Pathophysiology Flashcards
What’re the components of bone?
Bone matrix
- collagen
- ground substance
Minerals
Cells
- osteoblasts
- osteoclasts
- osteocytes
What’s the percentage of the composition of an average bone?
30% matrix
70% mineral
Explain what’s a collagen?
Collagen fibrils form a triple helix of polypeptide chains
Strength of bone affected by collagen fibre direction
Collagen fibrils overlap and form crosslinkages. Mineral deposited in spaces between collagen fibrils.
What’s the ground substance of the bone matrix?
Made up of proteoglycans deposited on a framework of hyaluronic acid
Proteogylcans are proteins which strengthen bone by forming compression resistant networks between collagen fibrils
Proteogylcns control ion movement.
Explain what are bone minerals?i
Mineral = hydroxyapatite HAP (made from fluid Ca-P compounds in matrix)
Provides compressional strength
Increases strength of bone far beyond what is provided by collagen and mineral components.
Strength = cast iron, half as strong as steel
Explain how mineralisation actually occurs in the bone
Mineralisation occurs when local conc of Ca and P is increased by the action of ALP, and after a certain concentration, crystals begin to form (initially amphorous CA-P that transform into HAP)
Ca:P in HAP = 1.3:1, and 2:1
OtheR molecules like Mg, Na, K and CO3- also present but not organised into specific crystals. HAP can incorporate other minerals like, strontium, heavy metals, and radioactive metals
20-30% of HAP remains amorphous, so that the minerals in the HAP are readily available when Ca deficient in blood
P
Are isotopes tolerated by any bone?
No, new bones have greater affinity for isotopes than old bone.
What does pathological calcification refer to?
Inhibitors inhibit Ca-P salt deposition in soft tissue, but they can sometimes fail and lead to HAP deposited in soft tissue
This can be
- dystrophic calcification (in dying tissue)
- metastatic calcification (associated with hypercalcemia)
What’re osteoblasts?
Bone making cells
Active on surface of bone
Produce bone matrix (osteoid) - non mineralised matrix with only collagen and ground substance
Once production of matrix is complete, they become osteocytes
What’re osteocytes?
Cells located in lacunae of bone matrix, in which they are osteoblasts which have been trapped in the bone.
They maintain bone structure
Linked with other osteocytes and osteoblasts through channels (minerals move through channels)
What are osteoclasts?
Bone resorbing cells
They remove bone during repair and remodel
Derived from macrophages (immune cell to combat infection) and do a similar scavenging job
What’re the structure classifications of bone?
Cortical
- makes up hard outer chill and gives shape
- concentric ting structure
- in long bones, cortical bone surrounds the medullary cavity
Spongy (Cancellous)
- internal layer at the end of long bones between cortical bone and medullary cavity
How do you classify bones by microscopic appearance ?
Woven bone
- collagen fibres randomly arranged
- contains many osteocytes
- found on new bone sites, and some bone disorders and tumours
- in an adult = pathological process
Lamellar bone
- collagen fibres arranged orderly
- laid down on pre existing framework (usually a woven framework)
How would you classify bones by origin?
Endochondral ossification
Intramembranous ossification
What is endochondral ossification?
- long bones grow using this method
- it’s the ossification of a cartilage model (ie. ossification centres)
- eg. long bones develop from 3 primary ossification centres (diaphysis and 2 epiphysis)
- bone growth occurs at the ends of diaphysis where layer of cartailage is actively growing, metaphysis/epiphysis is the location. And so cartilage is produced at the ends and pushed down towards diaphysis.
- when cartilage stops growing, it ossifies and plate closes with no more growth
What is intramenbranous ossification?
Forms bones of skull and face (flat bones;)
Occurs in fibrous tissue but has a centre ossification, which extends from the centre to the periphery of bone
Increase in circumference occurs by the ossification of adjacent fibrous tissue
What is referred by the term bone metabolism ?
Bone is rigid static structure, with constant turnover of minerals of the bone
Bone is flexible, bending forces applied and bone can remodel in response to forces applied
Explain the process of bone remodelling
Existing bone is resorber and new bone laid down, this happened continually in the body.
Repairs microscopic bone injuries, and is normally matched by the type of stress experiment by bone ie. areas of greatest stress = greatest thickness
Bone precursor cells located on surface of bone and in vascular channels
Phase 1- stimulus like hormones, drugs, physical stress activates precursor cells to osteoclasts
Phase 2- osteoclasts resorb bone leaving behind a resorption cavity. (2 weeks process)
Phase 3 - osteoblasts lining the resorption cavity lay new bone (4 month process)
Explain the bloody supply necessary for bones
Main blood supply = nutrient artery (enters bone during iniatal cartilage phase) supplies inner bone
Outer blood supply = periosteal arteries
Growth plate = own blood supply in which the blood vessels penetrate through the cartilage and allow ossification process
Why does a frvature cause significant bleeding?
Cause bones have an abundant blood supply
Discuss the complications of blood supply to the bone
Blood flow through these vessels is sluggish and the blood can deliver bacteria to the bone and lead to infection (osteomyelitis)
Bones such as the proximal femur and schaphoid are entriely covered by articular cartilage, and so blood vessels can’t penetrate through them for repair if there is a frvature at these regions
And so this can lead to AVN, osteochondritis, osteomyelitis, aseptic necrosis
Explain the hormonal control of calcium levels in the bone and blood
Vitamin D
- increases Ca retention
- potent effect in increasing Ca absorption from GIT and kidneys
- effects bone deposition and resabsorption
- activated in liver and kidneys. Synthetic VitD administered if liver and kidneys fail
Parathyroid hormone
- increases Ca removal (increases Ca in blood)
- increases Ca and P absorption from bone and into blood (stimulates osteoclasts)
- decreases Ca excretion in kidneys and increases P excretion
- PTH acts with VitD to increase Ca resorption from gut
Calcitonin
- increases Ca retention in bone (opposite of PTH)
- decreases activity of osteoclasts
- osteobalstic activty increased
What’s hyperparathyroidism?
Chronic hypoclcaemia and hypophosphataemia decrease bone mineralisation
PTH levels elevated = increase Ca resorption from bone and phosphate lost in urine
Explain the affect of three main hormones related to the growth of bone
Thyroid hormone
- major hormone up to 3 years of age then decreases in significance
GH
- stimulates cartilage production at growth plate (importance; 3-15 yo)
Androgens
- most important in age range 12-19. Causes the closure of growth plates
What other hormones play a part but minor in terms of bone growth?
Glucocorticoids decrease bone formation and increase bone resorption by inhibiting protein synthesis. There is significant bone loss in untreated diabetes msllitus
Hypercalcaemia is a common effect of cancer (Ca withdrawn from bone). Bone metastases cause local erosion. And some tumours produce substances with PTH type activity
Name the different types of fractures
Compound Torus Avulsion Compression Comminuted Pathological Stress (buttressing effect) Intra-articular (extends into joints, risk of developing 2 deg OA) Occult fractures (easily missed. Use CT if overlying strictures present. If non-displaced and no cortical disruption like stress, use MRI)
Name the different positioning of fracture lines
Transverse Oblique Spiral (multiple views needed) Greenstick Segmental
Explain how major injuries can be repaired
Haematoma formation
- occurs with vessel damage
- fibrin (protein substance involved in clotting of blood) forms initial framework for healing. Tissue damage = fibrinogen converted into fibrin at wound
Procallus
- fibroblasts, osteoblasts and capillaries move into the wound to produce granulation tissue
Callus
- osteoblasts deposit disorganised clumps of primitive bone matrix (woven bone). This is the callus
Formation of normal bone with replacement of woven bone
Remodelling of periosteal and endosteal surfaces
What’re the factors that can affect the remodelling of bone after a frvature?
Local blood supply
Type of fracture
- ie. spiral/oblique faster healing than transverse. Comminuted fracture can have avascular fragment that become sequestrated.
Fixation
- quality determines healing time.
- movemntment May lead to non union
- IM pins may disrupt blood supply
Age
Concurrent infection, disease, nutritional status
How do you evaluate if a fracture has completely healed?
Continuity of cortex
Calcified complete bridge of callus
No visible line
(Process of 6weeks with adequate fixation)
What are the complications of fracture repair?
Delayed union - due to motion, infection, age, pathological fracture
Non union - due to motion, avascularity, infection
Signs of non union
- smooth sclerotic edges with no callus
- sealed medullary cavity
- pseudoarthrosis (failure of fusion)
Malunion
- deformity of bone
- due to improper reduction or rotation or collapse during healing
Define the meaning of different types of abnormalities that can occur
Apalsia = failure to form Hypopalsia = fail to grow to normal size Dysplasia = abnormal growth Hyperplasia = overgrowth
What’s Spina bifida? Congenital or developmental abnormality
Incomplete closure of neural arches (mostly in lumbosacral)
May cause minor sensory loss (paraplegia)
Often only detected on X-ray
Explain what’s scoliosis and kyphosis? Congenital or developmental abnormality
Scoliosis = lateral spine curvature
Kyphosis = more posterioly curved
What’s a metabolic bone disease and give examples of some ?
Abnormal bone structure caused by altered or inadequate biochemical reactions due to genetics, diet, hormones
Ie. osteoporosis, osteomalacia,
Explain what is osteoporosis
Density or mass of bone reduced, but bone remains normal
- bone loss is generalised or regional
- spongy bone is worse affected
- women more suspectible than men: postmenopausal osteoporosis due to lack of Oestrogen. Oestrogen desensitises osteoclasts to PTH
Causes:
Hypertparahyroidism can cause it
Low Ca diet (excessive Ca can depress VitD and PTH)
High cortisol levels (ie. corticosteroid supplements or Cushings disease can decrease bone mass)
What’s regional osteoporosis
Associated with disuse or immobilisation
After 8 weeks, significant osteoporosis is present although it will develop faster in <20 yo and >50 yo
Exaplain the analysis of osteoporosis
Spinal radiographs = vertebral deformity and decreased density
Bone density analysis = post menopausal women in upper 3rd of population not at risk. Bone density should be > 100 mg/cm3 for compression fractures not to occur
Explain what is osteomalacia
Associated with a lack of VitD
Osteoid production occurs, but conversion of osteoid to bone is inadequate. Thus differntiating from osteoporosis
Due to:
- poor mineral intake
- lack of sunlight
- renal or hepatic disease including biliary obstruction
Known as rickets in children
Explain bone tumours and the form of bone tumour
Benign or malignant
They can be primary or secondary
Primary: vast majority are benign, young patients = most are benign Older patients = most are malignant Slight male predominance
secondary tumours:
metastatic (more common than primary)
spread of adjacent neoplasms,
malignant transformation of pre-existing benign lesions
Metastatic cancers are usually multifocal, adults (over 40 yo) (prostate, breast, kidney, lung), children (in 1st decade)
How is radiology involved in cancer diagnosis?
Bones involved
Specific site involved (cortex or medulla, epiphysis, diaphysis, or metaphysis)
Tumour margin and contour
Compare the differences between metastatic and being tumours?
Least amount of pathological damage occurs within benign tumours as they are localised and well defined geographic borders
They oress on surrounding structures causing compression and displacement, and even stress fractures
Invasive, illdegined tumours = malignant
Explain what is osteosarcoma
Malignant
90% in metaphysis of long bone, especially distal femur
Common = < 20 and >60
On radiographs: moth eaten sunburst appearance
Explain what is chondrosarcoma
Occurs in metaphysis and diaphysis Of long bones (esp. medullary cavity of femur, humerus and pelvis)
Causes a lucent defect in bone
Occurs in middle age and older
Explain what is fibrosarcoma
Occurs in middle age, rare
Metaphysis of femur and tibia
Lucent lesions with cortical destruction
Explain what is myeloma
Affects older than 50
Vertebrae involved
Where do metastatic bone tumours originate from?
Tumours of the breast, prostate and thyroid commonly metastasise to the bone
Explain what is osteomyelitis
Bacterial infection with staph aureus (common pathogen), affects children (growth plates of limbs usually) and elderly (metaphysis)
Exogenous infection: direct penetration of open wound
Haematogemous infection: spread from distant sites of body
Intense inflammation caused by periosteal elevation and draining sinuses in skin. AVN of bone fragments common leading to sequestrum formation.
Children; layer of new bone around site (involucrum)
