Fluid & Electrolyte Imbalances: Ca & Phos (Exam 1)

what are the major physiologic roles of calcium?

-neuromuscular activity

-cell membrane function

-platelet adhesion

-cardiac/smooth muscle function

where is most calcium stored in the body?

about 99% stored in bone

what are the normal ranges for total and ionized calcium?

-total Ca: 9-10.5 mg/dL

-ionized Ca: 4.5-5.6 mg/dL

what is the difference between total and ionized calcium?

-total calcium: bound + unbound calcium; most commonly measured

-ionized calcium: free, biologically active calcium

why must albumin be considered when interpreting total calcium?

because changes in albumin can alter total calcium even when biologically active ionized calcium remains normal

when should corrected calcium be calculated?

when total calcium is measured and albumin is abnormal

what is the corrected calcium equation?

corrected Ca = measured Ca + 0.8 * (4 - albumin)

how does PTH affect serum calcium?

it increases serum Ca by increasing calcium release from bone, increasing renal Ca reabsorption, and increasing renal activation of vitamin D

how does vitamin D affect serum calcium?

increases serum Ca primarily by increasing GI calcium absorption

how does calcitonin affect serum calcium?

decreases serum Ca primarily by increasing GI calcium absorption

how does acid-base status affect ionized calcium?

-alkalosis ---> increased Ca binding to albumin ---> decreased ionized Ca

-acidosis ---> decreased Ca binding to albumin ---> increased ionized Ca

how is hypocalcemia defined?

-total Ca

what are important causes of hypocalcemia?

-vitamin D deficiency

-hypomagnesemia ---> impaired PTH secretion

-hungry bone syndrome after parathyroid/thyroid surgery

-drugs such as loop diuretics, calcitonin, bisphosphonates, denosumab, and cinacalcet

what are the major symptoms of hypocalcemia?

most importantly neuromuscular excitability, including tetany and muscle cramps; CNS and cardiovascular effects may occur in more severe cases

how is chronic or asymptomatic hypocalcemia treated?

oral calcium with/without vitamin D (calcium goal 1000-1500 mg/day)

what is the key difference between calcium carbonate and calcium citrate?

calcium carbonate: requires acid ---> take with meals

calcium citrate: can be taken with or without meals

how much oral calcium should generally be given at one time?

limit to about 600 mg per does, so larger daily amounts are divided into multiple doses

how is acute, severe, or symptomatic hypocalcemia treated?

with IV calcium given over 30-60 minutes:

-calcium chloride 1 g IV

-calcium gluconate 2-3 g IV, which is preferred

why is calcium gluconate generally preferred over calcium chloride?

calcium gluconate is safer for peripheral administration, while calcium chloride is more irritating and carries greater risk of tissue injury with extravasation

how is hypercalcemia defined?

-total Ca >10.5 mg/dL

-ionized Ca >5.6 mg/dL

what are the major causes of hypercalcemia?

-malignancy

-primary hyperparathyroidism

-excess vitamin D or calcium

-drugs including thiazides and lithium

how can malignancy cause hypercalcemia?

tumors may secrete PTH-related protein (PTHrP), which mimics PTH, increase vitamin D activity, or increase bone resorption

what are important symptoms of severe hypercalcemia?

-fatigue

-constipation

-polyuria

-cardiac arrhythmias

-neurologic symptoms in severe cases

what is the first step in treating acute severe hypercalcemia/hypercalcemic crisis?

volume expansion with 0.9% NaCl:

-1-2 L bolus

-then 200-300 mL/hr until hemodynamically stable

why is normal saline used first in severe hypercalcemia?

it expands the ECF volume and helps dilute serum calcium and restore renal perfusion, allowing greater calcium excretion

how can calcium excretion be increased after volume restoration?

a loop diuretic, such as furosemide, may be used to increase urinary calcium excretion

when can hemodialysis be used for severe hypercalcemia?

when rapid calcium removal is needed, particularly in patients with significant kidney dysfunction

what is the role of calcitonin in hypercalcemia?

provides a rapid but temporary decrease in calcium by decreasing bone resorption and by decreasing renal calcium reabsorption (bridge therapy)

why is calcitonin only used as bridge therapy?

because tachyphylaxis develops within about 24-72 hours

what is the role of bisphosphonates in hypercalcemia?

they inhibit osteoclast-mediated bone resorption and are first-line agents for malignancy-associated hypercalcemia

what important adverse effect should you associate with bisphosphonates?

osteonecrosis of the jaw; also use caution in kidney impairment

when is denosumab useful for hypercalcemia?

for malignancy-associated hypercalcemia refractory to bisphosphonates or in kidney impairment

how does denosumab work?

it inhibits RANKL, reducing osteoclast survival/activity and therefore decreasing bone resorption

what is the normal serum phosphate range?

3-4.5 mg/dL

where is most phosphate found in the body?

about 85% in bones and teeth

what are important physiological roles of phosphate?

-ATP/energy production

-cell membrane function

-hemoglobin physiology

-major intracellular anion

how does vitamin D affect serum phosphate?

increases phosphate by increasing GI phosphate absorption

how does PTH affect phosphate?

PTH has mixed effects but importantly causes increased renal phosphate excretion, which tends to lower serum phosphate

how does FGF23 affect phosphate?

decreases serum phosphate by increasing renal phosphate excretion, decreasing calcitriol leading to decreased GI absorption, and decreasing PTH/bone resorption effects

how is hypophosphatemia defined?

serum phosphate

what are important causes of hypophosphatemia?

-decreased GI absorption ---> starvation, alcoholism, vitamin D deficiency, phosphate binders

-increased renal losses ---> hyperparathyroidism

-cellular redistribution ---> refeeding syndrome

why does refeeding syndrome cause hypophosphatemia?

a malnourished patient has depleted phosphate stores; feeding, especially carbohydrates, increases cellular energy demands and drives phosphate into cells for ATP production

what is the severity classification of hypophosphatemia?

-mild: 2-2.5 mg/dL

-moderate: 1-2 mg/dL

-severe:

when do symptoms of hypophosphatemia usually become clinically significant?

typically, when phosphate is

why can severe hypophosphatemia cause major systemic symptoms?

because it causes decreased intracellular ATP and impaired RBC oxygen delivery

how is mild-to-moderate, asymptomatic hypophosphatemia treated?

oral phosphate replacement, typically 250-500 mg QID, with gradual correction over several days

how is severe or symptomatic hypophosphatemia treated?

with IV phosphate (0.2-0.5 mmol/kg IV over 3 hours)

how do you choose between potassium phosphate and sodium phosphate for IV replacement?

-K

-K >3.5 mEq/L ---> sodium phosphate

why should IV phosphate be used cautiously in patients with hypercalcemia?

calcium and phosphate can bind/precipitate together, potentially causing tissue or renal deposition

how is hyperphosphatemia defined?

serum phosphate >4.5 mg/dL

what is the most important cause of hyperphosphatemia?

reduced kidney function, especially CKD or AKI, because phosphate excretion decreases. other causes include tumor lysis syndrome, rhabdomyolysis, and excess phosphate administration

why can hyperphosphatemia be dangerous?

excess phosphate complexes with calcium, potentially causing crystal deposition in soft tissue, kidneys, and vasculature

how is hyperphosphatemia generally treated?

-restrict phosphate intake/administration

-use phosphate binders to decrease GI absorption

-hemodialysis for acute/refractory hyperphosphatemia in CKD

what are the major phosphate binders?

-calcium acetate

-aluminum hydroxide

-sevelamer

-lanthanum

-sucroferric oxyhydroxide

-ferric citrate

how do phosphate binders work?

they bind dietary phosphate in the GI tract, preventing absorption and allowing phosphate to be eliminated in the stool

what important adverse effect should you associate with calcium acetate?

hypercalcemia