Patho sheet.bone #1 - Saja Al3ajarma

Bone


This sheet covers handout #1 no need to read the handout , only some additions are mentioned 

The human skeleton is a complex system well adapted to providing structural support translating the activity of skeletal muscle into movement and providing a protected environment for delicate internal organs.
In addition , the skeleton houses the body's blood-forming hematopoietic elements and serves as the major reservoir of calcium and a number of other minerals.

* congenital and hereditary diseases of bone :-
Congenital Disease of bone range from localized malformations to hereditary disorders associated with abnormalities affecting the entire skeletal system .
Some of the most common congenital structural lesions Aplasia which is a congenital absence of a digit or a rib. Formation of extra bones which is supernumerary digits or ribs. Abnormal fusion of bone like premature closure of the cranial sutures or congenital fusion of ribs .
Such malformations may occur as isolated , sporadic lesions or as components of a more complex syndrome .
Other conditions usually hereditary, includes those that interfere with bone growth and or maintenance of a normal osteoid matrix and ,as such, causes generalized skeletal abnormalities , these include achondroplasia and other forms of dwarfism , osteogenesis imperfecta , and osteopetrosis.

Achondroplasia :
Is an inherited disorder characterized by impaired maturation of cartilage in the developing growth plate .
-it is a major cause of dwarfism and is the most common of the congenital disorders of the growth plate which called (osteochondrodysplasia).
-The vast majority of cases caused by dominant mutations involving the gene coding for fibroblast growth factor receptor 3 (FGFR3) located on the short arm of chromosome 4 ; These mutations result in sustained activation of the (FGFR3) that in turn inhibits the normal proliferation of cartilage at the growth plates .
-Although it is an autosomal dominant disorder only 20% of patients present with a family history , the remaining 80% of cases apparently arises from a spontaneous new mutation .
-Achondroplasia is most commonly encountered as a non-lethal heterozygous condition .
Homozygous individuals are seen only rarely bcz abnormal development of the chest cavity leads to death from respiratory failure soon after birth .
In heterozygous the most conspicuous changes are marked , disproportionate shortening of the proximal extremities ,bowing of the legs and a lordotic posture (: exaggerated forward curvature of the lumbar and cervical regions of the spinal column) .
The cartilaginous growth plate contains hypoplastic or disorganized aggregates of chondrocytes instead of the long , orderly columns normally seen at this site .this means that the whole problem is in the growth plate .

Osteogenesis imperfecta ( O.I ) :
OI (=brittle bone disease ) is a group of hereditary conditions characterized by abnormal development of type I collagen. Type I collagen is a major component of normal osteoid . several different genetic defects have been shown to interfere with the normal synthesis of type I collagen . a number of the mutations appear to directly interfere with the synthesis and/or secretion of procollagen alpha I and procollagen alpha 2 , the peptide precursors of type I collagen molecule .
OI is not a single disorder but rather a spectrum of disorders of varying severity united by the common feature of abnormal collagen synthesis and resultant bone fragility .
Four major forms of OI have been identified the most common variants are inherited as autosomal dominant disorders . Autosomal recessive forms exemplified by the lethal type 2 variant are less common .
-recognition of the various subtypes of OI is important for genetic counseling of affected families .
-OI is characterized by the presence of multiple bone fractures .in the more sever forms of the disease bone fragility causes multiple fractures and fetal demise in utero or shortly after birth .
-In other variants , fractures may not appear until childhood and may raise concern about possibility of child abuse . the milder forms do not appreciably shorten life .
-other tissues containing type I collagen are also affected resulting in abnormal dentition , hearing loss and blue sclerae caused by scleral collagen (collagen type I is decreased so the choroid become transparent ) .

Osteopetrosis ( marble bone disease ):
a group of uncommon hereditary disorders caused by deficient osteoclast activity.
-both autosomal recessive and autosomal dominant are recognized .
-osteopetrosis can be inherited by mutations in the gene coding for colony-stimulating factor ; a cytokine required for osteoclast differentiation.
-mice transgenic for osteoprotegerin also develop osteopetrosis , this molecule actively inhibits osteoclast formation .
-a variant with carbonic unhydrase 2 deficiency that is needed by the osteoclasts for bone resorbtion is also described that gave additional explanation for the mechanism of osteopetrosis .
-defective osteoclastic activity in these patients result in the deposition of abnormally thickened ,heavily mineralized ,abnormally brittle (easily fractured and broken) bone, in addition to increased incidence of fractures ,patients with osteopetrosis also suffer from anemia , thrombocytopenia and an increased susceptibility to infections ,caused by a dramatic decrease in the amount of marrow space available for hematopoiesis .
-abnormally thickened bone may also compress nerve roots , accounting for the high frequency of cranial nerve palsies in these patients .
-patients may develop hepatosplenomegally due to extramedullary hematopoiesis .
- patients with osteopetrosis may benefit from bone marrow transplant to provide monocyte ,the precursors of normal osteoclasts.

Osteomyelitis :
The term designates inflammation of bone and marrow cavity .
-although a number of different agents may cause bone inflammation , by convention, the term is restricted to lesions caused by infectious agents .
-osteomyelitis may be acute or chronic ,debilitating illness.
-although any microorganism can cause osteomyelitis , the most common etiologic agent are pyogenic bacteria and mycobacterium tuberculosis.

** Pyogenic osteomyelitis :
-most cases of acute purulent osteomyelitis are caused by bacteria . the offending organisms reach the bone by one of the following routes:
1-hematogenous dissemination*
2-direct extension from a focus of acute infection in adjacent joint or soft tissue.
3-traumatic implantation after compound fractures (= fracture of the bone which is exposed to the skin so bacteria make break through ) or orthopedic surgical procedures.

-in most patients osteomyelitis is hematogenous in origin .
-staphylococcus aureus is the most causative organisms and its propensity to infect bone maybe related to the fact that it expresses several receptors for bone matrix components.
-other common pathogens include pneumococci and gram negative rods .
* E.coli and group B streptococci are important causes of osteomylitis in neonates after birth obtained from the birth canal , *while salmonella is an especially common pathogen responsible for osteomyelitis in patients with sickle cell disease.

-mixed bacterial infections including anaerobes are responsible for many cases of osteomyelitis developing after bone trauma .

-in up to 50% of cases of pyogenic osteomyelitis the causative organisms cannot be isolated bcz of previous antibiotic therapy,inadequate sampling for culture , or suboptimal culture method.

Morphology :

Acute osteomyelitis: intense neutrophilic infiltrate at the site of bacterial invasion ;
In children the site is metaphysis of long bone ( sluggish(=slow) blood flow allowing bacteria to settle)
In adults the site is vertebral bodies ( highly vascular ).

-the involved bone become necrotic within days due to compression of vascular spaces by increased pressure in the marrow cavity and high concentration of mediators and enzymes released .

-in long bones the infection might reach the periosteum leads to subperiosteal abscess ;these are common in children in whom the periosteum is more loosely attached to cortical bone.
-the infection might spread from the subperiosteum to adjacent soft tissue creating draining sinuses .

-Detachment of the periosteum may disrupt the blood supply to bone resulting in more extensive ischemic necrosis (bones take blood supply from periosteum ).
*in infants the loose periosteal attachment and connection between metaphyseal and epiphyseal vessels allow the infection to spread to epiphysis and joint capsule.
*extension of the infection to the joint is less common in adults bcz the periosteum is firmly attached to articular margins.

-Chronic osteomyelitis developes as a sequela of acute infection ;over time an influx of chronic inflammatory cells into the focus of osteomyelitis initiate a repair reaction that includes osteoclast activation ,fibroblast proliferation and bone formation .

-Residual necrotic bone termed the sequestrum may be resorbed by osteoclastic activity.
-larger sequestra are eventually surrounded by a rim of reactive bone termed the involucrum.
*when a well-defined rim of sclerotic bone surrounds a residual abscess the lesion is sometimes designated a Brodie abscess .

-viable organisms may persist in the sequestrated area for years after original infection.

-Chronic osteomyelitis may be complicated by the development of draining sinuses that open on the overlying skin and pathologic fracture (fracture occurs due to other reasons than pathogens eg.trauma ,tumors,…) .

-less common complications of chronic osteomylitis include squamous cell carcinoma developing in long standing sinus tracts and in exceptional cases sarcoma and secondary amyloidosis .

**Clinical features :
In its initial stages , pyogenic osteomyeitis causes systemic manifestations similar to those seen in other acute infections such as fever , malaise , and leukocytosis.

-local signs and symptoms of bone inflammation may be subtle and easily missed,particularly in infants and young children.
-conversely,local pain,swelling,and redness may occur in some adults in the absence of systemic complaints.
-Although radiographic studies play an important role in the diagnosis of acute osteomyelitis bone changes may not be visible on routine radiographs for more than a week after the onset of systemic manifestations , during this period significant bone destruction may occur .
*Radionuclide scans (eg. Gallium scans ) are more helpful in locating the site of infection early in the cause of osteomylitis .

-infection of bone demand vigorous and prolonged antimicrobial therapy and in some cases surgical debridement.
-Chronic osteomyelitis may supervene despite aggressive therapy especially if the diagnosis has been delayed or the course of antibiotic therapy has been too brief.

*complications of osteomyelitis include pathologic fractures ,bacteremia and endocarditis ,much less common complications are reactive systemic amyloidosis and squamous cell carcinoma with chronic sinus tract.

**Tuberculous osteomylitis:
Mycobacterial infection of bone has long been a problem in developing countries of the world , and with the resurgence of tuberculosis , It is becoming an increasingly important disease in industrialized countries as well.
-Bone infection complicates an estimated 1%-3% of cases of pulmonary tuberculosis ,the organisms
Usually reach the bone through the blood stream although direct spread from a contiguous focus of infection may also occur.
-With hematogenous spread , long bones and vertebrae are favored sites of localization.
-The lesions are often solitary , but they may be multicentric , particularly in patients with underlying immuno deficiency.
-*Because the tubercle bacillus requires fairly high concentration of oxygen , the synovioum , with its higher oxygen pressure , is a common site of initial infection.
-The infection spreads to the adjacent epiphysis , where it causes a typical granulomatous inflammatory reaction with caseous necrosis and extensive bone destruction .
-Tubrtculosis of vertebral bodies or Pott disease is an important form of tuberculous osteomyelitis .
*infections at this site causes vertebral deformity and collapse with secondary neurological deficit .
*extension of the infection to the adjacent soft tissue is fairly common in tuberculosis of the spine and often manifests as a cold abscess in the psoas muscle .

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SAJA AL-AJARMA