MSK- Physiology Flashcards
What are the functions of the skeleton?
- locomotion (movement)
- bone marrow: RBC production
- support
- endocrine regulation
- mineral storage
- protection
How many bones are there in the human skeleton?
206
How many axial and appendicular bones?
axial = 80 appendicular = 126
What are the classifications of bone?
- long bone
- short bone
- flat bone
- irregular bone
- sesamoid bone
Give some examples of each bone…
- long = femur, humerus
- short = carpals and tarsal bones
- flat = skull, scapula
- irregular = vertebrae, clavicle, mandible
- sesamoid = patella
What are the two types of bone?
woven and lamellar
Give some characteristics of woven bone?
- forms quicker than L
- mechanically weak
- no organisation
- no clear structure
- primary bone
Give some characteristics of lamellar bone?
- forms slower than W
- mechanically strong
- highly organised
- clear structure
- secondary bone
- many collagen fibres parallel to other fibres in same layer create osteons
When is woven bone present?
- in ALL foetal bones
- after fractures during repair process
- Paget’s disease
When comparing woven to lamellae what is the comparison in number of osteocytes?
woven bone = more osteocytes per unit volume and higher rate of turnover (spongy bone has NO osteocytes)
What are the two types of secondary bone?
Compact (dense/cortical)
OR
Trabecular (spongy/cancellous)
What are the different types of bone marrow and what do they produce?
Red- produces RBC’s in childhood
Yellow- nutrient reservoir in adults
What are epiphyses?
contain spongy bone and resist compression
What is the periosteum?
outer fibrous layer
What are Sharpies fibres?
perforating fibres attaching tendons (have a rich nerve supply)
What does bone marrow contain?
haemotopoietic tissue and adipocytes
What are the constitutes of bone and what percentages?
Organic compounds = 50-70%
Inorganic compounds = 20-40%
Water = 5-10%
What organic compounds make up bone?
type I collagen (90%), glycosaminoglycans
What inorganic compounds make up bone?
hydroxyapatite and calcium phosphates
What do collagen and minerals do to the bone?
collagen provides elasticity and minerals provide stiffness
What is endochondral ossification?
the formation of bone in which a cartilage skeleton is gradually replaced with a bone matrix
What are the 5 stages of endochondral ossification?
Bone collar formation Cavitation Periosteal bud invasion Diaphysis elongation Epiphysis ossification
What are the stages of bone collar formation?
- periosteum forms around the cartilage
- progenitor cells differentiate into osteoblasts
- osteoblasts secrete osteoid which lines the outer surface of the cartilage forming a bone collar
What are the stages of cavitation?
- calcification of central cartilage occurs (primary ossification centre)
- cartilage hardens, nutrients cannot diffuse to inner compartment therefore it degenerates
- cavities begin to form
What are the stages of periosteal bud invasion?
- periosteal blood vessels invade inner cavity
- through hole called nutrient foramen
- remaining cartilage is broken down by osteoclasts and osteoclasts secrete osteoid forming trabecular (spongy bone)
What are the stages of diaphysis elongation?
- epiphysis lengthens and medullary cavity formed
- blood vessels invade secondary ossification centres in epiphyses
What are the stages of epiphysis ossification?
- spongy bone is formed
- hyaline cartilage left on ends of bones = articular cartilage
- growth plate forms between primary and secondary ossification centres
What are osteoblasts derived from?
mesenchymal cells
What are osteoclasts derived from?
haematopoietic cells / monocytes
When do the growth plates fuse?
they ossify in mid 20’s
What is responsible for the lengthening of bones during childhood?
the growth plates
Which cartilage is particularly responsible to growth hormone and to sex hormones?
epiphyseal cartilage and undergoes increased activity at puberty when the growth spurt occurs
What are the cell layers of endochondral ossification )epiphysis - diaphysis) ?
Resting cartilage Hyperplasia (zone of) Hypertrophy (zone of) Ossification (zone of) Primary bone
What happens during the resting cartilage phase?
resting cartilage begins to divide
What happens during hyperplasia?
cells form column progeny
What happens during hypertrophy?
the cells grow and erode into the cartilage, chondrocytes are reabsorbed and calcified
What happens during ossification?
osteoblasts attach to the calcified substrate and lay down primary bone
What happens during primary bone stage?
at the same time bone is eroded and deposited on the outside of the bone shaft = appositional growth
What is intramembranous ossification?
The laying down of bone straight into mesenchyme
Which bones originate from intramembranous ossification?
Flat bones
When does the process of intramembranous ossification begin?
In 2nd trimester of embryonic life
What are the 4 stages of intramembranous ossification?
- Development of ossification centre
- Calcification
- Woven and trabeculae formation
- Periosteum formation
Describe the first stage of intramembranous ossification…
Development of ossification centre in the fibrous sheath
- progenitor cells transform into osteoblasts
- they secrete an organic extracellular matrix
Name and describe the second stage of intramembranous ossification…
Calcification
- deposition of calcium and other mineral salts
- extracellular matrix calcifies
- trapped osteoblasts become osteocytes
Name and describe the third stage of intramembranous ossification…
woven bone and trabeculae formation
- osteoid forms around embryonic blood vessels forming a random network of trabeculae (NO OSTEONS)
Name and describe the fourth stag of intramembranous ossification…
periosteum development
- peripheral mesenchyme forms into periosteum
- bone closest to periosteum thickens and becomes compact bone either side of central spongy bone
What are lacuna?
pockets where osteocytes sit
What are cannaliculi?
communication between osteocytes
What are perforating volksmann canal
blood from periosteum to blood in central canal
What are lamellae?
thin layers of matrix which comprise solid bone
What is the Haversian Canal?
a longitudinal canal containing blood vessels
When does intramembranous ossification occur?
- formation of flat bones of skull
- formation of jaw and clavicle
- internal fixation of bone healing (not plaster cast)
What is bone modelling?
- gross shape is altered, bone is added OR taken away
What is bone remodelling?
all of the bone is altered, old bone is replaced by new bone
What are the 4 stages of bone remodelling?
- activation
- resorption
- reversal
- formation
What happens in the activation step of bone remodelling?
osteoclasts gather in small pits on the surface of the bone called lacunae
What happens in the resorption step of bone remodelling?
Osteoclasts adhere to the surface of the bone and break down the bone in 2 ways:
- organic component broken down by acidification of matrix
- inorganic component broken down by lysosomial enzymes
What happens in the reversal step of bone remodelling?
- end of the resorption phase
- reverse cells (macro-phage like) remove debris
What happens in the formation step of bone remodelling?
- osteoblasts are attracted to the area by growth factors released from the breakdown of bone matrix
- osteoid secreted from osteoblasts forming a collagen matrix
- the osteoblasts then mineralise this to form new bone
What growth factors are release in the formation stage of bone remodelling?
TGF-beta and FGF’s (fibroblast growth factors)
What enzymes are released during the resorption phase of one remodelling?
collaginases and MMP-9
Describe the steps of osteoblastogenesis…
- wingless-int stimulates MSC’s»_space; osteoprogenitor cells
- osterix stimulates osteoprogentior cells»_space; osteoblasts
Describe the steps of osteoclastogenesis…
- PU-1 and M-CSF stimulates HSC’s»_space; osteoprogenitors
M-CSF stimulates 2 things:
1. proliferation of osteoclast progenitors
2. up-regulation of RANK expression
» osteoclast formation
Give 4 reasons for bone remodelling?
- response to loading (exercise)
- replace woven bone with lamellar bone
- repair damage
- obtain calcium
Osteoclasts have a high expression of what two things?
TRAP and cathepsin K
What does deregulated modelling lead to?
disease
What cells release RANKL?
osteoblasts
How do osteoblasts mineralise the extracellular matrix?
depositing hydroxyapatite crystals within the collagen fibres
How do the osteoblasts create sit for the calcium dn phosphate deposition?
secrete alkaline phosphatase
What is bone called before it is mineralised?
osteoid
What are osteoblasts called when bone is surrounded by a calcified matrix (after mineralisation)?
osteocytes
How much of the calcium we ingest is absorbed?
30%
What is the DRA of calcium?
800mg
What are the major sources of dietary calcium?
dairy products which make up 2/3 of our intake
What are the minor sources of dietary calcium?
cereal, vegetables (broccoli) and cereal
What is the average calcium intake per day?
1000mg
Where is calcium absorbed?
- ACTIVE absorption in the duodenum and jejunum
- PASSIVE absorption in the ileum and colon
When do we absorb a higher fraction of calcium?
when put on a low calcium diet- mediated by a greater production of calcitriol
- most calcium is absorbed by AT
What is the active form of vitamin D?
calcitriol
Which three important hormones are involved in the regulation of calcium and phosphate?
- vitamin D
- parathyroid hormone
- calcitonin
What is phosphate important form?
- biological processes
- energy
What is calcium important for?
- bones
- nerve impulses
What factors can make you more prone to lactose intolerance?
- increased age- onset mostly in adults
- ethnicity- those of African, Asian and Hispanic descent
- premature babies- small intestine does not produce lactase-producing cells until late in 3rd trimester
- diseases affecting the small intestine e.g. Crohn’s and Coeliac
- cancer treatment- e.g. radiotherapy targeting abdominal cancer
What cells secrete calcitonin and when do they secrete it?
C-cells in the thyroid due to an increase in serum calcium
What is the effect of increased calcitonin released?
lower bone reabsorption
In calcium reabsorption what is the amount of the calcium filtered by the glomerulus dependent on?
the GFR and ultrafiltrable calcium (not protein bound)
When is more calcium filtered by the glomerulus?
When GFR is high
How much of the filtered calcium is usually reabsorbed?
98%
When is more calcium reabsorbed?
if PTH is high
When is less calcium reabsorbed?
if Na+ is high
What is resorption?
the process or action by which something is reabsorbed
Resorption of calcium two methods…
- can be released rapidly from exchangeable calcium on the bone surface
- may be released more slowly by osteoclasts during bone resorption
Resorption of calcium two methods…
- can be released rapidly from exchangeable calcium on the bone surface
- may be released more slowly by osteoclasts during bone resorption
How does the parathyroid respond to a decrease in serum calcium?
- detected by chief cells
- PTH binds to G-coupled receptors on the outer membrane
- activates G protein
- catalyses the conversation of ATP to cAMP
3 x actions on the kidney:
1. increased calcium reabsorption
2. decreased phosphate reabsorption
3. increase rate of synthesis of 1,25-dihydroxy vitamin D (calcitriol)
What is hydroxyapatite made up of?
calcium and phosphate
What effect does the parathyroid hormone have on calcium and phosphate levels?
increased calcium re-absorption
decreased phosphate reabsorption
What effect does calcitonin have on calcium and phosphate levels?
decreased calcium and phosphate reabsorption
What effect does the thyroid hormone have on calcium and phosphate levels?
increased calcium and phosphate reabsorption
What effect does parathyroid have on the kidneys, bone and GI tract?
kidneys = increased activity of 1 alpha-hydroxylate, increased reabsorption of calcium in the DCT, decreased reabsorption of phosphate in the PCT bone = increased osteoclast activity, increased maturation of osteoclasts, decreased osteoblast collagen in matrix GI = increased calcium and phosphate reabsorption
What effect does calcitonin have on the kidneys, bone and GI tract?
kidneys = decreased calcium and phosphate re-absorption
bone = decreased osteoclast activity, increased osteoblast activity
GI tract = NO EFFECT
What effect does calcitriol have on the kidneys, bone and GI tract?
kidneys =increased calcium and phosphate reabsorption
bone = stimulates PTH, increases calcium
GI tract = increases absorption of calcium and phosphate in small intestine
After a high calcium meal what stimulates the release of Calcitonin from the thyroid gland?
gastrin
What does stimulation of osteoclast activity cause?
release of calcium from bones into the blood
What does stimulation of osteoblast activity cause?
uptake of blood calcium into the bone
What is the non-hormonal regulation of calcium and phosphate?
if there is a decrease in calcium and phosphate blood plasma levels the calcium and phosphate is released from hydroxyapatite crystals in bone.
What are the short and long term responses of calcium and phosphate regulation?
short term = non-hormonal
long term = hormonal
Parathyroid hormone is produced and secreted by what cells?
chief cells
Calcitonin is produced and secreted by what cells?
para-follicular cells of the thyroid gland
Which enzyme in the kidney converts 25-hydroxy Vit D into 1,25 dihydroxy Vit D?
1 alpha hydroxylase
How long does the catabolic process of bone remodelling take?
~ 3 weeks
How long does the anabolic process of bone remodelling take?
~ 3 months
What 4 cells are present in all bones?
- osteocytes
- osteoblasts
- osteoclasts
- macrophages
In mineralised bone what percentage do osteocytes make up?
90%
What is the function of osteoblasts?
they maintain the matrix and co-ordinate osteoblast/clast activity
What are osteoclasts derived from?
haematopoeitic stem cells (monocytes)
Where do osteoclasts lie?
In Howships lacunae
What colour do osteoclasts stain?
bright red
What is TRAP?
tartrate-resistant acid phosphatase
Which cells control the remodelling of bone?
osteoblasts
What colour do osteoblasts stain?
blue stain in cytoplasm (lots of RER)
What 3 things do osteoblasts secrete?
- osteoid
- OPG (osteoprotegerin)
- RANK ligand
Which cells have a high expression of TRAP?
osteoclasts
What is the role of RANK ligand?
binds to RANKL receptors on osteoclasts
What is bone resorption stimulated by?
- stimulated by RANKL in normal process
- stimulated by PTH in pathologic process (metastatic disease)
What is bone formation stimulated by?
performed by inhibiting osteoclasts and stimulating osteoblasts
OPG inhibits osteoclasts
Which family is OPG a member of?
tumor necrosis factor family (TNF)
How does OPG decrease resorption by osteoclasts?
binds to RANK ligand and blocks the RANK-RANK ligand interaction
What is coupling in bone remodelling?
bone formation occurs at site of previous bone resorption
Name 4 molecules that promote bone resorption…
- PTH
- RANKL
- Interleukin-1
- 1,25 dihydroxy vitamin D (stimulates RANKL expression)
What is osteomalacia?
a defective mineralization of the bone matrix in adults
What is the cause of osteomalacia and what does it cause?
- lack of vitamin D»_space; soft bones»_space; bowed legs
What is osteoporosis?
a reduction in bone mass (greater than 2 SD below the mean) with normal mineralisation
What is avascular necrosis?
death of bone tissue due to a lack of blood supply
Which type of bone does osteoporosis affect?
trabeculated bone
Which drugs should not be used to treat osteoporosis?
steroids
Where is avascular necrosis most common?
scaphoid and head of the femur
An increase in OPG results in what?
a decrease in osteoclast activity
An increase in RANKL leads to an increase in what?
osteoclast activity
What is the definition of a fracture?
a break in the continuity of a bone
When can fractures occur?
- non-physiological loads applied to normal bone
- physiological loads applied to abnormal bone
Are fractures more common in males or females?
males up to the age of the menopause, then more common in women over the age of 45.
Why do bones break?
rumour, metastises, metabolic bone disease
How do you define a fracture clinically?
Site Pattern Displacement Joint involvement Skin involvement
What are the 4 stages of bone healing and how long do they take?
- haematoma (hours)
- inflammation (days)
- repair (weeks)
- remodelling (months)
How can fractures be fixed?
- slings
- casts and splints
- external fixation
- internal fixation (extra-medullary e.g. plates or screws or intramedullary e.g. nails)
What factors influence the healing of a fracture?
- patient-smoking, age, nutrition
- tissue- bone type, bone site, vascularity, bone pathology, infection
- treatment- stability, apposition of fragments
Do cancellous or compact bones heal quicker?
cancellous heal quicker
What drugs should you not give to someone with a fracture?
NSAID’s as inflammation is required for the healing process
What is the management of fractures?
- reduce
- immobilise
- rehabilitate
What can the complications of fractures be categorised into?
early or late complications
give some examples of early complications of fracture healing?
local = vessel damage nerve damage, compartment syndrome, infection general = hypovolaemic shock, fat embolism
give some examples of late complications of fracture healing?
local = avascular necrosis, joint stiffness, malunion,non-union, osteoarthritis general = pressure sores, disuse>>osteoporosis, poor mobility, functional disability and social isolation
Give some examples of types of fractures…
- simple (closed)
- compound (open)
- greenstick
- comminuted fracture: the bone shatters into three or more pieces
- impacted: one whose ends are driven into each other. This commonly occurs with arm fractures in children and is sometimes known as a buckle fracture.
- incomplete
- avulsion- an injury to the bone in a location where a tendon or ligament attaches to the bone
- colles fracture- Colles fractures are very common extra-articular fractures of the distal radius that occur as the result of a fall onto an outstretched hand
What are the 4 stages of bone healing?
- haematoma
- inflammation
- repair
- remodelling
What happens in the haematoma stage of bone healing?
Blood vessels in the broken bone tear and hemorrhage, resulting in the formation of clotted blood, or a hematoma, at the site of the break. The severed blood vessels at the broken ends of the bone are sealed by the clotting process. Bone cells deprived of nutrients begin to die
What happens in the inflammation stage of bone healing?
- capillaries grow into the hematoma
- phagocytic cells clear away the dead cells
- osteoclasts resorb dead bone
- mesenchymal stem cells build cells for repair
What happens in the repair stage of bone healing?
Bony callous formation:
- fibroblasts form cartilage
- osteoblasts form osteoid
- progressive matrix mineralisation
What happens in the remodelling stage of bone healing?
- woven bone replaced by lamella
- increased bone strength
- vascularity returns to normal
Which bone type is laid down first in fractures?
woven bone and then lamellar bone then forms
Name the types of collagen and give examples of each?
Type I = skin, bone, teeth, ligaments, tendons Type II = cartilage Type III = reticulin Type IV = basement membranes Type V = placenta, hair
How is collagen synthesised?
Inside the cell within fibroblasts as procollagen
Then secreted into the extracellular space
What does collagen consist of?
3 individual polypeptide chains form tropocollagen = a left hand helix
3 left handed helices twist together to form a right hand triple helix (super helix)
What are the characteristics of tropocollagen?
300nm long
1.5nm in diameter
3 x polypeptide chains
What is the self- assembly of collagen fibres called?
fibrillogenesis
What is the order of the structure of a tendon?
Collagen Myofibril Fibril Muscle fibre Fascicle Tendon
What do ligaments attach?
bone to bone
What do ligaments allow?
mechanical stability of joints
guide joint motion
prevent excessive motion
more elastin
What do tendons attach?
muscle to bone
What do tendons do?
transmit tensile loads from muscle to bone produce joint torque stabilise the joint enable joint motion less elastin
What is the place called where tendons or ligaments insert?
the enthesis
The enthesis can be either…
Fibrous (formed through intramembranous ossification) OR Fibrocartilaginous (formed through endochondral ossification)
What does hyaline cartilage contain?
water, proteoglycans and collagen
What are the features of hyaline cartilage?
reduces friction, resists compressive loads, high water content, low cell content, NO blood supply
Where is hyaline cartilage found other than at entheses?
trachea and bronchi lower spine (sacral surface)
What type of cartilage is the iliac surface?
fibrocartilage
What cells synthesise hyaline cartilage?
chondroblasts
Where do chondroblasts differentiate from?
mesenchymal stem cells
What does the fibrous perichondrium encapsulating the cartilage contain?
progenitor cells and differentiated chondroblasts
What are the 3 structural classifications of joints?
- fibrous - adjacent bones united by fibrous connective tissue
- cartilaginous - joined by hyaline or fibrocartilage
- synovial - articulating surfaces of bones are not directly connected, have a joint cavity with synovial fluid
What are primary and secondary cartilaginous joints?
primary = made up of hyaline cartilage e.g. sterno-costal joints secondary = made up of fibrocartilage AND hyaline cartilage e.g. pubic symphysis, stereo manurial joint, intervertebral discs
What are the 3 functional classifications of joint?
- synarthrosis = immoveable (fibrous or cartilaginous)
- amphiarthrosis = slightly moveable (cartilaginous)
- diarthrosis = freely moveable (synovial)
Give the three types of fibrous joint and an example…
- suture = skull
- syndesmoses = interosseous membrane
- gomphosis = tooth
Give two types of cartilaginous joint and an example…
- synchondroses = ribs (PRIMARY)
2. symphyses = pubic symphysis (SECONDARY)
Give the 6 types of synovial joint and an example of each…
- hinge - elbow
- ball and socket - glenohumeral joint
- gliding- radio-ulnar
- condyloid- wrist
- saddle- thumb
- pivot - atlas and axis
What do synovial joints all contain?
articular cartilage and reinforcing ligaments
What three features/structures make up a synovial joint?
- articular cartilage
- synovial membrane
- synovial fluid
Growth that occurs through an increase in cell size is called….
hypertrophy
Name the type of cell in a growing bone that is stimulated to proliferate by IGF-1
chondroblast
Name a hormone that causes growth to stop at the end of puberty
testosterone
Name the hypothalamic hormone that inhibits GH secretion
somatostatin
