D’YOUVILLE COLLEGE
PMD 604 - ANATOMY, PHYSIOLOGY, PATHOLOGY II
Lecture 17: Physiology/pathology of bones & joints
G & H chapter 79 & Robbins chapters 5 & 21
1.
Bone Tissue:
• histology: supporting connective tissue; widely scattered cells in large
amount of extracellular space (matrix); well vascularized and capable of selfrepair/remodeling
- spongy (cancellous) bone: lacy latticework of trabeculae, with intervening
marrow spaces; found internally in bones
- compact (dense) bone: tightly packed tissue organized into cylindrical
units (osteons or Haversian systems) (figs. 79 - 4 to 79 - 6, fig. 21 - 3 & ppts. 1 to 6)
- osteocytes: embedded in matrix in lacunae; nourished by fluids from
nearest blood vessel (via canaliculi)
- osteoblasts: found in fibrous layer at surfaces (periosteum)
- osteoclasts: larger cells, present at resorption sites
- matrix: organic ground substance (osteoid) composed mostly of hyaluronic
acid and proteoglycan (mainly chondroitin sulfate) + high content of collagenous fibers
(upwards of 90%)
- impregnated with mineral salts (mainly calcium hydroxyapatite crystals);
resembles reinforced concrete & capable of resisting strong tensile & strong
compressive forces
• growth of long bone: long axial shaft (= diaphysis), contains hollow center
(medullary cavity) that contains bone marrow; expanded at each end (= epiphysis)
- first formed in cartilage, long bone becomes ossified by ingrowth of
osteogenic buds that lay down mineralized matrix
- ossification occurs at ends and in shaft of bone leaving a disc of
cartilage (epiphysial disc) as the remaining site for growth in length (ppts. 7 & 8)
2.
Bone Disorders - congenital:
• osteogenesis imperfecta: (aka 'brittle bone disease')
- genetic condition; variant forms - some recessive, some dominant
- faulty collagen development, especially in osteoid, disrupts normal
ossification, producing vulnerability to fractures
- disease in fetuses leads to excessive fractures & usually abortion
- characterized by tooth defects, scleral cyanosis, hearing loss & scoliosis (with
resultant respiratory complications)
• achondroplasia:
PMD 604, lec 17
- p. 2 -
- genetic condition, governed by dominant allele, involves automatic
activation of fibroblast growth factor receptors (FGFR); blocks formation of cartilage cells
- failure of cartilage formation in epiphyseal plates; produces various
skeletal deformations, including dwarfism; many patients survive
- homozygous dominant condition is more severe & generally lethal
PMD 604, lec 17
- p. 3 -
• osteopetrosis:
- genetic condition governed by recessive allele
- deficient osteoclast development results in abnormal bone formation
characterized by increased density; - resulting bone is brittle, prone to fracture
- sequelae: deficient marrow production (anemia, increased vulnerability to
infection) results from bony encroachment on medullary cavities
- thickened cranial floor causes cranial nerve deficits (blindness, deafness,
Bell's palsy) due to nerve compressions
- treatments: bone marrow transplant (osteoclasts derive from monocytes),
calcitriol (modestly successful)
3.
Bone Disorders - acquired:
• osteoporosis (figs. 21 - 1, 21 - 4 & ppts. 9 & 10):
- development of the condition is related to peak skeletal mass (a genetically
determined trait that is lower in Caucasians and Asians, especially females)
- progressive loss of bone mass appears to be due to resorption outpacing
deposition as one ages or as a post menopausal condition
- treatments include administration of vitamin D, calcium, osteoclast
inhibitors; estrogen therapy for postmenopausal patients carries risks (MI, thrombosis,
CVA & breast cancer)
- preventive approach: promote healthy bone development with sound
nutrition (especially adequate vitamin D & calcium) & exercise
• Paget's disease:
- possibly related to viral infection (emergence of latent virus from prior
measles or mumps infections) that stimulates osteoclasts; affects mostly aged 60 and
above
- involves foci of abnormal bone formation (pagetic bone); coarse & poorly
organized bone (osteitis deformans); may affect single bones (monostotic) or multiple
bones (polyostotic)
- characterized by repetitive periods of excessive resorption (vulnerability
to fracture), followed by 'exuberant' deposition and resorption & finally by an
osteosclerotic period of heavy bone deposition with reduced resorption
- excessive density of skull bones may affect head posture or even cause
compression fractures of cervical spine
• rickets & osteomalacia:
- rickets afflicts children and is caused by vitamin D deficiency due to dietary
insufficiency (uncommon in Western world); responds well to vitamin D & calcium
therapy
- osteomalacia afflicts adults and is due to malabsorption of vitamin D or
impaired renal retention of phosphate (causes deficient mineralization)
- involves vulnerability to fractures but may be asymptomatic for years
PMD 604, lec 17
4.
- p. 4 -
Disorders of Joints:
• normal joint morphology:
- synovial joints: located between bones articulating with each other
- epiphyses are coated with articular cartilage & are enclosed in a synovial
cavity that contains synovial fluid (lubricant) that is produced by synovial membrane;
joint is enclosed externally in ligamentous capsule (ppts. 11 & 12)
• osteoarthritis: (fig. 21 - 16b & ppts. 13 & 14)
- primary osteoarthritis due to age-related deterioration of joint cartilage
- secondary osteoarthritis (mostly in young people) is related to a contributing
factor other than age, e.g., stress of athletic activity, traumatic injury
- minimal involvement of inflammation
- lesions derive from thinning out of articular cartilage: fissures develop &
cysts of synovial fluid develop in these
- irritated synovial membrane produces osteophytes or spurs
- fibrosis of joint capsule derives from inflammatory damage
- treatment with analgesics and anti-inflammatory drugs is usually
beneficial
• rheumatoid arthritis: (RA)
- systemic condition affecting many other organs (heart, lungs, skin, etc.) as
well as joints; joints affected are in hands, wrists, ankles & feet (less emphasis on weightbearing joints)
- inflammatory disease that may have genetic basis, autoimmune basis or
infection basis; in 80% of cases, presence in blood of rheumatoid factor (antibody
against IgG) may substantiate the autoimmune etiology
- pathogenesis (figs. 5 - 23, 5 - 25 & ppts. 15 to 18) involves cellular
proliferation in synovial membrane, forming a sheet of cells (pannus) that overgrows
joint cavity (includes synovial membrane cells & inflammatory cells)
- cellular components of inflammation invade synovial fluid, attacking
articular cartilage and underlying bone (cytokine action)
- continued growth of pannus may cause fibrosis of joint capsule and eventual
fusion of joint (ankylosis)
- therapies include immobilizing affected joint(s), anti-inflammatory drugs
and painkillers
• gout:
- excessive uric acid in blood, attributable to impaired excretion by the kidneys,
(which may be provoked by drugs) or overproduction of uric acid (a waste product of
purine metabolism); genetic defect is also possible
- arthritis is caused by deposit of uric acid in joints; in advanced stages of
gout, deposits may also occur in soft tissues (tophi) such as tendons & subcutaneous
tissues (fig. 21 - 20 & ppt. 19
- men are afflicted more than women
PMD 604, lec 17
- p. 5 -
- asymptomatic period precedes attack of acute gouty arthritis; a second
asymptomatic period intervenes before chronic tophaceous gout appears
PMD 604, lec 17
5.
- p. 6 -
Disorders of Muscle:
• Duchenne muscular dystrophy:
- X-linked recessive allele is responsible, therefore young males are
predominantly affected; genetic defect involves deficiency of a protein (dystrophin) that
helps maintain integrity of sarcolemma
- absence of stable membrane interaction with extracellular matrix provokes
damage each time muscle fiber contracts; damaged muscle fibers can achieve some
self repair but are overwhelmed and eventually replaced by fat or fibrous tissue
- muscular clumsiness & weakness (skeletal muscle) or cardiac failure (cardiac
muscle) result
- contractures that develop can cause severe skeletal deformities (scoliosis or
severe lordosis), which compromise respiratory function; death usually results from
respiratory failure