Session 7 - Muscles

Question 1

Define Myalgia, Myasthenia, Myocardium, Myopathy and Myoclonus

Answer 1

Myalgia - Muscle pain
Myasthenia - Muscle weakness
Myocardium - Muscular component of the heart
Myopathy - Any disease of the muscles
Myoclonus - A sudden spasm of the muscles

Question 2

Explain the muscle hierarchy

Answer 2

1) Striated Muscles:
- Skeletal Muscle:
- Myoglobin, voluntary contraction (Direct nerve-muscle communication)
- Cardiac Muscle:
- Myoglobin, Involuntary contraction (indirect nerve-muscle communication)
2) Non-striated Muscle:
- Smooth muscle:
- No Myoglobin, Involuntary control (No direct nerve muscle communication)

Question 3

What is an indication of striated muscle death (muscle necrosis) and what problems can this cause?

Answer 3

When striated muscles die myoglobin is released into the bloodstream (myoglobinaemia) and then into the urine (myoglobinuria).
This removal by the kidney can cause renal damage and produces tea-coloured urine.

Question 4

Define a sarcolemma, sarcoplasm, sarcosome, sarcomere, sarcoplasmic reticulum

Answer 4

Sarcolemma: the outer membrane of a muscle cell
Sarcoplasm: Cytoplasm of a muscle cell
Sarcosome: The mitochondrion
Sarcomere: The contraction unit in striated muscle
Sarcoplasmic reticulum: The smooth ER of a muscle cell

Question 5

What are the different connective tissue layer in a muscle?

Answer 5

Endomysium - between muscle fibres
Perimysium - wrapping around fascicles
Epimysium - Surrounds the whole muscle

Question 6

In the tongue what are the roles of the extrinsic and intrinsic muscles?

Answer 6

N.B. This is just for the tongue and the definitions don’t strand true for the rest of the body

Extrinsic - muscles protrude the tongue, retract it and move it from side to side.
Intrinsic - muscles within the tongue that are not attached to bone. They allow the tongue to change shape but not change position - these aid swallowing

Question 7

What can be seen when looking at a transverse section of skeletal muscle?

Answer 7

• Striations formed by lined up sarcomeres (A, Dark, and I, light, bands)
• Each muscle is surrounded by thin connective tissue (containing nerves and capillaries)
• Dark longitudinal streaks are mitochondria
• Peripheral nucleii

Question 8

Why may some sections of the striation (sarcolemma’s) not lie up?

Answer 8

This allows the muscle fibre (cell) to contract to different degrees

Question 9

What are the different zones in a sarcomere?

Answer 9

A Band - Dark band, Myosin fibre (both single and overlapped with actin)
I band - Just actin fibres
Z line - Binding point of actin fibres
M line - Binding point of Myosin fibres
H zone - Myosin fibres only

Question 10

What is a sarcomere defines as?

Answer 10

The single contracting unit in striated muscle. The repeating unit between two Z lines

Question 11

What 3 muscle fibre types are there how do they appear and why?

Answer 11

• Slow twitch fibre - Type 1 - Slow Oxidative, high mitochondria, myoglobin and cytochromes (gives red colour)
• Intermediate - Type 2a - Fast oxidative and glycolytic (anaerobic) - many to high mitochondria, high myoglobin and cytochromes (gives red to pink colour)
• Fast - Type 2b - Fast glycolytic (anaerobic), poor capillary supply, anaerobic, low myoglobin, mitochondria, cytochromes (gives white/pale colour)

Question 12

When looking at the histology of cardiac muscle fibres what are the key identifying features?

Answer 12

• Striations
• Centrally positioned nuclei (1 or 2)
• Intercalating disks (allows for electrical and mechanical coupling made up of mainly gap junctions)
• Branching

Question 13

What are ANP and BNP

Answer 13

ANP - Atrial Natriuretic Peptide (Atrium)
BNP - Brain-Type Natriuretic Peptide (Ventricle)

These are released by the heart during heart failure. They reduce the arterial blood pressure by vasodilation and Na+ excretion which reduces blood volume (water excreted along with Na+)

Question 14

how does the heart get larger if after puberty hyperplasia stops?

Answer 14

Tissue gets larger via hypertrophy which is the enlargement of cells. But not by hyperplasia (the multiplication of cells)

Question 15

What are purkinje fibres?

Answer 15

Specialised conducting cells that conduct the cardia action potential faster and more efficiently than cardiomyocytes. This enables the contraction of the atria or ventricles to occur in a synchronous manner. They have extensive gap junctions

Question 16

Describe the conducting system of the heart

Answer 16

1) sinoatrial (SA) node sends an action potential along Brachman’s Bundles which stimulate the contraction of the atria. The potential is stopped from traversing to the ventricles through a layer of collagen bundles.
2) Atrioventricular (AV) node is stimulated and repeats the signal down the bundle of His to the apex of the heart where it passes down the right and left purkinje bundles to innervate the ventricles

Question 17

Bullet point the differences and similarities between cardiac and skeletal muscle

Answer 17

Both:
- Striated
- Similar contractile units
Differences:
- Cardiac cells have centrally orientated nuclei whereas skeletal are peripheral
- Cardiac muscle cells are branched
- Cardiac muscle have intercalated disks
- Few/no T tubules in SR
- 1 contractile cell type
- Sarcomere not so developed

Question 18

Outline some of the key features of smooth muscle cells

Answer 18

• Spindle shaped (fusiform) with a single central nucleus
• Not striated, No T-tubules
• Different form of actin and myosin interactions
• Slower, more sustained (hours to days) contraction, less ATP requires
• Responds to nervous, hormonal, drug or local blood gases
• Caveolae, small cave- like invaginations used to sample the external environment and initiate contraction

Question 19

Explain the action of contraction of a smooth muscle cell

Answer 19

Dense plaques on opposite sides of the cell are connected by dense bodies on myosin and actin fibres which contract using the same mechanism as skeletal muscle. This allows the cell to contract

Question 20

Where is smooth muscle found and why can its involuntary control be of clinical sygnificance

Answer 20

Found in contractile walls of cavities (modifies volume) such as in: vasculature, gut, respiratory and urinary tract
Because it is involuntary it is able to develop and “mind of it’s own” and can cause disorders such as: hypertension, asthma, IBD, Incontinence

Question 21

How are most smooth muscle cells innervated by the autonomic nervous system?

Answer 21

Autonomic nervous system fibres release neurotransmitters from varicosities into wide synaptic clefts on the smooth muscle cell surface

Question 22

What are the differences in mature muscle repair between muscle types?

Answer 22

Skeletal Muscle - CAN’T regenerate by mitotic division. But satellite cells regenerate the muscle via their mitotic activity (hyperplasia only occurs following injury and only of satellite cells)
Cardiac Muscle - Incapable of regeneration - upon damage fibroblasts invade and lay down scar tissue
Smooth Muscle - Retain ability to undergo mitosis

Question 23

Explain the 4 stages of skeletal muscle repair

Answer 23

1) Acute Phase - Blood clot formed, tissue disruption
2) Sub-acute phase - clot shrinks, new fibrous tissue formed
3) Chronic Phase - tissue fibres becoming organised
4) Fibre regeneration limited but remodelling continues

Question 24

Compare cardiac and smooth muscle

Answer 24

• In common - Central Nuclei, 1 contractile cell type, Act as a syncytium (communicate through Gap junctions)
• Differences - Smooth muscle does not contain sarcomeres, Electrical conduction - specialised (purkinje) cells/routes in cardiac muscle, No troponins in smooth muscle

Question 25

What does the innervation ration of skeletal muscle indicate?

Answer 25

- Small number of fibres per motor unit = fine control but low power - High number of fibres per motor unit = high power but low control

Question 26

What is a kranocyte, where they found and what is their role?

Answer 26

They reside over the terminal Schwann cell at the neuromuscular junction and are thought to anchor the nerve to the muscle.

Question 27

What is the role of T-tubules and what are they?

Answer 27

The transverse tubules are invaginations of the external membrane (sarcolemma) that are rich in ion channels. They carry the signal from the neuromuscular junction to all of the myofibrils within the cell. They are closely associated to SR where they form a triad for quick signal transfer with terminal cisternae.

Question 28

Detail the events leading to contraction of skeletal muscle

Answer 28

1) Initiation - Nerve impulse along motor neuron axon arrives at neuromuscular junction. 2) Impulse prompts release of acetylcholine (ACh) into synaptic cleft causing local depolarisation of sarcolemma. 3) Voltage gated Na+ channels open, Na+ ion enter cell 4) General depolarisation spreads over sarcolemma and into T-tubules 5) Voltage sensor proteins of T-tubule membrane change their conformation 6) Gated Ca2+ ion-release channels of adjacent terminal cisternae are released by step 5 7) Ca2+ ions are rapidly released into the sarcoplasm 8) Ca2+ binds to the TnC subunit of troponin and the contraction cycle is initiated 9) Ca2+ ions are returned to the terminal cisternae of SR

Question 29

What occurs in myasthenia gravis?

Answer 29

It is an autoimmune disease which targets AChR, blocking and destroying them. This reduces the number of endplate invaginations in the synaptic cleft and as such there is reduced synaptic transmission and ultimately intermittent muscle weakness

Question 30

What is the role of calcium in the contraction mechanism?

Answer 30

1- Calcium binds to TnC subunit of troponin, this results in a conformational change which moves tropomyosin away from actins binding sites 2- Myosin heads able to bind to actin and contraction begins

Question 31

After the binding of Ca2+ what sequence of events occurs during contraction?

Answer 31

1) Myosin cross bridge attaches to the actin myofilament 2) Working stroke - the myosin head pivots and bends as it pulls on the actin filament, sliding it towards the M line 3) As new ATP attaches to the myosin head, the cross bridge detaches 4) ATP hydrolysis drives the cocking of the myosin head back to it's original state

Question 32

What is the difference between a muscle insertion and origin point?

Answer 32

Origin - Bone, typically proximal, more stable (greater mass) Insertion - Tends to be distal, tends to moved by contraction

Question 33

What are the 5 muscle roles in movement?

Answer 33

Agonist - Prime Movers (main muscle responsible for a particular movement) Antagonist - Oppose prime movers Synergist - Assist prime movers but can't perform motion on their own Neutraliser - Prevent unwanted actions that an agonist can perform Stabiliser - Act to hold a body part immobile whilst another is moving

Question 34

Describe the 3 muscle lever types

Answer 34

1st class - See-saw, Effort and load on opposite sides of fulcrum 2nd class - Wheel barrow, effort is applied further away from fulcrum than load 3rd class - Fishing rod, effort is applied closer to fulcrum than load

Question 35

What is compartment syndrome?

Answer 35

This occurs when excessive pressure builds up inside an enclosed muscle space in the body (compartment) surrounded by fascia. This restricts blood flow to the compartment and can cause ischaemia. A fasciotomy may be needed to relieve pressure

Question 36

Define muscle tonicity and muscle strength

Answer 36

Tonicity - the tension in a muscle at rest. | Strength - the muscles ability to contract and create force in response to resistance

Question 37

What is muscle atrophy and hypertrophy and what is the replacement time of contractile proteins?

Answer 37

``` Atrophy = destruction > Replacement Hypertrophy = Replacement > destruction ``` The replacement time of contractile proteins is 2 weeks

Question 38

How long does motor neurone regeneration take and where does an incision have to occur for this to happen?

Answer 38

Nerve regeneration takes 3 months to occur and only of cut in the distal 1/3 of the nerve

Question 39

Describe the features of Duchene Muscular Distrophy

Answer 39

- Inherited through X linked recessive pattern (ie, effects boys primarily) - Mutation of dystrophin gene - Absence of dystrophin allows: - Excess Ca2+ into cell - Ca2+ into mitochondria which then swell and burst - Muscle cells burst - Creatine kinase and myoglobin very high in blood - Muscle cells replaced by adipose tissue - Skeletal muscle related symptoms and signs

Question 40

What are creatine kinase assays used for and what is it superseded by?

Answer 40

Creatine Kinase is used to convert creatine to phosphocreatine and is important in metabolically active tissues. As such it can be used to diagnose heart attacks (it is released when muscle tissue is damaged) It has been superseded by troponin I (not 1 the letter i) assays. This is because skeletal muscle and the brain can release creatine kinase

Question 41

How are troponin assays used and what parameters need to be followed?

Answer 41

- Troponin I and T form used for cardiac ischaemia - Readings must be taken within 20hrs (this is because most of the troponin is removed after this point) - Small changes are indicative of cardiac muscle damage but may have occurred a few day ago

Question 42

How does the botulism toxin (Botox) work and why can it cause damage to the CNS?

Answer 42

The toxin blocks neurotransmitter release at the motor endplate preventing the transfer of stimulation. As such the skeletal muscle remains in the non-contractile state (flaccid paralysis). If injected into a nerve it can travel to the CNS causing catastrophic damage

Question 43

How do organophosphates cause damage and what are the symptoms?

Answer 43

- Organophosphates inhibit the function of ACh esterase leading to overstimulation of post-synaptic neurones or muscle cells. ``` Muscarinic: S - Salivation L - Lacrimation = crying U - Urination D - Defecation G - GI tract problems E - Emesis = vomiting ``` ``` Nicotinic: M - Muscle cramps T - Tachycardia W - Weakness T - Twitching F - Fasciculations (small involuntary twitching) ```

Question 44

What is malignant hypERthermia?

Answer 44

Severe reaction to - succinylcholine - an autosomal dominant pattern - Causes massive contractile fasciculations - as a result of excess Ca2+ release - Excessive heat generated and CO2 released causing acidosis - Increased muscle breakdown leads to increased potassium concentration in blood hyperkalaemia

Question 45

Define flexion and extension

Answer 45

Flexion - The bending of a limb | Extension - The straightening of a limb