Table of contents
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Calcium Principles
- Normal: 2.2-2.6 mmol/L
- Ionic Ca2+: 1.1 - 1.3
- Serum Ca2+ 50% bound to protein
- Regulated by Vitamin D and PTH
- Mg2+ is a cofactor for PTH secretion. (i.e. see hypocalcemia, not corrected by dietary Ca2+.. probably has ↓ Mg2+ and is unable to secrete PTH
- NOTE:
- PTH causes ↑Ca2+, ↓ PO4
- Vitamin D3 (Calcitriol) causes ↑ Ca2+ and ↑ PO4
Hypocalcemia
- Total corrected calcium <2.2mmol/L
- Symptoms:
- HYPERPOLARIZATION
- Acute:
- MSK: tetany! parasthesia, laryngospasm,
- Neuro: Tetany, parasthesia, laryngospasm, hyperreflexia
- On Exam: Chvostek/Trousseau sign (very poor Sensitivity 25 and 30% respectively)
- CVS: ECG changes,
- Psych: delirium + Psych (emotional instability, anxiety, depression)
- Chronic:
- CNS: Lethargy, psychosis, basal ganglia calcification, Parkinson's, dystonia.
- CVS: prolonged QT interval --> Torsades de pointes (V tach)
- GI: steatorrhea
- Endo: Impaired insulin release
- SKIN: dry, scaling, alopecia, candidiasis.
- Ocular: cataracts
- MSK: generalized muscle weakness/wasting.
- APPROACH
- Is the patient hypocalcemic (correct for albumin)?
- PTH high or low?
- If PTH high, is phosphate low or normal?
- Is the Mg2+ level low? Hypomagnesemia can impair PTH secretion and action.
- Other Causes:
- Sepsis (unclear cause)
- Magnesium Depletion (unable to secrete parathyroid hormone)
- Alkalosis (reduces ionized fraction)
- Blood transfusions (citrate chelates Ca++ in banked blood, short lived, resolves when citrate metabolized)
- Drugs (heparin, theophylline, cimetidine, aminoglycosides)
- Pancreatitis
- Treatment:
- Correct underlying disorder
- Mild/asymptomatic (Ca2+ ionized <0.8 mmol/L)
- Increase dietary Ca by 1000 mg/d
- Calcitriol 0.25 mcg/d
- Symptomatic hypocalcemia (esp if ionized Ca2+ is <0.7mmol/L) --> need IV
- Two IV solutions:
- 10% Calcium Gluconate [100mg/mL]
- 10% Calcium Chloride [100mg/mL] (contains 3x elemental Ca++ than gluconate)
- Can order as IV calcium gluconate 1-2g over 10-20min followed by slow infusion if needed. (i.e. 0.5-2 mg/kg/hr of elemental calcium for ≥ 6hrs.
- Raise calcium to low normal >2.0-2.1mmol?L to prevent symptoms but keep PTH stimulation.
- Two IV solutions:
- Do not correct if asymptomatic and suspected to be transient
Hypercalcemia
- Symptoms
-
- Classically:
- DEHYDRATION! (polyuria, renal failure)
- Also:
- Bones (bone pain), weakness.
- Stones (Nephrolithiasis), Polyuria, Polydipsia-->Renal Failure/ Oliguria irrev.
- Groans (vomiting, abdo pain, PUD)
- Psychiatric overtones
- CV: HTN, Arrhythmia, Short QT, Calcification of Arteries
- With very high calcium can cause ST changes (do Ca++ in pts with ST changes)
-
Hypercalcemic crisis (>4mmol/L):
- Oliguria/anuria
- Mental status change (somnolence, coma)
- EMERGENCY!!
- Classically:
- Physiology
- High calcium in the nephron interferes with re-absorption, causes Calcium diuresis, leading to dehydration and renal failure.
- Hydration is the #1 therapy ---> Normal saline allows kidney re-perfusion, delivers sodium to the distal nephron, causing sodium diuresis and calcium follows.
- Causes:
- 90% - Hyperparathyroidism or malignancy
- Can be local (osteolysis of local bone) or:
- Humoral creating factor to activate bone resorption (i.e. PTHrP)
- 10% - Others (thyrotoxicosis, immobilization, drugs (lithium, thiazides)
- 90% - Hyperparathyroidism or malignancy
- Workup
- Urine Ca (if low, then familial hypocalciuric hypocalcemia)
- Electrolytes (Ca, Mg, PO4)
- Albumin (correction 0.2:10 Calcium increase to 10 decrease)
- CXR (Granuloma/malignancy)
- PTHrP
- Malignancies producing PTHrP: squamous cell carcinoma; lung, head, and neck cancer; lymphoma
- Treatment:
- 1. IV NS!!! (most important!)
- Calciuria usually causes dehydration = decreased Ca++ excretion. Giving volume helps excretion.
- 2. Loop Diuretics (not thiazides!)
- Usually lasix 40-80mg IV q2h titrate to achieve hourly urine output of 100-200 mL/hr
- Replace hourly urine output with Isotonic Saline
- 3. Calcitonin
- 4. Bisphosphonates
- 5. Steroids (if Hypervitaminosis D secondary to malignancy [granulomatous disease etc..])
- 6. Dialysis (Last resort!)
- 1. IV NS!!! (most important!)
-
Increase Urinary Ca2+ excretion Isonotic saline (4-5L) over 24hrs +/- loop diuretic (furosemide) but only if hypervolemic
Calcitonin (2013: NOT USED DUE TO CANCER RISK)
- 4 IU/kg IM/SC q12h
- Only works for 48h, rapid onset within 4-6h
Hydrocortisone (adjunct to calcitonin)
Diminish Bone Resorption Bisphosphonates
- Acts rapidly, but transient (0.3-0.5mmol/L reduction)
- Esp for malignancy-induced (peak effect 2-4d, normalize Ca in 4-7d)
- IV pamidronate 90mg IV over 2 hours
(reduce dose to 60mg for renal impairment) - IV Zoledronate 4mg IV over 15min
(equivalent to pamidronate in efficacy) - Plicamycin 25 mcg/kg IV over 4hrs repeat q2h - HISTORIC
(more rapid than pamidronate, toxic BM suppression)
- antineoplastic agent that inhibits bone resorption)
Mithramycin (rarely used)
- Hematotoxic and hepatotoxic
Decrease GI Ca2+ Absorption Corticosteroids in hypervitaminosis D and hematologic malignancies
Slow onset: (5-10d), need high doses
- i.e. Hydrocortisone 200mg IV daily in 2-3 divided doses
Dialysis LAST RESORT
- Indication:
- severe malignancy-assd hypercalcemia
- renal insufficiency
- heart failure
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