The Musular-Skeletal System Flashcards
Actin
thin filament which has binding site for myosin head
Myosin
Thick filament with a head that binds to actin
Tropomyosin
A fibre that is moved in the presence of calcium ions
Myofibrils
Long muscle fibres made of many sarcomeres
Sarcomere (including M and Z lines)
The part of the muscle that changes shape
Troponin
A protein that causes the movement of Tropomyosin which uncovers the binding site on actin
Sarcoplasmic reticulum
A network of smooth ER that sits around the muscle containing sarcoplasm
ATP (adenosine triphosphate)
Energy source for detaching/repositioning the myosin head
ADP (Adenosine Diphosphate
Bound to the myosin head
Muscle contraction
• The sliding filament theory says that the two proteins – actin and myosin – slide past each other inwards when the muscle contracts which shortens the muscle.
• When the muscle relaxes the fibres slide outwards which lengthen the muscle again
Sliding filament theory
• Starting point – skeletal muscles move by contracting and relaxing
• Muscles are made of muscle fibres and myofibrils. These fibres are made of functional units called
sarcomeres. These are the ‘stripes’ on cardiac and skeletal muscles
• Each sarcomere contains the two proteins
The two proteins
• Each sarcomere contains two types of proteins
• Thin fibres called actin with a tropomyosin fibre wrapped around them and another protein called troponin at regular intervals
• Thick fibres called myosin with globular heads that move
Anatomy of muscles
• Muscles are made up of muscle fibres
• A muscle fibre is made up of a large number of myofibrils which are wrapped in a smooth ER membrane –
the sarcoplasmic reticulum (SR)
• This SR contains sarcoplasm which is the cytoplasm of muscle cells
• The functional part of the myofibril – the sarcomere- is where the two proteins are found
The anatomy of the
sarcomere
Z line – the end of the sarcomere
M line – the middle of the sarcomere
Thin filament – action
Thick filament – myosin
The energy for muscle contraction
• Muscles contract using energy
• Energy is provided by a molecule called Adenosine Triphosphate (ATP) and is held in the bond between
the phosphate groups.
• When ATP looses a phosphate group (Pi) this releases energy and the molecule is converted to into Adenosine Diphosphate (ADP)
• ATP is hydrolysed (broken down) into ADP by ATPase (enzyme).
• ADP later gains a phosphate group and turns back into ATP which uses energy to remake the bond
Getting the action potential to the muscle
• Motor neurons link to muscles at neuromuscular junctions (like a synapse)
• The arrival of the action potential causes calcium ions to be releases from the covering of the myofibril called the sarcoplasmic reticulum which is network of endoplasmic reticulum surrounding the muscle fibres (the blue network)
Calcium ions (Ca2+ )
• Calcium ions bind to troponin molecules, stimulating them to change shape
• Troponin and tropomyosin proteins change position on the actin (thin) filaments
• Myosin binding sites are exposed on the actin molecules
Movement of globular heads
• The globular heads of the myosin molecules bind with these sites, forming cross-bridges between the two types of filament
• The myosin heads move and pull the actin filaments towards the centre of the sarcomere, causing the muscle to contract a very small distance
• ATP hydrolysis occurs at the myosin heads, providing the energy required for the myosin heads to release the actin filaments
• The myosin heads move back to their original positions and bind to new binding sites on the actin filaments, closer to the Z line
Muscular Dystrophy
• Muscular Dystrophy is not a single condition – it is a group of over 60 inherited
conditions. People may carry the gene without realising.
• There are many different types of MD. All types cause muscle weakness – which leads to
disability, but the areas affected and the severity of the symptoms are different
• the three most common types are Duchenne MD, Myotonic MD and Facioscapulohumeral MD
• its progressive and in some types fatal so whilst there is no cure there are treatments that can support quality of life
Causes of two most common types
• Duchenne MD results from a genetic mutation that leads to a lack of dystrophin, a protein that helps strengthen muscle fibres and protect them from injury. Inherited in an X-linked recessive manner.
• Myotonic MD is caused by an abnormal expansion of certain DNA sequences on one of two different genes. Inherited in an autosomal dominant manner.
• Recall – an change in the primary structure of a protein impacts the final size/shape and function (tertiary structure)
X linked recessive inheritance
• X-linked means that the gene causing the problem is found on the X chromosome.
• Girls have two X chromosomes, so if a girl has an altered gene on her X chromosome, it is less likely to affect ner because she has a normal copy oT the same gene on her other X chromosome.
• Boys only have one X chromosome, so if he has an altered gene on his X chromosome it will affect him.
Statistics and data
• In the UK, around 70,000 people have MD or a related condition. Less than 0.1% of the population.
• Duchenne MD is the most common type of MD. In the UK, about 100 boys are born with Duchenne MD each year, and there are about 2,500 people living with the condition in the UK at any one time.
• Myotonic MD is the second most common type of MD, affecting around 1 person in every 8,000.
• Facioscapulohumeral MD is thought to affect around 1 in every 20,000 people in the UK, making it the third most common MD.
Symptoms
• The symptoms of muscular dystrophy, and the age at which symptoms occur will be different in each person. Common symptoms could include:
• Muscle weakness
• Muscle stiffness or pain
• Changes in mobility, such as difficulty walking
• Difficulty in lifting things
• Increased occurrence of falls
• Some types of muscular dystrophy can affect the heart or the muscles used for breathing. In some severe cases, muscular dystrophy may have life-threatening complications
Impact on body systems on MD
• MS system – lack of strength and mobility
• Cardiorespiratory system – damage to heart and muscles supporting respiration
• Nervous system – depending on type of MD – vision/cognitive impairment could be present.
• Digestive system - dysphagia
Treatments
• Medication– steroids improve muscle strength and function but have side effects with long term use
• Physiotherapy– maintaining flexibility, strength and joints to slow progression
• Occupational therapy – aids at home to maintain quality of life
• Surgery (If type requires it) – fixing joints, cataracts, spinal fusion, tendon release, pacemaker fitting if needed
Rheumatoid arthritis
• Rheumatoid arthritis is a type of arthritis where your immune system attacks the tissue lining the joints on both sides of your body.
• It is an chronic autoimmune disease – there is no cure but treatments can manage symptoms.
• There is no definitive cause and other body systems can also be impacted. It is more common in women than men
Mechanism of damage
The synovium (inner membrane) covering your joints becomes sore and inflamed, releasing cytokines that damage nearby:
• bones
• cartilage – the stretchy connective tissue between bones
• tendons – the tissue that connects bone to muscle
• ligaments – the tissue that connects bone and cartilage
• If rheumatoid arthritis is not treated, these chemicals gradually cause the joint to lose its shape and alignment. Eventually, it can destroy the joint completely
Symptoms
• Pain – throbbing or aching
• Stiffness – worse in mornings and when inactive
• Swelling, warmth and redness (inflammation)
• Tiredness and a lack of energy
• A high temperature
• Sweating
• A poor appetite
• Weight loss
• Dry eyes– if the eyes are affected
• Chest pain – if the heart or lungs are affected
Complications
• Carpel tunnel syndrome – compression of nerves in the wrist
• Systemic inflammation
• lungs– inflammation of the lungs or lung lining can lead to pleurisy or pulmonary fibrosis, which can cause chest pain, a persistent cough and shortness of breath
• heart – inflammation of the tissue around the heart can lead to pericarditis, which causes chest pain
• eyes– inflammation of the eyes can lead to scleritis or Sjögren’s syndrome. Scleritis can cause eye redness and pain, whereas Sjögren’s syndrome can cause dry eyes
• blood vessels– inflammation of the blood vessels, known as vasculitis, is the thickening, weakening, narrowing and scarring of blood vessel walls. In serious cases, it can affect blood flow to your body’s organs and tissues and can be life threatening
• Cardiovascular disease
• Cervical myelopathy (compression of spinal cord at the top of spine not cervix)
Treatments - remember no cure…
• Goals - reduce inflammation in the joints, relieve pain, prevent or slow down joint damage, reduce disability, enable physical activity and reduce severity of flare ups
• Disease-modifying anti-rheumatic drugs (DMARDs) block the actions of the chemicals that the immune system produced that cause damage (including biologic medicines)
Disease-modifying anti-rheumatic drugs (DMARDs)
Two classes:
• Traditional– a wide range of functions that impact immune response such as Methotrexate (small molecules artificially produced)
• Biological– very targeted on specific pathways that inhibit the immune response (produced in living cells) - infliximab for example. – newest ones are called JAK inhibitors –Tofacitinib
