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Block 5 - Pulm and Skeletal > Skeletal Path > Flashcards

Flashcards in Skeletal Path Deck (56):

What are the two different kinds of bone?

Trabecular = spongy
Compact = cortical - has concentric haversian patterns, predominates near the periosteum


What does bone consist of?

Matrix - type 1 collagen, non collagenous proteins, hydroxyapatite (calcium and phosphorous)


What are osteoblasts?

Synthesize type I collagen and non collagenous proteins of matrix called osteoid until it is mineralized
Osteoid seam eventually mineralized by deposition of hydroxyapatite
Create local alkaline environment favorable for mineral deposition
Receptors for PTH, estrogen and vitamin d


What are osteocytes?

Pseudopodia communicate with each other and osteoblasts to control calcium and phosphorous homeostasis
Sensitive to mechanical forces and microfractures and send signals to osteoblasts to initiate remodeling or repair


What are osteoclasts?

Differentiate in response to M-CSF, RANKL, interleukin 1, and TNF
Dissolve mineral in matrix by acidifying extra cellular space
Excavations are called Howship's lacunae


What is the difference between woven bone and lamellar bone?

Lamellar - collagen fibers parallel and small uniform osteocytes throughout
Woven - formed quickly in response to injury, osteocytes more numerous and variable in size, collagen fibers not as arranged - low tensile strength, replaced by lamellar bone in time
Woven is abnormal in adult skeleton except a tendon insertions


What is the first step in the remodeling process?

Signals from osteocyte responding to physical stress in skeleton = mechanotransduction


How long does removing a unit of bone and replacing it take in middle age trabecular bone?

2-3 weeks for osteoclasts to remove one unit
3 months for osteoblasts to replace one unit


How does bone modeling contrast to bone remodeling?

Predominantly in developing and growing skeleton
As bone grows metaphysis must narrow to width of diaphysis - osteoblasts and osteoclasts key but not coupled as in remodeling


How does RANK signaling in bone remodeling happen?

RANKL on surface of osteoblasts - binds to RANK on osteoclast precursors to make them differentiate and mature


What can increase expression of RANKL on osteoblasts?

PTH, vitamin D3, or prostaglandins
Would result in increased osteoclasts and increased resorption of bone


What besides osteoblasts produces RANKL?

Activated T cells
Involved with bone loss around joint affected with RA


What is osteoprotegerin?

Decoy receptor for RANKL produced by osteoblasts and other cells - blocks interaction of RANK with RANKL
Competes with RANK and ratio regulates osteoclasts


How do osteoclasts activate osteoblasts?

Release anabolic cytokines like ILGF-1 and TGFbeta from digested bone matrix


What is one of the first things that happens after a bone fracture and why?

Local hemorrhage
Complete fracture disturbs periosteal, medullary and cortical vessels traversing haversian system


What is the first phase of bone repair?

Produced when hematoma from hemorrhage is source of kinins, prostaglandins, and inflammatory mediators such as FGF, PDGF, and TGFbeta


What happens towards the end of the inflammatory phase of bone repair?

After one week influx of angioblasts and fibroblasts produce procallus - soft and does not stabilize fracture


What is the second phase of bone repair?

Reparative phase
Blood clot is organized
Over several weeks osteoclasts remove necrotic bone at ischemic ends of fracture as chondroblasts and osteoblasts from progenitor cells in periosteum and medullary cavity produce cartilage (outside) and woven bone (inside) to form hard callus


What is the last phase of bone fracture repair?

Remodeling phase
Cartilage and woven bone replaced by lamellar bone
Lasts from months to years


What are the common causes of delayed healing of bone fractures?

Instability at fracture site
Poor bone quality
Remnants of necrotic bone
Poor nutrition


What are the two ways to get osteomyelitis?

Organisms delivered hematogenously (s aureus most common)
Infection directly from overlying ulcers, periodontal disease, or protrusion of fractures bone through skin (polymicrobial)


How does age of patient affect the pattern of osteomyelitis?

In hematogenous, depends on vascular pattern at physis
Neonate - metaphyseal vessels penetrate physis and extend into epiphysis so bacteria can lodge on either side
Actively growing - vessels don't penetrate growth plate - osteomyelitis develops in metaphysis
Adult skeleton - vessels communicate with epiphysis again


What are clinical manifestations of osteomyelitis?

Fever and pain at site of infection
Overlying soft tissue is swollen and erythematous


What is present on radiographs in osteomyelitis?

Early stages unremarkable - bone not resorbed yet
After a week or so - upregulation of RANKL and down regulation of OPG produce radiolucent lesion


What is sequestrum and involucrum?

S - fragments of necrotic bone left over in osteomyelitis that need to be removed
I - sleeve of new bone made by periosteal osteoblasts around dead infected bone once exudate penetrates cortex and elevates periosteum


What is granulomatous osteomyelitis?

Occurs in small percentage of tb
Most commonly thoracic and lumbar vertebrae - affected collapse and inf spreads into adjacent bones and soft tissue
More destructive than pyogenic osteomyelitis


How does Potts disease present?

Low grade fever
Weight loss
Possible scoliosis or kyphosis from vertebral fractures compressing spinal nerves


What is osteopetrosis?

Group of genetic diseases with decreased osteoclast function
Sclerosis or hardening of skeleton
Bones dense but abnormally brittle and fractures common
Can be cured by hematopoietic stem cell transplantation


What are effects of osteopetrosis?

Thickening of bones can compress cranial nerves
Hematopoiesis moves to spleen and liver - hepatosplenomegaly


What goes wrong in osteopetrosis?

Loss of carbonic anhydrase II prevents osteoclasts from acidifying extra cellular environment


What is osteogenesis imperfecta?

Synthesis of type I collagen is defective - defects in alpha 1 and 2 chains
Large spectrum of phenotypes from lethal to mild


What are clinical features of osteogenesis imperfecta?

Brittle bone - fracture common and heal slowly
Thin blue sclera, small misshapen teeth, of hearing deficits


What is osteomalacia?

Softening of bone caused by defective mineralization
Bones weak and prone to fracture from weight bearing
Widened seams line trabeculae


What is osteomalacia in children?

Soft bones as well as overgrowth of growth plates since mineralization of cartilage doesn't occur - line rib cage = rachitic rosary


What causes osteomalacia and rickets?

Commonly secondary to vitamin d deficiency
Partly affected by lack of PTH activity


When does the growing skeleton reach a peak bone mass?

By the third decade
Higher in men than women
Higher in blacks than whites


What is type I osteoporosis?

Increased osteoclast activity - Associated with abrupt loss of estrogen that increases lifespan and reduces lifespan of osteoblasts
Trabecular bone lost more quickly - fractures of vertebra and proximal femur predominate


How does estrogen normally keep osteoclasts in check?

By up regulating Fas ligand, activating apoptosis program in osteoclasts
By decreasing sensitivity of mature osteoclasts to RANKL


What is an additional effect of estrogen deficiency in post menopausal osteoporosis?

Increased production of inflammatory cytokines such as IL-7 and TNF - decreases activity of osteoblasts and has antiapoptotic effects in osteoclasts


What is type II osteoporosis?

Senile - Begins around 30 in men and women
Decreased osteoblasts activity
Slower bone loss than in type I


What is secondary osteoporosis?

Cushing and prolonged use of exogenous steroids accelerate bone loss - compromise osteoblasts function and decrease calcium absorption from gut --> stimulates release of PTH that activates osteoclasts
Immobilization of limb
Periarticular osteoporosis with RA


What is Paget disease of bone?

Basic MCU uncoupled - regions of bone where osteoclasts predominate and others where osteoblasts predominate
Classic histologic mosaic pattern


What happens in Paget disease of bone?

Begins with furious osteoclastic activity producing lytic lesion
Followed by profound osteoblasts activity
In time lesions become quiescent and leave sclerotic deformed bones that are structurally abnormal and weak


How does Paget disease of bone present?

Begins in mid adulthood and increases with age
Usually asymptomatic
Pain from microfractures most common sign
Weight bearing can cause degenerative secondary joint problems in the hips
Overgrowth of vertebra can compress spinal nerves


What are important facts to remember about degenerative joint disease/osteoarthritis?

It is asymmetrical
Stereotypically affects a few joints severely
Produces decreased mobility in fingers, spine, and affected joints
Ankylosis typically does not occur


How does degenerative joint disease present?

First appears in DIP joint of index finger
Spreads gradually to other digits
DIP joints distorted by osteophytes called heberden nodules
Knees, hips, and vertebra involved as disease progresses
No fever or malaise, no prominent inflammation


What is the leading cause of bilateral degenerative joint disease of the knees?



What does destruction of articular cartilage in degenerative joint disease result from?

Uncontrolled loss of extra cellular cartilaginous matrix
Loss of aggrecan thought to be primary event
ADAMTS 1, 4, 5 capable of degrading aggrecan


What are the two main constituents of extra cellular cartilaginous matrix?

Type II collagen - tensile strength
Aggrecan - highly hydrated and resists compression
Constantly remodeled like bone


What happens in degenerative joint disease once the cartilage starts to break down?

Chondrocytes die and articular surface becomes shaggy = fibrillation
Underlying bone becomes sclerotic
Cracks can form and synovial fluid goes through to form subchondral cysts
Eventual all cartilage goes away and bone on bone creates eburnated bone


What is important to remember about RA?

Dramatically inflammatory
Affects small joints
Ankylosis occurs


How does RA present?

Fever and malaise
Symptoms range from sore stiff joints to chest pain or SOB from inflammation of heart and lungs
Begins in 3rd or 4th decade of life
Starts in PIP joints


What are rheumatoid nodules?

In about 1/4 of patients
Under skin or in lung or heart
Central zone of fibrinoid necrosis surrounded by epithelioid macrophages, lymphocytes, plasma cells


What is the pathophysiology of RA?

Intimal lining of synovium is hyperplastic and synovium is infiltrated with lymphocytes including cd4 T cells, B cells, macrophages, and plasma cells
Macrophages produce inflammatory cytokines
Synoviocytes produce proteases, prostaglandins, and cytokines that perpetuate inflammation


Why do synoviocytes do in RA?

Invade joint space forming a sheet or pannus that covers articular cartilage and isolates it from metabolites in synovial fluid


What happens to bone and cartilage in RA?

Release of IL-1 and TNFalpha from reactive synovium encourages breakdown of cartilage matrix
RANKL from activated lymphocytes stimulates osteoclasts