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2025 PACUPrep BCCCP Preparatory Course

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  1. Pulmonary

    ARDS
    4 Topics
    |
    1 Quiz
  2. Asthma Exacerbation
    4 Topics
    |
    1 Quiz
  3. COPD Exacerbation
    4 Topics
    |
    1 Quiz
  4. Cystic Fibrosis
    6 Topics
    |
    1 Quiz
  5. Drug-Induced Pulmonary Diseases
    3 Topics
    |
    1 Quiz
  6. Mechanical Ventilation Pharmacotherapy
    5 Topics
    |
    1 Quiz
  7. Pleural Disorders
    5 Topics
    |
    1 Quiz
  8. Pulmonary Hypertension (Acute and Chronic severe pulmonary hypertension)
    5 Topics
    |
    1 Quiz
  9. Cardiology
    Acute Coronary Syndromes
    6 Topics
    |
    1 Quiz
  10. Atrial Fibrillation and Flutter
    6 Topics
    |
    1 Quiz
  11. Cardiogenic Shock
    4 Topics
    |
    1 Quiz
  12. Heart Failure
    7 Topics
    |
    1 Quiz
  13. Hypertensive Crises
    5 Topics
    |
    1 Quiz
  14. Ventricular Arrhythmias and Sudden Cardiac Death Prevention
    5 Topics
    |
    1 Quiz
  15. NEPHROLOGY
    Acute Kidney Injury (AKI)
    5 Topics
    |
    1 Quiz
  16. Contrast‐Induced Nephropathy
    5 Topics
    |
    1 Quiz
  17. Drug‐Induced Kidney Diseases
    5 Topics
    |
    1 Quiz
  18. Rhabdomyolysis
    5 Topics
    |
    1 Quiz
  19. Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
    5 Topics
    |
    1 Quiz
  20. Renal Replacement Therapies (RRT)
    5 Topics
    |
    1 Quiz
  21. Neurology
    Status Epilepticus
    5 Topics
    |
    1 Quiz
  22. Acute Ischemic Stroke
    5 Topics
    |
    1 Quiz
  23. Subarachnoid Hemorrhage
    5 Topics
    |
    1 Quiz
  24. Spontaneous Intracerebral Hemorrhage
    5 Topics
    |
    1 Quiz
  25. Neuromonitoring Techniques
    5 Topics
    |
    1 Quiz
  26. Gastroenterology
    Acute Upper Gastrointestinal Bleeding
    5 Topics
    |
    1 Quiz
  27. Acute Lower Gastrointestinal Bleeding
    5 Topics
    |
    1 Quiz
  28. Acute Pancreatitis
    5 Topics
    |
    1 Quiz
  29. Enterocutaneous and Enteroatmospheric Fistulas
    5 Topics
    |
    1 Quiz
  30. Ileus and Acute Intestinal Pseudo-obstruction
    5 Topics
    |
    1 Quiz
  31. Abdominal Compartment Syndrome
    5 Topics
    |
    1 Quiz
  32. Hepatology
    Acute Liver Failure
    5 Topics
    |
    1 Quiz
  33. Portal Hypertension & Variceal Hemorrhage
    5 Topics
    |
    1 Quiz
  34. Hepatic Encephalopathy
    5 Topics
    |
    1 Quiz
  35. Ascites & Spontaneous Bacterial Peritonitis
    5 Topics
    |
    1 Quiz
  36. Hepatorenal Syndrome
    5 Topics
    |
    1 Quiz
  37. Drug-Induced Liver Injury
    5 Topics
    |
    1 Quiz
  38. Dermatology
    Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
    5 Topics
    |
    1 Quiz
  39. Erythema multiforme
    5 Topics
    |
    1 Quiz
  40. Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS)
    5 Topics
    |
    1 Quiz
  41. Immunology
    Transplant Immunology & Acute Rejection
    5 Topics
    |
    1 Quiz
  42. Solid Organ & Hematopoietic Transplant Pharmacotherapy
    5 Topics
    |
    1 Quiz
  43. Graft-Versus-Host Disease (GVHD)
    5 Topics
    |
    1 Quiz
  44. Hypersensitivity Reactions & Desensitization
    5 Topics
    |
    1 Quiz
  45. Biologic Immunotherapies & Cytokine Release Syndrome
    5 Topics
    |
    1 Quiz
  46. Endocrinology
    Relative Adrenal Insufficiency and Stress-Dose Steroid Therapy
    5 Topics
    |
    1 Quiz
  47. Hyperglycemic Crisis (DKA & HHS)
    5 Topics
    |
    1 Quiz
  48. Glycemic Control in the ICU
    5 Topics
    |
    1 Quiz
  49. Thyroid Emergencies: Thyroid Storm & Myxedema Coma
    5 Topics
    |
    1 Quiz
  50. Hematology
    Acute Venous Thromboembolism
    5 Topics
    |
    1 Quiz
  51. Drug-Induced Thrombocytopenia
    5 Topics
    |
    1 Quiz
  52. Anemia of Critical Illness
    5 Topics
    |
    1 Quiz
  53. Drug-Induced Hematologic Disorders
    5 Topics
    |
    1 Quiz
  54. Sickle Cell Crisis in the ICU
    5 Topics
    |
    1 Quiz
  55. Methemoglobinemia & Dyshemoglobinemias
    5 Topics
    |
    1 Quiz
  56. Toxicology
    Toxidrome Recognition and Initial Management
    5 Topics
    |
    1 Quiz
  57. Management of Acute Overdoses – Non-Cardiovascular Agents
    5 Topics
    |
    1 Quiz
  58. Management of Acute Overdoses – Cardiovascular Agents
    5 Topics
    |
    1 Quiz
  59. Toxic Alcohols and Small-Molecule Poisons
    5 Topics
    |
    1 Quiz
  60. Antidotes and Gastrointestinal Decontamination
    5 Topics
    |
    1 Quiz
  61. Extracorporeal Removal Techniques
    5 Topics
    |
    1 Quiz
  62. Withdrawal Syndromes in the ICU
    5 Topics
    |
    1 Quiz
  63. Infectious Diseases
    Sepsis and Septic Shock
    5 Topics
    |
    1 Quiz
  64. Pneumonia (CAP, HAP, VAP)
    5 Topics
    |
    1 Quiz
  65. Endocarditis
    5 Topics
    |
    1 Quiz
  66. CNS Infections
    5 Topics
    |
    1 Quiz
  67. Complicated Intra-abdominal Infections
    5 Topics
    |
    1 Quiz
  68. Antibiotic Stewardship & PK/PD
    5 Topics
    |
    1 Quiz
  69. Clostridioides difficile Infection
    5 Topics
    |
    1 Quiz
  70. Febrile Neutropenia & Immunocompromised Hosts
    5 Topics
    |
    1 Quiz
  71. Skin & Soft-Tissue Infections / Acute Osteomyelitis
    5 Topics
    |
    1 Quiz
  72. Urinary Tract and Catheter-related Infections
    5 Topics
    |
    1 Quiz
  73. Pandemic & Emerging Viral Infections
    5 Topics
    |
    1 Quiz
  74. Supportive Care (Pain, Agitation, Delirium, Immobility, Sleep)
    Pain Assessment and Analgesic Management
    5 Topics
    |
    1 Quiz
  75. Sedation and Agitation Management
    5 Topics
    |
    1 Quiz
  76. Delirium Prevention and Treatment
    5 Topics
    |
    1 Quiz
  77. Sleep Disturbance Management
    5 Topics
    |
    1 Quiz
  78. Immobility and Early Mobilization
    5 Topics
    |
    1 Quiz
  79. Oncologic Emergencies
    5 Topics
    |
    1 Quiz
  80. End-of-Life Care & Palliative Care
    Goals of Care & Advance Care Planning
    5 Topics
    |
    1 Quiz
  81. Pain Management & Opioid Therapy
    5 Topics
    |
    1 Quiz
  82. Dyspnea & Respiratory Symptom Management
    5 Topics
    |
    1 Quiz
  83. Sedation & Palliative Sedation
    5 Topics
    |
    1 Quiz
  84. Delirium Agitation & Anxiety
    5 Topics
    |
    1 Quiz
  85. Nausea, Vomiting & Gastrointestinal Symptoms
    5 Topics
    |
    1 Quiz
  86. Management of Secretions (Death Rattle)
    5 Topics
    |
    1 Quiz
  87. Fluids, Electrolytes, and Nutrition Management
    Intravenous Fluid Therapy and Resuscitation
    5 Topics
    |
    1 Quiz
  88. Acid–Base Disorders
    5 Topics
    |
    1 Quiz
  89. Sodium Homeostasis and Dysnatremias
    5 Topics
    |
    1 Quiz
  90. Potassium Disorders
    5 Topics
    |
    1 Quiz
  91. Calcium and Magnesium Abnormalities
    5 Topics
    |
    1 Quiz
  92. Phosphate and Trace Electrolyte Management
    5 Topics
    |
    1 Quiz
  93. Enteral Nutrition Support
    5 Topics
    |
    1 Quiz
  94. Parenteral Nutrition Support
    5 Topics
    |
    1 Quiz
  95. Refeeding Syndrome and Specialized Nutrition
    5 Topics
    |
    1 Quiz
  96. Trauma and Burns
    Initial Resuscitation and Fluid Management in Trauma
    5 Topics
    |
    1 Quiz
  97. Hemorrhagic Shock, Massive Transfusion, and Trauma‐Induced Coagulopathy
    5 Topics
    |
    1 Quiz
  98. Burns Pharmacotherapy
    5 Topics
    |
    1 Quiz
  99. Burn Wound Care
    5 Topics
    |
    1 Quiz
  100. Open Fracture Antibiotics
    5 Topics
    |
    1 Quiz

Participants 432

  • Allison Clemens
  • April
  • ababaabhay
  • achoi2392
  • adhoward1
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Lesson 91, Topic 1
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Foundational Principles of Calcium and Magnesium Abnormalities in Critical Illness

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Foundational Principles of Calcium and Magnesium Abnormalities in Critical Illness

Foundational Principles of Calcium and Magnesium Abnormalities in Critical Illness

Objective

Describe the foundational principles of calcium and magnesium derangements in critically ill patients, including epidemiology, pathophysiology, clinical presentation, and risk factors.

1. Epidemiology and Incidence

Calcium and magnesium disturbances are among the most common electrolyte abnormalities in the ICU and correlate with adverse outcomes. Early recognition in high-risk cohorts, such as patients receiving massive blood transfusions, those on loop diuretics or proton-pump inhibitors, and the malnourished, enables timely prevention and treatment.

Table 1. Prevalence and Key Risk Factors in ICU Patients
Abnormality Prevalence (%) Key Risk Factors
Hypomagnesemia 50–60 Diuretics, sepsis, malnutrition
Hypocalcemia 60–70 Citrate exposure, alkalosis, hypomagnesemia
Hypermagnesemia 5–10 CKD, excessive exogenous magnesium
Hypercalcemia 2–4 Malignancy, hyperparathyroidism, vitamin D excess

Key Points:

  • Routine measurement of ionized calcium and serum magnesium is crucial for detecting dual deficiencies early.
  • Hypomagnesemia often coexists with hypocalcemia and impairs parathyroid hormone (PTH) action, delaying calcium correction.

2. Calcium Homeostasis Mechanisms

Parathyroid hormone (PTH), vitamin D, renal handling, and bone remodeling tightly regulate serum calcium within narrow limits. Disruptions in this intricate system lead to clinically significant derangements.

Calcium Homeostasis Flowchart A flowchart illustrating the negative feedback loop of calcium regulation. Low ionized calcium stimulates the parathyroid gland to release PTH, which acts on the bone and kidney. The kidney also activates Vitamin D, which acts on the intestine. These actions collectively increase serum calcium levels, which in turn inhibits further PTH release. Low Ionized Calcium Parathyroid Gland Bone↑ Resorption Kidney↑ Reabsorption↑ Vit D Activation Intestine↑ Ca Absorption PTH Active Vit D ↑ Ionized Calcium NegativeFeedback
Figure 1. Regulation of Calcium Homeostasis. A decrease in ionized calcium stimulates PTH secretion, leading to increased bone resorption, renal calcium reabsorption, and intestinal absorption (via Vitamin D activation), ultimately restoring serum calcium levels.
  • pH and Phosphate Effects: Alkalosis increases albumin-bound calcium, thereby lowering the physiologically active ionized fraction. Hyperphosphatemia can precipitate with calcium, also reducing the ionized level.
Clinical Pearl

Metabolic alkalosis, often resulting from aggressive diuretic therapy or mechanical ventilation, can precipitate symptomatic hypocalcemia by shifting ionized calcium into the albumin-bound pool, even if total serum calcium remains normal.

3. Magnesium Homeostasis Mechanisms

Magnesium is a predominantly intracellular cation, and its homeostasis is a balance between gastrointestinal absorption, distribution between compartments, and renal excretion. Serum levels represent only 1% of total body stores, making them a poor proxy for overall magnesium status.

Magnesium Homeostasis and Distribution A diagram showing magnesium distribution in the body. The central pool of extracellular magnesium (1%) exchanges with large intracellular stores in bone (60%) and muscle/soft tissue (39%). Intake is via GI absorption, and output is via renal excretion. Extracellular Mg²⁺ (~1% of Total) Bone (~60%) Muscle / Soft Tissue (~39%) GI Absorption (TRPM6) Renal Excretion (TAL, DCT)
Figure 2. Magnesium Distribution and Flux. The small extracellular pool is in dynamic equilibrium with large intracellular stores and is regulated by GI absorption and renal excretion.

Functional Roles:

  • Acts as a natural physiological calcium channel antagonist.
  • Essential cofactor for hundreds of enzymatic reactions, including ATP synthesis and use.
  • Modulates neuromuscular excitability and systemic vascular tone.

4. Pathophysiology of Calcium Abnormalities

Hypocalcemia and hypercalcemia result from disruptions in protein binding, hormone regulation, and renal or bone handling.

A. Hypocalcemia Etiologies

  • Citrate Chelation: Citrate in transfused blood products binds ionized calcium, reducing its availability.
  • Functional Hypoparathyroidism: Hypomagnesemia impairs PTH secretion and target-organ responsiveness. Sepsis and systemic inflammation can also blunt PTH release.
  • Binding and Precipitation: Alkalosis increases albumin binding, while hyperphosphatemia causes calcium phosphate precipitation.

B. Hypercalcemia Etiologies

  • Malignancy: Most common cause in hospitalized patients, via PTH-related peptide (PTHrP) secretion or direct osteolytic metastases.
  • Primary Hyperparathyroidism: Autonomous PTH secretion from an adenoma.
  • Other Causes: Vitamin D intoxication, granulomatous diseases (e.g., sarcoidosis), immobilization, and thiazide diuretic use.
Clinical Pearl

Always correct magnesium deficiency before aggressively repleting calcium. Hypomagnesemia creates a state of PTH resistance, and calcium administration will be ineffective until magnesium levels are normalized.

5. Pathophysiology of Magnesium Abnormalities

Magnesium disturbances profoundly affect the neuromuscular and cardiovascular systems. Hypomagnesemia is particularly insidious as it often manifests with other electrolyte derangements.

A. Hypomagnesemia Etiologies

  • Gastrointestinal Losses: Vomiting, diarrhea, high-output fistulas, or nasogastric suction.
  • Renal Wasting: Loop and thiazide diuretics, proton-pump inhibitors, and certain nephrotoxic drugs.
  • Malabsorption Syndromes: Chronic pancreatitis, inflammatory bowel disease, or short bowel syndrome.

B. Hypermagnesemia Etiologies

  • Impaired Excretion: Acute or chronic kidney injury is the most common cause.
  • Excessive Intake: Overuse of magnesium-containing laxatives or antacids, or iatrogenic overdose during treatment for eclampsia or arrhythmias.
Clinical Pearl

Maintain a high index of suspicion for hypermagnesemia in any patient with chronic kidney disease who presents with unexplained muscle weakness, hypotension, or respiratory depression, especially if there is a history of using over-the-counter magnesium-containing products.

6. Clinical Manifestations

Calcium and magnesium imbalances produce characteristic neuromuscular, cardiovascular, and respiratory signs that guide diagnosis and management. In patients with unexplained refractory arrhythmias or muscle weakness, both electrolytes should be measured concurrently.

Neuromuscular Effects

  • Hypocalcemia/Hypomagnesemia: Paresthesias, tetany (e.g., positive Chvostek/Trousseau signs), hyperreflexia, and seizures.
  • Hypercalcemia/Hypermagnesemia: Muscle weakness, fatigue, and diminished or absent deep-tendon reflexes.

Cardiovascular Effects

  • Hypocalcemia: QT interval prolongation, impaired contractility, and risk of ventricular arrhythmias.
  • Hypercalcemia: QT interval shortening and bradyarrhythmias.
  • Hypomagnesemia: PR and QT interval prolongation, torsades de pointes.
  • Hypermagnesemia: Hypotension, sinus bradycardia, and advanced heart block.

7. Impact of Chronic Diseases

Chronic conditions like kidney disease, cystic fibrosis, and malnutrition create a state of mineral dyshomeostasis that increases vulnerability during acute critical illness.

CKD and Dialysis

Phosphate retention and impaired activation of vitamin D lead to secondary hyperparathyroidism and complex bone mineral disorders. Magnesium accumulation is common in advanced CKD, requiring careful management of dialysate magnesium concentration to avoid toxicity.

Cystic Fibrosis & Malnutrition

Fat malabsorption reduces the uptake of vitamin D and magnesium. Altered calcium-to-magnesium ratios contribute to poor bone mineralization and other metabolic complications. It is important to monitor these ratios to guide appropriate supplementation.

8. Social Determinants of Health

Socioeconomic factors, health literacy, and barriers to access can directly impact the prevention and treatment of electrolyte disorders, both chronically and in the acute setting.

  • Medication and Food Access: Financial and insurance barriers may limit access to necessary supplements. Food insecurity and diets low in dairy, nuts, and leafy greens predispose individuals to chronic deficiencies.
  • Health Literacy: An inadequate understanding of supplementation regimens, dietary sources, and the importance of adherence can hinder effective management.
Clinical Pearl

Incorporate a social and dietary history into ICU assessments to identify nontraditional risk factors for electrolyte disorders. Engaging dietitians and social services early can provide crucial interventions that support clinical care.

References

  1. Shekhar S, Agarwal N, Patel D, et al. Prevalence of Hypomagnesemia in ICU Patients at a Tertiary Care Hospital and Its Impact on Disease Severity and Outcome. Indian J Crit Care Med. 2025;29(4).
  2. Mohamed AM, Elghazaly SK, Hassan SM, et al. An Assessment of Serum Magnesium Levels in Critically Ill Patients. Int J Crit Illn Inj Sci. 2023;13(3).
  3. Khan AM, Shaikh FY, Mehta S, et al. Calcium, Magnesium, and Phosphate Abnormalities in the Critically Ill. Emerg Med Clin North Am. 2014;32(2).
  4. Rodríguez-Ortiz ME, Moore SD, Covic A, et al. The Role of Disturbed Mg Homeostasis in Chronic Kidney Disease Progression and Cardiovascular Disease. Front Cell Dev Biol. 2020;8:543099.
  5. de Baaij JHF, Hoenderop JGJ, Bindels RJM. A Comprehensive Review on Understanding Magnesium Disorders. Int J Mol Sci. 2024;25(17).
  6. Dickerson RN. Fluids, Electrolytes, Acid-Base Disorders, and Nutrition Support. In: ACCP/SCCM Critical Care Pharmacy Preparatory Review and Recertification Course. 2016.
  7. Escobedo-Monge MF, García-González Á, Palacios G, et al. Magnesium Status and Ca/Mg Ratios in a Series of Children and Adolescents with Chronic Diseases. Nutrients. 2022;14(14):2941.
  8. Schwalfenberg GK, Genuis SJ. The Importance of Magnesium in Clinical Healthcare. Scientifica. 2017;2017:4179326.