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MSK > Physiology > Flashcards

Physiology Flashcards

1
Q

Physiological functions of skeletal muscles

A 
> Posture
> Purposeful movement 
> Respiratory movements 
> Heat production
> Contribution to whole body metabolism
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2
Q

Types of muscle tissue

A

There are 3.

  1. Skeletal muscles
  2. Cardiac muscle
  3. Smooth muscles

All capable of developing tension and producing movement through contraction.

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3
Q

Skeletal muscle

  • appearance
  • voluntary?
  • neurogenic/myogenic
  • source of calcium
  • contraction
A

> Striated (dark - myocin - and light - actin - bands)
Voluntary

> Innervated by somatic nervous system

> Neurogenic initiation of contraction

> Motor units

> Neuromuscular junction

> NO gap junctions

> Ca2+ ENTIRELY from sarcoplasmic reticulum

> Motor unit recruitment and summation of contractions = CONTRACTION

Parallel muscle fibres bundled by connective tissue.

Skeletal muscle fibres usually extend the entire length of muscle

Attached to skeleton by tendons

Unbranched
Multinucleate

Fibres are long cylinders - span entire length of muscle

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4
Q

Cardiac muscle

  • appearance
  • voluntary/involuntary
  • Neurogenic/myogenic
  • source of calcium
  • contraction
A

> Striated muscle
Involuntary
Innervated by autonomic nervous system

> MYOGENIC (pacemaker potential) initiation of contraction

> Gap junctions present

> NO neuromuscular junction

> Ca2+ from ECF and Sarcoplasmic reticulum (calcium-induced calcium release)

> Contraction depends on extent of heart FILLING with blood (preload)

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5
Q

Smooth muscle

A

> UNstriated
Involuntary muscle

> Autonomic nervous system

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6
Q

Are the cytoplasms of nerve cells and skeletal muscle cells continous?

A

NO.

Acetylcholine is the transmitter at Neuromuscular junction

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7
Q

What is the neurotransmitter in skeletal muscle?

A

Acetylcholine

Neuromuscular junction

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8
Q

What are skeletal muscles organised into?

A

Motor units

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9
Q

What is a motor unit?

A

A SINGLE alpha motor neuron and ALL the skeletal muscle fibres it innervates

The axon of the motor neurone branches as it nears its termination and each branch ends in a special type of synapse called the neuromuscular junction.

Myelinated neurone; then it divides into unmyelinated branches near to the muscle.

Indiviudal branches divide further into multiple fine branches, each ending in a TERMINAL BOUTON that forms a chemical synapse with the muscle membrane at the NMJ

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10
Q

The number of muscle fibres per motor unit depends on?

A

The functions served by the muscle.

Fine movement = FEWER fibres per motor unit (external eye muscles, facial expression)

Fine Few
More power

Power more important than precision (thighs) = hundreds to thousands fibres per motor unit.

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11
Q

A muscle fibre is made up of?

A

Myofibrils

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12
Q

What is the FUNCTIONAL unit of muscle fibres?

A

Sarcomere

Thousands of these are placed end to end to form a MYOFIBRILS.

Dozens to hundreds of myofibrils are packed into the muscle fibre like cigarettes in a pack.

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13
Q

Muscle fibre = muscle cell

A

just a reminder.

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14
Q

Myofibrils/sarcomeres contain

A

Myocin - thick (darker) filaments

Actin - thin (lighter) filaments

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15
Q

What structure attaches skeletal muscle to the skeleton?

A

Tendons

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16
Q

Each muscle cell (fibre) contains many…

A

myofibrils.

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17
Q

General structure of myofibrils

A

Alternating segments of thick and thin protein filaments

Actin and myocin are arranged into SARCOMERES

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18
Q

Where can a sarcomere be found? (Z line, m line, h zone, i band)

A

Between two Z-lines

Connect the thin filaments of 2 adjoining sarcomers

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19
Q

What are the sarcomere zones?

A

A-band
- Made up of thick filaments along with portions of thin filaments that overlap in both ends of thick filaments

H-zone
- Lighter area within middle of A-band where thin filaments don’t reach

M-line
- Extends vertically down middle of A-band within the centre of H-zone

I-band
- Consists of remaining portion of thin filaments that do not project in A-band

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20
Q

How is muscle tension produced?

A

By sliding of actin filaments on myosin filaments

Force generation depends upon ATP-dependent interaction between thick (myosin) and thin (actin) filaments

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21
Q

ATP is required for both…

A

Contraction and relaxation of skeletal muscle

during muscle contraction to power cross bridges

During relaxation to release cross bridges; to pump Ca2+ back into the sarcoplasmic reticulum

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22
Q

Excitation contraction coupling

A

Process whereby the surface action potential results in activation of the contractile structures of the muscle fibre

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23
Q

Ca2+ release in skeletal muscle

A

In skeletal muscle fibres, Ca2+ is released from the LATERAL SACS of the sarcoplasmic reticulum, when the surface acton potential spreads down the transverse (T) tubules.

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24
Q

Where is Ca2+ released from in skeletal muscle?

A

The lateral sacs of the sarcoplasmic reticulum

when the surface action potential spreads down the transverse (T) tubules.

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25
Q

What structure does the action potential have to travel down in order for calcium to be released?

A

T (transverse) tubules

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26
Q

What are T tubules?

A

Transverse tubules (T-tubules) are extensions of the sarcolemma (muscle cell membrane) that penetrate into the centre of skeletal and cardiac muscle cells.

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27
Q

Calcium is needed…

A

> Switch on cross bridge formation
Ca2+ is the link between excitation and contraction
Ca2+ is entirely derived from sarcoplasmic reticulum in skeletal muscle

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28
Q

Rigor mortis

A

In absence of ATP - stiffness can occur .

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29
Q

Magnesium ATPase? Myosin ATPase??

A

– questions

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30
Q

Gradation of skeletal muscle tension (strength of contraction) depends on…

A

Two primary factors.

  1. Number of muscle fibres contracting within the muscle
    - MOTOR UNITS allow simultaneous contraction of a number of muscle fibres
    - a stronger contraction could be achieved by stimulation of more motor units - MOTOR UNIT RECRUITMENT
    - Asynchronous motor unit recruitments during sub maximal contractions helps prevent muscle fatigue
  2. Tension developed by each contracting muscle fibre
    - depends on FREQUENCY of stimulation and SUMMATION of contractions
    - LENGTH of muscle fibre at the onset of contraction
    - Thickness of muscle fibre
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31
Q

Stimulation of more motor units is called..

A

Motor unit recruitment

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32
Q

In skeletal muscle, the action potential is..

A

Much SHORTER than the duration of the resulting TWITCH.

Possible to summate twitches to bring about a stronger contraction through repetitive fast stimulation of skeletal muscle.

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33
Q

Summation of twitches

A

Brings about a stronger contraction through repetitive fast stimulation of skeletal muscle.

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34
Q

What is a “twitch”

A

A single contraction

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35
Q

If a muscle fibre is restimulated after it has completely relaxed, the second twitch is….

A

the same magnitude as the first

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36
Q

If a muscle fibre is restimulated BEFORE it has completely relaxed, the second twitch is…

A

ADDED onto the first twitch

Resulting in SUMMATION

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37
Q

Tetanus

A

If a muscular fibre is stimulated so rapidly that it does not have an opportunity to relax at all between stimuli, a maximal SUSTAINED contraction occurs i.e. TETANUS

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38
Q

the tension developed by skeletal muscle increases with…

A

increasing FREQUENCY OF STIMULATION

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39
Q

Increased the frequency of stimulation is an important mechanism for..

A

MODULATING the force of contraction in skeletal muscle.

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40
Q

When can maximal titanic contraction be achieved?

A

When the muscle is at its OPTIMAL LENGTH before onset of contraction.

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41
Q

Developed tension depends on

A

The initial length of the skeletal muscle fibres

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42
Q

What is the optimum length of muscle

A

lo

Point of optimal overlap of thick filament cross bridges and thin filaments cross bridge binding sites.

Maximal titanic tension can be achieved.

i.e. its RESTING length

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43
Q

Two types of skeletal muscle contraciton

A
  1. Isotonic contraction

2. Isometric contraction

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44
Q

Isotonic contraction

A

Used for 1) body movements and 2) moving objects.

Muscle TENSION remains constant as the muscle length changes

Tension = constant

Length = changes

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45
Q

Isometric contraction

A

Used for 1) Supporting objects and 2) maintaining body posture

Muscle tension develops at constant muscle length

Tension = changes

Length = constant

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46
Q

The velocity of muscle shortening decreases as the load…

A

Increases

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47
Q

Each motor unit usually contains…

A

One type of muscle fibre.

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48
Q

Metabolic pathways that supply ATP in muscle fibres (3)

A
  1. Transfer of high energy phosphate from creatine phosphate to ADP - immediate source of ATP
  2. Oxidative phosphorylation - main source when O2 is present
  3. GLYCOLYSIS - main source when O2 is NOT present.
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49
Q

3 types of muscle fibres

A
  1. Slow oxidative type 1 (slow twitch)
  2. Fast oxidative Type IIa (intermediate twitch fibres)
  3. Fast glycolytic Type Iix fibres (fast twitch muscle fibres)
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50
Q

Slow oxidative type I fibres

> when are they used?

> types of metabolism used
(aerobic/anaerobic)

A

(slow-twitch fibres)

are used mainly for prolonged relatively low work aerobic activities e.g. maintenance of posture, walking

resistant to fatigue

“red” fibres

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51
Q

Fast oxidative type IIa fibres

> when are they used?

> types of metabolism used (aerobic/anaerobic)

A

Intermediate-twitch fibres

use both aerobic and anaerobic metabolism and are useful in prolonged relatively moderate work activities e.g. jogging

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52
Q

Fast Glycolytic Type IIx

> when are they used

> type of metabolism used

A

fast-twitch fibers

use anaerobic metabolism and are mainly used for short-term high intensity activities e.g. jumping

fatigue quickly.

“white” fibres

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53
Q

what is a reflex?

A

A stereotyped response to a specific stimulus

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54
Q

Stretch reflex is what kind of reflex?

A

Monosynaptic spinal reflex

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55
Q

Stretch reflex

  • negative feedback
  • posture
A

Negative feedback that resists passive change in muscle length to maintain optimal resting length of muscle

Helps maintain posture.

The sensory receptor is the muscle spindle and is activated by muscle stretch

Stretching the muscle spindle increases firing in the afferent neurons

The afferent neurons synapse in the spinal cord with the alpha motor neurons (efferent limb of the stretch reflex) that innervate the stretched muscle

Activation of the reflex results in contraction of stretched muscle

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56
Q

Muscle spindle

  • what is it
  • activated by?

what are the sensory nerve endings known as?

A

The sensory receptor.

Collection of specialised muscle fibres

AKA Intrafusal fibres

Found within BELLY of muscles and run parallel to ordinary muscle fibres (extrafusal fibres)

Sensory nerve endings = ANNULOSPIRAL fibres.

Have their own efferent (motor) nerve supply

Efferent neurons that supply muscle spindles are called GAMMA MOTOR NEURONS

Activated by muscle stretch

Stretching the muscle spindle increases firing in the afferent neurons

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57
Q

Stretching the muscle spindle does what?

A

Increases firing in the afferent neurons

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58
Q

In the stretch reflex, where do the afferent neurons synapse?

What do the synapse with?

A

In the spinal cord

synapse with the alpha motor neurons (efferent limb of the stretch reflex) that innervate the stretched muscle

Activation of the reflex results in contraction of stretched muscle.

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59
Q

How can the stretch reflex be elicited?

A

By tapping the muscle tendon with a rubber hammer.

This rapidly stretches the muscle resulting in its contraction

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60
Q

Knee Jerk

> Spinal segment
Peripheral nerve

A

L3, L4

Femoral nerve

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61
Q

Ankle jerk

A

S1, S2

TIbial nerve

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62
Q

Biceps jerk

A

C5-C6

Radial nerve

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63
Q

Triceps jerk

A

C6-C7

Radial nerve

64
Q

Sensory nerve endings of muscle spindles are known as?

A

Annulospiral fibres

65
Q

What are normal muscle fibres also known as?

A

Extrafusal fibres.

66
Q

Discharge from the muscle spindles sensory endings Increases as the…

A

muscle (and hence spindle) is stretched.

67
Q

Ɣ motor neurons

A

Adjust level of tension in the muscle spindles to maintain their sensitivity when the muscles shorten during muscle contraction

Gamma motor neurons are efferent neurons that supply muscle spindles.

68
Q

Does the contraction of intrafusal fibres contribute to the overall strength of muscle contraction?

A

No it does not.

69
Q

Intrinsic Muscle Disease

A

Genetically determined myopathies

Congenital myopathies: characteristic microscopic changes leading to reduced contractile ability of muscles

Chronic Degeneration of contractile elements - muscular dystrophy

Abnormalities in muscle membrane ion channels e.g. myotonia

Acquired myopathies

Inflammatory myopathies e.g. polymyositis, inclusion body myositis
Non-Inflammatory myopathies e.g. fibromyalgia

Endocrine mypoathies e.g. Cushing syndrome, thyroid disease

Toxic myopathies e.g. alcohol, statins

70
Q

Symptoms of muscle disease

A

> Muscle weakness/tiredness

> Delayed relaxation after voluntary contraction (myotonia)

> Muscle pain (myalgia)

> Muscle stiffness

71
Q

Electromyography

A

Electrodes detect the presence of muscular activity

Records frequency and amplitude of muscle fibres action potentials

EMG findings not pathognomonic of specific disease - will not provide the definitive diagnosis

EMG helps differentiate primary muscle disease from muscle weakness caused by neurological disease

Nerve conduction studies usually done at the same time as an EMG

72
Q

Nerve conduction studies

A

Determine the functional integrity of peripheral nerves

73
Q

Muscle enzymes

A

Creatine kinase

74
Q

Inflammatory markers

A

C reactive protein (CRP)

Plasma viscosity

75
Q

Investigations for neuromuscular disease

A

> Electromyography

> Nerve conduction studies

> Muscle enzymes

> Inflammatory markers

> Muscle biopsy

76
Q

3 types of joint

A

Synovial
Fibrous
Cartilaginous

77
Q

Fibrous joint (synarthrosis)

A

> Bones united by fibrous tissue

> Doesn’t allow any movement

> Bones of the skull in adults

78
Q

Cartilaginous joint (Amphiarthrosis)

A

> Bones united by cartilage

> Allow limited movement

> Examples - intervertebral discs; pubic symphysis ; part of sacroiliac joint; costochondral joints

79
Q

Synovial joints (Diarthrosis)

A

> Bones separated by a cavity (containing synovial fluid) and united by a fibrous capsule

> Synovial membrane

> Articular surfaces are covered with cartilage.

80
Q

Classifications of synovial joints

A
  1. Simple - one pair of articular surfaces (metacarpophalangeal joint)
  2. Compound synovial joint (more than one pair of articular surfaces) - elbow joint
81
Q

The inner aspect of the fibrous capsule is line with?

A

Synovial membrane

82
Q

Synovial membrane

  • what is it
  • what does it contain
A

Vascular connective tissue with capillary networks and lymphatics.

Contains SYNOVIAL CELLS (fibroblasts) which produce synovial fluid

83
Q

Synovial cells

A

Fibroblasts

Produce synovia fluid

84
Q

Role of joints during purposeful motion

A

> Stress distribution

> Confer stability

  • shape of the articular component
  • ligaments
  • synovial fluid acts as an adhesive seal that freely permits sliding motion between cartilaginous surfaces

> Joint lubrication

  • cartilage interstitial fluid
  • synovial membrane derived hyaluronic acid (mucin)
  • Synovial membrane-derived lubricin
85
Q

Upon what is the greatest share of loading energy?

A

Muscles and tendons.

86
Q

Hyaluronic acid

A

Mucin

Disaccharide polymer

Joint lubrication.

Derived form synovial membrane

87
Q

Lubricin

A

Derived from synovial membrane

Glycoprotein

Joint lubrication

88
Q

Synovial fluid

  • functions
A

> Lubricates joint

> Facilitates joint movements (reduce friction –> minimise wear and tear)

> Aids in nutrition of articular cartilage

> Supplies the chondrocytes (cartilage cells) with O2 and nutrients

> Removes CO2 and waste products

89
Q

Is synovial fluid a static poole?

A

No, it is continuously replenished and absorbed by the synovial membrane

90
Q

Why is synovial fluid viscous?

A

Due to the presence of hyaluronic acid (mucin)

91
Q

Viscosity and elasticity of the synovial fluid varies with…

A

Joint movement

92
Q

What cells are present in synovial fluid?

A

Mononuclear leukocytes

very few

93
Q

Rapid movement does what to synovial fluid?

A

Decreases its viscosity

Increases its elasticity

these properties become defective in a diseased joint e.g. in osteoarthritis.

94
Q

Gross appearance of synovial fluid

Cell count

A

Clear & colourless.

<200 WBC/mm^3

in inflammatory and septic arthritis, WBC count increases.

Synovial fluid turns red in traumatic synovial tap and in haemorrhagic arthritis

95
Q

Why would synovial fluid be red?

A

Due to trauma

Haemorrhagic arthritis

96
Q

Normal Synovial Fluid

A

Viscosity = high

Colour = Colourless

Clarity = transparent

Total WBC/mm^3 = <200

PMN leukocytes/mm^3 = <25

97
Q

Inflammatory synovial fluid

A

Viscosity = Low

Colour = Straw/yellow

Clarity = translucent

Total WBC/mm^3 = 2000-75000

PMN leukocytes/mm^3 = often >50

98
Q

Septic synovial fluid

A

Viscosity = Variable

Colour = Variable

Clarity = Opaque, milky

Total WBC/mm^3 = often>100,000

PMN leukocytes/mm^3 = often >75

99
Q

Articular (hyaline) Cartilage

  • function
A

> Low friction lubricated gliding surface. Helps prevent wear and tear.

> Distributes contact pressure to subchondral bone

> Composition of cartilage extracellular matrix and the interaction between the fluid and solid phase of the cartilage plays a significant role in determining the mechanical properties of cartilage

Elastic and sponge-like properties

Covers articular surfaces of bones

Has ECM made from WATER (70%), COLLAGEN (20%) - mainly type II contributes to elastic behaviour of cartilage.

PROTEOGLYCANS (10%)

100
Q

Structure of articular cartilage

A

From most superficial to deepest.

> Articular surface

> Superficial zone (includes articular surface) - 10-20%

> Middle zone (40-60%)

> Deep zone (30%)

> Calcified zone

> Subchondral bone

Chondrocytes present in each zone (not in subchondral bone)

Zones differ in ORGANISATION OF COLLAGEN FIBRES and RELATIVE CONTENT OF CARTILAGE COMPONENTS

101
Q

Which type of collagen is found in articular cartilage (for the most part)?

A

Type II collagen

finer than type I

Forms 3 dimensional mesh work

Contributes to elastic behaviour

102
Q

Articular cartilage - mechanical properties of water.

A

70% of cartilage wet weight.

Unevenly distributed - highest near articular surface. (80%)

Cartilage content decreases with age

Maintains resiliency of the tissue and contributes to the NUTRITION and lUBRICATION system

103
Q

Articular cartilage - mechanical properties of COLLAGEN

A

> 20% of wet weight

> Mainly type ii collagen (decreases with age)

> Maintains cartilage architecture

> Provides tensile stiffness and strength

104
Q

Articular cartilage - mechanical properties of PROTEOGLYCAN

A

> 10% cartilage wet weight

> Highest conc. is found in MIDDLE and DEEP zones

> Composed mainly of GLYCOSAMINOGLYCAN (chondroitin sulphate, keratin sulphate ) - GAGs

> These GAGs are bound to a core protein and often linked to hyaluronan

> Chondroitin decreases with age

> Responsible for compressive properties associated with LOAD BEARING

105
Q

What makes up over 98% of the cartilage volume?

A

Extracellular matrix

106
Q

ECM of articular cartilage

A

Synthesised, organised, degraded and maintained by CHONDROCYTES (less than 2% of total cartilage volume)

Articular cartilage is AVASCULAR and the chondrocytes receive nutrients and O2 via synovial fluid

Normal joints: Degradation does not exceed rate of replacement

107
Q

Negative factors/degradative factors in cartilage

A

Mettaloproteinase

Proteolytic enzymes - collagenase, stromelysin

108
Q

Changes in the relative amounts of the three major components of cartilage would…

A

Change the mechanical properties of the cartilage.

Joint disease would also occur if the rate of ECM degradation EXCEEDS the rate of its synthesis

109
Q

Catabolic factors of cartilage matrix turnover

A

Enhance degradation.

Stimulate proteolytic enzymes and inhibit proteoglycan synthesis.

  • TNFα
  • Interleukin 1
110
Q

Anabolic factors of cartilage matrix turnover

A

Stimulate proteoglycan synthesis and counteract effects of IL-1

  • Tumour growth factor (TGF β)
  • Insulin-like growth factor (IGF-1)
111
Q

MARKERS of cartilage degradation

A

> Serum & synovial keratin sulphate

– increased levels indicate cartilage breakdown

– level increases with age and patients with osteoarthritis

> Type II collagen in synovial fluid

– increased levels indicate cartilage breakdown

– evaluating cartilage erosion (osteoarthritis and rheumatoid arthritis)

112
Q

What causes rheumatoid arthritis

A

Synovial cell proliferation and inflammation

113
Q

Osteoarthritis - general cause

A

Cartilage and synovial composition and function deteriorate with age and repeated wear and tear

114
Q

Gouty arthritis

A

Deposition of salt crystals

Uric acid crystals

115
Q

Soft tissue rheumatism

A

Injury and inflammation to periarticular structures causes this.

Injury to tendon leading to tendonitis.

116
Q

Effects on subchondral bone following cartilage wear and tear

A

Cyst formation

Osteophyte formation (bony spurs)

Sclerosis in subchondral bone

Thickened capsule

Fibrillated cartilage

Synovial hypertrophy

117
Q

Gout

A

Deposition of needle shaped uric acid crystals

–> gouty arthritis

118
Q

Pseudo-gout

A

Deposition of rhomboid shaped calcium pyrophosphate crystals causes pseudo-gout.

119
Q

In skeletal muscle cell fibres - where are the nuclei

A

Periphery of the fibre

Cardiac muscle on the other hand, has their nuclei in the centre of the cell.

120
Q

What are muscle fibres grouped into? (F)

A

Bundles called FASCICLES.

A muscle contains several fascicles.

121
Q

Epimysium

A

Connective tissue that surrounds the muscle as a whole

122
Q

Perimysium

A

Connective tissue around a single fascicle.

123
Q

Endomysium

A

Connective tissue around a single muscle fibre.

124
Q

Cell found in cartilage

A

Chondrocytes (chrondroblasts when immature)

125
Q

Where are chondrocytes located?

A

Within a space in the ECM called a LACUNA.

126
Q

Lacuna

A

Structure that houses Chondrocytes

also house osteocytes

127
Q

Types of cartilage

A

> Hyaline cartilage (looks blue-white in colour and is translucent)

> Elastic cartilage

> Fibrocartilage

  • hybrid between tendon and hyaline cartilage.
  • bands of densely packed type I collagen
  • chondrocytes
  • surrounded by small amounts of cartilaginous ECM
  • white
128
Q

Haemopoiesis

  • in utero and babies
  • early twenties
A

Blood cell production

Begins in the BONE MARROW well before birth and by birth marrow is the site of haemopoesis

By early twenties, AXIAL and LIMB GIRDLE skeleton involved in blood production

129
Q

Composition of bone (histology lecture)

A

> 23% collagen
2% non-collagen
10%water
65% bioapatite (form of calcium phosphate - hydroxyapatite)

130
Q

Cortical bone

A

Makes up the shaft (diaphysis)

Hard shit

131
Q

Cancellous/trabecular/spongy bone

A

Occupies the ends of bone (epiphyses).

Fine meshwork of bone - looks like an Aero bar

Made of little tiny struts of bone forming a 3D matrix

LACKS haversian canals.

132
Q

Both types of bone are…

A

LAMELLAR (made up of layers)

133
Q

Osteon

A

Concentric circles of bone surrounding a canal

134
Q

Haversian canal

A

Microscopic tubes that allow blood vessels and nerves to travel through them

Surrounded by osteon

135
Q

Volkmann’s canal

A

Canals that run between haversian canals

136
Q

Osteoprogenitor cells

A

Located on bone surfaces. (e.g. under the periosteum)

- serve as a pool of reserve osteoblasts

137
Q

Osteoblasts

A

Bone forming cells found on surface of developing bone.

Plentiful RER and prominent mitochondria

138
Q

Osteocytes

A

Bone cell trapped within the bone matrix

139
Q

Osteoclasts

A

Large multinucleate cells.

Found on the surface of bone and are responsible for bone resorption

140
Q

Bone remodelling - Cutting cone

A

Osteoclasts will congregate and drill into the bone - tunnel

Blood vessel will grow into the tunnel, with osteoblasts which lay down new lamellar bone

Process continues until only the space of a Haversian canal remains

Collection of osteoclasts/blasts that participate in this process = BASIC MULTICELLULAR UNIT (BMU)

141
Q

Bone mineralisation

A

Osteoblasts secrete:

Collagen

Glycosaminoglycans (GAGs)

Proteoglycans

+ other organic components

collectively called osteoid

Bone made up of calcium phosphate crystals (hydroxyapatite)

142
Q

Younger osteons often…

A

obliterate older osteons

143
Q

Woven bone

A

The type/pattern of bone laid down after a break.

Collagen fibres are laid down in a haphazard fashion.

Not as strong.

Subsequently remodel into lamellar bone by being broken down by osteoclasts and reformed by new osteoblasts.

144
Q

Terminal Bouton

  • what is it surrounded by/
A

Individual branches of motor neurone axon further divide into multiple fine branches, ending in a terminal bouton.

Forms a chemical synapse with the muscle membrane at the NMJ

Release of Acetylcholine (ACh)

  • Surrounded by Schwann cell.
145
Q

α-Motoneurone

A

> Cell body in ventral horn of spinal cord (or brain stem)

> Myelinated axon

> Unmyelinated axon terminals (ending in terminal bouton)

> Presynaptic terminal bouton synapse at the ENDPLATE region of skeletal muscle fibre

146
Q

Skeletal Neuromuscular Junction

  • key features
A

1) Terminal bouton (and surrounding Schwann cell)
2) Synaptic vesicles
3) Synaptic cleft
4) End plate region of the sarcolemma

Synaptic vesicles (containing ACh) cluster at ACTIVE ZONES

Nicotinic ACh receptors are located at regions of the junctional folds that face the active zones

147
Q

Synaptic transmission at the skeletal neuromuscular junction

A
  1. Choline + Acetyl CoA –> CAT (choline acetyl transferase) = ACh
  2. ACh is actively accumulated in vesicles by specific ACh transporter
  3. Calcium concentration rises and binds to specific proteins on vesicle membrane.
  4. Release ACh cargo into the cleft and diffuses to post synaptic membrane
  5. Activate post junctional nicotinic ACh receptors.
  6. Acetylcholinesterase hydrolyses ACh into choline and acetate

Acetate diffuses out of the cleft.

148
Q

Neuromuscular Junciton - Pre-synaptic processes

A

> Choline is transported into the terminal by the choline transporter (symport with Na+)

> ACh is synthesised in the cytosol from choline and acetyl coenzyme A (acetyl CoA – supplied by mitochondria) by the enzyme choline acetyltransferase (ChAT, or CAT)

> ACh is concentrated in vesicles by the vesicular ACh transporter

> Arrival of the action potential at the terminal (1) causes depolarization and the opening of voltage-activated Ca2+ channels (2) allowing Ca2+ entry to the terminal (3)

> Ca2+ causes vesicles ‘docked’ at active zones to fuse with the presynaptic membrane (exocytosis) – ACh diffuses into the synaptic cleft (4) to activate post-synaptic nicotinic ACh receptors in the endplate region (5)

149
Q

Neuromuscular junction - Post-synaptic processes.

A

> ACh activates nicotinic ACh receptors located at the muscle end plate.

> Nicotinic ACh receptors (pentamer)
- opens when 2 molecules of ACh bind to exterior of receptor.

> Open channel is roughly equally permeable to Na+ and K+

> When the gate is open Na+ enters the muscle cell (influx) whilst K+ exits (efflux) simultaneously through many receptors at the ned plate

150
Q

Structure of Nicotinic ACh receptors at post synaptic membrane

A

Pentameric

Glycoprotein subunits that surround a central, cation selective, pore (formed by five M2 helices)

Opens when 2 molecules of ACh bind to the exterior of the receptor

(alpha, gamma, alpha, beta, delta - clockwise)

151
Q

Post synaptic processes (2) Electrical responses to Synaptically released ACh at end plate.

A

> ACh is stored and conenctrAted in vesicles

> Each vesicle contains a “quantum” of neurotransmitter

> Elctricial response to ONE quantum of transmitter is a MINITURE ENDPLATE POTENTIAL (m.e.p.p.)

> Many m.e.p.ps summate to produce end plate potential - a graded electrotonic response

> An e.p.p. that exceeds threshold triggers “all or none” propagated action potential that initiates contraction.

152
Q

End plate potential (e.p.p) triggers….

A

Opening of voltage activated Na+ channels causing a muscle action potential (AP)

1 AP in motor nerve triggers one AP in the muscle –> TWITCH

153
Q

How does an action potential propagate alongna muscle?

A

Muscle fibre has voltage activated Na+ channels.

AP propagates from the endplate over the length of the muscle fibres.

154
Q

How does the muscle action potential cause contraction?

A

Release of Ca2+ from intracellular stores.

AP propagates over the surface membrane of skeletal muscle fibre and enters T tubules

AP arriving at T tubule triggers release of Ca2+ from the sarcoplasmic reticulum –> contraction

155
Q

Termination of ACh action

A

Done by Acetylcholinesterase.

Hydrolysis of ACh to from choline and acetate

Choline taken up by choline transporter

Extremely efficient enzyme. Virtually all ACh molecules are hydrolysed once they unbind from receptor.

156
Q

Cement lines

A

The lines that are often visible surrounding the osteon are termed cement lines.
These are only found in osteons that have formed during remodelling (so not in original development).

MSK (11 decks)

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