Lecture 11 - Bone Physiology

Front 1

What four tissues comprise the skeletal system?

Back 1

Bones, ligaments, tendons, and cartilage

Front 2

Define ligaments

Back 2

bands of tough, fibrous collagen and elastin that connect bones to bones

Front 3

Define tendons

Back 3

rigid cords of tissue containing mostly collagen that secure muscle to bone

Front 4

Define cartilage

Back 4

connective tissue found in many parts of the body produced by chondrocytes; acts as a cushion between the bones of joints

Front 5

What is the difference between Axial and Appendicular Skeleton?

Back 5

Axial: skull and supporting bones, vertebra and ribs, 80 bones

Appendicular: limbs: 126 bones

Front 6

What is the approximate percentage of overall weight that is comprised by bones?

Back 6

~14%

Front 7

Name 5 functions of the skeletal system:

Back 7

1) support: hard framework, anchors organs

2) protection: surrounds organs such as brain, spinal cord, lungs

3) movement: provides framework for muscle attachment

4) storage: minerals (Ca and phosphorus) and some lipids are stored within bone

5) blood cell formation: occurs in the bone marrow

Front 8

What are bones primarily comprised of? What are the general properties of bone?

Back 8

Collagen protein and inorganic Hydroxyapatite

Also living cells

Strong yet light

Front 9

What is the general anatomy of bone?

Back 9

Compact bone is outside, whereas inside is spongy bone (lots of space occupied by bone marrow cells) and the medullary cavity (hollow space filled with yellow marrow)

Front 10

What is yellow marrow comprised of?

Back 10

Mostly fat cells and hematopoietic cells

Front 11

Bone is comprised of two things, what are they?

Back 11

Matrix and cells

Front 12

What is the matrix comprised of?

Back 12

Organic (collagen and a couple of other things) and inorganic (calcium and phosphorus)

Front 13

What is the organic matrix primarily comprised of?

Back 13

Provides strength and flexibility (~35% of adult bone mass)

Front 14

What is the inorganic portion of the matrix comprised of?

Back 14

Hydroxyapatite (an insoluble salt of calcium and phosphorus); provides stability ~65% of adult bone mass

Front 15

What are the remaining matrix components?

Back 15

Small amounts of magnesium, sodium, potassium, bicarbonate act as 'mortar' to bond Ca and phosphorus.

Also, 25% of adult bone mass is attributed to water.

Front 16

The bone is also an inorganic mineral Reservoir. What minerals and how much?

Back 16

> 99% of body's calcium stored within bones and teeth; ~85% of body's phosphorus stored in bone

Hydroxyapatite is Ca(10)-(PO4)(6)-(OH)2. Important to maintain calcium in diet.

Front 17

SKIP There are other bone associated proteins like Osteonectin. What role does this play?

Back 17

an acidic extracellular matrix glycoprotein that plays a vital role in bone mineralization, cell-matrix interactions, and collagen binding

Front 18

SKIP Another one is Osteocalcin. What does this do?

Back 18

Hormone that is pro-osteoblastic (bone-building); also stimulates insulin release.

Front 19

What are some common bone cells?

Back 19

Fibroblasts, osteoclasts, osteoblasts, endothelial cells, osteocytes

Front 20

What covers the outside of the bone?

Back 20

Periosteum, dividing into inner and outer layers

Front 21

What do osteoblasts and osteoclasts do?

Back 21

Osteoblasts - bone forming cells

Osteoclasts - bone resorbing cells

Front 22

What are lining cells?

Back 22

They line entire surface of bone.

Front 23

What are osteocytes?

Back 23

They are mature bone cells.

Front 24

Osteoblasts are responsible for which three things in forming bone matrix cells?

Back 24

Synthesis, deposition and mineralization

Front 25

What do osteoblasts also produce?

Back 25

Enzymes and osteoid (a mixture of collagen and proteins) to which hydroxyapatite binds

Front 26

Where are osteoblasts primarily found?

Back 26

At the surfaces of mature bones.

Front 27

What are osteoblasts regulated by?

Back 27

Express hormone receptors (vitamin D, estrogen, and parathyroid hormone)

Front 28

Discuss osteoclasts in detail

Back 28

are large, multi nucleated cells that eat bone.

function in self-created acidic environment

share lineage with blood cells, especially macrophages

mature osteoclasts form from fusion of precursors

Front 29

Besides bone eating, what are osteoclasts important for?

Back 29

blood calcium regulation

Front 30

Bone lining cells used to be what?

Back 30

Osteoblasts that have flattened

Front 31

What are bone lining cells responsible for?

Back 31

Immediate release of calcium from the bone if blood calcium is too low

Front 32

What do bone lining cells protect bone from?

Back 32

chemicals in the blood that dissolve crystals (such as pyrophosphate)

Front 33

What types of receptors do bone lining cells express?

Back 33

Express receptors for hormones and factors that initiate bone remodeling

Front 34

What main function do osteocytes serve?

Back 34

Mechanosensor cells that control the activity of osteoblasts and osteoclasts; secrete various growth factors that activate lining cells or osteoblasts

Front 35

Long branches of osteocytes allow for what?

Back 35

Intercellular contact

Front 36

Picture of bone cell lineage

Back 36

Front 37

Bone cells arise from which precursor cells? What are precursor cells?

Back 37

Bone marrow stem cells

Front 38

Osteoblasts and osteocytes arise from which stem cell?

Back 38

Mesenchymal stem cells

Front 39

Osteoclasts arise from which stem cells? What are these same stem cells used for?

Back 39

Hematopoietic stem cells - the same stem cells that blood cells derive from

Front 40

What type of structure does spongy bone have?

Back 40

'Spongy' honeycomb-like structure that forms the inner layer of bone tissue

Front 41

What about compact? AKA?

Back 41

AKA cortical bone, which is dense and compact, and forms the outer shaft of the bone

Front 42

Compact bone is composed of individual units called _______ which are what?

Back 42

Osteons - concentric rings of bone tissue with blood vessels and nerves in the center

Front 43

How do the concentric rings work?

Back 43

Within an osteons, collagen fibres and mineral salts align and run in opposite directions from layer to the next. There are many concentric tubes; each tube is a lamella. Having multiple layers prevents cracks from spreading

Front 44

What properties does spongy bone have?

Back 44

Lighter and less dense than compact bone. This is also bone material but interspersed with lots of spaces.

Front 45

What is spongy bone found?

Back 45

At the core of most flat and irregular bones; also at the ends of longs bones

Front 46

What is the general structure of spongy bone?

Back 46

lamellae form 'sheets'

Front 47

Spongy bone cannot handle much _____.

Back 47

Strain.

Front 48

Spongy bone contains ________.

Back 48

Red marrow.

Front 49

Spongy bone re-aligns with ________.

Back 49

Stress.

Front 50

What types of cells comprise the periosteum?

Back 50

Dense connective tissue layer cover

Front 51

Periosteum does what in addition to covering bone?

Back 51

Contains nociceptors (nerve endings) and serves as site of attachment for muscle and tendon

Front 52

What is the neonate/infant skeleton comprised of?

Back 52

Cartilage, not bone. Cartilage is produced by specialized cells called chondrocytes that make extracellular matrix composed of collagen fibers, elastin and proteoglycans.

Front 53

What happens during growth?

Back 53

Bone replaces cartilage, and bone formation outpaces bone resorption.

Front 54

How do osteoclasts eat bone?

Back 54

Secrete onto bone surface a lot of enzymes and acid which breaks down the region where they are, to be reabsorbed by the blood

similar to phagocytes in a way

Front 55

Why does resorption occur at all during growth?

Back 55

Need some resorption to mobilize calcium

Front 56

Where does ossification first begin?

Back 56

In the spongy bone

Front 57

What are some growth hormone effects?

Back 57

Indirectly promotes growth by stimulating liver production of insulin-like growth factors (IGFs)

- act directly on bone and soft tissues to bring about most growth-promoting actions

- stimulate protein synthesis, cell division, and lengthening and thickening of bones

Front 58

Which part of long bones express receptors and for what?

Back 58

The epiphyseal growth plate of long bones express receptors for many peptide growth hormones (IGFs, FGFs, TGF-beta).

the whole process is highly regulated.

Front 59

What happens during dwarfism?

Back 59

most common cause of dwarfismautosomal dominant - not sex-linked; you only need one mutation (one from both parents) - if you get just one bad copy, you're in trouble.

Gly380Arg always on, what you get is premature conversion of growth plate into bone; essentially bone is created way too fast .....not given enough time to grow (premature conversion of the growth plate into bone)

Front 60

What are some ways to increase bone resorption? Decrease?

Back 60

PTH, thyroid hormone, vitamin D metabolites, cortisol

calcitonin, gonadal steroids

Front 61

What are some ways to increase bone formation? Decrease?

Back 61

Growth hormone, gonadal steroids

cortisol

Front 62

Where is 99% of the body's calcium located?

Back 62

In the extracellular matrix; the calcified matrix of bone

Front 63

Where is 0.1% of calcium located?

Back 63

In the ECF

Acts as cement for tight junctions, role in myocardial and smooth muscle contractions, neurotransmitter release at synapses, role in excitability of neurons, cofactor in coagulation cascade

Front 64

Where is 0.9% stored?

Back 64

Intracellular, either ER or SR

Acts as signal in second messenger pathways; plays a role in muscle contract

Front 65

Calcium homeostasis in the blood picture

Back 65

Front 66

Important slide on calcium balance in the body

Back 66

Front 67

Roughly how much calcium is needed to be absorbed daily?

Back 67

200 mg

Front 68

Describe very general pathway

Back 68

Calcium > small intestine > blood or feces > blood to bone, to cells, or to kidneys > excess calcium secreted in urine

Front 69

How is calcium uptake/secretion controlled with respect to blood-bone?

Back 69

Bone calcium uptake: calcitonin

bone calcium secretion to blood: PTH (parathyroid hormone), Calcitriol, Cortisol

Front 70

How is calcium uptake/secretion controlled with respect to blood-cells?

Back 70

Into cells: electrochemical gradient

Into blood: active transport

Front 71

How is calcium uptake/secretion controlled with respect to blood-kidney?

Back 71

Into kidney: passive filtration

Out of kidney: Increase PTH or decrease calcitonin

Front 72

What's the deal with PTH?

Back 72

Essential primary regulator of Ca. Raises free plasma Ca levels by:

1) mobilizing calcium from bone

2) enhancing renal reabsorption of Ca

3) indirectly increases intestinal absorption of calcium (facilitates activation of VitD to stimulate Ca and PO4 absorption from intestine

Front 73

What is the general calcium/PTH feedback mechanism?

Back 73

Plasma Ca decreases > signals parathyroid glands > PTH increases > Plasma Ca increases (negative feedback to parathyroid glands)

Front 74

How fast acting is PTH?

Back 74

Rapid mechanism; occurs within minutes; stimulates bone resorption by pre-existing osteoclasts (which are sitting on bone waiting); inhibits collagen synthesis by osteoblasts; at kidneys, Ca reabsorption is stimulated

Front 75

Not a super important slide

Back 75

Front 76

What is Calcitriol?

Back 76

Vitamin D3

Front 77

How is calcitriol obtained?

Back 77

Synthesized from Vitamin D that has been obtained: a) through diet, or made in skin by the action of sunlight on precursors made from acetyl CoA

Front 78

What does calcitriol do?

Back 78

Reinforces the plasma Ca increasing effect of PTH by enhancing Ca uptake from the small intestine; also mobilizes Ca from bone and facilitates renal reabsorption of calcium

Front 79

A picture of the whole process

Back 79

Front 80

What are the four general steps in bone healing?

Back 80

Initial inflammatory response

spongy bone forms in first few days

blood vessels re-grow and spongy bone hardens

full healing takes 1-2 months

Front 81

Describe arthritis

Back 81

loss of cartilage; 90% of population have some osteoarthritis by age 40; over 100 forms including joint pain; chronic inflammation of joints; can be a normal age-dependent change; may also be pathological; age-related changes; decreased blood supply; trauma; loss of cartilage

Front 82

Age related atrophy - what is this?

Back 82

A decrease in bone mass, strength and bone resistance due to calcium loss

Front 83

What is the difference between osteoporosis and osteopenia?

Back 83

Osteoporosis - low bone mass and deterioration of bone tissue; Osteopenia is reduced bone mineral density

Front 84

More details on osteoporosis

Back 84

metabolic bone disorder resulting in a decline in bone density - bone resorption > bone deposition

Increased risk for fracture - vertebrae, hip, wrists

Front 85

What is osteoporosis attributed to?

Back 85

genetic and environmental factors: smoking, lack of exercise; loss of muscle mass; hormonal variations. associated after menopause; reduced bone mass begins by age 30 associated with a fall in estrogen level

Front 86

What is required for healthy bones?

Back 86

large amount of calcium, phosphorus, some fluoride, magnesium, iron, manganese; vitamin A helps osteoblasts function properly; vitamin C supports manufacture of collagen and differentiation of osteoblasts into mature osteocytes; vitamins K and B12 are needed for protein synthesis

Front 87

What about vitamin D?

Back 87

Important - promotes absorption of Ca and phosphorus from intestines; essential for bone mineralization, growth and repair

Front 88

Bone therapies

Back 88

Free vascular bone graft = bone + vessels

Bone auto and allografts (from self or cadavers)

Bone substitutes – rather than from cadaver origin

Stem cell therapies (enhance bone formation)