MSK Flashcards

1
Q

What is the structure of a collagen fibre?

A

AA chain
Collagen chain
3 collagen chains form helix
Group to form fibril
Group to form fibre

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2
Q

What is the primary structure of collagen?

A

Triple repeat of glycine and 2 other AAs
Allows collagen to form chains and crosslinks

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3
Q

What is the structure of type 1 tropocollagen?

A

3 collagen chains- 2 alpha 1 chains, 1 alpha 2 chains form 3-stranded tropocollagen molecule

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4
Q

What happens in processing of type 1 collagen?

A

Ends (P1NP, P1CP) are cleaved off and released into circulation

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5
Q

What does tropocollagen go on to form?

A

tropocollagen modules are assembled into a collagen fibril

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6
Q

What holds tropocollagen molecules and fibrils together?

A

tropocollagen molecule and the fibril are held together by covalent crosslinks (both intra and intermolecular) derived from lysine/hydroxylysine side-chains

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7
Q

What are the different ways of joining collagen?

A

Covalent cross links within and between helix and tropocollagen- needs copper
H bonds within triple helix- needs vit c

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8
Q

How is collagen broken down?

A

collagenases and cathepsin K in bone break down collagen
normal for repair and replacement
can become pathological

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9
Q

What happens when type 1 collagen breaks down?

A

The telopeptides (NTX and CTX) are removed

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10
Q

What are the types of collagen and what are they for?

A

Type I – bone, tendon, ligaments, skin
Type II – articular cartilage, vitreous
Type III – alongside Type I – wound healing
Type IV - basal lamina
Type V – cell surfaces
Type X – growth plate

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11
Q

What is the shape of long bones?

A

tubular shape with hollow shaft and ends
expanded for articulation with other bones

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12
Q

What is the shape of short bones?

A

cuboidal in shape

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13
Q

What is the shape of flat bones?

A

plates of bone, often curved, protective function

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14
Q

What shape are sesamoid bones?

A

round, oval nodules in a tendon

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15
Q

What are cortical bones?

A

Dense, solid, compact
only spaces are for cells and blood vessels.

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16
Q

What are trabecular bones?

A

Network of bony trabeculae, looks like
sponge, many holes filled with bone marrow.
Cells reside in trabeculae and blood vessels in holes

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17
Q

How is woven bone made?

A

Made quickly
Disorganised
No clear structure

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18
Q

How is lamellar bone made?

A

Made slowly
Organised
Layered structure

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19
Q

What is the adult bone composition?

A

10% water
50-70% mineral, hydroxyapatite
20-40% organic matrix (90% type 1 collagen)

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20
Q

What is the function of hollow long bone?

A

keeps mass away from neutral axis
minimizes deformation

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21
Q

What is the function of trabecular bone?

A

gives structural support while minimizing mass

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22
Q

What is the function of the weak ends of bones?

A

spreads load over weak, low friction surface

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23
Q

What is the function of flat bones?

A

Protective

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24
Q

What are the cells of bone and what are they like?

A

Osteoclast- multinucleated
Osteoblast- plump, cuboidal
Osteocyte- stellate, entombed in bone
Bone lining cell- flattened, lining the bone

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25
What cells do osteoblasts originate from?
Mesenchymal stem cells
26
What do osteoblasts do?
Form bone (osteoids) Produce type 1 collagen Mineralize the extracellular matrix by depositing hydroxyapatite crystal within collagen fibrils High Alkaline Phosphatase activity Make non-collagenous proteins Secrete factors that regulate osteoclasts i.e. RANKL
27
Where do osteoclasts originate from?
Haemopoietic stem cells
28
What do osteoclasts do?
Resorb bone Dissolve the mineralised matrix Breakdown collagen in bone High expression of TRAP and Cathepsin K
29
What are the stages of bone remodelling?
Resting phase Activation haemopoietic stem cells become osteoclasts Reversal phase- osteoclasts leave, influx of mesenchymal stem cells Formation- osteoblasts
30
What happens in bone modelling?
Gross shape is altered Bone added or removed
31
What happens in remodelling?
All of the bone is altered New bone replace old bone
32
Why do bones remodel?
Form bone shape Replace woven bone with lamellar bone Reorientate fibrils and trabeculae in favourable direction for mechanical strength Response to loading (exercise) Repair damage Obtain calcium
33
What is the average amount of calcium in the body and where is it?
1200g in the skeleton About 1g in the extracellular space
34
What is the purpose of calcium in the extracellular space?
Normal blood clotting Muscle contractility Nerve function
35
What are the 3 ways calcium can be in the blood?
Ionised, metabolically active Protein-bound, not metabolically active (mostly bound to albumin) Complexed, such as citrate, phosphate
36
What would happen in alkalosis to Ca?
Lower ionised Ca as more taken up by albumin Serum calcium stays normally
37
What is total serum calcium normally?
2.2-2.6mmol/L
38
What is ionised serum calcium normally?
ionised serum calcium is about 1.1 mmol/L
39
How can calcium get into the extracellular fluid?
Calcium taken in from diet, 30% absorbed Remove calcium from bone Excrete calcium from kidneys
40
How is calcium lost from the extracellular space?
Faeces Calcium reabsorption Bone formation
41
What are dietary sources of calcium?
Major: dairy (milk, yoghurt, cheese) Minor: veg, cereals, oily fish
42
How much calcium from diet is absorbed?
30%
43
Where is calcium from the diet absorbed?
Duodenum and jejunum for active absorption Passive absorption in ileum and colon
44
How can calcium be released from bone?
Rapidly released from exchangeable calcium on bone surface More slowly by osteoclast during bone resorption
45
What happens to calcium in the kidney?
Calcium is filtered 98% of filtered calcium is reabsorbed PTH increases absorption Sodium decreases
46
What determines how much calcium is filtered?
The glomerular filtration rate The ultrafiltrable calcium (Ionised, complexed)
47
Which hormone regulates serum calcium?
Parathyroid hormone made from PT glands with Ca sensing receptor
48
How do calcium sensing receptors affect PTH?
Calcium sensing receptor inhibits PTH secretion if calcium too high Low calcium = more PTH made and released
49
What does fibroblast growth factor do?
Regulates active form of vitamin D in response to phosphate Increase phosphate excretion
50
How does vitamin D influence intestinal calcium absorption?
1,25-dihydroxyitamin D binds to Vit D receptor 3 proteins made for active transport of calcium TRPV6 on lumen, calcium comes in from food via this Then goes into blood
51
What does calcitonin do?
Hormone produced by C cells in thyroid Secretion stimulated by an increase in serum calcium Lowers bone resorption Not that important in humans
52
What is PTH's action of the cell?
PTH acts on target cell One pathway makes cAMP One makes calcium
53
What does PTH do?
Reduces phosphate reabsorption Increases calcium reabsorption Increases hydroxylation of 25-OH vit D
54
What happens in a low calcium diet?
Less calcium absorbed Lower serum ionised calcium Higher PTH Exchangeable calcium quickly released form bone Increased bone resorption and increased fractional absorption by intestine Serum ionised calcium returns to normal
55
What is appositional bone growth?
Chondroblasts secrete new matrix on existing surfaces increases the bone width or diameter
56
What is interstitial bone growth?
Chondrocytes secrete new matrix within cartilage lengthening of the bone. occurs within the lacunae
57
What is endochondral ossification?
involves the formation of cartilage tissue from aggregated mesenchymal cells and the subsequent replacement of cartilage tissue by bone
58
What is the axial skeleton?
Vertical axis of body Skull Vertebrae Ribs Sternum
59
What is the apendicular skeleton?
Supports limbs Arms, legs, pelvis, shoulder, hands. feet
60
Functions of skeletal muscle
Produce movement Support soft tissues Maintain posture and position Communication Control openings of passageways Maintain body temperature
61
Characteristics of muscles
Responsiveness- response to chemical signals, stretch, electrical changes Conductivity- local electrical changes trigger excitation Contractility- shortens when stimulated Extensibility- can stretch Elasticity- returns to original length
62
Structure of a muscle
Myocyte (surrounded by endomysium) Muscle fascicle (bundle of cells, surrounded by perimyosium) Muscle proper (multiple fascicles surrounded by epimysium
63
What are T tubules?
Sarcolemma invaginations that help propagating action potential
64
What is the average size of a myofibre?
Average length: 5cm Average diameter: 100um
65
What is the sacroplasm?
Cytoplasm rich in glycogen to fuel contraction
66
How many sarcomeres per myofibril?
10,000
67
What is a sarcomere?
basic contractile unit of a myocyte composed of thin actin and thick myosin between the 2 Z discs
68
What does endomyosium surround?
individual muscle fibres
69
What does perimyosium surround?
a bundle of muscle fibres, forming a fascicle
70
What does epimyosium surround?
the entire muscle
71
What is the histology of a skeletal muscle fibre?
cylindrical long and unbranched multinucleated banding pattern with cross-striations of alternating light and dark bands light bands are divided by a Z disc (dark transverse line)
72
Describe the process of excitation-contraction coupling
- AP at neuromuscular junction travels down T-tubule to depolarise membrane - Depolarisation of the sarcolemma triggers opening of voltage-gated L-type Ca2+ channels - Calcium enters cell - activation of ryanodine receptors located in the sarcoplasmic reticulum - allows Ca to flow from the sarcoplasmic reticulum into the cytoplasm and further increases intracellular Ca conc - Ca binds to troponin-c - Conformational change reveals a binding site on actin for myosin head - ATP hydrolysis, providing energy for actin and myosin to slide past each other - Sarcomere shortens, contraction
73
What happens at the neuromuscular junction for skeletal muscle contraction?
- AP arrives - Calcium channels open, intracellular calcium increases - Triggers release of ACh from vesicles - ACh activates nicotinic ACh receptors on muscle fibre membrane - Depolarisation - ACh broken down by acetylcholinesterase
74
What does acetylcholinesterase do?
Breaks down ACh in synaptic cleft to allow membrane repolarisation
75
What is the Z line of the sarcomere?
where the actin filaments are anchored.
76
What is the M line of the sarcomere?
where the myosin filaments are anchored.
77
What makes up the I band of sarcomeres?
actin filaments
78
What is the A band of sarcomeres?
the length of a myosin filament, may contain overlapping actin filaments
79
What is in the H zone of a sarcomere?
myosin filaments
80
What is nebulin?
an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle
81
What are the functions of ligaments?
Attach bone to bone. Augment mechanical stability of joints. Guide joint motion. Prevent excessive motion
82
What do ligaments attach?
Bone to bone
83
What do tendons attach?
Muscle to bone
84
What are the functions of tendons?
Connect muscle to bone Aid joint stability Provide joint torque, motion and restraint
85
What is the exception to tendon?
Patellar tendon connects bone to bone and is a ligament
86
What is the general structure or tendons and ligaments?
Dense connective tissues consisting of mainly parallel fibres Extracellular matrix Fibroblasts which synthesise & remodel extracellular matrix Sparsely vascularised
87
How much of the tissue volume of tendons and ligaments is made up by extracellular matrix?
80%
88
What makes up the extracellular matrix in ligaments and tendons?
70% of tissue wet weight is water 30% solids [collagen, ground substance (proteoglycans and glycoproteins)] Has a hierarchical structure
89
What does the sparce vascularisation of tendons and ligaments mean?
Poor capacity for healing
90
What does the dense connective tissue of ligaments and tendons enable?
Enables the tissue to sustain high tensile strains
91
What is the major component of the tendon and ligament fibres?
Type 1 collagen (90-95%) Some type 3
92
What do proteoglycans do in tendons and ligaments?
Make up 1-5% of dry weight Regulate fibre diameter during fibrillogenesis Aid in keeping fibrils together Act as lubricant to aid collagen fibres gliding over each other
93
How is collagen synthesised and processed?
synthesized within fibroblasts as procollagen 3 individual polypeptide chains each coiled in L hand helix, then combine to form R hand helix Cross linking increases strength Secreted outside the cell Processed to remove terminal peptides (for tropocollagen) and self assembles into collagen fibrils
94
Describe process of fibrillogenesis
Collagen molecules group together to form microfibrils Microfibrils combine to form subfibrils Subfibrils combine to form fibrils (50-200nm diameter) Fibrils combine together to form fibres (3-7µm diameter) Fibres combine to form fascicles Fascicles group together to form tendon fibres
95
Order of fibrillogenesis
Collagen molecules Microfibrils Subfibrils Fibrils Fibres Fascicles Tendon fibres
96
What does elastin do?
Influences elastic properties of tendons and ligaments (↑ elastin =↑ elasticity)
97
Where would you find elastin?
Little in tendons and extremity ligaments More present in ligamentum flavum (between laminae of vertabrae)
98
What is the role of elastin in the spine?
protect spinal nerve roots provide intrinsic stability to spine
99
What are the differences between tendons and ligaments?
Tendons muscle to bone, ligaments bone to bone Tendons have higher collagen I (95-99% dry weight), ligaments 90% Tendons have very little elastin, ligaments have more Fibres highly organised in tendons, more random in ligaments
100
What does enthesis mean?
Place of insertion of a tendon or ligament into bone
101
What is a fibrous insertion?
formed through intramembranous ossification Calcified anchorage is by calcified collagen fibres (Sharpey’s fibres) into bone E.g. distal medial collateral ligament
102
What is a fibrocartilage insertion?
formed through endochondral ossification. Gradual change from collagenous ligament into fibrocartilage into mineralised cartilage into bone. E.g. proximal medial collateral ligament
103
What do tensile load result in?
Elongation of tissue between ends
104
What do compressive loads result in?
Contraction between tissue ends
105
What does the ligamentum flavum do?
Substantial proportion of elastin (60-70%) Connect laminae of adjacent vertebrae Function to protect spinal nerve roots Provide intrinsic stability to spine
106
What is the golgi tendon organ?
Encapsulated sensory receptors proprioceptors Activated by stretch or active muscle contraction. Located in tendons near the junction with the muscle (also in joint capsules) Consist of thin capsule enclosing collagen fibres penetrated by terminal branches of sensory neurones senses muscle tension
107
How does the inverse myotatic reflex work? (a protective reflex)
Stimulation of golgi tendon organ nerve impulse travels to spinal chord (afferent 1b neurones) synapse on interneurone α motor neurone innervating the muscle muscle relaxation (prevention of muscle and tendon damage)
108
How does aging affect the mechanical properties of tendons and ligaments?
Collagen content of tendon and ligaments decreases decreased tensile strength
109
How does pregnancy and postpartum affect the mechanical properties of tendons and ligaments?
tensile strength & stiffness in tendons decreases due to hormonal influences
110
How does physical training affect the mechanical properties of tendons and ligaments?
increase in tendon tensile strength and ligament-bone interface strength. ligaments become stronger and stiffer, collagen fibers increase in diameter
111
How does immobilization affect the mechanical properties of tendons and ligaments?
decrease in tensile strength of ligaments, more elongation, less stiff. decrease in cross-links. after 8 weeks of immobilization → 12 months to recover strength & stiffness
112
What can affect the mechanical properties of tendons and ligaments?
Physical training Aging Immobilization Pregnancy
113
What happens in ligaments and tendons up to 20 years of age?
number and quality of cross-links in collagen molecules increases increased tensile strength Collagen fibril diameter increased so increased tensile strength
114
What is the general pathway for tendon and ligament healing?
Short inflammatory phase (time course of days). Proliferative phase (time course of weeks). Remodelling and maturation phase (time course of months)
115
What is capacity of a tendon or ligament to heal dependent on?
Location and magnitude of injury
116
What takes place in the reparative phase of tendon and ligament repair? (3-6 weeks)
Formation of granulation tissue deposition of disordered collagen neovascularisation fibroblast proliferation. Extracellular matrix production including collagen III and glycosaminoglycans
117
What happens in the remodelling phase of tendon/ligament repair?
Decrease in cellular and vascular content of the repairing tissue. Increase in collagen I content. Collagen becomes more organised, properly oriented. Cross-linking with healthy matrix outside the injury occurs
118
What the functions of joints?
To allow movement in 3-dimensions To bear weight To transfer the load evenly to the musculoskeletal system
119
What tissues are associated with joints?
Bone Muscle Cartilage Synovium Synovial fluid Dense fibrous tissue/ capsule, tendons and ligaments
120
What are the 3 types of joints?
Fibrous e.g. teeth sockets Cartilaginous e.g. intervertebral discs Synovial e.g. metacarpophalangeal
121
What are the 3 functional ways to classify joints?
Synarthroses Amphiarthroses Diarthroses
122
What are synarthroses joints?
immovable joints, mostly fibrous (e.g. skull sutures)
123
What are amphiarthroses joints?
slightly moveable joints, most cartilaginous (e.g. intervertebral discs)
124
What are diarthroses joints?
freely moveable joints, mostly synovial (e.g. hip)
125
What are suture joints?
Occur only between bones of the skull (allow skull growth in development) Adjacent bones interdigitate Junction filled with very short tissue fibres Fibrous
126
What are syndesmoses joints?
Bones are connected by a cord (ligament) or sheet (interosseous membrane) of fibrous tissue. Amount of movement permitted is proportional to length of fibre Fibrous
127
What are gomphoses joints?
A peg-in-socket fibrous joint found only in tooth articulation Fibrous
128
What are synchondroses joints?
The bones are directly connected by hyaline cartilage. These are usually amphiarthroses ie. slightly moveable eg. costal cartilage of the ribs Cartilage
129
What are symphyses joints?
connecting cartilage is a pad or plate of fibrocartilage eg. Intervertebral discs Cartilage
130
How are intervertebral discs designed to take load?
water-binding proteoglycan-rich nucleus pulposus surrounded by tough fibrous annulus fibrosus – a shock absorber
131
What are synovial joints?
Articulating bones are separated by a fluid-filled cavity Most joints of the body fit into this category
132
What are the components of synovial joints?
Articular cartilage Joint capsule - inner layer is synovial membrane Joint (synovial) cavity - a space filled with synovial fluid Synovial fluid Reinforcing ligaments
133
What are bursa?
Fluid filled sacs lined by synovial membrane In some synovial joints
134
What are the 3 types of cartilage?
Elastic Hyaline Fibrocartilage
135
What are menisci?
Discs of fibrocartilage In some synovial joints
136
What is hyaline cartilage like?
Almost frictionless surface Resists compressive loads High water content Low cell content No blood supply
137
What composes cartilage?
Water Proteoglycans Collagen (type 2)
138
What is the purpose of synovial fluid?
Covers articulating surfaces with thin film Reduces friction during articulation
139
What is and makes up synovial fluid?
A joint lubricant Fluid, proteins, charged sugars that bind water eg. hyaluronate Modified from plasma by synovial membrane (synoviocytes)
140
What does the synovial membrane do?
Secretes synovial fluid components eg. Hyaluronate, and a source of inflammatory cells in rheumatoid arthritis Sits on the joint capsule Encloses synovial cavity
141
What is a fulcrum?
A synovial joint is the fulcrum of a lever system
142
What is a first class lever in joints? (elbow example)
the fulcrum is in the middle (the elbow joint) the force is at one end (the triceps muscle) and the resistance is at the other end (the weight being pulled)
143
How does a second class lever work? E.g. chewing
the fulcrum is at one end (eg. Temperomandibular joint) the force is at the other end (the muscles of the chin) and the resistance is in the centre (the muscles attached to the coronoid process).
144
How does a third class lever work?
the fulcrum is at one end (eg. elbow joint), the force is in the middle (the biceps muscle) and the resistance is at the other end (the weight being pulled).
145
What are the types of synovial joint?
Ball and socket- hip, shoulder Condyloid- knee Gliding- Carpals Hinge- elbow Pivot- vertebral Saddle- carpometacarpal
146
What in secondary bone contains the blood vessels?
Haversian canal
147
What forms via intramembranous ossification?
Flat bones of skull Some cortical bones
148
What is intramembranous ossification?
Formation of bone from membrane prescursor Bone deposited in primitive embryonic mesoderm without cartilagenous proformer Begins in 2nd trimester
149
Process of intramembranous ossification
Small clusters of progenitor cells within a primitive mesenchyme transform into osteoblasts Osteoblasts deposit isolated bone islands Islands gradually form open meshwork Osteoblasts continue to deposit until holes fill creating primary plate Over time woven bone remodelled to lamellar
150
What does endochondral ossification do?
Converts hyaline cartilagenous template into bone
151
When do cartilageneous proformers form?
2nd trimester
152
What is the process of endochondral ossification?
Shaft calcified and blood vessels grow into bone Osteoprogenitor cells differentiate into osteoblasts Osteoblasts lay down bone to form primary centre of ossification Proformer cartilage eroded away as new bone forms Secondary centres form in heads of bones By birth most bones have primary, some have secondary Cartilage remains on articular surface and epiphyseal growth plates
153
What layers form from endochondrial ossification?
Chondrocytes in resting cartilage divide creating columns of new cells in the zone of hyperplasia These cells enlarge and give rise to zone of hypertrophy, eroding extracellular matrix Remaining strands of matrix become calcified and osteoblasts can attach
154
What do type A and B synovial cells do?
Type A- phagocytic action Type B- rich in rER and secret synovial fluid
155
What is the histology of synovium?
Lines the inside of the joint capsule 1-4 layers of synovial cells Type A – phagocytes Type B – rich in rER Variable shapes – squamous to cuboidal Richly vascular, highly innervated
156
What are the functions of bones?
Support Protection Anchorage Mineral storage (most important calcium and phosphate) Blood cell formation (in red marrow), Triglyceride storage (yellow marrow of long bones) Hormone production (osteocalcin)
157
What are osteoprogenitor cells?
mitotically active stem cells in membranous periosteum and endosteum differentiate into osteoblasts when activated
158
What are epiphyses?
bone ends, covered by thin layer of hyaline cartilage
159
What is a diaphysis?
shaft, forms long axis of bone
160
What is the epiphyseal line?
between diaphysis and epiphyses, remnant of growth plate
161
What is spongy bone?
internal aka trabecular honeycomb of trabeculae, filled with red or yellow marrow
162
What is compact bone?
external layer, dense, smooth and looks solid
163
What is an osteon?
structural unit of compact bone
164
What is the inorganic component of bone?
hydroxyapatites (mineral salts), largely calcium phosphates
165
What makes up the organic component of bone?
Osteo cells and osteoid (containing collagen fibres and ground substance)
166
What is the normal range for uric acid in the blood?
Men 200-430 umol/l women: 140-360 umol/l
167
How soluble is uric acid?
Poorly soluble in plasma so easily forms crystals Lower pH = less soluble
168
Where does uric acid come from?
Metabolism of purines
169
What are 4 purines?
Adenine Guanine Hypoxanthine Xanthine
170
What are the sources of purines?
Diet Breakdown of nucleotides from tissues Synthesis in the body
171
How does uric acid leave the body?
Excreted in urine Breakdown in gut
172
What is the end substance of purines?
Uric acid
173
What foods contain purines?
Meat Offal – heart, liver & kidney Seafood - muscles Fish – herring and sardines Oatmeal, soya & yeast extracts Fructose – found in soft drinks Alcohol
174
What are some risk factors for gout?
Obesity Raised BP Raised triglycerides Male as oestrogen protective Diuretic Reduced kidney function as this reduced uric acid excretion
175
What is the pathway for uric acid formation?
Purines to xanthine to uric acid All converted by xanthine oxidase
176
What is the rate limiting step in uric acid synthesis?
Phosphoribose 1 pyrophosphate (PRPP) to 5’ phosphoribosylamine Enzyme: PRPP amido transferase
177
How does bone respond to exercise?
When you exercise regularly, your bone adapts by building more bone and becoming denser Mechanical stress stimulates remodeling
178
What is bone resorption?
Removing calcium from bone
179
What is a fracture?
breach in continuity of bone
180
When do fractures occur?
non-physiological loads applied to normal bone Physiological loads applied to abnormal bone
181
When are fractures more common?
Early years (0-24) or older years Post-menopausal women
182
What are some metabolic bone diseases?
Osteoporosis Paget’s Disease Osteogenesis Imperfecta
183
What would you use to describe fractures?
Site Pattern Displacement / angulation Joint involvement Skin involvement
184
What fractures are high energy?
Comminuted Segmental
185
What does displacement mean in fractures?
the abnormal position of the distal fracture fragment in relation to the proximal bone
186
What are the stages of fracture healing?
1: inflammatory 2: soft callus formation 3: hard callus formation 4: remodelling
187
What happens in the haematoma formation of fracture healing?
Haematoma forms within hours Inflammatory exudation Bleeding Decreased blood flow Periosteal stripping Osteocyte death
188
How does the soft callus form in fracture healing?
Soft callus forms in 2-3 weeks Progenitor cells in periosteum and endosteum develop into osteoblasts (intramembranous ossification) Ingrowth of capilliaries Proliferation of mesenchymal cells
189
What happens as the hard callus forms in fracture healing?
Hard callus forms weeks to 5 months Intramembranous ossification continues Callus undergoes endochondral ossification
190
How do you manage fractures?
Reduce Immobilise Rehabilitate
191
What happens in inflammation of fracture healing?
- Haematoma - Fibrin clot organisation - Neovascularisation - Cellular invasion: Haematopoietic cells (clear debris and express repair cytokines), Osteoclasts (resorb dead bone), Mesenchymal stem cells (building cells for repair)
192
What happens during the repair stage of fractures?
- Callus’ formation: Fibroblasts produce fibrous tissue (high strain) Chondroblasts form cartilage (strain <10%) Osteoblasts form osteoid (strain <1%) - Progressive matrix mineralisation - High vascularity
193
What happens in the remodelling stage of fracture healing?
Woven bone structure replaced by lamellar bone (osteonal remodelling) Increased bone strength Vascularity returns to normal Healing without scar - unique
194
How long does the repair stage of fracture healing last?
Weeks
195
How long does the remodelling stage of fracture healing last?
Months-years
196
How long does the inflammatory stage of fracture healing last?
Days (0-7 of fracture)
197
How can you fix fractures?
Slings Casts and splints Extra-medullary devices: plates and screws Intra-medullary devices: nails External Fixation
198
What patient factors influence fracture healing?
Age Nutrition Smoking Drugs – NSAIDs, steroids
199
What bone factors influence fracture healing?
Bone type: cancellous vs. cortical Bone site: upper limb vs. lower limb Vascularity / soft tissue damage Bone pathology - # in metastatic deposit does not heal infection
200
What are some early local complications of fractures?
Vessel damage Nerve damage Compartment syndrome infection
201
What are some general early complications of fractures?
Hypovolaemic shock ARDS VTE Fat embolism
202
What are some late local complications of fractures?
Malunion Non-union Avascular necrosis Ischaemic contractures Joint stiffness Myositis ossificans Complex regional pain syndrome Osteoarthritis
203
What are some late general complications of fracture?
Poor mobility Functional disability and social isolation Pressure sores Disuse osteoporosis Loss of income / job
204
What is angulation in a fracture?
Specific type of fracture displacement where the normal axis of the bone has been altered such that the distal portion of the bone points off in a different direction
205
Why do bones remodel?
Repair microdamage Respond to mechanical stimuli Store and release mineral
206
What is bone modelling?
Gross shape is altered Bone added or taken away
207
What is bone remodelling?
All of the bone is altered New bone replaces old bone
208
What happens in bone remodelling?
Signal sent out Osteoclasts arrive and attach to bone surface Secrete glycogen ions and absorb bone Signal to osteoblasts and they arrive Restore bone
209
What does coupling mean in bone turnover?
Bone formation occurs at sites of previous bone resorption Osteoblasts know where clasts have been
210
What does balance mean in bone turnover?
Amount of bone removed by osteoclasts should be replaced by osteoblastic activity
211
What hormones regulate bone turnover?
PTH Oestrogen and testosterone Active vit D Cortisol GH, IGF-1 Leptin and adiponection
212
What is the paracrine regulation of bone turnover?
Prostaglandins Interleukin-1 Tumour necrosis factor
213
What is the RANK Ligand pathway?
RANK Ligand signals to osteoclasts (secreted by osteoblasts, a key coupling pathway) OC precursors express receptor RANKL binds and precursor differentiates into osteoclast Binds to osteoclast Increases osteoclast activity and bone resorption
214
What does the OPG pathway do?
Decoy receptor for RANKL Secreted by osteoblasts Inhibits osteoclast differentiation and activity
215
What secretes RANK ligand?
Osteoblasts
216
What is sclerostin?
Osteocyte secreted protein Loss of function can increase bone density
217
What does sclerostin do?
Signals to osteoblast Inhibits bone formation Secreted with decreased oestradiol or PTH
218
What is phosphate involved in in physiology?
Phospholipid bilayers and maintains integrity Nucleotides and ATP Bones Kinases
219
What is normal serum phosphate?
0.8 – 1.5 mmol/l
220
What is the total amount of phosphate in the body?
500 - 800g 90% in bone
221
What happens in high phosphate?
Excess formation of hydroxyapatite Deposited in tissues other than bone
222
What is the recommended daily intake of phosphate?
700mg
223
What are the dietary sources of phosphate?
Protein: meat, dairy, soy, seeds and nuts
224
How is phosphate excreted?
Unbound phosphate is filtered (about 90%) 80% reabsorbed in proximal tubule 10% reabsorbed in distal tubule Maximum rate of reabsorption is limited, so excess is excreted
225
What regulates phosphate metabolism?
PTH 1,25 dihydroxyvitamin D FGF-23 (fibroblast growth factor)
226
What is the effect of PTH on phosphate?
Increases phosphate loss in kidney (via decreased tubular reabsorption) Increases active gut absorption via vitD
227
What produces FGF-23?
Osteocytes
228
What is FGF-23 produced in response to?
Rise in phosphate levels Dietary phosphate loading PTH 1,25 vitamin D
229
What does FGF-23 do?
Increases renal excretion of phosphate (by decreasing expression of Na transported in tubule) Decreases gut absorption of phosphate (by decreasing 1α-hydroxylation of vitamin D) Decreases whole body phosphate
230
What happens when serum phosphate rises?
Increase in FGF - decreases absorption Increase of PTH, feeds into FGF - decreased reabsorption Serum phosphate falls - FGF falls
231
How are calcium and phosphate generally regulated?
Calcium mostly regulated by hormones that increase serum calcium - PTH, vitamin D Phosphate mostly regulated by hormones that decrease serum phosphate - FGF-23, PTH
232
When does intramembranous ossification happen?
begins in-utero and continues into adolescence
233
What are slow twitch fibres?
ATPase hydrolyses ATP slowly Small Weakest contractions Myoglobin binds and stores oxygen Extensive blood vessels Red Mitochondria
234
What does more RANKL than OPG mean?
Bone resorption increased
235
What happens when there is more OPG than RANKL?
Osteoclast activity decreased