Bone Physiology Notes

Physiology Of Bone

• Bone or osseous tissue is a specialized rigid connective tissue that forms the skeleton. It consists of a special type of cells and tough intercellular matrix of ground substance.
• The matrix is formed by organic substances like collagen and it is strengthened by the deposition of mineral salts like calcium phosphate and calcium carbonate. Throughout life, the bone is renewed by the process of bone formation and bone resorption.

Functions Of Bone

1. Protective Function: Bones provide the framework and protect the soft tissues and vital organs of the body.
2. Mechanical Function: Bones support the body. In addition, by their attachment to the muscles and tendons, the bones act as levers to bring out various movements of the body.
3. Metabolic Function: Bones play an important role in the metabolism and homeostasis of calcium and phosphate in the body.
4. Hemopoietic Function: The red bone marrow in the bones is the site of production of blood cells.

Read And Learn More: Medical Physiology Notes

Classification Of Bone: Depending upon the size and shape, the bones are classified into five types:

1. Long bones – bones of the limbs
2. Short bones – bones in the wrist and ankle
3. Flat bones – skull bones, mandible, scapula, etc.
4. Irregular bones-vertebra
5. Sesamoid bones – patella.

Parts Of Bone: Long bones are formed by a cylindrical tube of bone tissue, which has three portions:

1. Diaphysis – the mid-portion or mid-shaft
2. Epiphysis – the wider extremity or the head on either end
3. Metaphysis – the portion between the diaphysis and epiphysis.

In growing age, a layer of cartilage called epiphyseal cartilage or epiphyseal plate or growth plate is present in between epiphysis and metaphysis. The epiphyseal plate is responsible for the longitudinal growth of the bones.

Composition Of Bone: Bone consists of the tough organic matrix to which the bone salts are deposited.

• Matrix:
  • The bone matrix is composed of protein fibers called collagen fibers, which are embedded, in the gelatinous ground substance. These collagen fibers form about 90% of the bone.
  • The ground substance is formed by ECF aim proteoglycans. The proteoglycans are chondroitin sulfate and hyaluronic acid which are concerned with the regulation and deposition of bone salts.
• Bone Salts: The crystalline salts present in bones are called hydroxyapatites, which contain calcium and phosphate. Apart from these substances, some other salts like sodium, potassium, magnesium, and carbonate are also present in the bone. The salts of the bone strengthen the bone matrix.

Structure Of Bone: The bone is covered by an outer white fibrous connective layer called periosteum and an inner dense fibrous membrane called endosteum. The tendons from the muscles are attached to periosteum. The heads (epiphysis) of bone are covered by hyaline cartilage. It forms the synovial joint with adjoining bones.

The bones have two layers of structures:

1. Outer compact bone
2. Inner spongy bone.

In most of the bones, both compact and spongy forms are present. However, the thickness of each type varies in different regions. The epiphysis contains large amount of spongy bone and outer thin compact bone. In diaphysis, the amount of compact bone is more and the spongy bone is very thin.

• Compact Bone
  • The compact or cortical bone is the hard and dense material forming about 80% of bone in the body. Its main functions are mechanical function and the protection of bone marrow.
  • The compact bone consists of minute cylindrical structures called osteones or Haversian systems which are formed by concentric layers of collagen. Collagen lamellae are called Haversian lamellae.
  • In the center of each osteon, there is a canal called the Haversian canal that contains the blood vessels, lymph vessels, and nerve fibers. The Haversian systems communicate with each other by transverse canals called Volkmann’s canal.
  • Within Haversian systems, there are small cavities called lacunae inside which the osteocytes are trapped. Osteocytes send long processes called canaliculi. The canaliculi from neighboring osteocytes unite to form tight junctions.
  • Marrow cavity: The compact bone has a large narrow cavity called marrow cavity or medullary cavity, which contains yellow bone marrow.
• Spongy Bone: The spongy or trabecular or cancellous bone forms 20% of bone in the body. It is made of bone spicules, which are separated by spaces. The spongy bone contains red bone marrow.

Cell Types Of Bone: Bone has three major types of cells:

1. Osteoblasts
2. Osteocytes
3. Osteoclasts.

 

1. Osteoblasts
   • Osteoblasts are the bone cells that are concerned with bone formation. These cells are situated in the outer surface of bone, the marrow cavity, and the epiphyseal plate.
   • The osteoblasts arise from the giant multinucleated primitive cells called the osteoprogenitor cells. The differentiation of osteoprogenitor cells into osteoblasts is accelerated by some hormones and some bone proteins called skeletal growth factors. The growth factors stimulate the growth of osteoblasts also.
   • Functions of osteoblasts
     1. Role in the formation of bone matrix: Osteoblasts are responsible for the synthesis of bone matrix by secreting type I collagen and a protein called matrix fetoprotein (MGP) or osteocalcin. The other proteins involved in the matrix synthesis are also produced by osteoblasts. Such proteins are transforming growth factor (TGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF).
     2. Role in calcification: The osteoblasts are rich in the enzymes alkaline phosphatase, which is necessary for the deposition of calcium in the bone matrix (calcification).
     3. Synthesis of proteins: Osteoblasts synthesize the proteins called matrix glycoprotein and osteopontin, which are involved in calcification.
     4. Fate of osteoblasts: After taking part in bone formation, the osteoblasts differentiate into osteocytes, which are trapped inside the lacunae of calcified bone.
2. Osteocytes
   • Osteocytes are the cells concerned with maintenance of bone. Osteocytes are small flattened and rounded cells embedded in the bone lacunae.
   • These bone cells are the main cells of developed bone and are derived from the matured osteoblasts. The cytoplasmic processes from osteocytes run into canaliculi and ramify throughout the bone matrix.
   • The processes from neighboring osteocytes have contact with each other forming tight junctions.
   • Functions of osteocytes
     1. Help to maintain the bone as living tissue because of their metabolic activity
     2. Maintain the exchange of calcium between the bone and ECF.
3. Osteoclasts: Osteoclasts are the bone cells that are concerned with bone resorption. Osteoclasts are the giant phagocytic multinucleated cells found in the lacunae of bone matrix. These bone cells are derived from hemopoietic stem cells via monocytes (CFU-M).
   • Functions of osteoclasts
     1. Responsible for bone resorption during bone remodeling
     2. Synthesis and release of lysosomal enzymes necessary for bone resorption into the bone-resorbing compartment.

Bone Growth: The embryo has a cartilaginous skeleton. The cartilage is composed of large amount of solid but flexible matrix. The matrix is derived from a protein called chondrin that is secreted by the cartilage cells or chondrocytes. Some of the cartilage is converted into bones.

• Ossification and Calcification
  • aversion of cartilage into bone is called the At the time of birth, the skeleton consists of 50% cartilage and 50% bone. At the age of two and thereafter, the skeleton has 35% cartilage and 65% bone.
  • The ossification is carried out by the osteoblasts, which enter the cartilage and lay down the matrix around them. Osteoblasts synthesize collagen fibers, which produce the matrix called osteoid. Then, calcium is deposited on the matrix. The deposition of calcium is called calcification.
• Growth in Length
  • During growth, the epiphysis at the end of each long bone is separated from the diaphysis by a plate of proliferative cartilage termed as epiphyseal plate.
  • Increase in the length of the bone occurs due to the formation of new bone from the epiphyseal plate. The thickness of the epiphyseal plate reduces as the length of bone increases. An increase in length of the bone occurs as long as the epiphyseal plates remain separated from the diaphysis (shaft).
  • The growth of the bone stops when the epiphysis fuses with the shaft. The process by which epiphysis fuses with the shaft is called epiphyseal fusion or closure. It occurs usually at the time of puberty. The width of the bone increases due to increase in the thickness of the periosteum or the outer layers of compact bone.

Bone Remodeling: Bone remodeling is a dynamic lifelong process in which old bone is resorbed and new bone is formed. Usually, it takes place in groups of bone cells called the basic multicellular units (BMU). The entire process of remodeling extends for about 100 days in compact bone and about 200 days in spongy bone.
Bone remodeling includes two processes.

1. Bone resorption: Destruction of entire bone matrix and removal of calcium (osteoclastic activity)
2. Bone formation: Development and mineralization of new matrix (osteoblastic activity).

Bone Resorption – Osteoclastic Activity

• Osteoclastic activity is the process that involves the destruction of bone matrix followed by the removal of calcium. Osteoclasts are responsible for bone resorption by their osteoclastic activity.
• The part of the bone to be resorbed is termed as bone-resorbing compartment. The osteoclast present in the bone-resorbing comportment attaches itself to the periosteal or endosteal surface of bone through volts-like membranous extensions. This process is mediated by the surface receptors called integrins. At the point of attachment, a ruffled border is formed by the folding of the cell membrane.
• Resorption of that particular bone-resorbing compartment occurs by some substances released from membranous extensions of osteoclasts such as:
  1. Collagenase
  2. Phosphatase
  3. Lysosomal enzymes
  4. Acids like citric acid and lactic acid.
• Sequence of events during bone resorption
  • Citric and lactic acid cause acidification of the area and decrease pH to 4
  • Lysosomal enzymes are activated at this pH
  • Activated enzymes digest or dissolve the collagen
  • Enzymes also dissolve the hydroxyapatite and form solution of bone salts
  • All the dissolved materials are now released into ECF
  • Some elements enter the blood
  • The remaining elements are cleaned up by the macrophages
  • A shallow cavity is formed in the bone-resorbing compartment.
• Bone Formation – Osteoblastic Activity
  • Osteoblastic activity is the process that involves the synthesis of collagen and formation of bone matrix that is mineralized.
  • Osteoblasts are concerned with bone formation. Osteoblasts synthesize and release collagen into the shallow cavity formed after resorption in the bone-resorbing compartment.
  • The collagen fibers arrange themselves in regular units and form the organic matrix called osteoid.
• Mineralization
  • Mineralization is the process by which minerals are deposited on bone matrix. The mineralization starts about 10-12 days after the formation of osteoid.
  • First, a large quantity of calcium phosphate is deposited. Afterward, the hydroxide and bicarbonate ions are gradually added causing the formation of hydroxyapatite crystals.
  • The process of mineralization is accelerated by the enzyme alkaline phosphatase secreted by osteoblast. The process also requires the availability of adequate amount of calcium and phosphate in the ECF.
  • The completely mineralized bone surrounds the osteoblast. Now, the synthetic activity of osteoblast is reduced slowly and the cell is converted into osteocytes. Later, the bone is arranged in concentric lamellae on the inner surface of the cavity. At the end of the formation of new bone, the cavity is reduced to from the Haversian canal.
• Significance of Bone Remodeling
  • In children
    • Thickness of bone increases
    • Bone obtains strength in proportion to the growth
    • Shape of the bone is realtered in relation to the growth of the body.
  • In adults
    • It is responsible for the maintenance of the toughness of bone
    • Ensures the mechanical integrity of the skeleton throughout life
    • Plays an important role in calcium homeostasis.
• Regulation of Bone Remodeling
  • Bone remodeling occurs continuously throughout life. So a balance is maintained always between the bone resorption and bone formation.
  • However, in persons like athletes, soldiers, and others in whom the bone stress is more, the bone becomes heavy and strong. This is because of the stimulation of osteoblastic activity and mineralization of bone by repeated physical stress.
  • Apart from the physical stress, a variety of hormonal substances and growth factors are involved in the regulation of bone resorption and bone formation.

Repair Of Bone After Fracture

• The process of healing after bone fracture involves joining of broken ends by the deposition of new bone.
• Various stages are involved in the repair of bone after fracture:

1. Formation of a hematoma between the broken ends of bone and surrounding soft tissues. Hematoma means swelling or mass of blood clot confined to a tissue or space due to rupture of blood vessel
2. Development of acute inflammation
3. Phagocytosis of hematoma, debris and fragments of bone by macrophages
4. Formation of granular tissue and development of new blood vessels
5. Development of new osteoblasts and formation of new bone called callus
6. Spreading of new bone to fill the gap between the broken ends of bones
7. Reshaping of new bone by osteoclasts, which remove excess callus and formation of canal in the new bone.

Applied PhysiologyDiseases Of Bone

1. Osteoporosis
   • Osteoporosis is the bone disease characterized by the loss of bone matrix and minerals. The meaning of the word osteoporosis is ‘porous bones. It occurs due to excessive bone resorption and decreased bone formation.
   • The loss of bone matrix and minerals leads to loss of bone strength associated with architectural deterioration of bone tissue. Ultimately, the bones become fragile with high risk of fracture. Commonly affected bones are vertebrae and hip.
   • Osteoporosis is common in women after 60 years. The various risk factors are given in Table.
2. Rickets: Rickets is a bone disease in children characterized by inadequate mineralization of bone matrix. It occurs due to vitamin D deficiency. Vitamin D deficiency develops due to insufficiency in diet or due to inadequate exposure to sunlight
   • Risk Factors For Osteoporosis
     1. Sedentary life
     2. Genetic factor
     3. Early menopause or ovariectomy
     4. Excessive smoking
     5. Excessive alcohol or caffeine intake
     6. Prolonged high intake of protein
     7. Prolonged medication with drugs like corticosteroids and cyclosporin
     8. Endocrine disorders like hypothyroidism Cushing’s syndrome, acromegaly and hypogonadism.
   • The deficiency of vitamin D affects the reabsorption of calcium and phosphorus from renal tubules resulting in calcium deficiency. It causes inadequate mineralization of epiphyseal growth plate in growing bones. This defect produces various manifestations.
   • Manifestations of Rickets
     1. Collapse of chest wall: Due to the flattening of sides of thorax with prominent sternum. This deformity of the chest with projecting sternum is called pigeon chest. It is also called chicken chest or pectus carinatum.
     2. Rachitic rosary: A visible swelling where the ribs join their cartilages. It is because of the development of nodules at sternal end of the ribs, which forms the rachitic rosary
     3. Kyphosis: The excess curvature of the upper backbone with convexity backward (forward bending or toward curvature). Severe kyphosis causes the formation of a hump (protuberance) which is called humpback, hunchback, or Pott’s curvature
     4. Lordosis: The excess forward curvature of backbone in the lumbar region
     5. Scoliosis: The lateral curvature of the spine
     6. Harrison’s sulcus: A groove in the rib cage due to pulling of the diaphragm inwards
     7. Bowing of hands and legs
     8. Enlargement of liver and spleen
     9. Tetany in advanced stages. The patient may die because of tetany involving the respiratory muscles. The causes for rickets are given in Table.
3. Osteomalacia: The rickets in adults is called osteomalacia or adult rickets. It occurs because of a deficiency of vitamin D. It also occurs due to prolonged damage of the kidney (renal rickets).
   • The characteristic features of osteomalacia:
     1. Vague pain
     2. Tenderness in bones and muscles
     3. Myopathy leads to waddling gait (gait means the manner of walking). In waddling gait, the feet are wide apart, and the walk resembles that of a duck.
   • Occasional hypoglycemic tetany.