Calcium and Phosphate Metabolism Quiz

Calcium and Phosphate Metabolism

•  Calcium and phosphate metabolism are crucial for bone health and overall body function.
• Bone is a dynamic tissue that undergoes continuous remodeling throughout life.
• Approximately 20% of bone is undergoing remodeling at any given time.

Bone Physiology

• Bone's primary functions include structural support, protection of organs and soft tissues, locomotion, mineral storage, blood cell production, and endocrine regulation.
• Bone matrix is composed of approximately 60% inorganic material, 10% water and 30% organic material.
• The inorganic portion consists primarily of hydroxyapatite crystals, embedded within a collagen matrix. This combination provides bone's strength and facilitates regeneration.
• Important ions, such as Na+, K+, Mg2+, CO32-, Ba2+, and Zn2+ are also present and moderate the crystallinity of bone minerals.

Bone - Organic Portion (Osteoid)

• Osteoid is the organic component of bone, composed predominantly of Type I collagen, making up 28% of the organic matrix.
• The triple helix structure of collagen provides structural support and contributes to bone's mechanical properties such as flexibility and resistance to tensile forces.
• Non-collagen structural proteins include proteoglycans, with their glycosaminoglycan core polypetides (e.g., hyaluronic acid) and organization of bone extracellular matrix and collagen fibrillogenesis. These components are crucial for organizing the bone extracellular matrix, promoting collagen fibrillogenesis, and participating in mineralization and bone formation.
• Specialized proteins such as osteocalcin are vital for osteoblast activity and osteoclast activity. Furthermore osteonectin and osteopontin have significant effects on cell adhesion, mineralization, and bone formation.
• Factors like RANKL and growth factors and cytokines are important for bone growth and remodeling and bone resorption regulation.

Bone - Inorganic Portion

• Hydroxyapatite crystals, (Ca10(PO4)6(OH)2) are the key inorganic component of bone, accounting for approximately 60-70% of its dry weight. These crystals are embedded in the collagen matrix, providing bone with its robust structural strength and facilitating bone regeneration.
• Other ions, such as sodium (Na+), potassium (K+), magnesium (Mg2+), carbonate (CO32-), barium (Ba2+), and zinc (Zn2+), also regulate the properties of bone minerals.

Bone Cells

• Osteoblasts: Responsible for bone formation. They synthesize and secrete matrix proteins, including Type I collagen and osteocalcin, and contribute to mineralization. Osteoblast activity is crucial in bone formation. Osteoclasts also play a key role in bone resorption.
• Osteoclasts: Primarily responsible for bone resorption. They degrade proteins in bone matrix via enzymes and acidification.

Bone Remodeling

• Osteoclasts dissolve bone matrix, and osteoblasts create new bone tissue. This interplay determines the growth and maintenance of bone tissue.
• Osteoblasts have receptors for hormones, cytokines, and growth factors for bone production and increase bone growth/strength.
• When osteoblasts become encased in bone matrix they differentiate into osteocytes.

Wolff's Law and Response to Bone Remodeling

• Bone remodels in response to the forces and stresses placed on it. This principle underlies how bone adapts to physical demands.
• Growth in bone diameter is directly related to the mechanical forces and gravity.
• Heavy use of heavy bones leads to increase bone density, while inadequate use leads to bone loss (atrophy).
• Spaceflight, paralysis, or prolonged immobilisation can cause significant bone loss due to reduced bone stress.
• Bone adapts to the stresses placed on it – if stressed a lot, it will grow thicker and denser. If not stressed, it will become thinner and weaker.

Controlling Bone Remodeling

• Hormones like parathyroid hormone (PTH) and calcitonin regulate bone remodeling, dictating when and where remodeling occurs.
• Mechanical stress dictates where remodeling is necessary, with high stress areas experiencing appositional growth.

Calcium and Inorganic Phosphate

• Important elements for structure & function of bone tissue.
• Total body calcium is approximately 1100g (90% in skeleton) and plasma calcium is 2.2-2.6 mmol/L.
• Calcium is present in bones, ATP, blood proteins, etc., where it regulates cell function, muscle & nerve function, enzyme co-factors, as well as second messenger for fertilization and mitosis regulation.
• Phosphate is also present in bone as well as found in ATP, other crucial blood components, where it acts to regulate cell function. The total body phosphate range is approximately 500-800g and 3-4.5 mg/dl in plasma.

Body Requirements

• Calcium requirements vary with age. Pregnant and lactating women need higher calcium intake.

Regulation of Plasma Calcium

• Plasma calcium is tightly regulated within a narrow range (2.4 mM, 9.4 mg/dl) with 50% of this being ionized calcium.
• Protein-bound calcium component comprises about 41%.
• The ionized fraction depends on pH; protein binding decreases as pH decreases.
• pH 7.45 (alkalosis) increases calcium binding and decreases ionized fraction, while pH 7.35 (acidosis) decreases calcium binding and increases ionized fraction.
• Correct calcium levels are crucial for proper neuronal function.

Total Calcium Measurement

• Incorrect measurement can occur due to low albumin levels (i.e., malnutrition).
• Corrected calcium measurements adjust for albumin level variations to provide a more accurate assessment of calcium status.

Calcium Transport in the Blood

• Ionized calcium is tightly regulated.
• The ionized fraction depends on the blood pH.
• Lower blood pH (acidosis) increases ionized calcium, while higher blood pH (alkalosis) decreases ionized calcium.

Calcium Homeostasis

• Calcium homeostasis is maintained by bone, kidney, and intestine via absorption and excretion, regulated by parathyroid hormone (PTH) and calcitonin.
• Vitamin D is important to regulate gut calcium absorption.

Regulation of PTH Secretion

• Calcium sensing receptors on chief cells regulate PTH secretion.
• When calcium levels are low, PTH secretion increases in order to increase calcium reabsorption and minimize calcium loss through excretion.
• When calcium is high, PTH secretion decreases to limit calcium reabsorption.

PTH on Bone

• PTH regulates bone function to maintain Calcium balance.
• Briefly, PTH will stimulate bone formation, but the long-term effect is stimulating bone resorption.

PTH on Kidney and Intestine

• PTH indirectly impacts calcium absorption in the gut via Vitamin D activation.
• PTH has direct impact on the kidneys to increase calcium reabsorption.

Kidneys and Calcium Excretion/Reabsorption

•  The kidneys play a role in calcium reabsorption/excretion.

Calcium Homeostasis

• Calcium homeostasis is complex and regulated by multiple systems: bone, intestine, kidneys, and hormones (PTH, Calcitonin, Vitamin D).
• These systems function in coordination to maintain calcium levels, supporting various critical cellular functions.

This quiz covers the essential aspects of calcium and phosphate metabolism and their role in bone health. Explore the dynamic nature of bone tissue, its physiology, and the composition of bone matrix. Test your understanding of the organic and inorganic components of bone.