2/23/99

Pathology II

 

Ch 21 – The Musculoskeletal System

 

Bone Development

1.      Long Bones—endochondral ossification-cartilaginous surfaces are replaced by bone.  Remaining cartilage serve as epiphyseal plates and articular surfaces

2.      Flat bones—develop by intramembranous ossification.  Mesenchymal cells differentiate directly into bone.  There is no cartilaginous phase

 

Bone consists of 3 types of cells

1.      Osteoblast-deposition of bone matrix and subsequent mineralization.  Synthesizes collagen, ground substance, and transports minerals for calcification of matrix.  Osteoid is bone matrix before it is calcified.  Osteoblasts are rich in alkaline phosphatase

2.      Osteoclast—secretes enzymes that dissolve the mineral and lyse the matrix.  In the presence of parathyroid hormone, bone resorption is caused by first releasing phosphorus and calcium, then digesting bone matrix.  This creates resorption lacunae (Howship’s), which are spaces or pits along bone surfaces.  Osteoclasts are rich in acid phosphatase.

3.      Osteocytes—osteoblasts that have become embedded and incorporated into osteoid matrix.  Communicate w/overlying osteoblasts by canaliculi through which cell processes extend.  They can form and resorb bone.

 

3 Major Hormones Control Calcium and Phosphate Metabolism

1.      parathyroid hormone—stimulates resorption

2.      calcitonin-inhibits resorption

3.      vit D metabolites-maintains normal plasma levels of calcium and phosphorus through actions on intestines, bones and kidneys

 

Congenial and Hereditary Diseases of Bones

·        may be isolated lesions or part of a complex syndrome, i.e. congenital absence of a rib versus Hurler’s syndrome, a metabolic disorder (facial deformity)

 

Achondroplasia

·        major cause of dwarfism

·        most common congenial disorder of growth plates—osteochondrodyslasia

·        impaired maturation of cartilage in growth plate – affects all bone formed from cartilage (long bones, etc)

·        autosomal dominant disorder – only 20% have family history – 80% arise spontaneous new mutation

·        shortening of proximal extremities, bowing of legs, lordotic posture

 

Osteogeneisis Imperfecta

·        “Brittle bone disease” – group of conditions w/abnormal development of type I collagen

·        4 major forms – most are autosomal dominant

·        type I collagen in skin, joints, and eyes

·        bones are fragile – multiple bone fractures occur, sclera appears blue

 

Osteoporosis

·        reduction of bone mass w/increased bone fragility

·        primary osteoporosis-very common, affects >15 million people in US—disease condition

·        senile osteoporosis—affects adults of both sexes – increased severity w/age

·        post-menopausal osteoporosis—important cause of fractures in older women—lifestyles choices

 

Pathogenesis

·        not a single disease

·        major factors related to osteoporosis:

1.      total bone mass is important determinant of subsequent risk of osteoporosis

·        genetic factors – physical activity – diet – hormonal status

·        men 30% higher bone density than women

·        blacks 10% higher bone density than whites

·        greatest risk is white women

2.      Age-related changes in bone density affect all individuals in both sexes

·        Dynamic tissue undergoing constant remodeling

·        Max density about age 35

·        Rate of loss 0.7% per year-greatest in spine and femoral neck

·        Age-related decreased in osteoblastic activity-new bone formation doesn’t equal bone loss-gradual attrition

3.      Hormonal factors play a significant role, esp in women

·        ERT reduces bone loss and decreases risk of fracture

·        Decrease estrogen-increase interleukin 1 (monocytes)—increase interleukin 6 (osteoblasts)—recruits osteoclasts which increases bone resorption

·        Cytokines and growth factors that promote bone formation are also affected by decrease estrogen

·        Estrogen deficiency may cause bone loss by increasing bone loss as well as by decreasing bone synthesis

4.      Genetic Factor

·        Determines max bone density achieved

·        Vit D receptors (VDR) molecule – certain variants are associated w/ lower bone density.

·        May be genetic component in pathogenesis of osteoporosis

5.      Mechanical Factors

·        Weight bearing – important stimulus for normal remodeling of bone

·        Physical inactivity associated w/accelerated bone loss

6.      Role of Diet

·        Max bone density determined partially by total dietary calcium, particularly before puberty

 

Morphology

·        Hallmark is loss of bone, particularly trabecular bone

·        Bony trabeculae are thinner, more widely spread apart, more susceptible to fracture

·        Postmenopausal-tends to be severe in vertebral bodies, fracture and collapse

·        Weight-bearing bones, femoral necks-a common site

·        Microscopically

·        Trabeculae thinning and Haversian canals widening

·        Osteoclastic activity present, but not dramatically increased

·        Mineral content of remaining bone is normal

 

Clinical Features

·        Asymptomatic in early stages

·        Later stages—osteopenia evident on plain films in vertebral bodies, pelvis, femur and other weight bearing bones

 

Tx

·        Estrogen reduces rate of loss-does not reverse structural changes in bone

·        Adequate dietary calcium before age 30 reduces risk later in life

·        Calcium supplementation later in life, may modest reduce rate of bone loss

·        Calcitonin administration (nasal gel) may promote bone mass

 

Rickets and Osteomalacia

·        Due to vitamin D deficiencies

·        Fundamental problem-defective mineralization of bone w/increase in non-mineralized osteoid

·        Note-in contrast to osteoporosis-total bone mass is decreased, but mineral content of remaining bone is normal

·        Rickets—occurs in children (developing bones)

·        Osteomalacia—adults (normal development is over) (softening)

 

Bone Diseases Associated w/Hyperparathyroidism

·        Excessive production of parathyroid hormone (PTH)

·        Serum calcium is elevated by following PTH effects

1. increased osteoclast activation – increase bone resorption – increase calcium mobilization
2. increase calcium resorption by renal tubules
3. increase synthesis vit D by kidneys—enhances calcium absorption from gut

·        Normally, the increase serum calcium would inhibit further PTH release.  Abnormal release of PTH is unaffected

 

Primary Hyperparathyroidism

·        autonomous secretion

·        adenoma of parathyroid gland

·        hyperplasia of gland

·        carcinoma of gland

·        ectopic hormone (i.e. bronchogenic ca)

 

Secondary Hyperparathyroidism

·        underlying renal disease—renal failure

·        defective synthesis of active vit D—decrease calcium absorption from gut—Osteomalacia and compensatory increase in PTH

 

Morphology

·        hallmark—increased osteoclastic activity w/bone resorption

·        cortical bone and trabecular (less) is lost and replaced by loose connective tissue

·        bone resorption is greatest in subperiosteal regions—surface appears eroded

·        “Brown tumor”—fibroblasts, osteocytes, and hemosiderin deposits from hemorrhage due to fractures of weakened bone—Most common in jaw—hyperparathyroidism

 

Osteomyelitis

·        infectious inflammation of bone and marrow cavity

·        acute or chronically debilitating

·        most common agents

·        Mycobacterium tuberculosis

·        Pott's disease—TB of the vertebrae

·        Pyogenic bacteria (50% of cases cannot be isolated)

·        Staphylococcus aureus (most common)

·        E. coli and group B streptococcus-neonates

·        Salmonella-common in sickle cell

·        Bone involvement

·        Adult—any area of bone may be involved

·        Children—metaphyseal plate is most common

 

Pyogenic Ostemoyelitis

·        Organisms reach bone by: