7 - HYPERcalcemia Flashcards
Normal Serum Calcium
8.5 - 10.5
mg/dL
Half calcium is protein bound
15% bound to anions
40% bound to albumin
Normal Ionized Serum Calcium
4.4-5.5
mg/dL
~1/2 of total serum Ca
does NOT vary with ALBUMIN
Free Ca+
Corrected Calcium Claculation
Corrected Ca+ =
( Total Measured Ca+ ) + 0.8 (4 - Measured Serum Albumin )
Normal Serum Albumin = 4 mg/dL
This can OVERestimate Ca+,
- *Ionized Ca+** should be obtained if patient is
- *critically ill** or if total is low <7.5mg/dL
Relationship between
Calcium & PTH
Calcium has a NEGATIVE feedback on PTH
via Calcium sensing Receptor
*LOW CALCIUM* –> PTH SERGE ^^
Bones
Stim Osteoclast –> bone REsorption
inhibits osteoBlasts & bone formation
Kidneys
INCREASE reabsorption of calcium, less calcium clearance
Stimulates hydroxlase –> INCREASE Vitamin D production
Gut
indirectly increases calcium absorption via stim of VITAMIN D production
Relationship Between
Calcium & Calcitonin
High Calcium** –> **High CALCITONIN
Hormone that INHIBITS osteoclastic bone resorption (breakdown)
Mechanism to return calcium levels to NORMAL, when too HIGH
Relationship between
Calcium & VITAMIN D
High phos / Low Ionized Ca+ leads to:
Active Vitamin D (Calcitriol)
VVVV
INHIBITS PTH Release
VV
INCREASE SERUM CALCIUM by:
Stimulating Calcium RELEASE from bones
Enhance Ca+ absorption in GI tract
HYPERcalcemia
Value?
Total Serum Calcium
> 10.5 mg/dL
Ionized Calcium
> 5.4 mg/dL
Etiology of HYPERcalcemia
Calcium in Circulation > Excretion of Ca+ (Urine / Bone desposition)
Caused by:
Accelerated Bone Resorption
Excessive GI absorption
Decreased Renal Excretion of Calcium
PRIMARY or SECONDARY HYPERthyroidism // MALIGNANCY
= 90% of HYPERcalcimia Cases
Drug Induced
Endocrine Disorders
Addison’s / Acromegaly / Throtoxicosis
Granulomatous Disorders
Sarcoidosis / Tuberculosis
Primary HYPERparathyroidism
MAJOR Cause of HYPERcalcemia
Caused by:
Parathyroid ADENOMA
innapropriate increase in PTH Secretion –> HIGH Ca+
High Normal Values <11mg/dL
w/ intermittent HYPERcalcemia
Secondary HYPERparathyroidism
MAJOR Cause of HYPERcalcemia
Associated with:
HYPERplasia of GLANDS
Observed in patients with CKD
Adaptive disease in the Setting of CKD:
Inability to activate VITAMIN D + Increased PHOS
Tertiary HYPERparathyroidism
Advanced RENAL failure –> Parathyroid Hyperplasia
May resolve after kidney transplant
Parathyroidectamy might be needed to help PTH levels
HIGH PTH EFFECTS
HYPEParathyroidism
KIDNEY
INCREASE renal absorption of CALCIUM
INCREASE renal EXCRETION of PHOS
Stimulate synthesis of calcitriol
INTESTINE
indirectly INCREASES absorption of Ca/P in Small Intestine
BONE
Stimulates osteoclast to RESORB bone –> ↑Ca+
inhibits osteoblast & bone absorption
Malignancy
effects on Calcium
Also accounts for ~90% of HYPERcalcemia
Calcium Levels > 13mg/dL
Solid Tumors + Leukemia
VVVV
INCREASED
Bone RESORPTION&GI ABSORPTION
high Ca
Drug Induced HYPERcalcemia
DISCONTINUE OFFENDING AGENTS
THIAZIDE DIURETICS
most common –> increase renal tubular reabsorption of CA
block NA rabsorption –> INCREASE Ca reabsorption
- *Lithium**
- *Resets PTH** hormone –> increased PTH
Vitamin A
INCREASE bone resorption (stim osteoclasts)
Moderate + Chronic HYPERcalcemia
Levels / Symptoms
12-14
GI:
Anorexia / N+V / Constipation
Renal:
PolyUria / PolyDipsia
MUSCLE WEAKNESS
Severe / Life-Threatening (ACUTE)
HYPERcalcemia
Levels / Symptoms
>14** or **RAPID INCREASE IN Ca
Any level can be considered ACUTE, as long as there is:
Rapid/Substantial Rise in Ca and S/Sx present
the ACUITY of the RISE in Calcium –> determines therapy
Profound DEHYDRATION
Renal Failure / CV+Neuromuscular Dysfunction / COMA
Signs / Symptoms of
CHRONIC HYPERcalcemia
Long Standing HYPERcalcemia:
HYPERparathyroidism / Sarcoidosis / CKD
Calcium Desposition in BV & organs
deposits in artherosclerotic lesions –> heart disease
deposit in skin –> calciphylaxis
deposit in kidney –> nephrocalcinosis (permanent kidney dmg)
HYPERCalcemia TREATMENT
CHART
Treatment for MILD+Asymptomatic
HYPERcalcemia
<12 mg/dL
Reduce dietary Calcium
<400 mg/day
by avoiding food/diet high in calcium
AVOID:
Thiazides / Lithium / Vitamin D
Stay well hydrated
Avoid IMMOBILIZATION –> precipitation
- *Moderate +**
- *HYPERcalcemia Treatment**
12-14 mg/dL
ASYMPTOMATIC –> treat like MILD
ACUTE RISE IN CA –> TREAT as SEVERE
Treatment for SEVERE
HYPERCalcemia
- *>15 mg/dL**
- *Symptomatic // ACUTE RISE**
PARENTERAL THERAPY
NS 0.9% + Loop Diuretic
Volume Expansion // Increase Ca+ EXCRETIOn
Calcitonin
used in SYMPTOMATIC patients –> rapidly DECREASES serum Ca+
Bisphosphonates
provides a sustained effect in lowering calcium
- *Dialysis**
- *last resort**, make sure there is NO CA in dialysis fluid
SALINE
Dose / MoA / ADR
Severe HYPERcalcemia Treatment
given with LOOP DIURETICS to help increase Ca excretion
Normal Saline 0.9%
corrects volume depletion –> euvolemia
200-300 ml/hr
adjusted to maintain UOP = 100-150 ml/hr
ADR:
Fluid Overload / Edema / Electrolyte abnormalities
Considerations:
Severity / age / comordities / no diuretics with renal/heart failure
CALCITONIN
Severe HYPERcalcemia Treatment
Works VERY RAPIDLY –> deceease serum calcium
Used for:
Acute + SYMPTOMATIC patients
Hormone from Thyroid
INHIBITS Osteoclatic Bone Resorption
(bone breakdown)
Plasma concentrations are
INCREASED when ionized Ca is HIGH
CALCITONIN
Dose / MoA / ADR
Severe HYPERcalcemia Treatment
SYMPTOMATIC PATIENTS
- Antagonizes PTH* // Decrease Bone Resorption
- *Increase calcium EXCRETION**
4 IU/k_g** **IM/SC**
works very RAPIDLY ↓**Ca 1-2 mg/dl within 4-6 hours**
–> DOSE AGGRESIVELY
**If Responsive –> REPEAT q6-12 hours** **@4-8IU/kg_
ADR:
Nausea / HYPERsensitivity / Tachyphylaxis
BISPHOSPHONATES
Severe HYPERcalcemia Treatment
Adsorb to surface of bone hydroxyapatitie
INHIBIT calcium release –> inhibit osteoclasts resorption
Most effective in HYPERcalcemia from:
Excessive Bone Resorption (vs other etiology)
MORE POTENT than Calcitonin + Saline
LAST LONG = 2-4 WEEK duration
Drug specific Dosing:
Zolendronic Acid / Pamidronate / Ibandronate
BISPHOSPHONATES
Dose / MoA
Severe HYPERcalcemia Treatment
Inhibit Calcium Release = inhibits osteoclasts
- *SLOW Infusion Rate** for patinets with Renal Dysfunction
- *2-4 Week duration**
- *ZOLENDRONIC ACID**
- *4mg IV** over 15 minutes
- *MOST POTENT** = PREFERRED, renal toxicity with 8mg dose
Pamidronate
60-90mg IV over 2 hours, fever
Ibandronate
2mg IV over 2 hours, dyspepsis / backpain
BISPHOSPHONATES
ADRs
Severe HYPERcalcemia Treatment
Osteonecrosis of JAW
w/ repetitive use
Acute Phase Reactions
bone pain / fever / flu like symptoms
AVOID if CrCl <30 ml/min // ESRD = renal dosage
Preventing HYPERcalcemia Recurrance in
MALIGNANCY
lower tumor burden
Metastatic BONE Disease:
Administer
- *PAMIDRONATE / ZOLENDRONIC ACID**
- *q 3-4 weeks**
Denosumab
for refractory HYPERcalcemia
no restriction in CKD patients, effect seen in 2-4 days
60 g SC w/ repeat dosing based on response
Role of GLUCOCORTICOIDS
in HYPERcalcemia
Used in:
Chronic Granulomatous Diseases = Sarcoidosis
Decreased Intestinal Calcium Absorption
Decreased Calcitriol Production
by activated mononuclear cells in lungs / lumph nodes
PREDNISONE 20-40 mg/day
effect in 2-5 days, can last days - weeks
HYPERcalcemia in HYPERparathyroidism
Usually CHRONIC + Asymptomatic
Long standing consequences:
Osteoporosis / Calcifications in organ systems
Use CALCIMEMETICS:
Sensipar = Cinacalcet
Parsabiv = Etelcalcetide
SENSIPAR
For Hypercalcemia in Hyperparathyroidism
Cinacalcet
Decrease PTH
by increasing sensitivity of calcium receptor on PT gland
30 - 60 - 90 mg QD WF
ADR:
decrease in SERUM Ca+ // NVD
ensure corrected Ca > 7.5mg/dL before dose titration
titration is q3-6 weeks
strong inhibitor of CYP2D6
PARSABIV
For Hypercalcemia in Hyperparathyroidism
Etelcalcetide
Binds to Calcium Sensing Receptor
on PT gland & enhances activation by serum calcium
5 mg IV bolus
3 x Week @ end of hemodialysis
Dose Adjustment:
Titrate dose in 2.5 or 5mg increments no more than < q4 weeks
Conversion from Cinacalcet/Sensipar:
D/C Sensipar for >7 days prior to initiating
ADR = Serum Calcium / adj dose if Ca <7.5mg/dL
DO NOT GIVE if HEMODIALYSIS session is MISSED
If miss >2 weeks of doses –> restart @ 5mg IV 3 x week
Calcitriol Induced HYPERcalcemia
TREATMENT of HYPERvitaminosis D
TRIOL = TRYING = ACTIVE VITAMIN D
Lasts 1-2 days due to short half life
D/C Calcitriol
INCREASE FLUID INTAKE / IV HYDRATION
w/ SALINE
Calcidiol Induced HYPERcalcemia
TREATMENT of HYPERvitaminosis D
-Diol - Lasts LONGER
AGGRESIVE THERAPY
Glucocorticoids
IV Bisphosphonates if symptomatic
