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Phase 1 Notes > MSK > Flashcards

MSK Flashcards

1
Q

Costs of disease

A

Direct - ambulatory, impatient
Secondary - mental health, complications
Indirect - loss of pay
Quality of life - pain, anxiety

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2
Q

4 classes of musculoskeletal diseases

A

Degenerative disease
Inflammatory disease
Metabolic disease
Injury

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3
Q

Osteoarthritis vs rheumatoid arthritis

A

Osteo - cartilage eroded so bones in joint rub together
Rheu - swollen inflamed synovial membrane in joint

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4
Q

What is the commonest joint disease worldwide?

A

Osteoarthritis
= 80% of over 75s

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5
Q

Describe inflammatory rheumatoid arthritis

A

Inflammatory cytokines forms a pannus which starts to grow over and damage the cartilage

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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.

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7
Q

What is osteogenesis imperfects?

A

Collagen not structured properly - gaps have lumps of mineral deposits so doesn’t function well

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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

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9
Q

Describe collagen breakdown

A

Proteinases, collagenases an cathepsin K break down collagen for repair and replacement

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10
Q

Breakdown of type 1 collagen forms?

A

NTX
CTX
(We can measure as markers in diseases)

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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

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12
Q

Purpose of skeleton

A

Transmits body weight
RBC production
Structural support + protects vital structures
Stores Ca, P, Mg

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13
Q

How many bones in the body?

A

206
Axial = 80
Appendicular - 126

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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

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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

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16
Q

Which bone structure is visible by eye?

A

Corticol vs trabecular

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17
Q

Types of bone structure (micro)

A

Woven - Disorganised, no clear structure made quickly

Lamellar - Organised, layered made slowly

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18
Q

% in bone compositions

A

50-70% mineral (provides stiffness)
20-40% organic matrix (collagen for elasticity)
5-10% water

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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

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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

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21
Q

Osteoblast origin?

A

Mesenchymal cell -> progenitor ->

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22
Q

Osteoblasts function

A

Form bone osteoid, produces Type 1 collagen an deposits hydroxyapatite crystals

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23
Q

Osteoclasts origin?

A

Hematopoietic stem cells
-> Monocyte
-> Macrophage
Osteoclasts = specialised macrophages

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24
Q

Functions of osteoclasts

A

Resort bone, breakdown collagen and dissolve mineralised matrix with acid.

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25
Q

Reasons for bone modelling

A

Replace woven with lamellar bone
Repair damage
Obtain calcium
Response to loading (exercise)
Store and release minerals

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26
Q

How does bone remodelling/ bone turnover occur?

A

Resting phase
Activation
Resorption - osteoclasts destroy
Reversal phase - osteoclasts apoptosis
Formation - osteoblasts fill pits

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27
Q

Modelling vs remodelling

A

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

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28
Q

Name some clinical problems

A

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

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29
Q

Where is 99% calcium in the body?

A

Skeleton (1200g)

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30
Q

Where is 1% of calcium?

A

Extracellular space (1g)
For blood clotting, muscle contractility and nerve function

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31
Q

How is calcium transported in the blood?

A

Ionised (metabolically active) - 45%
Protein-bound (not metabolically active) - 45%
Complexed to ions like citrate and phosphate - 10%

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32
Q

Normal concentration of calcium in blood?

A

Total serum = 2.4mmol/L
(Ionised serum = 1.1mmol/L)

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33
Q

What happens to ionised calcium in alkalosis?

A

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)

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34
Q

Sources of calcium

A

Dietary = absorption
Bone resorption
Kidneys = reabsorption

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35
Q

How much dietary calcium is absorbed?

A

Eat 500-1500mg and 30% absorbed
(Active absorption in duodenum and jejunum, passive absorption in ileum and colon)

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36
Q

Sources of dietary calcium

A

Mainly dairy
Minor - vegetables, Cereals, oily fish

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37
Q

What does the bone do when plasma calcium falls?

A

Rapid release of exchangeable calcium from bone surface spring bone resorption

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38
Q

How much calcium is reabsorbed in the kidneys?

A

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

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39
Q

How is serum calcium regulated?

A

When serum calcium decreases slightly, parathyroid glands detect and lots of parathyroid hormone is secreted.
Degradation occurs within minutes and fragments are excreted.

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40
Q

How is calcium levels detected in parathyroid cells?

A

Calcium inhibits PTH release
Active Vit D reduces PTH synthesis

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41
Q

Where does most Vit D come from?

A

Skin (UV-B)

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42
Q

What’s the main form of Vit D in blood (measured)?

A

25-OH vitamin D

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43
Q

What does 25-OH vitamin D split into?

A

High PTH forms:
1,25(OH)2 Vit D
High fibroblast growth factor 23 forms:
1,24,25 (OH)3 Vit D

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44
Q

What is calcitriol?

A

Active form of vitamin D - hydroxylated at position 1 and 25

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45
Q

Function of calcitriol?

A

Binds to vitamin D receptor and stimulates production of 3 key transport proteins TRPV6, PMCA and calbindin-D which absorb calcium in the intestines

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46
Q

What is calcitonin?

A

When high serum calcium, hormone produced by C cells in thyroid = lowers bone resorption

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47
Q

How does parathyroid hormone work?

A

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)

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48
Q

Fast vs slow PTH actions

A

Fast = renal reabsorption, exchangeable calcium released

Slow = bone resorption, increased intestinal calcium absorption

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49
Q

Interstitial vs appositional growth

A

I - growth from within (most tissue)
A - growth from outside (bone)

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50
Q

Endochondral vs intramembranous ossification (helps fetal bones grow longitudinally)

A

E - long bone growth by deposition on cartilage primordium
I - Only in flat bone with no cartilage precursor

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51
Q

How does endochondral ossification occur?

A

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

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52
Q

How does intramembranous ossification occur?

A

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

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53
Q

How does bones become wider in modelling?

A

Modelling drift - osteoblasts form new bone and osteoclasts resorbs old bone in different areas (so can also become curved)

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54
Q

What is osteonal tunnelling?

A

In compact, cortical secondary one, osteons are present
= primary osteons form during growth and secondary osteoid replace bone or mobilise minerals

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55
Q

What are osteons?

A

Layers of lamellar bone with osteocytes surrounding a Haversian canal of blood vessels.

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56
Q

Functions of skeletal muscle

A

Movement
Support soft tissue
Maintain posture
Communication
Maintain body temperature
Control of opening passageways

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57
Q

Characteristics of muscles

A

Excitability
Conductivity
Contractility
Extensibility
Elasticity

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58
Q

Describe muscle structure

A

Muscle fibrils -> muscle fibres -> muscle fasicules
Contains sarcomeres, sarcoplasmic and t-tubules

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59
Q

Describe sarcomere bands

A

A
I - Just actin
H - Just myosin
Z

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60
Q

A-actin vs tropomodulin vs Nebulin

A

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

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61
Q

What is titin?

A

Spring like protein anchors myosin to Z disc
(Largest protein of genome)

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62
Q

How many myosin heads in each filament?

A

300

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63
Q

Describe contraction of sarcomeres

A

ATP hydrolysed causes myosin head to release actin filament and progress along filament. Head then binds to new binding site and pulls actin along.

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64
Q

How often do sarcomeres contract?

A

5x/sec

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65
Q

How is contraction initiated at the neuromuscular junction?

A

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.

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66
Q

Three parts of troponin

A

Tn I - Inhibitory
Tn T - binds tropomyosin
Tn C - binds calcium

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67
Q

Describe actin structure

A

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.

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68
Q

Describe myosin structure?

A

2 heavy chains, 4 light chains

69
Q

What is botulinum toxin?

A

Most common cause of food poisoning blocks Ach release.
Can be used to treat uncontrolled muscle spasm

70
Q

Types of muscle fibres

A

1 - Slow oxidative - aerobic
2A - Fast oxidative - aerobic with mitochondria and glycogen
2B - Fast glycolytic - anaerobic with high glycogen

71
Q

Slow fibres are ____ the diameter of fast fibres

A

Half

72
Q

Describe glycolytic metabolism

A

Glycogen -> glucose -> pyruvic acid -> lactic acid
(2 ATP)

73
Q

What is phosphorcreatine?

A

Creatine kinase catalyses donation of phosphate to ADP to form ATP
(Reduced fatigue)

74
Q

What is muscle fatigue?

A

Decreased ATP synthesis
Lactic acid build up

75
Q

How to distinguish between muscles histologically

A

Cardiac - branched
Skeletal - multinucleate
Smooth - Unstriated

76
Q

Tendons vs ligaments function

A

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
Q

Tissue composition of tendons and ligaments

A

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
Q

Why are ligament fibrils crimped?

A

Enables some increase in length during tension

79
Q

Describe collagen structure of tendons and ligaments

A

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
Q

Hierarchical structure formation: 1-collagen synthesis

A

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
Q

Hierarchical structure formation: 2-collagen processing

A

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
Q

Hierarchical structure formation: 3-fibrillogenesis

A

Collagen -> microfibrils -> subfibrils -> fibrils -> fibres -> fascicles surrounded by endotenon -> tendon surrounded by epitenon

83
Q

Function of elastin

A

Elasticity in tendons (less) and ligaments. More present in ligamentum flavum (spine)

84
Q

Ligament vs tendon structure

A

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
Q

What is insertion of tendons and ligaments called?

A

Enthesis
(Fibrous / fibrocartilagenous)

86
Q

Fibrous vs fibrocartilagenous insertion

A

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
Q

How do tendons and ligaments manage load bearing?

A

Viscoelastic material
Results in elongation between original ends of tissue
Compression results in contraction between tissue ends
Mechanical cues affect healing, homeostasis

88
Q

Typical load-elongation curve

A

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
Q

Describe ligamentum flavum structure

A

Provides intrinsic stability to spine with lots of elastin (60-70%).

90
Q

What is a Golgi tendon organ?

A

Encapsulated sensory proprioreceptors intendons activated by stretch and muscles contraction. (Simple reflex causes muscle releaxation)

91
Q

What affects mechanical properties of ligaments and tendons

A

Age (collagen decreases)
Pregnancy + postpartum
Physical training
Immobilisation

92
Q

Tendon and ligament injury mechanism

A

Obesity
Direct trauma
Acute tensile failure
Strain, rupture
Avulsion from bone
Tendon overuse
Joint displacement
Can cause osteoarthritis

93
Q

Tendon and ligament repair

A

Inflammatory phase (days)
Proliferation phase (weeks)
Remodelling and maturation (months)

94
Q

3 functions of joint

A

Bear weight
Transfer load evenly to MSK
Allow 3D movement

95
Q

3 types of structural joints

A

Fibrous e.g. teeth sockets
Cartilaginous e.g. spine
Synovial e.g. hip

96
Q

3 types of functional joints

A

Synarthroses - immovable, mainly fibrous
Amohiarthroses - slightly moveable, mostly cartilaginous
Diarthroses - freely moveable, mostly synovial

97
Q

3 types of fibrous joints

A

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
Q

2 types of cartilaginous joints

A

Synchondroses - Bones directly connected by hyaline cartilage e.g. costal ribs
Symphyses - pad or plate of fibrocartilage e.g. intervertebral disc

99
Q

Components of synovial joints

A
  1. Articulate cartilage
  2. Joint capsule (synovial membrane)
  3. Joint cavity
  4. Synovial fluid
  5. Reinforcing ligament

(Also bursae and menisci)

100
Q

3 types of cartilage

A

Elastic - bend e.g. ears
Fibrocartilage - less ecm e.g. intervertebral discs
Hyaline - more ecm e.g. costal

101
Q

Components of hyaline cartilage

A

Frictionless surface
No blood supply (anaerobic)
Low cell content
High water content
Resists compressive loads

(Fibrocartilage is opposite)

102
Q

Zones of articular cartilage

A

Superficial
Middle - most cartilage here
Deep

103
Q

How is synovial fluid formed?

A

Modified plasma by synovial membrane contains charged sugars that bind to water and reduce friction

104
Q

Lever types of synovial joints

A

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
Q

Normal blood Uric acid levels

A

Men: 200-430umol/L
Women: 140-360umol/L

106
Q

What is Gout?

A

High uric acid levels in the blood cause uric crystals to deposit in joints = cause inflammation, swelling and pain

107
Q

What is Uric acid?

A

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
Q

How is uric acid excreted?

A

70% renal (in urine)
30% gut (breakdown)

109
Q

Why does gout affect big toe joints more?

A

Poor circulation

110
Q

Why are uric acids higher in men?

A

Oestrogen in women is protective as it promotes excretion

111
Q

Sources of dietary purines

A

Meat
Offal - heart, liver, kidney
Seafood
Oatmeal, soya, yeast
Soft drinks
Alcohol

112
Q

Risk factors for gout

A

Metabolic syndrome - obesity, raised no, raised triglycerides
Coronary heart disease
Diabetes

113
Q

Which medicine impact gout

A

Thiazide diuretics
Low dose aspirin
= kidneys affects excretion

114
Q

Management for Gout

A

Rest, ice, elevate
Anti inflammatory medication
Reduce alcohol and purine rich food
Loose weight
Switch by medication

115
Q

Action of allopurinol

A

If 2 or more attacks within a year
= Inhibits breakdown of purines to uric acid (xanthine oxidase)

116
Q

Uric acid formation

A

Purines -> xanthine -> uric acid
Both steps catalysed by xanthine oxidase

117
Q

Complications of gout

A

Damage to joints
Secondary infections
Nerve damage
Kidney stones
Gouty trophi - crystals in soft tissue

118
Q

Causes of increased turnover of nucleic acids

A

Malignant tissue
Increased tissue breakdown e.g. trauma, starvation, tumour lysis syndrome
Psoriasis (too many cells produced)

119
Q

What is rasburicase?

A

Medication prevents tumour lysis syndrome
= unrated-oxidase enzyme converts uric acid to allontoin which is more soluble in water and easily excreted

120
Q

What is Lesch-Nyhan syndrome

A

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
Q

What is hyperuricemia?

A

Over production/ Under excretion of uric acid or a combination

122
Q

Function of bones

A

Protect vital organs
Allow muscles to work
Store minerals and house marrow cells
Mechanical functions account for shape and size

123
Q

Why do bones respond to exercise?

A

Genetic predisposition
Arm building exercises
= Remodelling
= Denser bone

124
Q

How to calculate strain in bones?

A

Original length-new length of
——————————————
Original length of bone

125
Q

What is peak bone strain in running humans?

A

2000 x million

126
Q

Describe strain based feedback loop

A

Increased activity -> Higher than customary strains -> Bone formation
Vice versa

127
Q

Strain variables

A

Magnitude
Rate
Frequency
Dwell (hold periods)
Number of cycles

128
Q

Example of site specific strain

A

During a jump:
Skull = 170
Tibia = 850
X10,000 strain

129
Q

Does bone rely on just:
Site Specific Customary Strain Stimulus?

A

No! Also:
Sex
Age
Bio chemicals e.g. hormones
Drugs/medicines

130
Q

What is the mechanostat theory?

A

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
Q

How do bones respond to exercise stimulus

A

Occasional high magnitude high rate events
Bone responds to only a few loading cycles and rest periods increase effect

132
Q

What cells sense loading/disuse?

A

Osteocytes are mechanosensors (via hydrostatic pressure, direct cellular deformation and fluid flow shear stress) and mechanotransducers of the bone via many channels etc.

133
Q

How does loading change bone microstructure?

A

Osteocytes regulate activities of osteoblasts and osteoclasts via signalling molecules
= regulate bone resorption and restoration
= targets other organs e.g. heart, kidneys

134
Q

Other factors affecting intercellular communication during exercise

A

Age
Gender
Genotype
Diet
Environment

135
Q

Define a fracture

A

= Breach in continuity of bone

136
Q

When do fractures occur?

A

Non-physiological load applies to normal bone
Physiological load (normal) applied to abnormal bone (weak)

137
Q

When does incidence of fractures increase?

A

Puberty/ growth spurt
Post menopausal
Ageing

138
Q

Examples of abnormal bone

A

Tumours (benign/metastatic/malignant)

Metabolic bone disease (osteoporosis, osteogenesis imperfecta)

139
Q

Ways to describe fractures

A

Site (part of bone)
Pattern
Joint involvement (extra/intra-articular)
Skin involvement (open/closed + soft tissue damage)
Displacement / angulation (%)

140
Q

Fracture patterns unique to children

A

Growth plate affected but deformities remodel quickly

141
Q

4 stages of fracture healing

A

Haematology (hours)
Inflammation (days)
Repair (weeks)
Remodelling (months-yrs)

142
Q

Describe haemotome stage

A

Bleeding and blood clot at fracture site.
Decreased blood flow, periostea’s stripping and osteocyte death

143
Q

Describe inflammation stage

A

Fibrin clot forms
Neovascularisation
Cellular invasion:
- Haematoloetic cells clear debris
- Osteoclasts resort dead bone
- Mesenchymal stem cells build cells

144
Q

Describe repair stage

A

Fibroblasts form fibrous tissue = soft callus allow cartilage formation
Osteoblasts form osteoid
High vascularity
Progressive matrix mineralisation

145
Q

Describe remodelling stage

A

Woven bone is replaced by lamellar bone = increases strength
Normal vascularity and heals without a scar (unique)

146
Q

3 Principles of fracture management

A

Reduce (the fracture)
Immobilise (the part)
Rehabilitate (the patient)

147
Q

Types of fracture fixation

A

Sling
Casts and splints
Extra-medullary devices (plates and screws)
Intra-medullary devices (nails)
External fixation

148
Q

Factors that influence fracture healing

A

Patient - age, nutrition, smoking, drugs
Tissue - bone type, site, pathology, vascularity
Treatment - apposition of fragments, stability, micromotion

149
Q

Complications of fractures

A

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
Q

Regulation of bone turnover should be coupled and balanced

A

= Bone formation at sites of resorption
= Amount of bone removed is replaced

151
Q

Mediators of bone turnover

A

Hormones: PTH, Vit D, oestrogen, testosterone, cortisol, GH, leptin

Paracrine/autocrine: Prostaglandins, Interleukins (Inflammatory)

152
Q

What are RANK Ligands?

A

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
Q

What is OPG?

A

Osteoblasts release OPG which bind to RANK ligands so inhibit osteoclast differentiation and activity

154
Q

Describe Denosumab function

A

Monoclonal antibody binds to RANK ligands so blocks osteoclast formation and formation
= Treatment for osteoporosus

155
Q

What is sclerostin?

A

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
Q

What is Romosozumab?

A

Humanised anti-sclerostin increases bone formation and decreases resorption
(Osteoporosis treatment)

157
Q

Role of phosphate in physiology

A

Phospholipids
Repolarisation
Signalling pathways (cAMP)
Nucleotides
ATP
Kinases (switching genes on)
Hydroxyapatite (bones)

158
Q

How much phosphate in body?

A

Whole body 500-800g
90% in bone mineral

159
Q

Serum phosphate

A

0.8-1.5mmol/L

160
Q

Low phosphate problem

A

Can’t form bones
= Rickets or osteomalacia
= Pain, fractures

161
Q

High phosphate problems

A

Extra hydroxyapatite formed and deposited in tissues
= Calcified blood vessels
= Tumour calcinosis

162
Q

Dietary sources of phosphate

A

Protein
- Animals
- Dairy
- Soy
- Seeds and nuts

Recommend daily intake = 700mg

163
Q

How much renal phosphate is filtered?

A

Unbound phosphate (90%) is filtered in glomerulus
80% reabsorbed in proximal tubules
10% reabsorbed in distal tubules

164
Q

Regulation of phosphate metabolism

A

PTH = regulation of calcium but affects phosphate also
= Decreases tubular reabsorption of phosphate
1,25 vitamin F = Increases active gut absorption

165
Q

Key regulator of phosphate metabolism

A

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
Q

Genetic disorders of phosphate problems

A

Inherited rickets = low serum phosphate (XLH and ADR genes)

167
Q

What is Tumour-induced osteomalacia?

A

Osteomalacia with low phase (rare) and small benign mesodermal tumours.
= Osteomalacia heals when tumour removed

168
Q

Calcium vs phosphate regulation

A

Ca - regulated to increase = PTH, Vit D
P - regulated to decrease = PTH, FGF-23

169
Q

What causes stiffness in bone?

A

Minerals
(Collagen = toughness)

Phase 1 Notes (9 decks)

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