Exam 3 Week 1 Flashcards
2 Main Components of Cartilage (and their sub-components):
- ECM = 95% of Cartilage
a. Collagen is 40% of the ECM in it
b. Major component is GAG’s - Chondrocytes = 5% of Cartilage
3 Main Types of Cartilage:
- Hyaline
- Elastic
- Fibrocartilage
Locations of Hyaline Cartilage:
-
LEFT CAN*
1. Laryngeal Cartilages
2. Epiphyseal Growth Plate
3. Fetal Skeleton
4. Tracheal/Bronchial Rings
5. Costal Cartilages
6. Articular Surfaces of Long Bone
7. Nose
Describe the 2 Main components of Hyaline Cartilage:
-
Both originate from Mesenchyme*
1. Chondrocytes: “Owl’s Eye” Appearance”
2. Chondroblasts
ECM components of hyaline Cartilage:
- TYPE 2 Collagen
2. GAG’s and Glycoproteins
Define Perichondrium:
- Connective Tissue covering entire cartilage
- Made up of 2 Layers:
a. Outer FIBROUS: Which contains:
* Fibroblasts
* Type 1 Collagen/ ECM
* Blood Vessels
b. Inner CELLULAR Layer: Chondrogenic, contains chondroblasts/chondrocytes
How can the perichondrium’s fibrous layer be identified histologically?
The Type 1 Collagen it produces will stain PINK
Main Difference between the Perichondrium and the ECM of Cartilage:
The ECM is AVASCULAR and receives its nutrient supply only from the blood vessels in the fibrous perichondrium via DIFFUSION.
Describe the location and structure of chondroblasts and chondrocytes in the Chondrogenic Layer of the Perichondrium:
- Chondroblasts: Derived from Chondrogenic Cells IN the chondrogenic layer. They synthesize ECM and are ELONGATED parallel (sideways) to the cartilage surface.
- Chondrocytes: Derived from Chondroblasts. They become more OVOID and ROUNDED and are below the chondroblasts.
The space occupied by a chondroblast is called a _______.
Lacunae
What part of the perichondrium causes interstitial growth?
Chondrocytes: They divide to form groups of 4-8 chondrocytes called ISOGENOUS GROUPS (aka A Cell Nest)
Describe Chondrocytes as they appear in SEM:
- HIGH RER/Golgi content (for prod. of ECM)
- Irregular Membrane
- Euchromatic Nucleus (for prod. of ECM)
- Collagen fibers extending (being produced) from around the cell membrane
- Glycoproteins GLUING the cell to the ECM
Describe the 3 MAIN components of cartilage GROUND SUBSTANCE of the ECM:
- MAG’s (Multi-Adhesive Glycoproteins): Adhere the chondrocytes/chondroblasts to the ECM.
- Proteoglycans: HYDRATE the ECM by drawing in water to give RESILIENCE TO PRESSURE
- Intercellular Water
Describe why collagen fibers of Hyaline Cartilage are NOT visible in Light Microscopy:
- Type 2 Collagen fibers have the SAME REFRACTIVE INDEX as the ground substance surround them
- Therefore they have a “glassy” appearance, which is which it is called Hyaline Cartilage
Describe the 3 ways Matrix is labelled with respect to Isogenous Groups:
What is unique about these types of Matrix?
- Capsular Matrix: Immediately around a cell
- Territorial Matrix: Around the ENTIRE Isogenous group
- Inter-territorial: In between different groups
* These are HIGHLY BASOPHILIC and METACHROMATIC because they have INCREASED GAG’s and DECREASED COLLAGEN
How can capsular matrix best be stained?
PAS (Periodic Acid Schiff)
How do Proteoglycans draw water into the ECM of hyaline cartilage?
The GAG’s on them are HIGHLY SULFATED which makes them very hydrophilic (AND HYALURONIC ACID DOES TOO)
Difference between Appositional and Interstitial Growth:
- Appositional: Increases THICKNESS (width from top to bottom) of cartilage
- Interstitial: Increases LATERAL LENGTH of cartilage, but ONLY occurs in young cartilage (FROM WITHIN)
List hormones that have a POSITIVE and NEGATIVE effect on growth of cartilage:
- Stimulatory:
a. Growth hormone
b. Testosterone
c. Thyroxine - Inhibitory:
a. Estradiol
b. Hydrocortisone
Old cartilage is not very good at _______, and therefore it will _______.
- Regenerating
2. Be Calcified into BONE
Describe Articular Cartilage:
- Formed from REMNANTS of FETAL SKELETON cartilage template from developing bone
- Has NO PERICHONDRIUM –> So it’s in contact with bone directly (only ECM in between)
- Has 4 DISTINCT Layers:
a. Tangential Layer (superficial)
b. Transitional Layer (intermediate)
c. Radial Layer (deep)
d. Calcified Cartilage
What is unique about the radial layer of articular cartilage?
It is PERPENDICULAR to the surface
Describe Osteoarthritis:
Obesity leads to increased PRESSURE on the articular cartilage –> Causing DEGENERATION of it –> Which leads to bone-on-bone contact
How can elastic cartilage ECM be identified distinctly from hyaline cartilage histologically?
- ELASTIC fibers will stain YELLOW in the ECM (with Verhoeff’s-Van Gieson Stain)
- These fibers form a HONEYCOMB APPEARANCE
What is the function of Elastic cartilage and what property of it allows this function?
- To provide FLEXIBILITY and support
2. DESMOSINE and ISODESMOSINE of the elastic fibers allow this function
A unique function of Fibrocartilage:
Attachment of LIGAMENT to BONE
What is a unique identifiable feature of Fibrocartilage histologically?
The isogenous groups are LINEAR
What is Fibrocartilage ALWAYS associated with?
Hyaline Cartilage and OTHER FIBROUS TISSUES (it does not occur alone)
How are the collagen fibers arranged in fibrocartilage?
PERPENDICULAR to the direction of STRESS
2 Main Components of Bone:
- Cells
2. Calcified ECM
How does bone appear histologically?
Appears as COTTON CANDY-like “swirls” with “dots” (cells) dispersed between the swirls
Describe the ECM of bone:
- —->ORGANIC PORTION:
1. 90% Collagen (MAINLY TYPE 1, but also type 3,5,11,13)
2. 10% Non-Collagenous Proteins -GROUND SUBSTANCE
a. Proteoglycans
b. Glycoproteins
c. Growth Factors/Cytokines
d. Bone-Specific Proteins - BOTH ground substance and collagen become mineralized to form bone*
- —->INORGANIC PORTION:
1. Hydroxyapetite Crystals (Calcium Phosphate)
2. Trace Minerals (bicarb, citrate, mg, etc.)
Describe the differentiation of bone cells:
Osteoprogenitors –> OsteoBLASTS –> Osteocytes
Describe the appearance of osteoclasts:
HUGE, MULTI-NUCLEATED cells that are a type of monocyte
Osteogenic Cells:
- Derived from EMBRYONIC MESENCHYME STEM CELLS
- Spindle-shaped
- Found in the PERIOSTEUM and ENDOSTEUM –> Differentiate into Osteoblasts
Osteoblasts:
- BASOPHILIC
- Either appear as a CUBOIDAL LAYER (if secreting) or as a FLATTENED LAYER (if not secreting)
- CYTOPLASMIC PROCESSES allow them to contact other cells surrounding them
- HIGH RER/Golgi
- PAS (+) granules in cytoplasm –> GAG precursors that will be secreted into the ECM
- Cell rests inside LACUNAE
- Cytoplasmic Processes rest inside CANALICULI
Osteocytes:
- MATURE bone cells
- Cytoplasmic Processes are narrow and long –> Have GAP JUNCTIONS at their ends between cells
- HIGH HETEROCHROMATIN and LOW RER/Golgi
How will Osteoblasts, Osteocytes, and Osteoclasts be identifiable from one another histologcally?
- Osteocytes: FILL entire Lacunae
- Osteoblasts: DON’T QUITE FILL lacunae completely
- Osteoclasts: Surrounded by CALCIFIED matrix that forms a gap between the cell and its lacunae
Osteoclasts:
- HUGE, MULTI-NUCLEATED cells
- Reside in HOWSHIP’S LACUNAE: Depressions on the BONE SURFACE
- Have 3 Distinct regions:
a. Ruffled Border: Finger-Like invaginations of the cytoplasm around the cell
b. Clear Zone: Immediately inside the border, has MICROFILAMENTS to anchor the cell to the BONE SURFACE to isolate activity
c. Basal Region: Houses the organelles and multiple nuclei of the cell
Why does the osteoclast possess a ruffled border?
To INCREASE SURFACE AREA for bone resorption
How do osteoclasts resorb bone?
- They release LYSOSOMAL ENZYMES and H+ ions into the ECM that de-calcify and break down bone
- Then the material is taken back up and degraded completely
Bone-Lining Cells:
- Flat Cells with little cytoplasm and scant organelles –> DERIVED FROM OSTEOBLASTS (essentially an alternate fate to an osteoblast becoming an osteocyte)
- Found on the INNER and OUTER surfaces of NON-REMODELING BONE (i.e. They are PERIOSTEAL and ENDOSTEAL cells)
- Function in maintenance/nutrition of underlying cells
- Regulate movement of Ca2+ and PO4- in/out of cells
Periosteum/Endosteum:
- Non-Calcified CT layer that covers external/internal surfaces of bone
- NOT ARTICULAR SURFACES
- Composed of 2 Layers:
a. Outer Fibrous: Mostly COLLAGEN (dense) and Blood Vessels contained within this layer
b. Inner Cellular: Mostly Osteoprogenitors (Periosteal and Endosteal Cells)
What allows bone growth/remodeling?
- Elongation = INTERSTITIAL GROWTH of cartilage at the EPIPHYSEAL GROWTH PLATE
* **Growth of CARTILAGE, NOT BONE***** - Width increase = Appositional Growth of osteoprogenitors in the periosteum (bone ONLY exhibits appositional growth BECAUSE: It’s calcified so internal growth cannot occur because osteocytes have no room to divide)
Main Concept of Bone Remodeling:
It is a BALANCE between osteoblast and osteoclast activity
Immature Bone:
- AKA Primary or WOVEN bone
- Mostly osteocytes and IRREGULARLY arranged collagen
- Low Mineral Content (not very calcified)
- Replaced by MATURE bone, except in…
a. Tooth Sockets
b. Skull Sutures
c. Tendon Insertion Sites
Mature Bone:
- Secondary or LAMELLAR bone
- Made up of HAVERSIAN SYSTEMS (i.e. Osteons)
- Calcified Matrix is arranged in CONCENTRIC layers, SURROUNDING Haversian CANALS
- These canals carry blood vessels, nerves, and some loose CT in order to allow communication between osteons (which are immobile)
- Osteocytes (also in lacunae) are found BETWEEN or WITHIN concentric lamellae around a haversian canal
How are Osteons Arranged with respect to one another?
They line up along the LONG AXIS of the bone –> To support weight placed upon the bone
Differentiate between the 2 types of mature bone:
- Compact bone: DENSE AND HEAVY (possess numerous canaliculi for communication between haversian systems)
- Spongy (CANCELLOUS) Bone: Has inter-connected spaces within that are filled (in long bones) with:
a. RED MARROW (containing hematopoietic cells)
b. YELLOW MARROW (containing fat cells)
Why aren’t all haversian systems within a region of compact bone uniform in appearance?
Because the bone is CONSTANTLY undergoing remodeling throughout life
How are collagen fibers arranged within compact bone?
The fibers of ONE CONCENTRIC LAYER of an osteon will be PERPENDICULAR to the fibers of the following CONCENTRIC LAYER –> This is seen in an alternating fashion throughout all layers of the osteon to give TENSILE STRENGTH
What are Volkmann’s Canals?
- Canals that allow communication between ADJACENT OSTEONS, rather than HAVERSIAN CANALS which allow communication between Osteons with continuous haversian canals
- ALSO connect adjacent osteons to the:
a. Endosteum (at the marrow cavity)
b. Periosteum (on the oustide)
* ALLOWS for passage of nerves/vasculature through compact bone*
Outer/Inner Circumferential Lamellae:
- Form the circumference of THE ENTIRE BONE, not just lamellae surrounding a single osteon
- OUTER: Lines external surface of bone (but deep to the periosteum)
- INNER: Lines internal surface of bone (but deep to the endosteum)
Interstitial Lamellae:
REMNANTS of the old remodeled osteons (incomplete structure/no function) –> Lie BETWEEN newly laid, active osteons
Endosteum lines the _______, while periosteum lines the ______.
- INSIDE SURFACE OF HAVERSIAN CANALS
2. OUTSIDE SURFACE OF BONES
How are osteons formed?
- Longitudinal ridges along the PERIOSTEUM move AROUND A BLOOD VESSELS (which becomes the haversian canal) –> And FUSE to form an ENDOSTEUM (periosteum BECOMES endosteum = lining of the osteon)
- Osteogenic cells from the periosteum transform into OSTEOBLASTS –> Start producing ECM which forms ridges that close of periosteal capillaries as they meet
- Endosteum begins forming CONCENTRIC LAMELLAE
2 Types of Bone Development:
-
In BOTH processes, IMMATURE BONE FORMS FIRST*
1. Intramembranous: Dev. from WITHIN layer of CONDENSED MESENCHYME
2. Endochondrial: Via cartilage being replaced by bone
Intramembranous Bone Formation:
- Mesenchymal cells CONDENSE –> Form a Primary Ossification Center (Osteoprogenitor Cells form)
- There, Osteoblasts differentiate –> Start producing OSTEOID (bone matrix)
- They become trapped in their own secretion and become osteocytes
- Ossification Centers expand –> Form SPICULES as more osteoblasts aggregate
- Spicules FUSE –> Form TRABECULAE (the name for developing bone)
- Trabeculae fuse –> Form SPONGY BONE
- Simultaneously: Undifferentiated mesenchymal stem cells give rise to Bone Marrow Cells and blood vessels invade the area
- Periosteum forms (from surrounding mesenchymal cells)
- Ossification centers fuse to form mature bone
Ex: Flat Bones like the skull bones
Endochondrial Bone Formation:
- Outline of bone in HYALINE Cartilage
- In diaphysis –> Formation of Periosteum and Sub-periosteal bone collar for support
- Cartilage Matrix (including blood vessels) is CALCIFIED (locked into place)
- Formation of Periosteal Bud –> aka Primary Ossification Center (osteogenic cells and blood vessels)
- Sub-periosteal collar thickens –> Bone froms on the calcified cartilage
- Secondary Ossification Centers form in the epiphysis
- EPIPHYSEAL GROWTH PLATE forms between the primary and secondary ossification centers
- Fusion of Diaphysis and epiphysis MARROW CAVITIES
- Epiphyseal Plate continues to add new cartilage at EPIPHYSEAL end –> while it is replaced by bone at the DIAPHYSEAL end
- Epi. Growth Plate Disappears
Describe the 4 Distinct Zones of the Epiphyseal Growth Plate:
- Zone of Reserve Cartilage: Contains small, randmoly arranged inactive chondrocytes
- Zone of Proliferation: Contains rapidly mitotically dividing chondrocytes –> Making new cartilage
- Zone of Hypertrophy: Contains ENLARGED, STACKED chondrocytes with thin/little ECM between them
- Zone of Calcified Cartilage: Contains FUSED lacunae with calcified matrix and dead (apoptotic) chondrocytes
- Zone of Resorption: Bone is beginning to form here and osteoclasts resorb the calcified bone-cartilage complex
How can endochondrial bone formation be differentiated histologically from intramembranous bone formation?
In ENDOCHRONDRIAL –> Spicules will NOT appearentirely blue because there is some CARTILAGE still
i.e. Calcified Cartilage = Light Blue
Newly Formed Bone = DARK Blue
What does a bone fracture cause and how is it repaired?
- Causes: Hemorrhaging (because cells, matrix, and vessels are all damaged) –> Leads to CLOTTING
- Macrophages remove debris
- Fibroblasts proliferate in the Periosteum and Endosteum –> SURROUND the area internally/externally to ISOLATE THE INJURY
- This forms a FIBROCARTILAGE “Soft Callus”
- Intramembranous Bone Formation (by osteoblasts) allows elaboration of new bone –> i.e. HARD CALLUS
- AND Endochondrial Bone formation (differentiation of chondrocytes) allows new bone to be formed
- Callus is eventually resorbed and replaced by MATURE BONE as the process continues.
Why doesn’t Cartilage heal as well as bone?
Because it has NO BLOOD SUPPLY –> So it can’t receive the clotting nutrients necessary for repair to occur
Explain the role of bone in Calcium Balance:
- Bone possesses 99% of the body’s Calcium
2. Low Ca in diet = Bone RESORPTION
How does nutrition affect bone?
- Low Protein = Deficient Amino Acids –> Deficient Collagen production by Osteoblasts
- Low Dietary Ca OR Low Vitamin D (causing poor Ca absorption by small intestine) = Poorly Calcified bone –> RICKETS (in children) and OSTEOMALACIA (in adults)
Explain the role of Vitamins A, C, and D in bone maintenance:
- Vitamin A: Deficiency inhibits formation and growth. Excess accelerates ossification –> Makes bones fragile and results in SHORT STATURE
- Vitamin C: Deficiency results in SCURVY: Poor wound healing, bleeding gums, and poor bone repair
- Vitamin D: Deficiency inhibits formation and growth. Excess causes RESORPTION
* Must have NORMAL RANGE*
Parathyroid Hormone:
- Stimulates OSTEOCLASTS –> Released Ca to increase plasma levels
- Excess = Renders bone fragile and susceptible to fracture, may also lead to deposition of Ca in arterial walls and kidney
Calcitonin:
- Inhibits MATRIX RESORPTION –> Prevents Ca release into blood
Sex Hormones effect on Calcium:
- Influence bone growth and control CLOSURE of epiphyseal plate
- Excess: SMALL STATURE
- Deficiency: TALL STATURE
Growth Hormone effect on Calcium:
- STIMULATES epiphyseal growth
- In children, Deficiency = Dwarfism. Excess = Gigantism
- In Adults, Excess = Acromegaly
* i.e. Gigantism is the result of a PITUITARY TUMOR in childhood*
Osteoporosis:
- Primary Type 1: DECREASED ESTROGEN in menopausal women –> No longer able to inhibit osteoclasts –> Bone resorption occurs
- Primary Type 2: Increased resorption occurring in THE ELDERLY
- SECONDARY: Consequence of drug therapy with CORTICOSTEROIDS or of OTHER dosease processes –> Leads to resorption
What is the INORGANIC component of bone?
Hydroxyapatite (Calcium Phosphate)
3 Forms of Calcium in the plasma:
- Combined with Plasma Proteins (non-diffusible)
- Combined with Anionic Substances (diffusible, but NOT ionized)
- Ionized (DIFFUSIBLE) = Most Important
Sources of Dietary Calcium:
- Dairy
- Green Leafy Vegetables
- Soy/Tofu
- Nuts
PTH functions to ______, and it does so in these 3 ways:
- MOBILIZE and increase Plasma Ca
- Three different ways:
a. Bone Resorption
b. Increase Kidney Excretion of PO4-
c. Increased Intestinal Absorption (Vitamin D dependent)
* i.e. Increase Ca and Decrease Phosphate*
How does PTH increase bone resorption?
- Increases CYTOKINES in OsteoBLASTS
- Increases activity/proliferation of OsteoCLASTS
- HOWEVER –> Must not allow PO4- from resolved bone to combine with Ca released from bone –> So PTH increases PO4- EXCRETION by the kidneys
How does PTH increase Ca absorption?
It stimulates VITAMIN D SYNTHESIS in the kidney –> Which increases Ca absorption at the intestine
Vitamin D is a ______ which has function similar to a ____.
- Fat-Soluble Vitamin
2. Hormone
2 Types of Dietary Vitamin D:
Plant form = ERGOcalciferol (D2)
Animal form = CHOLEcalciferol (D3)
Describe the formation of Vitamin D:
- Skin contains 7-Dehydrocholesterol –> SUNLIGHT converts it into CHOLECALCIFEROL (D3)
- In the LIVER –> 25-hydroxylase converts it into 25-Hydroxycholecciferol (ACCUMULATION THEN EXHIBITS NEGATIVE FEEDBACK)
- In the KIDNEY –> 25-Hydroxycholecalciferol 1-Hydroxylase then converts it into 1,25-Dihydroxycholecalciferol
- In the INTESTINE –> This interacts with 3 things:
A.) Ca-binding Protein
B.) Alkaline Phosphatase
C.) Ca-Stimulated ATPase –> Which increases ABSORPTION!!
*However –> Excess plasma Ca INHIBITS PTH from stimulating 1-Hydroxylase AT THE KIDNEY
Actions of Vitamin D:
- Intestine: Increases Ca Absorption by…
A.) Increased Calbindin and Ca-Binding Protein synthesis
B.) Increasing Ca-Dependent ATPase synthesis –> Which pumps Ca into the blood - Bone: Mobilizes Ca and PO4- from bone by POTENTIATING PTH*** But in small quantities, promotes CALCIFICATION
- Kidneys: Inhibits Ca excretion BY stimulating Ca re-absorption
What is another name for 1,25-Dihydroxycholecalciferol?
CalciTRIOL
How SPECIFICALLY does CalciTRIOL elicit its effects?
Like a STEROID HORMONE: Either induces or represses transcription of its targets
How does Calcitonin elicit its effect?
It senses plasma calcium increase and –> INHIBITS OSTEOCLASTS to reduce bone resorption and lower plasma Ca levels
In what one way does Vitamin D act antagonistically to PTH, and why is this not a concern?
Vitamin D PROMOTES PO4- re-absorption at the distal tubule –> But PTH effects are FAR STRONGER
How would Liver Disease and Kidney Disease affect Vitamin D levels respectively?
Liver Disease = Deficient 25-Hydroxylase activity
Kidney Disease = Deficient 1-Hydroxylase activity
Besides Rickets, what complication does Vitamin D deficiency elicit in children?
- Pigeon Chest
2. Overgrowth of the CostoChondral Junction
Vitamin D deficiency will prevent with hypocalcemia, hypophosphatemia, but INCREASED _________.
Plasma Alkaline Phosphatase (ALP) from BONE
Describe Vitamin D RESISTANT Rickets:
- Mutation in the gene encoding the Vitamin D RECEPTOR
- Decreased Ca Absorption from diet
- Presents with: INCREASED plasma Vitamin D (CalciTRIOL) levels
- Has normal symptoms of Rickets AND ALSO ALOPECIA (hair loss)
Vitamin D Toxicity (Hypervitaminosis D):
- Vitamin D is fat-soluble so it can be stored in the body and is metabolized slowly
- Excess leads to: Loss of appetite, thirst, nausea, etc.
- Hypercalcemia (Increased Ca Absorption) –> BUT ALSO INCREASED BONE RESORPTION (because it potentiates PTH) –> Leads to deposition of Ca in the kidney arteries (soft tissue calcification)
2 Different ways PTH can cause HYPOcalcemia:
- Low PTH levels: (Hypoparathyroidism)
- High PTH levels: (Secondary Hyperparathyroidism) –> Vitamin D deficiency or Renal Failure (meaning deficient 1-Hydroxylase Activity) leads to EXCESS PTH to compensate
* Vitamin D deficiency = Plasma levels of 25- Hydroxyvitamin D would be low vs. Renal Failure = CalciTRIOL levels would be low*
Hypocalcemia Tetany:
- Also known as CARPOPEDAL SPASM
- Increased excitability of peripheral nerves caused by HYPOcalcemia
- Also causes STRIDOR (spasm of glottis)
- SEVERE: Causes Cardiac Arrhythmias
* Treat with Ca supplement and Vit D*
2 Causes of HYPERcalcemia:
- Excess PTH –> would show Increased PTH, Increased Ca, BUT DECREASED PO4-
- Excess Vitamin D –> would show Increased Vit D, Increased Ca, AND INCREASED PO4-
Symptoms of HYPERcalcemia:
Bones Moans Stones Abdominal Groans *Lethargy, Depression, Polyuria, Nausea*
2 Causes of HYPOphosphatemia:
- Vitamin D deficiency –> Causes deficient intestinal absorption of PO4-
- EXCESS PTH –> Causes increased excretion of PO4- by the kidneys
Symptoms of HYPOphosphatemia:
Problems with function of:
- Nerves
- Bone
- Red/White Blood Cell
- Muscle
2 Causes of HYPERphosphatemia:
- Renal Failure: Can’t excrete phosphate efficiently
2. HYPOparathyroidism: Not enough stimulus (from PTH) to excrete PO4-
Symptoms of HYPERparathyroidism:
- Calcification of Soft Tissue (accumulation with Ca binding to it in the arteries)
- Tetany (for same reason as HYPOcalcemia, because it is binding up all the Ca)
- Seizures
Describe Neurulation:
- It is the INDUCTION of the ectoderm –> Forms the PRIMORDIUM of the entire central nervous system
- This induction is done by the NOTOCHORD and PARAXIAL MESODERM –> Causes the ectoderm to differentiate into the NeuroEctoderm
- Ectoderm immediately DORSAL to the notochord –> Elongated to form the thickened, single layer NEURAL PLATE
- The longitudinal median NEURAL GROOVE appears on day 18 (with a NEURAL FOLD on each side)
- By end of 3rd week, neural plate consists of a WIDE CRANIAL PORTION (becomes the brain) and a NARROW CAUDAL PORTION (becomes the spinal cord)
- Caudal portion is forced to LENGTHEN as somites continue to develop in this region of the neural plate
- NEURAL FOLDS START TO FUSE –> Forms a narrow NEURAL CANAL which gets smaller as the cells of the wall of the neural tube proliferate
- The ends of the tube INITIALLY remain open to the amniotic cavity –> Openings called the ROSTRAL and CAUDAL NEUROPORES
Development of Neural Tube:
- As neural folds fuse, they CLOSE THE NEURAL GROOVE (starts on day 22 @ the occipital and cervical region)
- While tube fuses –> NeuroEctoderm cells along the crest of the neural folds SEPARATE
- Neural Crest cells PINCH OFF –> Neural tube is formed and the crest cells now lie on either side of the tube
- SURFACE ectoderm then becomes continuous above the tube (on the dorsal surface –> And the neural tube migrates deeper below the surface
What portion of the neural tube is the spinal cord derived from?
The closure of the neural tube CAUDAL to the 4th pair of somites will give rise to the spinal cord
What are the 2 neural tube derivatives (cell lines) from which the entire CNS is derived?
- Mesenchyme –> MICROGlial Cells
2. Neuroepithelium –> Neuroblasts and MACROglial cells
What portions of the CNS and PNS do the Neural Tube and Neural Crest give rise to respectively?
- —–>Neural Tube:
A.) CNS = Brain, Brain Stem, Spinal Cord
B.) PNS = Somatic Motor Portion and Visceral Preganglionic Motor Portion - —–>Neural Crest:
A.) CNS = Nothing
B.) PNS = Ganglions/Post-ganglionic motors, Sensory Ganglia, Dorsal Root Ganglia, Schwann Cells, Leptomeninges
Spinal Cord Development:
- Neural Tube is lined by thickened NEUROEPITHELIUM –> Forms the VENTRICULAR ZONE
- The cells of this zone migrate outward to form the INTERMEDIATE ZONE (mantle layer)
- Superficial to all of these is the MARGINAL ZONE
Deep to Superficial = Vent->Int->Marg - The Intermediate Zone THICKES at two paired regions:
A.) DORSALLY: Alar Plates –> Becomes the Dorsal Horns and Dorsal Gray Columns
B.) VENTRALLY: Basal Plates –> Becomes the Ventral AND Lateral Horns
DorsALAR—VentrASAL - Alar and Basal Plates are separated by the SULCUS LIMITANS (I.e. The Intermediate (Mantle) Zone forms the GRAY MATTER of the spinal cord)
We know that the intermediate zone of the neural tube forms the GRAY Matter, but what do the Marginal and Ventricular Zones, AND the Cavity of the neural tube form?
- Marginal Zone = White Matter
- Cavity = Central Canal
- Ventricular Zone = Ependymal LINING of the central canal
What forms AROUND the central canal and 3 zones of the spinal cord?
- The adjacent MESENCHYME condenses –> Forms PRIMORDIAL MENINX
- Has 2 Layers:
A.) Inner = Derived from Neural Crest Cells, forms LEPTOMENINGES ( Pia and Arachnoid Mater)
B.) Outer = Derived from Mesoderm, forms DURA MATER
Vertebrae develop from the ________ that surround the neural tube. The formation is specifically organized such that:
- PAIRED mesenchyme of the SCLEROTOME
- The sclerotome has 2 regions:
a. ) Densely Packed Cells: Form the Intervertebral Disc (SPECIFICALLY THE ANNULUS FIBROSUS) and PART of Vertebral Body
b. ) Loosely Packed Cells: Form the bulk of the vertebral body
* i.e. DISC in between is more dense to support weight*
From what does the Nucleus Pulposus of the Intervertebral Disc derive?
Remnants of the NOTOCHORD
Hemi-Vertebra:
When ONE PAIR of sclerotomes FAILS TO DEVELOP
Formation of the Vertebral Column:
- Remnants of sclerotome form –> Primordial Mesenchyme of the Vertebrae
- Appears at 5th week –> Until it forms cartilage and then ossification centers develop
- THREE main ossification centers:
a. Centrum
b. Body
c. TWO Neural Arch Centers - Neural Arches ossify FIRST (will become vertebral arch)
- Secondary ossification centers appear in the transverse processes –> Form RIBS (thoracic) and MAMMILARY PROCESSES (lumbar)
- Between ages 3-6, the 3 bones of each vertebrae fuse
Chordoma:
- Normally: Notochord remnants form the nucleus pulposus of the vertebral body
- If Notochord PERSISTS –> Forms a MALIGNANT TUMOR that may infiltrate BONE AT THE BASE OF THE SKULL***
What is recommended to prevent Neural Tube Defects?
FOLIC ACID supplementation (To prevent Spina Bifida)
Spina Bifida OCCULTA:
- Failure of EMBRYONIC HALVES OF NEURAL ARCHES to fuse at midline
- NO BULGE over bony defect –> No neurological deficits either
- May present with Lumbosacral TUFT OF HAIRS OR SKIN DIMPLE***
- This CYST usually contains DURA AND ARACHNOID MATER
Spina Bifida CYSTICA with MENINGOCELE:
- Failure of ONE OR MORE NEURAL ARCHES to fuse IN THE 4TH WEEK***
- BULGE PRESENT –> Because it contains MENINGES and CSF in the SubArachnoid Space***
Spina Bifida CYSTICA with MeningoMYELOCELE:
- Failure of ONE OR MORE NEURAL ARCHES to fuse IN THE 4TH WEEK***
- BULGE PRESENT –> But it contains MENINGES, CORD, AND NERVES***
- SEVERE NEUROLOGICAL DEFICITS**
* i.e. DISPLACED SPINAL CORD
Spina Bifida CYSTICA with MYELOSCHISIS:
Skin and Bony defect with OPEN SPINAL CORD –> Seen as a mass of neural tissue
Meroencephaly:
- Failure of ROSTRAL NEUROPORE to close –> Absence of a large part of the BRAIN AND SKULL
- Do not survive more than a few days even if they make it to term
From what do the Primary and Secondary Curvatures of the spine result respectively?
- Primary: During FETAL DEV. –> In relation to the FETAL POSITION
- Secondary: After 1 year of life (walking) –> Result of EXTENSION FROM the FLEXED fetal position and MAINTAINED by differences in thickness between anterior and posterior parts of intervertebral discs
Kyphosis:
- “Hunchback” –> Due to abnormal INCREASE in the THORACIC curvature of the spine
- Causes the vertebral column to curve POSTERIORLY
Lordosis:
- Anterior TILTING of the PELVIS –> Upper Sacrum is FLEXED/ROTATED antero-inferiorly
- Plus INCREASED EXTENSION of lumbar vertebrae –> Causes abnormal increases in LUMBAR KYPHOSIS
Scoliosis:
Abnormal LATERAL curvature of the spine –> Accompanied by ROTATION of the Vertabrae
“Epi” =
“Sub” =
- Epi = ABOVE
2. Sub = BENEATH
Dermatome:
Area of skin innervated by a single SPINAL nerve
For any one dermatome to exhibit loss of sensation, what must occur?
Loss of innervation from the primary dermatome AND both the dermatomes ABOVE AND BELOW it because of overlapping nerves
Which dermatome is affected by the Herpes Zoster virus?
Dermatome T9
The nerves of a somatic plexus are targeted towards _______ and therefore they are derived from ______.
- The Body Wall
2. VENTRAL RAMI
Hilton’s Law:
If a nerve crosses a joint, IT INNERVATES THAT JOINT.
4 Somatic Nerve Plexuses:
Cervical
Brachial
Lumbar
Sacral
3 Main Things to look for in X-Rays/Imaging:
- Cortical Lines Intact/Aligned
- Joint Spacing
- Bone/Joint Alignment
