
2) 3% NS
3) Vaptans not as effective b/c the receptor is constitutively active.
What is osmolar clearance (Cosm)?
Cosm = (Uosm x V) / P
What is the “typical” Cosm (osmolar clearance)?
< 3L per day
What Cosm indicates a solute diuresis?
> 3L per day
What is the Free water clearance equation?
FWC = Urine Volume x (1 - Uosm/Sosm)
What does a positive free water clearance mean?
FWC = Urine Volume x (1 - Uosm/Sosm)
(+) means that pt is making urine that is hypotonic to plasma.
(-) is opposite (hypertonic urine).
What is the electrolyte free water clearance equation?
EFWC = Vu x [1 - (Una+k/Sna + K)]
Meaning of:
1) positive EFWC
2) negative EFWC
(+) –> pt’s urine has lower electrolyte (Na + K) than in plasma –> cause rise in sNa.
(-) –> pt’s urine has higher electrolyte (Na + K) than in plasma –> cause drop in sNa.
PROBLEM: pt w/ post-obstructive diuresis. sNa = 135 Posm = 297 UOP = 300ml/hr Uosm = 450 Una = 73, Uk = 20 Is sNa expected to increase or decrease?
EFWC = 0.3L/h x (1 - 93/135) = 0.093L/h (positive)
positive means ‘hypotonic’ urine (less electrolytes than in plasma) –> rise in sNa.
can a pt with Uosm > Sosm get hypernatremia?
Yes, as long as the EFWC is positive.
PROBLEM: CHF pt on Bumex gtt. sNa 148 UOP 125cc/hr Una = 75 Uk = 15 Which fluid would not worsen fluid overload and would keep sNa the same (assuming pt NPO and not on any other IVF). A) 125ml/hr of NS B) 125ml/hr of 1/2NS C) 50ml/hr of D5W D) 75ml/hr of D5W E) 125ml/hr of D5/1/4NS
EFWC of urine = 50ml/hr (positive)
Answer:
C –> EFWC of D5W = 50ml/hr x (1 - 0) –> 50cc/hr given to pt (same as fH2O loss) –> net even fluid balance and net even water balance.
PROBLEM: CHF pt on Bumex gtt. sNa 148 UOP 125cc/hr Una = 75 Uk = 15 Which fluid would not worsen fluid overload and would decrease the sNa. A) 125ml/hr of NS B) 125ml/hr of 1/2NS C) 50ml/hr of D5W D) 75ml/hr of D5W E) 125ml/hr of D5/1/4NS
EFWC of urine = 50ml/hr (positive)
Answer:
D. EFWC of D5W here is 75cc/hr – net gain of 25cc/hr of fH20
What is the average US diet urine solute load?
~800mOsm
PROBLEM:
Can a pt with relatively low Uosm (150) to Posm (280) have a solute diuresis?
Yes.
Depends on urine volume.
If pt makes 10L urine/day at 150mosm/liter, then that is a Uosm 1500mosm per day.
Daily Uosm of American is ~800mosm/L so in this case there’s more Uosm being excreted per day than 800.
Using equation Cosm = Uosm x V/Posm = 150 x 10L/280 = 5.4L which is > 3L.
Average diet is < 3L/day.
Can pt’s with hypernatremia get intra-cerebraland subarachnoid bleeding?
Yes, can occur due to rupture of cerebral veins with marked decrease in brain volume.
What hypothalamic disorders lead to hypernatremia?
1) Primary hypodipsia
2) Reset osmostat in primary mineralocorticoid excess.
3) Adipsic DI
How does hypernatremia occur in primary aldo excess? How is it a form of “reset osmostat”?
Chronic Na retention/volume expansion leads to mild chronic ADH suppression (in effect, is state of reset osmostat)
How can one treat the hypernatremia in primary aldo excess?
Diuretics –> euvolemia –> less ADH suppression –> water reabsorption –> normonatremia
What is the typical Na range in primary aldo excess?
~143-147 mEq/L
How does hypernatremia occur in Adipsic DI? What is defective and what is intact?
There are combined defects in:
1) osmoreceptor function and
2) Thirst.
- Osmolar dependent ADH secretion is defective.
- But, volume regulated ADH secretion is intact!
Adipsic vs. central DI
Typical central DI pt cannot stimulate ADH release with either hyperosmolar or hypovolemic states.
Adipsic DI responds to hypovolemic stimuli.
Clinical presentation of adipsic DI?
1) typically asx since it is chronic.
2) Na ~155-190mEq/L
3) Pt may be hypovolemic + high renin/aldo –> hypokalemic met alk.
Classic pt with adipsic DI
obese w/ sleep apnea, venous thrombi during hypernatremia, thermoregulatory dysfxn, seizures, and increased mortality.
what are some causes of adipsic DI?
Congenital or acquired CNS lesions
Sarcoidosis
Obese pt w/ sleep apnea, DVT. You’re called for hypernatremia 160mEq/L not correcting w/ hypotonic fluid.
What is the diagnosis?
Adipsic DI
pt can’t secrete ADH in response to hyperosmolality thus no ADH to reabsorb water that the pt is getting.
But pt can concentrate urine w/ fluid restriction.
How can you treat adipsic DI?
DDAVP
…since they are able to concentrate urine but unable to secrete ADH to hyperosmolar stimulus.
what is primary nephrogenic DI due to?
it is hereditary mutation of AQP2 channel
What are some causes of 2* nDI?
Electrolytes: Hypercalcemia, Hypokalemia Pregnancy Drugs: - Lithium - Demeclocycline - Vaptans - Ampho B - Foscarnet - Aminoglycosides - Cidofovir - Methoxyflurane
