L3 - Physiology of Bone COPY

Question 1

HEALTHY BONE PHYSIOL - BALANCE

i) what is healthy bone a balance between?
ii) what does too much bone resorption lead to? (3)
iii) what does too much bone formation lead to?

Answer 1

i) bone formation and resorption
ii) too much resorption > osteoporosis, osteopenia and rickets
iii) too much formation > osteopetrosis

Question 2

CLASSFICATION OF BONE STRUCTURE

i) what are the two broad classifications of bone?

ii) which two structures can be seen macroscopically on
a) outside and b) inside of bone?

iii) what two things does the inner part of bone contain?
iv) which two structures can be seen microscopically? which is more organised and which is more immature?
v) which imagine depicts cancellous bone? which depicts woven bone?

Answer 2

i) long bone and flat bone

ii) macro - see cortical bone (outside)
- cancellous bone - spongy (inside)

iii) cancellous bone - spiculues and trabeculae
iv) see lamellar structures (organised) and woven structures (immature and disorganised)

v) A - cancellous
B - woven

Question 3

COMPOSITION OF BONE

i) what two main things does it comprise of?
ii) what are the three principle cell types? what is the role of each?
iii) what organic and inorganic componets make up bone?
iv) what is bone dominated by? are there many or few cells?
v) label diagram

Answer 3

i) living cells and acellular matrix

ii) osteoclasts - bone degred and remodelling
osteoblasts - regulate bone growth/degred, found on surface and produce protein component of acell matrix
osteocytes - quiescent mature cells embedded in matrix that maintain bone

iii) organic > cells and proteins
inorganic > minerals eg calcium and phosphate = hydroxyapatite

iv) bone is dominated by extracellular matrix + a few cells
v) A - osteoclasts, B - ECM, C - osteocytes, D - osteoblasts

Question 4

HAVERSIAN SYSTEM IN LAMELLAR BONE

i) what does this allow for?
ii) what is an osteon? what does it contain?
iii) what is found at the centre of an osteon? what is the role of this structure?
iv) what structures do osteocytes sit in? what is their role?(2)
v) where do lamellae sit?
vi) what is ground substance?
vii) label diagram

Answer 4

i) allows for communication system between cells immobilised in bone matrix

ii) osteon = functional unit of compact bone
- cylinder structure containing mineral matrix and osteocytes

iii) centre of osteon = haversian canal
- allows transport of fluid and nutrients to bone

iv) osteocytes sit in lacunae
- role to maintain osteon and have long processes that allow communication

v) lamellae sit around the haversian canal
vi) ground substance is hard ECM between osteocytes
vii) A - osteon, B - haversian canal, C - osteocyte, D - canaliculi, E - ground substance, F - lamellae

Question 5

OSTEOBLASTS

i) which cell type to osteoblasts give rise to? which tissue does this come from?
ii) are they post mitotic or do they divide?
iii) what will most osteoblasts undergo? how does osteoblast number change with age?
iv) what will a low % of osteoblasts become? where will this mature cells be found?

Answer 5

i) osteoblasts can give rise to osteocytes
- osteocytes arise from mesenchyme (precusor cells in bone marrow stroma)

ii) OBs are post mitotic

iii) most osteoblasts will undergo apoptosis
- number of OBs decreases with age

iv) a low % of OBs will become osteocytes which become locked in fluid filled lacuna

Question 6

OSTEOCLASTS

i) what is their main function?
ii) are the uni or multinucleate? can they proliferate?
iii) what lineage do they arise from? which cells also come from this precursor?
iv) what does this origin allow them to do? (3)
v) what is the ruffled border? what does this aid?

Answer 6

i) bone resorption

ii) multinucleate (15-20 close packed oval shaped nuc)
- yes they can proliferate

iii) arise from haematopoietic stem cells (same as monocytes)

iv) phagocytose bone matrix and crystals (pacman)
- secrete acids that solubilise CaPo4 in bone
- secrete proteolytic enzymes from lysosomes

v) ruffled border is a membrane that forms that encloses the bone that is trying to be resorbed

Question 7

BONE CONSTITUENTS

i) what makes up 70% of the extracellular matrix?
ii) which two types of strength does bone have? what does this allow?
iii) what are the two main acellular elements of bone and what are the roles of each?
iv) label diagram

Answer 7

i) 70% ECM is made of minerals eg calcium and phosphate

ii) bone = high compressive strength (withstand pressure)
and high tensile strength (withstand stretch and bend)
- allows bone to withstand high force without breaking

iii) 2 main acellular elements are collagen and hydroxyapatite
- collagen > protein that is flexible but strong
- hydroxyapetite > mineral that provides rigidity with small spaces between to withstand force (ca and phos crystals)

iv) A - collagen helix
B - hydroxyapatite crystals

Question 8

GLYCOSYAMINOGLYCANS

i) what part of bone are they found in?
ii) what type of structure do they have? what charge do they have?
iii) what do they attract and what do they repel?
iv) what do they resist?

Answer 8

i) found in ECM especially in cartilage / ground bone matrix

ii) long polysaccharides
- highly negative charge

iii) attract water and repel eachother
iv) resist compression

Question 9

GROWTH FACTORS

i) where are these found?
ii) what causes their release? what does this subsequently lead to? (2)
iii) describe the three steps of the bone remodelling sequence?

Answer 9

i) found suspended in matrix
ii) osteoclast action causes release which leads to proliferation and mineralisation of bone
iii) bone remod > activation (force from exercise etc) then resorption then new bone formation on top

Question 10

BONE CELLS REMODEL BONE

i) which cells resorb bone? what is the area called in which they do this?
ii) which factors are activated when bone is resorbed? what do they signal to?
iii) which cells are then attracted to the site? what do they do?
iv) where is new bone deposited? how is it layed down?
v) what are the two main factors governing bone remodelling?

Answer 10

i) osteoclasts resorb bone in Howships Lacuna
ii) growth factors are activated when bone is resorbed which signal to osteoprogenitor cells to differentiate into osteoblasts
iii) osteoblasts are attracted to the site of bone resorbtion and deposit bone here
iv) bone is depos on pre exisiting bone and layed down in different directions
v) recurrent mechanical stress and calcium homeostasis

Question 11

BONE FORMATION

i) what are the two types of bone that can form
ii) what does intramembranous bone formation involve?
iii) what does endochondral bone formation involve?

Answer 11

i) compact or cancellous bone
ii) intramembranous bone is bone formation that involves direct conversion of mesenchymal tissue into bone (occ in bones of the skull)
iii) in endochondral bone formation - bone replaces hyaline cartilage to grow the bone

Question 12

MECHANICAL STRESS & REMODELLING

i) what does mechanical stress inhibit and what does it promote?
ii) what can cause bone to rapidly weaken? give two examples
iii) which two cell types detect stresses?
iv) what type of bony spicules are seen in healthy bone? what is seen in osteoporosis?

Answer 12

i) inhibits bone resorption and promotes deposition
ii) lack of weight bearing exercise can cause bones to rapidly weaken eg prolonged bed rest and lack of gravity (space)
iii) surface osteoblasts and osteocyte networks detect stressors

iv) thicker and lots of bony spicules seen in healthy bone
- thinner and less bony spicules are seen in osteoporosis

Question 13

BISPOSPHONATES

i) which condition can they be used to treat?
ii) give an example? which endogenous molecule is it structurally similar to?
iii) what charge does it have? what does this allow it to bind?
iv) what do BPs principally do? how do they do this? (2)
v) what is the endogenous regulator of bone turnover?

Answer 13

i) osteoporosis
ii) alendronate - similar to inorganic pyrophosphate
iii) has a highly negative charge which allows it to bind calcium in bone

iv) BPs inhibit osteoclast mediated bone resorption
- accumulate on bone and are ingested by osteoclasts
- then interfere with osteoclast metabolism (stops them resorbing anymore bone)

v) inorganic pyrophosphate

Question 14

OTHER DRUGS USED FOR OSTEOPOROSIS

i) which drug encourages osteoblast formation of bone? what hormone is this drug a portion of?
ii) what pattern of application of this hormone activates osteoblasts rather than osteoclasts?
iii) which drug can prevent osteoclast maturation? what type of drug is this and what does it target?

Answer 14

i) teriparatide
- portion of human parathyroid hormone

ii) intermittent application of PTH activates OBs > OCs

iii) denosumab can prevent OC maturation
- monoclonal antibody that targets RANK ligand

Question 15

OSTEOPETROSIS

i) what is it? why does this happen? is it auto dom or recessive?
ii) which two channels may there be defects in? why does this result in disease?
iii) name two consequences assoc with nerve damage? why do you get nerve damage?
iv) why do you get brittle bones?
v) why do you get severe anaemia?

Answer 15

i) excessive bone growth as to osteoclasts cant remodel bone
- auto recessive

ii) defects in vacuolar proton pump (H+) or chloride channel
- results in disease as OCs need to secrete HCl in order to resorb bone - defect in one of these pumps means HCl cant be produced therefore excess bone growth

iii) blindness and deafness
- overgrowth of bone in skull foramina causes it to press on nerves

iv) brittle bones as normal spaces are filled in with bone making it thick and easily snapped as there is less give
v) anaemia due to areas where bone marrow should be is filled in with solid bone therefore less BM

Question 16

PHASES OF FRACTURE

i) what is the first stage? what are the two key components here?
ii) what is the second phase? what type of bone is present?
iii) what is the third phase? which type of bone is present?
iv) what is the final phase? what type of bone is present?
v) how long does it take for a fracture to heal in upper body and lower body?

Answer 16

i) stage 1 - reactive phase = haematoma and inflammation
ii) soft callus formation = woven bone/cartilage
iii) hard callus formation = lamella bone replaces woven bone
iv) remodelling = trabecular bone replaces lamellar bone

v) upper body takes 2-3 weeks to heal
- lower body takes >4 weeks to heal

Question 17

HORMONES OF CALCIUM REGULATION

i) what effect does parathyroid hormone have on plasma calcium? where is it made?
ii) give two other names for vitamin D? name the three areas its made? what effect does it have on plasma calcium?
iii) what does calcitonin do? where is it made? what can it be used as a treatment for?
iv) give five things required for healthy bone growth

Answer 17

i) PTH increases plasma calcium
- made in chief cells in parathyroid gland

ii) Vit D = calcitriol/1,25-do-hydroxy-cholecalciferol
- made in skin > liver > kidney
- increases plasma calcium

iii) calcitonin decreases plasma calcium by encouraging calcium to go into bone
- made in C cells in thyroid gland
- can be used to treat osteoporosis

iv) high calcium diet, vitamin D, hormones (testos and oes), exercise/bone loading, genetics

Question 18

PTH AND BONE RESORPTION

i) what cell does PTH bind its receptor on? what does this cause the cell to express?
ii) which cells are RANK receptors found on?
iii) what happens to this cell when rank R binds its ligand? what does this ultimately result in?
iv) what pattern of PTH release causes this?
v) what effect does OPG have on rank ligand? what role does it therefore play

Answer 18

i) PTH binds receptor on osteoblasts
- this causes OB to express Rank ligand

ii) rank receptors are on osteoclast precusor cells

iii) Rank lig binds receptor > causes OC precursor to differentiate and fuse > osteoclast
- results in bone resorption

iv) continuous PTH release

v) OPG hides rank ligand so OC progenitors cant recog it
- regulates the process and acts as a decoy receptor

Question 19

VITAMIN D PRODUCTION/ACTIVATION

i) where is it first synthesised? what form is it in? is it active or inactive?
ii) what effect do liver enzymes have? what intermediate is produced?
iii) what is the fully active version? where does conversion to this form take place?

iv) what does the fully active version of vitamin D cause in the
a) gut enterocytes, b) intestine, c) kidneys? what does this all result in?

Answer 19

i) in the skin as vitamin D3 (cholecalciferol) = inactive

ii) liver enzymes cause partial activation
- produce 25-OH cholecalciferol

iii) fully active is 1,25 di-OH cholecalciferol
- enzymatic activity in the kidneys

iv) fully active (1,25 di-OH cholecalciferol)
a) increased calbindin in gut enterocytes
b) increased intestinal abs of calcium
c) increased calcium resorption in the kidneys
- ultimately increases plasma calcium

Question 20

VITAMIN D

i) what effect does it have on the intestine?
ii) what does it stimulate the kidneys to do?
iii) which cells does it indirectly stimulate? is this a strong or weak effect?
iv) what does it facilitate? what does this allow?

Answer 20

i) increases intestinal abs of calcium by increasing calbindin
ii) stimulates kidneys to reabsorb calcium
iii) indirectly stim osteoclasts (weak effect)
iv) facilitates bone remodelling which allows increase of serum calcium

Question 21

CAUSES OF LOW PLASMA CALCIUM

i) give three things that can result in calcium loss
ii) which two things are associated with low calcium intake?
iii) dysfunction of which gland can cause low plas ca
iv) give five things that chronic hypocalcemia results in

Answer 21

i) pregnancy, lactation and kidney dysfunction
ii) insufficient ingestion of calcium and rickets (low vit D)
iii) parathyroid gland dysfunction
iv) chronic hypercalc > skeletal deforms (rickets), increased bone fractures, impaired growth, short stature, dental deformities

Question 22

ACUTE HYPOCALCAEMIA

i) what does this ultimately result in?
ii) which three signs are associated with the NMJ?
iii) give the two clinical signs that are seen and explain each
iv) how is gut motility affected?

Answer 22

i) increased exciteability
ii) arrhythmias, tetany and convulsions

iii) chvosteks sign - tap cheek and face will contract
- Trousseas sign - cut off blood supply to arm and muscles will flex uncontrollably

iii) gut motility is decreased

Question 23

LOW PLASMA CALCIUM AND EXCITABILITY

i) is calcium higher inside or outside the cell?
ii) what effect does hypocalcemia have on the cell membrane? what effect does it have in relation to the stability of the membrane?
iii) what does the altered stability of the membrane allow?

Answer 23

i) calcium is higher outside the cell
ii) hypocalc causes the membrane to be more exciteable and less stable
iii) less stable > more sodium is able to leak through

Question 24

HYPERCALCAEMIA AND EXCITABILITY

i) what effect does hypercalcaemia have on exciteability? how does it do this?
ii) give three key signs that may be seen due to this change in excite?
iii) what is seen in extreme circumstances?
iv) give two events seen in severe hypercalcemia

Answer 24

i) decreases excite by making the membrane more stable so it is less likely to fire
ii) constipation, depression and other psych disorders
iii) abnormal heart rhythms eg short QT
iv) severe > coma and cardiac arrest