Presentation on theme: "The following is material that is not all Dr"— Presentation transcript:
1 The following is material that is not all Dr The following is material that is not all Dr. Ciorciari's original thoughts and not fully referenced to give credit to all information cited. Further this is not considered an authoritative source but suggestions and perspectives that may aid in guiding your art of medicine
2 Sodium Disorders: Hyponatremia William Harper, MD, FRCPCEndocrinology & MetabolismAssistant Professor of MedicineMcMaster University
5 What is Appropriate Urine Concentration? Complete DIDefective osmoreceptor, normal AVP release to ECFv contractionHigh-set osmoreceptor: AVP release is sluggish/delayedAVP release at normal Posm but subnormal in amount
6 Osmolality Plasma Osmolality: Posm = 2 (Na) + glucose + urea Normal = 2 (140) = 290 ( mM)Urine Osmolality:Normal: mMMaximal dilution mM (USG )Maximal concentration mM (USG )Concentrated Urine: > 500 mM (at least!), USG > 1.017i.e. UOSM > POSM is not enough to R/O Diabetes Insipidus
7 Urine Specific Gravity USG Estimates solute concentration of urine on basis of weight as compared with an equal volume of distilled waterNormal Posm is % heavier than water so PSG =Each ↑ in UOSM mM ↑ USG by 0.1% (0.001)Therefore, USG of ~ UOSM mMLarger MW urinary OSM (glucose, radiocontrast, carbenicillin) if present will falsely elevate USGNothing falsely lowers USG
8 Hyponatremia Serum OSM Low Normal High *Note: all have ↑ADH ECFv * Low Marked hyperlipidemia(lipemia, TG >35mM)Hyperproteinemia(Multiple myeloma)HyperglycemiaMannitolHypotonicHyponatremia*Note: all have ↑ADHSIADH: inappropriateRest: appropriateECFv *LowHighNormalCHFCirrhosisNephrosisHypothyroidismAISIADHReset OsmostatWater Intoxication1° PolydipsiaTURP post-opRenal loss (UNa > 20)DiureticsThiazideK-sparingACE-I, ARBIV RTA, HypoaldoCerebral salt wastingExtra-renal loss (UNa <10)BleedingBurnsGI (N/V, diarrhea)Pancreatitis
9 Rx Hyponatremia When do you need to Rx quickly? Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na])(mmol)When do you need to Rx quickly?Acute (<24h) severe (< 120 mEq/L) HyponatremiaPrevent brain swelling or Rx brain swellingSymptomatic Hyponatremia (Seizures, coma, etc.)Alleviate symptoms“Quickly”: 3% NS, 1-2 mEq/L/h until:Symptoms stop3-4h elapsed and/or Serum Na has reached 120 mEq/LThen SLOW down correction to 0.5 mEq/L/h with 0.9% NS or simply fluid restriction. Aim for overall 24h correction to be < mEq/L/d to prevent myelinolysis
10 Rx Hyponatremia (Example) Na deficit (mmol) = 0.6 x wt(kg) x (desired [Na] - actual [Na])60 kg women, serum Na 107, seizure recalcitrant to benzodiazepines.Na defecit = 0.6 x (60) x (120 – 107) = 468 mEqWant to correct at rate 1.5 mEq/L/h: 13/1.5 = 8.7h468 mEq / 8.7h = 54 mEq/h3% NaCl has 513 mEq/L of Na54 mEq/h = x513 mEq Lx = rate of 3% NaCl = 105 cc/h over 8.7h to correct serum Na to 120 mEq/hNote: Calculations are always at best estimates, and anyone getting hyponatremia corrected by IV saline (0.9% or 3%) needs frequent serum electrolyte monitoring (q1h if on 3% NS).
11 Rx Hyponatremia Rx slowly (correct < 0.5 mEq/L/h, 10-12 mEq/L/d) Symptomatic/Acute: rapid Rx has resolved symptoms and brought serum Na up to 120 mEq/LAsymptomatic, mild, chronic hyponatremiaWant to prevent myelinolysisIncreased risk: Women, alcoholics, malnourishedECFv contractedBolus NS until BP, HR, JVP stableThen correct slowly with 0.9% NS or po saltECFv Normal or ECFv OverloadedFluid Restriction alone (exception: SAH, HI, post-neurosurgery)i.e. they do NOT need any IV or po salt!
13 SIADH Diagnosis Treatment Normal ECFv (or slightly increased) Hypothyroidism & AI ruled out↓ serum Na/OSMUOSM > 100 mM, UNa > 40 mEq/LLow plasma uric acid (< 238 umol/L) (1 mg/dL=59.48 µmol/L)TreatmentFluid RestrictionOral Salt, Hi-protein diet or Urea (30 g/d): promote solute diuresisLasix 20 mg po od-bid: Loop direct diminishes medullary gradientDemeclocycline mg bid (can be nephrotoxic)Lithium (induces NDI)IV salt solution:Rarely if ever needed (i.e. only if symptomatic with SZ/coma)Solution given must be of greater OSM than UOSM or in long run will just make hyponatremia worse (often IV NS not sufficient)
15 SIADH: Example UOSM fixed 600 mM due to ADH action 1L NS given: 300 mM (154 mM each of Na and Cl)All sodium will be excreted as renal sodium handling is intact in SIADH.300 mmoles of osmols given excreted in 500cc urine (300mmoles/500mL = 600 mM)Therefore net gain of 500 cc free water!1L 3% saline given: 1026 mmolesExcreted in 1.7L to keep UOSM 600 mMTherefore net loss of 700 cc free water!NOT advocating use of any IV NS (0.9% or 3%) in SIADH unless absolutely neccesary (i.e. SZ, coma). Most SIADH hyponatremia is chronic and should be corrected slowly with fluid restriction ONLY.
16 Reset Osmostat 25-30% of circumstances which cause SIADH Downward resetting of the threshold for both ADH release and thirst.Mild asymptomatic hyponatremia (Na mEq/L)Distinguish from SIADH by observing response to water load (10-15 mL/kg po or IV)Normal subjects and those with reset osmostat will secrete the entire water load over 4h without any worsening of the hyponatremiaAttempts to correct hyponatremia in reset osmostat are not needed and will cause severe thirst
17 Cerebral Salt Wasting Cerebral disease (particularly SAH) Mimics SIADH with hyponatremia except primary defect is salt wasting not water retention.Circulating factor which impairs renal tubular fn.Atrial natriuretic peptide?Brain natriuretic peptide?Endogenous ouabain?Plasma urate variable (normal or even lower than SIADH)Treatment is NS to correct ECFv contraction
18 SIADH v.s. Cerebral Salt Wasting CSWSerum Na↓ECFvNormalUNa↑↑↑UOSMUrine volumeN or ↓Serum urateUrine urateN or ↑
19 Rx Hyponatremia: acute SAH/Head injury May have SIADH, CSW or Both!Often difficult to tell whichFluid restriction inappropriate for CSW as may exacerbate ECFv contraction and precipitate cerebral vasospasm and subsequent cerebral infarctionIV NS inappropriate for SIADH if UOSM > 300 mM (will make hyponatremia worse)Rx with IV NS:Start with 0.9% NS (as per hypervolemic therapy to prevent cerebral vasospasm)If hyponatremia worsens on 0.9% NS (due to an SIADH component to hyponatremia) consider switch to 3% NSGoal: 0.5 mEq/L/h (only if symptomatic 1-2 mEq/L/h)Fludrocortisonemg/dMay also be beneficial in recalcitrant cases to alleviate CSW.
20 Indications for 3% NaCl Symptomatic hyponatremia (SZ, coma) Acute severe hyponatremia (<24h, < 120 mEq/L)SAH with hyponatremia worsening on 0.9% NaCl
21 Sodium Disorders Hypernatremia William Harper, MD, FRCPCEndocrinology & MetabolismAssistant Professor of MedicineMcMaster University
22 GI losses: Secretory diarrhea (cholera, VIPOMA, etc) don’t get hypernatremic as diarrheal fluid is isotonic to plasma, but the more common diarrheas due to viral/bacterial infections or osmotic diarrhea is hypotonic to plasma and therefore does cause hypernatremiaMineralcorticoid excess syndrome: they have persistent mild volume expansion which resets the osmostat regulating antidiuretic hormone release and thirst upward by several mEq/L. As a result, patients with primary aldosteronism usually have a stable plasma sodium concentration between 143 and 147 mEq/L.
24 Diabetes Insipidus Ddx Central (CDI)IdiopathicautoimmuneNeurosurgery, head traumaCerebral hypoperfusionTumorCraniopharyngioma, pituitary adenoma, suprasellar meningioma, pineal gland, metastasisInfiltrationFe, Sarcoid, Histiocytosis XNephrogenic (NDI)X-linked recessiveHypokalemiaHypercalcemia (2° to HPT in particular)Renal disease: after ATN, postobstructive uropathy, RAS, renal transplant, amyloid, Sickle cell anemiaSjogren’sDrugs:Lithium, 20% of chronic usersDemeclocycline, amphotericin, colchicine
25 What is Appropriate Urine Concentration? Complete DIDefective osmoreceptor, normal AVP release to ECFv contractionHigh-set osmoreceptor: AVP release is sluggish/delayedAVP release at normal Posm but subnormal in amount
26 Intact thirst & access to water Diabetes InsipidusIntact thirst & access to waterHi-normal serum sodium ( mEq/L)Polydipsia (crave cold fluids)Polyuria, Nocturia sleep disturbance1° treatment is pharmacologicalImpaired thirst or access to water:HypernatremiaInsufficiently concentrated urine1° treatment is free water (enteral or IV D5W)
27 Diabetes Insipidus Healthy out-patients DI with Intact thirst or access to waterHi-normal serum sodium ( mEq/L)Polydipsia (crave cold fluids)Polyuria, Nocturia sleep disturbance1˚ Psychogenic PolydipsiaLow-normal serum sodium ( mEq/L)Anxious middle-aged womenPsychiatric illness, phenothiazine (dry mouth)
29 1˚ Polydipsia: “What came first?” The Polyuria or the Polydipsia?The Chicken or the Egg? (Egg)
30 Water Deprivation Test Hold water intake for 2-3h prior to coming in.Continue to hold water & Monitor:Urine volume, UOSM q1hSerum Na, OSM q2hIf serum OSM/sodium do not rise above normal ranges & UOSM reaches 600 1˚ PolydipsiaIf serum OSM reaches mM & UOSM doesn’t ↑Diabetes Insipidus establishedEndogenous ADH should be maximal, check serum ADH2 green rubber stopper tubes, pre-chilled, on ice, need biochemistGive DDAVP 10 ug INCDI: UOSM ↑ by % (complete CDI), ↑ by 15-50% (partial CDI) with absolute UOSM > 345mMNDI: UOSM ↑ by up to < 9%, sometimes ↑ as high as 45% but absolute UOSM always < isotonic (290 mM)
31 Diabetes Insipidus Back to in-patients! Impaired thirst or access to waterElevated serum sodium/OSMUOSM < 500 mM, USG < 1.017If serum sodium/OSM not elevatedNot DI!UOSM and USG are irrelevant
32 Pituitary Surgery Triphasic response to surgery Phase 1: DI Axonal injury 2° surgery/swellingBegins after POD #1 (pre-existing DI can occur earlier)Lasts 1-5dPhase 2: SIADHAxonal necrosis of AVP secreting neurons with uncontrolled AVP releaseLasts 1-5 daysPhase 3: DIAxonal death with cessation of AVP productionUsually permanent
36 PNa U/O 400 150 100 100 50 50 1 6 11 POD # #1 DI #2 Normal Na #1 Na #2 (mEq/L)U/O(cc/h)400Na #1150Na #2U/O #11001005050U/O #21611POD #
37 DDAVP: 1ug IV/SC = 10 ug IN = 0.1 mg PO Treatment of DIRx DehydrationNS initially if ECFv contractionThen IV D5W or enteral free water to lower serum [Na]1-2 mEq/h if Na > 160, symptomatic (coma, SZ), acuteOtherwise mEq/hInsensible losses? (0.5 L/d)Do NOT replace U/O if giving DDAVPDDAVP (Desmopressin)Reduces U/O and therefore simplifies fluid therapyLong t½: duration 8-12h, up to 24hTherefore use judiciouslyDDAVP 1ug IV/SC x 1Only repeat if breaks-thru again (i.e. becomes hypernatremic with dilute polyuria)Once nasal mucosa stable can switch to intranasalAlso oral form DDAVP now availableDDAVP: 1ug IV/SC = 10 ug IN = 0.1 mg PO
38 Treatment of DI AVP, Aqueous vasopressin (Pitressin) Only parenteral form, 5-10 U SC q2-4hLasts 2-6hCan cause HTN, coronary vasospasmChlorpropamide (OHA which stimulates AVP secretion)mg po OD-bidOnly useful for partial DI, can cause hypoglycemiaHTCZ (induces volume contraction which diminishes free water excretion)mg OD-bidMainstay of Rx for chronic NDIAmiloride (blunts Lithium uptake in distal tubules & collecting ducts)5-20 mg po OD-bidDrug of choice for Lithium induced DIIndomethacin mg po bid-tid (PGs antagonize AVP action)Clofibrate 500 mg po qid (augments AVP release in partial CDI)Tegretol mg po od (augments AVP release in partial CDI)