ERIM ses ‘Overview General (ej 2015372:55 & 373:1350) + Disorders of serum sodium are generally due to as In total body water, not sodium + Hypor- or hypo-osmolality » rapid water shits» A in brain eal volume -» A MS, seizures Key hormones + Antidiuretic hormone (ADH): primary hormone that regulates sodium concentration Stimuli fr secretion: hyperosmolality, | effective arterial volume (EAV), angiotensin I ‘Action’ msertion of aquaporin-2 channels in collecting ducts -» passive water reabsorption urine osmolality is an indirect functional assay of the ADH-renal axis Use range: 60 mOsmiL (no ADH) to 1200 mOsm. (maximal ADH) * Aldosterone: primary hormone that regulates total body sodium (and ~. volume) ‘Stimuli for secretion: hypovolemia (via renin and angiotensin 1), hyperkalemia ‘Action: iso-osmetic reabsorption of sodium in exchange for potassium or Ht HYPONATREMIA Pathophysiology (sé 2015.72 + Excess of water relative to sodium; almost always due to T ADH + TADH may be appropriate (eg, hypovolemia or hypervolemia with 4 EAV) ADH may be Inappropriate (SIADH) Rarely, | ADH (appropriately suppressed), but kidneys unable to maintain nl [Na}un ‘THO intake (7° polydipso: ingestion of massive quantities (usually >12 Lid) of free Hi ‘overwhelms diluting ablity of kidney (normal dietary solute load ~750 mOsmié, Iminimum Usen = 60 mOsm.» excrete in ~12 L;1f HyO ingestion exceeds this amount -+ HiO retention) 4 solute intake ("tea & toost” & "beer potomania”) Lt dally solute load -» insufficient solute to excrete HiO intake (egif only 250 mOsm/d,minimum Usin = 60 mOsmil. -» excrete ii 4 LI Hi Ingestion exceeds this amount -» HiO retention) Workup (ASW 20125-1140; Ce Core 201:17:206; NEM 2015537255) + History: (1) acute vs. chronic (>48 h); (2) 2x severity; (3) risk for neuro complications (alcoholism, malnourished, cirrhosis, older females on thiazides, hypoxia. hypoK) + Measure plasma osmolality Hypotonic hyponatremia most common scenario; true excess of free HO relative to Na Isotonic hyponatremia: rare lab artifact from hyperlipidemia or hyperproteinemia Hypertonic hyponatremia: excess of another effective osmole (eg, glucose, mannitol) that draws H2O intravascularly; each 100 mg/dL T gic >100 mg/dL. 4 [Na] by 24 mEq/L. + For hypotonic hyponatremia, 7 volume status (vital signs, orthostatic, JVP, skin turgor, mucous membranes, peripheral edema, BUN, Cr, uric acid) + Uoum diagnostically useful in limited circumstances, because almost always >300 ‘exceptions: Voi <100 in T H,0 intake or 4 solute intake ‘moreover, Unum >300 # SIADH; must determine if ADH appropriate or inappropriate however, Usen important when deciding on treatment (see below) * Ifeuvolemic and T Usin evaluate for glucocorticoid insufficiency and hypothyroidism Figure 44 Approich to hyponatremia Hypotonic Hyponatremia Iypovolemic —euvolemie hypervoleme ae ¥ “Ne Hypovolemic: Euvolemic Hypervolemic Hyponatremia Hyponatremia Hypenetremia Tes aaa 7 Upg>20 Uy <10 Ps clinica history Usa <10 Uy >20 FEqg>1% FE my 400 Ugg 10D Us VF gg 1% Eng >1% ¥ x ¥ + X ¥ N Ronallocsee Extaronal SIADH1*polyipsia Reset CHF Penal ‘ineccoteid losses hpotyeism ‘iow sche osmastat Cimosis —_falure ‘on sere NophrostsHypovolemic hypotonic rremia (le, 14 total body Na, | TBWY) + Renal losses (Us. >20 mEq/L, FE, >1%): diuretics (esp. thiazides, at loop diuretics { tonicity of medullary interstitium and impair urine concentrating ability), salt- wasting nephropathy, cerebral salt wasting, mineralocorticoid deficiency + Extrarenal losses (Us, <10 mEgiL, FEsn <1%8): hemorrhage, GI loss (diarrhea), third- spacing (pancreatitis), | PO intake, insensible losses Euvolemic hypotonic hyponatremia (ie. ! TBW relative to total body Na) * SIADH (euvolemia or mild hypervolemia, inapprop T Uosm, approp. Ura, 1 BUN & UA) ‘malignancy: lung, brain, GI, GU, lymphoma, leukemia, thymoma, mesothelioma pulmonary: pneumonia, TB, aspergillosis, asthma, COPD, PTX, © pressure ventilation intracranial: trauma. stroke, SAH. seizure. infxn. hydrocephalus. Guillain-Barré synd. drugs: antipsychotics, antidepress. (esp. SSRs), chemotherapy, AVP. MDMA, NSAIDs miscellaneous: pain, nausea, postoperative state Endocrinopathies: TADH activity seen in glucocorticoid deficiency (co-secretion of ADH & ‘CRH) and severe hypotiyridsmlmyxedema coma ( CO & | GFR) Psychogenic polydipsia (Usin <100, | uric acid) usually requires intake >12 Lid + Low solute (1 Un. Usin) "tea & toast”; "beer potomania” + Reset osmostat: chronic malnutrition (J intracellular osmoles) or pregnancy (hormonal effects) + ADH physiology reset to regulate a lower [Na]saum Hypervolemic hypotonic hyponatremia (ie, | total body Na, | TBW) + LEAV ~ activation of RAAS -> T aldosterone and TT ADH + CHF (1 CO & renal venous congestion -» 1 EAV; Uns <10 mEq/L, FEw <1%) + Cirehosis (splanchnic arterial vasodilation + ascitat > | EAV; Un <10 mE@/L, FE, <1%) + Nephrotic syndrome (hypoalbuminemia -> edema -» | EAV; Uni, <10 mEgIL, FE ja <1%) + Advanced renal failure (diminished ability to excrete free HiO; Un, >20 mEqjL) ‘Treatment (ot Cove 201317206: NEM 201537255) Approach: depends on volume status, acwty of hyponatremia, and if symptomatic ‘Acuite sini! rapid correction of [Nia]jwom (2 mEq/Lh for the first 23 h) until sx resolve ‘Asx or chronic symptomatic: correct [Naren at rate of <0.5 mEq/L/h Rate of T Na should not exceed & (chronic) to & (acute) mEq/L/d to avoid central pontine ‘myelinolysis/osmotic demyelination syn. (CPM/ODS. paraplegia, dysarthria, dysphagia) severe (<120) or neuro sx: consider 3% NaCl + dDAVP (to prevent rapid ‘overcorrection) in consultation w/ nephrology (jo 201361571) + Frequent lab draws and IVF rate adjustments are cornerstones of treatment + Overly rapid correction: can lead to CPM/ODS. Should be emergently reversed w! ADAVP + D:W: partial neurologic recovery possible (GAN 20149729) + Effect of IV fluids (hupshwwamedealcomsodiumhun)) a [Natasa — [Na]won, TBW =e i) X 06(8) 0°05 (2: ital A[Na}unen per L infuse =" “TeV + | Keay 5 (6) 0045 (2) If [Na], = 110 mEq/L in 70 kg male: IVF type [Na]eonn TLIVET [Na], Rate to T [Na]. by 0.5 mEq/Uh S%NaCl_ B56 mEqiL 173 mF ql -25 mUh 3%NaCl 513 mEq/L 9.4 mEqlL -50 mUh 0.9% NaCl 154 mEq. 1 mEq/L ~500 muh wR 130 mi 05 mEq ~1000 muh however, above assumes entire infusate retained without any output of Na or HzO if Pt euvolemic, as in SIADH, infused Na will be excreted , 1 LINS (154 mEq of Na or 308 mOsm of solute in 1 L free H,O) given to Pe with SIADH with Unin = 616 -» 308 mOsm solute excreted in 0.5 L HO -» ret gain 0.5 L Hi0 > [Na}erwn - normal saline can worsen hyponatremia from SIADH if Usa > infusateoum + Hypovolemic hyponatremia: volume repletion with normal saline ata slow rate. ‘Once volume replete -» stimulus for ADH removed (wi very short ADH t,) -» kidneys excrete free HO - serum Na will correct rapidly (D:W +t ddAVP if overcorrection) + SIADH (ney 2007:356:2064,AKO 2015:5:35):free water restrict + treat underlying cause hypertonic saline (+ loop diuretic) if sx or Na fails to 1 w! free H,O restriction 1 L hypertonic saline (3% NaCl) will raise [Na]jwwn by ~10 mEq (see above) 50 mUh will t [Na] by ~0.5 mEqj/LJh; 100-200 miLih will t [Na] by ~1-2 mEq/Lh formula only provides estimate; -. recheck serum Na frequently (at least q2h) NaCl tabs: particularly if chronic and no CHF aaquaresis:? vaptans (vasopressin receptor antag) for refractory SIADH wwe 201837223) demeclocycline: causes nephrogenic Di, Us (rarely used)+ Hypervolemic hyponatremia: free water restrict mobilize excess Na & H:O (use loop diuretics; avoid thiazides) & T EAV (vasodilators to 1 CO in CHE colloid infusion in cirhosis) aquaresis: vaptans sometimes used; however, no proven mortality benefit, hypoNa recurs after stopping drug, risk of overcorrection, contraindicated in cirrhosis, and expensive (NEM 20153722207) HYPERNATREMIA Pathophysiology (cit Cre 2013-17206. Nejt 2015:37255) * Deficit of water relative to sodium by definition, all hypernatremic Pts are hypertonic + Usually loss of hypotonic fluid (ie, dehydration”); occasionally infusion of hypertonic fluid + And impaired access to free water (cg. intubation, A MS, elderly): hypernatremia is a powerful thirst stimulus, -. usually only develops in Pts wio access to H:O Workup PPE * Usim Una, volume status (vital signs, orthostatics, JVP, skin turgor, BUN, Cr) hye Figure 4-5 Approach to hypernatremia BIT Hrpornatromia 4,.»700-800 u<700-200 ¥ ‘ Xx Ug 25 Ue 100 pasate < “ Un 800 Ur200-600 Enteral Otose] [ja Overoed y oN IH.O ose TeCONCO,NF —CompleteO Part! DL imsencootess nwt cosmote aes - oe ciretes Tinvacelutar omaes Ser, Erese Extrarenal H:O 103s (Uses >700-800) + GLHLO loss: vomiting, NGT drainage, osmotic diarrhea, fistula + Insensible loss: fever, exercise, ventilation Renal H:0 loss (Usim <700-800) + Diuresis: osmotic (glucose, mannitol, urea), loop diuretics + Diabetes insipidus (j cio Endocr! Metb 2012973426) ‘ADH deficiency (central) or resistance (nephrogenic) Central: hypothalamic or posterior pituitary disease (congenital, trauma/surgery. ‘tumors, infltrative/lgG4); also idiopathic, hypoxic encephalopathy, anorexia, EtOH Nephrogenic (nat: 200:144 186) ‘congenital (ADH receptor V2 mutation, aquaporin-2 mutation; Ped Nepre 2012272163) drugs: lithium, amphotericin, demeclocycline, foscarnet, cidofovir metabolic hypercalcemia, severe hypokalemia, protein malnutrition, congenital ‘ubulointerstitia: postobstruction, recovery phase of ATN, PKD, sickle cell, ‘jgren’, amyloid, pregnancy (placental vasopressinase) DI usually presents as severe polyuria and mild hypernatremia ‘Other (Uns >700-800) + Na overload: hypertonic saline (eg, resuscitation w/ NaHCO), mineralocorticoid excess * Seizures, T exercise: intracellular osmoles > H,O shifts -» transient T [Na]jerun ‘Treatment + Restore access to HiO or supply daly requirement of HaO (21 Lid) + Replace free HO deficit (also replace concurrent volume deficit if appropriate): FreeH,0 deficit) = Nabe "40 py TV wt ba 06(8)-r 050% 140 MH hdry we 05 (8) or 045 (2) shortcut for typical 7O-kg man, free HO deficit (L) ~ ({Naluan ~ 140)/2 infusate = fNt}em — IN} A [Nan pe Linfsate Sarat £8, 1 L DSW given to 70-kg man w/ [Na] ~ 160 mEqJL will | [NaJerum by 3.7 mEq nb, do not forget to correct Na if hyperglycemia also present