Adult Fluid and Electrolyte Management - Hopkins

SEQ Calcium and Phosphate Homeostasis. Where does the negative feedback loop begin?

explain later

How do calcium and phosphate interact with the renal system?

Loop of Henle: calcium reabsorbed in ascending

PCT: calcium and phosphate reabsorbed

DCT: calcium (some phosphate) reabsorbed

What happens when dietary calcium is low?

1. decreased calcium

2. increased PTH secretion

3. increased osteoglast and osteoblast activity

4. calcium moves from bones to ECF

5. poor bone health

Why do we calculate corrected calcium? What is the equation?

calcium is highly albumin bound (45% ECF) → hypoalbuminemia may falsely lower measured calcium levels (higher availability of ionized calcium)

how to avoid this: order ionized calcium levels ($$), correct calcium in hypoalbuminemia

Correct Ca = [measured Ca] + 0.8 * (4g/dL - [measured albumin])

List the physiologically available calcium? (non-albumin bound 55% ECF)

1. cell membrane integrity

2. neuromuscular activity and smooth muscle contraction

3. endocrine and exocrine secretions

4. coagulation cascade and platelet adhesion

5. bone metabolism

What are the causes of hypocalcemia? what is considered hypocalcemia?

<8.5 mg/dL

1. poor intake/nutritional deficiency

2. organ dysfunction

   1. GI disease — poor absorbtion

   2. chronic kidney disease

3. Acute disease

   1. pancreatitis — Ca2+ precipitates

   2. tumor lysis syndrome — release of IC phosphate binds to Ca

4. Electrolyte abnormalities

   1. hyperphosphatemia

   2. hypomagnesemia

5. Iatrogenic causes

Describe the Iatrogenic causes of hypocalcemia

1. calcimimetics — calcitonin, cinacalcet

2. renal tubular dysfunction — loop diuretics, aminoglycosides, ampohotericin B, PPI’s, cyclosporin, cisplatin

3. decrease in vita D production — phenytoin, phenobarbital

4. direct binding — phosphate prducts, large volume blood transfusions (citrate)

List the acute manifestations of hypocalcemia

1. muscle cramps

2. tetany — Ca <7.0 mg/dL (ionized <4.3)

3. peri-oral paresthesia

4. Chvostek’s sign

5. Trousseau’s sign

6. QT prolongation (life threatening)

List the chronic manifestations of hypocalcemia

1. depression

2. anxiety

3. hallucinations

4. brittle nails

5. hair loss

6. skeletal abnormalities (fast bone turnover)

When should Calcium Chloride 10% be used over Calcium gluconat 10%?

During an emergency, code blue

if only peripheral access is available, calcium gluconate is preferred

What can happen if IV administration is too fast? What should you avoid doing when preparing IV therapy?

profound hypotension and ventricular fibrillation

avoid mixing into solns containing bicarbonate and phosphate

What is the elemental calcium in calcium chloride 10% vs calcium gluconate 10%?

Chloride: 27% (270mg/1g)

Gluconate: 9% (90mg/1g)

Which PO calcium products must be administered with food?

Calcium carbonate and caclium acetate. Calcium citrate can be with or without food

Give the treatment plan for a patient that is asymptomatic and assocatied with low albumin

no treatment necessary

Give the treatment plan for a patient that is asymptomatic or requires maintenance supplementation

1-3 grams oral elemental calcium per day in divided doses and give with meals

Give the treatment plan for a patient that is acute and symptomatic for hypocalcemia

1. 90-270mg IV elemental calcium per dose; can repeat after 1 hour as needed

2. continuous IV infusion of elemental calcium 50-100mg/hour

reminder to check sample prescriptions on slides

reminder

What are the ADE of calcium supplmentation?

1. constipation, gas

2. hypercalcemia due to overcorrection

3. hypercalciuria → risk of nephrolithiasis (kidney stones)

what are possible interactions with calcium supplementation? what is the soln?

1. oral iron products: decreased absorption of oral iron

2. fluoroquinolones: chelation with antibiotics → reduced antibacterial activity

3. tetracyclines: chelation with antibiotic 0> reduced antibacterial activity

solution: separate doses by 2 hours

what are the causes of hypercalcemia? (>10.5mg/dL)

1. Increased bone resorption

   1. malignancy — release protein that acts like PTH

   2. paget’s disease — impair cell remodeling

   3. hyperthyroidism — increased osteoclast

2. Increased GI absorption

   1. granulatomous diseases — produce enzymes convert vita D → active form w/o regard for feedback loop

3. impaired albumin binding: metabolic acidosis

4. impaired renal excretion

   1. adrenal insufficiency

   2. thiazide diuretics — blocks NaCl transporter in DCT

   3. lithium — increase absorption in loop of henle

Describe the manifestation of mild to moderate hypercalcemia

10.5-13mg/dL

asymptomatic

Describe the manifestations of severe, acute hypercalcemia

>13mg/dL

1. anorexia

2. n+v

3. constipation

4. polyuria

5. polydipsia

6. nocturia

Describe the manifestations of severe, acute crises hypercalcemia

>15mg/dL

1. acute renal failure

2. obtundation

3. cardiac arrythmias

Describe the manifestations of chronic hypercalcemia

1. nephrolithiasis

2. chronic renal failure

3. Ca-Phos product deposition in the blood vessels and organs

What is the first line treatment of hypercalcemia? what are things to be careful of?

IV Fluids: NS 200-300mL/hr

1. DO NOT USE in pts with renal impairment/HF → may have fluid overload or poor calcium excretion

2. take 1-2 days to see effect

3. give loop diuretics to minimize fluid overload and promote calcium excretion in kidneys

why is NS more appropriate than LR in hypercalcemia?

LR has calcium

What is the MOA of Calcitonin (Miacalcin)? Dosing? Onset? ADE?

MOA: inhibits bone resorption and prevents reabsorption of Ca in kidneys

Initial dosing: 4 units/kg/ q12h SUBQ (or IM if volume is >2mL)

Max dose: 8 units/kg q6h

Onset: 2hrs

ADE: hypersensitivity, flushing, n+v

How long should therapy with calcitonin continue for?

no more than 48hrs due to tachyphylaxis

if still hypercalcemic after therapy, move on to bisphosphonates

What is the MOA of bisphosphonates? Onset? Peak effect?

MOA: inhibit bone resorption via inhibition of osteoclast activity and maturation

Onset: 2 days

Peak effect at 7 days

What are the ADE of IV bisphosphonates?

1. fever

2. hypocalcemia

3. renal failure

4. musculoskeletal pain

5. osteonecrosis of jaw

6. atypical femur fracture

What is the brand name of Pamidronate? What is the fusion time?

Aredia

2-24 hours

What is the brand name of ibandronate? What is the fusion time?

boniva

1-2 hours

What is the brand name of zoledronate? What is the fusion time?

zometa

15 minutes

When should you use IV Bisphosphonates? when should you avoid it?

If IV fluids and Calcitonin do not fix hypercalcemia

avoid in pts with severe renal impairment

When should you use Denosumab (Xgeva)? MOA, initial dosing, onset?

To be used after adequate bisphosoate trial (after 7 days)

MOA: RANKL inhibitor — inhib osteoclast formation → decrease bone resorption

Dose: 120mg SUBQ once a week for 3 weeks, then q 4 weeks

What are the ADE of Denosumab?

1. hypocalcemia

2. osteonecrosis of jaw

3. atypical femur fracture

Describe osteonecrosis of the jaw. what can help?

progressive bone destruction of maxillofacial region

oral hygiene and antibiotics may help, but some patients will require surgical management

what are the nonpharmacologic treatments of hypercalcemia?

1. hemodialysis using low calcium dialysate: most appropriate in late/end stage renal disease

2. surgery: for malignancy or refractory hyperparathyroidism

What are the intracellular activity of organic phosphate? (ICF 14%)

1. mitochondrial activity

2. metabolis m fo CHO, fats, proteins

3. ATP formation

4. release O2 form RBCs to tissue

5. structure of cell membranes and nucleic acids

What are the causes of hypophosphatemia?

<2.5mg/dL

1. Decreased GI absorption due to phosphate binding meds

   1. sucralfate, Ca Mg Al containing products, sevelamer, lanthanum

2. Reduced renal tubular reabsorption

   1. hyperparathyroidism, vita D def, acetazolamide, sodium bicarb, severe burns

3. IC shifting of EC phosphate

   1. refeeding syndrome

   2. insulin

   3. dextrose solns

What are the manifestations of mild to moderate hypophosphatemia?

1-2.4mgdL

asymptomatic

What are the manifestations of severe hypophosphatemia?

<1mg/dL

1. parsethesia, confusion, seizures, coma

2. weakness, myalgia, resp failure

3. hemolysis

4. impaired myocardial contactions

What products should be

left off on slide 32