lecture 3 & 4 Flashcards
Physiology of Bone Metabolism
define osteoblasts
promote bone formation
what are osteoclasts?
promote bone resorption and are found on the growth surfaces of bone
what are osteocytes?
play a role in the transfer of mineral form the interior of bone to the growth surfaces
what is bone?
consists of an extracellular matrix composed of proteins and hydroxyapatite crystals with a small population of cells.
what does the bone matrix provide?
strength and stability
what is hard bone called?
cortical bone
what is soft/spongy bone called?
trabecular bone
once osteoblasts have performed their major job in bone growth what happens to them?
they become osteocytes
describe the life of a “bone cell”
starts out as an osteogenic cell to become an osteoblast to form bone matrix and then once complete it becomes an osteocyte maintaining bone tissue.
what is significant about the shape of the osteoclast?
large, multinucleate and have ruffled borders
what is the idea of the osteoclast?
sits on bony surface and seals itself using the ruffled borders to release enzymes onto bone surface and begins chewing up bone to release inorganic ions to release into circulation and osteoblast comes back to remodel that part of the bone
what is the osteoid?
organic part of the matrix
what are some facts about the osteoid?
makes up 1/3 of the matrix
includes proteoglycan, glycoproteins, & collagen -which contributes to flexibility and tensile strength of bone to resist stretching and twisting
why is collagen important?
it contributes to flexibility and tensile strength of bone to resist stretching and twisting. Multiple types: collagen type I,II,III.
where and what is type I collagen?
found in the bone
so how can we relate collagens to a cut in the skin?
collagen type III comes into the area and needs to be replaced by type II and if not replaced, colloids develop - tumor because of the production of so much collagen type III because it was not replaced
what type of collagen is cartilage?
collagen type II
what type of collagen is bone?
collagen type 1
what is ossification?
the makeup of bone. So it starts with gathering of osteoblasts from the center or center of ossification and move outward to make a bone
what are the two types of ossification?
intramembraneous and endochondral ossification
what types of bones are made from intramembraneous ossification?
flat bones of the skull except those at the base, clavicles.
since flat and long bones are made via intramembraneous ossification, what bone is the exception?
clavicle
intramembraneous ossification growth pattern?
it starts from the center and moves outward. As the osteoblasts mature, they become osteocytes and become like a mesenchyme added to the periosteum like a cover for the bone
how does endochondral ossification work?
bones are first modeled in hyaline cartilage eventually replaced by bone tissue and the process uses hyaline cartilage as the pattern for bone construction
what is found in the bones like the long bones that allows for them to grow, this is why we are all different heights?
epiphyseal plate
what is the epiphyseal plate?
a hyaline cartilage plate in the metaphysics at each end of the long bone that allows for growth. Over time the space in the epiphyseal space becomes smaller due to outward growth of the secondary ossification centers
what happens when girls go into puberty early?
estrogen load pulls growth hormone and epiphyseal plate close and they become shorter than they should be
in terms of growth what are the layers called, think about where the femur and tibia meet and the types of zones present. What are these zones called?
starting with the diaphysis and moving distally along the tibia, you have the zone of calcified cartilage, zone of hypertrophic cartilage, zone of proliferating cartilage
what is special about the zone of proliferating cartilage?
as long as this is maintained, the bone can continue to grow longer as a child
what is the term used to describe how bones get thicker?
appositional growth
how dose appositional growth work?
1) ridges in periosteum create groove for periosteal blood vessel
2) periosteal ridges fuse, forming an endosteum lined tunnel
3) osteoblasts in endosteum build new concentric lamellae inward toward the center of the tunnel, forming a new osteon
4) bone growth occurs outward as osteoblasts in periosteum build new circumferential lamallae. Osteon formation repeats as new periosteal ridges fold over blood vessels
what is marble bone disease?
marble like structure of the bone that breaks easily b/c bones need elasticity so that you can move easily
what are osteon?
the columns of the bone found in long bone used for weight bearing activities, when you have multiples of these they become covered with periosteum
what are normal blood calcium levels?
8.5-10.5 mg/dl
how is calcium released?
when calcium levels reach low levels below 8.5 signals are sent to parathyroid to release PTH which comes to trabecular bone to allow for calcium to be provided in the blood stream
where can we find osteons?
in the long bones, because osteon makeup is used for weight bearing activities
osteon bone unique feature about the lining of their collagen?
they have collagen lining in opposite directions to allow for easier movements of the body and prevent additional injury from occurring in the event a break occurs
what are corticol bones?
dense bones that contain passage ways for nerves, blood vessels and lymphatic ducts
what is the structural unit of compact bone?
osteon or haversian canals and these represent a weight bearing pillar. You can see concentric rings looking in the transverse plane surrounding the canals
each of the concentric rings you see in the osteon is called what?
lamella and these are a layer of bone matrix in which collagen fibers and mineral crystals align and run in a single direction; however adjacent lamella run in opposite directions to inhibit crack propagation and withstanding torsion stresses
If we use the femur bone as an example how would you describe the composition with respect to trabecular and cortical make-up
so the head, neck, and going into the body are comprised of trabecular bone and as we go toward the middle we see the makeup change to corticol bone to support the rest of the upper body
T/F, there are osteons in the trabecular bone?
F, there are no osteons in the trabecular bone; they also have compression and tension lines
why are gap junctions important in compact bone for osteocytes?
communication can occur between the osteocytes of the compact bone to allow nutrients to diffuse from one cell to the next.
what is compact bone?
external layer, arranged in osteons, lamellae are found around periphery and between osteons, central canals connected to each other by perforating canals
what is trabecular bone?
no osteons, arranged in trabeculae, major type of tissue in short, flat, irregular bones, much lighter than compact bones, supports red bone marrow
how does bone remodeling occur?
since osteoclasts are multinucleated and they have ruffled borders, these ruffled borders are used to attach to the bone matrix to allow for chewing to occur to release calcium. Once done, they move out of the way so osteoblasts can come in and repair the bone.
describe how calcium levels can maintain homeostasis from a clinical standpoint
when calcium levels deviate from the norm, if hypo/hyper calcemic the body begins to stress to keep up. If hypo, need help from Parathyroid gland to release PTH and goes to gut and kidney for help. Once you receive the necessary calcium you can become hypercalcemic which affects muscles and heart. So PTH cannot just be sent out, it has to be regulated.
How is PTH regulated?
PTH does not bind to osteoclasts and binds to osteoblasts and so osteoblasts release rank ligand and this binds to osteoclasts which then chews up bone and calcium provided to blood circulation
How is rank ligand regulated?
Under control of PTH, osteoblasts activate release a secondary molecule called osteoprotegerin which binds all the rank ligand and deactivate them
where do PTH bind inorder to release calcium into circulation?
osteoblasts
Where else can PTH release stores of calcium?
kidneys - which allows for the reabsorption of more calcium; note that PTH also aids in final hydrolyzation step in Vitamin D (1,25-cholcalciferol)so that this can go into intestines and start pulling more calcium.
why are osteoblasts so important?
they maintain the health of the bone by monitoring osteoclast activity and sending signals that initiate production of either/or by going to stem cells to produce more osteoclast
What is RANK ligand a major stimulator for?
both differentiation of preosteoclasts to osteoclasts and of the activity of mature osteoclasts
what do glucocorticoids do to RANK ligand and osteoprotegerin? What happens overall?
they increase RANK ligand production via osteoblastic cells and decrease the production of osteoprotegerin; the result is that more RANK ligand is available to bind to RANK on osteoclasts and promote bone loss
Why are integrins important to the osteoclast?
if they are not made properly they cannot communicate with the vitonectin (bone side) and properly glue in the osteoclast and so bone resorption is really uncontrolled and calcium levels become high
why is IL-6 important?
released alongside RANK ligand and binds to osteoclast to help mature pre-osteoclast develop by pulling other growth factors
Describe bone remodeling?
Bones are not stone or marble structures and are constantly remolded and after use of osteoclasts osteoblasts come back and make new bone release peptidoglycan and proteoglycan making up new matrix (osteoid) becoming osteocyte and then osteoid becomes mineralized. This happens throughout life
how is most bone formed?
endochondral ossification
what are the three steps in endochondral ossification?
step1: cartilage forms
step2: cartilage grows
step3: bone replaces the cartilage from the inside center outward
this usually only occurs during childhood when bones are developing, if it happens in adult hood it is not good because it could indicate a neoplasm
why does cartilage in the bone indicate?
it means it can be used to produce more growth for that bone
1) resting cartilage
2) chondrocyte proliferation
3) chondrocyte hypertrophy
4) cartilage calcification (bone growth)
5) erosion of calcified and bone deposition ossification
what happens when you fracture your bone?
haversion canals and Volkmann canals disrupted causes hematoma and bleeding occurs (hematoma) between broken pieces. Clean up hematoma through use of macrophages, then bring osteoblast/osteoclast, fibroblast come, collagen laid and new bone made. Takes 6-8 weeks to heal.
1) fracture hematoma
2) granulation tissue
3) bony callus formation
4) remodeling occurs over 6 month
what happens if bones are not perfectly aligned?
pseudoarthosis
what is Hematogenous osteomyelitis?
an infection inside bone and happens in metaphyseal portion of the bone. For the long bone, when arteries and vessel come to bone and artery. They need to enter bone and supply blood flow. Here, vessels enter *metaphyseal region of bone and loop around slowing circulation to the bone and causing bacteria deposition inside bone
what part of the bone is affected by Hematogenous Osteomyelitis?*
the metaphyseal area of the long bone
what is the most common type of metabolic bone disease?
osteoporosis
what is osteoporosis?
the activation of osteoclast at a high rate without remodeling. Usually characterized by bone loss and fractures.
how many different types of osteoporosis is there?
2 types: type 1 primarily occurs in postmenopausal women and type 2 occurs in persons of both sexes
what is the significance of Type 1 osteoporosis? Type 2 osteoporosis?
absolute increase in osteoclast activity, estrogen is pulled from body so no hormone can provide remodeling, only resorption; decreased osteoblast activity
how is peak bone mass maintained?
genetic factors, nutrition, and physical activity; whereas osteoporosis is facilitated by menopause and aging
how is osteoporotic vertebra characterized?
loss of horizontal trabaculae and thickened vertical trabeculae
what is osteomalacia?
results from inadequate mineralization of bone matrix; associated with vitamin D deficiency which reduces the rate of absorption of calcium across the lining of the intestines; it reduces calcium available to mineralize the bone; feeling of tiredness; rickets often results, we would metaphysical cupping and fraying and increase in the distance between the end of the shaft and epiphyseal center
what is osteopetrosis?
characterized by the production of excessive amounts of bone matrix. Patients develop brittle bones; i.e. - erlenmeyer flask deformity
what is scurvy?
characterized by the inability of osteoblasts to manufacture normal amounts of bone matrix (collagen). Decreased amounts of vitamin C leading to bleeding in joints, gums, and crooked teeth.
two primary hormones used to regulate calcium and phosphate metabolism?
1,25-dihydroxyvitamin D (calcitriol) and parathyroid (PTH)
normal limits of blood calcium?
between 8.5-10.5 mg/dL
what hormone protects against hypocalcemia?
PTH, which targets bone and kidneys
what hormone does PTH stimulate? signal
1,25-dihydroxyvitamin D; low circulating calcium
what is the active form of Vitamin D?
1,25-dihydroxyvitamin D, vitamin D must undergo two successive hydroxylation reactions to become active
1) 7-Dehydrocholesterol absorbed by the skin via UVB and converted to cholecalciferol (Vit D3)
2) cholecalciferol then converted to 25-hydroxycholecalciferol (25-OHD3) by the liver
3) the kidney then converts 25-hydroxycholecalciferol into 1,25-(OH)2D3 and 24,25-(OH)2D3
what role does vitamin D play?
Ca absorption and inorganic phosphate absorption by the small intestine. It regulates bone remodeling and renal reabsorption of Ca and inorganic phosphate
When vitamin D and its metabolites circulate in the blood, what are they bound too?
Vitamin D binding protein (DBP), which binds more than 85% of 1,25-hydroxyvitamin D
What does Vitamin D-binding protein do?
transports the highly lipophilic vitamin D and provides a reservoir of vitamin D that protects against vitamin D deficiency
what is the primary endocrine regulator of bone remodeling in adults?
PTH with normal levels of 1,25-dihydroxyvitamin D
where is the PTH receptor expressed?
on osteoblasts only therefore stimulating osteoblastic activity and stimulating osteoclastic activity indirectly through osteoblast derived paracrine factors
