week 5 - musculoskeletal system Flashcards

1
Q

two main types of ECM

A

interstitial connective tissue matrix and the basement membrane

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2
Q

what is the ECM

A

a complex network of proteins and polysaccharides that provides structural, adhesive and biochemical signalling support

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3
Q

where is the ECM

A
  • Dermal layer of skin
  • Bone
  • Tendon
  • Cartilage
  • Blood vessel walls
  • Vitreous body of the eye
  • Cornea
  • Basement membrane
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4
Q

functions of ECM

A

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

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5
Q

five classes of macromolecules found in acellular component of a tissue

A

collagens, elastin, proteoglycans, hyaluronan (glycosaminoglycan) and glycoproteins

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6
Q

main function of collagen

A

to provide tensile strength

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7
Q

types of collagen

A

fibrillar and sheet/network forming

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8
Q

structure of collagen

A

3 collagen peptides form a triple helix

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9
Q

where are collagens 1-5 found

A

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

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10
Q

function of sheet/network forming collagen

A

provides support/filter - allows movement across BM

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11
Q

fibres found in ECM

A

collagen and elastin

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12
Q

structure of elastin

A

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

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13
Q

when are collagen fibres uni-directionally aligned

A

when more strength is required eg. in tendons and ligaments - gives more resistance to mechanical load

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14
Q

what is ground substance

A

made of proteoglycans, glycosaminoglycans (GAGs) and glycoproteins
fills spaces between fibres and cells
amorphous, gel-like, non-fibrous substance surrounding cells

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15
Q

what are proteoglycans

A

GAGs (carbohydrate component) linked with a core protein

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16
Q

main function of a proteoglycan

A

highly negatively charged and so attract water - water retention and swelling property provides resistance to compressive forces
some can form aggregates

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17
Q

examples of GAGs and where they are found

A

hyaluronic acid - synovial fluid
chondroitin sulphate - cartilage
keratan sulphate - cartilage
heparan sulphate - BM

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18
Q

examples of proteoglycans and their location

A

aggrecan - cartilage
perlecan - BM
syndecan - cartilage
decorin - widespread in connective tissues

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19
Q

describe aggrecan

A

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

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20
Q

difference between proteoglycans, GAGs and glycoproteins

A
proteoglycans are a subclass of glycoproteins
GAGs form proteoglycans when linked with a core protein
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21
Q

glycoproteins found in ground substance and their functions

A

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

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22
Q

how are most ECM components synthesised

A

fibroblasts produce most ECM components

Fibroblasts secrete the fibrous proteins –> post translational modification -> assembled into fibres

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23
Q

synthesis of proteoglycans

A

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

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24
Q

describe collagen synthesis

A

synthesised as procollagen
post translational modifications are glycosylation and hydroxylation
protein assembly in the form of a triple helix

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25
Q

elastin synthesis

A

synthesised as tropoelastin
post translational modification is hydroxylation and then the proteins are assembled as a fibrillin scaffold and cross-linked fibres

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26
Q

when does tissue fibrosis occur

A

it is the result of abnormal responses to organ injury and results from the hyperproliferation of fibroblasts and excessive ECM synthesis

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27
Q

degradation of ECM by pathogens

A

some pathogens secrete collagenases that breakdown the ECM and provide access to the body so bacteria can then invade

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28
Q

how does the ECM act in epithelial tissue

A

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

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29
Q

components of BM in epithelial tissue

A

collagen 4, laminin, perlecan and nidogen

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30
Q

functions of BM in epithelial tissue

A

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

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31
Q

how does a disorder of BM lead to cancer

A

epithelial tumours are regarded as malignant once BM has been breached

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32
Q

describe some disorders of the BM

A

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

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33
Q

where is specialised connective tissue located

A
bone
cartilage
adipose tissue (fat)
blood
bone marrow, lymphoid tissue
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34
Q

what is the ECM in bone called

A

osteoid

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35
Q

what are the cellular components of bone and their functions

A

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

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36
Q

acellular components of bone

A
organic component makes up 30% - type I collagen and osteocalcin
inorganic component (70%) - hydroxyapatite
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37
Q

what synthesises cartilage

A

chondrocytes

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38
Q

components of cartilage

A

formed from type II collagen - cartilage also contains chondroitin sulphate, keratan sulphate, hyaluronic acid and aggrecan

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39
Q

types of cartilage

A

hyaline
elastic
fibrocartilage

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40
Q

what do the negative charges associated with aggrecan mean

A

means cartilage can attract water molecules

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41
Q

features of hyaline cartilage

A

few visible collagen fibres
avascular
has perichondrium - except articular cartilage

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42
Q

features of fibrocartilage

A

abundant collagen fibres
avascular
no perichondrium

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43
Q

features of elastic cartilage

A

contains elastic fibres
avascular
has perichondrium

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44
Q

location of hyaline cartilage

A

nasal septum, larynx, tracheal rings, articular surfaces, sternal ends of ribs, epiphyseal growth plate

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45
Q

location of fibrocartilage

A

IV discs, sternoclavicular joint, pubic symphysis

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46
Q

location of elastic cartilage

A

external ear, epiglottis, auditory tube

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47
Q

what disease does over-degradation of ECM lead to

A

osteoarthritis

48
Q

what does over-production of ECM lead to

A

fibrosis

49
Q

what conditions can disfunction of collagen IV lead to

A

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

50
Q

what is marfan syndrome and why does it occur

A

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

51
Q

what is Ehlers-danlos syndrome and why does it occur

A

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

52
Q

types of muscle tissue

A

skeletal muscle
cardiac muscle
smooth muscle

53
Q

structure of skeletal muscle

A

long, cylindrical cells with multiple nuclei

striated

54
Q

function of skeletal muscle

A

voluntary movement, locomotion

55
Q

location of skeletal muscle

A

attached to bones and occasionally attached to skin

56
Q

structure of cardiac muscle

A

branching cells with one or two nuclei per cell

striated

57
Q

function of cardiac muscle

A

as it contracts it propels blood into circulation - involuntary control
medium speed contractions

58
Q

location of cardiac muscle

A

walls of heart

59
Q

what advantage do the branching cells in cardiac muscle give

A

y shape of cells allows heart to have a conical shape and allows heart to contract around left or right cavities

60
Q

structure of smooth muscle cells

A

fusiform cells - can take on different shapes
one nucleus per cell
cells arranged closely to form sheets
no striations

61
Q

function of smooth muscle cells

A

propels substances or objects along internal passageways

involuntary control

62
Q

location of smooth muscle

A

mostly in the walls of hollow organs

63
Q

resting membrane potential

A

electrical gradient across the cell membrane

resting - membrane potential has reached a steady state and is not changing

64
Q

electrochemical gradient

A

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

65
Q

resting membrane potential in nerve and muscle

A

between -40 to -90 mV

66
Q

equilibrium potential is calculated using the..

A

Nernst equation

67
Q

are cells more permeable to K or Na

A

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

68
Q

equilibrium potential of K

A

-90mV

69
Q

equilibrium potential of Na

A

60mV

70
Q

sodium potassium pump

A

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

71
Q

skeletal muscle excitation process

A

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

72
Q

synaptic cleft

A

area between nerve axon and the cell membrane

73
Q

what are axons

A

long processes on neurons which are specialised to transmit action potentials long distances
axons of multiple neurons bundle together to form nerves,

74
Q

skeletal muscle excitation

from action potential to sodium influx

A

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

75
Q

what triggers calcium entry to cell

A

triggering of action potential through SA node, hormones, voltage or direct trigger etc.

76
Q

what occurs in the muscle excitation process after the sodium influx

A

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

77
Q

how is sodium entry triggered in smooth muscle cells

A

hormonal release

78
Q

what initiates the wave of depolarisation in myocardium

A

SA node (pacemaker of the heart)

79
Q

tetany

A

sustained contraction of a muscle as a result of rapid succession of nerve impulses
occurs only in skeletal muscle

80
Q

refractory period

A

brief period in time in which muscles will not respond to a stimulus

81
Q

muscle tonus

A

the tightness of a muscle

some fibres always contracted

82
Q

muscle fibre

A

a lot of proteins bundled together

83
Q

two contractile proteins in skeletal muscle

A

actin and myosin

84
Q

what is a sacromere

A

a myosin and actin unit bound at two ends by z lines

85
Q

structure of a myosin molecule

A

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

86
Q

structure of a thick myosin filament

A

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

87
Q

what is a myofibril

A

also known as a muscle fibril

rod-like unit of a muscle cell

88
Q

Structure of a thin filament

A

composed of troponin complex, tropomyosin and g actin in a double helix

89
Q

function of tropomyosin

A

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

90
Q

explain how troponin complex controls the position of tropomyosin

A

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

91
Q

troponin structure

A

a complex of three regulatory proteins (troponin c, i and t ) that is integral to muscle contraction in skeletal and cardiac muscle

92
Q

describe the myosin-actin interaction

A

ATP hydrolysis causes myosin to bind

when ADP and inorganic phosphate are released, myosin head undergoes conformational change so it can bind to actin

93
Q

structure of a myocyte

A
(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
94
Q

describe muscle excitation-contraction

A

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

95
Q

what is creatine

A

molecule capable of storing ATP energy

96
Q

muscle atrophy

A

weakening and shrinking of a muscle

97
Q

muscle hypertrophy

A

enlargement of a muscle

98
Q

steroid hormones

A

stimulate muscle growth and hypertrophy

99
Q

isometric contraction

A

produces no movement

100
Q

describe the sarcomere structure

A

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.

101
Q

sarcoplasmic reticulum

A

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

102
Q

pathogenesis of osteoarthritis

A

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

103
Q

what is osteoarthritis

A

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

104
Q

what is primary osteoarthritis

A

degenerative disorder - breakdown of cartilage and has no known cause

105
Q

secondary OA

A
OA caused by a known factor such as 
trauma
hip dysplasia 
infection 
diabetes
106
Q

OA risk factors

A
age 
genetics
gender (older women and younger men)
low vitamin C and D intake 
obesity 
joint trauma
occupation 
abnormal joint biomechanics
107
Q

what would be seen on an x-ray of a patient with OA

A

space between joints narrows
osteophytes present
subchondral sclerosis
cyst formation

108
Q

management of OA

A
medications 
physiotherapy 
walking aids
joint injections
surgical treatment
109
Q

surgical treatments for OA

A

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

110
Q

joint injections for OA

A

cortisone/corticosteroid - reduces inflammation response around joints and tends to have more rapid effects than NSAIDs
viscous supplement - hyaluronic acid injected into joint

111
Q

medications for osteoarthritis

A

paracetamol and non steroidal anti-inflammatory drugs (NSAIDs) for pain management
glucosamine and chondroitin sulphate supplements can slow or prevent degeneration of joint cartilage

112
Q

what does an OA joint look like

A

thickened capsule
cyst formation and sclerosis in subchondral bone
fibrillated cartilage
osteophytic lipping (irregular bone formation)
synovial hypertrophy
altered contour of bone

113
Q

sources of potential infection

A
blood and other body fluids
mucous membranes 
non-intact skin
secretions or excretions 
any equipment that could been contaminated
114
Q

standard precautions to avoid infection

A

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

115
Q

all PPE should be:

A

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