Exam 4 Flashcards
Composition of muscle tissue
- Muscle cells, myocytes
- Connective tissue, containing blood and nerves, transmits muscular contraction forces
Sarcoplasm
Striated muscle Cytoplasm
Sarcolemma
Striated muscle plasma membrane
Sarcoplasmic reticulum
Striated muscle smooth ER
sarcomere
Structural unit of myofibril in striated muscle
Myofilaments
Actin and myosin filaments in striated muscle
Myofibrils
Elongated contractile thread in striated muscle
Myofiber/muscle fiber
Single muscle cell in striated muscle
Skeletal muscle
• arises by fusion of myoblasts and differentiation
Mesoderm—> Myoblast—> Large multi nucleated cells—> syncytium + Differentiation in the skeletal muscle fibers
Endomysium
Sheath of fine connective tissue that surrounds individual muscle fibers, Fine RT fibers and ground substance, tiny nerves and blood vessels run parallel to muscle fibers
Perimysium
Thick CT sheath that surrounds groups of muscle fibers (Fascicles/bundles). Continuous with tendon fibers, large nerves and blood vessels
Epimysium
Dense CT cells that surrounds collection of fascicles (entire muscle). Major nerves and blood vessels
General features of myofiber
• Single cell, myocyte
•  Striated, voluntary
• Well developed Sarcoplasmic reticulum
• Multi nucleated
• Nuclei at cell periphery
Myofibril
• multiple myofibrils per cell
• tiny contractile threads within Sarcoplasm
• Extend entire length of cell, filled with myofilaments (Actin and myosin)
• Responsible for appearance of cross striations
Myofibril bands
Dark bands: A band divided by H band
M line: divides H band
Light band: I band divided by Z line
Sarcomere: length between adjacent Z lines
Thin filaments
Actin, tropomyosin, troponin
Extend from Z line through A band to edge of H band
Thick filaments
Myosin
Extends length of a band, thin cross-bridges extending from each myosin filament towards neighboring actin filaments
M line
• Dense line at center of H band
• Contains Myomesin, C protein, and other proteins for special arrangement
• lattice arrangement maintained by interconnection of thick myosin filaments
Z line/ The matrix
• region where ends of actin filaments attach in adjacent sarcomeres
• Alpha actinin protein, Titin, Nebulin, etc
Sarcoplasm
• between myofibrils
• Beneath Sarcolemma
• Around nuclei
• Mitochondria appear in the same area
• Numerous invaginations along cell surface, forming the T tubules
Sarcoplasmic reticulum
Network of cisterns and membranous tubules running between and around myofibrils
• Forms collars at A-I Junctions in skeletal and Z lines of cardiac
• binds and releases calcium
Skeletal muscle triads
T tubule + 2 terminal cisternae or sarcoRetic 
• Facilitates transmission of electrical impulse from Sarcolemma to Interior depths of cells at A-I junctions
Actin- thin filaments
1.) G actin: Globular actin Polymerizes to form F actin
2.) F actin: two helically wound strands of polymerized G Actin 
Myosin
• four light chains and two heavy chains
• Heavy chain: light meromyosin and heavy meromyosin
Heavy meromyosin
• Rod-like portion lies parallel to backbone of filament
• globular head, ATPase activity and actin-binding sites
• Polarized, globular heads directed away from midpoint of myosin filament
Regulatory molecules
Tropomyosin and troponin complex: Runs in groove between actin molecules and mask the myosin binding site
Calcium: relocates the complex to expose the actin-myosin binding site
Contraction of skeletal muscle causes:
Z lines closer together, H band and I band become thinner, A band stays the same thickness always
Neuromuscular junction/motor end plate
• myelin sheath lost as nerve fiber approaches surface of muscle cell
• Axon branches near surface of muscle cell, occupy recesses in muscle surface, a.k.a. synaptic troughs or primary synaptic cleft
• subneural apparatus/modified SR
•  Synaptic vesicles
Myasthenia gravis
• characterized by weakness and easy fatigue of muscles, caused by auto immune response to the ACh receptor
• Administration of AChE inhibitors has both diagnostic and therapeutic values
Motor unit
Motor neuron and the muscle fibers innervated by it, one to one ratio is very fine control
 Muscle spindle
Specialized stretch receptor in all skeletal muscles. Signal transmitted via afferent nerve fibers (Motor neurons)
Golgi tendon organ
Spindle shaped bodies comprised of collagen and enclosed by a thin capsule. Afferent/sensory fibers (ONLY) penetrate between the collagen fibers 
Cardiac muscle
• Arises by differentiation of individual myoblasts, not by fusion of cells
• striated, involuntary, T tubule system, single nucleus per cell, Intercalated discs, glycogen storage
Intercalated discs
1.) dark cross bands on longitudinal sections
2.) Occur where a Z line should be, observed at ends of a sarcomere
3.) Mark spots of cell cell attachments ( Fascia adherens, desmosomes, gap junctions)
Cardiac muscle dyads
T tubule + a terminal portion of adjacent SR
+ intercalated discs
Atrial granules
Part of atrial cardiac muscle cells, contain atrial natriuretic peptide that lowers blood pressure by decreasing renal tubules ability to reabsorb sodium and water
Smooth muscle
• Arises by differentiation of individual myoblasts, not by fusion of cells (some arise by differentiation from ectoderm: pupil, sweat glands, mammary glands)
• No striations, no T tubules, involuntary
Functions of smooth muscle
1.) contractility
2.) Conductivity
3.) production of extra cellular products (collagen, elastin, GAGs, proteoglycans, growth factors)
Where is smooth muscle located?
Walls of hollow viscera, walls of blood vessels, larger ducts of compound glands, arrector pili muscles
Dense bodies 
Comparable to Z discs of skeletal and cardiac muscle, they serve as anchor sites for actin- myosin interactions as well as intermediate filaments
• located at Inner aspects of sarcolemma and throughout cytoplasm 
Caveolae 
• Pinocytotic like invaginations of sarcolemma
• Like T tubules
• Modulate calcium availability and contraction
Smooth muscle innervation
Sympathetic: norepinephrine
Parasympathetic: acetylcholine
Bone
• mineralize during development
• Vascular
• Innervated
• Grows appositionally
Cartilage
• mineralization leads to degeneration
• Avascular
• Aneural
• grows appositionally and interstitially
Appositional growth
Chondroblasts in perichondrium differentiate into chondrocytes, start producing matrix, and add to existing cartilage
Interstitial growth
Proliferation and hypertrophy of existing chondrocytes. Can create an isogenous group
Chondroblast cell morphology
• reside near perichondrium
• Dense irregular CT, contains capillaries
• Oval shape, round or elongated nucleus
• Well developed rER (Active secretory pathway)
Chondrocyte cell morphology
• resides in lacunae
• Cartilage matrix, avascular, aneural
• round cells, small round nucleus, well developed rER, large Golgi, vesicles, lipid droplets, rich in glycogen
Composition of cartilage matrix (hyaline)
- Intracellular water
- Collagens (type II, some 4/6)
- Proteoglycans
- Multiadhesive glycoproteins
- Cells
Hyaline cartilage
• most common, type two collagen
• Lacuna and isogenous groups of chondrocytes
• perichondrium: tense CT with fibroblasts
• Appositional and interstitial
• Precursor of bones that developed by endochondral ossification
Cartilage matrices
- Capsular matrix
- Territorial matrix
- Interterritorial matrix
Articular cartilage
Hyaline cartilage on the articular surface of bones
• Absence of perichondrium, breakdown occurs in osteoarthritis
Elastic cartilage
• located: pinna of ear, walls of external acoustic meatus, auditory tube, epiglottis
• contains elastic fibers, lacuna and isogenous groups, perichondrium
Fibrocartilage
• Located: intravertebral disc, symphysis pubis, meniscus of knee joint, triangular complex of wrist
• less amorphous ground substance, more fibrous type I collagen (Resistant compression and shearing forces
•• Chondrocytes placed singularly, in rows or an isogenous groups
• NO Perichondrium
Cartilage repair
Limited availability due to:
1.) Lack of vascular supply, immobility of chondrocytes, special constraints limit chondrocyte deliberation
2.) Hyaline cartilage replaced with bone in calcification
3.) perichondral wounding is repaired by pluripotent progenitor cells producing dense CT rather than cartilage
Wolffs law
Bone will adapt to the loads under which it is placed using adaptive changing ( More frequent heavy loads = thicker and stronger bones)
Bone remodeling
1.) resting stage
— Osteoclast recruitment and activation
2.) Bone resorption
— Osteoblast recruitment an activation, osteoclast removal
3.) transition
— Matrix synthesis
4.) Bone formation
Osteoblasts
• formed by growth factor activation: CBFA1 and RUNX2
• Synthesis of organic matrix, osteoid
• deposits in organic components, located on bone surfaces
• Epithelioid appearance, cuboidal to columnar, basophilic
Surface receptors for parathyroid hormone
Osteoblasts, they bind PTH and regulate secretion of RANKL and OPG that caused the fusion of osteoclast precursors. This modulate calcium in the serum vs bone
Osteocytes
• osteoblasts surrounded by matrix, reduced protein synthesis, maintains matrix, regulates calcium levels
• Reside in lacuna, and have canaliculi which are tunnels that help osteocytes connect
Osteoclasts
• large, multi nucleated cells responsible for bone resorption
• Derived from GMP, the same precursor as macrophages
• Mature cells are amitotic, and abundant in lysosomes
• ruffled membrane adjacent to bone surface
Alpha-v-beta-3 integrins
Binds bone to osteoclast
Howships lacuna
Resorption pit, a depression in the surface of the bone where an osteoclast resides
Cancellous bone
Spongy bone, spicules or trabeculae of bone united to form a network found in the interior of bone
Compact bone
Dense bone, found on the bone exterior
Diaphysis
• Bone shaft between epiphyseal plates, mostly compact bone
• Contain periosteum (outside lining) and Endosteum (lining marrow cavity)
• has marrow cavity, blood cells, reticular cells, fibers
Epiphysis
• distal ends of long bones, cap of articular cartilage
• Medullary cavity is spongy and contains a marrow cavity
Periosteum
• fibrous outer layer, protection
• Osteogenic inner layer
• Blood vessels and nerves present
• sharpeys fibers (layer of anchoring collagen)
Endosteum
Between bone marrow and bone matrix, layer of osteoblasts, osteoclasts, and a few osteogenic cells
Haversian system
• entire system fully formed is an osteon
• In the middle is a Haversian canal that contains a capillary/vessel in the tunnel
• concentric lamellae of bone (around 10) 
Volkmann canals
Vascular passage that runs radially (Perpendicular to Haversian canal to connect them)
Interstitial lamellae
Remnants of partially reabsorbed osteons, no vessels, found in between osteons
Intramembranous ossification
• Skull, mandible, maxilla, clavicle
• MSC condense and differentiate to osteoblasts that secrete matrix, remain connected by thin cytoplasmic processes
• Matrix begins to calcify and spicules/tuberculate are seen
• osteocytes maintain processes that become canaliculi 
Endochondral ossification
• hyaline cartilage precursor template Forms a general shape of the bone out of cartilage
• Differentiation occurs as chondrocytes die and osteoblasts take presence 
Five zones of endochondral ossification
1.) zone of reserved cartilage
2.) Zone of proliferation
3.) Zone of hypertrophy
4.) Zone of calcified cartilage
5.) Zone of resorption
Fracture repair
Bone necrosis and blood clot —> Soft callous formation, granulation tissue —> Hard to callous formed, fibrocartilage and spongy bone —> New compact bone following Haversian system
Synovial joint
Membrane is made out of:
fibroblasts — type B cells (Secrete synovial fluid, lubrication and nutrition)
macrophages — type A cells (Remove debris as joint pivots)
Contains lining cells, not an epithelium, made of fibroblasts and macrophages
Cross bridge cycle: Actin + myosin
1.) resting fiber, myosin head is not attached to the actin
2.) Myosin head binds to actin and forms cross bridge to Actin
3.) phosphate is released from myosin head, causing conformational change in myosin 
4.)  Power stroke causes filament to slide, ADP is released
5.) A new ATP binds to myosin head, allowing it to release from actin
6.) ATP is hydrolyzed and phosphate bonds to myosin, causing energized myosin head to return to its original orientation
Excitation-contraction coupling in skeletal muscles
1.) terminal synapse releases acetylcholine
2.) Nicotinic acetylcholine receptor on postsynaptic cell accepts acetylcholine
3.) skeletal muscle voltage gated sodium channel activates
4.) transverse tubules voltage gated calcium channels open
5.)  Sarcoplasmic reticulum calcium release channel opens (Majority of calcium comes from here)
Ca2+ -ATPase function
• On the sarcoplasmic reticulum,it uptakes calcium from cytoplasm, clearing it from the muscles, allowing relaxation
Stepwise function of muscle contraction
Somatic motor neuron—> ACh released—> Sarcolemma: binds to nicotinic ACh receptor, opens ligand gated channels, sodium diffusers in depolarizing membrane, action potential produced —> Transverse tubules: conducts action potential to open voltage gated calcium channels—> Sarcoplasmic reticulum: releases calcium from SR—> Myofibrils: have binding spots for calcium to troponin, stimulating contraction
 Inverse relationship of force-velocity
The greater the force (load opposing contraction), the smaller the Vmax
Isometric contraction
Muscle fibers do not change in length (Force load is equal to the muscles capabilities)
Concentric contraction
Muscle fibers shorten (Joint angle decreases)
Eccentric contraction
Muscle fibers lengthen (joint angle increases)
Titin filament
Resting elastic protein, contributes to the resting length of muscles (Tension and contractibility depends on the length of the muscle fibers)
Ideal length-tension length
2.0-2.25 microm
Energy consumption of muscles
• 70% of ATP is used by myosin ATPase for contraction
• 30% of ATP is used for calcium ATPase for relaxation and sodium potassium ATPase for the electrochemical gradient
— Comes from aerobic respiration of fatty acids, and muscle glycogen/blood glucose during exercise
Creatine phosphokinase or creatine kinase
Help facilitate the rapid transfer of phosphates to create ATP out of ADP ( Phosphocreatine—> creatine)
CPK/CK: Indicator of muscle damage
CK – MM: Increases in muscular dystrophy, skeletal
CK – MB: Increase in heart disease, cardiac
Maximal oxygen uptake (aerobic capacity, VO2 max)
The maximum rate of oxygen consumption by aerobic cellular respiration. It is determined primarily by a persons age, size, and sex
Lactate threshold
The percentage of maximal oxygen uptake at which a significant rise in blood lactate levels occurs. For average healthy people, a significant amount of blood lactate appears when exercise is performed at about 50 to 70% of VO2 max
Oxygen debt
When a person stops exercising the rate of oxygen uptake does not immediately return to pre-exercise levels, it occurs slowly in order to repay the excess post exercise oxygen consumption
Type I Muscle fibers/slow oxidative fibers (red)
• Sustain a contraction for a long time without fatigue (Postural muscles)
• high oxidative capacity for aerobic respiration
• rich in capillaries, mitochondria, aerobic respiration enzymes, and myoglobin
Myoglobin
Red pigment that improves the oxygen delivery to the slow-twitch fibers to help sustain contraction
Type IIA Muscle fibers/Fast oxidative fibers (red)
• Used for walking
• fast twitch fibers with high oxidative capacity, resistant to fatigue
Type IIX muscle fibers/fast glycolytic fibers (white)
• Used for explosive actions, exercise
• Powerful high tension contractions but fatigue quickly
• Large stores of glycogen and glycolytic enzymes which allow for anaerobic metabolism
• The fast twitch fibers have fewer capillaries, mitochondria, and myoglobin

Reasons for muscle fatigue
1.) increase concentration of PO4 From the breakdown of phosphocreatine
2.) Decreased ATP hinders the action of the Ca2+ pumps
3.) increased ADP in the cytoplasm decreases the velocity of muscle shortening
4.) Depletion of muscle glycogen decreases the release of calcium from the SR 
Central fatigue
Muscle fatigue caused by changes in the central nervous system, such as reduced activation of muscles by motor neurons
Effects of endurance training on skeletal muscles
No enlargement, instead increased size and number of mitochondria, improved ability to obtain ATP from oxidative phosphorylation, less lactic acid produced, improved efficiency in extracting oxygen from blood
Effects of resistance training on skeletal muscles
Muscle enlargement. Muscle hypertrophy associated with the increase in size of myofibrils and the increase in the number of myofibrils within the muscle fibers
Myostatin
Inhibits activation of muscle repair, ridding of this might lead to larger muscles
Upper motor neurons
Motor cortex:  planning, initiating and directing voluntary movement
Brain stem: postural control, locomotion, basic voluntary movement
Basal ganglia: getting proper initiation of movement
Cerebellum: sensory motor coordination
Lower motor neurons
Spinal cord and brain stem circuits: reflexes
Skeletal muscles: contraction
— Lower neurons directly innervate muscles
Alpha motor neurons
Efferent nerve fiber: Innervates extrafusal muscle fibers, with fast conduction
Stimulation of alpha motor neurons causes muscle shortening
Gamma motor neurons
Efferent nerve fiber: innervates intrafusal fibers, With slow connection
Stimulation of gamma motor neurons causes isometric contraction of spindles and enhances the stretch reflex
Disynaptic reflex of Golgi tendon organs
1.) tension on tendon activates sensory neuron
2.) Sensory neuron stimulates interneuron
3.) Interneuron inhibits motor neuron
4.) Tension on tendon is reduced
Reciprocal innervations of muscles
1.) muscle stretch activates spindle apparatus
2.) Agonist muscle contracts in stretch reflex
3.) Antagonist muscle relaxes
Double reciprocal innervation of muscles
Example: stepping on a nail
1.) Flexor contract and extensor relaxes to withdraw foot
2.) Simultaneously, extensor contracts and flexor relaxes and contra lateral leg to support the weight
Troponin tests
Cardiac-specific troponin T or troponin I released into the blood when myocardial cells die
— relies on antibodies, better than CK tests
Single-unit smooth muscle
Ex. Digestive tract
• one autonomic neuron, smooth muscle cells connected by gap junctions to continue electrical pulse transmission (only one cell innervated)
Multi-unit smooth muscle
Ex. Lens control
• multiple autonomic neurons
• smooth muscle cells not connected by gap junctions, each cell innervated separately
Developmental dysplasia of the hip (DDH)
• biggest risk factor is first born, breech presentation and Incorrect swaddling/ family history
• hip instability, subluxation/dislocation of the femoral head and or acetabular dysplasia in a developing hip joint
Ortolani diagnosis
DDH, reduction maneuver (Femoral head is out, and we put it back in)
Barlow’s diagnosis
DDH, dislocation maneuver (Femoral head is in the right position, we push it out) 
Frank dislocation
Complete hip dislocation, irreducible, arthrogryposis, myelodysplasia
Late diagnosis of DDH
• Limited abduction
• Galeazzi: apparent leg length discrepancy
• Unilateral leg folding
• Barlow/Ortolani: signs may not be present after 2 to 4 months of age
Obstacles to reduction
• tight muscles, adductors, iliopsoas
• intra-articular obstacles: Capsular construction/ileus OS tendon, ligamentum teres, labrum, TAL, pulvinar 
Treatment of DDH
• <6mo: Pavlik harness, successful 95% — Contraindicated in children with muscular imbalance
• >6mo: closed reduction, arthrogram, Spica casting, abduction orthosis following cast
• Open reduction if: failure closed reduction, persistent subluxation, soft tissue interposition, unstable reduction
DDH treatment for children older than two years old
• Open reduction
• femoral shortening
• Acetabular procedure (Cut acetabulum and bring rim down)
When to refer for DDH
1.) abnormal exam, ultrasound, or X-ray
2.) baby born in breech position, ultrasound around six weeks of age
Legg-calve-Perthes disease (LCPD)
• most common in boys, positive family history, Low birth weight, secondhand smoke
• Vascular insult of femoral epiphysis leads to osteonecrosis, AVN

Stages of legg-calve-Perthes disease
1.) initial: infarction produces a smaller, sclerotic epiphysis with medial joint space widening
2.) Fragmentation: presence of subchondral loosened line, femoral head appears to fragment or dissolve, patchy density and lucencies
3.) Re-ossification: ossific nucleus undergoes re-ossification with new bone appearing as necrotic bone is reserved
4.) Healing or remodeling: femoral head remodels until skeletal maturity
Clinical presentation of LCPD
• insidious limp, can be painful or painless, hip thigh or knee pain
• Limited abduction and internal rotation, synovitis, muscle spasm, thigh atrophy, leg length discrepancy
• Poor prognosis in children older than seven, percent of head involvement, protracted disease course
Treatment goals for LCPD
1.) Restore range of motion
2.) Containment of femoral head
3.) good outcome more than likely, 60% of patients require no surgical intervention
When to refer for LCPD
• School aged children with thigh, hip, knee pain
• decreased ROM, atrophy
• Abnormal imaging or labs 
Slipped capital femoral epiphysis, SCFE
• posterior and inferior displacement of the femoral head in relation to the femoral neck at the proximal femoral growth plate (Between epiphysis and metaphysis)
• risk factor: males, obesity, family history, endocrine/hormones 
Clinical presentation of SCFE
• Pain in thigh or knee
• limp: external rotated gait
• Limited internal rotation and flexion
• Obligatatory external rotation of hip with passive flexion
Treatment/ referral of SCFE
• In situ fixation, osteotomy for deformity, epiphysiodesis, prophylactic pinning of normal side
• Immediately refer any SCFE needs, strictly nonweightbearing
Increased femoral anteversion
• hip rotation, increased medial rotation compared to lateral
• 40° in infants, 10 to 60° average an older children
• Increases until age 10 and then normalizes, more common in girls
Internal tibial torsion
• thigh foot angle is 5 to 30° normally, Diagnosis of ITT is greater than 10° internal with in-toeing gate
• no treatment necessary, resolves on its own
• Osteotomy for severe persistent deformity an older children
When to refer for internal tibial torsion
1.) recent specific change in gate
2.) Functional problem
3.) Persistent problem and older children (older than six)
4.) Family wants referral
Genu Varum, Bow legged
• Bowing distributed between femur and tibia
• Early/agile walkers, family history common, bilateral
• Spontaneous correction and Serial photos are helpful
Blounts disease
• Osteochondrosis, deformity focused as proximal medial tibia causing metaphyseal Beaking
• Brace treatment in children less than three
• Valgus proximal tibia osteotomy in children between three and four years old
When to refer for bowing 
1.) height less than 5th percentile
2.) Positive family history
3.) asymmetry
4.) Progressive condition
5.) Localized Varus deformity
Genu valgum, knock knees 
• symmetric, apparent after two years, remodels to normal by age 7
• Patellar instability can be associated
• Treatment: hemiepiphysiodesis, stapling, eight points, osteotomy
When to refer for genu valgum
1.) less than 10th percentile for height
2.) Asymmetry
3.) Deformity increasing after age 7-8
4.) History of metabolic disease/skeletal dysplasia
Metatarsus adductus
• medial deviation of forefoot on hind foot
• likely caused by intrauterine positioning
• Hip dysplasia, bilateral in around 50%
Clinical features of metatarsus adductus
• forefoot Adductus
• Hindfoot neutral
• Medial crease
• forefoot slightly supinated
• Full dorsiflexion
• Supple versus rigid
When to refer for metatarsus adductus
1.) stiff foot
2.) No self correction at six months
3.) Shoe problems
4.) Hindfoot in valgus (skewfoof) or Equinus (Clubfoot)
Congenital talipes equinovarus — clubfoot
• most common MSK birth defect, isolated deformity and 80%, genetic
• forefoot adductus, hindfoot equinus, varus, cavus, shortening of foot, atrophy of calf 
Club foot treatment
1.) after birth: Ponsetti serial casts
2.) braces until four years old needed to prevent recurrence
3.) Percutaneous Achilles tenotomy
4.) Occasionally requires anterior tibial tendon transfer has an older child
Flexible flat feet (flexible pes planovalgus foot)
• often notice on child is standing, fat pad disrupts view of the arch however arch is the present when on tippy toes • Where are the causes problems in adults