week 5 - musculoskeletal system Flashcards
two main types of ECM
interstitial connective tissue matrix and the basement membrane
what is the ECM
a complex network of proteins and polysaccharides that provides structural, adhesive and biochemical signalling support
where is the ECM
- Dermal layer of skin
- Bone
- Tendon
- Cartilage
- Blood vessel walls
- Vitreous body of the eye
- Cornea
- Basement membrane
functions of ECM
Anchors cells (through cell-ECM junctions)
Strongly influences embryonic development
Provides pathways for cellular migration (eg. wound repair)
Binds to growth factors – either concentrating them locally or removing them or sequestering them
Provides a residence for roaming phagocytic cells
Establishes and maintains stem cell niches
provides mechanical and structural support for most tissues
five classes of macromolecules found in acellular component of a tissue
collagens, elastin, proteoglycans, hyaluronan (glycosaminoglycan) and glycoproteins
main function of collagen
to provide tensile strength
types of collagen
fibrillar and sheet/network forming
structure of collagen
3 collagen peptides form a triple helix
where are collagens 1-5 found
type I - dermis, tendons, ligaments, bones, fibrocartilage
II - hyaline cartilage
III - liver, bone marrow, lymphoid organs, granulation tissue
IV - basement membranes
V - linker to basement membrane, cornea
function of sheet/network forming collagen
provides support/filter - allows movement across BM
fibres found in ECM
collagen and elastin
structure of elastin
structural protein arranged as fibres
assembly into these fibres requires the presence of a structural protein called fibrillar which gets incorporated into the elastin fibres
when are collagen fibres uni-directionally aligned
when more strength is required eg. in tendons and ligaments - gives more resistance to mechanical load
what is ground substance
made of proteoglycans, glycosaminoglycans (GAGs) and glycoproteins
fills spaces between fibres and cells
amorphous, gel-like, non-fibrous substance surrounding cells
what are proteoglycans
GAGs (carbohydrate component) linked with a core protein
main function of a proteoglycan
highly negatively charged and so attract water - water retention and swelling property provides resistance to compressive forces
some can form aggregates
examples of GAGs and where they are found
hyaluronic acid - synovial fluid
chondroitin sulphate - cartilage
keratan sulphate - cartilage
heparan sulphate - BM
examples of proteoglycans and their location
aggrecan - cartilage
perlecan - BM
syndecan - cartilage
decorin - widespread in connective tissues
describe aggrecan
its a multimolecular aggregate and is an important part of cartilage
assembles along a hyaluronic acid core to form a negatively charged aggregate
Interacts with type two collagen and together they resist tensile force but also provides resistance to deformation
difference between proteoglycans, GAGs and glycoproteins
proteoglycans are a subclass of glycoproteins GAGs form proteoglycans when linked with a core protein
glycoproteins found in ground substance and their functions
fibrillin controls deposition and orientation of elastin
fibronectin - linker role in BM, organises ECM and participates in cell attachment to BM
laminin is the primary organiser of BM layer - also interacts with the integrins that are present in the hemidesmosome and therefore has a role in maintaining the integrity of the dermo-epidermal junction
how are most ECM components synthesised
fibroblasts produce most ECM components
Fibroblasts secrete the fibrous proteins –> post translational modification -> assembled into fibres
synthesis of proteoglycans
fibroblasts produce the core protein of the proteoglycan - firstly in rER then there is the addition fo polysaccharide as disaccharide in Golgi
delivered to extracellular compartment by exocytosis and then is assembled with other ECM components
describe collagen synthesis
synthesised as procollagen
post translational modifications are glycosylation and hydroxylation
protein assembly in the form of a triple helix
elastin synthesis
synthesised as tropoelastin
post translational modification is hydroxylation and then the proteins are assembled as a fibrillin scaffold and cross-linked fibres
when does tissue fibrosis occur
it is the result of abnormal responses to organ injury and results from the hyperproliferation of fibroblasts and excessive ECM synthesis
degradation of ECM by pathogens
some pathogens secrete collagenases that breakdown the ECM and provide access to the body so bacteria can then invade
how does the ECM act in epithelial tissue
can lie underneath epithelia and endothelia
Can surround cells such as muscle fibres
Can separate two sheets of cells
Provides structural support for the epithelia of skin as well as a layer for selective permeablility
components of BM in epithelial tissue
collagen 4, laminin, perlecan and nidogen
functions of BM in epithelial tissue
support, binding to underlying connective tissue, mediates signals between cells and connective tissue, determines cell polarity, permits flow of nutrients, path for cell migration and is a barrier to downward growth
how does a disorder of BM lead to cancer
epithelial tumours are regarded as malignant once BM has been breached
describe some disorders of the BM
epidermolysis bullosa - attachment of epidermis to BM
goodpastures syndrome - autoantibodies to collagen IV destroy BM in glomerulus and lung
diabetes mellitus - thickening of BM in glomerulus changes permeability
where is specialised connective tissue located
bone cartilage adipose tissue (fat) blood bone marrow, lymphoid tissue
what is the ECM in bone called
osteoid
what are the cellular components of bone and their functions
Osteoblasts – matrix production (bone equivalent of fibroblasts) - make new bone cells and secrete collagen
Osteocytes – found in mature bone and were once osteoblasts but have now become surrounded and entrapped in their own matrix – regulate mineral homeostasis
Osteoclasts – involves in bone degradation or resorption – derived from monocyte-macrophage precursor – has multiple large nuclei and a ruffle border that releases powerful degradative acid and enzymes
acellular components of bone
organic component makes up 30% - type I collagen and osteocalcin inorganic component (70%) - hydroxyapatite
what synthesises cartilage
chondrocytes
components of cartilage
formed from type II collagen - cartilage also contains chondroitin sulphate, keratan sulphate, hyaluronic acid and aggrecan
types of cartilage
hyaline
elastic
fibrocartilage
what do the negative charges associated with aggrecan mean
means cartilage can attract water molecules
features of hyaline cartilage
few visible collagen fibres
avascular
has perichondrium - except articular cartilage
features of fibrocartilage
abundant collagen fibres
avascular
no perichondrium
features of elastic cartilage
contains elastic fibres
avascular
has perichondrium
location of hyaline cartilage
nasal septum, larynx, tracheal rings, articular surfaces, sternal ends of ribs, epiphyseal growth plate
location of fibrocartilage
IV discs, sternoclavicular joint, pubic symphysis
location of elastic cartilage
external ear, epiglottis, auditory tube
what disease does over-degradation of ECM lead to
osteoarthritis
what does over-production of ECM lead to
fibrosis
what conditions can disfunction of collagen IV lead to
alport syndrome - hereditary kidney disease - structural abnormalities and dysfunction in glomerular BM as well as BM in other tissues - mutations in collagen IV genes and results in progressive loss of kidney function
what is marfan syndrome and why does it occur
result of mutations in fibrillin gene
affects connective tissues of skin, bone, blood vessels and other organs and tissues
causes vision problems, heart/aortic defects, abnormally long and slender limbs, fingers and toes
what is Ehlers-danlos syndrome and why does it occur
result of mutations in collagen genes and others
affects connective tissues of skin, bone, blood vessels and other organs and tissue
causes hypermobility and stretch, fragile skin
types of muscle tissue
skeletal muscle
cardiac muscle
smooth muscle
structure of skeletal muscle
long, cylindrical cells with multiple nuclei
striated
function of skeletal muscle
voluntary movement, locomotion
location of skeletal muscle
attached to bones and occasionally attached to skin
structure of cardiac muscle
branching cells with one or two nuclei per cell
striated
function of cardiac muscle
as it contracts it propels blood into circulation - involuntary control
medium speed contractions
location of cardiac muscle
walls of heart
what advantage do the branching cells in cardiac muscle give
y shape of cells allows heart to have a conical shape and allows heart to contract around left or right cavities
structure of smooth muscle cells
fusiform cells - can take on different shapes
one nucleus per cell
cells arranged closely to form sheets
no striations
function of smooth muscle cells
propels substances or objects along internal passageways
involuntary control
location of smooth muscle
mostly in the walls of hollow organs
resting membrane potential
electrical gradient across the cell membrane
resting - membrane potential has reached a steady state and is not changing
electrochemical gradient
combination of electrical and chemical gradient
eg. active transport of a positive ion out of cell creates a chemical gradient
input of energy to transport ions across a membrane creates an electrical gradient
resting membrane potential in nerve and muscle
between -40 to -90 mV
equilibrium potential is calculated using the..
Nernst equation
are cells more permeable to K or Na
more permeable to K so resting membrane potential is much closer to E(k) than E(Na) - E = equilibrium potential
around -70mV because a small amount of Na leaks into cell
equilibrium potential of K
-90mV
equilibrium potential of Na
60mV
sodium potassium pump
sodium is pumped out and potassium is pumped in by sodium-potassium ATPase
it pumps 3 Na ions out and 2 K ions in
less K because negative proteins are in cell
skeletal muscle excitation process
Cell changing its negative potential to a positive potential (action potential depolarises) comes down neural tissue
Arrives on muscle fibre at a point called neuromuscular junction
Results in chemical release at junction between nerve axon and cell membrane
The junction releases neurotransmitter at synaptic cleft
Release vesicles of acetylcholine that moves across junction and binds to receptors on muscle cells and promotes change in the permeability of that muscle cell membrane
Binding of acetylcholine opens a channel – this channel is permeable to sodium ions so cell becomes more positive
synaptic cleft
area between nerve axon and the cell membrane
what are axons
long processes on neurons which are specialised to transmit action potentials long distances
axons of multiple neurons bundle together to form nerves,
skeletal muscle excitation
from action potential to sodium influx
neuronal action potenial travels along the axon of a motor neuron and arrives on muscle fibre at neuromuscular junction
At NMJ the axon terminal releases a chemical messenger or neurotransmitter called acetylcholine (ACh)
ACh molecules diffuse accrocs synaptic left and bind to receptors on muscle cells
a channel in the ACh receptor opens and positively charges ions can pass through the muscle fibre causing it to depolarise - membrane potential of muscle fibre becomes less negative
this triggers voltage-gated sodium channels to open
sodium ions enter muscle fibre and action potential rapidly spreads along entire membrane to initiate excitation-contraction coupling
membrane depolarises immediately after
what triggers calcium entry to cell
triggering of action potential through SA node, hormones, voltage or direct trigger etc.
what occurs in the muscle excitation process after the sodium influx
sodium influx will generate an action potential in the sarcolemma
the action potential travels down the t tubules into interior of the cell which triggers the opening of calcium channels in the membrane of adjacent sarcoplasmic reticulum
calcium diffuses out of SR and into sarcoplasm
arrival of calcium in sarcoplasm initiates contraction of the muscle fibre
how is sodium entry triggered in smooth muscle cells
hormonal release
what initiates the wave of depolarisation in myocardium
SA node (pacemaker of the heart)
tetany
sustained contraction of a muscle as a result of rapid succession of nerve impulses
occurs only in skeletal muscle
refractory period
brief period in time in which muscles will not respond to a stimulus
muscle tonus
the tightness of a muscle
some fibres always contracted
muscle fibre
a lot of proteins bundled together
two contractile proteins in skeletal muscle
actin and myosin
what is a sacromere
a myosin and actin unit bound at two ends by z lines
structure of a myosin molecule
myosin head is what confers energy into movement
tail regions wrap around each other making it double stranded
double stranded myosin heads can attach and detach without loosing positioning on sarcomere
structure of a thick myosin filament
myosin heads are coming off in all directions meaning myosin can attach to actins all around it - no restrictions in shortening
this 3D structure also means we have smooth movements
what is a myofibril
also known as a muscle fibril
rod-like unit of a muscle cell
Structure of a thin filament
composed of troponin complex, tropomyosin and g actin in a double helix
function of tropomyosin
has importance on myosin-actin interaction - allows muscle to contract and shorten
depending on its positioning it can inhibit actin-myosin interaction, preventing the muscle from shortening
explain how troponin complex controls the position of tropomyosin
troponin C is the calcium binding site on the complex – when calcium binds there is conformational change which is transduced along the complex
troponin T amplifies the shape change by transducing the effect along the troponin complex molecule – moves troponin I which sits in contact with the tropomyosin – this amplification from calcium binding is enough to pull tropomyosin molecule away from grove – stopping inhibition allowing myosin to bind
troponin structure
a complex of three regulatory proteins (troponin c, i and t ) that is integral to muscle contraction in skeletal and cardiac muscle
describe the myosin-actin interaction
ATP hydrolysis causes myosin to bind
when ADP and inorganic phosphate are released, myosin head undergoes conformational change so it can bind to actin
structure of a myocyte
(skeletal muscle cell) contains thousands of myofibrils which run parallel to myocyte, typically for its entire length attaching to sarcolemma at either end SR surrounds myofibrils SR is closely associated with t tubules SR stores calcium
describe muscle excitation-contraction
SR releases calcium
calcium binds with troponin complex to expose the active binding sites on actin
myosin head bridges the gap and attaches to binding sites creating a power stroke - pulls actin filament towards m line - this makes the sarcomere shorten and so the muscle contracts
ATP attaches myosin heads and energises them for another contraction
what is creatine
molecule capable of storing ATP energy
muscle atrophy
weakening and shrinking of a muscle
muscle hypertrophy
enlargement of a muscle
steroid hormones
stimulate muscle growth and hypertrophy
isometric contraction
produces no movement
describe the sarcomere structure
sarcomere is the segment between two neighbouring parallel z lines
I-band: The area adjacent to the Z-line, where actin myofilaments are not superimposed by myosin myofilaments.
A-band: The length of a myosin myofilament within a sarcomere.
M-line: The line at the center of a sarcomere to which myosin myofilaments bind.
Z-line: Neighbouring, parallel lines that define a sarcomere.
H-band: The area adjacent to the M-line, where myosin myofilaments are not superimposed by actin myofilaments.
sarcoplasmic reticulum
smooth endoplasmic reticulum found in smooth and striated muscle; it contains large stores of calcium, which it sequesters and then releases when the muscle cell is stimulated
pathogenesis of osteoarthritis
initial increase in water content makes cell swell then there is a decrease in water content with chronicity - ECM becomes less robust
decrease in proteoglycan synthesis, collagen cross-linking and in the size of aggrecan, GAG and hyaluronic acid
what is osteoarthritis
progressive disorder of the joints caused by gradual loss of cartilage and resulting in the development of bony spurs and cysts at the margins of joints
what is primary osteoarthritis
degenerative disorder - breakdown of cartilage and has no known cause
secondary OA
OA caused by a known factor such as trauma hip dysplasia infection diabetes
OA risk factors
age genetics gender (older women and younger men) low vitamin C and D intake obesity joint trauma occupation abnormal joint biomechanics
what would be seen on an x-ray of a patient with OA
space between joints narrows
osteophytes present
subchondral sclerosis
cyst formation
management of OA
medications physiotherapy walking aids joint injections surgical treatment
surgical treatments for OA
arthroscopy - camera inserted into joint
cartilage transplantation - cartilage taken non-weight-bearing joints or cartilage from joint is grown in Petri dish then implanted
joint replacement - worn cartilage is removed and replaced with a synthetic material
joint injections for OA
cortisone/corticosteroid - reduces inflammation response around joints and tends to have more rapid effects than NSAIDs
viscous supplement - hyaluronic acid injected into joint
medications for osteoarthritis
paracetamol and non steroidal anti-inflammatory drugs (NSAIDs) for pain management
glucosamine and chondroitin sulphate supplements can slow or prevent degeneration of joint cartilage
what does an OA joint look like
thickened capsule
cyst formation and sclerosis in subchondral bone
fibrillated cartilage
osteophytic lipping (irregular bone formation)
synovial hypertrophy
altered contour of bone
sources of potential infection
blood and other body fluids mucous membranes non-intact skin secretions or excretions any equipment that could been contaminated
standard precautions to avoid infection
hand hygiene at the 5 specific moments
care in the use of disposal of sharps
correct use of personal protective equipment for contact with all blood, body fluids, secretions and excretions (except sweat)
providing care in a suitably clean environment with adequate decontaminated equipment
safe waste disposal
safe management of used linen
all PPE should be:
located close to point of use
stored to prevent contamination in a clean, dry area
single use items
disposed of after use in correct waste stream
reusable PPE items such as non-disposable goggles must have a decontamination schedule
