Bones - healing/calcium/vit d/collagen Flashcards

(69 cards)

1
Q

What are the 2 types of bone structures?

A

Compact/Cortical bone - closer to the surface

Trabecular/Cancellous/Spongy Bone

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2
Q

What are the 2 types of bone made?

A

Woven bone
- Immature, made rapidly, collagen laid down randomly

Lamellar bone
- Mature bone, collagen laid down in parallel sheets for strength

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3
Q

What is the structure in a compact bone?

A

Made up of Osteons/Haversian Systems, which consist of…

Haversian canals - blood, nerve, lymphatic supply
Columns composed of lamellae
Canals linked together by Volkmans Canals
Lacunae home for osteocytes
Osteoblasts line the surface of the Haversian canals
Osteoclasts found on surface of bone matrix

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4
Q

What are functions of bone?

A
Mechanical support: Keep us upright
Transmission of forces created by muscle contraction
Protection of vital organs
Calcium homeostasis
Haematopoiesis
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5
Q

What is the process for bone remodelling?

A

ACTIVATION
Osteoblasts sense damage and produce RANKL

RANKL can…

  1. Stimulate osteoclasts
  2. Bind to monocytes to induce formation into osteocytes in presence of M-CSF

RESORPTION
Osteoclasts secrete collagenase to digest collagen and HCL to dissolve hydroxyapatite into calcium and phosphate released into the blood stream, resorbed bone area form Howships Lacuna

REVERSAL
Osteoblasts secrete OPG to bind to RANKL and stop the activity of osteoclasts to stop bone resorption (osteoclasts die by apoptosis)

FORMATION
Osteoblasts secrete osteoid seam to lay down new collagen = osteoid

TERMINATION
This osteoid eventually becomes mineralised via deposit of calcium and phosphate to produce hydroxyapatite

QUIESCENCE
Osteoblasts become incorporated into the bone matrix as osteocytes or become quiescent surface bone lining cells

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6
Q

What is the effect of oestrogen on bone remodelling?

A

Increase expression of OPG to block RANKL
Blocks RANKL with competitive inhibitors(similar to OPG)

… to reduce osteoclast activity

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7
Q

What cells secrete OPG and RANKL?

A

Osteoblasts

Stromal cells

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8
Q

What is the net result of each bone remodelling cycle?

A

Osteon - package of bone where collagen fibres are aligned

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9
Q

What is the first stage in fracture healing?

A

Haematoma - Within 24 hours

Rupture of blood vessels causes the formation of a haematoma.
Haematoma acts as a fibrin mesh which seals the fracture site and provides a scaffold for the influx of inflammatory cells, fibroblasts and support for new capillary growth.

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10
Q

What is the second stage of fracture healing?

A

Soft Callus - After a week

Growth factors…
- Platelet derived growth factor - PDGF
- Fibroblast growth factor - FGF
- Transforming growth factor beta - TGF-beta
Activate osteoprogenitor cells in the periosteum, medullary cavity to stimulate osteoclast and osteoblast activity.

Mass of predominantly uncalcified tissue formed between fracture

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11
Q

What is the third stage of fracture healing?

A

Bony Callus - 3 weeks+

Activated osteoprogenitor cells deposit woven bone
Activated mesenchymal cells surrounding fracture differentiate into chondrocytes that make fibrocartilage and hyaline cartilage

Newly formed cartilage undergoes endochondral ossification forming contiguous network of bone - bridging fracture ends - converting callus to woven bone

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12
Q

What is the 4th and final stage of fracture healing?

A

Remodelling - 12 weeks+

Callus matures as it becomes weight-bearing and portions that are not stressed, are resorbed - this reduces the size of callus + outline of fractures are re-established as lamellar bone
Woven bone replaced by lamellar bone and excess callus resorbed
Healing process complete with restoration of medullary cavity

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13
Q

What can impede fracture healing?

A
  • Inadequate immobilisation - prevents normal callus maturation = delayed or non-union
  • Displace/comminuted fractures can lead to deformity
  • Open fractures - risk of nutrition
  • Malnutrition
  • Skeletal dysplasia - congenital abnormalities
  • Excessive trauma - systemic complications
  • Avascular necrosis
  • Intra-articular fracture
  • Weakened bone - by radiation/disease/tumour
  • Older age
  • Diabetes
  • Smoking
  • Drugs - steroids
  • Dependant on bone fractured
    • Tibia heals more slowly
    • Fractures of the diaphysis heal slower than of the metaphysis
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14
Q

Why can fractures involving joints have impaired healing?

A

Synovial fluid contains fibrinolytic agents - preventing haemotoma formation

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15
Q

What are the 2 types of ossification?

A

Intramembraneous ossification

- Bone develops directly within a sheet of mesenchymal or immature connective tissue
- Ossification of flat bones of the face, skull bones, clavicles 

Endochondral ossification

- Bone develops by replacing hyaline cartilage which acts as a template
- Ossification of bones at the base of skull and long bones, fractures
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16
Q

What is the role of osteocytes?

A

Regulate calcium in and out of cells

Canaliculi junctions for communication with other cells on the bone surface

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17
Q

What type of cells are osteoblasts?

A

Plump, cuboidal cells, single nuclei

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18
Q

What type of cells are osteoclasts

A

Large mutlinucleated cells

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19
Q

How can you estimate bone turnover?

A

Bone marrow biopsy from iliac crest

Stain with tetracycline at 2 different times to see rate of bone formation

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20
Q

What are clinical markers for bone formation?

A

P1NP - pro-collagen peptides

Alkaline phosphatase - released by osteoblast during mineralization of osteoid

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21
Q

What are clinical markers for bone resorption?

A

CTX - released from collagen breakdown

NTX

Acid phosphatase - if osteoclast very active

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22
Q

Difference between periosteal apposition and endosteal resorption?

A

Periosteal apposition - thickening of periosteum

  • Common in men - have stronger bones
  • Estrogen suppresses this
  • Androgens stimulate this

Endosteal resorption - resorption of inner layer
- More in females as they age

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23
Q

What is the recommended minimum vitamin D intake for female, male, adolescent, osteoporotic patient?

A

Average adult - 700mg

Female - 350mg
Male - 450mg
12-19 - 750mg
Osteoporosis - 1500mg

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24
Q

What are the 3 forms that calcium exist as in the blood?

A
  1. Free, ionic in the blood
  2. Bound to albumin
  3. Bound to anions - phosphate, citrate
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25
What is free calcium essential for?
Muscle contraction Release of neurotransmitters and hormones Enzyme activity Blood coagulation
26
What is adjusted calcium?
Total free calcium adjusted for albumin concentration. Gives a better reflection of ionised calcium in the blood as this is the calcium that is physiologically active Diseases can cause low albumin which can adjust calcium levels and mask total free calcium
27
How does calcium affect PTH and what is the role of PTH in calcium homeostasis?
LOW calcium INCREASES PTH production PTH... - Increase calcium reabsorption in the kidneys - Stimulate osteoblasts to secrete RANKL to stimulate osteoclasts for bone resorption - Calcitriol increases calcium absorption in the gut (PTH converts calcidiol to calcitriol in the kidneys) - Increase phosphate excretion in the kidneys
28
What must be present for the release of PTH?
Magnesium
29
What is the affect of calcium on calcitonin and what is its role in calcium homeostasis?
HIGH calcium stimulates calcitonin - Decreases bone resorption, stops osteoclasts - Decreases calcium resorption in the kidneys - Decreases phosphate resorption in the kidneys
30
What effect does alkalosis have on calcium-protein binding in the blood?
Increased calcium binding with proteins Decreased free calcium in the blood
31
What effect does acidosis have on calcium-protein binding in the blood?
Decreases binding of calcium with proteins Increased free calcium in the blood
32
What are symptoms of hypocalcaemia?
Calcium level <2.2mmol/L Muscle spasm, cramps, tetany Paraesthesia Cardiac abnormalities Seizures Coma Chvosteks sign - facial nerve twitch
33
What causes hypocalcaemia?
- Renal failure - Hypoparathyroidism - Vitamin D deficiency/malabsorption - Pancreatitis/Rhabdomyolysis - Adrenal insufficiency - Genetics
34
What are signs and symptoms for hypercalcaemia?
Ca > 2.6mmol/L Nausea Constipation Peptic ulcers Mental disturbance/depression Renal failure, renal stones, polyuria Soft tissue calcification Thinning of bones - PTH driving resorption of bone
35
What are causes of hypercalcaemia?
- Hyperparathyroidism - primary - Hypercalcaemia of malignancy - lung, breast, blood - tumours produce a factor that acts similar to PTH = PTHrP - Vitamin D intoxication - Sarcoid, GH excess, Vitamin A excess, Addisons - Drugs - lithium, thiazides - Idiopathic infantile hypercalcaemia - Familial benign hypercalcaemic hypocalciuria Always check PTH when have high calcium
36
What form of vitamin D to we test in the blood and why?
Calcifidiol - 25-hydroxycholecalciferol Reflects the production Testing the active form uses PTH so would be skewed
37
What are causes of vitamin D deficiency?
- low sunshine exposure - low dietary supply - low absorption - obesity - high loss/utlisation
38
Who are at increased risk of vitamin D deficiency?
- Dark skinned individuals - Concealing dress style - Little UVB exposure - Obesity - Adolescents - Frail elderly - Exclusively breast-fed babies - Winter - Co-morbidities - renal disease, coeliac disease, liver disease, GI disorders, CF, TB, HIV
39
What diseases can occur as a result of vitamin D deficiency?
- Osteomalacia in adults | - Rickets in children
40
What are clinical symptoms of vitamin D deficiency?
- Non-specific - Fatigue - Generalised muscle, joint and bone pain - Hyperalgesia - Fragility fractures - Waddling gait
41
What is the process of Vitamin D metabolism?
7-dehyrdocholesterol in the skin - inactive (activated by UV) Cholecalciferol in the blood - inactive (activated by 25-hydroxylase) 25-OHD - Calcidiol in the liver - inactive (activated by 1alpha hydroxylase) 1-25OH2D - Calcitriol in the kidney - ACTIVE
42
What is the active form of vitamin D and what is its role in calcium metabolism?
Calcitriol - activated in the kidney Increases absorption of calcium and phosphate in the GI tract Increases reabsorption of calcium and phosphate in the kidneys Increases osteoclast activity of bone Increases calcium and phosphate in the blood
43
What is the role of calcium on vitamin D metabolism?
Low calcium stimulates release of PTH PTH activates 1-alpha hydroxylase 1-alpha hydroxylase converts calcidiol to active calcitriol
44
What is the role of FGF23?
Suppresses kidney reabsorption of phosphate to increase urinary excretion Blocks activation of calcidiol into calcitriol Blocks PTH (secreted by osteocytes)
45
What is the effect of calcitriol on bone?
Stimulates bone resorption - Stimulates FGF23 - Inhibits activation of calcidiol - Inhibits release of PTH
46
What are the 3 main amino acids in collagen?
Glycine Proline Hydroxyproline
47
What is the structure of collagen?
Procollagen: 3 alpha chains of repeating amino acid triplet (Stablised by collagen proteases and hydrogen bonds) Tropocollagen: Triple helix of collagen
48
Why is vitamin C crucial for collagen?
Vitamin C is a cofactor for the collagen proteases that hydroxylate collagen which is key for stability
49
Where are the 4 types of collagen found in the body?
Type I: Bone, Skin, Tendons Type II: Cartilage Type III: Reticulin, Blood vessels Type IV: Basement membranes
50
What is the role of elastin, what is it made of and where is it found?
Recoil and stretch Elastin + Fibrillin-1 + Fibrillin-2 crosslinked Found in blood vessels, ligaments, skin and lungs
51
What are properties of proteoglycans?
Negative charge which traps water in tissues Keep cells hydrated and cushioned Resist compression High content in cartilage Protein core and chain of sugars Fill space between cells Hyaluronic acid, aggregan, fibromodulin, decorin
52
What are symptoms of vitamin C deficiency and what is it called?
Scurvy ``` Swollen, bleeding gums Bruising Poor wound healing Skin lesions Joint pain/weakness ```
53
What are signs and symptoms of Marfans Syndrome?
``` Long, tall human - long fingers/toes Scoliosis Flexible joints Stretch marks on the skin Aorta dilation, aneurysm, dissection, rupture Mitral valve prolapse ```
54
What kind of inheritance is Marfan syndrome and what is the mutation?
Autosomal dominant inheritance Mutations in Fibrillin-1 gene
55
What kind of inheritance is osteogenesis imperfecta and what is the mutation?
Autosomal dominant inheritance Type I collagen mutation of glycine
56
What are signs and symptoms of osteogenesis imperfecta?
Brittle bones - deformities, fractures Eyes - blue sclarae Teeth - Small, blue teeth Ears - Hearing loss
57
What are the main 2 types of EDS?
Autosomal dominant inheritance Classic - Mutation in type 5 collagen Vascular - Mutation in type 3 collagen
58
What are signs and symptoms of EDS?
Stretchy skin Easy bruising Flexible joints
59
What other types of EDS can you have if the mutation is not in collagen?
Mutations in the enzymes in collagen synthesis Kyphoscoliotic EDS - defect in lysyl hydroxylase Musculocontractual EDS - defect in collagen peptides
60
What is Alport Syndrome - signs and mutation?
X linked dominant Mutations in type 4 collagen ``` Haematuria Proteinuria Renal insufficiency - renal failure Renal hypertension Hearing loss Eye issues ``` *** Differential diagnosis - Goodpasture's Syndrome - similar presentation of glomerulonephritis - caused by anti-GBM antibodies ***
61
What bone disease has normal calcium, phosphate, ALP, PTH values?
Osteoporosis
62
What bone disease has... decreased calcium and phosphate increased ALP, PTH values?
Osteomalacia
63
What bone disease has... normal calcium, phosphate, PTH increased ALP values?
Paget's disease
64
What disease has... decreased phosphate increased calcium, ALP, PTH values?
Primary hyperparathyroidism
65
What would be the lab values of secondary hyperparathyroidism? (CKD)
Decreased calcium | Increased phosphate, ALP, PTH
66
What are early complications of fractures?
Compartment syndrome Infection Fat embolism Thromboembolism
67
What are immediate complications of fractures?
Nerve palsy Haemorrhage Skin tear Ischaemia
68
What are late complications of fractures?
``` Malunion Non-union Delayed union Osteoarthritis Avascular necrosis Growth disturbance Stiffness and pain Osteomyelitis ```
69
What are causes of pathological fractures?
``` Pagets Tumours - benign/malignant Bone metastases Infection Osteogenesis imperfecta Osteomalacia/rickets Osteoporosis ```