Calcium Metabolism and Regulation Quiz

Calcium, Phosphate, and Magnesium

• These are essential minerals found in various tissues and body fluids, including bones and teeth.
• Understanding their distribution, homeostasis, and pathophysiology is crucial.

Learning Objectives

• Understand the distribution of Calcium, Phosphate, and Magnesium in the human body.
• Understand Calcium, Phosphate and Magnesium homeostasis.
• Learn the pathophysiology of homeostatic disorders in these elements.
• Identify different roles of the laboratory case studies.

Calcium

• An essential mineral element found in multiple tissues and fluids, notably bones, teeth, and body fluids.

Sources of Calcium

• Nuts
• Vegetables (e.g., lentils, cabbage)
• Dairy products (e.g., milk, cheese, egg yolk)
• Fish (e.g., salmon, sardines)

Biological Functions of Calcium

• Muscle contraction (including heartbeat)
• Metabolic and endocrine functions
• Component of bones and teeth (calcification)
• Blood coagulation
• Transmission of neuromuscular impulses
• Second messenger (e.g., glucagon)
• Enzyme activation (e.g., ATPase)
• Maintains cell membrane integrity

Forms of Plasma Calcium

• Ionized Calcium: Physiologically active fraction, affects cellular effects and PTH control.
• Bound Calcium: Physiologically inactive, mainly bound to albumin (50%) and complexed with ions.
• Complexed Calcium: Salts (e.g., bicarbonate, citrate, phosphate, lactate).
• Total Calcium = Ionized + Bound + Complexed.
• Normal range in mg/dL: 8.4-10.1.
• Normal range in mmol/L: 2.2-2.5

Distribution and Absorption of Calcium in the Body

• Three major body calcium pools:
  • Intracellular Calcium: Located in mitochondria and endoplasmic reticulum, levels vary from 100 nmol/L to > 1.00 µmol/L and affects cellular signaling, enzyme activation, and muscle contractions.
  • Bone Calcium: Almost 99% of total body calcium, 99% is mineralized, and a small 1% pool exchanges with extracellular calcium.
  • Remainder circulates mainly in blood and other extracellular fluids (ECF), approximately 10,000x higher basal concentration in cells compared to plasma, with serum calcium at ~2.20 mmol/L.
• Calcium Absorption Mechanisms: Simple diffusion and active transport (Ca++ pump).

Factors Influencing Calcium Absorption

• pH: Acidic pH increases calcium absorption, while alkaline pH reduces it.
• Dietary composition: Higher protein diet increases calcium absorption by 15%, while a low protein diet results in about 5% calcium absorption.
• Fatty acids: Reduce calcium absorption.
• Minerals (e.g., phosphates, magnesium): Decrease calcium absorption.
• Other factors: Age, health status, hormonal factors.

Calcium Regulation

• GI uptake
• Renal clearance
• Bone
• Endocrine system (PTH, Vitamin D metabolites, Calcitonin)

Calcium Homeostasis - PTH and Vitamin D action

• Mechanisms explain how PTH and Vitamin D maintain calcium levels in the body.

Calcium Homeostasis - Calcitonin action

• Calcitonin's role in regulating calcium levels through feedback mechanisms.

Clinical Importance of Calcium

• Hypercalcemia: Serum Calcium level >11.0mg/dL, Normal Range: 9.0 - 11.0 mg/dL.
• Hypocalcemia: Serum Calcium level <8.5 mg/dl, Normal Range: 9.0 - 11.0 mg/dl.
• Normal Levels: 2.20 to 2.60 mmol/L

Pathophysiology of Calcium Metabolism

• Disorders of homeostatic regulators (PTH, Vitamin D, Calcitonin).
• Disorders of effector organs (Gut, Kidney).
• Disorders of the skeleton.

Hypocalcaemia: Potential Causes

• Hypoproteinaemia
• Decreased intake (vitamin D deficiency, dietary malabsorption)
• Renal disease
• Decreased flux from bone (PTH deficiency, congenital/idiopathic, parathyroid ablation)
• Magnesium deficiency
• Bone resistance to PTH
• Ureamia
• Magnesium deficiency
• Pseudohypoparathyroidism
• Drug-induced (e.g., Mithramycin)

Potential Causes (continued)

• Increased bone uptake (post-parathyroidectomy, post-thyroidectomy, hyperthyroidism).
• Extra-skeletal chelation (e.g., acute pancreatitis, Hyperphosphataemia, renal failure).
• Drug therapy (e.g., frusemide, EDTA, calcitonin, mithramycin, anticonvulsants, phenytoin, barbiturates).
• Sample integrity issues (contamination, IV fluids, anticoagulants).

Symptoms of Hypocalcemia

• Convulsion
• Arrhythmia
• Tetany
• Spasm
• Stridor (breathing difficulty)

Hypercalcaemia: Potential Causes

• Hyperparathyroidism (primary, tertiary, multiple endocrine neoplasia)
• Malignancy (solid tumours, haematological malignancies)

Potential Causes (continued)

• Renal failure (post-dialysis, acute renal failure)
• Increased renal absorption (thiazide diuretics, familial hypocalciuric hypercalcemia)
• Miscellaneous (Addison's disease, Myxoedema, Acromegaly, vitamin A toxicity, Phaeochromocytoma, idiopathic hypercalcaemia of infancy)
• Non-malignant / Non-parathyroid causes (hyperalbuminaemia, dehydration, artefactual, increased intake / absorption, vitamin D intoxication, sarcoidosis, milk alkali syndrome, Iatrogenic, IV infusion)
• Increased bone resorption (thyrotoxicosis.

Clinical Symptoms Associated with Hypercalcemia

• Neuropsychiatric (lethargy, depression, confusion, coma).
• Cardiovascular (ECG changes – reduced QT interval, prolonged PR interval).
• Gastrointestinal (anorexia, nausea, vomiting, abdominal pain, constipation).
• Renal (polyuria, polydipsia, volume depletion, reduced glomerular filtration).

Laboratory Investigation of Calcium Disorders

• Routine measurement: Total Calcium.
• Adjusted (Corrected) Calcium: Values adjusted for albumin changes.
• Investigation of Hypocalcaemia: Sorting out common causes
• Investigation of Hypercalcaemia: Sorting out common causes)
• Pre-analytical factors: In vivo and in vitro factors affecting serum total or free calcium measurements (tourniquet use and venous occlusion, changes in posture, exercise, hyperventilation, fist clenching, alimentary status, alterations in protein binding.

Magnesium

• Essential mineral, involved in various bodily functions.
• Sources include green vegetables, animal sources, dairy products, cereals, potatoes, and beans.
• Distribution: Bone (67%), intracellular (31%), extracellular (~2%).-
• Normal Serum Level: 1.5 - 1.8 mEq/L (0.85 – 1.10 mmol/L).
• Physiologic roles: Enzyme activation, neuromuscular irritability, bone formation, effects on muscle contraction.
• Magnesium metabolism.
• Clinical Significance: Hypomagnesaemia (<7mmol/L), mild, moderate and severe cases. Hypermagnesaemia.
• Symptoms of Hypomagnesaemia: Lethargy, muscle weakness, drowsiness, tetany, tremor, twitching, agitation, vertigo, confusion, cardiac arrhythmias, seizures, nausea, vomiting.
• Causes of magnesium depletion: Renal losses (Diabetes Mellitus, Alcoholism, Hypercalcemia, Hyperaldosterone, Renal Tubular disorders). Gastrointestinal Tract related problems (Diarrhea, vomiting, malabsorption, laxatives and proton-pump inhibitors).

Laboratory Investigation of Magnesium

• Conditions that necessitate Mg investigations: Pre-eclampsia in pregnancy, cardiac arrhythmia, persistent hypokalaemia, tetany after calcium therapy.
• Sample collection.
• Possible samples: Including serum Mg, Red Blood Cell Mg, and Leukocyte Mg, and muscle Mg measurements.

Phosphate

• Inorganic, measured in blood.
• Physiochemical forms include monovalent (H2PO4-) and divalent (HPO42-), with the ratio determined by pH.
• Normal levels vary by age.
• Distribution: Major intracellular ion, with 85% found in bones and teeth, around 15% in soft tissue, and approximately 10% extracellular.
• Physiological roles: High-energy reactions (ATP), calcium balance, intermediary metabolism (proteins, fats, carbohydrates), gene transcription, and cell growth, buffer for body fluids, phospholipids, nucleotides, and other nucleic acids.
• Phosphate Regulation.
• Phosphate Homeostasis.
• Clinical Significance: Hypophosphatemia and hyperphosphatemia.
• Common causes of hypophosphatemia: Intracellular shift, decreased net intestinal phosphate absorption, decreased absorption, intracellular phosphate loss, lowered renal phosphate threshold.
• Common causes of hyperphosphatemia: Decreased renal phosphate excretion, Increased extracellular phosphate load, increased phosphate intake.
• Differential diagnosis for phosphate imbalances and related issues.

Test your knowledge on calcium metabolism, its biological functions, and the roles of various hormones like parathyroid hormone and calcitonin. This quiz covers essential concepts about calcium sources, binding proteins, and physiological effects. Perfect for students studying biochemistry or human physiology.