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Questions and Answers
What condition is characterized by excessive nerve excitability and muscle contraction due to low calcium levels in the blood?
What hormone is primarily responsible for raising blood calcium levels?
Which of the following is NOT a function of calcitonin?
What is the first stage of the fracture healing process?
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What mineral is primarily composed of phosphorus and calcium and occurs naturally in bones and teeth?
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Which of the following statements is true regarding osteoporosis?
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Which hormone helps the gut absorb calcium and prevents the kidneys from losing calcium?
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What process describes the increase in the diameter of a tissue?
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What structure lines the inner surface of bones, including the medullary cavity?
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Which factor is responsible for chondrocytes dying in cartilage?
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What occurs in the epiphyseal plate?
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What is the role of osteomacs in bone remodeling?
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What hormone leads to the early closure of the growth plate?
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Which mineralization step involves the production of collagen fibers by osteoblasts?
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What condition is characterized by limb bones stopping growth early due to a genetic mutation?
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Which enzyme is involved in the resorption of collagen during mineral resorption?
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What is the primary function of calcium in the body?
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What is the term for abnormal calcification occurring in tissues like the eyes and arteries?
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What is the primary function of osteoclasts in bone tissue?
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Which type of bone has a spongelike appearance and contains trabeculae?
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What term describes the small canals that connect osteocytes in bone tissue?
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Which mineral constitutes the majority of the inorganic component of bone matrix?
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During intramembranous ossification, what is the first step in bone development?
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How are flat bones such as the skull developed?
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What is the role of red bone marrow?
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Which statement accurately describes the structural arrangement of compact bone?
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What happens to osteoblasts once they have completed their function?
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What is the primary component of the organic matrix in bone tissue?
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Study Notes
Bone Tissue
- Bone is a constantly remodeling tissue that supports and protects the body, enabling movement.
- It also serves as a site for blood stem cell formation.
- Flat bones consist of compact bone on the outer layer and spongy bone on the inner layer, without a marrow cavity.
Bone Cell Process
- Osteogenic cells in the endosteum and periosteum differentiate into osteoblasts.
- Osteoblasts produce unmineralized bone matrix (osteoid).
- Mineralization occurs as calcium and phosphate infiltrate the osteoid, hardening it.
- After becoming trapped in the hardened matrix, osteoblasts become osteocytes, residing in lacunae.
- Canaliculi are tube-like extensions from lacunae, connecting osteocytes.
Osteoclasts
- Osteoclasts originate in bone marrow from pre-monocytes.
- Their function is to dissolve bone, creating resorption bays that reabsorb bone material.
- Osteoclasts have microvilli on one side and a ruffled border resembling a comb.
Bone Matrix
- Bone is composed of approximately 1/3 organic tissue and 2/3 minerals by weight.
- The organic component includes collagen, along with glycosaminoglycans (GAGs), proteoglycans, and glycoproteins.
- The mineral component is primarily hydroxyapatite (calcium phosphate) with a smaller proportion of calcium carbonate.
- This combination of organic and mineral components provides strength and toughness.
- Minerals resist compression, while collagen resists tension.
- Acids dissolve minerals leaving collagen behind.
Compact Bone
- Compact bone is composed of osteons (Haversian systems): cylinders of tissue with concentric layers of matrix surrounding a central (Haversian) canal.
- Each layer of matrix within an osteon is called a lamella.
- Osteocytes within osteons are interconnected.
- Perforating canals (Volkmann's canals) connect central canals perpendicularly, providing passage for blood vessels.
- Lamella classification:
- Interstitial lamellae are irregularly shaped and fill spaces between osteons.
- Circumferential lamellae encircle the entire bone.
- Concentric lamellae are circular and arranged around the central canal of each osteon.
Spongy Bone (Cancellous Bone)
- Spongy bone has a sponge-like structure with trabeculae (thin plates or beams of bone).
- Trabeculae contain few osteons.
- Spaces within spongy bone are filled with red bone marrow, offering strength with minimal weight.
Bone Marrow
- Bone marrow is soft tissue found within the medullary cavity of long bones or the spaces within spongy bone.
- Red bone marrow resembles thick blood and comprises a mesh of reticular fibers and immature cells, making it hematopoietic tissue (blood formation).
- Yellow marrow is predominantly adipose tissue containing mesenchymal stem cells.
- Red marrow distribution includes the axial skeleton and cranium (pelvis, thoracic, cranial).
- Yellow marrow distribution is primarily in long bones (legs, arms).
- The distribution of red and yellow marrow can change with age.
Bone Development
- Flat bones of the skull, scapula, and mandible develop through intramembranous ossification.
- Other bones develop through endochondral ossification.
Intramembranous Ossification
- Mesenchyme condenses.
- Osteogenic cells develop.
- Osteoblasts form osteoid.
- Minerals are deposited within the osteoid.
- Osteoblasts become trapped and differentiate into osteocytes.
- Osteoclasts remodel the central region, while osteoblasts remodel the surface.
- Remaining mesenchymal cells become the periosteum.
Endochondral Ossification
- Cartilage formation: Mesenchymal cells transform into chondrocytes.
- Cartilage growth: Chondrocytes proliferate and enlarge.
- Cartilage death: Chondrocytes die due to nutrient deprivation.
- Blood vessel invasion: Blood vessels penetrate the cartilage matrix, bringing osteogenic cells.
- Bone deposition: Osteoblasts deposit bone on the existing cartilage matrix.
Epiphyseal Plate (Metaphysis)
- A cartilaginous layer separating the diaphysis of a long bone from its epiphysis.
- Growth of the bone occurs here.
Metaphysis
- The transitional zone between the diaphysis and epiphysis.
- Consists of five zones of activity:
- Reserve cartilage
- Cell proliferation
- Cell hypertrophy
- Calcification
- Bone deposition
Bone Remodeling
- Approximately 10% of bone tissue is recycled annually.
- Osteoclasts (primarily in bone marrow) break down bone, while osteoblasts rebuild it.
- Osteomacs regulate osteoblast activity, maintaining bone surface homeostasis.
Bone Growth
- Interstitial growth (length): Occurs at the metaphysis.
- Appositional growth (width): Occurs at the bone surface.
- Bones respond to physical stress: Osteoblasts build up bones under use, osteoclasts break down unused bones.
- Imbalance in these processes leads to bone deformities.
Miscellaneous Growth
- Bone growth accelerates during puberty.
- More osteogenic cells and chondrocytes are produced in epiphyseal plates.
- Testosterone and estrogen stimulate osteoblast activity differently, with estrogen leading to early closure of the growth plate.
- Anabolic steroids can hasten the closing of the epiphyseal plate.
Abnormal Growth
- Achondroplastic dwarfism: Limb bones stop growing prematurely due to a genetic mutation.
- Pituitary dwarfism: Congenital or acquired, not caused by tumors (can be due to head trauma).
- Pituitary gigantism: Caused by an adenoma (benign tumor on the pituitary gland).
Mineralization
- Minerals are removed from blood plasma and deposited in bone tissue.
- Osteoblasts produce collagen fibers that spiral along the osteon in alternating directions.
- These fibers become mineralized, hardening the matrix.
- Mineral concentration must reach the solubility product to initiate crystallization, followed by positive feedback for further, rapid crystallization.
- Ectopic ossification is abnormal calcification in tissues like eyes, brain, or arteries.
Mineral Resorption
- Osteoclasts dissolve bone to release minerals into the bloodstream.
- Resorption occurs at the ruffled border of osteoclasts.
- Osteoclasts release H+ ions, attracting Cl- ions to form HCl, which dissolves minerals like hydroxyapatite.
- Enzymes involved in resorption:
- Acid phosphatase for phosphate
- Cathepsin K for collagen breakdown.
Mineral Resorption (Why?)
- Phosphate is essential for the formation of essential molecules: DNA, RNA, ATP, phospholipids.
- Calcium is crucial for various functions including:
- Muscle contraction
- Neuron communication
- Blood clotting
- Exocytosis
Mineral Homeostasis
- Phosphate concentration changes have minimal impact.
- Changes in calcium levels of as little as 8% can be detrimental.
- Hypocalcemia (calcium deficiency):
- Excessive nerve excitability and muscle contraction.
- Sodium channels are less permeable, affecting membrane potential.
- Hypercalcemia (calcium excess):
- Excess calcium at the cell surface reduces sodium channel permeability, depressing the nervous system.
Homeostasis:
- Dependent on calcitriol (active vitamin D), calcitonin, and parathyroid hormone (PTH).
- Calcitriol increases intestinal calcium absorption and reduces renal calcium loss.
- Calcitonin decreases calcium levels by reducing osteoclast activity and increasing renal calcium excretion.
- PTH stimulates osteoclast and osteoblast activity, regulating calcium levels.
Rickets
- A condition caused by a lack of calcium.
Calcitriol
- Derived from vitamin D. Increases blood calcium by enhancing intestinal calcium absorption and reducing kidney calcium loss.
Calcitonin
- Secreted by C cells of the thyroid gland when calcium levels rise excessively.
- Reduces osteoclast activity rapidly (within 15 minutes) and increases renal calcium loss.
- Of greater significance in children, with minimal effects in adults.
- Calcitonin deficiency does not cause any adult diseases.
Parathyroid Hormone (PTH)
- Secreted by the parathyroid glands.
- Primarily regulates blood calcium levels.
- Stimulates kidney production of an enzyme essential for the final step in calcitriol synthesis.
- Other critical functions related to calcium regulation.
Healing of Fractures
- Typically takes approximately 8-12 weeks.
- Stages of healing:
- Fracture hematoma (1): Blood clot forms from broken vessels.
- Granulation tissue (2): Fibrous tissue, formed by fibroblasts, is infiltrated by capillaries.
- Callus formation (3): Soft callus of fibrocartilage replaced by hard callus of bone within 6 weeks.
- Remodeling (4): Spongy bone is replaced by compact bone over the next 6 months.
Osteoporosis
- The most prevalent bone disease.
- Characterized by loss of bone mass and increased brittleness, resulting from decreased organic matrix and minerals.
- Post-menopausal women are at highest risk.
- The average bone mass can be reduced by 30% by age 70.
- Hormone replacement therapy (HRT) can slow progression, but is insufficient on its own.
- Prevention is key:
- Exercise
- Calcium intake (1000 mg/day) between ages 25 and 40.
- Medications for treatment:
- Fosamax, Boniva, Reclast: Target osteoclasts.
- Evista: Estrogen agonist.
Other Key Terms:
- Chondrocytes: Cells that form fibrocartilage.
- Hydroxyapatite (Hap): A mineral rich in phosphorus and calcium, found naturally in bones and teeth.
- Osteoid: A gelatinous, unmineralized substance that forms the matrix of bone.
- Endosteum: A thin membrane of connective tissue lining the inner surface of bones, including the medullary cavity and Haversian canals.
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