A&P Quiz 3

3 types of cartilage

Hyaline

• Provides support, flexibility, and resilience

• Most abundant type

• Collagen fibers

• Articular (joints), costal (ribs), respiratory (larynx), nasal cartilage (nose tip)

Elastic

• Similar to hyaline, but contains elastic fibers

• External ear and epiglottis

Fibrocartilage

• Thick collagen fibers

• Has great tensile strength

• Menisci of knee, intervertebral discs

Growth of cartilage

Cartilage grows in 2 ways:

Appositional growth - cartilage-forming cells in perichondrium secrete matrix against external face of existing cartilage.

• New matrix laid down on surface of cartilage.

Interstitial growth - chondrocytes within lacunae divide and secrete new matrix, expanding cartilage from within

• New matrix made within cartilage

Calcification of cartilage occurs during normal bone growth in youth, but can also occur in old age

• Hardened cartilage is not the same as bone

Functions of bones

Mechanical functions

1. Support - for body and soft organs

2. Protection - of brain, spinal cord, and vital organs

3. Movement - levers for muscle action

Warehouse

4. Mineral and growth factor storage - calcium and phosphorus, and growth factors reservoir

5. Blood cell formation - hematopoiesis occurs in red marrow cavities of certain bones

6. Fat storage - fat, used for an energy source, is stored in bone cavities

7. Hormone production - osteocalcin secreted by bones helps to regulate insulin secretion, glucose levels, and metabolism. Does not affect the bone directly.

Classification of bones

Long bones

• Longer than they are wide

• Limb bones

Short bones

• Cube-shaped bones (in wrist and ankle)

• Sesamoid bones form within tendons (ex patella). Vary in size and location between individuals

Flat bones

• Thin, flat, slightly curved

• Sternum, scapulae, ribs, most skull bones

Irregular bones

• Complicated shapes

• Vertebrae and hip bones

bone structure slide 12

Gross anatomy - compact and spongy bone

Compact bone - dense outer layer on every bone that appears smooth and solid

Spongy bone - made of of a honeycomb of small, needle like or flat pieces of bone called trabeculae

• Open spaces between trabeculae are filled with red or yellow bone marrow

Gross anatomy - structure of short, irregular, and flat bones

• Thin plates of spongy bone (dipole) covered by compact bone

• Compact bone sandwiched between connective tissue membranes:

  • Periosteum covers outside of compact bone

  • Endosteum covers inside of compact bone

• Bone marrow is scattered throughout spongy bone; no defined marrow cavity

• Hyaline cartilage covers area of bone that is part of a movable joint

Gross anatomy - structure of a long bone

• Structure of typical long bone

  • All long bones have a shaft (diaphysis), bone ends (epiphyses), and membranes

    • Diaphysis: tubular shaft that forms long axis of bone

      • Consists of compact bone surrounding central medullary cavity that is filled with yellow marrow in adults

    • Epiphyses: ends of long bones that consist of compact bone externally and spongy bone internally

      • Articular cartilage covers articular (joint) surfaces

    • Between diaphysis and epiphysis is epiphyseal line

      • Remnant of childhood epiphyseal plate where bone growth occurs

gross anatomy - membranes

Periosteum - white, double-layered membrane that covers external surfaces except joints

• Fibrous layer - outer layer consisting of dense irregular connective tissue and perforating fibers (Sharpey’s fibers) that secure the periosteum to the underlying bone matrix

• Osteogenic layer - inner layer abutting bone with osteogenic stem cells that give rise to most bone cells

Endosteum - connective tissue membrane covering internal bone surface and trabeculae of spongy bone

• Lines canals that pass through compact bone

• Like periosteum, contains osteogenic cells that can differentiate into other bone cells

Gross anatomy - hematopoietic tissue and bone markings

Hematopoietic tissue in bones

• Red marrow is found within trabecular cavities of spongy bone and dipole of flat bones, such as sternum

  • In newborns, medullary cavities and all spongy bone contain red marrow

  • In adults, red marrow is located in heads of femur and humerus, but most active areas of hematopoiesis are flat bone dipole and some irregular bones (such as the hip bone, vertebral bodies)

Bone markings

• Sites of muscle, ligament, and tendon attachment on external surfaces

• Areas involved in joint formation or conduits for blood vessels and nerves

• Three types of markings:

  • Projection: outward bulge of bone

    • May be due to increased stress from muscle pull or is a modification for joints

  • Depression: bowl- or groove-like cut-out that can serve as passageways for vessels and nerves, or plays a role in joints

  • Opening: hole or canal in bone that serves as passageways for blood vessels and nerves

Microscopic anatomy of bone - cells of bone tissue

1) Osteogenic cells - mitotically active (divide) stem cells in periosteum and endosteum

• Also called osteoprogenitor cells

• When stimulated, they differentiate into osteoblasts or bone-lining cells

• Some remain as osteogenic stem cells

2) Osteoblasts - bone-forming cells that secrete unmineralized bone matrix called osteoid

• Osteoid is made up of collagen and calcium-binding proteins

• Collagen makes up 90% of bone protein

• Osteoblasts are actively mitotic

3) Osteocytes - mature bone cells in lacunae that no longer divide

• Maintain bone matrix and act as stress or strain sensors

  • Respond to mechanical stimuli such as increased force on bone or weightlessness

  • Communicate information to osteoblasts and osteoclasts to remodel the bone

4) Bone-lining cells - flat cells on bone surfaces, help maintain matrix (along with osteocytes)

• On external bone surface, lining cells are called periosteal cells

• On internal surfaces, they are called endosteal cells

5) Osteoclasts - derived from hematopoietic stem cells that also become macrophages

• Giant, multinucleate cells function in bone resorption (breakdown of bone)

• Cells have ruffled membrane to increase surface area for enzyme degradation of bone

Microscopic anatomy of compact bone - osteon, lamellae, central canal, perforating canals, lacunae, canaliculi, osteoblasts, interstitial lamellae, circumferential lamellae

Compact bone (also called lamellar bone) consists of:

Osteon (Haversion system)

• Structural unit of compact bone

• Elongated cylinder parallel to the long axis of bone

  • Acts as tiny weight-bearing pillars

• Made of several rings of bone matrix called lamellae

• Lamellae contain collagen fibers that run in different directions in adjacent rings

  • Withstands stress and resist twisting (torsion)

  • Bone salts are found between collagen fibers

Canals and canaliculi

• Central (haversion) canal runs through core of osteon

• Perforating (Volkann’s) canals - canals lined with endosteum that occur at right angles to central canal

  • Connect blood vessels and nerves of periosteum, medullary cavity, and central canal

• Lacunae - small cavities that contain osteocytes

• Canaliculi - hairlike cannals that connect lacunae to each other and to central canal

  • Allow communication between all osteocytes of osteon (nutrients and waste transport)

• Osteoblasts that secrete bone matrix maintain contact with each other and osteocytes via cell projections with gap junctions

Interstitial and circumferential lamellae

• Interstitial lamellae

  • Lamellae that are not part of osteon

  • Some fill gaps between forming osteons; others are remnamts of osteons cut by bone remodeling

• Circumferential lamellae

  • Just deep to periosteum, but superficial to endosteum, these layers of lamellae extend around entire surface of diaphysis

  • Help long bone to resist twisting

Spongy bone

• Appears poorly organized but is actually organized along lines of stress to help bone resist stress

• Trabeculae, like cables on a suspension bridge, confer strength to bone

  • No osteons are present, but do contain irregularly arranged lamellae and osteocytes interconnected by canaliculi

  • Capillaries in endosteum supply nutrients

Chemical composition of bone - organic and inorganic

Organic components

• Includes osteogenic cells, osteoblasts, osteocytes, bone-lining cells, osteoclasts, and osteoid

  • Osteoid is 1/3 of organic bone matrix, secreted by osteoblasts

    • Consists of ground substance and collagen fibers, which contribute to high tensile strength and flexibility of bone

    • Resilience of bone is due to sacrificial bonds in or between collagen molecules that stretch and break to absorb shocks and prevent fractures

    • Bonds re-form

Inorganic components

• Hydroxyapatites (mineral salts)

  • Makeup 2/3 of bone by mass

  • Consist mainly of calcium phosphate crystals in and around collagen fibers

  • Responsible for hardness and resistance to compression

• Bone is half as strong as steel in resisting compression and as strong as steel in resisting tension

• Lasts long after death bc of mineral composition

Bone development - ossification + types

• Ossification (osteogenesis) - the process of bone tissue formation

  • Formation of bony skeleton begins in month 2 of fetal development

  • Postnatal bone growth occurs until early adulthood

  • Bone remodeling and repair are lifelong

• From week 8, fibrous membranes and hyaline cartilage of fetal skeleton are gradually replaced with bone tissue

Types:

• Endochondral ossification

  • Bone forms by replacing hyaline cartilage

  • Bones are called cartilage (endochondral bones)

  • Form most of skeleton

• Intramembranous ossification

  • Bone develops from fibrous membrane

  • Bones are called membrane bones

Formation of the bony skeleton - endochondral ossification and main steps

Endochondral ossification

• All bones inferior to base of skull, except clavicles

• Uses previously formed hyaline cartilage models

• Requires breakdown of cartilage prior to ossification

• Begins at primary ossification center in center of shaft

  • Blood vessels infiltrate perichondrium, converting it to periosteum

  • Mesenchymal cells specialize into osteoblasts

5 main steps:

1. Bone collar forms around diaphysis of cartilage model

2. Central cartilage in diaphysis calcifies, then develops cavities

3. Periosteal bud invades cavities, leading to formation of spongy bone

4. Diaphysis elongates, and medullary cavity forms; secondary ossificaiton centers appear in epiphyses

5. Epiphyses ossify; hyaline cartilage remains only in epiphyseal plates and articular cartilages

Formation of the bony skeleton - intramembranous ossification and main steps

Intramembranous ossification

• Begins with fibrous connective tissue membranes formed by mesenchymal cells

• Forms frontal, parietal, occipital, temporal, and clavicle bones

4 major steps:

1. Ossification centers are formed when mesenchymal cells cluster and become osteoblasts

2. They secrete osteoid, which is then calcified

3. Trabeculae are laid down between blood vessels

4. Lamellar bone replaces woven bone under the periosteum (compact bone) and red marrow appears

Postnatal bone growth

• Long bones grow lengthwise by interstitial (longitudinal) growth of epiphyseal plate

• Bones increase thickness through appositional growth

• Bones stop growing during adolescence

  • Some facial bones continue to grow slowly through life

• Growth is in length and thickness

Growth in length of bones

• Interstitial growth requires presence of epiphyseal cartilage in the epiphyseal plate

• Epiphyseal plate maintains constant thickness

  • Rate of cartilage growth on one side balanced by bone replacement on other

• Epiphyseal plate consists of 5 zones:

1. Resting (quiescent) zone

2. Proliferation (growth) zone

3. Hypertrophic zone

4. Calcification zone

5. Ossification (osteogenic) zone

Growth in Length of Long Bones

1) Resting quiescent zone

• Area of cartilage on epiphyseal side of epiphyseal plate that is relatively inactive

2) Proliferation (growth) zone

• Area of cartilage on diaphysis side of epiphyseal plate that is rapidly dividing

• New cells formed move upward, epiphysis is pushed away, causing lengthening

3) Hypertrophic zone

• Area with older chondrocytes closer to diaphysis

• Cartilage lacunae enlarge and erode, forming interconnecting spaces

4) Calcification zone

• Surrounding cartilage matrix calcifies; chondrocytes die and deteriorate

5) Ossification zone

• Chondrocyte deterioration leaves long spicules of calcified cartilage

• Spicules are then eroded by osteoclasts and covered with new bone

• Ultimately replaced with spongy bone

• Medullary cavity enlarges as spicules are eroded

Growth in length of long bones - the end

• Near end of adolescence, chondroblasts divide less often

• Epiphyseal plate thins, then is replaced by bone

• Epiphyseal plate closure occurs when epiphysis and diaphysis fuse - connected at the epiphyseal line

• Bone lengthening ceases

  • Females: occurs around 18 years of age

  • Males: occurs around 21 years of age

Growth in width (thickness)

• Appositional growth (growth in width) can occur throughout life

• Bones thicken in response to increased stress from muscle activity or added weight

• Osteoblasts beneath periosteum secrete bone matrix on external bone

• Osteoclasts remove bone on endosteal surface

• Usually more building up than breaking down which leads to thicker, stronger bone that is not too heavy

Hormonal regulation of bone growth

• Growth hormone: most important hormone in stimulating epiphyseal plate activity in infancy and childhood

• Thyroid hormone: modulates activity of growth hormone, ensuring proper proportions

• Testosterone (males) and estrogen (females) at puberty: promote adolescent growth spurts

  • End of growth by inducing epiphyseal plate closure

• Excesses or deficits of any hormones cause abnormal skeletal growth

Bone remodeling, bone resorption, bone deposit

Bone remodeling

• About 5–7% of bone mass is recycled each week

• Bone remodeling consists of both bone deposit and bone resorption

  • Occurs at surfaces of both periosteum and endosteum

Bone resorption

• Resorption is function of osteoclasts 

  • Dig depressions or grooves as they break down matrix

  • Secrete lysosomal enzymes and acids that digest matrix

  • Acidity converts calcium salts to soluble forms

• Osteoclasts also phagocytize demineralized matrix and dead osteocytes

  • Once resorption is complete, osteoclasts undergo apoptosis

• PTH (parathyroid hormone) activates osteoclasts

Bone deposit

• New bone matrix is deposited by osteoblasts, stimulated mechanically, and by availability of materials (proteins, Ca²⁺ and phosphate ions)

Control of remodeling

• Remodeling occurs continuously but is regulated by genetic factors and two control loops: hormonal and mechanical

Hormonal controls

• Negative feedback loop that controls blood Ca 2+ levels

• Free (ionic) calcium (Ca 2+) is required for vital processes

• 99% of 1200-1400 grams of calcium are found in bone

• Intestinal absorption of Ca 2+ requires vitamin D

• Parathyroid hormone (PTH) - produced by parathyroid glands in response to low blood calcium levels

  • Stimulates osteoclasts to resorb bone

  • Calcium is released into blood, raising levels

  • PTH secretion stops when homeostatic calcium levels are reached

• Calcitonin - produced by parafollicular cells of thyroid gland in response to high levels of blood calcium levels

  • Effects are negligible, but at high pharmacological doses it can lower blood calcium levels temporarily

Clinical - homeostatic imbalance

• Even minute changes in blood calcium levels can cause severe neuromuscular problems

  • Hypocalcemia: low levels of calcium cause hyperexcitablility

  • Hypercalcemia: high levels of calcium cause nonresponsiveness

    • Sustained high blood calcium levels can lead to deposits of calcium salts in blood vessels or kidneys and formation of kidney stones

•  Hormonal controls (cont.)

  • Other hormones play a role in bone density and turnover

    • Glucocorticoids (cortisone) - increase osteoclast activity

    • Sex hormones (also steroids) - decrease (favor deposition)

Control of modeling - mechanical + wolf’s law

Response to mechanical stress

• Bones react to stresses, like when weight bears on them or muscles pull on them

• Wolf’s law states that bones grow or remodel in response to demands placed on them

  • Stress usually tends to bend bones

  • Bending compresses one side, stretches other side

  • Diaphysis is thickest where bending stresses are greatest

Wolf’s law also explains:

• Handedness (right- or left-handed) results in thicker and stronger bone of the DOMINANT upper limb 

• Curved bones are thickest where most likely to buckle

• Trabeculae form trusses along lines of stress

• Large, bony projections occur where heavy, active muscles attach

  • Weight lifters have enormous thickenings at muscle attachment sites of most used muscles

• Bones of fetus and bedridden people are featureless because of lack of stress on bones

Different roles of hormonal and mechanical controls

Hormonal controls determine if and when remodeling occurs in response to changing blood calcium levels, but mechanical stress determines where it occurs

Fracture classification

Fractures are breaks

• During youth, most fractures result from trauma

• In old age, most result from weakness of bone due to bone thinning

Fracture classification

• Position of bone fragments after fracture

  • Nondisplaced - retain normal position

  • Displaced - out of alignment

• Completeness of break

  • Complete - broken all the way through

  • Incomplete - not broken all the way through

• Whether skin is penetrated

  • Open (compound) - skin is penetrated

  • Closed (simple) - skin is not penetrated)

• Can also be described by location of fracture, external appearance, and nature of break

Common types of fractures

The old

• Comminuted - bone fragments into 3+ pieces; common in the aged, whose bones are more brittle

• Compression - bone is crushed; common in porous bones (ie osteoporotic bones) subjected to extreme trauma, as in a fall

The young

• Spiral - ragged break occurs when excessive twisting forces are applied to a bone; common sports fracture

• Epiphyseal - epiphysis separates from the diaphysis along the epiphyseal plate; tends to occur where cartilage cells are dying and calcification of the matrix is occurring

Children

• Depressed - broken bone portion is pressed inward; typical of skull fracture

• Greenstick - bone breaks incompletely, much in the way a green twig breaks. Only one side of the shaft breaks; the other side bends. Children

Fracture treatment and repair

• Treatment involves reduction, the realignment of broken bone ends

  • Closed reduction - physician manipulates to correct position

  • Open reduction - surgical pins or wires secure ends

• Immobilization of bone by cast or traction is needed for healing

  • Time needed for repair depends on break severity, bone broken, and age of patient

4 major stages of repair:

1) Hematoma formation

• Torn blood vessels hemorrhage, forming mass of clotted blood called a hematoma 

• Site is swollen, painful, and inflamed

2) Fibrocartilaginous callus formation

• Capillaries grow into hematoma and bring fibroblasts 

• Fibroblasts secrete collagen fibers to span break and connect broken ends 

• Cells (fibroblasts and chondroblasts) begin reconstruction of bone

  • Create cartilage matrix of repair tissue

• This mass of repair tissue is called fibrocartilaginous callus

3) Bony callus formation

• Osteoblasts form spongy bone (trabeculae) within matrix of fibrocartilaginous callus

• Callus is converted to bony (hard) callus of spongy bone (about 2 months)

4) Bone remodeling

• Begins during bony callus formation and continues for months

• Excess material on outside and inside the bone is removed

• Compact bone is laid down to reconstruct shaft walls

• Final structure resembles original structure, responds to same mechanical stressors

Bone disorders

• Imbalances between bone deposit and bone resorption underlie nearly every disease that affects the human skeleton.

• Three major bone diseases:

  • Osteomalacia and rickets

  • Osteoporosis

Osteomalacia - bones are poorly mineralized

• Osteoid is produced, but calcium salts not adequately deposited

• Results in soft, weak bones, pain upon bearing weight

Rickets - osteomalacia of children

• Results in bowed legs and other bone deformities because bone ends are enlarged and abnormally long

Causes for both: vitamin D deficiency or insufficient dietary calcium

Osteoporosis - group of diseases in which bone resorption exceeds deposit

• Matrix remains normal, but bone mass declines

  • Spongy bone of spine and neck of femur most susceptible

    • Vertebral and hip fractures common

• Risk factors for osteoporosis

• Most often aged, postmenopausal women

  • Affects 30% of women aged 60–70 years and 70% of women by age 80

  • Estrogen plays a role in bone density, so when levels drop at menopause, women run higher risk

  • Men are less prone due to protection by the effects of testosterone (which last throughout life)

• Additional risk factors for osteoporosis:

  • Insufficient exercise

  • Diet poor in calcium and protein

  • Smoking, Genetics, Hormone-related conditions

  • Hyperthyroidism

  • Diabetes mellitus

  • Consumption of alcohol or certain medications

Osteoporosis - treatment

Traditional treatments

• Calcium

• Vitamin D supplements

• Weight-bearing exercise

• Hormone replacement therapy (estrogens) – discouraged, now coming back??

  • Slows bone loss but does not reverse it

  • Controversial because of increased risk of heart attack, stroke, and breast cancer. NOW idea is until 65 it's OK!

Recent drugs for osteoporosis are osteoclast inhibitors:

• Bisphosphonates: decrease osteoclast activity and number

  • Partially reverse osteoporosis in spine

• Denosumab 

  • Monoclonal antibody shown to reduce fractures in men with prostate cancer

  • Improves bone density in elderly by preventing activation of osteoclasts by osteoblasts