1. The Diagnosis of and Therapy for Common Fluid and Electrolyte Imbalances Angela Heithaus, MD, PS Internal Medicine Seattle Healing Arts Center

2. Leonardo da Vinci 24 YO M comes to see you complaining that after 2 days of vomiting and diarrhea without fever or abdominal pain or hematochezia that he becomes light headed when standing and thought at one point he was going to pass out. 24 YO M comes to see you complaining that after 2 days of vomiting and diarrhea without fever or abdominal pain or hematochezia that he becomes light headed when standing and thought at one point he was going to pass out. On exam there is no abdominal tenderness On exam there is no abdominal tenderness

3. Questions What should you document/check? What should you document/check? How should you treat? How should you treat?

6. Volume Depletion

7. Loss of isotonic fluid from the extracellular fluid at a rate exceeding net intake. Loss of isotonic fluid from the extracellular fluid at a rate exceeding net intake. Can occur through: Can occur through: gastrointestinal tract (vomiting, diarrhea, bleeding) gastrointestinal tract (vomiting, diarrhea, bleeding) skin (sweat, burns) skin (sweat, burns) lungs (bronchorrhea, pleural effusion, evaporation) lungs (bronchorrhea, pleural effusion, evaporation) urine (diuretics, osmotic diuresis, salt wasting nephropathies, and hypoaldosteronism) urine (diuretics, osmotic diuresis, salt wasting nephropathies, and hypoaldosteronism) acute sequestration in the body in a "third space" that is not in equilibrium with the extracellular fluid (GI obstruction, crush injury, bleeding, acute pancreatitis) acute sequestration in the body in a "third space" that is not in equilibrium with the extracellular fluid (GI obstruction, crush injury, bleeding, acute pancreatitis)

8. History and Symptoms of Volume Depletion History vomiting, diarrhea, diuretic use, or polyuria (may identify the source of fluid loss) Symptoms Symptoms lethargy, easy fatiguability, thirst, muscle cramps, and postural dizziness (volume depletion) lethargy, easy fatiguability, thirst, muscle cramps, and postural dizziness (volume depletion) Generalized weakness, irritability, maybe twitching, seizures (if also severely hyponatremic) Generalized weakness, irritability, maybe twitching, seizures (if also severely hyponatremic) muscle weakness, polyuria, polydipsia, confusion muscle weakness, polyuria, polydipsia, confusion (from concomitant electrolyte and acid-base disorders) (from concomitant electrolyte and acid-base disorders)

9. PEx findings in Hypovolemia BP, HR, and JVD BP, HR, and JVD BP drops in upright position BP drops in upright position ‘orthostatic hypotension’ – after two to five minutes of quiet standing, one or more of the following is present: ‘orthostatic hypotension’ – after two to five minutes of quiet standing, one or more of the following is present: At least a 20 mmHg fall in systolic pressure At least a 20 mmHg fall in systolic pressure At least a 10 mmHg fall in diastolic pressure At least a 10 mmHg fall in diastolic pressure Symptoms of cerebral hypoperfusion (dizziness) Symptoms of cerebral hypoperfusion (dizziness) HR increase by more than 10-20 bpm HR increase by more than 10-20 bpm Decreased JVD Decreased JVD Skin Skin Increased pigmentation, decreased turgor, dry axilla Increased pigmentation, decreased turgor, dry axilla Mucous membranes Mucous membranes Tongue and oral mucosa dry Tongue and oral mucosa dry

10. Laboratory Studies Urine Urine urinalysis can be normal urinalysis can be normal sodium concentration < 25 meq/L and may be as low as 1 meq/L sodium concentration < 25 meq/L and may be as low as 1 meq/L chloride concentration low chloride concentration low osmolality >450 mosmol/kg osmolality >450 mosmol/kg specific gravity > 1.015 specific gravity > 1.015 oliguria oliguria Blood Blood Elevated serum sodium = dehydration Elevated serum sodium = dehydration If [Na] WNL then pt not dehyrated but hypovolemic If [Na] WNL then pt not dehyrated but hypovolemic Elevated BUN/plasma creatinine level Elevated BUN/plasma creatinine level HCT (relative polycythemia) and plasma albumin level HCT (relative polycythemia) and plasma albumin levelincreases

11. Replacement Therapy IVF Bolus IVF Bolus 5cc/kg over 20 minutes 5cc/kg over 20 minutes Usually rounded to 500cc for adults and extended to 30 minutes Usually rounded to 500cc for adults and extended to 30 minutes Normal Saline (isotonic) best Normal Saline (isotonic) best Ringers lactate (has bicarb) if >4 liters will be given Ringers lactate (has bicarb) if >4 liters will be given This prevents development of metabolic acidosis This prevents development of metabolic acidosis IV Catheters IV Catheters 18 gauge best 18 gauge best

12. Replacement Therapy Precautions Excess NS can cause pulmonary edema in some pts: Excess NS can cause pulmonary edema in some pts: Elderly pts with hx of CHF Elderly pts with hx of CHF Pts with known severe VHD Pts with known severe VHD Renal failure pts Renal failure pts In these pts use 3cc/kg over 30 minutes for boluses and listen to lungs often, measure SaO2 if possible In these pts use 3cc/kg over 30 minutes for boluses and listen to lungs often, measure SaO2 if possible

13. Answers What should you document? What should you document? Orthostatic BP/HR- (pt still hypovolemic?) Orthostatic BP/HR- (pt still hypovolemic?) How much volume should you replete and how fast? How much volume should you replete and how fast? Bolus 500cc over 30 minutes Bolus 500cc over 30 minutes Which type of fluid should you use? Which type of fluid should you use? Normal Saline (isotonic) best Normal Saline (isotonic) best Ringers lactate (has bicarb) if >4 liters anticipated Ringers lactate (has bicarb) if >4 liters anticipated This prevents development of metabolic acidosis This prevents development of metabolic acidosis

14. Leonardo continued… When have you given enough IVF? When have you given enough IVF? Recheck orthostatic pressures and sx Recheck orthostatic pressures and sx If still orthostatic? If still orthostatic? Rebolus, repeat cycle until asymptomatic, making urine, mucous membranes moist Rebolus, repeat cycle until asymptomatic, making urine, mucous membranes moist

16. Sophia Loren 70 YO F with H/O HTN on HCTZ presents C/O nausea and malaise x 1 month 70 YO F with H/O HTN on HCTZ presents C/O nausea and malaise x 1 month PEx is WNL PEx is WNL Labs: Na+ 121 Labs: Na+ 121

17. Clinical Manifestations of Hyponatremia Plasma Na+ 125-130 meq/L nausea and malaise Plasma Na+ <115-120 meq/L headache, lethargy, and obtundation and eventually seizures, coma and respiratory arrest

18. Differential Diagnosis for Hyponatremia In almost all cases, results from the intake (either oral or intravenous) and subsequent retention of water In almost all cases, results from the intake (either oral or intravenous) and subsequent retention of water In almost all cases, occurs because there is an impairment in renal water excretion, due most often to an inability to suppress ADH release In almost all cases, occurs because there is an impairment in renal water excretion, due most often to an inability to suppress ADH release

19. ADH Elevated Elevated Effective circulating volume depletion Effective circulating volume depletion Heart failure, cirrhosis, thiazide diurectics Heart failure, cirrhosis, thiazide diurectics Syndrome of Inappropriate ADH secretion Syndrome of Inappropriate ADH secretion Hormonal changes Hormonal changes Adrenal insufficiency, hypothyroidism, pregnancy

20. Evaluation of Patients with Hyponatremia Assess volume status of patient Assess volume status of patient Hypovolemia: orthostatic, dry mucous membranes Hypovolemia: orthostatic, dry mucous membranes Hypervolemia: peripheral edema, pulmonary edema, JVD, ascites Hypervolemia: peripheral edema, pulmonary edema, JVD, ascites For Euvolemic pt: For Euvolemic pt: Check TSH Check TSH Check urine osmolarity for SIADH (inappropriately concentrated urine- should be dilute in this setting) Check urine osmolarity for SIADH (inappropriately concentrated urine- should be dilute in this setting)

21. Treatment of Hyponatremia Initial treatment in such patients typically consists of gradual correction of the hyponatremia via water restriction or the administration of isotonic saline (or oral salt) Initial treatment in such patients typically consists of gradual correction of the hyponatremia via water restriction or the administration of isotonic saline (or oral salt) More aggressive therapy is indicated in patients who have symptomatic or severe hyponatremia (plasma sodium concentration below 110 to 115 meq/L). More aggressive therapy is indicated in patients who have symptomatic or severe hyponatremia (plasma sodium concentration below 110 to 115 meq/L).

23. Gabriele Falloppio 60 yo male with diarrhea x 1 wk, no vomiting; good PO intake, comes to see you because of mild intermittent leg cramps 60 yo male with diarrhea x 1 wk, no vomiting; good PO intake, comes to see you because of mild intermittent leg cramps PEx is unremarkable, there is no abdominal tenderness or neurological deficit PEx is unremarkable, there is no abdominal tenderness or neurological deficit Labs reveal K of 2.9, otherwise WNL Labs reveal K of 2.9, otherwise WNL

24. Hypokalemia GI, urinary losses GI, urinary losses Mild loss, K+ between 3.0 and 3.5 meq/L Mild loss, K+ between 3.0 and 3.5 meq/L usually produces no symptoms usually produces no symptoms replace lost K+ and treat underlying disorder (such as vomiting, diarrhea) replace lost K+ and treat underlying disorder (such as vomiting, diarrhea) treatment is usually started with 10 to 20 meq of potassium chloride given two to four times per day (20 to 80 meq per day), depending on the severity of hypokalemia and on whether hypokalemia developed acutely or is chronic treatment is usually started with 10 to 20 meq of potassium chloride given two to four times per day (20 to 80 meq per day), depending on the severity of hypokalemia and on whether hypokalemia developed acutely or is chronicpotassium chloridepotassium chloride sequential monitoring of plasma K+ is essential to determine continued requirements, with frequency of monitoring dependent on the severity of hypokalemia sequential monitoring of plasma K+ is essential to determine continued requirements, with frequency of monitoring dependent on the severity of hypokalemia

25. Severe Hypokalemia Symptoms generally do not become manifest until the serum K+ is below 3.0 meq/L Symptoms generally do not become manifest until the serum K+ is below 3.0 meq/L Muscular abnormalities Muscular abnormalities muscle cramps, rhabdomyolysis, and myoglobinuria muscle cramps, rhabdomyolysis, and myoglobinuria Cardiac arrhythmias and ECG abnormalities Cardiac arrhythmias and ECG abnormalities PAC, PAT, PVC, AVB, VT PAC, PAT, PVC, AVB, VT Renal abnormalities Renal abnormalities impaired urinary concentrating ability (which may be symptomatic with nocturia, polyuria and polydipsia impaired urinary concentrating ability (which may be symptomatic with nocturia, polyuria and polydipsia

27. Enrico Fermi 60 YO M comes in for physical exam which is WNL; labs reveal Ca 12.6 60 YO M comes in for physical exam which is WNL; labs reveal Ca 12.6 Is further evaluation indicated and if so, what? Is further evaluation indicated and if so, what?

28. Calcium Range 8.5-10.6 mg/dL Range 8.5-10.6 mg/dL Plasma Ca2+ concentration includes all the Ca2+ in the plasma, of which only about 45 percent circulates in the physiologically important ionized or unbound state. Plasma Ca2+ concentration includes all the Ca2+ in the plasma, of which only about 45 percent circulates in the physiologically important ionized or unbound state. Common exception occurs in patients with hypoalbuminemia in whom the concomitant decrease in ion binding leads to a reduction in the total plasma Ca2+ concentration without change in the ionized form Common exception occurs in patients with hypoalbuminemia in whom the concomitant decrease in ion binding leads to a reduction in the total plasma Ca2+ concentration without change in the ionized form if albumin <2.0 g/dL (roughly 2.0 g/L less than normal), then the corrected plasma Ca2+ concentration would be 7.5 + (2 x 0.8) or 9.1 mg/dL, which is normal if albumin <2.0 g/dL (roughly 2.0 g/L less than normal), then the corrected plasma Ca2+ concentration would be 7.5 + (2 x 0.8) or 9.1 mg/dL, which is normal

29. Differential Diagnosis of Hypercalcemia Hyperparathyroidism Hyperparathyroidism >90% of ambulatory cases >90% of ambulatory cases Primary hyperparathyroidism is most often due to a parathyroid adenoma Primary hyperparathyroidism is most often due to a parathyroid adenoma Cancer Cancer solid tumors and leukemias solid tumors and leukemias Local resorption of bone induced by metastases (mediated by local release of cytokines such as tumor necrosis factor and interleukin-1) or the production of humoral osteoclast activators, particularly PTH-related protein Local resorption of bone induced by metastases (mediated by local release of cytokines such as tumor necrosis factor and interleukin-1) or the production of humoral osteoclast activators, particularly PTH-related protein Hyperthyroidism Hyperthyroidism 15-20% of patients can develop mild hypercalcemia 15-20% of patients can develop mild hypercalcemia

30. Evaluation of Hypercalcemia Correct diagnosis in 95% of cases by evaluating: Correct diagnosis in 95% of cases by evaluating: History History PEx PEx CXR (r/o malignancy or sarcoidosis) and CXR (r/o malignancy or sarcoidosis) and Lab data: PTH (serum intact), PTHRP related peptide, serum protein electrophoresis (r/o multiple myeloma), creatinine Lab data: PTH (serum intact), PTHRP related peptide, serum protein electrophoresis (r/o multiple myeloma), creatinine Primary hyperparathyroidism is often associated with borderline or mild hypercalcemia with the serum calcium concentration often being below 11 mg/dL (2.75 mmol/L) Primary hyperparathyroidism is often associated with borderline or mild hypercalcemia with the serum calcium concentration often being below 11 mg/dL (2.75 mmol/L)

31. Treatment Goals in Hypercalcemia Lowering serum Ca++ level Lowering serum Ca++ level Saline administration to produce volume expansion and increase urinary Ca++ excretion (oral hydration + high salt diet) Saline administration to produce volume expansion and increase urinary Ca++ excretion (oral hydration + high salt diet) Concurrent tx with biphosphonates) +/- calcitonin (decrease bone resorption) Concurrent tx with biphosphonates) +/- calcitonin (decrease bone resorption) Oral phosphate 250-500 mg QID (decrease absorption in gut) Oral phosphate 250-500 mg QID (decrease absorption in gut) Correcting or decreasing underlying disease Correcting or decreasing underlying disease Hyperparathyroidism Hyperparathyroidism