Lecture 1: Pathophysiology of Bone & Osteoarthritis Flashcards

1
Q

What are some characteristics of skeletal cartilage?

A
  • No nerves or blood supply
  • Surrounded by dense perichondrium (connective tissues that supply nutrients)
  • Replaced by bone later
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2
Q

What are the different types of skeletal cartilage?

A
  • Hyaline (joints) & most common
  • Elastic (external ear) more flexible
  • Fibrocartilage (invertebrate discs), resistys forces of compression
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3
Q

What are the functions of bone?

A
  • Structural: Support, Protection, Movement
  • Mineral Storage: Ca2+ & PO42-
  • Lipid storage
  • Blood cell formation (haematopoeisis in marrow cavities of long bone)
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4
Q

What are the classifications of bone?

A
  • Long bone (Humerus/femur): long shaft and 2 distinct ends. Compact bone on exterior with spngy inner bone marrow
  • Short bone (Carpal and Tarsal (hands)): cube like, thin compact bone with surrounding spongy bone mass
  • Flat Bone (sternum, skull): Thin flattened and curved, compact bone with spongy layer between
  • Irregular Bone (Hip bones/vertebrate): complicated shaope, spongy bone with thin layer of compact
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5
Q

What is the main bone composition and 2 types of bone?

A
  • 70% mineral (Ca2+ and PO42-)
  • 22% protein
  • 8% water
  • Compact: Mechanical and protective, dense bone tissue on outside and copvered by periosteum (thick membrane)
  • Spongy: Interior of bone, fibres and lamellae, storage and stem cells
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6
Q

What are the Diaphysis, Medullary Cavity, Epiphyses, Metaphysis, Periosteum and Endosteum parts of a long bone?

A
  • Diaphysis: Long part
  • Medullary Cavity: Interior spongy bone & cavity filled with yellow marrow (adipose)
  • Epiphyses: End of bone filled with spongy bone for haematopoeisis
  • Metaphysis: narrow area where new bone derived
  • Periosteum: Thick fibrous membrane and attachment for muscles and tendons (BVs, nerves)
  • Endosteum: Thin membrance of connective tissue lining inner surface of bony tissue
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7
Q

What are the main structural features of compact and spongy bone?

A
  • Compact: Dense outer layer, Structural unit: osteon. Rings of osteocytes in matrix, centre of each osteon = Bvs, nerves. Canals connect osteons
  • Spongy: No osteons, Honeycomb of matrix spikes = trabeculae. Irregulary arranged osteocytes, Haematopoeisis, spaces between trabeculkae have marrow which supplies nutrients and forms RBC & WBC
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8
Q

What are the 4 main cell types?

A
  • Osteoprogenitor
  • Osteoblasts
  • Osteocytes
  • Osteoclasts
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9
Q

What are Osteoprogeniotor cells?

A
  • Stem cells
  • Develop into osteoblasts
  • Found in deep layers of periosteum
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10
Q

What are Osteoblast cells?

A
  • Immature bone cells
  • Bone formation & regulate mineralisation
  • Differentiate into osteocytes
  • Found in periosteum and endosteum (growing parts)
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11
Q

What are Osteocyte cells?

A
  • From osteoblasts
  • Mature bone cells
  • Terminally differentiated
  • Are entrapped in matrix
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12
Q

What are Osteoclast cells?

A
  • Derived from stem cells
  • Bone Resorption
  • Secrete acids and digestive enzymes
  • Dissolve matrix and release minerals
  • Found in endosteum
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13
Q

Why does long bone growth and remodeling happen and what happens basically?

A
  • Allows bone to respond to physical loads and repair micro damage
  • Remodelling turns over bone to prevent accumulation of brittle material
  • Bone resorbing (osteoclasts) and bone forming (osteocytes/blasts) form basic multicellular unit (BMU)
  • Sequential activity: Bone resorbs then bone forms. Need to be in equilibrium (no change in bone mass)
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14
Q

What is the mechnaism of remodeling?

A
  • Initiation of BMU: Response of osteocytes in response to loading or microdamage, signalled by hormones, cytokines & growth hormone
  • Activation: Bone surface becomes populated with osteoclast precursors (digesting)
  • Resorption: Osteoclasts mature and remove mineralised bones by releasing lysosmal enzymes then dissolved matrix is trancytosed across osteoclast cells and secreted into interstitial fluid then blood, causes release of IGF, FGF which recruits osteoblasts
    Reversal: Osteoclast activity declines and rep[laced by osteoprogenitor cells
    Formation: Osteoprogenitor cells become osteoblasts, secretes type 1 collagen and undergoes mineralisation
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15
Q

What is the method of osteoclast resorption?

A
  • Osteoclast adheres to bone through integrin creating sealing zone and secretes HCl and proteases
  • Integrin engagement results in signals that target acidyfying vesicles (proton pump complex)
  • Fusion of vesicles with membrance generates polarised cell capable of secreting acids for bone resorption
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16
Q

What is osteoarthritis?

A
  • Degenerative disorder of joints, causes pain and disability
  • Affects knee, hip, spine, hands
  • Obesity and age = risk factors
  • Primary OA (cause is unknown + cant change risk (age))
  • Secondary OA - specific cause such as previous injury, gout or RA
17
Q

What is the pathophysiology of osteoarthritis

A
  • Complex chronic degenerative disease of synovial joints: Breakdown of articular cartilage and proliferative changes to surrounding bone
  • Active disease and joints subjected to large loads and strain
  • Numerous repair mechanisms to attempt to restore normal function
  • Rate of damage is greater than repair, shock-absorbing cartilage is destroyed
  • Narrowing of joint space and overgrowth of bone -> inflammation of synovium and effusion (swelling)
18
Q

What are some risk factors of oesteoarthritis

A
  • Over 50
  • female
  • Previous injury
  • Family history
19
Q

How can you diagnose osteoarthritis?

A
  • Typical mechanical pain symptoms and physical joint findings of OA with an individual with risk factors
  • No validated tool
  • Typical features seen on x-ray, space narrowing, bone spurs, subchondral cysts
20
Q

What are the main symto0ms of osteoarthritis?

A
  • Persistent pain
  • Limited morning stiffness
  • Reduced function
  • Hands: nodes (swellings and cysts)
  • Intensity of pain when moving
  • Joint instability
  • Fatigue
  • Joints cracking, grinding
21
Q

What is the molecular pathophysiology of osteoarthritis?

A
  • Hypertrphic chondrocytes generate matrix degradation products and pro-inflammatory mediators for repair
  • Stimulate chrondrocyte and synovium proliferation
  • Increased vascularity and bone turnover
22
Q

What are the main non-pharmaceutical treatment strategies for osteoarthritis?

A
  • Excercise
  • Weight management
  • Information on how to deal with pain
23
Q

What are the pharmacological management of pain?

A
  • Lowest effective dose for shortest time
  • Topical NSAID for knee osteoarthritis and oral if topical is uneffective with a gastroprotective treatment
  • Not paracetamol/weak opiods/ glucosamine/ strong opioids
  • Referral: if joint pain is impacting life and non-surgical is ineffective