Ch. 6

How Osteoclasts Work

1. Actively transport H into the space between osteoclast cell and bone. (H pump) 2. Cl- ions follow by electrical attraction 3. HCl forms and dissolves minerals in bone. 4. Osteoclasts secrete enzymes (Cathepsin K) that digest AAs in collagen and break it down.

Growth of bones into adulthood

Bone Elongation Appositional Growth

Osteoblast

Bone building cells. Synthesis and secrete collagen fibers to build ECM of bone tissue and initiate calcification. Once surrounded and trapped by their secretions → Osteocytes.

Inorganic Components of Bone

Calcium Phosphate (mineral salts). Resist compression and support weight without sagging. BRITTLE

Hydroxyapatite

Calcium phosphate - main mineral salt in osseous tissue. Helps resist compression and support weight.

Nutrient Foramen/Foramina

Holes in periosteum for vasculature

Metaphysis

Narrow portion of a long bone between the epiphysis and diaphysis

Diaphysis

Shaft or central part of a long bone.

Vitamin C

Stimulate osteoblasts and are needed for synthesis of collagen fibers.

Vitamin A

Stimulates activity of osteoblasts.

Compact Bone

Strongest form of bone. Few spaces. Protection and support. Forms the diaphysis of long bones and the external layer of all bones.

Resorption

The re-absorption of already deposited Ca back into the blood. Dissolving of bone and release of minerals into the blood. Directed by osteoclasts.

Bone Elongation

cCartilage grows on epiphyseal side of plate, leaving bone on diaphyseal side. Chondrocytes grow and proliferate on epiphyseal side of plate. New chondrocytes replace old ones that are destroyed be calcification. With adulthood the plate becomes a line, bone replaces all remaining cartilage.

Medullary Cavity

Bone marrow is here

Calcitriol

(Vitamin D): Raises blood calcium. How it works: • Increases intestinal absorption • Promotes urinary reabsorption of calcium ions • Increase resorption from skeleton (stimulates osteoclasts) A deficiency leads to abnormal bone softness • Rickets in children. How it is synthesized: • UV radiation causes keratinocytes to convert cholesterol into cholecalciferol • Liver converts cholecalciferol into calcidiol • Kidney converts calcidiol into calcitriol

Epiphyseal Plate

(growth plate): In adolescents, contains hyaline cartilage that facilitates lengthening

Fracture Repair

1. Hematoma formation (reactive phase) - 6-8 hours after fracture. Blood vessels break and clot forms. a. Inflammation - blood delivers WBC - phagocytes remove cellular debris. Osteoclasts removed damage bone. 2. Fibrocartilage callus forms. a. 3 weeks - fibroblasts from periosteum deposit collagen 3. Bony callus formation a. 3-4 months b. Osteoblasts produce trabeculae and spongy bone 4. Bone Remodeling - a. Spongy bone replaced by compact bone b. Typically wider than initial bone - stronger in result to stress.

Bone Classifications

1. Long Bones - Longer than wide. Bodily movement in one direction. Levers acted upon by muscles. Ex. Humorous or Femur 2. Short Bones - Width = Length. Glide across one another in multiple directions. Ex. Tarsals and Carpals 3. Flat Bones - Usually not flat, but curved. Muscle attachment and protection of soft organs. Ex. Sternum and Cranial Ribs 4. Irregular Bones - Everything else. Ex. Vertebrae and Ethmoid 5. Sesamoid Bone - "Sesame Seed" Develop in tendons in response to friction. Vary amongst individuals after birth. Ex. Patella and Pisiform

6 Functions of skeletal system

1. Support - structural framework and point of attachment 2. Physical Protection - brain, spinal cord, internal organs 3. Movement - anchor for skeletal muscles 4. Electrolyte Balance - Ca+2 and PO-4 storage 5. Hematopoiesis - Production of blood in red bone marrow. WBC (immunity) and RBC (gas transport) 6. Triglyceride Storage - yellow bone marrow

What is the physiologic significance of bone being a composite?

A composite is made up of multiple compounds that provide different benefits that counteract and minimize the negatives of each individual compound. The organic matter in the bone matrix provides flexibility to counteract the brittleness of the inorganic minerals, while the minerals provide sturdiness to counteract the organic matter. This makes bone a composite that is strong, capable of resisting compression, and resilience to stressors.

Composite

A compound that is made up of multiple compounds - the negatives counteract each other and the final product is stronger.

Mesenchyme

A loosely organized, mainly mesodermal embryonic tissue that develops into connective and skeletal tissues, including blood and lymph.

Sesamoid Bone

A small independent bone or bony nodule developed in a tendon in response to friction, typically in the hands and feet. Pisiform in wrist Vary amongst individuals

Ectopic Calcification

Abnormal calcification. Calcium likes collagen, but most tissue has calcium inhibitors that prevent the matrix from calcifying. A deficiency of this inhibitor results in the mineralization of collagen. (Ex. lungs, brain, eyes, muscles, tendons, arteries)

Cathepsin K

An enzyme secreted by osteoclasts that is capable of digesting collagen by breaking down the amino acids. Essential for resorption.

Ossesous Tissue

Bone connective tissue with a hardened matrix from minerals, calcium phosphate. Interacts with all other organ systems because it is a calcium reservoir. It contains nerves and vasculature. Continually remodels itself (bones get bigger) in response to use and stress.

Intramembranous Ossification

Bone forms directly within mesenchyme, no cartilage intermediate. ➢ Mesenchyme in the general shape of bones is the site where cartilage formation and ossification occurs (around week 6). 1. Ossification Center - Mesenchyme cells cluster and differentiate into osteogenic stem cells, which become blasts. Site of a cluster is called ossification center. Blasts secrete matrix (collagen) until they are surrounded. 2. Calcification - blasts becomes cytes in lacunae connected by canaliculi. Inorganic molecules harden OC matrix. 3. Trabeculae - ECM develops into trabeculae that fuse to form spongy bone around the blood vessels in the tissue. 4. Periosteum - mesenchyme condenses at the periphery and develops into periosteum. Eventually compact bone replaces the surface layers of the spongy bone. (P-CB-SB-CB-P)

What is the physiologic significance of hypertrophy and hyperplasia of chondrocytes for bone lengthening?

Bones length via the epiphyseal plate, which consists of layers of cartilage at various stages. Chondrocytes grow in size and in number pushing the epiphysis further away from the diaphysis. As the cartilage grows, osteoblasts produce new bone on the diaphysis side calcifying and killing the cartilage, and lengthening the shaft of the bone. It is the hypertrophy and hyperplasia of the chondrocytes that drives the lengthening of the bone.

Organic Components of Bone

Collagen (protein). Strength and resilience, resist tension, gives flexibility. BENDY

What is the physiologic significance of collagen in bone matrix?

Collagen is main organic matter in the bone matrix. Collagen provides strength, resilience, and also flexibility. It is this bendiness that counteracts the brittleness of the inorganic minerals also present in the bone matrix.

Osteon

Compact bone structural unit Lamellae: Concentric cylinders of matrix. Collagen fibers alternate directions providing strength. ➢ Interstitial Lamellae - old osteons stay around, not full circles. Lacunae: Holes in the lamellae where osteocytes live. Canaliculi: Connect lacunae allowing osteocytes to communicate Central Canal: Middle of each osteon and contains blood vessels and nerves needed for nutrients, waste removal, and for sensing tearing or tension. Perforating Canals: Perpendicularly join central canals

How could you tell if bone tissue was spongy or compact?

Compact bone tissue is made up of osteons that resemble onions because they have concentric layers of matric called lamellae. As new osteons form, the old lamellae can still be seen taking up the space between osteons. Spongy bone on the other hand resembles swiss cheese. The trabeculaes that make up spongy bone tissue form in a lattice like structure, along a bone's line of stresses, with open spaces being filled with bone marrow.

Influence of selectively destroying chondrocytes in an embryo on the probability of successful endochondral ossification.

Decrease. Chondrocytes in the cartilage model proliferate and increase in size, increasing the length of cartilage model. Chondrocytes in the center are cut off from nutrients due to calcification and they eventually die. As they die they leave behind a hole that osteoblasts deposit bone over, forming trabeculae. Endochondral ossification ends with osteoblasts depositing bone over disintegrating cartilage from the chondrocytes and osteoclasts breaking that down forming the medullary cavity

Influence of premature closing of an epiphyseal plate on an individual's height.

Decrease. The epiphyseal plate is a growth plate that allows the bones of adolescents to lengthen. New cartilage grows on the epiphyseal side of the plate, which is calcified and turned to bone on the diaphysis side of the plate, lengthening the bone and pushing the epiphyseal plate along. If this was closed early, an individual would stop growing prematurely.

Influence of eliminating vitamin C from an individual on bone remodeling.

Decrease. Vitamin C is needed for the synthesis of collagen. Bone remodeling is a balanced process by which bones change and react to various stresses. Bone of little use are broken down and removed by osteoclasts, which is balanced by the deposit of new bone by osteoblasts. To deposit new bone, osteoblasts synthesis and secrete extracellular matrix, including collagen fibers. Without vitamin C, osteoblasts would not be able to build new bone and keep up with the osteoclasts, this could lead to diseases such as Paget's disease.

Calcitonin

Decreases blood calcium. Secreted from thyroid gland. How it works: • Antagonizes PTH - Stimulates Osteoblasts and Inhibits Osteoclasts • Little effect in adults because kidneys purge excess calcium. • Children need calcitonin(bone deposit) and calcitriol(intestinal absorption) for bone growth

Hypocalcemia

Deficiency of blood calcium. Results in a more negatively charged ECF, which causes sodium channels to open more easily. This leads to an excitability of the nervous and muscular system → muscle spasms, tremors, suffocation, etc..).

Influences on Bone Growth

Dietary Chemicals - calcium, phosphate, manganese, fluorine, magnesium Vitamins - Vitamin A (stimulates blast acvitiy. Vitamin C (synthsis of collagen). Vitamin D (promotes absorption of calcium). Vitamin K and B12 (sysnthesis of protein) Hormones - GH, IGFs, TH, and insulin stimulate osteoblast cell division. Sex Hormones - maintenance of bone

Epiphysis

End part of a long bone, initially growing separately from the shaft.

How could you tell if epiphyseal cartilage was articular cartilage or the epiphyseal plate?

Epiphyseal cartilage becomes articular cartilage on the ends of the bones, at the joints. It creates a bumper for where two bones connect. The epiphyseal plate forms at the metaphysis, in between the diaphysis and the epiphysis of a bone, it functions as a growth plate in adolescents.

What would happen if the epiphyses of long bones were not enlarged?

Epiphyses are found at joint surfaces, at the ends of bones. They need to be enlarged to increase the surface area where tendons and ligaments can attach the bone. If they were not enlarged the joints would be weakened.

Hypercalcemia

Excessive blood calcium. Rare because the kidneys can get rid of excess calcium. Results in more positively charged ECF, which makes it difficult for sodium channels to open. Causes a depression of nervous and muscle system → muscle weakness, sluggish reflexes, cardiac arrest. Caused by hyperthyroidism, TB, acute renal failure.

Osteoporosis

Extensive loss of bone mass and brittleness. Individuals are at risk of fracture (hip, wrist, and vertebral column). 80% women because of cutoff from estrogen, which inhibits resorption.

Yellow Bone Marrow

Fatty marrow of long bones. As you get older, space from RBM is filled with YBM, but in times of need RBM can migrate into spaces.

What is the physiologic significance of flat bones?

Flat bones are broad and thin and serve as attachment points for muscle. Flat bones, such as the sternum, can also protect internal organ. The physiological significance of flat bones is to provide an area for muscle to attach to and to protect our soft organs, like our heart and lungs. You could also include examples of the flat bones... sternum, ribs, scapula, cranial bones.

Osteogenesis

Formation of bone in embryo Growth of bones into adulthood Remodeling of bones Repair of fractures

Soft Callus

Fracture Healing. 3 Weeks. Fibroblasts from periosteum deposit collagen and chondrocytes from periosteum produce fibrocartilage.

Hard Callus

Fracture Healing. 3-4 Months. Osteoblasts produce trabeculae and spongy bone.

Appositional Growth

Growth in width. Bone is created near periosteum by osteoblasts (widening bone) and bone is removed near endosteum by osteoclasts (widening medullary cavity).

Red Bone Marrow

Hemopoietic - produces blood. In children, it's in every bone. In adults it is found in hips, ribs, sternum, vertebrae, humerus, and femur.

Osteoclast

Huge cells concentrated in the endosteum. Side of cell that faces bone surface has a deeply folded plasma membrane (increase SA). Releases powerful lysosomal enzymes and acid that digests the protein and mineral components of the ECM.

How could you tell by looking at a skeleton if an individual had a mesenchyme as an embryo?

If the skeleton has bones, then it had mesenchyme as an embryo. All ossification processes in any embryo begin with mesenchyme forming in the shape and location of future bones and giving rise to either osteoblast stem cells or chondroblast stem cells.

What would happen if osteoclasts were more active than osteoblasts, during bone remodeling?

In bone remodeling the osteoclasts are responsible for removing bone of little use, while osteoblasts build up bone that is stressed. If osteoclasts are more active then the osteoblasts are unable to keep up and there ends up being a higher proportion of spongy bone than compact bone present resulting in weaker bones. Paget's disease

Influence of preventing ossification center formation during intramembranous ossification on the chances of having brain damage as an adult hit on the head.

Increase. Ossification centers form during intramembranous ossification as clusters of osteoblasts that secrete matrix material necessary of osseous tissue. This form of ossification is used for flat bones like the cranial bones, so without ossification centers, cranium bones could not develop to protect the brain.

Formation of bone in embryo

Intramembranous Ossification Endochondral Ossificatoin

What would happen if intramembranous ossification failed?

Intramembranous ossification is the process of building bones in the embryo from mesenchyme. It produces spongy bone that is later remodeled into compact bone and is responsible for building flat bones. If this process failed, bones such as your sternum or cranial ribs would not form.

Carpopedal Syndrome

Involuntary contraction of the hand. Caused by hypocalcemia.

Spongy Bone

Less organized bone tissue located on interior of bone. Lightweight, but strong. Forms much of the epiphysis of the internal cavity of long bones. (looks like a sponge)

Endosteum

Lines medullary cavity - Reticular CT and osteogenic cells

Achondroplastic Dwarfism

No cartilage changes. DNA mutation prevents cartilage growth. Long bones stop growing in childhood - normal torso with short limbs.

Influence of removing canaliculi on the ability for osteoclasts to communicate?

No change. Canaliculi are small channels that connect lacunae in osteons and trabeculaes. These channels allow osteocytes to communicate. Osteoclasts reside in pits they ate into the bone either at the periosteum or endosteum.

Influence of removing yellow bone marrow on the ability of the immune system to fight infection.

No change. Yellow bone marrow's main function is triglyceride storage. It is the red bone marrow that is responsible for the production of red blood cells and white blood cells that fight infection in the immune system.

Remodeling

Ongoing replacement of old bone with new bone tissue. Involves bone resorption, the removal of collagen and minerals by osteoclasts and the addition of minerals and collagen by blasts. Bone is constantly being replaced, some more than others. Distal portion of femur (knee region) is replaced every 4 months.

6 Types of Fractures

Open/Compound - Bone punctures skin Comminuted - Lots of little bits. Bone is crushed and fractured into many little pieces. Greenstick - Partial fracture. (snapping a green stick) Impacted - Force on a long bone, one of fracture is jammed into the other side of fracture. Pott - Distal end of fibula. Colles - Distal end of radius

How could you tell if you were observing osseous tissue?

Osseous tissue is a connective tissue with a hard, calcified matrix due to the presence of calcium phosphate. That also makes osseous tissue a calcium reservoir for other systems. It contains nerves, blood vessels and cells called osteocytes. Osseous tissue has to capability to remodel itself and change in response to new stresses.

What would happen if osteoblasts could not dissolve bone during appositional growth?

Osteoblasts do not dissolve bone, they build bone. Osteoclasts are responsible for dissolving bone and during appositional growth this is important because at the bone grows in width, the medullary cavity also needs to grow in width. The osteoclasts on the endosteum dissolve the bone so the chamber grows in size with the bone.

What would happen if osteoblasts were selectively destroyed from a bone?

Osteoblasts secrete collagen fibers and other substances that make up the matrix of bone tissue. Once the matrix has been secreted, the osteoblasts become osteocytes, and the matrix itself is calcified, becoming bone. Without the osteoblasts bone would not be able to form.

Periosteum

Outside compact bone. Dense irregular CT and osteoblasts for bone growth. Melds into tendons and ligaments

Epiphyseal Line

Persistent line of compact bone at the E.P. after the growth is complete and cartilage depletes in adults (gets used up).

Calcium and Phosphate Imbalance

Phosphate - nucleotides and nucleic acids. ATP. If the phosphate blood level changes, it has little effect because these areas that use phosphate are no changing very much. Calcium - Change in calcium blood can be very deleterious. Needed for neural function, muscle contraction, blood clotting

Hematopoiesis

Production of new blood.

Parathyroid Hormone (PTH)

Raises blood calcium level and it secreted for the parathyroid gland How it works: • Stimulates Osteoclasts and Inhibits Osteoblasts • Promotes calcium resorption by the kidneys • Promotes calcitriol synthesis in the kidneys

Antiresorptive Drugs

Slows progression of osteoporosis. Bisphosphonates inhibit osteoclasts. Selective Estrogen Replacement Modulators mimic estrogen.

Trabeculae

Spongy Bone structural unit

What is the physiologic significance of hypertrophy and hyperplasia of chondrocytes for endochondral ossification?

The chondrocytes in the middle of the cartilage model grow in number and in size, which eventually causes them to be cut off from nutrients causing them to die. When the chondrocytes die, they leave behind the space that is to become the primary ossification center and eventually the medullary.

What would happen if secondary ossification centers could not form during endochondral ossification?

The formation of secondary ossification centers occur in the epiphyses of the bone at the time of birth resulting in formation of spongy bone. After ossification is the formation of articular cartilage & epiphyseal plate (growth plate). Without the formation of the secondary ossification center, the rest of the steps needed for growth wouldn't be completed.

What is the physiologic significance of the skeletal system?

The skeletal system provides a structural framework and point of attachment for the human body and is an anchor for skeletal muscles, enabling movement. It physically protects the spinal cord and internal organs, such as the brain. The skeletal system also has the capacity to store calcium and phosphate ions, which are essential for neuron communication and muscle contractions throughout the body.

Osteology

The study of bone.

Paget's Disease

When osteoclasts > osteoblasts. Osteoblasts try to keep up but only form weak spongy bone that bends and fracture easily.

Endochondral Ossification

bone forms within hyaline cartilage that develops from mesenchyme. ➢ Mesenchyme in the general shape of bones is the site where cartilage formation and ossification occurs (around week 6). 1. Cartilage Model - Mesenchyme cells cluster together and form Chondroblasts. They secrete ECM producing a cartilage model surrounded by perichondrium. 2. Growth - Chondroblasts become chondrocytes and CM grows in length by cell division of chondrocytes (interstitial growth). Appositional growth is in width and is due to ECM. Surrounding ECM begins to calcify and central chondrocytes enlarge (hypertrophy) and die because they are cut off from nutrients. When they die they leave behind holes. 3. Primary Ossification Center -Nutrients enter middle of CM and cells differentiate into osteoblasts. Osteoblasts gather along outer edge of diaphysis and starts on outside works inward. (Perichondrium starts to form bone known as periosteum). OC grows as calcified cartilage disintegrates and osteoblasts deposit bone over cartilage remnants forming trabeculae. Nutrients cannot penetrate the calcified matrix, so cells in the middle start to die forming a cavity. Bone doesn't collapse because there is a 'bone collar' already formed. Bone can still be getting longer. 4. Medullary Cavity - As POC grows towards ends of bone, osteoclasts break down some of the newly formed spongy bone trabeculae, creating the medullary cavity. 5. Secondary Ossification Center - Formed in epiphyses (around time of birth). Bone formation is similar to POC, except spongy bone remains, no medullary cavities form, and ossification goes from in to out. 6. Articular Cartilage - The hyaline cartilage that covers the epiphyses becomes articular cartilage. Prior to adulthood, a line of hyaline cartilage remains between diaphysis and epiphysis (epiphyseal growth plate).