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Showing posts with label Anatomy and Physiology. Show all posts
Showing posts with label Anatomy and Physiology. Show all posts

Wednesday, December 2, 2020

காதில் இரைச்சல், What is tinnitus?

கேட்பது இசையா, இரைச்சலா என நாம் உணர்ந்து கொள்வதற்காகப் படைக்கப்பட்ட காதுக்குள்ளேயே இரைச்சல் ஏற்படுவது பலருக்கும் பெருந்தொல்லையாக இருக்கும்.

இந்தியாவில் பத்தில் ஒருவருக்கு இந்தப் பிரச்சினை உள்ளது. உலக அளவில் முதியோருக்கு ஏற்படும் முக்கிய உடல்நலப் பிரச்சினைகளில் இதுவும் ஒன்று.


What Exactly is Hyperacusis?

Hyperacusis is a little known condition that seems to arise from a problem in the way the brain perceives noise. The underlying cause of the condition is elusive, however its impact on people who suffer with it is well documented. The condition of hyperacusis often leads to pain and discomfort when sufferers are exposed to louder sounds. While we say louder, we don’t mean very loud, in fact most people would consider the level of the sound as normal.

People suffering with the condition find some sounds intolerable, for instance, vehicle noise, the sound of a fan, the shuffling of papers. While all sound can be perceived as too loud, high frequency sounds in particular cause real issue for someone with Hyperacusis. This can have a dramatic effect on the lives of people who suffer with the condition, sometimes it can be difficult if not impossible to function during a normal day. We have seen the condition contribute to social isolation, phonophobia (fear of normal sounds), and depression.

What is tinnitus?

Tinnitus happens when we consciously hear a sound that does not come from any source outside the body. It is not a disease, but a symptom of an underlying problem.

The noise is usually subjective, meaning that only the person who has tinnitus can hear it.

The most common form is a steady, high-pitched ringing. This can be annoying, but it does not usually indicate a serious condition.

In fewer than 1 percent of cases, it may be objective. This means that other people can hear the noise. This type of noise may be caused by cardiovascular or musculoskeletal movements in the person’s body. This can be a sign of a medical emergency.

Symptoms

Tinnitus involves the sensation of hearing sound when no external sound is present. Tinnitus symptoms may include these types of phantom noises in your ears:

  • Ringing
  • Buzzing
  • Roaring
  • Clicking
  • Hissing
  • Humming

The phantom noise may vary in pitch from a low roar to a high squeal, and you may hear it in one or both ears. In some cases, the sound can be so loud it can interfere with your ability to concentrate or hear external sound. Tinnitus may be present all the time, or it may come and go.

There are two kinds of tinnitus.

  • Subjective tinnitus is tinnitus only you can hear. This is the most common type of tinnitus. It can be caused by ear problems in your outer, middle or inner ear. It can also be caused by problems with the hearing (auditory) nerves or the part of your brain that interprets nerve signals as sound (auditory pathways).
  • Objective tinnitus is tinnitus your doctor can hear when he or she does an examination. This rare type of tinnitus may be caused by a blood vessel problem, a middle ear bone condition or muscle contractions.

காது இரைச்சல் (Tinnitus) என்பது ஒரு தனிப்பட்ட நோயல்ல; உடலில் இருக்கும் ஒரு நோயின் வெளிப்பாடு; அறிகுறி. காது இரைச்சலுக்கான காரணம் காதிலும் இருக்கலாம்; உடலின் வேறு பகுதியிலும் இருக்கலாம்.

சில மனநோயாளிகள்கூடக் காதில் இரைச்சலும் குரலும் கேட்பதாகக் கூறுவார்கள். காது, காதிலுள்ள எலும்புகள், காதிலிருந்து மூளைக்குச் செல்லும் காது நரம்பு, மூளை ஆகியவற்றில் எது பாதிக்கப்பட்டாலும் காதில் இரைச்சல் ஏற்படும்.

காதுக்குள் வண்டு ரீங்காரம் செய்வது போன்றோ, `இஸ்ஸ்ஸ்…’ என்ற இரைச்சலோ, குக்கர் விசில் அடிப்பது போன்றோ, புயல் மாதிரிப் பேரிரைச்சலோ கேட்பதாக இருந்தால் அந்த நபருக்கு ‘காது இரைச்சல்’ இருப்பதாக அர்த்தம். இந்த இரைச்சலின் தன்மை ஆளுக்கு ஆள் வேறுபடும். ஒருவருக்கு இரைச்சல் தொடர்ச்சியாகக் கேட்கும்; இன்னொருவருக்கு விட்டு விட்டுக் கேட்கும். ஒரு சிலருக்கு இரைச்சல் தாங்கமுடியாத அளவுக்குக் கடுமையாக இருக்கும்.

பாதிப்புகள் என்ன?

சுற்றுப்புறம் அமைதியாக இருந்தால், காதுக்குள் இரைச்சல் அதிகமாகக் கேட்கும். குறிப்பாக, இரவில் இது அதிகம் தொல்லை தரும். உறக்கம் வராது. மனக் குழப்பத்துக்கு அடிபோடும். நினைவாற்றல் குறையும். மன அழுத்தம் அதிகரிக்கும். பகல் நேரப் பணியில் கவனம் செலுத்துவது சிரமம் தரும். உடல் சோர்வாக இருக்கும்.

காரணம் என்ன?

காது இரைச்சலுக்குப் பல காரணங்கள் உண்டு. அவற்றைத் தற்காலிகக் காரணங்கள், நிரந்த காரணங்கள் என்று பிரித்து வைத்துள்ளது மருத்துவம். காதுமடலைச் சேர்த்துச் சிறு துவாரமாகக் காதுக்குள் செல்கிற வெளிக்காதுக்குழலில், இயற்கையாகச் சுரக்கிற மெழுகு உருண்டு திரண்டு கட்டியாகிக் காதை அடைத்துக்கொண்டால், அயல் பொருட்கள் ஏதாவது அடைத்துக்கொண்டால், காளான் தொற்று ஏற்பட்டால் காதுக்குள் இரைச்சல் கேட்கும். இவையெல்லாமே தற்காலிகமாகக் காது இரைச்சலை உண்டாக்குபவை.

காதில் உள்ள அழுக்கை / அயல் பொருளை அகற்றிவிட்டால் அல்லது காளான் தொற்றுக்குச் சிகிச்சை பெற்றுவிட்டால் காது இரைச்சலில் இருந்து விடைபெறலாம். ஜலதோஷம் பிடிப்பதால்கூடச் சில நேரங்களில் தற்காலிகமாகக் காது இரைச்சல் உண்டாகும்.

அதேநேரத்தில் சில காரணங்களால் காது இரைச்சல் நிரந்தரமாகிவிடும். முதுமை இதற்கு முக்கியக் காரணம். வயதாக வயதாக நடுக்காது எலும்புகள், காக்ளியா எனும் நத்தை எலும்பு மற்றும் காது நரம்பிழைகள் சிதைவடைவதால் காதுக்குள் இரைச்சல் தொடங்குவது வழக்கம். காதுக்குப் போகும் ரத்தம் முதுமையில் குறைவதாலும் காதில் இரைச்சல் ஏற்படுவதுண்டு.

வெளிக்காதையும் நடுக்காதையும் பிரிக்கிற செவிப்பறையில் துளை விழுந்துவிட்டால், காது இரைச்சல் ஏற்பட அதிக வாய்ப்பு உள்ளது. இதுபோன்று நடுக்காதுக்குள் நீர் கோத்துக்கொண்டால், சீழ் பிடித்துவிட்டால் காது இரைச்சல் ஏற்படும். நடுக்காதில்தான் நம் உடலிலேயே மிகச் சிறிய எலும்புகளான சுத்தி, பட்டடை, அங்கவடி எலும்புகள் உள்ளன.

இவற்றில் ‘எலும்பு முடக்கம்’ (Otosclerosis) எனும் நோய் தாக்கும்போது, எலும்புகள் இறுகி, ஒலி அதிர்வுகள் காது நரம்புக்குச் செல்வது தடைபடும். அப்போது காது மந்தமாவதோடு, இரைச்சலும் கேட்கும். அடுத்து, தொண்டையையும் காதையும் இணைக்கிற ‘காது – மூக்கு -தொண்டைக்குழாய்’ (Eustachian tube) அழற்சி அடைந்து, வீங்கிக் கொண்டாலும் காது இரைச்சலுக்கு வழி அமைக்கும். காதில் அடிபட்டாலும் இந்தப் பிரச்சினை ஏற்படலாம்.


What causes tinnitus?

Tinnitus (pronounced tin-NY-tus or TIN-u-tus) is not a disease. It is a symptom that something is wrong in the auditory system, which includes the ear, the auditory nerve that connects the inner ear to the brain, and the parts of the brain that process sound. Something as simple as a piece of earwax blocking the ear canal can cause tinnitus. But it can also be the result of a number of health conditions, such as:

  • Noise-induced hearing loss
  • Ear and sinus infections
  • Diseases of the heart or blood vessels
  • Ménière’s disease
  • Brain tumors
  • Hormonal changes in women
  • Thyroid abnormalities

Tinnitus is sometimes the first sign of hearing loss in older people. It also can be a side effect of medications. More than 200 drugs are known to cause tinnitus when you start or stop taking them.

People who work in noisy environments—such as factory or construction workers, road crews, or even musicians—can develop tinnitus over time when ongoing exposure to noise damages tiny sensory hair cells in the inner ear that help transmit sound to the brain. This is called noise-induced hearing loss.

Service members exposed to bomb blasts can develop tinnitus if the shock wave of the explosion squeezes the skull and damages brain tissue in areas that help process sound. In fact, tinnitus is one of the most common service-related disabilities among veterans returning from Iraq and Afghanistan.

Pulsatile tinnitus is a rare type of tinnitus that sounds like a rhythmic pulsing in the ear, usually in time with your heartbeat. A doctor may be able to hear it by pressing a stethoscope against your neck or by placing a tiny microphone inside the ear canal. This kind of tinnitus is most often caused by problems with blood flow in the head or neck. Pulsatile tinnitus also may be caused by brain tumors or abnormalities in brain structure.

Even with all of these associated conditions and causes, some people develop tinnitus for no obvious reason. Most of the time, tinnitus isn’t a sign of a serious health problem, although if it’s loud or doesn’t go away, it can cause fatigue, depression, anxiety, and problems with memory and concentration. For some, tinnitus can be a source of real mental and emotional anguish.

Why do I have this noise in my ears?

Although we hear tinnitus in our ears, its source is really in the networks of brain cells (what scientists call neural circuits) that make sense of the sounds our ears hear. A way to think about tinnitus is that it often begins in the ear, but it continues in the brain.

Scientists still haven’t agreed upon what happens in the brain to create the illusion of sound when there is none. Some think that tinnitus is similar to chronic pain syndrome, in which the pain persists even after a wound or broken bone has healed.

Tinnitus could be the result of the brain’s neural circuits trying to adapt to the loss of sensory hair cells by turning up the sensitivity to sound. This would explain why some people with tinnitus are oversensitive to loud noise.

Tinnitus also could be the result of neural circuits thrown out of balance when damage in the inner ear changes signaling activity in the auditory cortex, the part of the brain that processes sound. Or it could be the result of abnormal interactions between neural circuits. The neural circuits involved in hearing aren’t solely dedicated to processing sound. They also communicate with other parts of the brain, such as the limbic region, which regulates mood and emotion.

What should I do if I have tinnitus?

The first thing is to see your primary care doctor, who will check if anything, such as ear wax, is blocking the ear canal. Your doctor will ask you about your current health, medical conditions, and medications to find out if an underlying condition is causing your tinnitus.

If your doctor cannot find any medical condition responsible for your tinnitus, you may be referred to an otolaryngologist (commonly called an ear, nose, and throat doctor, or an ENT). The ENT will physically examine your head, neck, and ears and test your hearing to determine whether you have any hearing loss along with the tinnitus. You might also be referred to an audiologist who can also measure your hearing and evaluate your tinnitus.

What if the sounds in my ear do not go away?

Some people find their tinnitus doesn’t go away or it gets worse. In some cases it may become so severe that you find it difficult to hear, concentrate, or even sleep. Your doctor will work with you to help find ways to reduce the severity of the noise and its impact on your life.

Are there treatments that can help me?

Tinnitus does not have a cure yet, but treatments that help many people cope better with the condition are available. Most doctors will offer a combination of the treatments below, depending on the severity of your tinnitus and the areas of your life it affects the most.

  • Hearing aids often are helpful for people who have hearing loss along with tinnitus. Using a hearing aid adjusted to carefully control outside sound levels may make it easier for you to hear. The better you hear, the less you may notice your tinnitus. Read the NIDCD fact sheet Hearing Aids for more information.
  • Counseling helps you learn how to live with your tinnitus. Most counseling programs have an educational component to help you understand what goes on in the brain to cause tinnitus. Some counseling programs also will help you change the way you think about and react to your tinnitus. You might learn some things to do on your own to make the noise less noticeable, to help you relax during the day, or to fall asleep at night.
  • Wearable sound generators are small electronic devices that fit in the ear and use a soft, pleasant sound to help mask the tinnitus. Some people want the masking sound to totally cover up their tinnitus, but most prefer a masking level that is just a bit louder than their tinnitus. The masking sound can be a soft “shhhhhhhhhhh,” random tones, or music.
  • Tabletop sound generators are used as an aid for relaxation or sleep. Placed near your bed, you can program a generator to play pleasant sounds such as waves, waterfalls, rain, or the sounds of a summer night. If your tinnitus is mild, this might be all you need to help you fall asleep.
  • Acoustic neural stimulation is a relatively new technique for people whose tinnitus is very loud or won’t go away. It uses a palm-sized device and headphones to deliver a broadband acoustic signal embedded in music. The treatment helps stimulate change in the neural circuits in the brain, which eventually desensitizes you to the tinnitus. The device has been shown to be effective in reducing or eliminating tinnitus in a significant number of study volunteers.
  • Cochlear implants are sometimes used in people who have tinnitus along with severe hearing loss. A cochlear implant bypasses the damaged portion of the inner ear and sends electrical signals that directly stimulate the auditory nerve. The device brings in outside sounds that help mask tinnitus and stimulate change in the neural circuits. Read the NIDCD fact sheet Cochlear Implants for more information.
  • Antidepressants and antianxiety drugs might be prescribed by your doctor to improve your mood and help you sleep.
  • Other medications may be available at drugstores and on the Internet as an alternative remedy for tinnitus, but none of these preparations has been proved effective in clinical trials.

Can I do anything to prevent tinnitus or keep it from getting worse?

Noise-induced hearing loss, the result of damage to the sensory hair cells of the inner ear, is one of the most common causes of tinnitus. Anything you can do to limit your exposure to loud noise—by moving away from the sound, turning down the volume, or wearing earplugs or earmuffs—will help prevent tinnitus or keep it from getting worse.

What are researchers doing to better understand tinnitus?

Along the path a hearing signal travels to get from the inner ear to the brain, there are many places where things can go wrong to cause tinnitus. If scientists can understand what goes on in the brain to start tinnitus and cause it to persist, they can look for those places in the system where a therapeutic intervention could stop tinnitus in its tracks.

In 2009, the National Institute on Deafness and Other Communication Disorders (NIDCD) sponsored a workshop that brought together tinnitus researchers to talk about the condition and develop fresh ideas for potential cures. During the course of the workshop, participants discussed a number of promising research directions, including:

  • Electrical or magnetic stimulation of brain areas involved in hearing. Implantable devices already exist to reduce the trembling of Parkinson’s disease and the anxieties of obsessive-compulsive disorder. Similar devices could be developed to normalize the neural circuits involved in tinnitus.
  • Repetitive transcranial magnetic stimulation (rTMS). This technique, which uses a small device placed on the scalp to generate short magnetic pulses, is already being used to normalize electrical activity in the brains of people with epilepsy. Preliminary trials of rTMS in humans, funded by the NIDCD, are helping researchers pinpoint the best places in the brain to stimulate in order to suppress tinnitus. Researchers are also looking for ways to identify which people are most likely to respond well to stimulation devices.
  • Hyperactivity and deep brain stimulation. Researchers have observed hyperactivity in neural networks after exposing the ear to intense noise. Understanding specifically where in the brain this hyperactivity begins and how it spreads to other areas could lead to treatments that use deep brain stimulation to calm the neural networks and reduce tinnitus.
  • Resetting the tonotopic map. Researchers are exploring how to take advantage of the tonotopic map, which organizes neurons in the auditory cortex according to the frequency of the sound to which they respond. Previous research has shown a change in the organization of the tonotopic map after exposing the ear to intense noise. By understanding how these changes happen, researchers could develop techniques to bring the map back to normal and relieve tinnitus.
Thanks
https://invizear.com/hyperacusis/
https://www.hindutamil.in
https://www.medicalnewstoday.com
https://www.nidcd.nih.gov

https://www.mayoclinic.org/diseases-conditions/tinnitus

Tuesday, June 19, 2018

Five Ways to Use Quantum Technology Every Day.


Quantum technology

Quantum technology is a new field of physics and engineering, which transitions some of the properties of quantum mechanics, especially quantum entanglement, quantum superposition and quantum tunnelling, into practical applications such as quantum computing, quantum sensors, quantum cryptography, quantum simulation, quantum metrology and quantum imaging.

The field of quantum technology was first outlined in a 1997 book by Gerard J. Milburn which was then followed by a 2003 article by Jonathan P. Dowling and Gerard J. Milburn, as well as a 2003 article by David Deutsch. The field of quantum technology has benefited immensely from the influx of new ideas from the field of quantum information processing, particularly quantum computing. Disparate areas of quantum physics, such as quantum optics, atom optics, quantum electronics, and quantum nanomechanical devices, have been unified under the search for a quantum computer and given a common language, that of quantum information theory.

The Quantum Manifesto was signed by 3,400 scientists and officially released at the 2016 Quantum Europe Conference, calling for a quantum technology initiative to coordinate between academia and industry, to move quantum technologies from the laboratory to industry, and to educate quantum technology professionals in a combination of science, engineering, and business.



Applications

Sensing

Quantum superposition states can be very sensitive to a number of external effects, such as electric, magnetic and gravitational fields; rotation, acceleration and time, and therefore can be used to make very accurate sensors. There are many experimental demonstrations of quantum sensing devices, such as the experiments carried out by the nobel laureate William D. Phillips on using cold atom interferometer systems to measure gravity and the atomic clock which is used by many national standards agencies around the world to define the second.

Recent efforts are being made to engineer quantum sensing devices, so that they are cheaper, easier to use, more portable, lighter and consume less power. It is believed that if these efforts are successful, it will lead to multiple commercial markets, such as for the monitoring of oil and gas deposits, or in construction.

Secure communications

Quantum secure communication are methods which are expected to be 'quantum safe' in the advent of a quantum computing systems that could break current cryptography systems. One significant component of a quantum secure communication systems is expected to be Quantum key distribution, or 'QKD': a method of transmitting information using entangled light in a way that makes any interception of the transmission obvious to the user.

Computing

Quantum computers are the ultimate quantum network, combining 'quantum bits' or 'qubit' which are devices that can store and process quantum data (as opposed to binary data) with links that can transfer quantum information between qubits. In doing this, quantum computers are predicted to calculate certain algorithms significantly faster than even the largest classical computer available today.

Quantum computers are expected to have a number of significant uses in computing fields such as optimization and machine learning. They are famous for their expected ability to carry out 'Shor's Algorithm', which can be used to factorise large numbers which are mathematically important to secure data transmission.


Monday, February 6, 2017

What is Muscle physiology




·        Voluntary muscles (supplied by somatic nerves)
o       Skeletal muscle: for locomotion, positional change & convection of respiratory gases.
·        Involuntary muscles: (supplied by autonomic nerves)
o       Cardiac muscle: for pumping the blood
o       Smooth muscle: motor of internal organs & blood vessels. 



Feature
Smooth
Cardiac
Skeletal
Myofibrils
Absent
Present
Present
T tubules
Absent
Short & broad
Long & thin
Depolarization
Spontaneous
Spontaneous
Upon stimulation
Summation
Possible
Not possible
Possible
RMP
Unstable
Stable
Stable
Source of Ca
Extracellular
SR
SR
Neuromuscular junction
Not well defined
Not well defined
Well defined



SKELETAL MUSCLE

·        The muscle mass is separated from neighbouring tissues by à fascia
·        Beneath the fascia, the muscle is covered by à epimysium
·        Muscle fiber bundle or fascicule is covered by à perimysium
·        Each muscle fiber is covered by à endomysium
·        Muscle cell or fibers are à multinucleated with peripheral nuclei located just beneath the sarcolemma.
·        Each striated muscle fiber is invested by a cell membrane à the sarcolemma, which surrounds the sarcoplasm, several mitochondria (sarcosomes) & myofibrils.


Structure of a myofibril
Each myofibril consists of a number of two alternating bands:
Light band: I band - Isotropic in nature (contain only actin filaments)
Dark band: A band - Anisotropic in nature (actin & myosin filaments overlap in this region)

(Isotropic: when polarized light is passed thru the muscle fiber, the light rays are refracted at the same angle)
Z lines or Z plates (plate-like proteins) subdivide each myofibril into striated compartments called sarcomeres (2μm long).


Sarcomere:
The portion of myofibril in btwn two Z lines.
It is the structural & functional unit of skeletal muscle.
H zone: lies in the middle of A band. Contains only myosin filaments.
M line: situated in the middle of H zone. It is formed by myosin binding proteins.

Sarcomere consists of myofilaments à action & myosin filaments
Actin Filaments: Thin filaments, Extend to z line, I band & upto H zone of A band.
Myosin Filaments: Thick filaments, Situated in A band, including the H zone.

During contraction: H zone & I band are shortened and the Z lines come closer.

Types of Skeletal Muscle proteins
Contractile proteins: Actin, Myosin
Regulatory proteins:
·        Skeletal & cardiac muscle – tropomyosin, troponin
·        Smooth muscle - Calmodulin
Nebulin: responsible for positioning of action.
Titin (connectin)

Contractile protein connected with Z disc: Actin
Contractile protein connected with M disc: Myosin
Titin is connected with z disc & M disc


MYOSIN
Myosin I – present in sperms
Myosin II - present in sarcomere (skeletal muscles)

·        Each myosin filament consists of a bundle of myosin-II molecules.
·        Each myosin molecule is made up of 6 polypeptide chains: 2 heavy chains & 4 light chains
·        At one end, the 2 heavy chains twist around each other to form a double helix – the tail.
·        At the other end, both the chains turn away in opposite directions & form – globular head.
·        Each myosin head is attached with 2 light chains (one regulatory & one essential).
·        Each myosin head has 2 sites: an actin binding site & a motor domain with a nucleotide binding pocket (for ATP or ADP + Pi)
·        Conformational changes in the head–neck segment allow the myosin head to “tilt” when interacting with actin (sliding filaments).
·        In the central part of myosin filament (H zone) à Myosin head is absent.

ACTIN
·        Each actin molecule is called F actin & it is a polymer of a small protein called G actin.
·        Actin molecules in actin filament are also arranged in the form of a double helix, which is positioned by the equally long protein nebulin.
·        Each F actin molecule has an active site for the attachment of myosin head.

During rest, Actin is detached from myosin by relaxing (inhibitory) proteins:
·        Tropomyosin: covers the myosin binding sites on F-actin molecules.
·        Troponin which is formed of 3 subunits:
o       Troponin T: binds to tropomyosin
o       Troponin I: binds with actin & prevents the filaments from sliding when at rest
o       Troponin C: has two regulatory bindings sites for Ca2+ at the amino end

Other proteins of the muscle:
·        Actinin: Attaches actin filament to Z line.
·        Desmin: binds Z line with sarcolemma.
·        Nebulin: runs parallel to actin filaments.
·        Titin (connectin): Connected to M line (at its carboxyl end) & Z line (at its amino end). Provides elasticity to the muscle.
Longest known polypeptide chain & comprises 10% of the total muscle mass.

[when the muscle is stretched, titin unfolds itself.
If the stretching is more, it offers resistance & protects the sarcomere from overstretching.]

·        Dystrophin: connects actin filament to to the membrane of muscle cell. It is connected to sarcoglycans of the sarcolemma.
·        Merosin binds the sarcoglycans to the collagen fibrils of the extracellular matrix.

Mutation of these proteins leads to muscular dystrophy (Duchenne muscular dystrophy, limb-girdle dystrophy, congenital muscular dystrophy) implying the degeneration of muscle fibers with increasing muscular weakness.

Sarcotubular System
Formed by: T tubules & L tubules (sarcoplasmic reticulum)

T tubules: Formed by transverse invaginations of the sarcolemma.
Function:
They act as the inward pathway for action potential.
It contains DHPR which are volt sensitive receptors.
Sarcoplasmic Retiuculum (L tubules)
The ER is modified as longitudinal tubules with terminal expansion called – cisternae which store Ca ions & contain RYR1.

Triad of skeletal muscle: T tubule along with terminal cisternae on either side.
They are situated at the junction btwn A band & I band.
When AP reaches DHPR on T tubules, it opens RYR1 on the cisternae à Ca efflux from the cisternae into sarcoplasm.
The released Ca binds with troponin C & uncovers the active sites for myosin on actin.

               

Skeletal muscle formed of:
·        Central contractile part – contains sk. Muscle fibers
·        Peripheral non-contractile ends – elastic non-contractile stretchable tissues
Contraction of sk muscle à shortening of central contractile part (In the form of shortening of sarcomeres.

Types of sk muscle contraction:
Isometric contraction
Isotonic contraction
Shortening of central contractile part = lengthening of peripheral non-contractile parts
Shortening of central contractile part as well as shortening & stretching of peripheral ends.
Total length is constant
Total tension is constant.
Eg: During upright position in lower sk muscles to maintain the body posture.
Could be associated with shortening or lengthening (Lifting or placing down of object with a constant tension (eg: picking of precious objects very slowly).
No external work done.
External work done
In cardiac muscle, this represents isovolumetric contraction, bcoz the muscle length determines the atrial or ventricular volume.)
In cardiac muscle, this represents isobaric contraction, bcoz the muscle force determines the atrial or ventricular pressure.

Auxotonic contractions: muscle length & force both vary simultaneously.
Afterloaded contraction: An isotonic or auxotonic contraction that builds on an isometric one.

                     

Types of skeletal muscle fibers depending on myosin ATPase activity:
Type I or slow twitch fibers – have small diameter
Type II or fast twitch fibers – have large diameter. Have two subtypes, FR (2 A) & FF (2 B).
Each motor unit contains only one type of fiber, this classification also applies to the motor unit.

Based on contraction time, skeletal muscles are classified into two types:
Feature
Red (slow) muscles
Pale (fast muscles)
Fiber type
Type I fibers are more
Type II fibers are more
Myoglobin content
High, so it is red ( for short-term O2
storage)
Less  (FF<< FR)

Blood supply
Rich
Relatively Less
Mitochondria
Rich
Relatively Less
Sarcoplasmic retiuculum
Less extensive
More extensive
Latent period
Long
Short
Power of Contraction
Less powerful
More powerful
Duration of contraction
Sustained contraction (longer contraction time)
Brief and rapid contractions.
Fatigue
Occurs slowly
Occurs quickly (FF > FR)
Energy source
Depends on cellular respiration (aerobic) 
Have ­ conc. of fat droplets (high-energy substrate reserves)
Rich in oxidative enzymes
Depends on glycolysis (anaerobic)
Rich in glycogen (FF > FR)
Examples
Back muscles & gastrocnemius
Soleus (for upright position), Hand muscles & ocular muscles

Each fiber type can also be converted to the other type.
If, prolonged activation of fast-twitch fibers leads to a chronic ­ in cytosolic Ca2+ conc. fast-twitch fibers will be converted to slow-twitch fibers & vice versa.

Motor End-plate (MEP)
It is a type of chemical synapse where transmission of stimuli from a motor axon to a skeletal muscle fiber occurs.
Neurotransmitter à ACh
Receptors at the subsynaptic muscle membrane: NM(nicotinergic)-ionotropic cholinoceptors
The N-cholinoceptor of the MEP (TypeNM) has 5 subunits: (2α, 1β,1γ, 1δ), each containing 4 membrane spanning α-helices.

Unlike voltage-gated Na+-channels, the open probability po of the NM-cholinoceptor is not increased by depolarization, but is determined by the ACh conc. in the synaptic cleft.

Endplate potential:
It is the change in the RMP (-90mV) when an impulse reaches the NMJ. It is a graded potential.

At RMP, binding of ACh molecule to the two α-subunits à brief opening of channel (specific to cations such as Na+, K+, Ca2+) à influx of Na+ ions mainly (& a much lower outflow of K+) à Depolarization of the subsynaptic membrane à endplate potential (EPP)

Miniature end plate current:
Release of a small quantity of Ach from the axon terminal à Single-channel currents à that are summated à yielding miniature end-plate current when spontaneous exocytosis occurs & a vesicle releases a quantum of ACh activating thousands of NM-cholinoceptors.

Miniature end plate current: May occur spontaneously due to rupture & release of few Ach into synaptic cleft due to muscular contraction.
Can be described as fibrillation – can’t be seen with naked eye.
If they can be seen with naked eye – they are called twitches.

But generation of a postsynaptic action potential requires a motor neuron that triggers exocytosis of a 100 vesicles à opening of 200,000 channels at the same time à neurally induced end-plate current (IEP)


End-plate current (IEP) is dependent on:
·        No. of open channels = total number of channels (n) x the open-probability (po)
[po is determined by the conc. of ACh in the synaptic cleft (up to 1 mmol/L)]
·        Single-channel conductance γ
·        Membrane potential, Em, since the electrical driving “force” (= Em–ENa,K) becomes smaller when Em is less -ve.
[ENa,K = common equilibrium potential for Na+ & K+ (@ 0mV).
It is also called the reversal potential bcoz the direction of IEP (= INa + IK), which enters the cell when Em is -ve (Na+ influx > K+ outflow), reverses when Em is positive (K+ outflow > Na+ influx).

IEP = n . po . γ . (Em – ENa, K)

Because neurally induced EPPs in skeletal muscle are much larger (depolarization by 70 mV) than neuronal EPSPs (only a few mV), single motor axon action potentials are above threshold.

The EPP is transmitted electrotonically to the adjacent sarcolemma, where muscle AP’s are generated by means of voltage-gated Na+ channels à muscle contraction.

Termination of synaptic transmission in MEPs occurs by
(1) Rapid degradation of ACh in the synaptic cleft by acetylcholinesterase localized at the subsynaptic basal membrane, and
(2) Diffusion of ACh out of the synaptic cleft

Neuromuscular blockers
A motor end-plate can be blocked by certain poisons & drugsà muscular weakness & paralysis.

Botulinum neurotoxin: inhibits the discharge of NT’s from the vesicles.
α-bungarotoxin in snake venom: blocks the opening of ion channels.

Receptor blocker:
·        Competitive inhibitors to ACh: Curare-like substances such as (+)-tubocurarine à used as muscle relaxants in surgical operations. Displace ACh from its binding site but do not have a depolarizing effect of their own.
·        ACh-like substances: suxamethonium, succinylcholine or carbamylcholine act like Ach & keep the muscle in a depolarized state.
·        Since they are not destroyed by acetylcholinesterase, the muscle remains in a depolarized state for a long time à paralysis bcoz permanent depolarization also permanently inactivates Na+ channels near the motor end-plate on the sarcolemma.

Drugs stimulating Neuromuscular Junction:
·        Decurarinization: The inhibitory effect of curare can be reversed by cholinesterase inhibitors such as neostigmine.
·        These agents ­Ach conc. in the synaptic cleft, thereby displacing curare.
·        Entry of anticholinesterase agents into intact synapses à ­Ach conc. à paralysis due to permanent depolarization.


Motility and Muscle Types
Active motility is due to either:
·        Interaction of energy-consuming motor proteins (fueled by ATPase) such as myosin, kinesin & dynein with other proteins such as actin or
·        Polymerization & depolymerization of actin & tubulin.

Motor Unit of Skeletal Muscle
Smooth muscle (single unit type) & cardiac muscle fibers pass electric stimuli to each other thru gap junctions or nexus, while
Skeletal muscle fibers are not stimulated by adjacent muscle fibers, but by motor neurons.
[In fact, muscle paralysis occurs if the nerve is severed].

Motor unit (MU): One motor neuron together with all muscle fibers innervated by it.
To supply its muscle fibers, a motor neuron splits into collaterals with terminal branches.
A given motor neuron may supply only 25 muscle fibers (mimetic muscle) or well over 1000 (temporal muscle).

Motor pool: all ant. horn cells & the innervated muscle fibers for one sk. Muscle.
Not all the ant. horn cells are active at the same time i.e not all sk. Muscle fibers contracting at the same moment. There is alternative activity to avoid fatigue.
Recruitment of motor units: gradation of sk. Muscle contraction.
­stimulus strength à activation of more motor units à ­ force of contraction.
­ Frequency of action potential generated by motor cortex.
Graded muscle activity:
·        It is possible because a variable number of motor units can be recruited as needed.
·        The more motor units a muscle has, the more finely graded its contractions.
·        Contractions are much finer in the external eye muscles (2000 motor units), than in the lumbrical muscles (100 motor units).
·        Larger the number of motor units recruited, the stronger the contraction.
·        The no. & type of motor units recruited depends on the type of movement involved (fine or coarse, intermittent or persistent contraction etc.).
·        Strength of each motor unit can be increased by à ­ the frequency of neuronal impulses, as in the tetanization of skeletal muscle.

Stimulation of muscle fibers
Release of Ach at the MEP of sk. muscle à end-plate current that spreads electrotonically à  activation of fast voltage-gated Na+ channels in the sarcolemma à firing of an AP that travels rapidly along the sarcolemma of the entire muscle fiber & penetrates deep into it thru T tubules

[C:N - Genetic defects of these Na+ channels slow down their deactivation à hyperexcitability à extended contraction & delayed muscle relaxation (myotonia).]

The extended muscular activity à ­ K+ efflux to ECF à hyperkalemia à ¯ muscular resting potential à inactivation of Na+ à temporary muscle paralysis (familial hyperkalemic periodic paralysis)

Electromechanical coupling
The conversion of excitation of a muscle into a contraction.

In the skeletal muscle:
·        This process begins with the AP that excites the voltage- sensitive dihydropyridine receptors (DHPR) of the sarcolemma in the region of the triads.
·        The DHPR are arranged in rows & directly opposite them in the adjacent membrane of the SR are rows of Ca2+ channels called ryanodine receptors (RYR1 in sk. muscle).
·        Every other RYR1 is associated with a DHPR.
·        RYR1 open when they directly “sense” by mechanical means an AP-related conformational change in the DHPR.
·        In skeletal muscle, DHPR stimulation at a single site is enough to trigger the coordinated opening of an entire group of RYR1 à ­ reliability of impulse transmission.


In the myocardium:
·        Each DHPR is part of a voltage-gated Ca2+ channel (L-type) of the sarcolemma that opens in response to an action potential.
·        Small quantities of EC Ca2+ enter the cell thru this channel à opening of myocardial RYR2 (trigger effect of Ca2+ or Ca2+ spark).

Ca2+ ions stored in the SR now flow thru the opened RYR1 or RYR2 channels into the cytosol à ­ [Ca2+]i à saturation of the Ca2+ binding sites on troponin-C à canceling of the troponin-mediated inhibitory effect of tropomyosin on filament sliding à strong (high affinity) actin-myosin-II binding.

[C:N - In patients with genetic defects of RYR1, general anesthesia à massive release of Ca2+ à intense muscle contractions à rapid & life threatening increase of body temperature: malignant hyperthermia.]

Sliding filament mechanism of muscle contraction

ATP: essential for filament sliding & hence, for muscle contraction.
Myosin heads act as the motors (motor proteins) of this process à due to their ATPase activity. 
·        Myosin heads connect with actin filaments at a particular angle forming à cross-bridges.
·        Conformational change in the region of nucleotide binding site of myosin, (the spatial extent of which is increased by concerted movement of the neck region) à tilting down of myosin head à power stroke (drawing the thin filament a length of 4–12nm).
·        The head then detaches & “tenses” in preparation for the next “oarstroke” when it binds to actin anew.

·        Kinesin independently advances on the microtubule by incremental movement of its 2 heads, as in tug-of-war. In this case, 50% of the cycle time is “work time” (duty ratio = 0.5).

·        Btwn two consecutive interactions with actin in skeletal muscle, myosin-II “jumps” 36nm (or multiples of 36) to reach the next suitably located actin binding site (C3, jump from a to b).
·        Meanwhile, the other myosin heads working on this particular actin filament must make at least another 10 to 100 oarstrokes of around 4–12nm each.
·        The duty ratio of a myosin head is therefore à 0.1 to 0.01.
·        This division of labor by the myosin heads ensures that a certain percentage of the heads will always be ready to generate rapid contractions.

When filament sliding occurs:
·        Z plates approach each other à shortening of I band
·        Overlap region of thick & thin filaments becomes larger à shortening of H zone
·        Length of the filaments remains unchanged.

Max. muscle shortening occurs à When the ends of thick filaments bump against the Z plate à overlapping of the ends of thin filaments.
Shortening of the sarcomere therefore occurs at both ends of the myosin bundle, but in opposite directions.



Contraction cycle
Binding of ATP to each of the 2 myosin heads (with the aid of Mg2+) à M-ATP complex lying at 45° angle to the rest of the myosin filament à weak affinity of myosin for actin binding.

Influence of ­ cytosolic Ca2+ conc. on the troponin–tropomyosin complex à activation of myosin’s ATPase by actin à hydrolysis of ATP (ATP à ADP + Pi) à formation of A-M-ADP-Pi complex à lifting of myosin heads (conformational change) à ­actin-myosin association constant by 104.

1st step of power stroke: Detachment of Pi from the complex à 40° tilt of the myosin heads à sliding of actin & myosin filaments past each other.

2nd step of power stroke: Release of ADP initiates à final positioning of the myosin heads
The remaining A-M complex (rigor complex) is stable & can again be transformed into a much weaker bond when the myosin heads bind ATP anew (“softening effect” of ATP,D4).

­ flexibility of muscle at rest is important for: processes such as cardiac filling or the relaxing of the extensor muscles during rapid bending movement.

If the cytosolic Ca2+ conc. remains high, the D1 to D4 cycle will begin anew. This depends mainly on whether subsequent AP’s arrive. Only a portion of the myosin heads that pull actin filaments are “on duty” (low duty ratio) to ensure the smoothness of contractions.

The Ca2+ ions released from the sarcoplasmic reticulum (SR): continuously pumped back to the SR actively by Ca2+-ATPase (SERCA).

If the RYR-mediated release of Ca2+ from the SR is interrupted, the cytosolic Ca2+ conc. rapidly drops & filament sliding ceases (resting position).

Parvalbumin:
·        It is a protein occuring in the cytosol of fast-twitch muscle fibers (type F).
·        Accelerates muscle relaxation after short contractions by binding cytosolic Ca2+ in exchange for Mg2+.
·        Its binding affinity for Ca2+ is higher than that of troponin, but lower than that of SR’s Ca2+-ATPase.
·        It therefore functions as a “slow” Ca2+ buffer.
During isotonic contractions (where muscle shortening occurs): The course of the filament sliding cycle as described above takes place.

During strictly isometric contractions (tension increases but length remains unchanged): tilting of the myosin heads & the filament sliding cannot take place.
Instead, the isometric force is created thru the deformation of myosin heads.

Skeletal muscle cramp: no ATP
For the myosin head to return back to its resting state, it needs to be energized.
Lack of ATP à sk. muscle cramps
May occur due to ischemia as decreased blood supply à decreased ATP supply.
If it occurs during death à rigor morse.

Muscle fibers of a dead body do not produce any ATP. So, after death:
·        Ca2+ is no longer pumped back into SR
·        ATP reserves needed to break down stable A-M complexes are depleted.
This results in stiffening of the dead body or rigor (firmness) mortis, which passes only after the actin & myosin molecules in the muscle fibers decompose.

Sk. Muscle relaxation is active due to two factors:
·        Energization of myosin head: binding of ATP to myosin head to bring it back to resting state.
·        Active Ca reuptake by longitudinal tubules (by Ca2+ ATPase).


Mechanical Features of Skeletal Muscle
AP’s generated in muscle fibers à ­[Ca2+]i à triggering of contraction
In skeletal muscles, gradation of contraction force is achieved by:
·        Variable recruitment of motor units
·        Changing the AP frequency
Single stimulus always à max. Ca2+ release à max. single twitch of sk. muscle fiber if above threshold (all-or-none response).
But a single stimulus does not induce max. shortening of muscle fiber: bcoz it is too brief to keep the sliding filaments in motion long enough for the end position to be reached.
Muscle shortening continues only if à a 2nd stimulus arrives before the muscle has completely relaxed after the first stimulus.

Effects of two successive stimuli:
3 different effects are noticed depending upon the interval btwn the two stimuli:
Beneficial effect: when the 2nd stimulus falls after the relaxation period of 1st twitch, 2 separate curves are obtained but the force of 2nd twitch is greater due to ­ temp. à ¯viscosity of muscle after 1st twitch.
Superposition: if the 2nd stimulus falls during relaxation period of 1st twitch, 1st curve is superimposed by the 2nd curve.
Summation: If 2nd stimulus is applied during contraction period, 2 contractions are summed up & single curve is obtained with an amplitude gr8r than the simple muscle curve.

Treppe or Staircase Phenomenon
Gradual increasein force of contraction of muscle when it is stimulated repeatedly with a maximal strength at a low frequency. It is different from summation & tetanus.

Tetanus: summation of contraction without relaxation due to marked ­ in the frequency of excitation.
Tetany: ­ neuromuscular excitability due to hypocalcemia caused by hypoparathyroidism etc

Tetanus
·        It is the sustained maximum contraction of the motor units.
·        It occurs if the frequency of stimulation becomes so high that the muscle can no longer relax at all btwn stimuli.
[It occurs at 20 Hz in slow-twitch muscles & at 60–100 Hz in fast-twitch muscles].
·        Muscle force during tetanus is as much as 4 times larger than that of single twitches.
·        The Ca2+ conc., which decreases to some extent btwn superpositioned stimuli, remains high in tetanus.

Contracture: Not caused by AP’s, but by persistent local depolarization due to:
·        ­[K+]o (K+ contracture) or
·        Drug-induced intracellular Ca2+ release, e.g., in response to caffeine.

The contraction of tonus fibers (specific fibers in external eye muscles & in muscle spindles) is also a form of contracture.
·        Tonus fibers do not respond to stimuli acc. to the all-or-none law, but contract in proportion with the magnitude of depolarization.
·        Magnitude of contraction of tonus fibers regulated by à variation of the cytosolic Ca2+ conc. (not by action potentials!)
·        The individual contractions cannot be detected bcoz the motor units are alternately (asynchronously) stimulated.  
[When apparently at rest, muscles such as the postural muscles are in this involuntary state of tension]

Resting muscle tone:
Continuous & partial contraction of muscles with certain degree of tension. It is maintained by different mechanisms:
·        In skeletal muscle: Regulated by reflexes (reflex tone). It is neurogenic i.e due to the arrival of normal AP’s at the individual motor units. It increases as the state of attentiveness increases.
·        In Smooth & cardiac muscle: It is myogenic i.e muscle themselves control the tone. It depends upon Ca2+ level & no. of cross bridges.

Muscle extensibility
A resting muscle containing ATP can be stretched like a rubber band.
The force required to start the stretching action (extension force at rest) is very small, but increases exponentially when the muscle is under high elastic strain.

Musscle’s resistance to stretch à keeps the sliding filaments in the sarcomeres from separating.
It is due to 2 factors:
·        Fascia (fibrous tissue) – to a small extent
·        Titin (connectin): giant filamentous elastic molecule incorporated in the sarcomere (6 titin molecules per myosin filament).
In the A band: Titin lies adjacent to a myosin filament & helps to keep it in the center of the sarcomere.
In the I band: Titin molecules are flexible & function as “elastic bands” that counteract passive stretching of a muscle & influence its shortening velocity.

Extensibility of titin molecules:
·         Titin molecules can stretch up to 10 times their normal length in sk. muscle & somewhat less in cardiac muscle.
·         It is mainly due to frequent repetition of the PEVK motif (proline-glutamate-valine-lysine).
·         In very strong muscle extension, which represents the steepest part of the resting extensibility curve (_D), globular chain elements called Ig C2 domains also unfold.
·         The quicker the muscle stretches, the more sudden & crude this type of “shock absorber” action will be.

Types of tension in sk. Muscle:
During rest: passive tension – minimal binding btwn actin & myosin, minimal baseline contraction. Sk. Muscle length is shorter than the distance btwn origin & insertion. This leads to their minimal stretching.
During voluntary movement: active tension + passive tension = total tension
[Active force is determined by the magnitude of all potential actin myosin interactions. Hence it varies in accordance with the initial sarcomere length]




Vmax: Maximal velocity of shortening of sarcomere after loading.

Lmax = 2 to 2.2 μm
Maximal length of sarcomere at which maximal tension will be developed.
It is the max. active (isometric) force (F0) that a skeletal muscle can develop from its resting length.

When (L< Lmax):
Sarcomeres shorten & part of thin filaments overlap à so only forces smaller than F0 develop.

When L = 70% of Lmax (sarcomere length: 1.65 μm): Thick filaments make contact with the Z disks & F becomes even smaller.
When L > Lmax:
The muscle is greatly pre-extended & can develop only restricted force bcoz à no. of potentially available actin–myosin bridges is reduced.
When extended to 130% or more of Lmax, the extension force at rest becomes a major part of the total muscle force.

Functional differences btwn cardiac muscle & skeletal muscle:

Skeletal muscle
Cardiac muscle
More extensible
Less extensible, so the passive extension force at rest is greater.
Functions in the plateau region of its length–force curve.
Operates in the ascending limb (below Lmax) of its length–force curve without a plateau.
So, the ventricle responds to ­ diastolic filling loads by ­ its force development (Frank–Starling mechanism).

Extension also affects troponin’s sensitivity to Ca2+ à steeper curve
AP’s are of shorter duration.
Uses IC Ca2+, so no plateau phase.
AP’s are of much longer duration bcoz  gK¯ & gCa­ temporarily after rapid inactivation of Na+ channels à slow influx of EC Ca2+ à plateau phase of AP.
As a result, the refractory period does not end until a contraction has almost subsided. So, tetanus cannot be evoked in cardiac muscle.
Contains motor units.
Has no motor units. The stimulus spreads across all myocardial fibers of the atria & ventricles à all-or-none contraction of both atria & thereafter, both ventricles.
No change
Duration of AP can change the force of contraction (which is controlled by the variable influx of Ca2+ into the cell).


If shortening does not occur à Maximal force & small amount of heat develops.
Greater the force (load) à lower the velocity of an (isotonic) contraction.
Without a stress load à Max. velocity & a lot of heat develops. So, light loads can be picked up more quickly than heavy loads.


The total amount of energy consumed for work & heat is greater in isotonic contractions than in isometric ones.
Muscle power: product of force & shortening velocity.
N· m · s–1 = W

Frank Starling Law
Force of contraction is directly proportional to the initial length of muscle fibers within physiological limits.

Energy Supply for Muscle Contraction
Direct source of chemical energy for muscle contraction à ATP
A muscle cell contains only a limited amount of ATP– only enough to take a sprinter.
So, spent ATP is continuously regenerated to keep the [ATP]i constant, even when large quantities of it are needed.


The three routes of ATP regeneration are:
1. Dephosphorylation of creatine phosphate (for short term peak performance)
2. Anaerobic glycolysis (for medium term high performance, occurs in cytoplasm, faster, produces few molecules of ATP)
3. Aerobic oxdn of glucose & fatty acids (for long term performance, occurs in mitochondria, needs O2, slower, produces large no. of ATP)

Creatine phosphate (CrP):
·        Provides chemical energy needed for rapid ATP regeneration (as routes 2 & 3 are relatively slow)
·        CrP reserve of the muscle is sufficient for short-term high-performance bursts of 10–20 s (e.g., for a 100-m sprint).

              mitochondrial creatine kinase
ADP -------------------------------------- > ATP & Cr

Anaerobic glycolysis
Occurs later than CrP dephosphorylation (after a max. of 30 s).
                                     glucose-6-phosphate
Muscle glycogen -----------------------> Lactic acid (lactate + H+)
Yields 3 ATP molecules for each glucose residue

Aerobic oxidation of glucose & fatty acids
·        Takes place @ 1 min after less productive anaerobic form of ATP regeneration.
·        Glucose must be imported from the liver where it is formed by glycogenolysis & gluconeogenesis.
·        Imported glucose yields only 2 ATP for each molecule of glucose, bcoz one ATP is required for 6-phosphorylation of glucose.

During light exercise: lactate is broken down in the heart & liver whereby H+ ions are used up.
During strenuous exercise: Anaerobic glycolysis must be continued along with aerobic oxdn if it does not supply sufficient quantities of ATP.
For sustained exercise: Aerobic regeneration of ATP from glucose (about 32 ATP per glucose residue) or fatty acids is required.

Cardiac output = HR x stroke volume
·        Total ventilation must be ­ to meet the ­ metabolic requirements of the muscle; the HR then becomes constant.
·        The several minutes that pass before this steady state is achieved are bridged by:
o       Anaerobic energy production
o       ­O2 extraction from the blood
o       Depletion of short-term O2 reserves in the muscle (myoglobin).
·        The interim (short term) btwn the 2 phases is perceived as the “low point” of physical performance.

O2 affinity of myoglobin > Hb, but lower than that of respiratory chain enzymes.
Thus, myoglobin is normally saturated with O2 & can pass on its O2 to the mitochondria during brief arterial O2 supply deficits.

Endurance limit:
In top athletes = 370W (@0.5 HP)
Mainly dependent on the speed at which O2 is supplied & speed of aerobic oxdn.
When the endurance limit is exceeded à steady state cannot occur à continuous ­ in HR

The muscles can temporarily compensate for the energy deficit but the H+-consuming lactate metabolism cannot keep pace with the persistently high level of anaerobic ATP regeneration.
An excess of lactate & H+ ions à lacticacidosis

When endurance limit exceeds by 60%: it is equivalent to max. O2 consumption à sharp ­ in plasma lactate conc. à  anaerobic threshold at 4 mmol/L
No significant increase in performance can be expected after that point (as lactic acid inhibits myosin ATPase as it is very sensitive to acidic pH à Limits sk. Muscle endurance)

Plasma lactate
Aerobic threshold: 2mmol (can be tolerated for prolonged periods of exercise)
Anaerobic threshold: 4mmol (indicate that the performance limit will soon be reached)
Exercise must eventually be interrupted, not bcoz of ­lactate conc., but bcoz of ­ acidosis.

Systemic drop in pH à ­ inhibition of chemical rxns needed for muscle contraction à ATP deficit à rapid muscle fatigue à stoppage of muscle work
                                     

CrP metabolism & anaerobic glycolysis enable the body to achieve 3 times the performance possible with aerobic ATP regeneration, although for only about 40 s.
These processes à O2 deficit that must be compensated for in the post-exercise recovery phase (O2 debt)
The body “pays off” the O2 debt by:
·        Regenerating its energy reserves
·        Breaking down the excess lactate in the liver & heart.

The O2 debt after strenuous exercise is much larger (up to 20 L) than the O2 deficit for several reasons.

PhysicalWork
There are three types of muscle work:
+ve dynamic work: requires muscles involved to alternately contract & relax (e.g., going uphill).
-ve dynamic work: requires muscles involved to alternately extend while braking (braking work) & contract without a load (e.g., going downhill).
Static postural work: requires continuous contraction (e.g., standing upright).
Many activities involve a combination of 2 or 3 types of muscle work.
Outwardly directed mechanical work is produced in dynamic muscle activity, but not in purely postural work.

Purely postural work
Force x distance = 0
Chemical energy is still consumed & completely transformed into a form of heat called maintenance heat (= muscle force x duration of postural work).
­ in blood flow is prevented as the continuously contracted muscle squeezes its own vessels. The muscle then fatigues faster than in rhythmic dynamic work.

Light to moderate exercise: HR soon levels out at a new constant level, and no fatigue occurs.

Strenuous exercise:
·        Muscles require up to 500 times more O2 than when at rest.
·        At the same time, the muscle must rid itself of metabolic products such as H+, CO2 & lactate. Muscle work therefore requires drastic cardiovascular & respiratory changes.
·        In untrained subjects (UT): CO rises to a maximum of 15–20 L/min during exercise
·        Work-related activation of the sympathetic nervous system:
­ the HR up to 2.5 fold
­ the SV up to 1.2 fold

Very strenuous exercise:
·        Must soon be interrupted bcoz the heart cannot achieve the required long-term performance.
·        ­CO: provides more blood for the muscles & the skin (heat loss).
·        Blood flow in the kidney & intestine: reduced by the sympathetic tone below the resting value. Ps rises while Pd remains constant à moderate increase in the mean pressure.

Smaller the muscle mass involved in the work à higher the increase in B.P
Hence, the B.P increase in arm activity (cutting hedges) is higher than that in leg activity (cycling).
[C:N- In patients with coronary artery disease or cerebrovascular sclerosis, arm activity is therefore more dangerous than leg activity due to the risk of myocardial infarction or brain hemorrhage.]

Muscular blood flow
At the maximum work level, blood flow in 1 kg of active muscle rises to: 2.5 L/min @10% of the max. CO
Hence, no more than 10 kg of muscle (<1/3 the total muscle mass) can be fully active at any one time.
Vasodilatation (for ­blood flow) achieved thru: local chemical influences (PCO2­, PO2­, pH¯) or NO release.

During physical exercise:
Feature
Resting value
During exercise (max. value)
Ventilation (V.E)
7.5 L/min
90 to 120 L/min
Respiratory rate

40–60 min–1max
Tidal volume

2 L
O2 consumption (V.O2)
0.3 L/min
3 L/min (due to­O2 consumption in tissues)
Respiratory equivalent (V.E/V.O2)
25 (i.e 25 L of air has to be ventilated to take up 1 L of O2 at rest)
40–50
Pulmonary transit time
(Minimal time sufficient for gas exchange)
0.75s
0.25s (Time less than 0.25s, no proper gas exchange)

¯pH & ­ temp. shift the O2 binding curve towards the right.

O2 consumption: calculated as the arteriovenous difference in O2 conc. =
avDO2 (L/L blood) x Blood flow (L/min)

Maximum O2 consumption (V.O2 max) is defined as:
V. O2 max = HRmax· SVmax · avDO2max

Ideal measure of physical exercise capacity: V.O2 max per body weight



Physical Fitness and Training

Physical exercise capacity can be measured by using à ergometry.
Ergometry: assesses the effects of exercise on physiological parameters such as V.O2, respiration rate, HR & plasma lactate conc.

Measured physical power (performance) is expressed in: watts(W) or W/kg body weight (BW).

In bicycle ergometry: a brake is used to adjust the watt level.
In “uphill” ergometry: a treadmill is set at an angle α.
Margaria step test: the test subject is required to run up a staircase as fast as possible after a certain starting distance.

Short-term performance tests (10–30 s): measure performance achieved thru rapidly available energy reserves (CrP, glycogen).
Medium-term performance tests: measure performance fueled by anaerobic glycolysis.
Longer term aerobic exercise performance:  measure performance fueled thru oxdn of glucose & FFA by measuring V.O2 max.

In strenuous exercise (2/3 the max. physical capacity or more), aerobic mechanisms do not produce enough energy, so anaerobic metabolism must continue as a parallel energy source à lactacidosis.

Physical training
Raises & maintains the physical exercise capacity.

There are 3 types of physical training strategies:
Motor learning
Endurance training
Strength training
­ rate & accuracy of motor skills
Improves submaximal long-term performance
Improves max. short-term performance level
e.g., typewriting
e.g., running a marathon
e.g., in weight lifting
These activities primarily involve the CNS
To ­ the oxidative capacity of slow-twitch motor units*

To ­ muscle mass by ­ the size of the muscle fibers (hypertrophy) & to ­ the glycolytic capacity of type F motor units.

*e.g., by ­ the mitochondrial density, ­CO à ­ V. O2 max à ­ heart weight à ­SV & ­ tidal volumes à very low resting HR & respiratory rates.

Trained athletes: can therefore achieve larger increases in CO & ventilation.
In individuals practicing endurance training, exercise-related rise in the lactate conc. is also lower & occurs later than in UT.

V.O2 max of a healthy individual is limited by à  the cardiovascular capacity & NOT the respiratory capacity.

Excessive physical exercise causes à muscle soreness & stiffness (not due to lactic acid accumulation), but sarcomere microtrauma à muscle swelling & pain.

During exercise: contraction of muscle squeezes the blood vessels.
Veins are squeezed à  impaired venous drainage à so the metabolites & lactic acid cannot escape.
[Exercise increases venous drainage for the veins in between the sk. Muscles.]
Since the arterial blood pressure is high, it can overcome the sk. Muscle pressure & flow thru them.

Accumulation of metabolites (due to protein breakdown & lactate production) in the sarcomere à ­ osmotic pressure à extraction of water from ECF à swelling à ¯ blood flow à reflex tension à pain

Muscle ache à sign of microinflammation.

Fatigue: decreased sk. Muscle contraction
Neuromuscular fatigue: repeated stimulation of sk. Muscle by motor nerve. It is due to ¯ time for Ach production.

Depression: ¯ descending motor signals from the brain (motor efferent impulses), despite no sk. muscle work being done.

Muscle fatigue: may be peripheral or central.
Peripheral fatigue: caused by the exhaustion of energy reserves & accumulation of metabolic products in the active muscle. This is particularly quick to occur during postural work.

Central fatigue: characterized by work-related pain in the involved muscles & joints that prevents the continuation of physical exercise or decrease the individual’s motivation to continue the exercise.

Myasthemia Gravis
My – muscle, Athemia – weakness, Grave – generalized
Autoimmune disease leading to formation of antibodies against Ach receptors.
Anticholinesterase is given to increase Ach conc. so that Ach can find the receptors.

·        Digitalis à blocks Na/K pump in the heart
·        Single action potential is called à Spike potential
·        All or none rule: nerve & cardiac muscle.
·        The Na channels have 2 gates: activation gate (outside) & inactivation gate (inside).
·        The cell membrane contains more K+ leaky channels than Na. So the inside of the membrane become –ve.
·        Ionic basis for depolarization: Decreased membrane potential due to Na+ influx.
·        Peak of ascending limb of depolarization at à 35mv
·        We are using ATP not immediately during the action potential.
·        But it is used later after the action potential and during the resting potential to stabilize the membrane.
·        Motor neuron – ant. (ventral) horn cell.

·        At the motor end plate: Voltage gated Ca+ chanels
·        ACh receptors in neuromuscular junction: Ionotropic, ligand gated, nicotinic cholinergic, Na+ channels
·        Partial depolarization depends on the amount of Ach released.
·        Threshold level = -ve 40 – 45mV

Thanks :medicalpptonline.blogspot.com