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27-2-2014
pathology –sheet # 6
Rawan hattab
Last time .. we talked about gout disease.. and we said , the crystals that deposited in gout are :
mono sodium urate crystals which have slender needle shaped crystals .
gout disease is associated with hyperuricemia also we said it is characterized by acute asymptomatic
heperuricemia at start then acute attacks of gout ..after that ,the a symptomatic free intervals
between the attacks and finally chronic tophaceous gout which is associated with destruction of the
joints .
pseudogout : it is named pseudogout but it has nothing to do with the gout .. it's also called
chondrocalcinosis " (chondro from cartilage and calcinosis from calcium )"
In pseudogout there is deposition of calcium pyrophosphate crystals not mono sodium urate crystals
as in the gout ." the type of crystals is different "
pseudogout can be monoarticular " only one joint " or polyarticular .. and the most commonly affected
joint is a knee joint followed by the wrists,elbows,shoulders, and ankles , but in the gout disease it was
the big toe .
Approximately 50% of patients with pseudogout experience significant joint damage and destruction
which also can be seen in the gout disease.
* something important to differentiate between the gout and pseudogout is the shape of crystals :
in gout :they are slender needle shaped crystals " long crystals "
in pseudogout : crystals are rectangular or rhomboid in shape and small .
Infectious arthritis :
it is caused by infection and the most common type of infection is caused by bacteria .. it is also called
suppurative arthritis due to pus production .
Microorganisim can reach the joints through different pathways during
1- hematogenous dissemination : from the blood to joints "
2-contiguous spread from an adjacent infected point of infection like:
A- osteomyelitis which is infection to the adjacent point of cartlige.
- osteomyelitis can spread to the joint space and cause arthritis .
B- any abscess in the soft tissues around the joint in the muscles , tendons and ligaments can also
spread inside the joint causing infectious arthritis .
Infectious arthritis is serious problem , acute onset ,destruction of the joint space , pus filling the
joint , decrease in the range of movement in the joint.
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27-2-2014
pathology –sheet # 6
Rawan hattab
Infectious arthritis is suppurative because most of the time it is caused by bacteria , and the causative
organism depends on the patient age and the underlying diseases .
The most common cause of suppurative arthritis in Children under the age of 2 years is haemophilus
influenza type B
in older children and adults the main cause is staphylococcus aureus .
another bacteria which is neisseria gonorrhoeae called " gonococcus arthritis " is usually seen in
adolescence, teens and young adults .
If Arthritis or osteomyelitis developed in Individuals with sickle cell anemia the causative organism is
salmonella bacteria .
Clinical features of suppurative arthritis :
most of the time it is out of acute onset , sudden pain , swelling , erythema ,redness of the joint .
Most of the time the knee joint is affected .
the constitution of systemic symptoms are fever ,leukocytosis " elevated Wbcs count on peripheral
bood and elevated ESR "erythrocyte sedimentation rate " ESR is a non specific measure of
inflammation either this inflammation is infectious in origin or non – infectious .
Even the autoimmune causes of inflammation can elevate the ESR , so they took a sample of blood
and examine the rate by which the RBCS sediment .. the more sticker samples due to inflammation,
the examination will take longer time and the ESR will be high .
In Gonacoccal infection usually the infection is subacute not acute ,the subacute infection is a phase
between the acute sudden onset and chronic phase.. it maight takes weeks to appear .
The subacute infection is typical to gonococcal infections.
In 90% of non-gonococcal suppurative arthritis ,any joint might be affected but the knee joint is the
most commonly affected joint , and usually the infectious arthritis is a single joint disease "
monoarticular rather than plyarticular .
Aspiration of the joint fluid will revel pus neutrophil in addition to the infectious organism that can be
cultured from the fluid .
Treatment : by using antibiotics because it is bacterial infection ..
 Destruction might be involved ,and in some cases it can be transformed to the chronic phase .
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27-2-2014
pathology –sheet # 6
Rawan hattab
BONE DISEASES
Bone diseases classified into : 1- congenital diseases and we won't go through them
2- acquired diseases " osteoporosis ‫ هشاشة العظام‬and osteomalacia " vitamin D deficiency "
3- infection diseases " osteomyelitis " ( osteo means bone and myelitis means infection or
inflammation )
4- bone tumors
Osteoporosis :
it is an acquired condition characterized by reduced bone mass , leading to bone fragility and bone
fracture due to the reduction in the matrix that composes the bone.
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Usually there is a balance between the osteoblast " a cell responsible for the synthesis of bone "
and the osteoclast " a cell responsible for the dissolution of bone " osteoporosis occurs when the
dynamic balance between osteoblast and osteoclast tilt in favor of resorption .
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In children and young adults the osteblastic activity predominates, because there is bone growth
until we reach the peak of bone mass during the early adulthood after that , the osteoblastic
activity started to decrease and osteoclastic activity goes on ,as a result, imbalance and resorption
of bone will occur also there will be progression to osteopenia then osteoporosis .
The causes of osteoporosis are either primary ,( associated with aging "senile osteoporosis " or
the postmenopausal state in women , in females both are acted at the same time " senile and
postmenopausal state ")
or secondary osteoporosis which can be related to 1- endocrine disorders "mainly diseases of
parathyroid glands because they are related to calcium and bone growth ,
2- gastrointestinal disorders either nutritional deficiencies of certain elements or malabsorption
of certain elements that are needed for growth .
3- Certain drugs especially corticosteroids which are used to treat rheumatoid arthritis or other
autoimmune diseases can cause osteoporosis .
Keep in mind that the primary causes are the most common.
Note : some people are suffering from celiac disease "‫ "حساسية القمح‬it is a malapsorbtion disorder,
malapsorbtion to many elements ,one of them is calcium which is needed for bone growth , those
patients are more susceptible to osteoporosis , this is an example of secondary causes .
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pathology –sheet # 6
Rawan hattab
The reduction in the estrogen level following menopause will lead to different mechanisms ,we will
not go through them but at the end , low level of estrogen will stimulate the osteoclastic activity
and resorption of bone will occur . so osteoporosis risk is higher in females .
The peak bone mass is the maximum bone mass that person can attain, and it is affected by his/her
genetic status , physical activity "exercises will cause bone growth and bone remodeling so the bone
will be stronger and the bone mass will be higher than those with sedentary lifestyle " and
nutrition : nutritional status especially calcium and milk supplements during early childhood and
adulthood .
All these factors can affect the maximum bone mass the person can attain .
After the maximum peak bone mass ,the osteoblastics activity start to decrease or even stop and
the osteoclastics activity will take over . with age there is no increase in osteoclastic activity but the
balance will be shifted toward the osteoclastic activity . but in menopausal status there is
stimulation of osteoclasts that's why menopausal women are more susceptible to osteoporosis .
In osteoporosis there's decrease in replicative activity of osteoprogenitor cells in the bone "which
are stem cells that synthesize osteobalsts and bone forming cells .
Also in aging process the osteblastics activity decrease , there is a decrease in activity of matrix
growth factors , all growth factors which lead to bone growth will decrease, also with aging physical
activity is reduced due to some disorders, all of these factors lead to increase osteoclastics activity .
In menopause there's reduction in estrogen and there's stimulation to certain inflammatory
mediators " IL-1 .IL-6 , TNF ", IL-6 will activate certain pathway called " RANK-RANKL" that activates
the osteoclastics activity .
Most people will reach their peak bone mass during early adulthood , actually, there's no
specific age but in early adulthood the bone growth will stop , the greater the peak bone mass ,the
late occurrence of osteoporosis .
Normally , the bone loss will occur , averaging 0.5 % per year at the end the accumulating effect will
cause reduction in the bone mass .
The most affected bones are the trabecular bones e.g ( vertebrae ) and cortical bones e.g(compact
bones like head of femur).
head of femur , hip joint and the vertebrae are the most common affected sites by osteoporosis .
The resultant increase in the risk of fractures because the bone is fragile and weak.
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27-2-2014
pathology –sheet # 6
Rawan hattab
Morphology :
The hallmark of osteoporosis is a loss of bone , the loss is in the matrix of bone ( osteoid and
proteins " due to resorption by osteoclasts , but the minerals of bone are not affected , this is
important feature in order to differentiate osteoporosis from osteomalacia and rickets" where
there is vitamin D deficiency and minerals loss ( Ca ,Mg, etc "demineralization of bone" ) .
In senile osteoporosis , the most commonly affected bone is cortical bone ,mostly head of femur
and sometimes fracture of femoral head occurs which is serious fracture and very difficult to repair
because the patient already has osteoporosis and there is defection in bone growth .
Note: senile means aging .
Bones are composed of matrix " osteoid and proteins " in addition to minerals mainly calcium .
In osteoporosis the most affected component is the matrix but in osteomalacia the most affected is
the minerals " demineralization of bone ."
In postmenopausal state the vertebrae is the mostly affected bone " trabicular bone " .
in senile the femoral neck is affected .
In females the vertebrae and femoral neck can be affected .
Here, just to compare between the normal vertebrae and the osteoporotic one , notice the normal
thickness of vertebrae " left side " and after osteoporosis collapsing occurs , the thickness is
decreased . notice the trabecular meshwork"( there is no compact bone " spongy bone " ) it is a
meshwork with osteoporosis , the trabeculae will thicken and shorten that's why there will be
compression of vertebrae and females length might be reduced so it increases the risk of
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pathology –sheet # 6
Rawan hattab
fractures.
Osteoporosis is painless disease , but if fracture happened there will be pain , and some patients
may have compression fractures in vertebrae and back pain will appear because any compression
will compress the nerve roots .
Rickets and osteomalacia :
Both are manifestations of vitamin D deficiency , rickets occurs in children while osteomalacia in
adults .
The clinical manifestations will differ because in children the growth plate is still open so the effect
will be bowing of the limbs and bossing of facial and head bones ." the most typical features in
children " .
The fundamental defect is vitamin D deficiency , vitamin D is required for calcium absorption from
the gut and calcium deposition on the bones, as a result the primary defect in the bone will be
demineralization " loss of minerals "so it is a mineral disease rather than a matrix disease .
Rickets and osteomalacia are predisposing factors to fracture , due to bone fragility .
OSTEOMYELITIS
It is inflammation of bone tissues and the bone marrow .
most of the inflammations are caused by infections and most of the infections are byogenic which
means " they are bacterial in origin and there is pus production " .
osteomyelitis can be secondary to systemic infections but more frequently occurs as isolated
primary focus of disease , it can be acute, subacute, or chronic .
any microorganism can cause osteomyelitis but the most common are byogenic bacteria especially
staphylococcus aureus in addition to that, chronic osteomyelitis caused by mycobacterium
tuberclerosis .
byogenic osteomyelitis is acute osteomyelitis not chronic , chronic osteomyelitis usually caused by
Tb.
Routs of infection :
1- Hematogenous spread " bacteria gain access to bone through blood "
2- Extension from an infection in adjacent joint or soft tissue . e.g ( someone has byogenic
arthritis or abscess around bone can spread to adjacent bone )
3- Traumatic implantation " if someone had a fracture and this fracture associated with a
wound , bacteria could contaminate that wound and cause osteomyelitis .
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27-2-2014
pathology –sheet # 6
Rawan hattab
The most common way is through the blood because bone is a hard organ , bacteria can't
gain access to it easily except in children because the growth plate is still open , that's why if
they have suppurative arthritis, infection could spread to epiphyses of the adjacent bones .
Causes :
Byogenic bacteria are the most cause of acute osteomyelitis and staphylococcus aureus is the
most frequent causative organism .
E-coli and group B streptococci also can cause osteomyelitis especially in neonates " up to 3
months of age "
salmonella is a common pathogen in patients with sickle cell disease as in suppurative
arthritis .
morphology:
bone has an infection " infiltration by acute and chronic inflammatory cells ..neutrophils in
acute phase later on infiltration by lymphocytes ,monocytes and macrophages takes place ,
so the bone tissues will damage " dead necrotic bone " .
the area of dead necrotic bone with inflammatory cells called sequestrum .
sequestrum can be surrounded by an a shell of reactive bone called involucrum .
periosteum is a fibrous tissues covering the bone , it is loosely attached to bone in children
and firmly attached in adults , so in children the infection could spread to subperiosteal space
causing subperiosteal abscesses " collection of neutrophils and pus " , this subperiosteal
abscesses exacerbating the condition .
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Rupture of the periosteum can lead to abscess formation in the surrounding soft tissue that
may lead to a draining sinus or sinus tract because there will be point where pus is drained
from bone to the surrounding tissues and finally to the skin , this is one of the complications
of osteomyelitis which is difficult to treat .
Clinical features of osteomyelitis :
It is an acute infection especially if it was "byogenic osteomyelitis" , fever , malaise , bone
pain ,swelling, hotness ,leukocytosis similar to arthritis .
Symptoms also can be subtle with only unexplained fever ,especially in neonates , there is
only fever , no localizing symptoms " previously mentioned " , but adults can experience pain
. keep in mind that unexplained fever might be the only symptom in infants .
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Treatment :
It Is a combination between antibiotics because it is serious infection and surgical debridement' "
removal of necrotic tissues " because if necrotic tissues still present further infection will happen ,
despite of this , quarter of patients could develop chronic osteomyelitis .
Complications of osteomyelitis :
In infants the infection can spread into the adjacent joints to cause suppurative arthritis because the
epiphyseal plate is still open .
Pathological fractures : area of inflammation and damage is very weak and it is more susceptible to
fracture .
Secondary amyloidosis : deposition of amyloid material , any infection in the body especially chronic
infection and inflammation or any autoimmune disorder can be associated with secondary amyloid
deposition.
Endocarditis " inflammation of the inner layer of the heart ".
Sepsis " when bacteria gain access to the blood and cause generalized sepsis and bacteremia ".
Development of squamous cell carcinoma in patients with chronic draining sinus .
Rarely osteocarcinoma could arise in a background of chronic osteomyelitis, symptoms are similar
to osteomyelitis but the histological appearance is different . but chronic ostemyelitis rarely could
lead to secondary osteocarcinoma . .
Tuberculous osteomyelitis :
It is the cause of chronic osteomyelitis which is caused by mycobacterium tuberculosis , most of the
time the patient already has a pulmonary Tb that could be complicated by bone Tb .
Bone infections complicate an estimated 1% to 3% of cases of pulmonary Tb .
The spread to the bone can be either through the blood " hematogenous spread " in this case the
infection goes to long bones and vertebrae or direct spread from adjacent infection .
Pulmonary Tb are characterized by having mediastinal lymph nodes which are close to the
vertebrae Column that's why mediastinal nodes could transmit the infection to the vertebrae
column.
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pathology –sheet # 6
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Synovium is a common site of initial infection " the synovial covering of the cartlige " later on can
spread to the adjacent epiphysis then metaphysic of the bone causing chronic osteomyelitis .
Tb osteomyelitis characterized by granulmatous inflammation , caseous granuloma and extensive
bone destruction.
A special disease that is infection of the vertebral bodies by Tb can cause massive deformity of
vertebrae and collapse of vertebrae and posterior displacement of vertebral column due to
displacement by Tb ,this disease is called " pott disease ".
Pott disease is a Tb of the vertebral column associated with deformities and changes that could
compress neural exit canal and causes neurologic deficits .
Good luck ..don't hesitate to contact me if you have any question .
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