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Microanatomy Muscle Weakness
Exam Prep
275
Histology
Graduate
10/01/2016

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Term
Myofibril
Definition
Group of microfilaments running lengthwise in a muscle cell (myofiber), seen as dots in cross-section
Term
Myofiber
Definition
Individual muscle cell, anatomical syncytium, multinucleate running length of cell
Term
Epimysium
Definition
Surround entire muscle, dense irregular CR, contains vascular and nerve supply
Term
Perimysium
Definition
Surround 1 fascicle, less dense irregular collagenous CT, contains smaller branches of nerves and blood supply
Term
Endomysium
Definition
Surrounds 1 muscle fiber, loose CT, reticular and collagen; contains capillaries and fine neuronal branches
Term
Myotendonous junction
Definition
Point where muscle meets dense regular CT (e.g. muscle meets tendon)
Term
Myotubes
Definition
Myoblasts which fuse end to end, central nuclei when immature; develop from paraxial mesoderm; develop into myofibers
Term
Muscle satellite cells
Definition
Persistent stem cells, mononucleate, between fibers, regenerative, only used when necessary
Term
Terminal cisterna
Definition
Dilated flattened end of Sarcoplasmic Reticulum containing ryanodine receptors which release Ca to start contraction
Term
Triad
Definition
T-tubule + 2 SR terminal cisternae, located at A-I junction in skeletal muscle; site of excitation-contraction coupling
Term
DHPR-RyR in skeletal muscle
Definition
Conformational change in DHP receptor --> change in associated RyR --> RyR opens for Ca to leave SR and enter cytosol
Term
Which type of skeletal muscle has prominent glycogen?
Definition
White muscle
Term
Which type of skeletal muscle has more mitochondria?
Definition
Red muscle
Term
I band, H band, A band in contraction
Definition
I band narrower, H band narrower, A band same size
Term
Myomesin and C protein
Definition
Anchor thick filaments of sarcomere to other filaments, titin at M-line
Term
M-line thick filament anchoring proteins
Definition
Myomesin and C protein
Term
Titin
Definition
Accessory protein extending from M-line to Z-line, important for stabilizing thick filaments
Term
Thin filament polarization
Definition
Highly polarized with positive (+) end binding at Z-line via alpha-actinin
Term
Alpha-actinin
Definition
Binds + end of actin filaments to Z-line
Term
Nebulin
Definition
Runs length of filament, helps bind thin filament to Z-line; keep thin filament lengthwise in place
Term
Tropomyosin
Definition
Filament runs in grooves between F-actin molecules; goes deeper into the actin molecule to expose TnC during contraction; troponin-tropomyosin complex
Term
Troponin
Definition
Binds tropomyosin via TnT; binds Ca via TnC; binds actin via TnI, inhibiting actin-myosin interaction
Term
Muscle intermediate filaments
Definition
Desmin and vimentin; secure Z-lines in adjacent myofibrils; attach Z-lines to sarcolemma for overall stability
Term
Clinical correlation of Muscular Dystrophy
Definition
Mutation in dystrophin complex which helps anchor/organize/secure to sarcolemma; leads to progressive weakness and death
Term
Sensory nerve fiber
Definition
Form muscle spindles, monitor changes in muscle length
Term
Motor nerve fiber
Definition
Stimulate contraction; supplied by 1 neuron (1 neuron can supply many fibers); connect through NMJ
Term
Motor neuron
Definition
Present in ventral horn of spinal cord, sends out long processes into muscle cells, connect at NMJ
Term
Motor unit
Definition
Motor neuron + all muscle fibers it controls (1:1 eyes, 1:many in thighs); all contract in unison; myelinated axons with many arborizations
Term
Axon terminus
Definition
No myelin sheath, dilate at NMJ; synaptic vesicles with ACh, many mitochondria; sits in primary synaptic cleft
Term
Clinical Correlate: ALS
Definition
Denervation of 1 group at a time; groups of atrophying muscle fibers with their affected motor neurons; mostly in anterior horn in brain, leading to loss of motor control
Term
Clinical Correlate: Myasthenia gravis
Definition
Auto-antibodies block ACh receptors at NMJ, junctional folds are lost and synaptic cleft widens; progressively weaker muscles
Term
Sliding Filament Model of Contraction
Definition
Motor neuron AP to NMJ --> ACh release in synaptic vesicles, bind receptors on myofiber --> depolarization signal to T-tubules to DHP receptors --> act on RyR, Ca release from SR --> Ca binds TnC, expose myosin-binding site --> myosin head bind actin, ATP hydrolysis to release --> myosin pull actin past, repeated cross-bridge cycling --> Ca pumped back into SR
Term
Clinical Correlate: Rigor Mortis
Definition
No O2 to make ATP, Ca diffuse in cytosol to bind troponin, myosin-actin cannot decouple; muscles contracted until myosin heads degrade
Term
Slow-twitch muscle fibers
Definition
Red muscle, oxidative, endurance, Type I; abundant mitochondria, myoglobin, blood supply, wider Z-lines, small NMJ
Term
Fast-twitch muscle fibers
Definition
White muscle, glycolytic, strength, Type II; abundant glycogen, fatigue quickly, less blood supply, fewer mitochondria
Term
Dystrophin
Definition
Binds Z-lines to plasma membrane; keep everything in order; complex associated with laminin in basal lamina
Term
Succinic dehydrogenase
Definition
Stain used to tell red muscle and white muscle apart; most muscles have different ratios of white:red muscle but have both
Term
Layers of heart (3)
Definition
Epicardium (CT with mesothelium, fatty), Myocardium (muscular wall), Endocardium (thin CT with endothelium, lines vessel of heart)
Term
Important characteristics of cardiac muscle (3) - basic
Definition
Striated; involuntary; functional syncytium, not structural syncytium (act in unison)
Term
Additional important characteristics of cardiac muscle
Definition
1-2 nuclei per cell; end-to-end attachment by intercalated disks; central nuclei; branching fibers; high endurance; intermediate size (smaller in atria); rhythmic contraction; sarcomere like skeletal; organelles near poles of nuclei
Term
Area around nucleus in cardiac muscle
Definition
Pale area (glycogen) and cluster of organelles
Term
Cardiac muscle in LM
Definition
Fibers vary in shape and size due to branching
Term
Cardiac muscle innervation
Definition
No direct innervation! Impulse initiated by cells in conduction system; regulated by autonomic nervous system, conduction through normal cells and PURKINJE fibers
Term
Cardiac muscle in EM
Definition
Most mitochondria, lipid droplets, and glycogen; Dyad at Z-band; DHPR dispersed (not tetrads), intercalated disks
Term
Intercalated disks
Definition
Physically attach and electrically couple adjacent cells (end-to-end)
Longitudinal: gap junctions, demosomes
Transverse: Fascia adherents, maculae adherents (desmosome)
Term
Cardiac mitochondria
Definition
Densely packed cristae; produce high levels of ATP for greater endurance
Term
Impulse conduction in cardiac muscle
Definition
SA node --> AV node --> AV bundle --> bundle branches; passes through Purkinje fibers
Term
Nodal fibers
Definition
Smaller diameter, more CT separation, attach by gap junctions
Term
Purkinje fibers
Definition
Large diameter, low density, more glycogen; couple by gap junctions; branching bundles in subendocardium toward apex
Term
Smooth muscle characteristics
Definition
Spindle shape (thicker in middle); central nucleus; couple with gap junctions, contract in unison; ANS control; smallest diameter; single or group innervation
Term
Examples of smooth muscles
Definition
Walls of tubular/sac-shaped organs; blood vessels; uterus (contraction), GI (peristalsis); slow sustained contraction with low ATP usage
Term
Smooth muscle nuclei
Definition
Single central, elongated nucleus; corkscrew appearance when contracted; organelles near nucleus, eosinophilic
Term
Bouton en passant
Definition
swelling of ANS axons with NT in vesicles; enlargement of passing fiber, NTs diffuse across space by cell
Term
Single-unit vs. Multi-unit smooth muscle
Definition
Single-unit - nerve fiber synapse on few fibers, spread to more cells by gap junctions; single unit (BV, GI, uterus)
Multi-unit - individual innervation (vas deferens, iris)
Term
Dense body
Definition
Anchor actin, IF, similar to Z-line, attach sarcoplasm to sarcolemma; joined in network by IFs, transmit contractile forces
Term
Caveolae
Definition
Invagination of smooth muscle cell membrane; look like pits, close to SR, similar function to t-tubules, allow Ca entry
Term
Smooth muscle actin filaments
Definition
Different isoforms; caldesmon, calponin, NO TROPONIN, leitonin, insert into dense bodies
Term
Smooth muscle myosin filaments
Definition
Side-polar; stack of myosin dimers; no bare zone; surrounded by rosette of thin filaments
Term
Smooth muscle contraction
Definition
Stretch-activated ion channels; NT from ANS; open Ca channels; affected by hormone activation as well
Term
Smooth muscle activation
Definition
Ca mostly from extracellular source, not stored in cell (no t-tubules)
Term
Calmodulin
Definition
Important protein in smooth muscle; binds Ca, complex activates MLCK, which phosphorylates myosin, activating the actin-binding site
Term
Smooth muscle ATP hydrolysis
Definition
Slow leading to sustained contraction; can maintain in "latch state"
Term
Smooth muscle contraction
Definition
Shorten cell in all directions, "bubbles", due to Ca-CaM interaction; change in length not due to sarcomeres but longer thin filament lengths
Term
Smooth muscle organization - large-scale
Definition
Well-defined layers/longitudinal arrangement - peristalsis/tone
Interlacing bundles - expand quick or over long time - uterus/bladder
Term
Additional capabilities of smooth muscle
Definition
Make collagen type III + IV, other ECM molecules; make Collagen type I and elastin in tunica media of BV; divide in response to injury
Term
CNS Components
Definition
Brain, spinal cord, optic nerve, retina, olfactory tract+bulb
Term
CNS characteristics
Definition
Derive from neural tube; oligodendrocytes form myelin, 4 specialized glia
Supporting cells: astrocyte, microglia, oligodendrocyte, ependymal cells
Term
PNS characteristics
Definition
Derive form neural crest; Schwann cells myelinate; satellite cells
Afferent (inward, sensory) and Efferent (outward, motor)
Motor --> Somatic and Autonomic --> Sympathetic and Parasympathetic --> Enteric (gut motility)
Term
Nerve cell function
Definition
Transmit impulse in response to stimuli; process information; activate muscle; heart rhythm; regulate effectors (glands), homeostasis with endocrine system
Term
Gray vs. White matter
Definition
Gray matter: many neurons, cell bodies, glia and axons, less myelinated
White matteR: more myelinated axons (lipid), axons, glia, few cell bodies
Term
Neuron
Definition
Functional unit of nerve tissue, make action potential, electrical or chemical activation, NOT REPLACED IN ADULTHOOD, average neuron receives 1500 synapses
Term
Neuron cell body
Definition
Large euchromatic nucleus with 1+ large nucleoli, large RER, abundant Golgi, free polysomes (Nissl bodies), lipofuchsin bodies, neurofilaments, melanin inclusions (rare); large cell body
Term
Lipofuchsin body
Definition
Lysosomes which can no longer function and accumulate junk; occurs because neurons last entire lifetime
Term
Axon
Definition
Branch into smaller collateral branches; contact cells at boutons; axon hillock --> axon terminal; MT's with + end distal
Term
Dendrites
Definition
Multiple, form dendritic tree; form on cell body or axon; never myelinated; receptive surface at synaptic junction, specific MAPs (MAP2); Nissl bodies present in proximal area
Term
Chromatolysis
Definition
Loss of Nissl bodies, oddly located nucleus (due to injury), return to normal if successful recovery
Term
Glial cell body size
Definition
Much smaller than neuron cell body
Term
Electrical synapse
Definition
Specialized gap junction, channels allow current flow, rare - places where synchrony needed (smooth muscle, retina, bronchioles)
Term
Bipolar cells
Definition
One main dendritic process, one main axonal process
Retina, olfactory epithelium, some interneurons
Term
Multipolar cells
Definition
Multiple dendritic trees, one axon (common); includes pyramidal cells
Term
Pyramidal cells
Definition
Multiplar neuron, large extensive dendritic trees
Term
Pseudounipolar neuron
Definition
Special sensory, 1 main branch coming out from body with axon going one way and dendrite going the other way; information goes in ONE way toward CNS (dorsal root ganglion!)
Term
PNS Neurotransmitters
Definition
Acetylcholine, Norepinephrine, Epinephrine, some peptides, Nitric Oxide (NO)
Term
CNS Neurotransmitters
Definition
Glu (excitatory), GABA, Gly (inhibitory), dopamine, serotonin, acetylcholine, norepnephrine
Term
NT Synthesis
Definition
Synthesized in cell body, transport to axon in vesicles
Term
Glia
Definition
Large % of CNS; support + regulate microenvironment of neurons, can divide; only see nuclei by LM; form BBB, sequester ions or excess NT, form myelin, scar formation
Term
Astrocyte
Definition
Helps form BBB, star-shape, sequester excess ions; form glial scar; IF is GFAP
Term
Radial glia
Definition
Present only in development - important for axon guidance; loss may be linked to inability to regenerate nervous tissue
Term
Oligodendrocyte
Definition
Myelinate ONLY in CNS; can myelinate many axons/neurons
Term
CNS Myelination
Definition
Axon forms and reaches synapse --> axon secretes neuregulin (more made = thicker myelin sheath) --> myelin sheath made
Missing Oligo --> missing myelin sheath in segment --> slow signal or lack of propagation of signal
Dark cytoplasm in EM, reaches out to axons
Term
Microglia
Definition
Inflammatory and immune response; mesodermal origin; give rise to CNS macrophages and monocytes
M1 remove debris, M2 repair; timing + presence important
Term
Ependymal cell
Definition
Epithelium lining ventricles and central canal of spinal cord, makes CSF; single layer, cuboidal-columnar; taller in choroid plexus
Term
Satellite cell
Definition
Flat, surround cell body in peripheral ganglia, support neurons, regulate environment; closer encapsulation in DRG than in ANS
Term
Schwann cell
Definition
PNS myelination; only 1 segment of 1 axon; can divide at site of nerve injury, help guide regenerating axons
Term
Myelin sheath
Definition
Formed by Oligo/Schwann due to neuregulin secretion; alternating dark and light in EM (dark = myelin)
Each segment made by wrapping around of single Schwann cell or single process of oligodendrocyte
Term
Wrapping of myelin sheath
Definition
Occurs in spiral, squeezes cytoplasm out of own cell; major dense line and intraperiod line
Term
Major dense line
Definition
Fused cytoplasmic surfaces in myelin spiral (darkest)
Term
Intraperiod line
Definition
Fused extracellular surfaces in myelin spiral (lighter than major dense line)
Term
Mesaxon and components
Definition
Winding part of Schwann cell/oligodendrocyte; inner mesaxon = inner end of spiral; outer mesaxon = outer end of spiral
Term
Myelin-forming unit size
Definition
About 200 µm between Nodes of Ranvier (site of saltatory conduction)
Term
Schmidt-Lanterman cleft
Definition
Tubular channel when outer cytoplasm of myelinating cell near nucleus attaches to inner cytoplasm near the axon it has wrapped around; important for maintenance and turnover of myeling and cytoplasmic components; cone-shaped space/imperfection
Term
CNS/PNS specific proteins and glycoproteins
Definition
CNS - Nogo-A/Nogo66, MAG, OMgp
PNS - MBP, PLP, P0
Term
Epineurium
Definition
Dense CT, looser extending in to fill spaces, continuous to dura mater
Term
Perineurium
Definition
2-5 layers of squamous myoepithelial connected by tight junctions; basal lamina around each layer, BV present, form Blood-Nerve barrier
Term
Endoneurium
Definition
Engulf Schwann cell and axon; reticular collagen, few fibroblasts; loose CT
Term
PNS cell bodies
Definition
Present in ganglion, nerves DO NOT contain neuronal cell bodies
Term
Somatic motor system
Definition
Large alpha neurons in ventral horn, send axon out, synapse on individual muscle fiber, no synapses in pathway until skeletal muscle
Term
Autonomic motor system
Definition
2 cell pathway: column in inf. lat. spinal cord send out ventral root to autonomic ganglion --> effector organs
Term
Sympathetic ganglia
Definition
Located together in sympathetic chain
Term
Sensory/spinal ganglia
Definition
Psuedounipolar; large cell body, central nuclei, close cluster, continuous capsule by satellite cell; dense CT capsule around all; peripheral receptor to spinal cord
Term
Autonomic ganglia
Definition
Input from presynaptic neurons, multipolar, eccentic nuclei, more scattered neurons, discontinuous satellite cell layer
Term
Sympathetic nervous system
Definition
Fight or flight, function under stress; 2 chains along vertebral column (paravertebral/chain ganglia), few unpaired along aorta; preganglionic axons cholinergic, postganglionic axons usually adrenergic
Term
Paravertebral ganglia
Definition
Chain of ANS ganglia along vertebral column; 2 paired chains
Term
Prevertebral ganglia
Definition
Few unpaired ganglia along aorta, belongs to ANS
Term
Parasympathetic nervous system
Definition
Rest and relax; ganglia close to or in target organ (terminal ganglia); preganglionic axon from S2-S4 or CN 3,7,9,10; long preganglionic axon; short postganglionic axon; ACh used for both
Term
Terminal ganglia
Definition
Parasympathetic ganglia close to or inside target organs
Term
Cranio-sacral outflow
Definition
Preganglionic Parasympathetic axons originating from S2-S4 or CN 3, 7, 9, 10
Term
Sympathetic + Parasympathetic innervation
Definition
Innervate all same organs EXCEPT sweat glands and adrenal glands only have sympathetic innervation
Term
Secondary NT neuromodulator examples (3)
Definition
Sympathetic ACh activate nicotinic (fast) or muscarinic (slow) receptors
Norepinephrine produce vasoconstriction + inhibit further release at neurovascular junction
Co-transmission (e.g. ACh and VIP) at secretomotor junction
Term
Enteric nervous system
Definition
GI for peristalsis and secretion; independent operation, regulated by Para/Sympathetic systems; ganglia in 2 plexuses; susceptible to Crohn's IBS, infectious diarrhea, food poisoning
Term
Myenteric plexus
Definition
Auerbach's plexus, ganglia of Enteric NS; between circular and longitudinal layers of muscle
Term
Submucosal plexus
Definition
Meissner's plexus, ganglia of Enteric NS; just deep to mucosal layers (inside muscular layers)
Term
Hirschsprung Disease
Definition
Developmental absence of ganglia in enteric NS; ANS can somewhat replace by inserting into gut with ganglia scattered throughout length of gut, diagnosed early
Term
Presynaptic NMJ specializations
Definition
Enriched mitochondria, neurofilaments, ACh in synaptic vesicles which fuse with active zone, capping by non-myelinating Schwann cells
Term
Active zone
Definition
Are where synaptic vesicles fuse with the membrane to release ACh into the neuromuscular junction
Term
Postsynaptic specialization
Definition
High density of ACh receptors, junctional folds to increase surface area (primary and secondary), enriched mitochondria
Term
Smooth muscle motor nerve endings
Definition
NT released from varicosities further away, no NMJ, 1 varicosity per unit of muscle cells (1 or many)
Term
Lambert-Eaton Disease
Definition
Antibodies to presynaptic Ca channels, impair ACh release
Term
Myasthenia gravis antibodies
Definition
Antibodies to postsynaptic ACh receptors
Term
Botulinum toxin
Definition
Bacterium, block synaptic vesicle fusion
Term
Tick paralysis
Definition
Tick salivary gland, inhibit Ach release
Term
Clinical Correlation: Autoimmune diseases (2) and Neurotoxins (5)
Definition
Lambert-Eaton disease and Myasthenia gravis
Botulinum toxin, tick paralysis, bungarotoxin, latrotoxin, tetanus toxin
Term
Bungarotoxin
Definition
Snake, block ACh receptor
Term
Latrotoxin
Definition
Spider, too much synaptic vesicle fusion, ACh release
Term
Tetanus toxin
Definition
Bacterium, block fusion from GABA; not enough inhibitory signal throughout nervous system
Term
Sensory nerve ending adaptation
Definition
Fast-adapting available for new stimulus quickly (fine touch); slow-adapting resents over longer time (pain)
Term
Pacinian corpuscule
Definition
Vibration detected in deep dermis or hypodermis; free nerve fiber in tissue, tissue deformation due to pressure causes depolarization in nerve ending --> action potential
Term
Somatosensory receptor types (6)
Definition
Mechanoreceptor (pressure, vibration, sound), Photoreceptor, Nociceptor (tissue damage/pain), Chemoreceptor (O2, pH, organic molecules), Proprioceptor (position), Thermoreceptor (temperature)
Term
Free nerve ending
Definition
No capsule, associated with unmyelinated axons/non-myelinating Schwann cells, epidermis or hair bulb; pain, temp touch; cornea; silver stain to see;
Term
Expanded tip ending
Definition
Expansion of denuded terminal tips, associated with special non-neuron cells (e.g. Merkel's disk)
Term
Merkel's disk
Definition
Large nerve ending near Merkel cell (lobed nucleus); basal layer of epidermis; respond to light touch, steady pressure (slow-adapting)
Term
Merkel cell
Definition
Lobed nucleus, many secretory vesicles, near nerve terminal, associated with Merkel's disk
Term
Ruffini Ending
Definition
Detects continuous touch or pressure (slow-adapting)
Term
Encapsulated endings
Definition
Skin: Pacinian corpuscules, Ruffini endings, Meissner's corpuscules
Muscle: Muscle spindles, Golgi tendon organs
Oropharynx/eye: Krause's end bulbs
Surrounded by layers of CT and capsules (corpuscules)
Term
Meissner's corpuscule
Definition
Cylindrical, perpendicular to skin; horizontal stacks of flattened Schwann cells; axon end in spiral course; present in dermal papillae esp. glabrous skin; fast-adapting to light touch, texture, rapid or irregular pressure
Term
Extrafusal fibers
Definition
Give power to muscle (functional contractile element)
Term
Intrafusal fibers
Definition
Encapsulated sensory ends; sense stretch, pressure, length, and spatial position
Term
Muscle spindles
Definition
Skeletal muscle; intrafusal fibers present (nuclear bag or chain fibers in capules); afferent and efferent innervation
Term
Nuclear chain fiber
Definition
Nuclei lined up along length
Term
Nuclear bag fiber
Definition
Nuclei bunched, piled up on top of each other
Term
Muscle spindle afferent innervation
Definition
Large caliber myelinated Ia fibers (every spindle receives one) - terminal complex is primary sensory ending, smaller caliber myelinated II fibers - ending is secondary sensory ending
Term
Muscle spindle efferent innervation
Definition
gamma-motor neuron; contracts intrafusal fibers, adjust spindle sensitivity
Shorter intrafusal fiber --> less stretch required to excite spindle afferents
Term
Muscle spindle reflex
Definition
Passive stretch --> Ia afferent fires --> activate alpha-motor neuron of flexor AND activate inhibitory interneuron synapsing on alpha-motor neuron of extensor --> flexion
Term
Examples of muscle spindle reflex
Definition
Biceps tendon reflex test (C5-C6 integrity)
Knee-jerk reflex (lumbar spinal integrity)
Term
Effects on knee-jerk reflex
Definition
Lose descending motor control - more robust response
Dorsal or ventral root damage - no reflex at all
Term
Golgi Tendon Organ
Definition
At myotendinous junction; arranged in series with skeletal muscle cells
Innervated by free Ib afferent nerve, interwoven with collagen fibers, no efferent innervation (more sensitive to tension force)
More sensitive to muscle contraction than stretch (monitor load or tension on muscle)
Term
Protective Golgi tendon reflex
Definition
Muscle contraction in flexor --> stretch Golgi tendon organ --> 1b myelinated sensory fiber activated --> fire alpha-motor neuron innervating extrafusal fibers of flexor AND inhibit interneuron synapsing on alpha-motor neuron of flexor --> contract extensor, relax flexor, release heavy load
Term
Muscle spindle capsule
Definition
Circumferential lamellae of flattened fibroblasts, joined by desmosomes; capsular space contains tissue fluid
Term
Bone functions
Definition
Structural: posture, movement, protect organs, support soft tissues
Endocrine: osteocalcin regulate insulin production, signal fat to produce adiponectin
Metabolic: Hematopoiesis, storage/metabolism of minerals
Term
Center of ossification
Definition
Where bone growth primarily occurs; in long bone, starts in diaphysis (primary), separately later at epiphysis (secondary)
Term
Diaphysis
Definition
Shaft of bone, mostly hollow with marrow inside
Term
Metaphysis
Definition
Bone starts to narrow into shaft below epiphyseal line
Term
Epiphysis
Definition
Bone ends, joint surfaces, muscle attachment points
Term
Flat bone material
Definition
Inner and outer cortex of compact bone, internal diploe of cancellous bone; no marrow cavity, marrow in trabeculae of spongy bone
Term
Dynamic structure of bone
Definition
Repair, remodel, optimize structure throughout lifetime; prevent overmineralization (become brittle), imbalance leads to fracture susceptibility
Term
Levels of structure
Definition
Bone crystal + collagen --> collagen fibril --> collagen fiber --> lamella with Haversian canals --> osteon --> cortical/cancellous bone
Term
Cancellous bone
Definition
Trabecular; Spongy; plates in interconnected struts (trabeculae), more porous; flat bones of skull, end of long bones, vertebrae
Term
Compact bone
Definition
Cortical; densely packed bone matrix, more bone than space; outer cortex of all bones, shaft of long bones
Term
Lamellar vs. Woven bone
Definition
Woven - tissue in random fashion, laid down first
Lamella - organized layers of tissue
Term
Bone ECM contents and their functions
Definition
Organic material (e.g. collagen) - flexibility, tensile strength
Inorganic material (e.g. Ca) - rigidness, compressive strength
Term
Ground section vs. Decalcified section
Definition
Ground - study inorganic component
Decalcified - study organic parts
Term
Organic ECM components
Definition
90% Collagen Type I, 10% ground substance with proteoglycans (GAGS, proteoglycans, hyaluranon, aggrecan) and 4 glycoproteins (osteocalcin, osteonectin, osteopontin, sialoproteins)
Term
Osteocalcin
Definition
Hormone; bind hydroxyapatite; stimulate insulin production and fat metabolism
Term
Osteonectin
Definition
Bind calcium, regulate mineralization (organic ECM of bone)
Term
Osteopontin
Definition
Bind hydroxyapatite, adhere cells to matrix
Term
Sialoproteins
Definition
Cell adhesion in bone (organic ECM of bone)
Term
Inorganic ECM of bone
Definition
Ca compound crystals; fiber formation THEN calcification
Term
Osteoid
Definition
Initial bone deposits that have undergone fiber formation but not calcification
Term
Osteoprogenitor cells
Definition
Determined, not differentiated; mesenchymal origin; inner periosteum or endosteum linings; look like fibroblast; divide into osteoblasts
Term
Osteoblast
Definition
Synthesize bone, secrete collagen and ground substance as osteoid and matrix vesicles (make mineral part)
Receptors for PTH and Vit D3 to regulate osteoclast activity, Ca levels
Term
Osteoblast location/composition
Definition
Surface of remodeling bone; cuboidal; looks like protein-secreting cell; gap junctions, fewer than osteocytes; estrogen receptors; alkaline phosphatase on surface (marker for cell turnover rate)
Term
Osteoblast transition
Definition
Become osteocytes when surrounded by matrix they make OR quiescent bone lining cells which can later become osteoblasts
Term
Osteocyte
Definition
Buried in mineralized bone matrix, reside in lacunae; communicate through canaliculi, connect by gap junction; small amount of resoprtion through osteolytic osteolysis
Term
Osteocyte composition
Definition
Reduced rER, reduced Golgi, mineral homeostasis, mechanosensory in stimulation of remodeling; heterochromatic nucleus, glycogen accumulation
Term
Osteoclast
Definition
Resoprtion of bone; large, multinucleate (syncytium), along resoprtion surface in resorption bay/Howship's lacunae
Stimulated by PTH, inhibited by calcitonin
Term
Canaliculi
Definition
Long cell process of osteocyte running in small, fluid-filled canal space through mineral
Term
Howship's lacunae
Definition
Resoprtion bay - "bites" osteoclast has taken out of bone
Term
Ruffled border and clear zone
Definition
Zone of osteoclast contact with bone; actin in clear zone around ruffled border sealing region to bone surface
Term
Osteoclast composition
Definition
Eosinophilic (much protein), increased MT, rER, Golgi, lysosomes; releases acid to dissolve mineral crystals
Term
Woven bone
Definition
Immature, primary; area of rapid growth; only in adults during fracture repair or pathology, non-lamellar; can become cortical or cancellous, replaced by lamellar bone; random fibers and mineral; highly cellular; more ground substance, more porosity, less dense
Term
Lamellar bone
Definition
Mature, throughout life; sheets of aligned collagen (lamellae), found in cancellous and compact tissue; slow deposition, more organized, stronger, resist loads better
Term
Circumferential lamellae
Definition
Linear sheet encircling bone; outer lamella deep to periosteum, inner lamella near endosteum
Term
Haversian system
Definition
Layers of lamellae around Haversian canal; long tubular, branching, longitudinal through bone, formed from secondary remodeling; only in compact bone where internal blood supply needed; increases with age
Term
Cement line
Definition
Border of Haversian system; osteocytes communicate via canaliculi inside cement lines but cannot cross through
Term
Haverisan canal
Definition
Vascular channel through center of osteon with blood vessels and nerves
Term
Volkmann's canals
Definition
Vascular channel linking neighboring osteons' Haversian canals
Term
Interstitial lamellae
Definition
Remnant of old Haversian system, result of remodeling
Term
Periosteum
Definition
Cover exterior of bone except articular surface, continuous with tendon CT and skeletal muscles; appositional growth
2 layers: outer fibrous layer and inner cellular layer
Term
Endosteum
Definition
thin 1 layer CT over interior surface of bone, cellular
Term
Cartilage overview
Definition
External surface of bone at joint (articular surface at synovial/cartilagionus joint); extensive, semi-rigid ECM, mostly avascular, interstitial AND appositional growth; much ground substance and water, viscoelastic
Term
Cartilage function
Definition
Support/flexible soft tissue, skeletal precursor; cushion and move joints
Term
Cartilage types
Definition
Hyaline (most, type II), elastic (Type II + elastic), fibrocartilage (type I)
Note: types are Collagen types present
Term
Perichondrium
Definition
dense, Type I collagen, surround cartilage structures (except articular surface of joints, fibrocartilage areas), BV present
Outer fibous layer, inner cellular layer; appositional growth through chondroblasts near here
Term
Chondrogenic cells
Definition
Inner layer of perichondrium, committed stem cells differentiating into chondroblasts
Term
Chondroblasts
Definition
Inner layer of perichondrium, secrete cartilage matrix until completely surrounded (appositional growth)
Term
Chondrocyte
Definition
Chondroblast completely surrounded by matrix, located in lacunae; mitosis continues and forms up to 8 cells in isogenous group; active basophilic and clear areas
Term
Isogenous group
Definition
Small grouping of up to 8 cells from one parent in (hyaline) cartilage with territorial matrix in between
Term
Chondrocyte ultrastructure
Definition
Irregular border and filipodia (young); standard secretory cells (older), heterochromatic with many accumulations of lipid, glycogen (aging) - distinguish by location at end of bone tissue
Term
Cartilage ECM
Definition
Sulfated GAGs, basophilic (PAS +ve), fibers, ground substance, glycoproteins (chondronectin); sulfated GAGS make matrix basophilic (eosinophilic if not preserved well)
Term
Territorial and Interterritorial matirx
Definition
Territorial is more recent deposit, closer to chondrocytes, higher [GAG], less water, near lacuna
Term
Cartilage Ground substance
Definition
Sulfated GAGs, proteoglycan, hyaluronan, aggrecan aggregates (more extensive than in bone)
Term
Cartilage water
Definition
60-80% weight, bind aggrecan aggregates, provide more resilience and resist compression
Term
Derivative of cartilage
Definition
Most mesoderm except branchial arch from neural crest ectoderm
Term
Cartilage canals
Definition
Nutrition source for very rapidly growing cartilage
Term
Cartilage appositional growth
Definition
Inner surface of perichondrium, chondroblasts secreting matrix to periphery
Term
Cartilage interstitial growth
Definition
Mitotic divisions and matrix made by chondrocytes enclosed in matrix; leads to rapid length growth without disrupting articular suface - essential for endochondral ossification
Term
Cartilage degeneration
Definition
Deep in cartilage, no sufficient access to nutrients in perichondrium; atrophy, more water, calcification, arthritic changes at joint surfaces(?)
Term
Cartilage regeneration
Definition
Very limited; produce matrix too slow to repair damage; can be replaced by vascularized CT in acute injuries or remain as fibrous tissue
Term
Hyaline cartilage
Definition
Most common, type II collagen, glassy, non-fibrous matrix
Fetal and growing skeleton pre-ossification, persist at growth plate until skeletal maturity, articular surface of synovial joint, respiratory tract, medial end of ribs
Term
Elastic cartilage
Definition
Most cellular, larger cells than hyaline; yellowy and opaque, elastic fibers and sheets seen with H&E
Eustachian tubes, external auditory canals, larynx, epiglottis
Term
Fibrocartilage
Definition
Type I collagen, no perichondrium, near dense CT, fibrous-looking matrix; isogenous clusters of columns; great tensile strength
Annulus fibrosis, tendons around bony prominences, symphysis pubis, ligaments, joint menisci; places with compressive and tensile stresses in different directions
Term
Osteoarthritis
Definition
First found by changed structure of articular cartilage; surface becomes undulating w/ shred-like projections; loss of cartilage affects underlying bone; chronic inflammation affects synovial fluid and membrane
Term
Joint
Definition
Arthrosis, meeting place between bones
Term
Fibrous joint
Definition
Least mobile, 2 bones united by fibrous CT, essentially fixed
Term
Fibrous joint examples (3)
Definition
Sutures, Syndesmoses, Gomphoses
Term
Suture
Definition
Joint between bones of skull - squamous or serrated
Term
Syndesmoses
Definition
Sheath of fibrous tissue (e.g. interosseous membrane)
Term
Gomphoses
Definition
Fibrous articulation between tooth and alveolar bone via Sharpey's fibers
Term
Cartilaginous joint types (2)
Definition
Synchondroses and Symphyses; more mobile than fibous
Term
Synchondroses
Definition
Primary cartilaginous joint - temporary during growth (growth plates); hyaline cartilage replaced once growth ceases by synostosis (bony union) of epiphysis and diaphysis in long bone
Term
Synostosis
Definition
Bony union to replace hyaline cartilage in long bone - union of epiphysis and diaphysis
Term
Symphyses
Definition
Secondary cartilaginous joint; bone surface covered by fibrocartilage, then hyaline cartilage; limited movement, fuse with age (e.g. intervertebral disk)
Term
Synovial joint Part 1
Definition
Diarthroses - bony articulation in contact, not continuity with one another; low friction due to synovial fluid; articular surface with hyaline cartilage, no nerves or BVs, arched collagen configurations; fibrous joint capsule cuff around articular end
Term
Synovial membrane
Definition
Lines non-articular parts of synovial joint; contains A cells (remove debris) and B cells (secrete components of synovial fluid)
Term
Synovial joint part 2
Definition
RIchly innervated, rich blood supply, many anastomoses; bursae around joints near areas where tendons insert into bones
Term
Transition form articular cartilage to bone
Definition
Bone --> Calcified cartilage --> Radial layer --> Transitional layer ---> Tangential layer; orientation of cells and fibers varies (transverse near articular surface, longitudinal/perp in radial layer)
Term
2 types of bone formation and original derivative
Definition
Intramembranous ossification, endochondrial ossification; both formed from mesenchyme
Osteoid --> woven bone --> lamellar bone
Term
Intramembranous officiation (I.O.)
Definition
Directly from mesenchyme; formed by periosteum of all bones; occurs in middle (diaphysis) of bone - differentiation into osteoblasts
Flat bones of skeleton (skull, face), non-weight bearing, low compressive strain
Term
I.O. Vascularization and condensation
Definition
Vascularization and condensation of vascular tissue at primary ossification center; begins at 8 weeks gestation; mesenchymal cells aggregate
Term
I.O. Differentiation and deposition
Definition
Mesenchymal stem cell --> osteoprogenitor --> osteoblast --> lay down osteoid --> mineralize into woven bone spicules --> larger trabeculae; nearby mesenchymal cells proliferate and differentiate
Term
I.O. Bone modeling
Definition
Bone develop around BV, BV bring in osteoclast to shape bone as size increase, osteoblasts lay down lamellar bone, inside of flat bone maintained as cancellous bone, apposition from periosteum forms outer cortical surfaces; mesenchyme membranes retained as inner and outer periosteum
Term
Endochondral Ossification
Definition
Cartilaginous precursor; allow for growth in length without disrupting joint surface; begin in week 12 gestation, continue into adulthood
Term
E.O. Primary ossification center
Definition
Chondrocytes stop proliferating, hypertrophy, make collagen type X, induce perichondrium cells to become osteoblasts which form bony collar; chondrocytes lose blood supply (bony collar) and die, matrix calcifies, secretion of signaling factors
Term
E.o. Primary ossification - osteogenic bud
Definition
Enters vacated area from dead chondrocytes, osteoprogenitor cells make osteoblasts, which start depositing bone; mixed spicules of woven bone and calcified cartilage; zone of ossification spreads in both directions
Calcified cartilage = basophilic; new bone = eosinophilic
Bud persists as nutrient artery
Term
Secondary ossification center
Definition
Form at both epiphyses of forming bone; start with hypertrophy of chondrocytes, proceed in same method as primary ossification; complete ossification except at growth plate and articulate surface; bone formed on diaphyseal side of growth plate
Term
Physis
Definition
Growth plate, site of continued lengthwise interstitial growth of cartilage; persists until the epiphyseal plate ossifies after puberty to end bone growth
Term
Zones of secondary ossification
Definition
Zone of reserve cartilage, Zone of proliferation, Zone of hypertrophy, Zone of calcification, Zone of ossification
Term
Zone of reserve cartilage
Definition
Cartilage with some mitotic activity, mostly resting
Term
Zone of proliferation
Definition
Fast chondrocyte proliferation, form isogenous rows parallel to growth
Term
Zone of hypertrophy
Definition
Chondrocytes mature, hypertrophy, start to die
Term
Zone of calcification
Definition
Chondrocytes dead, matrix becomes calcified
Term
Zone of ossification
Definition
Osteoprogenitor cells invade, become osteoblasts, deposit bone, mixed spicules, resorbed or replaced by lamellar bone
Term
Bone modeling
Definition
Coordinated deposition and resorption of bone at different sites along surface; reshape bone in response to stress; higher rate during growth and development, slower in adults
Term
Metaphyseal "waisting"
Definition
Old metaphysis incorporated into diaphysis
Term
Diaphyseal enlargement and drift
Definition
Increase bone diameter; alter curvature of bone
Term
Secondary remodeling process
Definition
Cutting cone by osteoclasts, closing cone by osteoblasts; concentric ring deposited from outside edge towards center; BV and nerves enter to form Haversian canal
Term
Secondary remodeling in cancellous bone
Definition
Only occurs at trabeculae surface; no Haversian canals, osteoclast and osteoblast activity at the same location
Term
Factors that increase osteoclast activity
Definition
PTH, Thyroid hormone, glucocorticoids
Term
Factors that decrease osteoclast activity
Definition
Osteoprotegerin, Estrogen, Calcitonin
Term
Increased PTH (bone)
Definition
Causes osteoblasts to stimulate maturation of osteoclasts by release of M-CSF and RANK ligand (RANKL)
Term
RANKL
Definition
RANK ligand secreted by osteoblast, interacts with RANK receptor on osteoclast to stimulate differentiation and maturation
Term
Decreased PTH (bone)
Definition
Osteoblast release osteoprotegerin (OPG), binds RANKL to prevent interaction with RANK receptor, "decoy", decrease osteoclast differentiation
Term
Estrogen (bone)
Definition
Increase osteoblast production of OPG, prolong life of osteoblast
Term
Calcitonin (secondary remodeling)
Definition
Directly inhibit osteoblast activity; made by parafollicular cells of thyroid gland
Term
Vitamin D (bone)
Definition
Necessary for bone mineralization
Term
Growth hormone (bone)
Definition
Stimulate bone formation
Term
Thyroid hormone (bone)
Definition
Increase osteoclastic resorption if levels too high
Term
Glucocorticoids (bone)
Definition
Increase bone resorption, increase bone formation
Term
Bone aging and osteoporosis
Definition
Abnormal coupling of resorption and deposition in secondary remodeling; sensitive to hormonal levels (reduced estrogen after menopause); can be too much resorption leading to weak, porous bones; increased mineralization (brittle)
Term
Fracture repair phases (4)
Definition
Inflammation, Soft Callus, Hard Callus, Secondary Callus (Callus reduction)
Fracture repair same independent of cause unless non-union
Term
Fracture types
Definition
Closed, open (protrude through surface), comminuted (several pieces), greenstick (bone bows, not completely disrupted)
Closed heals fastest, break often incomplete in children (greenstick)
Term
Fracture repair: Inflammation
Definition
BVs rupture throughout, blood flows into fracture forming hematoma which coagulates and stabilizes; osteogenic response due to periosteum disruption; first 4 days, overlap with soft callus stage
Term
Fracture repair: Soft Callus Stage
Definition
Blood clot permeated with fibrous CT and cartilage, repair cells; clot becomes fibrous temporary callus to tie bone fragments together; bone vessels regrow, both types of ossification occur for 3-4 weeks
Term
Fracture repair: Hard Callus Formation (Primary Callus)
Definition
Woven bony callus; formed by intramembranous ossification (external callus-osteoblasts differentiate at perichondrum) and endochondrial ossification (internal callus); ~6 weeks to form, noticeable years later; BV supplying callus allow osteoclasts to enter and resorb dead bone fragments; 2-3 months until bony union forms
Term
Fracture repair: Secondary Callus (callus reduction)
Definition
Woven bone becomes lamellar by intracortical remodeling with osteons forming; remove excess bone from exterior of periosteal collar, restore medullary cavity; healing time average is 1+ year depending on many factors
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