Best Dx/Best Rx: Disorders of Water and Sodium = Balance

From: Subject: Best Dx/Best Rx: Disorders of Water and Sodium Balance Date: Wed, 3 Jun 2009 21:16:08 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0159_01C9E490.837F9590" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0159_01C9E490.837F9590 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1001.htm Best Dx/Best Rx: Disorders of Water and Sodium = Balance

Disorders of Water and=20 Sodium Balance

Richard H. Sterns, MD, FACP
Medical = University of=20 Rochester School of Medicine and Dentistry

Hy= ponatremia
Hy= pernatremia
Di= abetes=20 Insipidus (DI)
Ed= ema
Vo= lume=20 Depletion

Hyponatremia=20

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features

Low plasma sodium concentration=20
Usually associated with low plasma osmolality = level and=20 body fluids that are too dilute

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Differential = Diagnosis

Hyponatremia = without=20 Hypo=96osmolality=20

Hyperglycemia=20
Intravenous hypertonic mannitol therapy =
Intravenous γ-globulin = therapy=20
Irrigant absorption (prostatectomy or = intrauterine=20 surgery)=20
Pseudohyponatremia
- Severe hyperlipidemia=20
- Multiple myeloma=20
- Macroglobulinemia =

Acute Hyponatremia (Water Intoxication)=20

Neurologic syndrome that develops when large = volumes of=20 water are retained within a short period (< 48 hr)=20
- Headaches=20
- Weakness=20
- Nervousness=20
- Vomiting=20
- Progresses to disorientation, delirium, = tremulousness,=20 convulsions, and coma=20
- Dilated pupils=20
- Bilateral Babinski signs may appear=20
- Hemiparesis may appear
Causes=20
- Postoperative stress; can be fatal in women = and young=20 children=20
- Oxytocin infusion=20
- Cyclophosphamide=20
- Psychotic self-induced water = intoxication=20
- Marathon running=20
- Ecstasy (MDMA) use
Best Tests=20
- Serum electrolytes=20
  - Serum sodium concentration < 130 = mEq/L=20
  - Arterial sodium concentration may be lower = than the=20 venous
- CT scan: shows cerebral edema in severe = cases, rules=20 out other causes of neurologic findings
Best Therapy=20
- Severe symptoms: do not delay therapy while = awaiting=20 imaging=20
- Increase plasma sodium concentration by = 4=966 mEq/L to=20 decrease cerebral edema and stop seizures
- Stop free-water intake=20
- Hypertonic 3% saline=20
  - Dose: 1=962 ml/kg of body weight to raise = plasma=20 sodium by 1=962 mEq/L/hr for 2=963 hrs; for severe neurological = symptoms give=20 100 100 ml by bolus infusion repeated in 10 minutes x 2 if no = clinical=20 improvement=20
  - Best infused in 100 ml containers to avoid = excessive=20 dose=20
  - Avoid increasing plasma sodium = concentration by >=20 12 mEq/L in first day of therapy or by > 6 mEq/L/day = thereafter=20
- Concurrent loop diuretic 40 mg I.V.=20
  - Furosemide=20
  - Bumetanide=20
  - Torsemide =

Chronic Hyponatremia=20

Hyponatremia that evolves over the course of = ≥ 48=20 hr=20
Abnormality in vasopressin secretion, except = in renal=20 failure=20
Rarely fatal=20
May become life-threatening if patient rapidly = ingests=20 large volume of water=20
Patients may have gait disturbances and an = increased=20 risk of falls at plasma sodium concentrations less than 128 = mEq/L=20
Plasma sodium concentrations < 115=96120 = mEq/L produce=20 the following symptoms:=20
- Anorexia=20
- Nausea=20
- Vomiting=20
- Muscle weakness=20
- Muscle cramps=20
- Irritability=20
- Personality changes=20
- Slow response
Plasma sodium concentrations < 110 mEq/L = produce the=20 following symptoms:=20
- Stupor=20
- Tremulousness=20
- More rarely, seizures
Causes=20
- Advanced renal failure
- Thiazide diuretics=20
- Hypovolemia, including Addison = disease=20
- Obsessive consumption of beer=20
- Edematous conditions, including the = following:=20
  - Congestive heart failure=20
  - Cirrhosis=20
  - Nephrotic syndrome
- AIDS=20
- Syndrome of inappropriate antidiuretic = hormone=20 secretion (SIADH) (water is retained without abnormal sodium = balance, volume=20 depletion, or edema); may indicate the following:=20
  - Malignancy=20
  - Chest infection=20
  - Tuberculosis=20
  - Pneumonia=20
  - Hypopituitarism with glucocorticoid = deficiency=20
  - Hypothyroidism
- NSAIDs may exacerbate other causes of=20 hyponatremia

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Best=20 Tests

History and Physical=20 Examination=20

Exclude disorders that can lower plasma sodium = concentration without causing hypotonicity
Diet, fluid intake, GI fluid losses, and use = of=20 diuretics, antidepressants, or other antidiuretic drugs
Signs of volume depletion or edema=20
Check for signs of disorders known to cause = SIADH=20
Evaluate severity of neurologic symptoms to = determine=20 the need for urgent therapy

Laboratory Tests=20

Plasma sodium concentration=20
Urinary sodium and/or chloride = concentration=20
- Urinary sodium < 20 mEq/L without edema = indicates=20 hypovolemia=20
- Urinary chloride < 20 mEq/L without edema = indicates=20 hypovolemia in patients with metabolic alkalosis due to gastric = fluid losses=20 (urinary sodium may be > 20 mEq/L)=20
- Urinary sodium > 40 mEq/L with normal = renal=20 function and in the absence of diuretics indicates SIADH =
BUN and serum uric acid=20
- Elevated in hemodynamic abnormalities, low = in=20 SIADH
Uric acid=20
- More reliable indicator of volume status = than=20 BUN
Serum potassium and bicarbonate=20
- Levels are normal in SIADH
Hypokalemia and metabolic alkalosis=20
- Suggest diuretic therapy or vomiting =
Hypokalemia and acidosis=20
- Suggest diarrhea or laxative abuse =
Hyperkalemia and acidosis=20
- Suggest adrenal insufficiency=20

Withdrawal of Hyponatremic=20 Drugs=20

Exclude another cause for hyponatremia before=20 attributing electrolyte disturbance to a drug=20
To diagnose drug-induced hyponatremia, = eliminate the=20 drug and see if water excretion returns to normal (may take 1=962 wk = in=20 thiazide-induced hyponatremia)

Response to=20 Isotonic Saline=20

Patients with subclinical edematous conditions = retain=20 the sodium and develop edema=20
Volume-depleted patients=20
- Water diuresis (dilute urine) emerges and = hyponatremia=20 improves; avoid overly rapid correction
Patients with SIADH=20
- Hyponatremia persists and may worsen; seek a = specific=20 etiology and follow up carefully if no cause for SIADH is = found=20

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Best=20 Therapy

Increase plasma sodium concentration by at = least 4=20 mEq/L/day=20
Restrict free water until plasma sodium begins = to=20 increase=20
Limit oral fluid intake to 500=961,000 ml/day, = depending=20 on the severity of electrolyte disturbance=20
Avoid thiazides=20
Excessive correction of chronic hyponatremia = may cause=20 neurologic injury (osmotic demyelination syndrome)=20
- Confusion=20
- Psychotic or catatonic behavior=20
- Pathologic crying=20
- Movement disorderSwallowing=20 dysfunction=20
- Progressive unresponsiveness=20
- Spastic quadriparesis=20
- Avoid by maintaining rates of correction = < 10=9612=20 mEq/L/day and 18 mEq/L/48 hr=20
- Aim for an increase of serum sodium = concentration by 8=20 mEq/L/day or less
Hyponatremic seizures=20
- Treat with hypertonic saline and=20 anticonvulsants=20
- Initial correction by 1 to 2 mEq/L/hr with = total=20 correction < 10 to 12 mEq/L/day

Reversible Defects in Water Excretion=20

Hypovolemic hyponatremia=20
- 0.9% sodium chloride I.V.=20
- Discontinue once hypovolemia is corrected = and plasma=20 sodium concentration begins to increase=20
- Use saline cautiously, if at all, in = hypokalemic=20 patients who require potassium replacement=20
- Potassium replacement raises plasma sodium=20 concentration
Diuretic-induced hyponatremia=20
- Easily corrected by the following:=20
  - Adequate diet=20
  - Replacement of potassium deficits=20
  - Discontinuance of thiazide diuretics =
- I.V. saline usually not required =
Severe hyponatremia=20
- Monitor plasma sodium concentration every = 6=968 hr=20 during first 2=963 days of therapy=20
- If water diuresis threatens to increase = plasma sodium=20 too much, give oral water or 5% dextrose in water to slow the rate = of=20 correction or administer desmopressin to stop the water = diuresis=20

Persistent Defects in Water = Excretion=20

SIADH=20
- Water restriction alone is slow to resolve=20 hyponatremia=20
- Furosemide is a useful adjunct: 20 mg p.o., = b.i.d. (or=20 equivalent dose of bumetanide or torsemide)=20
- Oral salt or slow infusion of 3% saline = (approximately=20 15 ml/hr)=20
- Demeclocycline: high cost and long duration = of action=20 limit its effectiveness=20
  - Dose: 600 to 1,200 mg/day =
- Conivaptan: intravenous vasopressin receptor = antagonist to induce an "aquaresis" (increased urinary water losses = without=20 change in urinary sodium and potassium losses) in hospitalized=20 patients
Edematous conditions=20
- Do not give saline=20
  - Will not improve hyponatremia and worsens=20 edema
- Loop diuretics plus ACE inhibitor=20
  - Particularly effective in patients with = congestive=20 heart failure

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Best = References

Adrogue HJ, et al: N Engl J Med 342:1581, 2000 = [PMID = 10824078]=20

Sterns RH, et al: QJM 96:549, 2003 [PMID=20 12897339]

Ellison DH, Berl T: N Engl J Med 356:2064, 2007 = [PMID=20 17507705]

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Hypernatremia=20

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Loss of water not adequately replaced or = excessive salt=20 intake=20
Causes=20
- Electrolyte-free water losses through skin = and=20 lungs=20
- Diabetes insipidus=20
- Electrolyte abnormalities=20
- Drugs=20
- Pregnancy=20
- Excess urea excretion=20
  - Protein feeding=20
  - Catabolism=20
  - Resolution of renal failure =
- Hypotonic losses=20
  - Sweat=20
  - Vomiting=20
  - Cathartics=20
  - Glycosuria=20
  - Diuretics
- Salt poisoning (oral or parenteral) =
Acute onset (salt poisoning)=20
- Neurologic symptoms=20
  - Seizures=20
  - Coma=20
  - Hyperventilation=20
  - Hyperreflexia=20
  - Hypertonia=20
  - High fever
- Plasma sodium levels > 170 mEq/L often = fatal=20
Chronic hypernatremia=20
- Lethargy to coma, depending on severity of = electrolyte=20 disturbance=20
- Signs and symptoms of extracellular fluid = volume=20 depletion

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Differential = Diagnosis

Impaired thirst=20
Excessive insensible or GI water losses =
Osmotic diuresis=20
Diabetes insipidus

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Best=20 Tests

History and Physical=20 Examination=20

Serum electrolytes=20
Water deficit =3D normal body water (1 - serum = [Na⁺]/140) (amount of water that will return the serum = sodium=20 concentration to normal)=20
- Diabetic patients with hyperglycemic = dehydration need=20 more

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Best=20 Therapy

Correct severe volume depletion before = correcting=20 hypernatremia=20
Hypotensive patient: rapid infusion of = isotonic=20 saline=20
Hemodynamically stable patient: pure-water=20 replacement=20
Edematous patient: diuretics plus = electrolyte-free=20 water=20
- Electrolyte-free water I.V. in a 5% dextrose = solution=20 (D5W) at < 500 ml/hr for patients who cannot drink=20
- Monitor serum sodium concentration and urine = output=20 frequently and adjust fluids appropriately
Correcting hypernatremia too rapidly can cause = cerebral=20 edema=20
Reduce serum sodium concentration by ≤ = 10=9612=20 mEq/L/day=20
Electrolyte-free water intake should exceed = free-water=20 losses by ≤ 2 L daily=20
Acute salt poisoning: rapid infusions of=20 electrolyte-free water plus a loop diuretic (without waiting for serum = electrolyte test) may prevent irreversible brain injury=20
Diabetic dehydration=20
- Prevent hypovolemia following correction of=20 hyperglycemia=20
  - 1=962 L 0.45% isotonic saline at a rate = that exceeds=20 urine output
- Carefully monitor serum sodium = concentration, blood=20 glucose level, and urine output to tailor fluid replacement to = needs=20
- Avoid rapid correction of hypertonicity in = severe=20 hyperglycemia to prevent cerebral edema

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Best = References

Adrogue HJ, et al: N Engl J Med 342:1493, 2000 = [PMID = 10816188]=20

Fried LF, et al: Med Clin North Am 81:585, 1997 = [PMID=20 9167647]

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Diabetes = Insipidus=20 (DI)

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

A disorder of water conservation=20
- Neurogenic: deficient secretion of = vasopressin=20
- Nephrogenic: unresponsiveness of kidneys to = normally=20 secreted hormone
Polyuria (> 3=964 L of urine/day)=20
Nocturia=20
Polydipsia

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Differential=20 Diagnosis

Primary polydipsia

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Best=20 Tests

Urine osmolality level: < 250 mOsm/kg in DI = despite=20 hypernatremia=20
Serum osmolality level=20
Serum sodium concentration=20
MRI of the brain: bright spot on posterior = pituitary is=20 absent or greatly diminished in pituitary DI

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Best=20 Therapy

Water replacement

Neurogenic DI=20

1-desamino-8-D-arginine vasopressin (DDAVP), = parenteral=20 or intranasal=20
Chlorpropamide: 125 to 250 mg once or twice a = day=20 (higher doses risk hypoglycemia)=20
Carbamazepine: 100 to 300 mg twice = daily=20
Thiazide diuretics: for patients with mild=20 disease=20
Limit dietary salt and protein =

Nephrogenic DI=20

Limit dietary salt and protein=20
Thiazide diuretics=20
Indomethacin: 2 mg/kg/day=20
Amiloride: for prevention of lithium-induced = nephrogenic=20 DI

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Best=20 References

Verbalis JG: Rev Endocr Metab Disord 4:177, 2003 = [PMID = 12766546]=20

Sands JM, et al: Ann Intern Med 144:186, 2006 [PMID=20 16461963]

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Edema

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Swelling of the soft tissues caused by excess = saltwater=20 in the extracellular space=20
Retention of dietary or infused sodium with = impaired=20 ability to excrete saltwater

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Differential=20 Diagnosis

Renal disease (nephrotic syndrome, nephritic=20 disease)=20
Congestive heart failure=20
Cirrhosis=20
Premenstrual fluid retention=20
Long-term diuretic or cathartic use=20
Idiopathic edema

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Best=20 Tests

History and physical examination=20
- Signs and symptoms depend on underlying = cause=20
- Dyspnea on exertion, orthopnea indicate left = ventricular failure or nephritic edema=20
- Large volumes may cause shortness of breath, = gastric=20 reflux, or infection=20
- Tissues can be indented or pitted by the = examiner's=20 fingers=20
- Seek signs of heart, renal, or liver = disease=20
Urinalysis=20
Serum albumin=20
Liver function tests=20
Chest x-ray=20
Plasma B-type natriuretic peptide (BNP): = levels are=20 increased in heart failure

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Best=20 Therapy

Dietary salt restriction=20
Diuretics=20
- Define effective dose early=20
- Induce fluid loss gradually, increasing the = dose until=20 desired weight is reached=20
- Inpatients can be managed more precisely = with=20 continuous infusion=20
- Diuretic resistance=20
  - Loop diuretics plus thiazide or metolazone = and/or=20 acetazolamide=20
  - Monitor carefully to avoid large potassium = and=20 sodium losses=20
  - Loop diuretics can predispose to hearing = loss,=20 particularly at high doses via bolus injection in patients = receiving other=20 ototoxic drugs
- Complications=20
  - Azotemia=20
  - Volume depletion=20
  - Thiazides and loop diuretics can cause the = following:=20
    - Hypokalemic alkalosis=20
    - Hyperglycemia=20
    - Hyperuricemia (sometimes with clinical=20 gout)
  - Thiazides can cause hypercalcemia in = patients with=20 underlying conditions that increase calcium absorption (e.g., = sarcoidosis)=20 or bone reabsorption (e.g., hyperparathyroidism)=20
  - Avoid thiazides in patients with high = fluid=20 intake=20
  - Potassium-sparing agents (e.g., = triamterene,=20 amiloride, spironolactone) may cause hyperkalemia=20
    - Do not give with potassium = supplements=20
    - Use with caution in patients with renal=20 insufficiency and those taking ACE inhibitors or angiotensin II = blocking=20 agents
Cirrhotic patients with ascites but no = peripheral=20 edema=20
- Limit weight loss to 0.5 kg/day =
Repeated large-volume paracenteses plus I.V.=20 albumin=20
- Alternative to diuretics=20
- Avoids intravascular volume depletion =
- Afterward, diuretics can prevent = reaccumulation of=20 ascitic fluid

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Best=20 References

Brater DC: N Engl J Med 339:387, 1998 [PMID = 9691107]=20

O'Brien JG, et al: Am Fam Physician 71:2111, 2005 = [PMID=20 15952439]

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Volume=20 Depletion

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Loss of saltwater from the extracellular fluid = at a rate=20 that exceeds intake=20
Characterized by the following:=20
- Increased heart rate=20
- Fatigue=20
- Thirst=20
- Muscle cramps=20
- Rapid weight loss=20
- Low jugular venous pulse rate=20
- Hypotension on standing or during physical=20 exertion=20
- Hypotension in recumbency=20
- Tissue ischemia=20
- Shock in severe cases =

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Differential=20 Diagnosis

Diarrhea=20
Fluid sequestrated in the abdominal cavity = (pancreatitis=20 or peritonitis) or in the soft tissues (crush injuries with = rhabdomyolysis or=20 burns)=20
Renal salt wasting from diuretics=20
Osmotic diuresis caused by glycosuria=20
Recovery phases of acute tubular necrosis or = obstructive=20 uropathy=20
Toxic nephropathies=20
Adrenal insufficiency

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Best=20 Tests

Hematocrit: increases in proportion to the = contraction=20 of plasma volume=20
Serum albumin: may be increased
Urinary sodium: usually < 20 mEq/L except = in=20 metabolic alkalosis (in which the urine chloride is low) or when renal = sodium=20 wasting is the cause of the condition=20
Serum creatinine: changes very little=20
BUN: increased disproportionately to the = increase in=20 creatinine=20
Azotemia may be blunted in patients with a = poor dietary=20 protein intake and may be exacerbated in patients who are catabolic, = bleeding,=20 or receiving steroid therapy

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Best=20 Therapy

Increase dietary intake of salt=20
Oral solutions containing electrolytes, sugar, = and amino=20 acids=20
I.V. fluids when fluids cannot be taken = orally=20
Hypotensive patients: isotonic saline given as = rapidly=20 as possible until tissue perfusion is adequate =

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Best=20 References

McGee S, et al: JAMA 281:1022, 1999 [PMID = 10086438]=20

Greenberg A: Ann J Med Sci 319:10, 2000 [PMID=20 10653441]

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The author has received honoraria from = Astellas, the=20 manufacturer of Conivaptan.

February=20 2009

=A9 2009 BC Decker Inc. All = rights=20 reserved.=20

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