Bone tissue and skeletal system Flashcards
what is the skeletal system
an organ system with bones, cartilage, ligaments, and tendons
makes up about 20& of body mass
what are the three well known functions of the skeletal system
support - the body (mandible and maxilla support the teeth)
protection - encloses and protects important organs (ex. ribcage and skull)
movement - limbs, breathing
what are the four lesser known functions of the skeletal system
electrolyte balance - skeleton stores Ca and P
acid-base balance - buffers blood against major pH changes (hydroxyapetite CaPO4)
blood formation - stem cells in red bone marrow make red blood cells
triglyceride storage - yellow bone marrow is an energy resovoir of adipose tissue
how many bones do we have at birth, explain
we are born with 270 bones but as full grown adults we have 206
(around 25 years of age)
some bones fuse together
ex. illium ischium, pubis fuse together
ex. skull bones with sutures
ex. fusion of sacrum and coccyx
what are the cellular and matrix components of osseous tissue
osteoblasts, osteoclasts, osteocytes, stem cells
collagen fibers, CaPO4, CaCO3, ground substance
what is an osteogenic cell
stem cell which generates osteoblasts
multiply and differentiate
located in endosteum (lines the channels), periosteum
located in places where they need more osteoblasts (need new bone)
what is an osteoblast
cell that forms bone matrix
non mitotic
form collagen fibers and ground substance
making glycosaminoglycans, proteoglycans, and glycoproteins
explain how osteoblasts become osteocytes
as the osteoblast is laying down the bone matrix around itself, it traps itself in the lacunae, making it an osteocyte
it grows cytoplasmic processes (extensions of the plasma membrane)(basically arms) for when it is trapped in the matrix
what is an osteocyte
cell that maintains bone tissue
formerly osteoblasts that are trapped in matrix in small cavities called lacunae
connected by canaliculi
maintains bone tissue by adding and removing tissue
maintains bone/blood concentration of Ca2+ and PO43-
by dissolving bone and putting these ions into blood.
what are canaliculi
little tunnels in bone matrix which allows osteocytes to communicate with their appendages
what are osteoclasts
cells derived from hematopoietic stem cells (different lineage than osteogenic cells)
multiple hematopoietic stem cells fuse together to form an osteoclast (osteoclast possesses multiple nuclei)
HP stem cells are in red bone marrow (all blood cells are derived from HP stem cells)
osteoclasts possess conspicuous microvillie which increase the surface area so that they can come into contact with the matrix to break it down more easily
they dissolve bone matrix and therefore change the composition of blood (of Ca2+ and PO43-
what are the organic and inorganic components of bone matrix
organic
-collagen fibers
-ground substance (glycosaminoglycans, proteoglycans, glycoproteins)
inorganic
-85% hydroxyapatite (CaPO4)
-10% CaCO3
-5% other ions (depend on what you eat/drink/where you live)
we get the inorganic stuff from out diet
describe the process of bone formation
occurs through the process of calcification (mineralization)
1. osseous tissue is saturated with CaPO4 and CaCO3 (a supersaturated solution)
2. deposition of collagen (collagen is made by osteoblasts)
3. CaPO4 and CaCO3 crystallize on the collagen fibers
rock candy is made this way
uniport Ca pummps pump Ca out of other body cells so that they dont crystallize and form bone, killing the cells
explain bone is a composite
composite of minerals and collagen
minerals provide strength
collagen provides flexibility
reshaping bone is based on activity level
skyscrapers move (they need to be flexible)
too much minerals/not enough collagen = easy breaking bone
what is osteomalacia
rickets disease
very flexible bones
presents during growth spurts
caused by lack of minerals in bone
mostly due to dietary deficiency in Ca, P, or vitamin D
can also be genetic (hereditary rickets)
^patient has kidney problems so that they cant hang onto vitamin D and the kidney cleans the blood of vitamin D and it is excreted with urine
very rare in the US
what is osteogenesis imperfecta
very brittle bones
caused by lack of collagen
typically congenital
there is a defect in the gene which codes for collagen producing stuff
what are the two types of bone tissue
compact bone and spongy bone
what is compact bone
located in the external surfaces of all bones
dense, calcified tissue (osteons)
what is spongy bone
located in heads of long bones and in the middle layer of flat bones
loosely organized tissue
spongy appearance but calcified and hard
is the precursor to compact bone
has lots of empty space
-trabeculae = the web like pattern of bone
-empty spaces = filled with bone marrow
there are no central canals in spongy bone
(it is already vascularized bc the bone marrow is the blood supply)
what is an osteon
the basic structural unit of compact bone tissue
composed of one central canal and many concentric lamellae
the radius of an osteon is determined by how far away the last layer can be and still be getting a blood supply
thats why there are multiple osteons squished together (more central canals)
blood is the complete opposite tissue
osteocytes lay down collagen in different layers in opposite directions for each lamellae in order to make the matrix much stronger
what is bone marrow
soft, highly vascularized tissue with stem cells
located in:
1. the spaces among trabeculae of spongy bone
2. central canals of compact bone
3. the internal chamber (marrow cavity) of long bones
2 types: red and yellow
what is red bone marrow
bone marrow that produces blood and blood cells
has hematopoietic tissues
what is yellow bone marrow
fatty adipose tissue made of triglycerides
only in adults
stays yellow unless someone has severe anemia (a bad accident with lots of bleeding) or chronic anemia
acts as an energy resovoir
how does bone marrow change with age?
infants have only red bone marrow
children (1-10) the red bone marrow begins to convert to yellow bone marrow at the center of long bones (only a little bit here)
adolescent (10-20) the majority of bone marrow is yellow now
adult (20+) basically all of long bones are yellow bone marrow
what is a bone marrow transplant
taking healthy bone marrow (usually from hip) and transplanting it into another person
person who cannot create hematopoietic stem cells
ex. person with leukemia (WBC cancer) needs BM transplant
they need the stem cells so that they can differentiate
what is osteogenesis
the development of bone
two types:
intramembranous ossification
endochondrial ossification
generally what is intramembranous ossification
bone development that occurs within a membrane (mesenchyme)
develops all flat bones
generally what is endochondrial ossification
bone development that occurs within cartilage and then forms bone
develops all long bones
building the cartilage model and replacing it with bone
begins at about the 6th week of fetal development
ends at around 20 years of age
how does osteogenesis begin
cleavage of a zygote into the eight cell stage which cleaves into a blastula
gastrulation of the blastula to form the gastrula
gastrula possesses the ectoderm (outside) mesoderm (middle) and endoderm (inside) –> primary germ layers
what are primary germ layers
the three layers (ectoderm, mesoderm, and endoderm) of the gastrula from which tissues arise
ectoderm - epidermis and nervous system
endoderm - lining of digestive and respiratory tract
mesoderm - forms into the mesenchyme
what is the mesenchyme
a loosely organized tissue that forms connective tissues (including bone tissue)
where all bone development begins
typically very vascularized
possess a lot of different stem cells which dictate what kind of tissue it will become
what is the end product of intramembranous ossification
sandwich of spongy bone with compact bone as bread
in detail:
periosteum with fibroblasts
osteogenic stem cells
compact bone
endosteum with osteogenic stem cells
spongy bone
endosteum with osteogenic stem cells
compact bone
osteogenic stem cells
periosteum with fibroblasts
explain the process of intramembranous ossification
- the mesenchyme condenses
mesenchyme possesses fibroblasts and osteogenic stem cells
blood vessels form into the mesenchyme which feed it - the blood vessels form the framework
the osteogenic cells begin to surround the blood vessels - the osteogenic cells lay down bone
the osteogenic cells do mitosis and differentiate into osteoblasts which lay down bone (trabiculae) along blood vessels
the remaining mesenchyme becomes bone marrow
this is spongy bone - blood vessels migrate away from mesenchyme
the osteogenic cells move with the blood vessels, building osteons (compact bone) as they go
this happens from both sides of the mesenchyme, forming the compact bone bread
fibroblasts travel through the blood vessels and build the periosteum after the layer of osteogenic stem cells on both sides
explain the process of endochondrial ossification
- the hyaline cartilage model is formed
a long bone possesses lacunae with chondrocytes (just hyaline cartilage) - blood vessels bring osteogenic stem cells
form the bony collar (layer of bone outside of cartilage)(basically ice cream coated with hardened chocolate layer)
there needs to be room inside of the cartilage for the blood vessels and osteogenic cells to get in - chondrocytes in lacunae undergo hypertrophy
they grow super duper big and break down the matrix, weakening the cartilage model
blood vessels are then able to get into the model
osteogenic stem cells follow and build spongy bone in the same process as IM ossification
(forming trabiculae and then osteons)
this first happens in the middle (forming primary cavity) and then happens at both ends (forming secondary cavities)
what is the end product of endochondrial ossification
secondary marrow cavity surrounded by compact bone
hyaline cartilate (epiphyseal plate)
primary marrow cavity surrounded by compact bone
hyaline cartilage (epiphyseal plate)
secondary marrow cavity surrounded by compact bone
what are the different kinds of growth and remodeling of bone
happens after bones have developed
2 types:
interstitial growth (growing longer)
appositional growth (growing wider)
where does interstitial growth happen
happens at epiphyseal plate
under x rays, you can see the epiphyseal plate in children but in adults it is all gone (you can still see the epiphyseal line)
there are two ends of the epiphyseal plate: metaphysis
this is where the bone growth happens: mitosis of the catilage which lengthens and ossifies to create more bone
what are the zones of metaphysis/process of interstitial growth
- zone of reserve cartilage
just regular hyaline cartilage that isnt in the metaphysis - zone of cell proliferation - chondrocytes multiplying and lining up in rows of small, flattened lacunae
- zone of cell hypertrophy - cessation of mitosis, enlargement of chondrocytes, and thinning of lacunae walls
- zone of calcification - temporary calcification of cartilage matrix between columns of lacunae
so that the growing cartilage does not collapse bc its not strong enough to hold your body up - zone of bone deposition - breakdown of lacunae walls, leaving open channels, death of chondrocytes, bone deposition by osteoblasts, forming trabeculae of spongy bone
blood vessels with osteogenic cells go in and do all of that stuff to form osteons
explain the two types of dwarfism
pituitary dwarfism - everything is proportional but everything is just smaller
all bones stop growing
due to a growth hormone deficiency in the pituitary gland which normally will cause interstitial growth
achondroplastic dwarfism - possess a proportional torso of average size but appendages arent proportional
long bones stop growing during childhood
no problem with development of flat bones
hyaline cartialge in long bones cant do interstitial growth
what is appositional growth
growing in girth from superficial surface
deposition of new osseous tissue at the bone surface by osteogenic cells that are in the periosteum
they become osteoblasts and build bone appositionally (in diameter)
this is what creates the circumferential (outer) lamellae which surrounds ALL of the osteons in the middle
what is the relationship between interstitial and appositional growth
IS and APP growth can happen at the same time
APP growth can always happen without IS growth
what are the multiple different categories of bone fractures
stress fracture - due to abnormal stress (falls, impact, etc.)
pathological fracture - bone is weakened due to disease (cancer, osteoporosis, etc.) and breaks as a result
closed - doesnt break through skin
compound - breaks through skin
in position - no reducing required
out of position/displaced - requires the bone to be reduced
incompletely broken/greenstick - bone hasnt broken all the way through but is bent
comminuted - bone broken in 3+ pieces, usually also displaced
why might a bone fracture need to be reduced (what is that)
reducing a bone is putting it back in its place so that it wont be deformed when it heals
out of position bones need reducing
how long does it taken uncomplicated stress fractures to heal?
8-12 weeks
explain the process of healing bone fractures
- formation of a hematoma
broken blood vessels form a blood mass that possesses fibroblasts, macrophages (clears broken bone fragments), and osteoclasts (smooths bone over the rough breakage)
osteogenic cells become abundant (in periosteum and endosteum) within 48 hours (undergo massive mitosis to help build bone back
blood clot forms into granulation tissue - formation of soft callus
osteogenic cells differentiate into chondroblasts which build cartilage
produces a soft callus of fibrocartilage model (NOT HYALINE)
this is similar to endochondrial ossification and interstitial growth - conversion to a hard callus
osteogenic cells produce osteoblasts which produce the hard callus
hard callus is a bony collar which outlines joint where the bone is broken (not in model, but around it)
acts as a temporary joint that solidifies and supports regrowth of new bone
you wear a cast for 4-6 weeks so that you can form this
similar to building a bone collar in endochondrial ossification - remodeling
hard callus persists for 3-4 months then forms into bone –> exactly like IS growth
the osteoblasts deposit spongy bone and superficially it becomes compact bone
the remnant of the hard callus can be seen after healing on an x ray (appears as a little bump over the place where the break happened)
how is bone a metabolically active organ
bone is constantly exchanging between self maintenance, growth and remodeling
and exchange of calcium and phosphorous with the body
by way of blood vessels
what is mineral deposition and resorption
how bone tissue exchanges minerals with the body
mineral deposition builds bone
minerals are extracted from blood plasma and deposited into bone tissue
(lower amount of Ca and P in the blood)
bone forms this way (calcification/mineralization)
mineral resorption breaks down bone
minerals are extracted from bone tissue and released into blood plasma
(higher amount of Ca and P in the blood)
why doesnt mineral deposition happen in all tissues
most cells have uniport Ca pumps using ATP pump calcium out of cells
what is ecctopic ossification
osseous tissue in places other than bone
can be anywhere
forms a calculus - a calcified mass in a soft organ
ex. arteriosclerosis
plaque buildup in endothelium of blood vessels
can cause a heart attack
ex. kidney stones are calculi
how does mineral resorption occur
osteoclasts possess ruffled borders (foldings of plasma membrane) which increase surface area for resorption
they possess hydrogen pumps which secrete H+ into the matrix of bone
Cl- is electrically attracted to H
forms HCl (pH=4) which dissolves bone minerals
(bone experiment in lab –> acid pulls out minerals making bone flimsy)
secretes acid phosphatase which digests collagen
breaks down collagen and minerals have no where to crystallize and they can then go into the blood stream
what is the balance between bone cells
there is balance between osteocytes and osteoblasts which do mineral deposition and osteoclasts which do resorption
^^ creates the balance of continual turnover of bone
about 10% of skeletal tissue is remodeled per year
^ releasing minerals into blood
repairing micro-fractures
reshaping bones due to use
what are some examples of bone remodeling because of use
leg muscles that attach to tibial tuberosity
increased muscle movement increases the size of the tibial tuberosity in order to support the muscles
the hip muscles that are involved in walking are attached to the greater trochanter of the femur
infants dont have a greater trochanter since they dont walk but it forms once they start learning how to walk
braces
what are characteristics of bone remodeling
releasing minerals into blood (osteoclasts breaking down bone)
repairing micro fractures (dont even know that it has happened
reshaping of bones due to use - change in use of muscles changes shape of bones
explain how braces work
teeth are embedded in the spongy bone of the mandible - they dont actually touch bone, they are connected by the periodontal ligament
braces are needed when the alignement is off and they are trying to move the teeth
they attach a wire to teeth and pull it to one side or another
very slow process
there is a compression side and a tension side.
the compression side is where the orthodontic force is pulling the teeth to - causes more osteoclasts to be expressed and therefore more bone to be broken down on that side
the tension side is where the orthodontic force is pulling the teeth away from - causes more osteoblasts to be expressed and therefore more bone to be produced on that side.
what is osteoporosis
severe loss of bone density over time
one of the most common bone diseases
occurs to a point where the bones are so brittle that they can have pathological fractures
who is affected by osteoporosis
mostly develops in the 40s and shows symptoms in the 60-70s
there is no way to prevent it – everybody gets it as you age
post menopausal women are at higher risk
why are post menopausal women more affected by osteoporosis
menopause is the stopping of the reproductive cycle
when this happens, estrogen levels decrease
normally, ovulation causes the release of estrogen and estrogen inhibits osteoclasts from breaking down bone
without this there is no proper regulation of osteoclasts
explain how osteoporosis can cause problems in the body
about 30-50% of bone tissue is lost by about 70 years old
affects mostly spongy bone
can cause spine problems – spine compression – kyphosis – very convex (hunchback) spine
can happen to everyone
what are treatments of osteoporosis
injections of Denosumab (active ingredient of things like Prolia, Xgeva, etc.)
this behaves just like estrogen (competitively inhibits RANKL receptor) without the hormonal effects of actual estrogen.
what is the importance of PO43-?
DNA, RNA, ATP, phospholipids, acid base homeostasis, etc.
what is the importance of Ca2+
communication, exocytosis, muscle contraction, blood clotting
communication between neurons – the release of a neurotransmitter through exocytosis is triggered by Ca
Ca has to bind to a protein (troponin) so that actin and myosin can bind leading to muscle contraction
maintaining the resting membrane potential
^^outside of the cell is positive and inside of the cell is negatively charged
all cells need this to function, especially muscle and nervous cells
what is RANKL
receptor activator of nuclear factor Kappa beta-ligand
is a chemical ligand that is released when they want to stimulate the development of osteoclasts
explain how osteoblasts/cytes causes differentiation of osteoclasts
osteoblasts/cytes do two things: make and deposit collagen, and make and release RANKL (receptor activator of nuclear factor Kappa Beta-ligand)
when RANKL is released into the ECM, they travel to the transmembrane protein RANKL receptor on a hematopoietic stem cell
this causes the stem cell to differentiate into osteoclasts
explain how estrogen inhibits osteoclast production
estrogen acts as a competetive inhibitor on the RANKL receptor. It binds to this receptor on a hematopoietic stem cell so that RANKL cannot bind
therefore, there is no differentiation of the stem cell into osteoclasts
estrogen prevents osteoclast overproduction
(with a lack of estrogen (like in postmenopausal women) osteoclasts are produced too much)
how are blood calcium levels regulated – what are the extremes
by hormones
hypercalcemia and hypocalcemia
what is hypercalcemia
rare disease
too much blood Ca2+ levels
makes it hard to send messages
less excitability of nervous and muscle tissue
sluggish reflexes, depression, coma
there are so many Ca ions on the outside of the cell blocking the negative glycolipids that the positive charge on the outside is so large compared to the negative inside charge
what is hypocalcemia
too little blood Ca2+
has a wide variety of causes
- vitamin D deficiency
- diarrhea (short term hypocalcemia)
- thyroid tumors and underactive parathyroids
- pregnancy and lactation
can lead to physiological problems
excess excitability of nervous and muscle tissue
tremors, spasms, cardiac failure
too easy to send messages
there are not enough Ca2+ ions on the outside of the cell so that the charge is a smaller positive than what it should be
since the difference in charge is so little, it is much easier to send messages (its almost spontaneous)
what is calcium homeostasis and what does it involve
maintaining the balance of the membrane potential
involves dietary intake, urinary/fecal loss, exchanges with bone
in a healthy person
-if you ingest too much Ca, you will excrete it or store it in bone
-if you dont ingest enoguh Ca, you will take it from bone and put it in blood
what are the three hormones that regulate Ca homeostasis
calcitriol (vit d)
parathyroid hormone
calcitonin
what are endocrine glands
glands that are highly vascularized an secrete hormones into the blood stream so that they can have their physiological effect
what kind of gland is the thyroid
endocrine
what is resorption
the reverse of sorbtion (the binding of two things)
pulling Calcium off of collagen and putting it in blood
what is absorption
taking something outside of the body and taking in anything with the digestive tract (tubes not cells)
once it is in the cells, it is absorbed
what is reabsorption
reabsorbing something that was in the body but is about to be excreted as waste
what is calcitriol and what (and how) does it do for Ca levels
calcitriol is the active form of vitamine D (produced in the skin, liver, and kidneys)
behaves like a hormone but is not derived from an endocrine gland (^)
calcitriol raises blood Ca levels
-increases Ca absorption by the small intestine
-increases Ca reabsorption in the kidneys (not excreting it out)
-increases Ca resorption from the skeleton
how does calcitriol cause increased Ca2+ resorption
increases the production of osteoclasts indirectly
calcitriol is a steroid hormone (it can pass through the PM (lipid soluble))
calcitriol goes into an osteocyte/blast and activates kinases which activate enzymes which activates RANKL production
RANKL then goes on to activate the RANKL receptor on hematopoietic stem cells, causing their differentiation into osteoclasts (secreting H+ and acid phosphatase)
this is why we need vitamin D
found in supplements
its also put in milk bc a lot of people used to drink milk (now its put into orange juice)
what is parathyroid hormone and what (how) does it do to blood calcium levels
parathyroid hormone is secreted by the parathyroid gland which sits posterior to the thyroid gland and lateral to the pharynx (and trachea/esophagus)
increases calcium levels in 4 ways:
- increases osteoclasts for more bone resorption in the same way as calcitriol
- it is not steroid based so it cannot pass through the plasma membrane
-PTH binds to a PTH receptor (transmembrane protein) on the PM of an osteocyte/blast
-when it binds, it stimulates the release of a G protein which travels to adenylate cyclase which converts ATP into cAMP
-cAMP goes on to activate kinases which activates enzymes which increases RANKL production (just like calcitriol does) - promotes Ca2+ reabsorbtion in kidneys
-less Ca is lost into the urine (increases blood Ca levels) - promotes the final step of calcitriol synthesis
- the hydroxylating of calcidiol in the kidneys
- enhances the amount and effect of calcitriol - inhibits collagen synthesis by osteoblasts
- inhibiting bone deposition
- conservation of calcium
what is calcitonin and what (and how) does it do for blood Ca levels
hormone secreted by the thyroid gland (anterior to the trachea)
lower Ca2+ levels in 2 mechanisms:
- osteoclast inhibition
-less Ca resorption from skeleton
-stops osteoclasts in two ways:
— in HP stem cells, there are calcitonin receptors that, when calcitonin binds, release a G protein which turns off adenylate cyclase (no ATP is converted into cAMP and no mitosis and differentiation)
— in osteoclasts, there are calcitonin receptors that, when calcitonin binds, the G protein is relesed and activates adenylate cyclase to convert ATP to cAMP, activating kinases which activates enzymes which shuts down the H+ pumps and shuts down the release of acid phosphatase - osteoclast stimulation
-more deposition of Ca into the skeleton
- calcitonin tells osteoblasts to make more collagen through a more complicated secondary messenger system
calcitonin and parathyroid work _________
antagonistically to balance blood Ca levels so that it is just right for the membrane potential
