Electrolyte Disturbances Hypercalcemia, Hyponatremia, Hypernatremia, Hyperkalemia

Hypercalcemia

Etiology Hypercalcemia results when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in bone. Sources of calcium are most commonly the bone or the gastrointestinal tract

Etiology Hypercalcemia is a relatively common clinical problem. Elevation in the physiologically important ionized (or free) calcium concentration. However, 40 to 45 percent of the calcium in serum is bound to protein, principally albumin; , increased protein binding causes elevation in the serum total calcium.

Increased bone resorption Primary and secondary hyperparathyroidism Malignancy Hyperthyroidism Other - Paget's disease, estrogens or antiestrogens in metastatic breast cancer, hypervitaminosis A, retinoic acid

Increased intestinal calcium absorption Increased calcium intake Renal failure (often with vitamin D supplementation) Milk-alkali syndrome Hypervitaminosis D Enhanced intake of vitamin D or metabolites Chronic granulomatous diseases (eg, sarcoidosis) Malignant lymphoma Acromegaly

Etiology Hyperalbuminemia 1) severe dehydration 2) multiple myeloma who have a calcium-binding paraprotein. This phenomenon is called pseudohypercalcemia (or factitious hypercalcemia)

Other causes Chronic lithium intake Thiazide diuretics Pheochromocytoma Adrenal insufficiency Rhabdomyolysis and acute renal failure Theophylline toxicity Familial hypocalciuric hypercalcemia Immobilization Total parenteral nutrition

Primary hyperparathyroidism Activation of osteoclasts leading to increased bone resorption in primary hyperparathyroidism (also cancer). Adenoma (80%) Hyperplasia (15-20%) Carcinoma (<1%)

Secondary hyperparathyroidism Due to increased PTH in response to decreased calcium ESRD

Tertiary hyperparathyroidism An autonomous nodule develops after longstanding secondary hyperparathyroidism

Familial hypocalciuric hypercalcemia (FHH) Mutation in the Ca-sensing receptor in parathyroid and kidney which increases the Ca set point May also increase the PTH ( parathyroid isn’t sensing Calcium)

Malignancy PTHrP- PTH related peptide (squamous cell lung cancer, renal, breast, bladder) Cytokines (TNF, INTERLEUKIN-1) OAF: Local osteolysis (breast cancer, multiple myeloma) Tumoral effect (Hogkins / NHL)

Vitamin D Excess Granulomas (sarcoid, TB, histo) Vitamin D Intoxication

Increased bone turnover Hyperthyroidism Immobilization Paget’s disease Vitamin A

Miscellaneous Thiazides (increase resorption in kidney) Ca-based antacids (Milk-Alkali Syndrome) Adrenal insufficiency

Clinical Manifestations Bones stones abdominal groans psychic moans

Bones Osteopenia Osteitis fibrosa cystica (seen in severe hyperparathyroidism only)

Osteitis Fibrosa Cystica Cysts, fibrous nodules, salt and pepper appearance on X-ray

Stones Nephrolithiasis Nephrocalcinosis Nephrogenic Diabetes Insipidus

Abdominal Groans Anorexia Nausea Vomiting Constipation Pancreatitis Peptic ulcer disease

Psychic Moans Fatigue Depression Confusion

Labs Free Calcium Measured or Calculated( Measured Ca+(0.8x(4.0-alb) or use med-math? PTH (irma assay) PTH rp VIT D , VIT A PO4 URINE CALCIUM- 24 HRS

Short QT and widened T-wave

Treatment Normal Saline (4-6L per day) FILL THE TANK Furosemide-CALCIURESIS Start after patient is intravascularly repleted Bisphosphonates- Inhibits osteoclast activity(reducing bone resorption and turnover) malignancy and ?Immobilization 28 hrs half-life( zolendronate, pamidronate)

Treatment SQ/IM( not nasal spray)Calcitonin 4 u/kg q12 hrs increase to 8 units q 12 hrs Onset 6-8 hours,duration 2-3 days Steroids( targets OAF, 5-A Hydroxylase) Onset 24-48 hrs days

Primary Hyperparathyroid Surgery (JCEM 2009) Age <50 yrs, GFR <60ml/min, Cal 1 mg/dl above normal, DEXA <-2.5 Medical Bisphonates,Calcitonin,estrogen,serm Early DEXA scans

Hypercalcemia Quiz PTH Increased Cal Increased PO4 decreased What do I have? PRIMARY HYPERPARATHYROIDISM

quiz PTH DECREASED CAL INCREASED PO4 DECREASED/ INCREASED- EITHER WHAT IS IT? MALIGNANCY

QUIZ PTH DECREASED CAL INCREASED PO4 INCREASED WHAT IS IT? VIT D EXCESS/ BONE TURNOVER

QUIZ PTH NORMAL CAL INCREASED PO4 DECREASED FHH

QUIZ PTH INCREASED CAL DECREASED PO4 INCREASED CKD / PSEUDOHYPOPARATHYROIDISM

QUIZ PTH INCREASED CAL DECREASED PO4 DECREASED VIT D DEF

Hyponatremia Santosh Reddy MD

DEFINITION Defined as Serum Sodium less than 136 meq/lt 4 % of hospitalized patients NEJM 2000:342:1581-9( Adrogue,Madias)

Hyponatremia Disorders of sodium are generally due to changes in total body water, not sodium Hyper- or Hypo- osmolality watershifts changes in brain cell volume changes in mental status, seizures

Hyponatremia: pathophysiology Excess water compared to sodium, almost always due to increased ADH The increased ADH may be: Appropriate (e.g. hypovolemia or hypervolemia with too little effective arterial volume)EAV. Inappropriate (e.g. SIADH)

Workup Measure plasma osmolality to determine if hypo, hyper, or isotonic hyponatremia Urine Osmolality Serum NA Urine NA

Hypertonic Hyponatremia Excess of another effective osmoles, such as mannitol, glucose Each 100mg/dL of glucose above 100 causes a decrease in Na by 1.8 mEq/L

Isotonic Hyponatremia Lab artifact from hyperlipidemia or hyperproteinemia

Hypotonic Hyponatremia Most common scenario True excess of water compared to Na

Hypotonic Hyponatremia hypovolemic euvolemic hypervolemic UNa<10 UNa>20 FeNa<1% FeNa>1% UNa>20 UNa<10 FeNa>1% FeNa<1% CHF, cirrhosis, nephrosis Renal failure Renal losses Extrarenal losses Pt’s clinical history Uosm>100 Uosm<100 Uosm var. SIADH, adrenal insuff, hypothyroidism Primary polydipsia, low solute Reset osmostat

Hypovolemic Hypotonic Hyponatremia Renal losses: Thiazides or other diuretics, salt-wasting nephropathy, adrenal insufficiency Extra-renal losses: GI losses (diarrhea), third-spacing (pancreatitis), inadequate intake, insensible losses

Euvolemic Hypotonic Hyponatremia SIADH pulmonary-pneumonia, asthma, COPD, PTX, +pressure ventilation, small cell lung cancer intracranial-trauma, stroke, hemorrhage, tumors, infection, hydrocephalus drugs-antipsychotics, antidepressants, thaizides misc-pain, nausea, post-op state Endocrinopathies (adrenal insuff, hypothyroidism) Reset osmostat ( exercise, seizures)

Low solute “tea & toast”, “beer potomania” – increased free water intake with greatly decreased solute load Maximum rate of water excretion on a normal diet is 10-12 L per day – more than this you overwhelm the excretory capacity of the kidney

Hypervolemic Hypotonic Hyponatremia CHF: low effective arterial volume (EAV)  ADH Cirrhosis: ascites causes low EAV ADH Nephrotic syndrome: hypoalbuminemia causes low EAV  ADH Advanced renal failure

Methods to increase Na Restrict free water range 800-1.2 lt per day Remove stimulus for ADH (volume replete, increase EAV, treat pulmonary pathology, etc) Demeclocycline (ADH antagonist) 300MG BID TO QID Normal saline after NA deficit is calculated

Treatment NA deficit: HYPOTONIC EUVOLEMIA TBW ( 60 % MEN : 50% WOMEN) x (DESIRED NA----MEASURED NA ) Ex: 100 kg Man, MEASURED NA 120 TBW 60 MEQ x 12( D--- M sodium) 720 MEQ PER 24 HOURS

Treatment 0.9 % : 154 meq/ LT 3% : 514 meq / LT GIVE : 4. 6 LT OF 0.9 % NACL 1.4 LT OF 3 % NACL

Treatment of Euvolemic Hyponatremia Asymptomatic: correct at rate of < 0.5 mEq/L/hr Symptomatic: initital rapid correction of Na (2 mEq/L/hr) until symptoms resolve Rate of correction should NOT exceed 12mEq in a 24 hour period, or 18mEq in a 48 hour period to avoid Central pontine myelinosis (CNS demyelination  changes in mental status, paralysis, pseudobulbar palsy) NEPHROLOGY 1994;4:1522-30

Treatment Conivaptan( vaprisol): Aquaresis:blocks the activity of AVP ,free water excretion,without losses of NA/K EVEREST trial for CHF Tolvaptan( Salt 1 and 2 trials) V2 receptor antagonist( hypervolemic or Euvolemic)

Hypernatremia Santosh Reddy

Definition Increase in the serum sodium concentration greater than 145 meq /L

Hypernatremia Usually loss of hypotonic fluid, can also be infusion of too much hypertonic fluid Hypernatremia is a strong thirst stimulus, so usually only affects pts w/o access to water (intubated, altered mental status,insensible losses nursing home patient)

Hypernatremia By definition, all pts are hypertonic Can be Hypovolemic Hypervolemic Euvolemic

Workup: Hypernatremia Check volume status (vitals, orthostatics, JVP, skin turgor, mucous membranes, BUN, Cr) If hypovolemic, check Uosm and UNa to determine whether free water loss is renal or extra-renal If euvolemic, check Uosm to evaluate for complete or partial DI

Hypernatremia hypovolemic euvolemic hypervolemic UOsm300-600 UOsm>600 UNa>20 UNa<20 Exogenous hypertonic saline, Mineralocorticoid excess Renal losses Extrarenal losses Uosm<300 Uosm 300-600 Uosm >600 Complete DI Partial DI, reset osmostat Intracellular osmole generation

Hypovolemic Hypernatremia Renal water losses: osmotic diuresis from glucose/mannitol Extra-renal water losses: diarrhea, insensible (fever, exercise)

Euvolemic Hypernatremia Diabetes Insipidus: central or nephrogenic Seizures, exercise: intracellular osmole generation  water shifts  transient increase in Na Reset osmostat( I,I,I)

Hypervolemic hypernatremia Hypertonic saline administration Mineralocorticoid excess: causes ADH suppression

Free water deficit = TBW x (SerumNa-140) Treatment Replete free water deficit Free water deficit = TBW x (SerumNa-140) 140 D5 W replacement Restore access to water Correct volume status

Treatment Must replete free water deficit via IVF or enteral feeds Correct at rate < 0.5 mEq/L/hr to avoid cerebral edema Must consume > 1L H2O/day

Treatment For hypovolemia hypernatremia For Hypervolemic hypernatremia Correct with ¼ or ½ NS For Hypervolemic hypernatremia Correct with D5W and a loop diuretic

Treatment DI: Central: desmopressin Nephrogenic : Salt restriction + Thiazides Amiloride, Nsaids. V 1 A AND V2 receptor blockage trials

Hyperkalemia

Hyperkalemia Transcellular shifts Decreased excretion by kidneys Normal GFR a)Normal aldosterone (CHF,Cirrhosis) b)Hypoaldosterone(Diabetes etc)

Hyperkalemia: Transcellular shifts Acidosis, Beta-blockers insulin deficiency dig intoxication massive cellular necrosis hyperkalemic periodic paralysis

Hyperkalemia: decreased excretion Decreased GFR (AKI) Hypoaldosteronism with a normal GFR (due to low renin, low aldosterone, or decreased response to aldosterone)

Hyperkalemia: symptoms Weakness Paresthesias Palpitations Peaked T waves on EKG (look like they might hurt to sit on) Other EKG findings: increased PR interval, widened QRS, sine wave pattern, PEA

Peaked T waves

Sine wave

Workup Rule out pseudohyperkalemia (IVF + KCl, hemolysis due to venipuncture, increased plt or WBC) Rule out transcellular shift Assess GFR If normal GFR, calculate TTKG

TTKG: Trans-Tubular Potassium Gradient (UrineK/PlasmaK)/(UrineOsm/PlasmaOsm) TTKG tells you how well aldosterone is working TTKG<7  decreased effective aldosterone function TTKG>7  normal aldosterone function

Treatment Calcium Gluconate/Calcium Chloride: stabilizes cell membranes 1-2 amps I.V 1-3 mins onset lasts 20-30mins Insulin:drives K into cells regular Insulin 10 units IV with 1-2 amps of D50 Beta-2 agonists: drives K into cells; Albuterol 10-20mcg inh or IV 0.5mg Onset 30-60 mins

Treatment Bicarbonate: drives K into cells in exchange for H 1-3 amps Onset 15-30 mins last 60 mins Kayexalate: exchanges Na for K in gut 30-90 mg PO/PR Onset 1-2 hrs Diuretics;decreases total body K; IV lasix hemodialysis: decreases total body K