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Fluid & Electrolytes

Fluid & Electrolytes Crib Sheet

Nicholas J. Mayer, D.O. Internal Medicine & Nephrology


Nicholas Mayer D.O.

Fluid & Electrolytes Hello, I am a nephrologist who created a personal crib sheet as I studied for my Nephrology boards. These crib sheets were initially created from my overall understanding of the subject material, to which I added the evidence that supports our current practice, along with some key testing points for the boards. I have since polished them so that they are useful to the students and residents that I teach. I hope they can be useful to you, and would appreciate any feedback that you may have. Enjoy! Nicholas J. Mayer


Nicholas Mayer D.O.

Fluid & Electrolytes Volume (sodium) management: Water and salt are handled differently by the body:

Men are 60% water Women are 50% water

- Water distributed Intra- & Extra- cellularly - Sodium remains in the Extra- cellular space only - If given 1 Liter of IV NS, 25% will contribute to the intravascular / plasma compartment

Intravascular 25%


Blood pressure:

HTN will develop from derangements of systems involved in sodium management Nature Reviews Neph 2015; 11:555

- RAAS system hyperactivity acting upon both the mineralacorticoid receptor and directly on the vasculature ↓ AA pressure via myogenic reflex ↑ Sympathetic activity ↓ distal NaCl delivery to Macula densa

Three factors promote renin secretion:

Angiotensinogen →(renin)→ Angiotensin1 →(ACE)→ Angiotensin2 →(Zona glom)→ Aldo → MR → +ENaC Clinical result: ↑BP ↓K ↑Bicarb

- Sympathetic nervous system, which has both afferent nerves from & efferent nerves to the kidney - Excess body sodium - Increased intake - Iotragenesis: NSAIDs, steroids, -glitazones, insulin - Disorders of auto-regulation - disordered function of endothelium, such as impaired release of NO - disordered function of vascular wall, such as stiffening with calcification or collagen accumulation Sodium management in the kidney results from pressure naturesis. - feedback mechanism relies on BP in the kidney, as demonstrated by the following experiments: - give aldo and MAP will ↑ to a point and level off, take aldo away and MAP ↓ to nl - put restrictor on renal artery so renal BP unchanged, and MAP will ↑ indefinitely - As MAP within kidney elevates, Na+ excretion increases BPk ≈ Na+ excretion - People with HTN have some derangement of the renal pressure naturesis curve - The production of prostanoid (PGE) is important in both volume expansion and contraction: - PGE in cortex dilates AA and encourages renin release when volume contracted - PGE in medulla maintains high rates of NaCl excretion when volume expanded - NSAIDs are clinically important as they disturb the production of prostanoid (PGE) Pressure naturesis in kidney has several potential mechanisms: - Short: RA stretch → ↑ANP → medullary DT salt loss + ↓ENaC + ↓NaK-ATPase + ↓RAAS - Intermediate: ↓RAAS system - Long: ↓SNS tone


Nicholas Mayer D.O.

Fluid & Electrolytes

Starling forces govern the distribution of the extracellular volume between the intravascular (capillary) and extravascular (interstitial) spaces. The net hydrostatic pressure (P) initially forces salt water out of the capillary into the interstitium until the net oncotic pressure (∏) in the capillary is equal to or greater than the hydrostatic pressure.

Edematous states: - All have salt retention but salt retention alone not enough (hyperaldo doesn’t usually have edema) - Disorders of Starling forces result in edema: ↑ Pc: relaxation of pre-capillary sphincter (CCB), venous occlusion (DVT), RHF ↓ ∏c: hypo-albuminemia ↑ ∏i: occlusion of lymphatics, capillary leak (↑permeability coefficient) - Drugs that lead to edema: salt retention: pre-capillary sphincter dilation:

NSAIDs, steroids, -glitazones, insulin dihydroperidine CCB


Nicholas Mayer D.O.

Fluid & Electrolytes - Gene defects leading to HTN (majority relate to ↑ENaC): - Primary Aldosteronism with Adrenal Adenoma - Workup: 1. Aldo/renin ratio > 20 with aldo > 16 (renin normally < 3) 2. Confirm with 24 hour urine for: Cr, Na, K and aldo on high salt diet (≥ 14 mCg is +test) 3. CT abdomen looking for adenoma 4. Adrenal vein sampling - TX: Aldactone, Amilioride, or adrenalectomy for failure of medication with adenoma - Liddle Syndrome Trans Assoc Am Phys 1963; 76: 199 - clinical hyperaldostereronism with ↑BP, ↓K, alkalosis, but ↓ renin & ↓ aldosterone - Unresponsive to aldactone - Mechanism: activating mutation of ENaC: with a mutation of the ENaC carboxy-terminus, nedd4-2 cannot bind to and ubiquinate the ENaC channel, making endocytosis (inactivation) impossible Cell 1994; 79:407 JASN 1999; 10:2527 JASN 2005; 16: 3167 - TX: Amilioride or Triamterene. - Congenital adrenal hyperplasia (CAH) - Only an estimated 5% of patients with CAH have clinical hyperaldosteronism - Etiology: either 11b deficiency with virulization or 17a deficiency without sex hormones - Presentation as neonate to young adult with failure to thrive, genital ambiguity, or virulization - Workup: - clinical hyperaldostereronism with ↑BP, ↓K, alkalosis, but ↓ renin & ↓ aldosterone - 24 hr urine tetrahydrocortisol (THF) / tetrahydrocortisone (THE) > 6 - TX: life-long glucocorticoid replacement

17α deficiency ↑BP ↓ K

11 β hydroxy deficiency Virulization

- Apparent mineralocorticoid syndrome (AME): - Acquired inhibition or Genetic mutation of 11 β hydroxysteroid dehydrogenase-2 (11βHSD-2) which metabolizes cortisol→ cortisone (cortisol activates mineralocorticoid receptor) - Acquired inhibition: glycyrrhizimic acid (licorice), bile acids, Grapefruit juice, Itraconazole - Workup: - clinical hyperaldostereronism with ↑BP, ↓K, alkalosis, but ↓ renin & ↓ aldosterone - 24 hr urine tetrahydrocortisol (THF) / tetrahydrocortisone (THE) > 6 - TX: Amilioride, aldactone; consider dexamethasone if ENaC blockade ineffective (Grade 2B)


Nicholas Mayer D.O.

Fluid & Electrolytes

- Glucocorticoid responsive hyperaldosteronism (GRA): - uncommon gene rearrangement that puts ACTH in charge of mineralocorticoid production. - Called glucocorticoid remedial HTN b/c dexamethasone suppresses aldo in GRA. Hypokalemia variably present b/c ACTH secreted in diurnal fashion. - Renin low with normal aldosterone level (different than others that have low renin, low aldo) Also, chimerism results in increased production of 18-oxocortisol & 18-hydroxycortisol - TX: dexamethasone (decrease cortisol synthesis) - Progesterone induced hypertension (Geller syndrome) - uncommon syndrome of activating mineralocorticoid receptor during pregnancy. - AD genetic abnormality of MR in which receptor is constitutively activated, so steroids that normally display antagonist properties (progesterone, spironolactone) now activate the receptor - Gordon Syndrome (pseudohypoaldosteronism type 2 (PHA2)) Arch Intern Med 1978; 138(4):607 - Familial HTN (AD) with ↑K and acidosis, also hypercalciuria with nephrolithiasis - Mechanism: defective WNK kinase type 1 & 4 possibly resulting in any of the following: - disorder at the level of the distal tubule resulting in underutilization of CD a) overactive NaCl channel in DT (thiazide sensitive channel) - disorder at level of collecting duct (CD) where ENaC conducts charge of -60mV b) ↓K channel → lumen very electronegative → ↑Cl absorption c) ↑Cl- absorption between cells of CD (claudin) → lumen less electronegative → ↓K secretion (remember -60 mV gradient drives K secretion) - TX: Thiazide & low-salt diet

Cell 2001; 104: 545


Renal artery stenosis and HTN

(see hypertension review)


Nicholas Mayer D.O.

Fluid & Electrolytes - Salt-losing disorders (most syndromes are genetic) - Bartter Syndrome Nature Genetics 1996; 13: 183-188 - Found in children with ↓BP, ↓K, alkalosis who have ↑renin & ↑aldo levels, - Urine loss of Ca and Mg notable - Mechanism: SIX forms that ↓ NK2Cl channel of TAL as if on loop diuretic: - NK2Cl (type 1), ROMK (type 2), basolateral Cl channel (type 3), Bartin mutation (type4) - CaSR stimulation (type 5)reduces expression of ROMK - AG abx may cause reversible barters syndrome by blocking paracellular Mg/Ca - Barttin defect will cause ClC-Kb dysfunction resulting in neonatal barters with deafness - TX: life-long K & Mg supplementation, high-dose K-sparing diuretics, NSAIDs? - Gittleman Syndrome Nature Genetics 1996; 12: 24-36 - Clinically: Salt craving with ↓BP, ↓K, alkalosis who have ↑renin & ↑aldo levels - urine loss of Mg notable, but with hypocalciuria (↓ urine calcium) - Mechanism: ↓ NaCl channel of DT as if on thiazides KI 1998; 54: 720-30 - TX: life-long K & Mg supplementation, Amilioride (better than spironolactone), NSAIDs? - Pseudohypoaldosteronism (PHA-1) - Found in children with ↓BP, ↑K, acidosis who have ↑renin & ↑aldo levels, - No urine loss of Ca or Mg - Mechanism: ↓ MR (AD) or ENaC (AR) in CD as if on amilioride (AR is severe and unrelenting, AD will resolve with age) - TX: high salt diet (much worse if ENaC disease) - Secondary Pseudohypoaldosteronism (PHA-2) Acquired tubular injury from: UTI, AIN, Sickle cell, SLE, Amyloidosis, Myeloma, post-renal txp

Magnesium physiology Etiology: Reduced intake due to malabsorption or PPI Redistribution Reduced renal reabsorption at distal nephron at TRPM6: J Fam Pract 2005; 54(2): 174 - EtoH - CNI - Pentamidine - Hypercalcemia - Diuretics - AG - Foscarnet - Familial hypomagnes - Cisplatin - Aritolinib (Tx SCLCa) - DM There are no hormones that regulate magnesium levels; the magnesium level itself influences it’s excretion. A diagnostic approach to hypomagnesemia release upon urine magnesium and calcium levels


Nicholas Mayer D.O.

Fluid & Electrolytes Potassium physiology - Symptoms depend upon: magnitude, acuity of onset, K shift vs total-body K change, - EKG changes: serum K ≈ resting potential (RP) of cells Hyperkalemia = Peaked T-waves ↑ K = ↓ RP = high cell sensitivity Hypokalemia = U-wave in precordial leads, QT prolongation & Osborne waves (water tower R’)

- Potassium Shifting: - Momentary shifts in K+ are important for homeostasis in order to handle K loads with meals. - ECF contains about 70 mEq, intracellular space contains about 3500 mEq - with exercise, K leaks into interstitial space and may cause vasodilation; so ↓K may → rhabdo - Re-feeding Syndrome: ↑ glucose administration → ↑ insulin → intracellular shift of K & Phos (therefore, do not give dextrose IVF when a patient has hypokalemia)


Nicholas Mayer D.O.

Fluid & Electrolytes - Excretion of K - Renal excretion 90%, GI excretion 10%, - All the potassium exits the kidney from the collecting duct (only 10% of freely filtered K delivered to CD) - Determinants of CCD K secretion (2 usually opposite and balanced processes): 1) ENaC activity ≈ Mineralocorticoid activity 2) distal delivery of Na+ (ENaC is an ion channel, thus generates a negative charge. The -ve lumen sucks K out) - Renal Tubular Acidosis (RTA) will effect potassium excretion. RTA type 1 & 2 will ↑ distal delivery of Na+ → ↑ ENaC & ↑ K excretion Diabetics often have Hypo-reninemic Hypoaldosteronism resulting in RTA type 4


Nicholas Mayer D.O.

Fluid & Electrolytes - Hypokalemia: - Cell shifts: Hypokalemic periodic paralysis: Ca-Ch mutation (AD) or ↑thyroid & muscle K+ Ch mutation (remember: ↑thyroid can occur with amiodarone & iodine contrast dye) TX: KCl + Acetazolamide - GI loss = 24-hr urine K < 20 mEq/day - ↓K + no acid-base disturbance with white clay ingestion (also low phos and iron) - ↓K + non-gap acidosis with secretory diarrhea = small intestine effect - ↓K + alkalosis +/- hypernatremia with osmotic diarrhea = colon effect (laxatives) or congenital choridorrhea (high sweat chloride) or villous adenoma - Renal loss = 24-hr urine K > 20 mEq/day or Urine K/Cr ratio > 13 mEq/g (TTKG unreliable) - ↑ ENaC activity → salt retention → HTN - ↑ distal tubule Na+ delivery → salt loss → low / normal BP - TAL and DT defects: barters, diuretics, gittlemans, ↓Mg⁺⁺ (loss of ROMK inh; with PPI) - acidosis: diminished Cl- gradient of S2 in PT → ↓Na reabs → distal Na delivery - non-reabsorbed anions (PCN, ketoanions, salicylate, HCO3 with vomit)

- Hyperkalemia - Pseudohyperkalemia (hemolysis and artifact) more often when cold, hemolysis or with leukocytosis (CLL). - Excess K intake: coconut, red clay, match heads, noni juice, PCN G potassium, PRBC, supplements - Cell shifts: - cell injury: rhabdo, tumor lysis, hemolysis, ischemia - toxins/drugs: digoxin (inh Na/K ATPase), tetrodotoxin (puffer fish), succinylcholine (AchR more widely distributed on cells of chronically ill or paralyzed → ∴ this group ↑sensitive) - DKA/ NKHS: lack of insulin and hypertonic state, NOT acidosis. - Hyperkalemic periodic paralysis with ↑Na ch on muscles (young men) + cold/rest after exercise - Impaired renal excretion is the only cause of sustained hyperkalemia: Medicine that effects RAAS system, Tubulo-interstitial disease, RTA 4, Obstruction, Genetic - The 5 reasons for ↑K with Cardiac surgery: succinylcholine, K admin with hypothermia, PRBC, epsilon amino caproic acid (mineral acid), cardioplegic (↑K) solutions 10

Nicholas Mayer D.O.

Fluid & Electrolytes Water management: Physiology of water management: ADH stimulated by ↑ plasma osmolality (Osmotic stim) & ↓ intravascular volume (Non-Osmotic stim) ADH stimulates V1aR to ↑Vascular tone & V2R to ↑H2O reabsorption in CD by ↑AQP2 Urine concentration can range from: 50 mOsm ←→ 1200 mOsm (affecting urine volume) Although active sodium transport occurs in both the TAL and DCT, the countercurrent mechanism that makes the medullary interstitium hypertonic is only preserved by TAL ADH can ↑ medullary π interstitium by ↑ NaK2Cl transporters in TAL & ↑urea transporters in CD

Using urine studies to understand water handling by the kidneys: Urine osmolality helps us to understand how much ADH there is. Urine osmolytes include K & Na, as well as other active osmoles such as urea, glucose, & mannitol. Urine osmolality is the concentration of these urine osmolytes. Urine osmolality is the ratio of these osmolytes in the urine to the volume of water in the urine. ADH promotes aquaporins to reabsorb water from the urine in the collecting duct. The less ADH you have, the less water will be re-absorbed, the more water remains in the urine, the lower the concentration of these osmoles in the urine, the lower the urine osmolality. Absent ADH, there will be no reabsorption of water, and the urine will be very dilute. Large ADH secretion ➞ large reabsorption of water from the urine, making the urine concentrated. ↓ ADH ≈ ↓ U osm

↑ ADH ≈ ↑ U osm


The maximal low concentration of these osmoles in urine is about The maximal high concentration of these osmoles in urine is about

50 1200

mOsm/L. mOsm/L.

Urine osmolality is effectively a biomarker for ADH, which cannot be measured due to it’s short half-life.

Polyurea can be related to either a water diuresis or a solute diuresis. Consider medications that would increase urine output such as diuretics or SGLT2 inhibitors Psychogenic Polydipsia with a low serum sodium + psych history. A water diuresis as is seen with Diabetes Insipidus (DI) is the urination of electrolyte free water. Free water loss (FWL)

= Electrolyte-free water loss

= V ( 1 - Una + Uk / Pna )

If Uk + Una = 0, then 100% of urine is electrolyte free and all urine is water lost. If Uk + Una = Pna, then 0% of the urine is electrolyte free and no water is being lost in urine. A solute diuresis is the urination of water with many osmoles determined by the solute excretion rate. Solute excretion rate

= Solutes / day =

Urine mOsm / L


L / day of urine

Solutes in urine that contribute to osmolality are electrolytes (sodium & potassium) and other non-electrolyte osmoles (glucose, manitol, urea) the daily osmotic load is typically ~ 600 mOsm, but can be calculated easily The urine output is related to both the Uosm & the solute excretion rate. Both a water diuresis with DI and a solute diuresis can be present simultaneously. If a patient with DI has a Uosm is 100 mOsm / L, then ↑ solute intake would ↑ the urine volume. Example: UO would ↑ from 6 liters with 600 mOsm/day to 12 liters with 1200 mOsm/day 11

Nicholas Mayer D.O.

Fluid & Electrolytes Hyponatremia - Pathogenesis of Hyponatremia - Pseudohyponatremia with an increased amount of solids in plasma “diluting” serum sodium. Evaluation looks for an osmolal gap or for the true serum sodium by Direct Potentiometry. - Hyperosmolar hyponatremia: some effective osmoles pass freely between intracellular and extracellular compartments (urea, EtOH, methanol, ethylene glycol), and some do not (glucose, mannitol, glycineirrigant). Those that do not move freely translocate sodium and create a “displacement” artifact. Posm = Na x 2 + BUN / 2.8 + Gluc / 18 + EtOH / 4.6 - Non-osmotic secretion of ↑ADH due to ↑ vagal N. tone for reasons such as poor baroreceptor stim: - Hypovolemia: - Hypervolemia: - Spinal cord injury - Nausea

Diarrhea, renal salt loss after toxin (platinum), Addison's dz, CSW, ... CHF, Cirrhosis due to arterial under-filled state

- Hyponatremia despite maximally dilute urine

( Uosm < 100 )

- Psychogenic polydipsia - Beer potomania: low salt intake means limited ability to remove water - Because so much water intake is required in the setting of a normal diet and normal renal function to become hyponatremic, there is often another etiology for hyponatremia with polydipsiainduced hyponatremia (tea-toast, anorexia, SIADH, Thiazide diuretic, fixed isosthenuria) - Hyponatremia with urine that is not maximally dilute ( Uosm > 100 ) - Thiazide

( typically: elderly women, ↑water drinkers, ↓protein intake )

- ↓ urinary dilution: ↓ salt reabsorption in the distal tubule, but no ∆ π interstitium - Hypokalemia results in Na shifting into cells - Hypovolemia with cation depletion stimulates non-osmotic ADH release - Renal disease with fixed isosthenuria or poor urine output - SIADH = too much ADH in euvolemia (no perceivable hemodynamic issue) - Etiology: ↑ body free water → dilution → ↓ serum sodium concentration ↓ body sodium due to volume expansion with ↑ body free water → ↓ RAAS Med Clin No Am 1963; 47(4): 915

Acquired: SSRI, DDAVP, Ecstasy, Carbamazepime, Clorpropramide (for DM2) Acquired with hormonal issues: hypopituitarinism (↓cortisol), Thyroid disease Congenital SIADH with activating mutation of V2R - Dx: low Sosm + U osm > 100 + Euvolemic + Una+ > 30 mEq/L


salt loss with volume expansion = ----------------------------------------------------- = free water retention in CD

↓ serum Na+ (↓Sna+) --------------------------------------↑ serum H2O

- “Cerebral salt wasting” (CSW) is primarily salt loosing with water retention. Only way to make diagnosis is clinically with volume (salt) depletion and very hard to do. - Reset osmostat: if give water, will dilute urine once reach new normal. SIADH will never dilute urine. - Consider GI or adrenal dysfunction: SIADH always has normal K & bicarb. If ↓K & alkalosis, then vomiting? If ↓K & acidosis, then laxative? If ↑K and acidosis, then adrenal insufficiency?


Nicholas Mayer D.O.

Fluid & Electrolytes - Diagnosis: - Evaluation:

1) Hypo-osmolar (low S osm) ? 3) Volume status

2) Elevated urine osmolality (U osm > 100) ? 4) Urine Na > or < 30

- If Serum Osmolality normal or high, then pseudohyponatremia: Hyperlipidemia, Dysproteinemia - If hypovolemic and Una > 30, then DDx: diuretics, or bicarbonaturia with RTA / alkalosis / low aldo - If hypervolemic and Una < 30, then DDx: nephrotic syndrome, cirrhosis or CHF - If volume status ?, give isotonic IVF: Hypovolemia will have ↑Sna & ↑Una, SIADH will ↓Sna & ↑Una


Nicholas Mayer D.O.

Fluid & Electrolytes - Treatment of hyponatremia:

Am J Med 2013; 126: S1 - S42


What is underlying etiology?


Therapy options?

(see above)

- Stop Thiazides - Water restriction - includes all fluids (PO & IV) - Prescribe a restriction that is > 500 mL below the 24 hour urine volume - Predictors of failure: - 24-hour urine volume < 1500 mL - P na < U na+k - U osm > 500 mOsm/kg H2O - Rate of correction - Acute hyponatremia ( < 48 hours) there is no limit to correction. (Marathon runners, Ecstasy) - Chronic hyponatremia ( > 48 hours) correction must be slow due to shift of intracellular osmoles Cerebral edema from ↓ Posm can result in ↓ coordination → seizures → herniation Cerebral edema more likely in women than men NDT 2013; 28: 2206 Osmotic Demyelination (ODS) with overcorrection ↑ Posm can shrink brain in < 72 hr - IF Symptomatic: 1 mEq/L/hr until ↑ 4-6 mEq/L should be enough Semin Neph 2009; 29:282 - Limit: < 12 mmol/L in 1st 24 HR, < 18 mmol/L in 1st 48 HR. JASN 1994; 4: 1522 - Limit < 8 if high risk of ODS: Sna < 105, EtOH-ism, Thiazide use, ↓K, or Malnutrition - Must measure Sna frequently (every 4-6 hours) as urinary water losses are unpredictable - Hypertonic saline - Indications: - Acute hyponatremia ( < 48 hours ): post-operatively; self-induced acute water intoxication with psychosis / schizophrenia, ecstasy use, or endurance exercise such as marathon running - Symptoms of high intracranial pressure like Headaches, Seizures or Coma - Correction with mild - moderate symptoms with a low risk of brain herniation: - Patients at higher risk of severe symptoms are elderly females - 3% NaCl infusion at 0.5 to 2 mL / kg / h - Correction with Acute hyponatremia or severe symptoms - 100 mL of 3% NaCl over 10 minutes x3 as needed - Goal in severe chronic hyponatremia is ↑ by 4-6 mmol/L (but, daily limits still apply) Clin J Sport Med 2008; 18: 111.

Neurology 2008; 70: 1023-29.

Semin Neph 2009; 29:282

- What is expected rate of change of Sna if 3% NaCl is given at rate of 1 ml/kg/hr ? Because 3% NaCl has 513 mEq/L, or 0.5 mEq/mL. when given 1 mL / L of TBW / hr = ↑ serum sodium 0.5 mEq/hr Given that weight in Kg ≈ 2x TBW, 1 mL/Kg/hr = 2 ml / L of TBW / Hr x 0.5 mEq/hr = ↑ serum sodium by ~ 1 mEq/hr This calculation does not consider ongoing urinary, GI, or insensible water losses, therefore, the serum sodium must be closely monitored. - Desmopressin + 3% NaCl: can consider giving for very severe hyponatremia in order to remove potential for over-correction by urinary water loss by inducing iatrogenic SIADH Rx: DDAVP 2 ug IV Q8 start prior to initiation of 3% NaCl at 0.3 mL/kg/hr AJKD 2013; 61(4): 571

- Management of over-correction: - High Risk: Sna < 105, Alcoholism, Drugs, Thiazide use, Hypokalemia, or Malnutrition - DDAVP to prevent further water losses 2 - 4 ug IV Q 8 cJASN 2008; 3: 331-6 - Replace water PO or IV (D5W at 3 mL/kg/hr) - Re-lowering recommended with overcorrection Am J Med 2013: 126(10A): S5


Nicholas Mayer D.O.

Fluid & Electrolytes - Loop diuretics (reduce maximal renal concentrating capacity) with liberal NaCl intake Follow changes in Uosm, if still high, then not helping - Vaptans - Tolvaptan (only treatment with evidence to support therapy) SALT 1 & SALT 2 trials - Tolvaptan achieved short-term symptom benefit in CHF (B) EVEREST JAMA 2007; 297: 1319 - Start in hospital and monitor Sna Q8 during initiation 2 - 3% in SALT trials had overcorrection - monitor LFT if use > 30 days & stop if ALT > doubles - Urea 15 g PO BID - as osmotic diuretic, reduced naturesis - same efficacy as vaptans in study of 12 pts

Am J Med 1980; 69(1): 99 cJASN 2012; 7(5): 742

- Demeclocycline not to be used EVER with concern for kidney injury, light sensitivity, & liver injury - Decompensated heart failure - Fluid restriction (level of evidence C) JACC 2013; 62: e147 - Loop diuretic: not shown to improve Sna - Hypertonic saline only for severe symptoms (with loop) - Tolvaptan achieved short-term symptom benefit (B) EVEREST JAMA 2007; 297: 1319 - CVVHF with customized replacement fluid [Na+] by adding D5W to post-filter Pre-filter RF is [Na+] = 140 mEq/L, given at 2 L per hour Post-filter RF is D5W with [Na+] = 0 mEq/L, given at A L per hour CRRT [Na+] mEq/L = [(140 mEq/L x 2L)+(0 mEq/L x A)] / (2L + A) - Sub-Arachnoid Hemorrhage (SAH) - Common pathology in hyponatremic neurosurgical unit pts - Differential diagnosis of hyponatremia in neurosurgical unit - Most often SIADH (euvolemic) - Inappropriate IVF (hypervolemic) - Adrenal insufficiency (euvolemic) - Drugs and CSW (hypovolemic) unlikely - Hypertonic saline for severe symptoms: - Bolus 100 mL 3% NaCl over 10 min x2 PRN - Goal to increase Sna 4-6 mmol/L and ↓ symptoms

Postgrad Med J 2009; 85: 171 J Clin Endocrin Metabol 2012; 97: 1423 J Clin Endocrin Metabol 2014; 99: 291

J Clin Endocrin Metabol 2014; 99: 291

- Hypovolemic hyponatremia, volume expansion with NS will ↑ GFR + ↑delivery of Na and fluid to distal tubule + ↓ADH release (will correct with saline alone faster than expected) 3)

Treatment Algorithm


Nicholas Mayer D.O.

Fluid & Electrolytes Hypernatremia - Pathogenesis of Hypernatremia - Hypernatremia is ALWAYS synonymous with hypertonicity - Hypernatremia happens when water loss is accompanied by inadequate compensatory intake



2[Na+] + BUN/2.8 + Gluc/18


Na + K ➀ ↑ NaCl intake ----------- = -----------------------------------------------TBW ➁ ↓ water intake or ➂ ↑ water loss

1. High NaCl intake without adequate water intake (seawater ingestion, ICU patients) 2. Insufficient water intake: - very young - very old with neurocognitive disorders - Thirst / Osmoreceptor lesions ( almost always accompanied by central DI ) - AGING (defect in sensation of thirst) - congenital developmental anomalies - germinomas - craniopharyngioma - anterior communicating artery (rupture clipping) - primary aldosteronism (true reseting of osmoreceptors upwards) 3. Inappropriately high water losses - Insensible with sweat or breath - GI with vomiting or Osmotic diarrhea (laxative) where stool osmolality = Na + K + osmole ( remember that with secretory diarrhea (cholera), stool osmolality = Na + K ) - Renal when Una + Uk < Pna → electrolyte free water is being excreted - Osmotic diuresis (glucose, mannitol, urea) - Diabetes Insipidus (if cannot concentrate the urine)



Urine Solute ---------------------Urine Volume


K + Na + osmoles ----------------------------water volume

- Diagnosis: A) Check urine osmolality (Uosm): - Osmotic Diuresis = Uosm intermediate (usually 300 - 600) - Diabetes Insipidus (DI) = Uosm ≤ Posm (usually < 300) B) Water deprivation test in order to determine which type of DI ➞ Water restriction & monitor hourly Uosm. ➞ give DDAVP & monitor Uosm every 30 min for ~ 2 hours Step One: • Normal response to water deprivation is Uosm > 800, indicating ADH release and effect are intact. Step Two: • If Uosm < 800 but stable with 2+ successive hourly measurements despite rising Posm (Sna+), then DI • If Sna > 145, then DI Step Three: • If DDAVP results in ↑ Uosm & ↓ UO of > 50%, then Complete central DI (polyurea can wash out the medullary interstitial gradient, leading to a mild concentrating defect, not correctable by a single dose of DDAVP) • If DDAVP results in ↑ Uosm & ↓ UO of 15 - 50%, then Partial central DI


Nicholas Mayer D.O.

Fluid & Electrolytes - Diabetes insipidus (hypernatremic and Uosm < 800) - From lack of vasopressin - Gestational DI with increased vasopresinase from the placenta - Central DI - Acquired (brain disease) Autoimmune = idiopathic trauma neoplasia (breast ca) vascular granulomatous (histoplasmosis) - Congenital (AD >> AR) AD: loss of Vasopressin gene due to Neurophysin II miscoding AR: Wolfram Syndrome with central DI, DM, Deaf - Nephrogenic DI = poor response to vasopressin at the level of the kidney due to decreased expression of AQP2 - Congenital: V2R (90%) >> AQP2R (10%, AR, + obstructive nephropathy) - Acquired: Drugs: Li++ (enter via ENaC, Tx with amilioride), tenofovir, demecl. Cation: ↑Ca++ & ↓K+ Tubular: Ureteral obstruction & Renal insufficiency (ARF or CKD) - Another way to look at acquired NDI: - Impaired function of medullary TAL with - Impaired function of CD with

↑Ca++, loop diuretics ↑Li++, obstr uropathy, ↓K+

- Special situations: - Post-pituitary resection often with triphasic DI pattern: Initial injury ↓ADH release and polyurea/DI ensues; however, ADH leakage from degenerating neurons briefly causes SIADH, interrupting central DI. Watch for hyponatremia, especially if on DDAVP, around post-op days 4-8.

Hypernatremia management: - Acute management: 1) Restore Euvolemia first: with Hypovolemia, give volume expansion with isotonic fluids with Hypervolemia, give loop diuretics 2) No concern for overcorrection cJASN 2019; 14(5): 656 3) Replace FWD with PO fluids (NG), use IV D5W if cannot use gut. FWD = TBW x ( 1 - 140 / Serum Sodium ) - Diagnosis: - If hypernatremia at time of testing, then no need for water deprivation test because the patient is already water deprived. - If DI present, give DDAVP to to hyperntremic patient in order to determine if central or peripheral - Treatment of DI: Central DI: Gestational DI: Partial Central DI: Polydipsia: Lithium toxicity: Nephrogenic DI:

DDAVP DDAVP Chlorpropramide & Carbamazepime (↑ periph action ADH) ↓water intake Acetazolamide NEJM 2016; 375: 2008 HCTZ + ↓ sodium diet to maintain hypovolemia, NSAIDs by ↓GFR


Nicholas Mayer D.O.

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Fluid and electrolytes  

Review of Fluids and Electrolytes for medical school students, residents and nephrology fellows.

Fluid and electrolytes  

Review of Fluids and Electrolytes for medical school students, residents and nephrology fellows.