Regulation of Calcium Metabolism

Calcium Metabolism

• Calcium is crucial for various physiological processes, including muscular contraction, membrane permeability, endocrine and exocrine secretions, enzyme regulation, and coagulation.
• Calcium stabilizes membrane potentials, and its imbalance can lead to manifestations such as muscle spasms, cardiac arrhythmias, and seizures.

Regulation of Calcium Metabolism

• Three tissues play a central role in calcium regulation: bone (and teeth), intestine, and kidney.
• Three hormones are involved in calcium regulation: parathyroid hormone (PTH), calcitonin, and activated vitamin D3.
• Three cell types are involved in calcium regulation: osteoblasts, osteocytes, and osteoclasts.

Parathyroid Hormone (PTH)

• PTH is produced by the parathyroid gland and raises calcium levels in the blood.
• PTH regulates blood calcium levels by promoting bone resorption, increasing calcium reabsorption in the kidney, and stimulating vitamin D activation in the intestine.

Calcitonin

• Calcitonin is produced by the thyroid gland and lowers calcium levels in the blood.
• Calcitonin is secreted in response to elevated calcium levels and opposes the effects of PTH in the bone and renal tubule.
• Calcitonin's main action is to inhibit osteoclastic bone resorption, decreasing plasma calcium concentration.

Calcium Stores in the Body

• The adult human body contains approximately 1-1.3 kg of calcium, with 99% stored in bones and teeth.
• The remaining 1% is distributed between soft-tissue cells and extracellular fluid.

Forms of Calcium in Blood

• Total calcium concentration in blood is 10 mg/dL.
• 40% of calcium is bound to plasma proteins, mainly albumin.
• Free, ionized calcium is the only biologically active form of calcium.

Acid-Base Abnormalities and Calcium

• Acid-base abnormalities alter ionized calcium concentration by changing the fraction of calcium bound to plasma albumin.
• In acidemia, free ionized calcium concentration increases.
• In alkalemia, free ionized calcium concentration decreases.

Roles of Calcium in the Body

• Calcium plays a role in signal transduction, neurotransmitter release, and muscle contraction.
• Calcium is a structural component in bone matrix and is involved in bone formation.

Calcium Balance

• Renal and gastrointestinal systems maintain a balance of calcium, with net excretion of calcium by the kidney equal to net absorption from the gastrointestinal tract.
• Bone remodeling involves the simultaneous formation of new bone and resorption of old bone.

Role of Phosphate in the Body

• Phosphate is involved in the formation of ATP, serves as a biologic buffer, and can modify protein functions.
• Phosphate can act as a biologic buffer and modulate protein functions.

Regulation of Calcium Metabolism

• The body maintains homeostasis of calcium and phosphate concentrations through various mechanisms.
• Calcium and phosphate are essential for various physiological processes, including muscular contraction, membrane permeability, endocrine and exocrine secretions, enzyme regulation, and coagulation.

Physiological Processes Involving Ca2+

• Muscular contraction
• Membrane permeability
• Endocrine and exocrine secretions
• Enzyme regulation
• Coagulation

Calcium Stabilizes Membrane Potentials

• Hypocalcemia (low calcium levels) can lead to muscle spasms, cardiac arrhythmias, and seizures due to enhanced membrane excitability.
• Hypercalcemia (high calcium levels) reduces membrane excitability, leading to muscle weakness and stupor.

Acid-Base Abnormalities and [Ca2+]

• Acid-base abnormalities alter the ionized Ca2+ concentration by changing the fraction of Ca2+ bound to plasma albumin.
• In acidemia, the free ionized Ca2+ concentration increases due to the excess of H+ ions binding to albumin.
• In alkalemia, the free ionized Ca2+ concentration decreases due to the deficit of H+ ions binding to albumin.

Roles of Calcium in the Body

• Signal transduction (neurotransmitter release)
• Second messenger
• Structural component in bone matrix
• Muscle contraction
• Bone formation

Calcium Balance

• Renal and GI: Net excretion of Ca2+ by the kidney equals net absorption of Ca2+ from the gastrointestinal tract.
• Bone remodeling: new bone is formed, and old bone is resorbed. Bone resorption is stimulated by parathyroid hormone.

Role of Phosphate in the Body

• Formation of adenosine triphosphate (ATP)
• Phosphate can serve as a biologic buffer
• Phosphate can act as a modifier of proteins, altering their functions.

Calcium and Phosphate Reabsorption

• PTH inhibits phosphate reabsorption in the proximal convoluted tubule of the nephron (phosphaturic action of PTH).
• Phosphaturia: the phosphaturic action of PTH causes the phosphate resorbed from bone to be excreted in the urine, allowing the plasma ionized Ca2+ concentration to increase.

Actions of Parathyroid Hormone (PTH)

• Inhibits phosphate reabsorption
• Stimulates Ca2+ reabsorption
• Stimulates Vitamin D synthesis

PTH and Small Intestine

• PTH indirectly stimulates intestinal Ca2+ absorption via activation of vitamin D.

Vitamin D Synthesis

• Renal cells produce 1,25-dihydroxycholecalciferol (active metabolite) or 24,25-dihydroxycholecalciferol (inactive metabolite) depending on the status of Ca2+ in the body.
• 1α-Hydroxylase activity is regulated by changing the activity of the 1α-hydroxylase enzyme.

Actions of Vitamin D

• Increases plasma levels of both Ca2+ and phosphate
• Promotes mineralization of new bone
• Has coordinated actions on the:
  • Intestine: increases both Ca2+ and phosphate absorption
  • Kidney: stimulates both Ca2+ and phosphate reabsorption
  • Bone: stimulates osteoclast activity and bone resorption

Pathophysiology of Vitamin D

• Rickets: vitamin D deficiency causes rickets in children, leading to softening of bones
• Osteomalacia: new bone fails to mineralize in adults, resulting in bending and softening of weight-bearing bones

Bone Mass in Balance

• Osteoblasts deposit new bone
• Weight-bearing activities
• Calcium/Vitamin D
• Estrogen/Testosterone

Resorption/Bone Loss

• Osteoclast cells digest bone
• Inactivity
• Deficient nutrition
• Low Estrogen/Low Testosterone