MSK physiology Flashcards
Where does endochondral ossification take place?
All bones below the skull except for the clavicle
When does endochondral ossification start
2 months in utero
What does endochondral ossification use as a blueprint
Hyaline cartilage for ossification
1st stage of endochondral ossification
Perichondrium becomes vascularised:
Blood vessels supply new nutrients to mesenchymal cells, causing differentiation
Newly formed osteoblasts gather at the diaphysis wall to form a bone collar.
The starting point for ossification
Primary ossification centre
2nd phase of endochondral ossification
Chondrocytes within a central cavity enlarge causing the matrix to calcify
Calcified matrix impermeable to nutrients, causing cell death
Central clearing forms where cells have died (supported by the bone collar)
Healthy chondrocytes elsewhere cause elongation
3rd phase of endochondral ossification
Periosteal bud invades cavity-causing formation of spongy bone
Bud consists of artery, vein, lymphatics and nerves. It also delivers osteogenic cells.
Osteoclasts degrade cartilage matrix while osteoblasts deposit new spongy bone
Bone continues to elongate elsewhere
4th phase of endochondral ossification
The primary ossification centre continues to enlarge
Osteoclasts break down the newly formed spongy bone
The medullary cavity begins to form
Cartilaginous growth now only with epiphysis
The bony epiphyseal surface begins to form
A secondary ossification centre may appear at one or both epiphysis
5th phase of endochondral ossification
Epiphyses ossify
Secondary ossification centres usually only appear after birth
Longer bones more likely to have two secondary centres
Short bones have only one centre irregular bones may have several
Cartilage now remains on bone surfaces and at epiphyseal plates
When does intramembranous ossification occur
In utero before week 8
From what does intramembranous ossification occur
All bone formed from hyaline cartilage and fibrous membrane
What bones are formed from intramembranous ossification
Cranial bones and clavicles formed this way mostly flat bones
First stages of intramembranous ossification
Early in development, you have mesenchymal stem cells that aggregate to form osteoblast by differentiate
Form an ossification centre
Osteoblasts begin to secrete osteoid (unmineralised bone)
2nd stages of intramembranous ossification
Peripheral mesenchymal cells continue to differentiate.
Osteoblasts secrete osteoid inward towards the ossification centre.
Osteoblasts become trapped in osteoid, causing differentiation into osteocytes.
Osteoid calcified and hardened after several days
3rd stages of intramembranous ossification
Osteoid continues to be deposited and assembles in a random manner around the embryonic blood vessels
Finely woven trabeculae formed
Mesenchyme begins to differentiate into periosteum
4th stages of intramembranous ossification
Lamellar (compact) bone replaces woven bone at the outer edge
Layered
Internal spongy bone remains
Vascular tissue within trabecular spaces forms red marrow
Osteoblasts remain on bone surfaces to remodel when needed
Summary of intramembranous ossification
Bone forms from membrane or cartilage
Mostly flat bones
Mesenchymal cells differentiate
Osteoblasts direct growth
Woven bone forms
Lamellar bone and outer periosteum forms
Surface osteoblasts remodel as reacquired (stress)
What is cartilage
Type of connective tissue
Function of bones
Storage of minerals (eg. calcium hydroxyapatite)
Transmission of body weight
Protection of vital organs and structures
Anchorage - lever system for movement
Determination of body shape
Raises body from the ground against gravity
Houses bone marrow to facilitate haematopoiesis
Types of bones
Long bones
Short bones
Flat bones
Sesamoid bones
Irregular bones
Pneumatic bones
Bone Development classification
Bones are classified into three groups according to their method of development (ossification)
3 groups include:
- membranous bones
- cartilaginous bones
- Membrocartilaginous bones
Membranous bones
Also called dermal bone
These bones have an Intramembranous method of ossification
Membranous sheets formed by condensation of mesenchyme
Example of membranous bones
Flat bones of the skull
Bones of face
Maxilla
Zygomatic
Cartilaginous bones + example
Have Intracartilaginous method of ossification
Example:
Ribs
Vertebrae
Bones of limb
Membrocartlagenous bones
Have both types of ossification
Intramembranous
Intracartilgenous
Example of membrocartilagenous bone
Occipital
Temporal
Sphenoid bone
Mandible & Clavicle
Regional classification of bones
Axial Skeleton
Appendicular skeleton
Axial skeleton
Bones of head and trunk
Consists of 80 bones
E.g skull bone
Rib cage
Vertebral column
Ossicles of middle ear
Appendicular skeleton: what does it include + examples
Includes: Pectoral girdle
Upper extremity
Pelvic girdle
Lower extremity
E.g: Tibia
Fibula
Ulna
Radius
Long bones
Have more length than width
Contain a tubular shaft called the diaphysis
The ends of the long bone are called epiphysis
Contains red marrow in the cavities of spongy bone (red blood cell production)
Epiphyseal line
2 types:
- Typical long bone
- The miniature long bone
Typical long bones
Have considerable length
e.g humerus, Radius, ulna, femur, tibia, fibula
Miniature long bone
Have short length
E.g
- Metacarpals & phalanges of the hand
- Metatarsals & phalanges of foot
Short bones
Have almost the same length width and thickness
Irregularly shaped
Have limited movement
Spongy bones with an outer covering of the compact bone
E.g bone of wrist & ankle
Flat bone
Thin and curved plates
Have a broad surface for muscle attachment
e.g sternum & ribs
Irregular bones
Have irregular shape with several processes
Eg hip bone + bones of the face
Sesamoid bones
Bony nodules embedded in tendon or muscle
The number is not fixed
Acts as a pulley and protects the tendon from a trauma
Sesamoid example
The knee cap (patella), embedded in tendon of quadriceps femoris muscle
Accessory bones
Not always present in the body
Further divided into 3 groups:
Supernumerary bones
Wormian bones
Hetrotropic bones
Supernumery bone
Bones are the extra centre of ossification which doesn’t fuse with the main bone
E.g
OS Vesalianum, adjacent to tuberosity of 5th metatarsal bone
Wormian bone
Extra bones in skull structure
E.g lambdoid bone
Heterotropic bone
Form in muscles of other soft tissue
E.g Riders bone
Characteristics of skeletal cartilage
Contains lots of water which helps resist tension and compression
Characteristics of short, irregular and flat bones
Thin plates of spongy bone covered by compact bone
No well-defined cavity for the bone marrow to sit-in
Hyaline cartilage covers surfaces involved with joints
What is diaphysis made up of?
The compact bone surrounding the medullary cavity
In adults, it contains yellow bone marrow which is high in fat
What do epiphyses contain
Spongy bone within compact bone and cartilage on the joint surface
What is the epiphyseal line a remnant of?
Epiphyseal plate
What is the periosteum
What does endosteum do
Covers the internal spongy bone layer as well as canals pass-through.
Where can you find red marrow
Cavities of spongy bone
Microscopic anatomy of the bone
Osteogenic cell
Lacuna
Osteocyte
Osteoblast
Osteoclast
Canaliculi
Lamellae
What are osteogenic cells
Stem cells that differentiate are found in the periosteum and endosteum
If the bone is growing these flattened or squamous cells can differentiate into other types at certain times
What do osteoblasts do?
Build bone
Scerete bone matrix that consists of collagen and other proteins and therefore causes bone growth
They are actively mitotic and cube-shaped while active
What happens when osteoblasts are surrounded by bone matrix
Differentiate to become osteocytes
Osteocytes function
Mature cells that monitor and maintain the bone matrix communicating information to other cells
Bone lining cells
Flat cells found on the surface of the bone
Help maintain the matrix
Bone classification on a microscopic level
Primary (Woven): Rough Plan *
Made quickly
Disorganised
No clear structure
Secondary (Lamellar): Final Piece * Made slower
Organised
Clearly structured
Osteoclast
Large cells with multiple nuclei use enzymes to break down bone. This is a normal process called resorbtion that releases minerals to be transferred into the blood
What is an osteon
Series of lamellae which are hollow tubes arranged like the rings of a tree trunk.
Within each lamella are collagen fibres running in a specific direction with crystals of bone salts in between
As we proceed inward the next lamellae will have its fibres running in another direction all the way to the centre
It’s the alternating pattern that gives compact bone its ability to withstand torsion
Central canal
The open region at the centre containing blood vessels and nerve fibres that serve the cells in that osteon
Perforating canal
The shorter canal that perpendicularly allows for connections to run all the way from the periosteum to the central canal of the medullary cavity
What are lacuna filled with
Osteocytes
Connected by cannaliculi
What is interstital lamallae
Fill in gaps between osteons
Circumferential lamellae
makeup circumference of diaphysis surrounding all the osteons
Chemical composition of bone
Organic components
Cell (osteoblasts, osteocytes)
Osteoid (organic part of bone matrix) - made up of ground substance + collagen fibres which are secreted by osteoblasts
Inorganic components
Hydroxyapatites (crystals of calcium phosphate) - account for hardness of bone
3 Important hormones involved in calcium and phosphate regulation
Vitamin D
Parathyroid hormone
Calcitonin
Where is 99% of calcium stored
in bone
Why do we need to regulate calcium and phosphate levels
Calcium is important for muscle contraction, nerve conduction
Phosphate is important for biochemical processes and energy
When does parathyroid hormone secrete calcium (stimulated)
When there is a decrease in plasma Ca2+
What does parathyroid hormone target
Bone
Kidney
What effect does parathyroid hormone have on the bone (summary)
to break down minerals so calcium and phosphate can enter plasma. This increases calcium and phosphate levels in plasma
What effect does parathyroid hormone have on the kidneys
Targets enzymes 1 alpha hydroxylase. This converts 25 OH cholecalciferol to 1,25 DiOH cholecalciferol (calcitriol)
What is the name of the active form of vitamin D ?
calcitriol
Calcitriol function
Calcitriol stimulates bone to break down minerals into calcium and phosphate.
Calcitriol has a negative feedback on the parathyroid gland
Calcitriol also stimulates the GIT to increase calcium and phosphate absorption
Calcitriol targets the nephrons
PCT: Stimulates the reabsorption of calcium increasing plasma calcium levels
DCT: Stimulates reabsorption of calcium as well increasing plasma calcium levels
Vitamin D synthesis + activation
U.V reacts with 7 Dehydrocholesterol and converts it to cholecalciferol (Vitamin D3) -this takes place in the skin
In liver vitamin D3 (cholecalciferol) gets converted to 25 OH cholecalciferol (calcidiol)
In kidney 25Oh cholecalciferol gets converted via enzyme in the kidneys (1 alpha hydroxylase) into 1,25 diOH cholecalciferol
Inactive form of vitamin D
25 OH cholecalciferol
Vitamin D and parathyroid hormone
Increase calcium plasma levels
Role of calcitonin
Decrease in calcium plasma levels
What stimulates the secretion of calcitonin
Increase in calcium plasma levels stimulates the thyroid gland to secrete calcitonin
What does calcitonin have the opposite effect as
Parathyroid hormone
Osteoblast vs osteoclast
Osteoblast: build bone
Osteoclast: break down bone
Process of the breakdown of minerals in the bone due to PTH
Osteoblast has a PTH receptor when PTH binds it does three things:
- Osteoblast proliferation
- Stimulate the expression of RANK ligand on the osteoblast
- stop osteoblast from making osteoprotegerin (OPG)
Preosteoclast expresses a receptor called the RANK receptor.
The rank ligand expressed on the osteoblast will bind to the RANK receptor of the osteoclast, as it is no longer inhibited by OPG
This causes the osteoclast to proliferate and differentiate. The proliferation + differentiation of osteoclast is further stimulated by macrophage colony-stimulating factor(MCSF) binding to the C-FMS receptor of osteoclast.
(Pre)osteoclast → Active osteoclast and will become multinucleated
Active osteoclast will secrete HCl eating away at the bone causing bone resorption and allowing minerals (Calcium + phosphate) to leave
What does Osteoprotegerin do?
Inhibits the activity of RANK ligand binding onto another receptor for example the RANK receptor of the (pre) osteoclast
Causes of bone fracture
Trauma
Vitamin A deficiency
Low bone density
Age
What do fractures lead to?
Tears and destroys blood vessels which carry nutrients to the bone
How is a fracture classified?
The first stage of fracture healing
Hematoma formation
Blood accumulates forming the hematoma this causes the death of some cells and swelling and pain associated with the area.
2nd stage of fracture healing
Fibrocartilaginous callus formation (soft callus). This occurs a few days after hematoma formation
Blood vessels are regrowing
Type of meshwork from granulated tissue forms the callus
Outside the fracture where the periosteal is, the external callus is formed.
Granulation tissue fills in the gap where the fracture is and rejoins the fractured bones together
Essentially what the soft callus does
What is the third stage of fracture repair
REPAIR: Bony callus formation
The soft callus previously formed will become a bony callus with the help of other tissue
New blood vessels are formed
Final stage of fracture healing
REMODEL: Bone remodelling stage
The bony callus will remodel to become fine bone therefore healing occurs
Compact bone is laid down and osteoblastic activity is also increased
Osteomyelitis
When a bacteria (staphylococcus) van infects a bone during a fracture or through the bloodstream
Once infected the person starts feeling severe pain and swelling of the bone injured site
The bacteria usually affects the ends of long bone
The bacteria causes necrosis of the cells so the bone cells begin to die, pus formation and previously strong bones will become weak
If left untreated osteomyelitis becomes chronic and a lot of bone cells can begin to die
What is spongy bone
Trabecular bone makes up the inner bone
Compact bone
Dense bone made up of osteons
Forms outer bone
Ends of long bone
Epiphyses the ends of the long bone are separated by metaphysis to the centre of the bone
The Centre of the bone (shaft) called
Diaphysis
The hollow centre of the bone is called and what does it contain
Medulla which can contain bone marrow
What are osteoblasts responsible for
Building bone
Have a single nucleus and sits on the bone surface
What are osteoclasts responsible for?
Breaks down bone, and multinucleated
resorbing cells. They contain large amounts of lysosomes.
What are osteocytes and can you differentiate them from other bone cells
mature bones cells from trapped osteoblasts
Cytoplasmic projections, single nucleus
Osteoprogenitor cells
Progenitor cells that become osteoblasts
Cells of the bone
Osteocytes
Osteoblasts
Osteoclasts
Osteoprogenitor
What makes up the periosteum
Surrounds compact bone, also contain pain fibres
outer fibrous layer: protects bones and provides attachment for tendons and ligaments
inner cellular layer: contains osteoprogenitor cells differentiate into osteoblasts (secretes bone matrix) and chondroblasts (produce cartilage)
What surrounds the periosteum
Blood vessels which penetrate bone through canals allowing to supply inside of bone
What is the functional unit of compact bone
Osteon
What is a ligament
Binding one bone to another bone
Made up of fibrous connective tissue
Ligaments aids mechanical joint stability and guide joint motion. Ligaments also prevent excessive motion.
Hierarchy of ligament structure
Tendon vs Ligament
joint classification by degree of movement
Synarthroses
Immobile
Mostly fibrous
Eg. Between skull sutures, manubriosternal joint
Amphiarthroses
Slightly Mobile
Mostly cartilaginous
Eg. Intervertebral discs, pubic symphysis
Diarthroses
Freely mobile
Mostly synovial
Eg. Hip,shoulder joint, elbow joint
Joint classification by structure
Fibrous
- Held together by fibrous tissue
Cartilaginous
- Held together by cartilage
Synovial
- Held together by a synovial fluid-filled capsule
- All have articulations of cartilage, a joint capsule, a joint cavity, synovial fluid, and reinforcing ligaments
- In some joints bursa (eg. in the hip) or menisci (eg. In the knee) are present
Types of synovial joints
Hinge joint
Pivot joint
Ellipsoid/ Condyloid joint
Gliding/Plane joint
Ball and socket joint
Saddle joint
BSHPEP
Ball and Socket joint
Ball & Socket
- A ball within a socket (pretty much as the name suggests)
- Wide range of movement in all planes
- Shoulder and hip joint
Condyloid joint/Ellipsoid joint
Condyloid
- Oval sitting within the oval cavity
- Movement in two planes
- Metacarpophalangeal
Hinge joint
Hinge Joint
- Elongated oval in a curved socket
- Large range of movement in a single plane
- Elbow
Pivot joint
Pivot
- Bone pivots around an axis
- Allows a large amount of rotation
- C1/C2
Saddle joint
Saddle
- Two saddle-shaped surfaces articulating
- Movement in two planes
- Thumb
Gliding Joint
Gliding
- Two flat surfaces articulating
- Limited movement in 2 planes
- Carpal joints
What is cartilage + characteristics?
Avascular, flexible tissue
It contains:
cartilage cells (chondrocytes)
Proteoglycans
Glycosaminoglycans
Collagen fibres
Elastic fibres
Function of chondrocytes
Cartilage cells that secrete extracellular matrix
Types of cartilage
Hyaline cartilage
Elastic cartilage
Fibrocartilage
Components of hyaline cartilage
The appearance of hyaline cartilage
Smooth or glassy appearence
Where can you find hyaline cartilage
Nose
Trachea
Larger bronchi
Cartilages of the larynx
Articular surfaces of movable joint
Epiphyseal plates of long bone
Costal cartilage
Perichondrium what is it?
Dense connective tissue covers the surface of hyaline cartilage except for on the surface of movable joints
Contains vascular supply to cartilage
Two layers: outer fibrous
inner chondrogenic
Contains: Type 1 collagen fibres + fibroblast
Where are chondroblasts found
inner layer of perichondrium
Chondroblasts differentiate to become
Chondrocytes
Types of collagen
Type I
Type II
Type III
Type IV
Type I collagen
Strongest and most abundant form
Found in tissues where increased tensile strength is required:
Bone
Tendon
Cornea
Skin
Type II collagen
Spongy type that absorbs shock from compressive forces
Found in tissues where compressive forces occur
Cartilage
Vitreous Body
Nucleus Pulposus
Type III collagen
Webby type that assists with pulling forces
Found in tissues where pulling force occurs
Blood vessels
Uterine Tissues
Fetal Tissues
Granulation Tissues
Type IV collagen
Located in basement membrane to provide stabilisation of the cell
Kidney
Ear
Eye
Skin
Collagen synthesis
- Guests: glycine (the most abundant amino acid in collagen). There is only a single collagen chain known as preprocollagen
- Water + Lemon: hydroxylation + Vitamin C (in order for hydroxylation to occur you need vitamin C)
- Sweets: Glycosylation (formation of hydrogen&disulfide bond). The bonds result in a triple helix (procollagen)
The first three steps occur in R.E.R → Golgi Body → leave the cell
- Guests Leave Home: Procollagen leaves cells via exocytosis
- Procollagen → Tropocollagen undergoes proteolytic cleavage. Tropocollagen is insoluble in water
- Covalent bonds between 3 tropocollagen (enzyme lysyl oxidase. copper is also required) → collagen
Osteogenesis imperfecta
If there is a problem in glycosylation in collagen synthesis then there will be a defect in forming a proper triple helix
Vitamin C deficiency
Scurvy
Maturation of bone cell
Mesenchymal stem cell/osteoprogenitor → Osteoblast → osteocyte → Osteoclast
What do osteoblasts secrete
osteoid
What does osteocyte regulate?
Existing bone
How are osteocytes formed?
When osteoid is mineralised with crystals of hydroxyapatite, the osteoblasts are trapped within the bone and become less synthetically active osteocytes. differentiate and form osteocytes. Supplies nutrition to bone
What type of cell is an osteoclast
Phagocytic cells
Erode and recycle bone matrix
Work with osteoblasts to maintain calcium homeostasis. It also responds to mechanical stress
What is bone remodelling?
Old, brittle bone tissue is removed or resorbed and replaced by new tissue
Continuous process
Bones are resorbed by osteoclasts and remade by osteoblasts
When does bone remodelling occur
Reshaping bones after a fracture
Repairing micro-cracks - form when bones are under stress
Composition of lamellae
Organic part → collagen
Inorganic part (hydroxyapatite) → calcium phosphate
What is in the centre of each osteon
Haversian canal
Blood supply and innervation
What is the medullary canal lined by
spongy/cancellous bone
What is the epiphysis made up of
spongy bone mostly
Spongy bone is made up of crosslinking roads called trabeculae- add resistance to mechanical stress
Bone Formation
- Osteoblasts sense microcracks at their location e.g bones are bearing too much weight
- Osteoblasts secrete Rank L(receptor activator of nuclear factor Kappabeta ligand)
- Rank L binds to RANK receptors on the surface of nearby monocytes
- Monocytes fuse together to form a multinucleated osteoclast cell (RANK L also helps the osteoclast to mature and activate in order to start resorbtion bones)
- Osteoclast secretes lysosomal enzymes (collagenase mostly) and digests collagen in the organic matrix
Secretes HCl which dissolves hydroxyapatite into calcium and phosphate ions
- This drill pits on the bone surface known as Howship’s Lacunae
- Ions enter Bloodstream
- There is a scattering of osteocytes in the bony matrix and when they get freed up by the dissolving bone they get phagocytosed by osteoclasts
- Osteoblasts also secrete osteoprotegerin. Binds to RANKL. This slows down the activation of osteoclasts
- Once osteoclasts have completed their job undergoes apoptosis
- Following bone resorbtion osteoid seam is secreted (a substance to fill in lacunae created by osteoclasts)
- Calcium and phosphate deposit on the seam forming hydroxyapatite
- As osteoblasts keep producing new bony material, many get trapped within tiny lacunae and become osteocytes
What is Wolff’s Law
Bones that bear a lot of weight remodel at a high rate
What is RANK L responsible for in bone remodelling
Initiate remodelling
What is osteoprotegerin responsible for in bone remodelling
Turn off remodelling
How do osteoclast and osteoblast communicate and signalling
Communicate via cytokines, OPG and RANK signalling
Cytokines are:
REDUNDANT: Diff types can perform one job
PLEIOTROPIC: can initiate effect on many diff tissues
What is RANKL
Receptor activator of nuclear factor kappa-B ligand
Expressed by osteoblasts
Plays an important osteoclast formation, function and survival
What is RANK
Receptor activator of nuclear factor kappa-B
Located on osteoclast precursors and mature osteoclasts
What is OPG
Osteoprotegerin
Binds to and inhibits RANKL
Expressed by osteoblasts and other tissues including spleen, bone marrow, heart, liver and kidneys
Protective against bone loss
Give an example of a long bone.
Humerus.
Give an example of a flat bone.
The skull.
Give an example of an irregular bone.
Vertebrae.
What is the axial skeleton?
The part of the skeleton consists of the head and trunk.
What are osteoblasts derived from?
Mesenchymal stem cells.
What is the function of osteoblasts?
They synthesise a type 1 collagen-rich matrix, osteoid. (They contain large amounts of RNA for this function).
What are osteoclasts derived from?
Hematopoietic stem cells.
Give 5 reasons for bone remodelling?
- Replace woven bone for lamellar.
- Response to exercise.
- Repair damage.
- Obtain calcium.
- Form bone shape.
What type of bone does endochondral ossification produce?
What type of bone formation uses a cartilaginous pro-former?
Endochondral ossification.
Describe primary bone.
Newly formed, poorly organised. Calcium is in an amorphous form. This bone is heavy and weak.
Describe secondary bone.
Organised collagen. Calcium is in a crystalline form (hydroxyapatite). This bone is lighter and stronger and replaces primary bone.
In the blood approximately how much calcium is bound to plasma proteins?
About 50% is bound to plasma proteins, notably albumin.
In the blood approximately how much calcium is ionised?
Just less than half.
In the blood approximately how much calcium is complexed?
A very small amount is complexed, bound to citrate/phosphate etc.
What are the 3 ways in which the calcium in the blood is distributed?
- Ionised - metabolically active and is the most important for cellular function.
- Bound to plasma proteins - non metabolically active.
- Complexed e.g. citrate, phosphate.
What is the affect of alkalosis on ionised calcium?
Alkalosis increases the pH, this increases the negative charge on albumin and so affects ionisation as more calcium binds to albumin and less is ionised.
Give 4 sources of calcium.
- Dairy products.
- Oily fish.
- Cereal.
- Broccoli.
Where in the intestine is calcium actively absorbed?
Duodenum and jejunum.
Where in the intestine is calcium passively absorbed?
Ileum and colon.
Where does the majority of Ca2+ reabsorption happen in the kidney?
At the PCT.
Where does active Ca2+ reabsorption happen in the kidney?
DCT - this is where PTH will act.
Where in the body can Calcium come from to enter the blood?
- Absorbed from the intestine.
- Resorbed from bone.
- Reabsorbed at the kidney.
What do C-cells release?
Calcitonin.
What is the effect of low phosphate levels in the body?
Poor mineralisation of bone can result in rickets, osteomalacia, pain and fractures etc.
Give 3 dietary sources of phosphate.
- Protein.
- Dairy.
- Seeds and nuts.
Give 3 regulators of phosphate.
- PTH.
- 1,25-(OH)2-vitD.
- FGF-23 = major regulator!
What is the action of PTH with regards to phosphate homeostasis?
It increases phosphate absorption at the intestine and decreases phosphate reabsorption at the kidney.
What triggers the release of FGF-23?
- High phosphate levels.
- PTH.
- 1,25-(OH)2-vitD.
What is the action of FGF-23?
It acts to decrease phosphate levels!
1. It increases phosphate excretion at the kidneys.
- It decreases 1-hydroxylase meaning less 1,25-(OH)2-vitD is produced and so less phosphate will be absorbed from the intestine.
What is the function of PHEX?
It breaks down FGF-23 when phosphate levels have decreased.
What could happen if there was a dysfunction of PHEX?
FGF-23 wouldn’t be broken down and so serum phosphate would be very low and urinary phosphate would be high. You would be unable to mineralise bone - osteomalacia.
What is klotho and what is its function?
Klotho is a transmembrane protein that modifies FGF receptors making them specific for FGF-23.
What would be the affect on FGF-23 if you were vitamin D deficient?
You would have low phosphate levels as less will be absorbed from the intestine and so FGF-23 would be low as its trigger is high phosphate levels.
Define coupling.
Bone formation occurs at sites of previous resorption.
Define balance in osteoblast/osteoclast communication.
The amount of bone removed by osteoclasts should be replaced by osteoblastic activity.
What would be the affect on bone if you had unopposed RANK ligands?
There would be increased bone loss as more osteoclasts would be stimulated due to the lack of OPG.
What is the affect of increased activity on bone?
Increased activity means there are higher than customary strains on the bone and so you get bone formation.
What is the affect of decreased activity on bone?
Decreased activity means there are lower than customary strains on the bone and so you get bone loss.
What is osteomalacia?
An inability to mineralise bone.
What is the usual cause of osteomalacia?
Vitamin D deficiency.
What is the DEXA T score range for osteopenia?
-1.5 -> -2.5.
What is the DEXA T score range for osteoporosis?
-2.5 or lower.
Name 4 risk factors FRAX uses in determining the 10-year probability of osteoporotic fracture.
- Family history of parental hip fracture.
- Smoking status.
- Use of glucocorticosteroids.
- Diagnosis of rheumatoid arthritis.
In osteoporosis what would the blood tests of bone profile look like?
Everything would be normal! Normal calcium, phosphate, PTH, alkaline phosphate etc. Osteoporosis is a problem with bone density, not mineralisation.
What compound is a marker of increased bone turnover?
Alkaline phosphatase.
What type of muscle fibres are slow-twitch?
Type 1.
By what process do type 1 muscle fibres get energy?
Oxidative processes and so have lots of mitochondria.
What type of muscle fibres are very sensitive to fatigue?
Type 2b.
What type of muscle fibres would be found in postural muscles?
Type 1.
By what process do type 2a muscle fibres get energy?
Oxidative and glycolytic energy processes.
By what process do type 2b muscle fibres get energy?
Glycolytic processes.
What type of muscle fibres are fast twitches?
Type 2a and 2b.
Define fracture.
A breach in the continuity of bone.
When muscle fibres are stained to demonstrate the presence of fibrillar ATPase, which muscle fibres appear darker stained?
Type 1 muscle fibres, they have lots of fibrillar ATPase for oxidative energy processes and lots of mitochondria.
What 5 things need to be considered in describing a fracture?
- Site - which bone? Proximal/distal?
- Pattern - oblique, transverse, spiral etc.
- Displacement - % displaced, angulation.
- Joint involvement (intra-articular).
- Skin involvement - breach in skin is an orthopaedic emergency.
What are the 3 principles of fracture management?
- Reduce the fracture, and alignment.
- Immobilize the fracture - stability!
- Rehabilitate the patient.
What contains more type 1 collagen, ligament or tendon?
Tendon.
Briefly describe the composition of ligaments and tendons?
Dense connective tissue consisting of parallel fibres. There are fibroblasts that synthesise and remodel the ECM. The tissue is sparsely vascularised.
What percentage of ligaments and tendons is the extracellular matrix (ECM)?
80%.
What is the name of the connective tissue that surrounds the fascicles of a tendon?
Endotenon.
What is the name of the connective tissue that surrounds tendons?
Epitenon.
What are the entheses?
Where a tendon or ligament inserts into the bone.
What are the two types of insertion into entheses?
- Fibrous.
- Fibrocartilage.
How is a fibrous insertion formed?
Through intramembranous ossification.
How is a fibrocartilage insertion formed?
Through endochondral ossification. There is a gradual change: ligament -> fibrocartilage -> mineralised cartilage -> bone.
Name 3 things that can decrease the tensile strength of tendons.
- Ageing.
- Pregnancy and postpartum.
- Immobilisation.
What can increase tendon and ligament tensile strength?
Physical training.
Give 3 functions of joints.
- Allows movement in 3 dimensions.
- Bears weight.
- Transfers load evenly onto the musculoskeletal system.
Give an example of a fibrous joint.
Teeth, sutures in the skull etc.
Give an example of a cartilaginous joint.
Intervertebral discs, costal cartilages etc.
How are joints classified functionally?
Functional classification focuses on the amount of movement at a joint.
Give an example of a synarthroses joint.
Sutures in the skull, teeth etc.
Give an example of an amphiarthroses joint.
Costal cartilages, intervertebral discs etc.
Give an example of a diarthrosis joint.
Hip joint.
What are bursae?
Fluid filled sacs lined by synovial membrane.
What are menisci?
Discs of fibrocartilage.
What is the function of hyaline cartilage in a synovial joint.
It provides a frictionless surface and acts to resist compressive loads.
Describe hyaline cartilage.
High water content, low cell content and no blood supply.
What is the function of synovial fluid?
It lubricates the joint by covering the articulating surfaces. It acts to reduce friction.
What are the clinical consequences of high uric acid?
Hyperuricemia can lead to the formation of uric acid crystals. These crystals are deposited in the joints and can cause inflammation, pain, swelling and redness. Hyperuricemia
What clinical condition can be caused by hyperuricemia?
Gout.
What is the end product of purine metabolism?
Uric acid.
What is the effect on the solubility of uric acid if the pH decreases?
It becomes less soluble.
Give 2 examples of purines.
- Guanine.
- Adenine.
What is the function of purines?
They are important building blocks of DNA and RNA.
Name 5 dietary sources of purines.
- Meat.
- Offal; liver, heart, kidney.
- Seafood.
- Soya, yeast extracts.
- Fructose.
Why are men more commonly affected by gout than women?
Oestrogen promotes uric acid excretion.
Give 5 risk factors of gout.
- CHD.
- Diabetes.
- Obesity.
- High blood pressure.
- Excessive alcohol consumption.
What does a bone profile blood test look at?
- Minerals.
- Proteins.
- Enzymes.
What would the bone profile for osteomalacia look like?
- Low serum calcium.
- Low serum phosphate.
- High parathyroid hormone (release is triggered by low Ca2+).
What is the function of T-tubules?
Conduct stimulatory impulses.
What connective tissue binds fasciculi to form muscles?
Epimysium.
What connective tissue binds muscle fibres to form fasciculi?
Perimysium.
What connective tissue is found in between each muscle fibre?
Endomysium.
A patient has low calcium but normal phosphate. What two hormones are responsible?
PTH and calcitonin.
Give 3 places where osteoporotic fractures are common.
- Hip.
- Wrist.
- Vertebral column.
What enzyme, expressed in osteoclasts, resorbs bone?
Cathepsin K.
What is the average recommended daily intake of calcium?
700mg.
What has been injured in the knee that results in hyperextension?
Posterior cruciate ligament.
How would you describe a fracture with more than 2 bone fragments?
Comminuted.
Which component of bone confers the mechanical property of stiffness?
Mineral
Which of these are dietary sources of phosphate?
Chicken
Which of these factors is the main regulator of serum calcium concentration?
Parathyroid hormone
Which is true of both tendons and ligaments?
Can sustain high tensile strength
Which is a physiological function of synovial fluid?
Reduce friction with joint movement
Which is true of the anterior cruciate ligament?
It is much less commonly injured than the posterior cruciate ligament
It is much less commonly injured than the posterior cruciate ligament
It is often injured in twisting injuries
It resists posterior translation of the tibia
It resists valgus force on the knee
It is often injured in twisting injuries
Which bone cells sense strain in the skeleton?
Osteocytes
Osteocytes are osteoblasts which become embedded in the bone matrix. They sense mechanical strain and send signals to osteoblasts to increase bone formation when strain is high, and decrease formation when strain is low. Therefore high strain activity leads to bone formation and immobility leads to bone loss. Osteoclasts resorb bone and osteoblasts form bone.
Which of these is the third stage of fracture healing?
Repair
Which is true of skeletal muscle?
Fast-twitch fibres have mainly aerobic metabolism
Contraction is generated by attachment and detachment of myosin heads on actin filaments
Fast-twitch fibres have mainly aerobic metabolism
It has an inherent rhythm
Skeletal myocytes are mononucleated
Contraction is generated by attachment and detachment of myosin heads on actin filaments
