BMS150 Wk 9

Skeletal Muscles in Action - Fiber Types

• There are two main types of muscle fibers: Type I (Slow) and Type II (Fast)
• Type I fibers:
  • Smaller in size
  • Innervated by smaller nerve fibers
  • More capillaries to supply higher amounts of oxygen
  • Lots of mitochondria to support high levels of oxidative metabolism
  • Lots of myoglobin, giving a reddish appearance
• Type II fibers:
  • Larger in size
  • Innervated by larger nerve fibers
  • Lots of SR for rapid Ca2+ release
  • Lots of glycolytic enzymes present
  • Energy can be derived from oxidative metabolism and anaerobic metabolism, with subtypes:
    • Type IIA (Fast Oxidative Glycolytic fibers)
    • Type IIB (Fast Glycolytic fibers)

Fiber Type Characteristics

• Contraction Time:
  • Type I: Slow
  • Type II: Faster (Type IIA), Fastest (Type IIB)
• Size of Motor Neuron:
  • Type I: Small
  • Type II: Bigger (Type IIA), Really big (Type IIB)
• Resistance to fatigue:
  • Type I: Very resistant
  • Type II: Fatigues quickly (no mitochondria)
• Activity used for:
  • Type I: Low-force, endurance (postural muscles)
  • Type II: High-force, quick fatigue (jumping)
• Force Production:
  • Type I: Slow, lower magnitude
  • Type II: Quick, higher tension
• Mitochondrial density:
  • Type I: High
  • Type II: Some (Type IIA), None (Type IIB)
• Capillary density:
  • Type I: High
  • Type II: Medium (Type IIA), Low (Type IIB)
• Oxidative capacity:
  • Type I: High
  • Type II: Low (Type IIA), None (Type IIB)
• Glycolytic capacity:
  • Type I: Minimal
  • Type II: Medium (Type IIA), High (Type IIB)
• Major Storage Fuel:
  • Type I: Fat
  • Type II: Glycogen (Type IIA), Glycogen (Type IIB)

Skeletal Muscle Energy Systems

• There are 3 different metabolic systems responsible for recycling AMP and ADP back into ATP:
  • Phosphagen system
  • Glycogen-Lactic acid system
  • Aerobic system
• In the absence of oxygen, pyruvate is converted into lactate, which diffuses out of the muscle cells into the interstitial fluid and blood
• The Glycogen-Lactic acid system can sustain maximal muscle contraction for 1.3-1.6 minutes

Cori Cycle

• Glucose is converted into pyruvate in the muscle
• Pyruvate is converted into lactate, which is then transported to the liver
• In the liver, lactate is converted back into glucose through gluconeogenesis
• The Cori cycle has an overall net loss of 2 ATP
• The purpose of the Cori cycle is to recycle lactate back into glucose

Aerobic System

• In the presence of oxygen, pyruvate is broken down into carbon dioxide, water, and energy via the citric acid cycle and ETC
• The aerobic system can be used for unlimited duration, as long as nutrients in the body last
• Examples of sports that use the aerobic system include marathons and cross-country skiing

Skeletal Muscle Energy - Summary

• There are 3 different muscle metabolic systems to supply the various degrees of energy required for various activities
• The Phosphagen system provides energy for power surges (8-10 seconds)
• The Glycogen-Lactic acid system provides energy for intermediate athletic activities (60-90 seconds)
• The Aerobic system provides energy for prolonged athletic activities (unlimited duration)

Skeletal Muscle Recovery

• Energy systems must be replenished after exercise
• Phosphocreatine can be used to replenish ATP levels
• The Glycogen-Lactic acid system replenishes both phosphocreatine and ATP
• Oxidative metabolism can replenish all systems: ATP, phosphocreatine, and glycogen-lactic acid system
• Additional oxygen is needed to replenish energy stores - "oxygen debt"

Skeletal Muscle Recovery - Oxygen Debt

• After exercise, stored oxygen must be replenished by breathing extra amounts of oxygen above normal requirements
• In heavy exercise, all stored oxygen is used within ~1 minute of aerobic metabolism
• An additional 9 liters of oxygen are needed to provide for reconstituting the phosphagen system and the lactic acid system
• The total oxygen that must be "repaid" is 11.5 liters

Pain - Introduction

• Pain is an unpleasant sensation and emotional experience associated with actual or potential tissue damage.
• The emotional aspect of pain makes it unique and able to impact mood and quality of life.
• Pain perception is very subjective and can vary greatly between individuals.

Types of Pain and Abnormal Sensation

• Dysesthesia: any abnormal sensation described by a patient as unpleasant.
• Paresthesia: a sensation that is typically described as "pins-and-needles" or "prickling", but is not notably unpleasant.
• Analgesia: reduction or loss of pain perception.
• Anaesthesia: reduced perception of all touch and pain sensation.
• Hypoalgesia: decreased sensation and raised threshold to painful stimuli.
• Hyperalgesia: exaggerated pain response from a normally painful stimulus.
• Allodynia: abnormal perception of pain from a normally non-painful mechanical or thermal stimulus.
• Hyperesthesia: exaggerated perception of a touch stimulus.
• Causalgia: burning pain in the distribution of a peripheral nerve.

Physiology of Nociception

• Nociceptors are widely distributed through multiple depths in the skin and visceral organs.
• Types of nociceptors:
  • Thermal nociceptors: activated by temperatures > 45 C or less than 5 C.
  • Mechanical nociceptors: activated by intense pressure applied to a structure.
  • Polymodal nociceptors: activated by high-intensity mechanical, chemical, or thermal stimuli.
  • Silent nociceptors: receptors that are widely distributed through viscera and skin, but do not normally transmit pain information.
• Nociceptors can detect a wide range of stimuli, including:
  • Cold and heat
  • Low pH and free radicals
  • Capsaicin
  • Prostaglandins
  • Bradykinin
  • Histamine
  • Substance P
  • Serotonin
  • ATP

Neuroanatomical Pain Pathways

• The spinothalamic tract is the major nociceptive sensory pathway.
• Peripheral afferent pain fibers of both A-δ and C types have their cell bodies in the dorsal root ganglia.
• The central extensions of these nerve cells project, via the dorsal root, to the dorsal horn of the spinal cord.
• Within the spinal cord, many of the thinnest fibers (C fibers) form a discrete bundle, the tract of Lissauer.
• Peripheral afferent fibers usually terminate within the same segment as their spinal nerve.
• The fibres of the spinothalamic tract usually cross over (2nd order neurons) two or three levels superior to where the 1st-order neurons enter the spinal cord.

Additional Details

• The concept of fast pain and slow pain:
  • Fast pain: well-localized, sharp pain carried by A-delta fibres.
  • Slow pain: poorer-localized, duller pain carried by C-fibres, tends to last longer.

Muscular Dystrophies

• Muscular dystrophies are a group of inherited muscle disorders leading to progressive weakness and muscle wasting, characterized by muscle fiber necrosis and regeneration.
• Three types of muscular dystrophies will be discussed: Duchenne Muscular dystrophy, Becker Muscular dystrophy, and Myotonic dystrophy.

Duchenne Muscular Dystrophy

• Etiology: X-linked, loss-of-function mutation of the structural protein dystrophin, typically associated with deletion or frameshift mutations resulting in a severe, progressive phenotype.
• Epidemiology: Most common muscular dystrophy, affecting 1 in 3500 live male births.
• Pathogenesis: Dystrophin is a key component of the dystrophin glycoprotein complex, which spans the plasma membrane, linking the cytoskeleton of the muscle fiber with the basement membrane.
• Pathophysiology: Defects in the complex can lead to sarcolemma tears, calcium influx, and ultimately muscle fiber necrosis.
• Pathology: Chronic muscle damage that outpaces the capacity for repair, leading to muscle fiber degeneration, regeneration, and replacement by collagen and fat cells.

Becker Muscular Dystrophy

• Less severe than Duchenne Muscular Dystrophy, with fewer extra-muscular symptoms.
• Affects more proximal-located muscles (thigh and hip), often causing myalgic pain.

Myotonic Dystrophy

• Type I: More severe, with more extra-muscular symptoms such as dysphagia, constipation, and uterine muscle abnormalities.
• Type II: Less severe, with fewer extra-muscular symptoms.
• Diagnosis: Based on history, clinical findings, and genetic testing.
• Prognosis: Reduced life expectancy, with a mean age of death of 54 years, commonly due to respiratory and cardiac disease.

Statin Myopathy

• Most common drug-related myopathy, affecting 9-17% of those on statin therapy.
• Pathophysiology: Decreased cholesterol concentrations may impact sarcolemma, and depletion of CoQ10 (Ubiquinone).
• Clinical Features: Myalgias and muscle weakness after exercise, often severe enough to discontinue or switch medication.

Myasthenia Gravis (MG)

• Etiology: Autoimmune condition associated with autoantibodies directed against acetylcholine receptors.
• Epidemiology: Prevalence of 150-200 per 1 million, more common in young females and older males.
• Thymic abnormalities (thymoma or thymic hyperplasia) are associated with MG and may contribute to immune dysregulation and development of auto-antibodies.

The Pharyngeal Arches

• A pharyngeal arch consists of a core of mesenchyme covered externally by ectoderm and internally by endoderm.
• The mesenchyme is derived from mesoderm in the third week, and later from neural crest cells that migrate into the pharyngeal arches during the fourth week.
• Each pharyngeal arch contains a pharyngeal arch artery, a cartilaginous rod, a muscular component, and sensory and motor nerves.

Pharyngeal Grooves and Pouches

• The pharyngeal endoderm lines the internal aspects of the pharyngeal arches and passes into diverticula, forming pharyngeal pouches.
• There are four pairs of pharyngeal pouches, with the fifth pair being rudimentary or absent.
• The endoderm of the pouches contacts the ectoderm of the pharyngeal grooves, forming a double-layered pharyngeal membrane.

Development of the Pharyngeal Apparatus

• The pharyngeal arches begin to develop early in the fourth week, with neural crest cells migrating into the ventral parts of the future head and neck regions.
• The first pair of pharyngeal arches, the primordium of the jaws, appears as surface elevations lateral to the developing pharynx.
• By the end of the fourth week, four pairs of pharyngeal arches are visible externally.

Bony and Cartilaginous Derivatives of the Pharyngeal Arches

• The first pharyngeal arch separates into two prominences: the maxillary prominence and the mandibular prominence.
• The maxillary prominence gives rise to the maxilla, zygomatic bone, and a portion of the vomer.
• The mandibular prominence forms the mandible and the squamous temporal bone.
• The second and third pharyngeal arches form the hyoid bone.
• The first and second pharyngeal cartilages give rise to the ossicles of the middle ear and the styloid process of the temporal bone.
• The fourth and sixth pharyngeal arches give rise to the laryngeal cartilage.

Muscular Derivatives of the Pharyngeal Arches

• The first pharyngeal arch gives rise to the muscles of mastication, muscles of the middle ear, and the tensor tympani.
• The second pharyngeal arch gives rise to the stapedius, stylohyoid, posterior belly of the digastric, auricular, and muscles of facial expression.
• The third pharyngeal arch gives rise to the stylopharyngeus.
• The fourth pharyngeal arch gives rise to the cricothyroid, levator veli palatini, and constrictors of the pharynx.
• The sixth pharyngeal arch gives rise to the intrinsic muscles of the larynx.

Pharyngeal Pouches

• The first pharyngeal pouch expands into a tubotympanic recess, which forms the tympanic cavity and mastoid antrum.
• The second pharyngeal pouch gives rise to parts of the palatine tonsils.
• The third pouch develops into parathyroid glands and a thymus.
• The fourth pouch develops into parathyroids.

Development of the Thyroid

• The thyroid gland is the first endocrine gland to develop in the embryo, forming 24 days after fertilization from a median endodermal thickening in the floor of the primordial pharynx.
• The thyroid gland descends in the neck, passing ventral to the developing hyoid bone and laryngeal cartilages.
• For a short time, the thyroid gland is connected to the tongue by a narrow tube, the thyroglossal duct.
• By 7 weeks, the thyroid gland is usually located in its final site in the neck, and the thyroglossal duct usually degenerates.

Learn about the two main types of muscle fibers, Type I (Slow) and Type II (Fast), their characteristics and functions.