Hypercalcaemia

OVERVIEW

  • highly regulated cation
  • involved in: cell death, duration and strength of cardiac muscle contraction, muscle contraction in blood vessels, airways and uterus, coagulation, bone metabolism, neurotransmitter and hormone release…
  • Ca2+ exists in the extracellular plasma two states:
    1. free ionized state and
    2. bound to other molecules (mostly albumin, rest – beta-globulins, phosphate, citrate)
  • ionized Ca2+ concentration is inversely related to pH -> an increase in pH results in a decrease in ionized Ca2+

Calcium levels

  • total Ca2+ range = 2.2-2.5mmol/L (55% bound, 45% ionized)
  • ionized Calcium range (50%) = 1.1-1.3mmol/L
  • protein bound Ca2+ range (40%) = 0.95-1.2mmol/L
  • complex Ca2+ (10% – calcium phosphate, salts) = 0.05mmol/L

CALCIUM METABOLISM

Vitamin D

  • group of related sterols
  • cholecalciferol is formed in the skin -> in liver to 25-hyrdroxcholecalciferol -> in kidney proximal tubules to 1,25-dihydroxycholecalciferol -> this then helps calcium absorption in the intestine.
  • controlled by parathyroid hormone

-> increases intestinal absorption of Ca2+
-> increases renal Ca2+ reabsorption
-> mobilises bone Ca2+ and PO43

Parathyroid hormone

  • secretion increased by hypocalaemia & hypomagnesaemia
  • secretion decreased by hypercalcaemia & hypermagnesaemia

-> mobilses Ca2+ from bone
-> increases renal Ca2+ reabsorption
-> increases renal PO43 excretion
-> increases formation of 1, 25-dihyroxycholecalciferol.

Calcitonin

  • antagonist of parathyroid hormone
  • secreted by the parafollicular cells of the thyroid gland in response to:
    – hypercalcaemia
    – catecholamines
    – gastrin

-> inhibits the mobilisation of bone Ca2+
-> increases renal Ca2+ and PO43- excretion

SUMMARY OF CAUSES

  • intake: Ca2+, vitamin A or D, hypoMg2+, hypovolaemia, TPN
  • redistribution: immobilization, malignancy, hyperparathyroidism, sarcoid, lithium, adrenal insufficiency, endocrine causes (thyrotoxicosis, acromegaly, phaeo)
  • output: urinary – thiazides

CAUSES BASED ON FREQUENCY

Common

  • malignancy (bone mets, humoral hypercalaemia) -> inappropriate release of PTH-related peptide from tumour cells, associated with lung, breast, prostate, colon and T-cell malignancies and MM
  • post-hypocalaemic hypercalcaemia (recovery from pancreatitis, ARF, rhabdomyolysis)
  • primary hyperparathyroidism (adenoma)
  • adrenal insufficiency
  • prolonged immobilisation
  • disorders of Mg2+ metabolism
  • TPN
  • hypovolaemia
  • iatrogenic Ca2+ administration

Less Common

  • granulomatous disease – sarcoidosis, Tb, beryliosis, leprosy, histoplasmosis -> increase in 1,25(OH)2D production from macrophages in granuloma
  • vit A and D intoxification
  • endocrine causes: thyrotoxicosis, acromegaly, phaeochromocytoma
  • chronic lithium therapy
  • secondary hyperparathyroidism (renal failure -> decreased renal conversion of 25-hydroxyvitamin D -> 1,25(OH)2D -> decreased Ca2+ absorption -> increased PTH secretion)
  • tertiary hyperparathyroidism (over-activity from prolonged hyperstimulation -> require a parathyroidectomy)

HISTORY

  • goal = to quantify severity of hypercalcaemia and find cause (malignancy, diet, immobilisation, medications)
  • all symptoms exacerbated by presence of renal failure
  • “stones, bones, groans and psychic moans”
  • GI – symptoms of smooth relaxation = constipation, anorexia, nausea, vomiting
  • NEURO – lethargy, hypotonia, confused, coma
  • RENAL – polyuria, dehydration, stones, dehydration
  • CVS – arrhythmias

EXAMINATION

  • dehydration
  • level of consciousness
  • exam to find cause (ie. malignancy)

INVESTIGATIONS

(1) to confirm malignancy or bony involvement (x-ray, CT, bone scan)
(2) to assess bone turnover (ALP)
(3) to assess PTH

  • U+E – renal failure
  • Mg2+ and K+
  • Ca2+ and phosphate
  • to adjust Ca2+ for albumin: add 0.1mmol/L to Ca2+ for each 5g/L that albumin below 40g/L
  • ECG: shortened QTc, Osborn or J wave
  • lipase (can cause pancreatitis)

MANAGEMENT

  • quantify severity

Increase Ca2+ Excretion

  • N/S IVF @ 200-300mL/hr to promote renal elimination of Ca2+
  • loop diuretics – decrease resorption of Ca2+ in the Loop of Henle
  • steroids (hydrocortisone 100mg QID): inhibits the effects of Vit D, decrease intestinal absorption of Ca2+, increase renal elimination of Ca2+, inhibit osteoclast-activating factor -> useful in granulomatous disease but not in malignancy

Reduce Ca2+ Release

  • calcitonin – lowers Ca2+ within 24-48 hours
  • bisphosphonates (pamidronate 90mg IV) – potent inhibitors of osteoclast activity
  • plicamycin and gallium
  • inorganic phosphate -> risks Ca2+ precipitation

Others

  • stop drugs that might increase Ca2+ (thiazides, vitamin A and D, Ca2+)
  • restrict intake
  • correct K+ and Mg2+
  • mobilize to reduce calcium release from bone
  • stop digoxin (hypercalcaemia and digoxin traditionally thought to cause arrhythmia)
  • surgery -> parathyroidectomy

VIDEO

Hypercalcaemia by CritIQ:


References and Links


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.