MSK Flashcards
(169 cards)
1
Q
Costs of disease
A
Direct - ambulatory, impatient
Secondary - mental health, complications
Indirect - loss of pay
Quality of life - pain, anxiety
2
Q
4 classes of musculoskeletal diseases
A
Degenerative disease
Inflammatory disease
Metabolic disease
Injury
3
Q
Osteoarthritis vs rheumatoid arthritis
A
Osteo - cartilage eroded so bones in joint rub together
Rheu - swollen inflamed synovial membrane in joint
4
Q
What is the commonest joint disease worldwide?
A
Osteoarthritis
= 80% of over 75s
5
Q
Describe inflammatory rheumatoid arthritis
A
Inflammatory cytokines forms a pannus which starts to grow over and damage the cartilage
6
Q
Describe collagen fibre structure
A
Amino acids Gly-X-Y residue repeated form collagen chains. Twist together with a1 and a2 strands to form a triple helice tropocollagen. Covalent cross links hold tropocollagen and collagen fibrils. Multiple fibrils form a collagen fibre.
7
Q
What is osteogenesis imperfects?
A
Collagen not structured properly - gaps have lumps of mineral deposits so doesn’t function well
8
Q
Describe types of cross links
A
Covalent (2 lysine) = within and between tropocollagen needs copper
Hydrogen (OH-proline) = within tropocollagen requires Vit C to convert Fe3+ to Fe2+
Intermolecular (3 OH-lysine) = pyridinolines between tropocollagen
9
Q
Describe collagen breakdown
A
Proteinases, collagenases an cathepsin K break down collagen for repair and replacement
10
Q
Breakdown of type 1 collagen forms?
A
NTX
CTX
(We can measure as markers in diseases)
11
Q
Types of collagen and what they form?
A
1 - bone, tendon, ligaments, skin
2 - articulate cartilage
3 - wound healing
4 - basal lamina
4 - cell surface
12
Q
Purpose of skeleton
A
Transmits body weight
RBC production
Structural support + protects vital structures
Stores Ca, P, Mg
13
Q
How many bones in the body?
A
206
Axial = 80
Appendicular - 126
14
Q
Types of bone shapes
A
Long - tubular with hollow shaft
Short - cuboidal shape
Flat - plates often curved e.g. skull
Irregular - various shapes e.g. vertebrae
Sesamoid - round, oval nodules e.g. patella
15
Q
Types of bone structure (macro)
A
Corticol (compact) - Dense, solid, only spaces are for cells and blood vessels
Trabecular (spongy) - Network of bony struts looks like a sponge. Many holes of bone marrow and blood vessels, cells in trabeculae
16
Q
Which bone structure is visible by eye?
A
Corticol vs trabecular
17
Q
Types of bone structure (micro)
A
Woven - Disorganised, no clear structure made quickly
Lamellar - Organised, layered made slowly
18
Q
% in bone compositions
A
50-70% mineral (provides stiffness)
20-40% organic matrix (collagen for elasticity)
5-10% water
19
Q
How a whole bone structure contributes to function?
A
Hollow long bone - keeps mass away from neutral axis, minimises deformation
Trabecular bone - minimises mass, gives structural support
Wide ends - spreads load over weak, low friction surface
20
Q
Cells of the bone
A
Osteoclasts - multinucleate
Osteoblasts, plump cuboidal near bone surface
Osteocytes - most abundant stellate, entombed in bone
Bone lining cells - flattened, lining the bone
21
Q
Osteoblast origin?
A
Mesenchymal cell -> progenitor ->
22
Q
Osteoblasts function
A
Form bone osteoid, produces Type 1 collagen an deposits hydroxyapatite crystals
23
Q
Osteoclasts origin?
A
Hematopoietic stem cells
-> Monocyte
-> Macrophage
Osteoclasts = specialised macrophages
24
Q
Functions of osteoclasts
A
Resort bone, breakdown collagen and dissolve mineralised matrix with acid.
25
Reasons for bone modelling
Replace woven with lamellar bone
Repair damage
Obtain calcium
Response to loading (exercise)
Store and release minerals
26
How does bone remodelling/ bone turnover occur?
Resting phase
Activation
Resorption - osteoclasts destroy
Reversal phase - osteoclasts apoptosis
Formation - osteoblasts fill pits
27
Modelling vs remodelling
M - Gross shape is altered when we grow, for formation and resorption
R - all of bone is altered and new bone replaces old bone and mobilise mineral for homeostasis e.g. child birth
28
Name some clinical problems
10 - osteoporosis (osteoclasts not kept in check)
13 - trauma
Osteogenesis imperfecta - collagen defect
Osteopetrosis - osteoclasts
Rickets - Vit D
Scurvy - Vit C deficiency
Cancers
Brittle bone - less collagen
29
Where is 99% calcium in the body?
Skeleton (1200g)
30
Where is 1% of calcium?
Extracellular space (1g)
For blood clotting, muscle contractility and nerve function
31
How is calcium transported in the blood?
Ionised (metabolically active) - 45%
Protein-bound (not metabolically active) - 45%
Complexed to ions like citrate and phosphate - 10%
32
Normal concentration of calcium in blood?
Total serum = 2.4mmol/L
(Ionised serum = 1.1mmol/L)
33
What happens to ionised calcium in alkalosis?
At high pH, albumin binds strongly to calcium so there is less ionised calcium = depolarisation of nerves and contraction of hand and feet small muscles (tetany)
34
Sources of calcium
Dietary = absorption
Bone resorption
Kidneys = reabsorption
35
How much dietary calcium is absorbed?
Eat 500-1500mg and 30% absorbed
(Active absorption in duodenum and jejunum, passive absorption in ileum and colon)
36
Sources of dietary calcium
Mainly dairy
Minor - vegetables, Cereals, oily fish
37
What does the bone do when plasma calcium falls?
Rapid release of exchangeable calcium from bone surface spring bone resorption
38
How much calcium is reabsorbed in the kidneys?
98% of filtered is reabsorbed passively in proximal tubules, loop of henle and active in distal tubules. (Active transport is regulated by parathyroid hormone)
- Less reabsorbed when Na+ is high
39
How is serum calcium regulated?
When serum calcium decreases slightly, parathyroid glands detect and lots of parathyroid hormone is secreted.
Degradation occurs within minutes and fragments are excreted.
40
How is calcium levels detected in parathyroid cells?
Calcium inhibits PTH release
Active Vit D reduces PTH synthesis
41
Where does most Vit D come from?
Skin (UV-B)
42
What’s the main form of Vit D in blood (measured)?
25-OH vitamin D
43
What does 25-OH vitamin D split into?
High PTH forms:
1,25(OH)2 Vit D
High fibroblast growth factor 23 forms:
1,24,25 (OH)3 Vit D
44
What is calcitriol?
Active form of vitamin D - hydroxylated at position 1 and 25
45
Function of calcitriol?
Binds to vitamin D receptor and stimulates production of 3 key transport proteins TRPV6, PMCA and calbindin-D which absorb calcium in the intestines
46
What is calcitonin?
When high serum calcium, hormone produced by C cells in thyroid = lowers bone resorption
47
How does parathyroid hormone work?
Increases bone resorption, calcium reabsorption (by decreasing phosphate reabsorption) in kidneys
and calcium absorption in intestines (indirectly through vitamin D metabolism)
(Uses secondary messengers on bone and kidney cells)
48
Fast vs slow PTH actions
Fast = renal reabsorption, exchangeable calcium released
Slow = bone resorption, increased intestinal calcium absorption
49
Interstitial vs appositional growth
I - growth from within (most tissue)
A - growth from outside (bone)
50
Endochondral vs intramembranous ossification (helps fetal bones grow longitudinally)
E - long bone growth by deposition on cartilage primordium
I - Only in flat bone with no cartilage precursor
51
How does endochondral ossification occur?
mesenchymal stem cells differentiate into chondrocytes and central cells become hypertrophic = direct blood vessels and osteoblasts to replace cartilage template.
Invasion of osteopenia bud forms primary centre and then secondary centres established. Lengthening via growth plates which then close
52
How does intramembranous ossification occur?
Condensation of mesenchymal cells into a flat sheet
Osteoblasts precursors form on surface
Differentiation into mature active osteoblasts
Osteoid formation
Mineralisation and incorporation of osteocytes
Further osteoid formation
53
How does bones become wider in modelling?
Modelling drift - osteoblasts form new bone and osteoclasts resorbs old bone in different areas (so can also become curved)
54
What is osteonal tunnelling?
In compact, cortical secondary one, osteons are present
= primary osteons form during growth and secondary osteoid replace bone or mobilise minerals
55
What are osteons?
Layers of lamellar bone with osteocytes surrounding a Haversian canal of blood vessels.
56
Functions of skeletal muscle
Movement
Support soft tissue
Maintain posture
Communication
Maintain body temperature
Control of opening passageways
57
Characteristics of muscles
Excitability
Conductivity
Contractility
Extensibility
Elasticity
58
Describe muscle structure
Muscle fibrils -> muscle fibres -> muscle fasicules
Contains sarcomeres, sarcoplasmic and t-tubules
59
Describe sarcomere bands
A
I - Just actin
H - Just myosin
Z
60
A-actin vs tropomodulin vs Nebulin
a-actin = Anchors actin to Z disc and prevents depolarisation
Tropomodulin = Prevents further formation of actin at the end of H band
Nebulin = acts as a ruler
61
What is titin?
Spring like protein anchors myosin to Z disc
(Largest protein of genome)
62
How many myosin heads in each filament?
300
63
Describe contraction of sarcomeres
ATP hydrolysed causes myosin head to release actin filament and progress along filament. Head then binds to new binding site and pulls actin along.
64
How often do sarcomeres contract?
5x/sec
65
How is contraction initiated at the neuromuscular junction?
Nerves release acetylcholine and depolarises postsynaptic membrane. Excitation spreads along t-tubules and causes sarcoplasmic reticulum to release calcium. This binds to troponin C and releases tropomyosin. A conformational change allows myosin heads to form cross link.
66
Three parts of troponin
Tn I - Inhibitory
Tn T - binds tropomyosin
Tn C - binds calcium
67
Describe actin structure
F-actin filaments made up of monomers of globular protein G-actin.
F-actin makes a chain of two alpha helices with tropomyosin wrapped around.
68
Describe myosin structure?
2 heavy chains, 4 light chains
69
What is botulinum toxin?
Most common cause of food poisoning blocks Ach release.
Can be used to treat uncontrolled muscle spasm
70
Types of muscle fibres
1 - Slow oxidative - aerobic
2A - Fast oxidative - aerobic with mitochondria and glycogen
2B - Fast glycolytic - anaerobic with high glycogen
71
Slow fibres are ____ the diameter of fast fibres
Half
72
Describe glycolytic metabolism
Glycogen -> glucose -> pyruvic acid -> lactic acid
(2 ATP)
73
What is phosphorcreatine?
Creatine kinase catalyses donation of phosphate to ADP to form ATP
(Reduced fatigue)
74
What is muscle fatigue?
Decreased ATP synthesis
Lactic acid build up
75
How to distinguish between muscles histologically
Cardiac - branched
Skeletal - multinucleate
Smooth - Unstriated
76
Tendons vs ligaments function
Tendons - muscle to bone aids joint stability, motion, restraint and provides torque
Ligament - bone to bone prevents excessive movement and guides mechanical stability of joint
77
Tissue composition of tendons and ligaments
Dense connective tissue of parallels collagen fibres sustains high tensile strength
Fibroblasts synthesise and remodel (20% cell volume)
Extracellular matrix (80%)
Sparsely vascularised so heals poorly
78
Why are ligament fibrils crimped?
Enables some increase in length during tension
79
Describe collagen structure of tendons and ligaments
Type 1 collagen (90-95% weight) with some collagen 3.
Proteoglycans (1-5% weight) regulate fibre diameter, acts as lubricant and keeps fibrils together
80
Hierarchical structure formation: 1-collagen synthesis
Within fibroblasts, precursors procollagen consists of 3 individual polypeptide chains in a left hand helix.
These combine in a right handed triple helix with bonding between to enhance strength
These are secreted outside the cell and terminal peptides are removed so self assembles into collagen fibres.
81
Hierarchical structure formation: 2-collagen processing
Collagen synthesis inside cell and secreted into the Extracellular space. Self assembles into collagen fibrils as terminal regions are cleaved off and covalent cross links form.
82
Hierarchical structure formation: 3-fibrillogenesis
Collagen -> microfibrils -> subfibrils -> fibrils -> fibres -> fascicles surrounded by endotenon -> tendon surrounded by epitenon
83
Function of elastin
Elasticity in tendons (less) and ligaments. More present in ligamentum flavum (spine)
84
Ligament vs tendon structure
L - lower collagen 1 (90% weigh), high elastin, more random fibres, blood from insertion
T - higher collagen 1 (90-99% weight), little elastin, organised fibres, blood from paratenon and tendon sheath
85
What is insertion of tendons and ligaments called?
Enthesis
(Fibrous / fibrocartilagenous)
86
Fibrous vs fibrocartilagenous insertion
Formed through intramembranous ossification- stem cells directly differentiate into osteoblasts (Sharpeys fibre)
Vs
Formed through endochondral ossification - stem cells differentiate into chondryocytes and then follow bone remodelling (collagen out ligament to fibrocartilage to mineralised cartilage to bone)
87
How do tendons and ligaments manage load bearing?
Viscoelastic material
Results in elongation between original ends of tissue
Compression results in contraction between tissue ends
Mechanical cues affect healing, homeostasis
88
Typical load-elongation curve
Toe region - small increase in load straighten crimped fibres
Linear region - straight and stiff increase rapidly with load
Maximum deformation - Maximum tensile strength of tissue
Yield point - after there is complete failure of collagen fibres
89
Describe ligamentum flavum structure
Provides intrinsic stability to spine with lots of elastin (60-70%).
90
What is a Golgi tendon organ?
Encapsulated sensory proprioreceptors intendons activated by stretch and muscles contraction. (Simple reflex causes muscle releaxation)
91
What affects mechanical properties of ligaments and tendons
Age (collagen decreases)
Pregnancy + postpartum
Physical training
Immobilisation
92
Tendon and ligament injury mechanism
Obesity
Direct trauma
Acute tensile failure
Strain, rupture
Avulsion from bone
Tendon overuse
Joint displacement
Can cause osteoarthritis
93
Tendon and ligament repair
Inflammatory phase (days)
Proliferation phase (weeks)
Remodelling and maturation (months)
94
3 functions of joint
Bear weight
Transfer load evenly to MSK
Allow 3D movement
95
3 types of structural joints
Fibrous e.g. teeth sockets
Cartilaginous e.g. spine
Synovial e.g. hip
96
3 types of functional joints
Synarthroses - immovable, mainly fibrous
Amohiarthroses - slightly moveable, mostly cartilaginous
Diarthroses - freely moveable, mostly synovial
97
3 types of fibrous joints
Sutures - only between skull for growth (short tissue fibres)
Syndesmosome - bones connected by cord or sheet of fibrous tissue e.g. tibia and fibula
Gomphoses - peg-in-socket only in tooth articulation
98
2 types of cartilaginous joints
Synchondroses - Bones directly connected by hyaline cartilage e.g. costal ribs
Symphyses - pad or plate of fibrocartilage e.g. intervertebral disc
99
Components of synovial joints
1. Articulate cartilage
2. Joint capsule (synovial membrane)
3. Joint cavity
4. Synovial fluid
5. Reinforcing ligament
(Also bursae and menisci)
100
3 types of cartilage
Elastic - bend e.g. ears
Fibrocartilage - less ecm e.g. intervertebral discs
Hyaline - more ecm e.g. costal
101
Components of hyaline cartilage
Frictionless surface
No blood supply (anaerobic)
Low cell content
High water content
Resists compressive loads
(Fibrocartilage is opposite)
102
Zones of articular cartilage
Superficial
Middle - most cartilage here
Deep
103
How is synovial fluid formed?
Modified plasma by synovial membrane contains charged sugars that bind to water and reduce friction
104
Lever types of synovial joints
1 - fulcrum is in middle e.g. triceps
2 - fulcrum is at one end and force at other end e.g. mandible
3 - fulcrum at one end and force is at middle e.g. biceps
105
Normal blood Uric acid levels
Men: 200-430umol/L
Women: 140-360umol/L
106
What is Gout?
High uric acid levels in the blood cause uric crystals to deposit in joints = cause inflammation, swelling and pain
107
What is Uric acid?
Purines from diet, breakdown of nucleotides and synthesis in body
Breakdown of purines forms Uric acid e.g. adenine, guanine, xanthine
Poorly soluble in plasma and less soluble in lower pH
(So Gout affects big toe more due to poor circulation)
108
How is uric acid excreted?
70% renal (in urine)
30% gut (breakdown)
109
Why does gout affect big toe joints more?
Poor circulation
110
Why are uric acids higher in men?
Oestrogen in women is protective as it promotes excretion
111
Sources of dietary purines
Meat
Offal - heart, liver, kidney
Seafood
Oatmeal, soya, yeast
Soft drinks
Alcohol
112
Risk factors for gout
Metabolic syndrome - obesity, raised no, raised triglycerides
Coronary heart disease
Diabetes
113
Which medicine impact gout
Thiazide diuretics
Low dose aspirin
= kidneys affects excretion
114
Management for Gout
Rest, ice, elevate
Anti inflammatory medication
Reduce alcohol and purine rich food
Loose weight
Switch by medication
115
Action of allopurinol
If 2 or more attacks within a year
= Inhibits breakdown of purines to uric acid (xanthine oxidase)
116
Uric acid formation
Purines -> xanthine -> uric acid
Both steps catalysed by xanthine oxidase
117
Complications of gout
Damage to joints
Secondary infections
Nerve damage
Kidney stones
Gouty trophi - crystals in soft tissue
118
Causes of increased turnover of nucleic acids
Malignant tissue
Increased tissue breakdown e.g. trauma, starvation, tumour lysis syndrome
Psoriasis (too many cells produced)
119
What is rasburicase?
Medication prevents tumour lysis syndrome
= unrated-oxidase enzyme converts uric acid to allontoin which is more soluble in water and easily excreted
120
What is Lesch-Nyhan syndrome
Rare inherited disease
X linked so affects boys
Leads to neurological, cognitive and behavioural problems
HPRT enzyme recycles purines back to precursor nucleotides. When enzyme is missing, increased production of uric acid
121
What is hyperuricemia?
Over production/ Under excretion of uric acid or a combination
122
Function of bones
Protect vital organs
Allow muscles to work
Store minerals and house marrow cells
Mechanical functions account for shape and size
123
Why do bones respond to exercise?
Genetic predisposition
Arm building exercises
= Remodelling
= Denser bone
124
How to calculate strain in bones?
Original length-new length of
——————————————
Original length of bone
125
What is peak bone strain in running humans?
2000 x million
126
Describe strain based feedback loop
Increased activity -> Higher than customary strains -> Bone formation
Vice versa
127
Strain variables
Magnitude
Rate
Frequency
Dwell (hold periods)
Number of cycles
128
Example of site specific strain
During a jump:
Skull = 170
Tibia = 850
X10,000 strain
129
Does bone rely on just:
Site Specific Customary Strain Stimulus?
No! Also:
Sex
Age
Bio chemicals e.g. hormones
Drugs/medicines
130
What is the mechanostat theory?
Our skeleton contains many small units with its own regulated mechanostat that have fixed settings
E.g. below or above strain figures cause bone loss or formation
131
How do bones respond to exercise stimulus
Occasional high magnitude high rate events
Bone responds to only a few loading cycles and rest periods increase effect
132
What cells sense loading/disuse?
Osteocytes are mechanosensors (via hydrostatic pressure, direct cellular deformation and fluid flow shear stress) and mechanotransducers of the bone via many channels etc.
133
How does loading change bone microstructure?
Osteocytes regulate activities of osteoblasts and osteoclasts via signalling molecules
= regulate bone resorption and restoration
= targets other organs e.g. heart, kidneys
134
Other factors affecting intercellular communication during exercise
Age
Gender
Genotype
Diet
Environment
135
Define a fracture
= Breach in continuity of bone
136
When do fractures occur?
Non-physiological load applies to normal bone
Physiological load (normal) applied to abnormal bone (weak)
137
When does incidence of fractures increase?
Puberty/ growth spurt
Post menopausal
Ageing
138
Examples of abnormal bone
Tumours (benign/metastatic/malignant)
Metabolic bone disease (osteoporosis, osteogenesis imperfecta)
139
Ways to describe fractures
Site (part of bone)
Pattern
Joint involvement (extra/intra-articular)
Skin involvement (open/closed + soft tissue damage)
Displacement / angulation (%)
140
Fracture patterns unique to children
Growth plate affected but deformities remodel quickly
141
4 stages of fracture healing
Haematology (hours)
Inflammation (days)
Repair (weeks)
Remodelling (months-yrs)
142
Describe haemotome stage
Bleeding and blood clot at fracture site.
Decreased blood flow, periostea’s stripping and osteocyte death
143
Describe inflammation stage
Fibrin clot forms
Neovascularisation
Cellular invasion:
- Haematoloetic cells clear debris
- Osteoclasts resort dead bone
- Mesenchymal stem cells build cells
144
Describe repair stage
Fibroblasts form fibrous tissue = soft callus allow cartilage formation
Osteoblasts form osteoid
High vascularity
Progressive matrix mineralisation
145
Describe remodelling stage
Woven bone is replaced by lamellar bone = increases strength
Normal vascularity and heals without a scar (unique)
146
3 Principles of fracture management
Reduce (the fracture)
Immobilise (the part)
Rehabilitate (the patient)
147
Types of fracture fixation
Sling
Casts and splints
Extra-medullary devices (plates and screws)
Intra-medullary devices (nails)
External fixation
148
Factors that influence fracture healing
Patient - age, nutrition, smoking, drugs
Tissue - bone type, site, pathology, vascularity
Treatment - apposition of fragments, stability, micromotion
149
Complications of fractures
Early:
Local - vessel, nerve damage, infection, compartment syndrome
General - ARDS, VTE, fat embolism, hypovolaemic shock
Late:
Local - Ischaemia, joint stiffness, osteoarthiritism avascular necrosis
General - poor mobility, loss of income/social/function
150
Regulation of bone turnover should be coupled and balanced
= Bone formation at sites of resorption
= Amount of bone removed is replaced
151
Mediators of bone turnover
Hormones: PTH, Vit D, oestrogen, testosterone, cortisol, GH, leptin
Paracrine/autocrine: Prostaglandins, Interleukins (Inflammatory)
152
What are RANK Ligands?
Hormones and cytokines cause osteoblasts to release RANK ligands
Osteoclasts progenitor cells express RANK receptors. RANK ligands bind and cause it to differentiate and activity.
153
What is OPG?
Osteoblasts release OPG which bind to RANK ligands so inhibit osteoclast differentiation and activity
154
Describe Denosumab function
Monoclonal antibody binds to RANK ligands so blocks osteoclast formation and formation
= Treatment for osteoporosus
155
What is sclerostin?
Osteocytes secreted protein decreases bone formation by inhibiting Wnt signals on osteoblasts
Loss of function causes high bone density so therapeutic target for osteoporosis
156
What is Romosozumab?
Humanised anti-sclerostin increases bone formation and decreases resorption
(Osteoporosis treatment)
157
Role of phosphate in physiology
Phospholipids
Repolarisation
Signalling pathways (cAMP)
Nucleotides
ATP
Kinases (switching genes on)
Hydroxyapatite (bones)
158
How much phosphate in body?
Whole body 500-800g
90% in bone mineral
159
Serum phosphate
0.8-1.5mmol/L
160
Low phosphate problem
Can’t form bones
= Rickets or osteomalacia
= Pain, fractures
161
High phosphate problems
Extra hydroxyapatite formed and deposited in tissues
= Calcified blood vessels
= Tumour calcinosis
162
Dietary sources of phosphate
Protein
- Animals
- Dairy
- Soy
- Seeds and nuts
Recommend daily intake = 700mg
163
How much renal phosphate is filtered?
Unbound phosphate (90%) is filtered in glomerulus
80% reabsorbed in proximal tubules
10% reabsorbed in distal tubules
164
Regulation of phosphate metabolism
PTH = regulation of calcium but affects phosphate also
= Decreases tubular reabsorption of phosphate
1,25 vitamin F = Increases active gut absorption
165
Key regulator of phosphate metabolism
FGF-23 (fibroblast growth factor 23)
Produced by osteocytes in response to rise in phosphate, dietary phosphate loading, PTH and 1,25 vitamin D
= Decreases expression of Na transporter and increases renal excretion of phosphate
= Decreases 1a-hydroxylation of vitamin and so decreases gut absorption of phosphate
166
Genetic disorders of phosphate problems
Inherited rickets = low serum phosphate (XLH and ADR genes)
167
What is Tumour-induced osteomalacia?
Osteomalacia with low phase (rare) and small benign mesodermal tumours.
= Osteomalacia heals when tumour removed
168
Calcium vs phosphate regulation
Ca - regulated to increase = PTH, Vit D
P - regulated to decrease = PTH, FGF-23
169
What causes stiffness in bone?
Minerals
(Collagen = toughness)
