Random Flashcards
1
Q
primary cartilaginous joints consist of what?
examples?
secondary cartilaginous joints consist of what?
examples:
A
Primary: HYALINE
- in SKULL between SPHENOID and OCCIPITAL Bones
- in BONE between DIAPHYSIS and EPIPHYSIS
- between 1ST RIB and STERNUM
- Secondary: FIBROCARTILAGE with HYALINE at edges
- between INTERVERTEBRAL DISCS
- MANUBRIOSTERNAL JOINT
- PUBIC SYMPHYSIS
2
Q
- Gliding/Planar joints movement:
- Hinge joints movement:
- Pivot joints movement:
- Ellipsoid/Condyloid joints movement:
- Saddle/Sellar joints movement:
- Ball and Socket joints movement:
A
- Gliding/Planar joints movement:
VERY SMALL AMOUNT MOVEMENT ie. Sacroiliac - Hinge joints movement:
SINGLE PLANE ie elbow and knee - Pivot joints movement:
ROTATION ie proximal radioulnar, axis/atlas of spine - Ellipsoid/Condyloid joints movement:
2 PLANES ie radiocarpal joint (wrist), metatarsophalangeal - Saddle/Sellar joints movement:
CIRCUMDUCTION (no rotation) ie thumb - Ball and Socket joints movement:
ALL MOVEMENTS, ROTATION, CIRCUMDUCTION
3
Q
steps of Endochondral Ossification
A
- Chondrocytes increase in number while Matric Calcifies around it
- Chondrocytes die and leave behind CALCIFIED CARTILAGE Shell
- BLOOD VESSELS come into the PERICHONDRIUM. differentiation of OSTEOBLASTS will form PERIOSTEUM
- BLOOD VESSELS and FIBROBLASTS come into the CALCIFIED CARTILAGE. OSTEBOBLASTS cause CARTILAGE to be REPLACED BY TRABECULAR BONE
- PRIMARY OSSIFICATION CENTRE - wave of Ossification spreads and OSTEOCLASTS REABSORB T BONE from the centre to leave MARROW CAVITY
- Periosteum bone grows inwards and becomes COMPACT BONE
- BLOOD and OSTEOBLASTS MIGRATE to the EPIPHYSIS to form bone
- SECONDARY OSSIFICATION - Trabecular bone in epiphyses leaves 2 areas of Cartilage: ARTICULAR CARTILAGE and EPIPHYSEAL GROWTH PLATE
4
Q
1.Osteoblasts have high levels of what?
- what do Osteoblasts secrete?
- what is the origin of osteoblast / what cell is it differentiated from?
- which Transcription Factors are required to form osteoblast?
- which other cells may form instead?
- What Inhibits Osteoblasts in the case of Excessive Bone Formation?
A
- ALKALINE PHOSPHATASE
ER, Golgi, Secretory Vesicles - OSTEOID - UNCALCIFIED BONE MATRIX
as well as OSTEOCALCIN (Bone Formation Marker)
and TYPE 1 COLLAGEN
GROWTH FACTORS
PROSTAGLANDINS - MESENCHYMAL STROMA CELLs
- SOX9
RUNX2
OSX - Sox9 can also form ADIPOCYTE or commonly CHONDROCYTE
- SCLEROSTIN - INHIBITS OSTEOBLASTS
5
Q
- Skeleton makes up how much of body weight
- how much of the body’s calcium is in the bones
A
17%
- 98% of calcium as hydroxyapatite
6
Q
what is the major structural protein in the body that provides strength and flexibility
A
TYPE 1 COLLAGEN
7
Q
- how are Osteoclasts Nucleus?
- Osteoclasts have a Ruffled Border for Secretion of what?
- Express high levels of what to generate this? and otherwise?
- what do Osteocyte Precursors express and how are they activated?
- Activation of this receptor causes activation of what?
- what is used to Inhibit Bone Resorption when excessive
- what can be used to Increase Osteoclast Rectuitment?
- What is the use for Cl- Channels in Osteoclasts
- Enzyme/protease secreted from Osteoclasts for degradation of Type 1 Collagen?
- Dysfunctional Osteoclasts can cause what disease?
- where might the Mutations be in the Osteoclasts in case of this disease?
A
- MULTINUCLEATE
- RUFFLED BORDER: H+ ENZYME SECRETION
and proteolytic enzymes - High levels of CARBONIC ANHYDRASE
for H+ GENERATATION
and TRAcP (TARTRATE-RESISTANT ACID PHOSPHATASE) which acts as a marker for resorption
- RANK RECEPTOR
- activated by RANK LIGAND (RANKL) on OSTEOBLAST/OSTEOCYTE BINDING - RANK Activation ACTIVATES NFkB TRANSCRIPTION FACTOR (NUCLEAR FACTOR kB)
-> differentiation into Mature Osteoclast - OPG (OSTEOPROTEGERIN)
- BINDS RANK L on OSTEOBLAST therefore can’t activate osteocyte precursor - CYTOKINES INCREASE Osteoclast RECRUITMENT
- secretes Cl- for HCL FORMATION
- ACIDIC ENVIRONMENT to DISSOLVE HYDROXYAPATITE - CATHEPSIN K enzyme degrades TYPE 1 COLLAGEN
- OSTEOPETROSIS (INCREASES BONE MASS)
- CARBONIC ANHYDRASE MUTATION
PROTON PUMP MUTATION
CL- CHANNEL MUTATION
CATHEPSIN K MUTATION
8
Q
- Bone Formation Markers (Osteoblasts):
- Bone Resorption Markers (Osteoclasts):
A
- Bone formation markers:
OSTEOCALCIN
ALKALINE PHOSPHATASE
Collagen TELOPEPTIDES - Bone Resorption markers:
PYRIDINIUM CROSS-LINKS (not resorbed)
TRAcP (TARTRATE RESISTANT ACID PHOSPHATASE)
9
Q
- how often is the Skeleton renewed?
- How long does the Bone Remodelling cycle take?
- how long is Resorption phase with Osteoclasts?
- How long is the Reversal phase with Osteoblasts?
A
- every 7-10 years
- 4-6 MONTHS
- Resorption: 10 DAYS
- Reversal phase: 3 MONTHS
10
Q
what do Osteocytes produce?
A
- RANK L (osteoclast activation)
- SCLEROSTIN (inhibits osteoblast activation when excessive)
- NITRIC OXIDE / NO (bone resorption)
- PROSTAGLANDINS
11
Q
- what is Osteoporosis?
- what is Paget’s Disease?
- what can cause High Bone Mass Disease?
A
- Osteoporosis: increased bone RESORPTION so low bone density
- Paget’s : OVERACTIVE OSTEOCLASTS so low bone mass
- LOSS of SCLEROSTIN -> High bone mass from Osteoblasts
12
Q
What may inhibit the production of some interleukins like IL6 (cytokine)
A
SEX STEROIDS
13
Q
Differences between Tendons and Ligaments:
A
Tendon:
- Bone to Muscle
- PARALLEL bundles
- MORE COMPACT
tendon forces usually uniaxial
Ligament:
- ELASTIC
- CROSS-CONNECTING, IRREGULAR BUNDLES (NOT parallel)
in ECM: MORE PROTEOGLYCANS, MORE ELASTIN, MORE COLLAGEN TYPE I
MORE CARTILAGINOUS PROTEINS ie. AGGRECAN, CARTILAGE TYPE II
14
Q
- what are Axial Tendons derived from?
- what are Head Tendons derived from?
- what are Limb Tendons derived from?
- the initiation of which tendons is Muscle Dependent
A
- SOMITES -> AXIAL TENDONS
- NEURAL CREST CELLS -> HEAD TENDONS
- LIMB LATERAL PLATE -> LIMB TENDONS
- AXIAL TENDONS initiation is MUSCLE DEPENDENT but later on independent
(Head and limb initiation is muscle independent but further development is Dependent)
15
Q
- what is the earliest known tendon/ligament marker?
- which factors support Tenocyte Differentiation to form Tendons
- what regulates downstream Tendon-related Genes during development?
A
- SCX (expression decreases after birth)
- EGR1 and MKX (persist after birth)
- SCX
16
Q
- what is meant by Viscoelastic property Creep?
- what is meant by Viscoelastic property Hysteresis?
- what is meant by Viscoelastic property Stress-Relaxation?
- in a Stress-Strain curve what is the Toe Region?
- above what strain is there Failure
A
- Creep: DEFORMATION OVER TIME - Time dependent deformation under constant load
- UNLOADING curve is different to the LOADING curve
- ability to REDUCE STRESS OVER TIME. time dependent DECREASE IN LOAD REQUIRED to MAINTAIN MATERIAL at Constant Strain
- < 2%. crimpled fibres STRAIGHTEN
- 4-8%
17
Q
- how is Collagen made and by which Genes
- how many different collagen types are there?
- collagen triple-helix is made up of which monomers?
A
- COL1AL -> ALPHA 1 chain
COL1A2 -> ALPHA 2 chain
2x alpha 1 chains and 1x Alpha 2 chain combine to form TRIPLE HELICLE PROCOLLAGEN
- SECRETED into ECM
- CLEAVAGE of N- and C- TERMINAL PROPEPTIDES
- PYRIDINIUM CROSS LINKING
- 28 TYPES
- AMINO ACID repeats wound into triple helix and aligned in elongated fibrils
18
Q
- important roles of Collagen?
- where is Type 1 found?
- where is Type 2 found?
- where is Type 3 found?
A
- main role: CONNECT BONES TOGETHER
place for BONE FORMATION
TENSILE STRENGTH,
CHEMOTAXIS,
CELL ADHESION and MIGRATION,
TISSUE REMODELLING and GROWTH
WOUND HEALING
Maintaining TISSUE STRUCTURE and FUNCTION - TYPE 1: BONE, SKIN
- TYPE 2: CARTILAGE
- TYPE 3: Extensible Connective Tissue ie SKIN, LUNG,
VASCULAR SYSTEM
19
Q
- Scurvy is due to a lack of what?
- Symptoms in Scurvy:
- what can you get from Lack of TYPE 1 collagen (mutation)?
- what is caused by Mutations in TYPE 5 Collagen
A
- Lack of VITAMIN C
- BONES BREAK EASILY,
FRAGILE CAPILLARIES
BLEEDING,
BRUISING,
INTERNAL HEMORRHAGE,
TEETH LOOSEN - type 1: OSTEOGENESIS IMPERFECTA
- type 5: EHLERS DANLOS SYNDROME
20
Q
- what Increase in Tendon Injury?
- what do these contribute to?
- what do they interact with and why?
A
- PROTEOGLYCANS
- STRUCTURAL INTEGRITY
- Interact with COLLAGEN
for FIBRILLOGENESIS and ORGANISATION of collagen
(for joint stability)
21
Q
Elastic Fibres regulate the activity of which Growth Factor?
other functions?
- Elastin is mainly found in IFM region co-localised with what?
and associated with what
A
- TGF BETA family
- REGULATE CELL FUNCTION
- co-localised with FIBRILLIN 1 and 2
associated with COLLAGEN TYPE 6
22
Q
which disease is caused by a Mutation in the FNB1 Gene
A
MARFAN SYNDROME
- DISORDER OF CONNECTIVE TISSUE
23
Q
Tendons and Ligaments are mostly made up of which 3 elements
A
- TYPE 1 COLLAGEN
- PROTEOGLYCANS
- ELASTIN (can stretch 150% of original length)
(ligaments have more of each)
24
Q
- why do Proteoglycans such as Aggrecan have large Hydrodynamic volume and swelling?
- what is this swelling pressure counteracted/ held together by?
- together these enable joints to do what?
A
- have LARGE OSMOTIC AFFECT
- Core Protein is covalently linked to at least one GLYCOSAMINOGLYCAN (GAG) which carry NEGATIVE CHARGES
->ATTRACT CATIONS ie NA+
->WATER FOLLOWS
water held in matrix
- LARGE HYDRODYNAMIC VOLUME -> SWELLING
- swelling is held together by the Resistance of COLLAGEN FIBRES in cartilage
- enable joints to RESIST MECHANICAL LOAD / COMPRESSIVE FORCE
while maintaining HIGH TENSILE STRENGTH
25
Q
- which cartilage type Lacks a True Perichondrium?
- which cartilage type is Avascular and Aneural
- Zones in Articular cartilage:
what is the Tide Mark?
how do orientation of Collagen Fibres change?
A
- FIBROCARTILAGE
(TMJ, Menisci, Intervertebral Discs, Pubic symphysis) - HYALINE / ARTICULAR is AVASCULAR and ANEURAL
- ZONE 1: TANGENITAL
ZONE 2: TRANSITIONAL
ZONE 3: RADIAL
ZONE 4: CALCIFIED CARTILAGE
TIDE MARK: Separates CALCIFIED CARTILAGE
COLLAGEN Fibres in zone 1 are PARALLEL
in zone 4 they are STOOD ON THEIR ENDS (more resistant)
26
Q
- what are the 3 components of Synovial Fluid?
- what is Viscosity?
- what is Shear Rate
- what is the equation for Viscosity?
- which component provides Viscosity to synovial fluid in fluid-film lubrication and why?
- what do we get as shear rate increases
A
- LUBRICIN - PROTEOGLYCAN
encoded by prg4 gene
secreted by articular cartilage and synovium
HYALURONAN (HA) / HYALURONIC ACID - GAG
composed of glucuronic acid and n-acetylglucosamines
synthesised at plasma membrane
PHOSPHOLIPIDS
ie Sphingomyelin, Phosphatidylcholine, Phosphatidylethanolamine
prove HYDROPHOBICITY to articular surface (LUBRICATION)
- VISCOSITY is the INTERNAL FRICTION of a FLUID
- SHEAR RATE = FLUID SPEED COMPARED TO SURFACE that it is sliding from
- VISCOSITY = SHEAR STRESS / SHEAR RATE
decrease viscosity, increase shear rate
- HYALURONAN (HA) provides VISCOSITY to synovial fluid due to its HIGH MOLECULAR WEIGHT and CONCENTRATION
- INCREASE SHEAR RATE -> SHEAR THINNING derived from HA alignment molecule (= VISCOSITY DECREASING)
27
Q
in Fluid Film Lubrication what is the..
- Squeeze model?
- Boosted Model?
- Electrohydrodynamic Model?
A
- SQUEEZE: as two surfaces are squeezed together, FLUID SQUEEZED OUT OF GAPS
- GENERATING HYDROSTATIC PRESSURE - BOOSTED: WATER MOVES INTO CARTILAGE
- INCREASE HYALURONIC ACID CONC. in FLUID-FILM - ELECTROHYDRODYNAMIC:
MOVING. DEFORMATION OF SURFACE
- TRAPS PRESSURIZED FLUID
28
Q
what is meant by Lambda Ratio
A
MINIMUM FILM THICKNESS (hmin) in relation to the composite surface Roughness (Ra1, Ra2)
Boundary lubrication: <1
Fluid Film lubrication: >3
mixed lubrication: 1 < and < 3
29
Q
- what is an early indicator of Osteoarthiritis?
- what is Aggrecan cleaved by
- what are released in Aggrecan Cleavage causing Swelling
A
- OA: PROSTEOGLYCAN LOSS
- AGGRECAN CLEAVAGE:
METZINCINS - MMPs and ADAMTSs - GLYCOSAMINOGLYCANS / SUGARS RELEASED and escape
