Lecture 2, Skeletal System and Ca2+ Homeostatis

Question 1

The Skeletal System

Answer 1

The skeletal system refers to the bones of the body, but also the cartilages, ligaments and connective tissues that stabilize and inter-connect the bones
five primary functions:
1. structural support - provides a framework for tissues and organs (to anchor themselves) to attach to
2. protection of soft organs and delicate tissues
A. eg. ribs protect the heart and lungs from physical trauma
3. storage of minerals
A. primarily calcium (Ca2+ - 99%) and phosphate ions (PO43-)
4. blood cell production
A. red and white blood cells, and platelets are produced in red bone marrow
B. red bone marrow fills the cavities of many bones
5. leverage
A. provides a lever on which muscles act upon to generate force

Question 2

Bone Anatomy Review

Answer 2

the epiphysis is an expanded area found at each end of a long bone (takes the weight of force)
* the metaphysis is the narrow zone connecting the epiphysis to the shaft of a long bone
* the diaphysis is the long and tubular shaft of a long bone
bone exists in two layers:
* spongy bone: consists of a branching, open network of struts and plates that resembles latticework
◦ aka trabecular or cancellous bone
* compact bone: thin, dense layer of bone that surrounds spongy bone
◦ aka cortical bone
epiphysis and metaphysis have both spongy and compact bone but diaphysis only has compact bone

Question 3

Periosteum

Answer 3

periosteum is a connective tissue that wraps around the diaphysis
- has two layers: a fibrous outer layer and cellular inner layer
-fibrous layer contains sharpey’s fibers
- cellular layer contains fibroblasts, osteogenic cells and osteoblasts
* contains an extensive network of blood vessels, lymphatic vessels and sensory nerves
* allows for nerves and blood to pass through to the bone, and also allows for tendon and ligament attachment

Question 4

Endosteum and nutrient foramen

Answer 4

• the endosteum is an incomplete cell layer that lines the medullary cavity
  ◦ ALSO covers spongey bone and lines the central canals
• the nutrient foramen is a tunnel that penetrates the diaphysis and provides access for the nutrient artery and vein

Question 5

Osteon

Answer 5

• the osteon is the structural unit of compact bone
• osteocytes account for most of the cell population in bone
• each osteocyte cell (one only) occupies a lacuna, which is a pocket sandwiched between layers of matrix
• one lacuna is will only ever contain one osteocytes
• lacunae is not the same as lamallae
  ◦ lamellae: thin layers of matrix (is the matrix)
  ◦ lacunae: a pocket within the matrix that contains an osteocyte
• canaliculi are narrow passageways extending from the lacuna into the lamellae
• canaliculi are important in interconnecting all the lacunae to vascular passageways, allowing the osteocytes to receive nutrients and dispose of waste products

Question 6

Bone Cell Types

Answer 6

-> osseous tissue is a type of connective tissue that consists of cells at various stages of the life cycle
Osteoprogenitor (osteogenic) cell
* a type of stem cell that resides within bone
* has the ability to divide into osteoblasts
* plays a major role in healing fractures
* strengthens bones growing up

Osteoblast
* a premature bone cell in the periosteum
* bone builders
* secrete collagen and chrondroitin into the matrix of bone

Osteocyte
* mature bone cells present in the lacunae
* important in bone turnover and repair
* occasionally referred to as osteoblasts that are “trapped” within the matrix of the bone
* help build up the matrix of the bone

Osteoclast
* a type of bone cell that originates from hematopoietic progentor cells
* resisdes on the surface of the bone
* multi-nucleated
* functions in bone resorption; the breakdown of the bone

Question 7

Bone cell types (2)

Answer 7

the process of producing new bone matrix is known as ossification or osteogensis
* occurs normally throughout the lifespan, but increases during periods of growth (fetal development and childhood) and post-injury
the process of dissolving the bone matrix is known as osteolysis or bone resorption
* osteolysis occurs normally throughout the lifespan
* is important in regulating calcium and phosphate ion concentrations in the body

Question 8

Osteogenesis (bone development)

Answer 8

osteogenesis occurs throughout the life span
* occurs during embryonic development in form of new bone formation
* occurs during childhood and adolescence during normal childhood development and puberty
* occurs during adulthood in the form of bone remodelling
bone can be considered a replacement tissue
* for bone to develop, it requires a model tissue to use as a template

two types of ossification:
intramembranous ossification: the differentiation of mesenchymal cells directly into bone cells
* mesenchymal cells (stem cell) are used as a model framework for the born tissue to use as a template
* responsible for the development of the bones of the skulls, the mandible, the clavicle and sesamoid bones

endochondral ossification: the formation of bones cells in place of hyaline cartilage cells
* the cartilage cells do not become bone cells, but are instead used as a TEMPLATE for bone cells to form
* responsible for the development of most bones, excepts for bones listed above

Question 9

Osteogenesis - Intramembranous Ossification

Answer 9

intramembranous ossification: the differentiation of mesenchymal cells directly into bone cells
intramembranous ossification begins during embryonic development
a. mesenchymal cells begin to cluster and secrete osteoid (collagen matrix), which crystallizes
◦ this becomes the ossification center
b. as the matrix further ossifies, some osteoblasts become trapped inside bone pockets, and differentiate into osteocytes (matured, trapped osteoblasts)
c. formation of trabeculae and periosteum, and introduction of vascularization - necessary to keep the osteocytes viable
d. compact bone develops superficial to the spongy bone, and some blood vessels together to form red bone marrow

Question 10

Osteogenesis - endochondral ossification

Answer 10

endochondral ossification: the formation of bone cells in place of hyaline cartilage cells
* cartilage is an avascular tissue and thus takes relatively longer to heal than other tissues
a/b) mesenchymal cells form a hyaline cartilage model/template
* chondrocytes near the center increase in size and die, leaving cavities that are later filled with calcified matrix
* the center with calcified matrix becomes the primary ossification centre
c) perichondrial cells located on the edges of the cartilage turn into osteoblasts and form a superficial layer of bone
* perichondrium -> periosteum
* capillaries penetrate the cartilage, forming a nutrient artery
* ossification extends along the periosteum towards both ends of the cartilage
d) cartilage grows at the epiphysis as bone continues to form at primary ossification center
* remodelling of the primary ossification center results in the formation of a medullary center
* increases in both length and width
e) capillaries and osteoblasts migrate towards the epiphyses
* secondary ossification centers develop
f) epiphyses are filled with spongey bone
* cartilage remains in the epiphyseal plate
* articular cartilage remains, and is eventually reduced to a thin superficial layer
bone growth occurs through puberty
* at the end of puberty, the epiphyseal plate narrows and eventually disappears
* this is called epiphyseal closure, and signals the end of interstitial bone growth

Question 11

Bone Remodelling

Answer 11

process in which the matrix of a bone is resorbed (dissolved) and replaced by a new bone by osteoblasts
* occurs normally, throughout the lifespan but increases post-injury or following periods of increased mechanical stress or load (ex. exercise)

Question 12

Interstitial growth

Answer 12

growth in bone length that occurs in the lacunae

Question 13

Appositional Growth

Answer 13

growth in bone width (in thickness) that occurs due to new bone being deposited on the periosteum, and resorbed from the endosteum
- osteogenic cells differentiate into osteoblasts and deposit matrix to the surface

Question 14

Ossification

Answer 14

the laying down of new bone material (including osteocytes and calcium salts + osteiod)

Question 15

Calcification

Answer 15

the formation of calcium salts and crystals within tissue
* calcification is a step within the Ossification process (but not vice versa)
the majority of bone development occurs during embroyonic development
* during childhood, sine cartilage will still be replaced with bone, but the predominant form of bone development is interstitial and appositional growth
* in adulthood, some cartilage remains but only bone remodelling will occur

Question 16

Interstitial growth zones

Answer 16

interstitial growth occurs at the epiphyseal plate in long bones
reserve zone - closer to the epiphysis
* contains small chondrocytes that secure the epiphyseal plate to overlaying ossesous tissue in the epiphysis
* do not actively participate in bone growth (just an anchor)

proliferative zone
* contains slightly larger chondrocytes that create new chondrocytes to replace the old/dead cells

hypertrophic zone
* contains older/younger chondrocytes (older ones shift downwards)

calcification zone
* old chondrocytes die and disintegrate (die in the pocket of matrix that will be filled with new bone cells)

ossification zone
* osteoblasts lay down new bone (fill everything else with new bone matrix)

Question 17

Bone: A Reservoir for Ca2+

Answer 17

bone serves as a mineral reservoir, containing over 99% of the body’s total calcium stores, 99% of the body’s phosphate stores, and 80% of the body’s carbonate
* bone contains ions in the form of hydroxyapatite
hydroxyapatite: an inorganic mineral consisting of crystals of calcium (Ca), phosphate, and hydroxyl/hydroxide (OH-) ions
* by weights ~1/3rd of bone is osteoid and ~2/3rd is hydroxyapatite (minerals)
the role of the bone as a reservoir for calcium is particularly important, because calcium plays a crucial role in normal neurological function and muscular activity

Question 18

bone remodelling allows for the regulation of plasma [Ca2+]

Answer 18

• plasma [Ca2+] that is too low or too high may result in various pathological conditions, like cardiac arrhythmia
  if plasma [Ca2+] is too high, hormones will be released to stimulate osteoblast activity
• increase bone formation
• Ca2+ from the plasma stored in bone
  if plasma [Ca2+] is too low, hormones will be released to stimulate osteoclast activity
• increased bone resorption
• Ca2+ is released from the bone into the plasma (thyroid hormone)

Question 19

Ca2+: Other Homeostatic Control Mechanisms

Answer 19

the kidneys: (help control calcium)
* Ca2+ is normally excreted into the tubules of the kidney, and then reabsorbed into the blood
* the amount of Ca2+ reabsorbed into the blood can be regulated to minimize and maximize the amount of Ca2+ excreted in the urine
* decreased reabsorption -> decreased plasma [Ca2+]
the gastro-intestinal tract:
* not all Ca2+ ingested is absorbed by the GI tract
* Ca2+ absorption by the GI tract is under hormonal control

Question 20

Clinical Application: Paget’s Disease

Answer 20

Paget’s disease is a condition in which osteoclasts are overactive, resulting in a greater rate of bone resorption
* the osteoblasts try to increase their activity and lay down new bone, however they cannot keep up with the osteoclasts
* over time, this results in bones that are weak, brittle, misshapen, and prone to fracture
* the cause of Paget’s disease is unknown, but some research suggests it may be genetic, environmental, and/or associated with aging
* treatment: drugs that decrease the activity of osteoclasts (such as bisphosphonates), and surgery in some cases