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MSK and Skin
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Hyaline Cartilage
Most common type
Avascular
ECM contents: TYPE 2 COLLAGEN, chondroitin sulfate, keratan solfate, hyaluronic acid, chondronectin
Found the most throughout our body
Elasic Cartilage
Type 2 collagen + elastic fibers
Avascular
requires special stains for elastic fibers (ex. Verhoeff, Silver Stain)
ECM Content: Elastic Fibers + Same as Hyaline cartilage (TYPE 2 COLLAGEN, chondroitin sulfate, keratan solfate, hyaluronic acid, chondronectin)
Found in ear and nose
Fibrocartilage
dense network of type 1 collagen fiber bundles
Avascular
intermediate between dense CT and hyaline
Found in intervertebral discs and some ligaments
Chondroblast
Immature precusor cell of cartilage
Chondrocyte
Main cell of cartilage
Lacunae
Space/cavity of matrix where condrocyte is located
Perichondrium
Sheath of dense CT surrounding cartilage (contain blood, nerves, lymphatics)
Chondrogenesis
making cartilage—mesenchymal cells turn into chondrocytes that build a gel-like matrix
Condense: Mesenchymal cells gather into a tight nodule
Differentiate: They become chondroblasts/chondrocytes (driven by SOX9)
Build matrix: Cells secrete type II collagen + proteoglycans forming cartilage
Mature & expand: Chondrocytes sit in lacunae and proliferate
Interstitial Cartilage Growth
Mitotic division of pre-existing chndrocytes
Appositional Growth
Differentiation of perichondrial cells
Bone Matrix
Inorganic Portion
mostly hydroxyapatite crystals (65% of dry weight)
Organic Portion - 95% Type 1 Collagen (some type 5)
Chroitin sulfate, keratan sulfate, hyaluronic acid
Periosteum
Layer of non-calcified connective tissue
Surrounds the outer bone except at the sunovial articulations and muscle attachments
Contain osteoprogenitor cells and osteoblasts
Sharpey fibers
attach periosteum to bone surface
Endosteum
Thin layer of connective tissue lining the marrow cavities of bone
houses osteoprogenitors, osteoblasts, and osteoclasts for bone remodeling and repair
Osteoblasts
Derived from osteoprogenitor cells
Stellate shaped but can be cuiboidal near bony surface
Found at surface of bone matrix
Will appear basophilip during active phase
Main Role = Osteoid Deposition
Have parathyroid hormone receptors
Communicate via gap junctions
Become entrapped in a lacunae surrounded by matrix > osteocyte
Osteocytes
Mature cells of bones (entrapped in their own lacunae)
Main Role = maintenance of the bone matrix
Abundant cell processes extend in canaliculi
communicate via gap junctions
Abundant Heterochromatin
Osteoclasts
Derived from the mononuclear phagocyte system
Large, motile, multinucleated
Have calcitonin receptors on their cell surface
Signals from osteoblasts stimulate osteoclasts
MCSF - stimulates Osteoclats to undergo mitosis
RANKL - causes OC to become multinucleated and begin bone resorption (breakdown of bone)
Canaliculi
Related to Osteocytes, nutrient/waste exchange and cell-to-cell signaling
Osteoprotegerin
Signal from Osteoblats to Osteoclasts
inhibits osteoclasts by blocking RANKL receptors
Macroscopic Bone Classification
Spongy (trabecular or Cacellous)
bony spicules
surrounded by marrow
Traveculae lined by osteoblasts on both sides
Surrounded by compact bone
Compact (Dense)
no traveculae or marrow cavity
Haversian system (osteon)
Microscopic Bone Classificaiton
Primary
Immature bone
Many osteocytes and type 1 collagen
Low mineral content
First bone laid down during fetal growth or repair
Secondary
Mature Bone (lamellar)
Calcified matrix arranged in layers
Osteocytes in lacunae
Haversian System (Osteon)
the basic unit of compact bone
concentric rings (lamellae) of hard bone wrapped around a central canal with blood vessels and nerves
Osteocytes sit in spaces between the rings and connect through tiny canals (canaliculi)
Interstitial Lamellae
thin, irregular layers of old lamellar bone that fill the spaces between osteons in compact bone
Intramembranous Ossification
Type of Osteogenesis
Mesenchyme > Osteoblasts > Osteoid > Flat Bone Formation
Mesenchyme condensates near vascular centers
Osteoblants begin making osteoids
Calcification leads to trabeculae formation
Traveculae create spongy bone and Periosteum + endosteum develop
Lamellae are formed
Endochondral Ossification
Type of Osteogenesis
Hyaline cartilage mold replaced by Bone Matrix
Long Bone Formation
length growth at the epiphyseal (growth) plates
Zone of Reserve Cartilage
1st zone of Epiphyseal Growth Plate
Inactive cartilage wating to enter mitosis
Zone of Proliferation
2nd zone of Epiphyseal Growth Plate
Cartilage undergoing mitosis
Zone of Hypertrophy
3rd zone of Epiphyseal Growth Plate
Chondrocytes undergo hypertrophy
they grow getting closer to the zone of calcified cartilage then die
Zone of Calcified Cartilage
4th zone of Epiphyseal Growth Plate
Chondrocytes die, osteoblasts begin depositing osteoid on their remains
Zone of Resorption
5th zone of Epiphyseal Growth Plate
Bone deposition and remodeling begin
Matrix Calcification
Osteocalcin secreted by osteoblasts bind Calcium
Osteoblasts secrete alkaline phosphatase
The vesicles housing alkaline phosphatase serve as the foci for the formation of hydroxyapatite crystals (exclusive to bone)
Process continues until collagen is embedded in calcified material
Calcium Mobilization
Mainly resorbed from spongy bone
PTH: inhibits osteoblasts causing them to secrete osteoclasts stimulating factor
Matrix is broken down and calcium is delivered to interstitial fluid (when Ca is low)
Fracture Repair
When bone breaks, blood vessels break too causing hemmorhages
Osteocytes die locally
blood clots
granulation tissue formed from fiibroblasts
Callus formed with cartilage bars
bony sleeve surrounds callus
blood vessels enter callus
Spongy bone replaces callus which is then replaced with compact bone
excess bone resorbed
bone returns to normal shape
Glial Cells
Support and protection of the neurons
short processes
Neruons
Structural and functional unit of the nervous system
From Neuroectoderm (CNS) or neural crest (PNS)
Cell Body - trophic center of the neuron
several dendrites - shorter processes that transmit impulses toward cell body, receive stimulus at synapses
Axon - transmits impulses away
Multipolar Neuron
Most abundant
1 axon, 2 dendrites
Dendritic Arbor - very branched dendritic processes
Bipolar Nueron
Rare
1 Dendrite 1 Axon
Special sensory system (retina, olfactory, inner ear)
Unipolar Neuron
Spinal ganglia
Longer branch of dendrites that go to the periphery and to the CNS
Anaxonic Neuron
Lacks true axon
present in the CNS
does not produce action potential
regulates local electrical charges of adjacent neurons
Axosomatic Synapse
Axon connected to cell body to send signals
Axodendritic Synapse
Axon sending signals to a dendritic spine
Axoaxonic Synapse
Axons sending signals to other axons
Excitatory Neurotransmitters
Causes membrane depolarization (Na+ mediated)
ACh, Glutamate, Serotonin
Inhibitory Neurotransmitters
Causes membrane hyperpolarization (Cl- mediated)
GABA, glycine
Anterograde Transport
From the cell body > Synapse
Kinesin motor ( - > + )
Retrograde Transport
From synapse > cell body
dynein motor ( + > - )
Oligodendrocytes
insulates CNS axons
allows faster action potential propagation
derived from neuroectoderm
Each oligodendrocyte myelinates up to 30 CNS axons
mostly in glial cells in white matter
Oligodendrocytes Nissil Stain
small nuclei with dark chromatin and a little cytoplasm
Oligodendrocytes H & E stain
fried egg appearance
Astrocytes
multiple processes going all around
Provide physical and metabolic support
maintenance of blood-brain barrier
largest glial cell
nuclei: salt and pepper pattern
Intermediate filament = GFAP
Astrocytes GFAP Stain
star shaped cell
Astrocytes H&E stain
irregular, potato shaped nuclei
Ependymal Cells
Columnar cells that line the ventricles of the brin and central canal of spinal cord
Single layer of cuboidal to columnar cells
clear cytoplasm, rounded nuclei
Has both microvilli and cilia
Microglial cells
phagocytes of CNS
scavengers of the CNS responding to tissue damage
part of the mononuclear phagocyte system
Schwann Cells
Surrounds and insulates PNS axons
allows for faster action potentials
saltatory conduction - one node of Ranvier to the next
one per axonal segment
Satellite Cells
Structural and metabolic support for neuron cell bodies
Electrically insulates PNS cell bodies
around the cell body of the PNS neuron
Indistinct cell boundaries
Gray matter
in the periphery of the brain / Central part of spine
most neuronal perikarya - cellular portion
White Matter
Central part of the brain / Periphery of spine
wher eaxons are concentrate
Cerebellar Cortex Molecular Layer
Thick outer layer with a lot of neuropils and scattered neuronal cell bodies
Cerebellar Cortex Purkinjie Cells
Thin and large
dendrites extend throughout the molecular layer as a branching basket of nerve fibers
Axons through granular layer
Cerebellar Cortex Granular Layer
thick inner containing small dense neurons
Spinal Cord Anterior Horns
gray matter
contain cell bodies of large motor neurons
make up the ventral roots
Spinal Cord Posterior Horns
Contain interneurons which receive sensory fibers from neurons in the spinal ganglia
Dura Mater
dense irregular connective tissue
organized as an outer periosteal layer and an inner meningeal layer
Arachnoid Meninges
Shet of connective tissue in contact with dura mater
loosely arrange trabeculae composed of collagen and fibroblasts
Arachnoid Villi - penetrate the dura mater and enter blood filled venous sinuses - function in releasing excess CSF to blood
Pia Mater
flattened, mesenchymal derived cells closely applied to entire surface of CNS tissue
Blood Brain Barrier
Prevents circulating blood substances from reaching CSF/CNS
More functional barrier than most tissue
tight junctions, basement membrane, astrocyte foot processes
Cerebrospinal fluid
made by ependymal cells of choroid plexus
consists of ependyma and vascularized pia mater, projecting many thin folds
CSF is reabsorbed by arachnoid granulations and drained into dural venous sinuses
Myelination Steps
Contact & Recognition – The oligodendrocyte (CNS) or Schwann cell (PNS) recognizes and attaches to the axon.
Membrane Wrapping – The glial cell membrane begins to spiral around the axon multiple times.
Compaction – The layers of membrane squeeze together tightly, expelling cytoplasm and forming a dense myelin sheath.
Maturation – Nodes of Ranvier are established, and the myelin sheath stabilizes to enable fast saltatory conduction.
Small Cells
Not typically fully myelinated
in close relation with schwann cells, but no full myelinated layers wrapped around
Skeletal Muscles
Long, cylindrical
multi nucleated - located in periphery of the cell
striations caused by alternating thin and thick filament
Fascicle
Bundle of muscle fibers
Epimysium
Connective tissue arround muscle
Perimysium
Connective tissue around fascicles
Endomysium
connective tissues around individual myofibers
Sarcomere
A sarcomere is the repeating structural and functional unit of a myofibril, extending from one Z-disc to the next. It is responsible for muscle contraction.
SR/T-Tubule System
SR - Calcium Reservoir
T-Tubules - Invaginations of sarcolemma
Two SR cisternae flanking a section of t-tubule = Triad
exclusive to skeletal muscle
found at A-I band junction
Muscle Contraction Steps
ACh released at NMJ
ACh binds to receptors on sarcolemma
depolarizing wave spreads via T-tubules
Depolarization opens Ca2+ channels in SR
Ca2+ enters the sarcoplasm
Myasthenia Gravis
autoimmune disorder in
antibodies block or destroy ACh receptors at the neuromuscular junction, leading to impaired transmission of nerve signals to muscles
symptoms: droopy eyelid
Slow Type 1 Muscle Fibers
Slow contractions, prolonged time, little fatigue
rich in mitochondria and myoglobin (dark red appearance)
Fast Type 2b Muscle Fibers
rapid short term contractions
anareobic metabolism, few mitochondria
rapid fatigue
Z-discs (lines)
define the boundaries of a sarcomere
anchor actin
M-line
center of the sarcomere
stabilizes and anchors myosin
Fast Type 2A
oxidative-glycolytic
Intermediate of Type 1 and 2A
Good balance between fast and slow
A Band
Dark region
contains entire length of thick filaments
I-Band
light region
only contain thin filaments and span between two sarcomeres
H-Zone
central part of the A-Band with only thick filaments
Duchenne’s Muscle Dystophy
Defective Dystrophin
skeletal Muscle fibers start to lose structure
Mostly boys
Cardiac Muscle Features
Striations
Intercalated Discs
Sparse SR
Underdeveloped T-tubules
T-tubules and some SR form a complex - dyad
can be found at the Z - disc
abundant large mitochondria
Gap junctions!
Smooth Muscle Features
no sasrcomere
rudimentary SR
myosin shape differs
dense boies
Contraction requires binding of Calcium to Calmodulin - activation of MLCK
Caveoli and Gap junctions!
Skeletal Muscle Regeneration
limited capacity for regeneration
satellite cells may differentiate into skeletal muscle cells
Cardiac Muscle Regeneration
no satellite cells, no capability for regeneration
hear attacks - fibroblasts - scar formation
Smooth Muscle Regeneration
High capability for regeneration
repairs itself