1. Infections of bone
Osteomyelitis

2. Inflammatory and Infective diseases of bones and joints
Enlist common inflammatory and infective disorders of bone and joints.
Describe pathogenesis and management of inflammatory and infective disorders of bone and joints.
Describe functional and structural derangements in inflammatory and infective disorders of bones and joints.
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Reference: Robbins Basic Pathology, 8th edition (pages 820 – 824).

3. Osteomyelitis Etiology:
Refers to inflammation of bone and bone marrow.
2ry to complications of any systemic infection.
Manifest as primary solitary focus.
Etiology:
Caused by all organisms, including viruses, parasites, fungi, and bacteria.
Most commonly occurs due to infections by bacteria and Mycobacteria:
Pyogenic bacteria “Pyogenic Osteomyelitis”
Can be caused by:
Viruses, fungi, parasites and bacteria.

4. Pyogenic Osteomyelitis
Usually occurs in children and young adults.
Causative agent: almost always by bacteria
1.Staphylococcus aureus-90% (most common-why?)= adherence receptor to marrow matrix
2.Haemophilus & G-B Streptococci– neonates
3.Salmonella- (common in sickle cell disease)
4.E.coli, Kelibseilla& Pseudomonas : common in Genitourinary tract infection, intravenous drug abusers, diabetics- DSF.
5.Salomenlla infection ( sickle cell disease)
Why is Staph the most common pathogen causing osteomyelitis?
Answer: it expresses receptors for bone marrow matrix component such as collagen, thereby facilitating its adherence to bone tissue.

5. How do these organisms reach the bone?
Three routes for spread:
Hematogenous spread (most common)
Seeding of bone after bacteremia e.g. staph aureus.
Direct inoculation- open fracture
Spread from an adjacent site of infection.
The location of the bones influenced by:
The osseous vascular circulation, which varies with age
In neonates: metaphysis spread epiphysis, growth plate is still open.
In child: restricted to metaphysis due to growth plate closure.
Region of the bone affected:
Infant and children :(long bones)-tibia, femur, humerus.
Adults: (small bones) - vertebrae, pelvic bones
Most cases of pyogenic Osteomyelitis are secondary to hematogenous spread of S.aureus. to the metaphysic of bone

6. Pathogenesis

7. Pathogenesis of hematogenous osteomyelitis.
The epiphysis, metaphysis, and growth plate are normal. A small, septic microabscess is forming at the capillary loop.
Expansion of the septic focus stimulates resorption of adjacent bony trabeculae. Woven bone begins to surround this focus. The abscess expands into the cartilage and stimulates reactive bone formation by the periosteum.

8. C.The abscess, which continues to expand through the cortex into the subperiosteal tissue, shears off the perforating arteries that supply the cortex with blood, thereby leading to necrosis of the cortex.
D.The extension of this process into the joint space, the epiphysis, and the skin produces a draining sinus. The necrotic bone is called a sequestrum. The viable bone surrounding a sequestrum is termed the involucrum.

9. Organism from Septic focus = boil
Blood vessel
Metaphysis of long bone
Acute inflammation
Formation of PUS
Subperiosteal abscess
Soft tissue
Surface
Periosteal elevation +
Septic thrombosis
Sinus tract

10. Stoppage of blood supply Enzymatic destruction
Periosteal elevation +
Septic thrombosis
Stoppage of blood supply +
Enzymatic destruction
New bone formation
Death of part of bone
Sequestrum
Involucrum

11. Morphology Depends upon the stage& location of Osteomyelitis
Acute, Subacute and Chronic Osteomyelitis

12. Morphology Depends upon the stage of Osteomyelitis
Acute Osteomyelitis: Acute inflammation
within 48hrs, spread within the shaft of the bone haversian system  Periosteum (in child is loosely attached to the cortex)  cell death and pus formation  lifting the periosteum (ischemic and suppurative injury) impaired blood supply 
(1) Segmental bone necrosis (sequestrum)
(2) subperiosteal abscess.
Rupture of Periosteum  abscess in surrounding soft tissue  drain to surface via a draining sinus tract.

13. SEQUESTRUM Bone, chronic osteomyelitis - Medium power
 In the center of the field is a bone fragment that is surrouded by a mononuclear cell infiltrate. There are only a few neutrophils. The dead bone must be removed before the lesion can resolve. Osteoclasts may not survive in the inflammatory milieu, so the necrotic bone must be removed surgically.
Question:
What organism would you expect to culture from a pyogenic osteomyelitis? Answer:
Staphylococcus aureus is the most common organism isolated from hematogenously spread osteomyelitis

14. Morphology
Chronic disease:
> after first week- Is characterized by replacement of acute inflammatory cells by chronic inflammatory cells.
Cytokine stimulation:
(1) Osteoclastic bone resorption.
(2) Ingrowth of fibrous tissue.
(3) Deposition of reactive bone in periphery-
 A sleeve of new bone formation may surround the infected necrotic area
This reactive new bone is k/a involucrum.

15. Involucrum Sequestrum
Leg, chronic osteomyelitis - Gross  This photograph is from a patient with chronic osteomyelitis of the midshaft of the tibia. A large fragment of necrotic cortex is visible deep within the draining sinus. This necrotic bone is called the sequestrum. The reactive periosteum has formed a collar of reactive bone around the chronic draining lesion. The reactive bone is called the involucrum.

16. Clinical findings Most frequent manifestation:
Acute systemic illness: Fever, Chills, severe throbbing pain over the affected area.
reluctance to use affected extremities.
Some times subtler, no fever only localized pain and unexplained fever (neonates& adult).
Acute flare-ups may mark the clinical course of chronic infection
On examination:
Localized area of tenderness
Erythema and Swelling.

17. Investigations:
CBC- Leukocytosis
Raised ESR + CRP
X ray
Early stage (10 days) - may be normal.
Slow periosteal elevation
Lytic focus of bone destruction with surrounding sclerosis.
Radionuclide bone scan:
Best for detection ( even in early cases)
Localized increased uptake of traces
Needle aspiration
Blood cultures
Bone biopsy and culture

18. Knee, osteomyelitis-Radiograph
in this radiograph, a lytic lesion can be seen in the distal metaphysis of the femur.     
Questions: Why is this lesion in the metaphysis? Answer:
The location of the lesion depends upon the route by which bacteria gain access to the bone.
The most common route is hematogenous.
The metaphysis is quite vascular and hence is often the site where infection localizes.
Knee, osteomyelitis-Radiograph  
in this radiograph, a lytic lesion can be seen in the distal metaphysis of the femur.     

19. Sequestration of bone
In area of destruction

20. Technitium scan: Three-phase bone scan of both legs
Technitium scan: Three-phase bone scan of both legs. Increased uptake in the right tibia
Gram stain reveals numerous PMN with gram positive cocci in cluster
Bone scan
Gram stain
Technitium scan: Three-phase bone scan of both legs. Increased uptake in the right tibia
Gram stain reveals numerous PMN with gram positive cocci in cluster

21. Draining sinus Squamous cell carcinoma Chronic osteomyelitis.
In this patient with chronic osteomyelitis, the skin overlying the infected bone is ulcerated and a draining sinus (dark area) is evident over the heel.
After amputation of the foot, a sagittal section shows a draining sinus (straight arrow) that connects the infected bone with the surface of the ulcerated skin. The white tissue (curved arrow) is invasive squamous cell carcinoma, which arose in the skin

22. Complications Most important Draining Sinus tract to the skin surface
Danger of Squamous cell carcinoma developing at orifice of sinus tract.
Extension of infection to adjacent joint  pyogenic arthritis.
Septicemia and infective endocarditis
Chronic Osteomyelitis
Others
Fractures
Retardation of growth from damage to epiphyseal cartilage.
Amyloidosis Pyogenic arthritis (immobiltiy)
Osteogenic sarcoma (rare).
Treatment: surgical drainage + antibiotic
Differential diagnosis
from cellulitis: In case of osteomyelitis, tenderness is out of proportion to soft tissue swelling
from pyogentic arthritis: In case of pyogenic arthritis, there is exaggerated immobility of the joint but lack of point of tenderness over the metaphysis.

23. Tuberculous Osteomyelitis
Endemic disease, immigrates& immunosuppressant pt.
Age:- adolescent& Young-adult, a few in adult.
Occurs secondary to tuberculous infection located elsewhere.
Active tuberculosis of lung.
TB of GIT and lymph nodes.
Spread: blood borne, Direct extension, draining lymphatics.
Localized solitary
Epidemiology:
Rare in developed countries, but still occurs in developing countries.
Rising incidence ( immigrants and HIV positives)

24. Pott’s disease . 40% of cases Thoracic and lumbar vertebra.
Infection begins at the anterior margin of vertebral body near inter-vertebral disc.
Complete destruction of inter-vertebral disc with partial destruction of two adjacent vertebrae. Collapse of vertebral bodies anteriorly.
infection breaks through intervertebral discs to involve multiple vertebrae and extends into the soft tissues forming abscesses. .
Pott’s disease
Abscess formation common.
Thoracic region: paraspinal abscess
Lumbar region : abscess may track down behind fascia of psoas muscle to form a palpable abscess in iliac fossa (= psoas abscess).
Inflammation in TB: low grade
Therefore abscess = cold abscess.

26. Clinical findings: Pathology: Back pain Stiffness,
Fever, night sweats and weight loss.
* Complications:
Deformity (scoliotic or kyphosis) ,
Neurological abnormalities (Pott’s paraplegia, 2ry spinal cord compression)
Tuberculous arthritis, sinus tract formation, psoas abscess, and amyloidosis.
Pathology:
Granulomas with caseous necrosis on histology.

27. Spinal TB - Potts Disease

28. Caseous necrosis Gross: Tuberculosis of spine.
Yellowish cheesy material characteristic of caseous necrosis is very evident.
Caseous necrosis

29. Langhans Giant cell Caseous necrosis
Microscopy: tuberculosis of spine showing granulomatous inflammation.
Caseous necrosis

30. SKELETAL SYPHILIS
Etiology: Syphilis (Treponema pallidum) and yaws (Treponema pertenue) both can involve bone.
Now: infrequent because the disease is usually diagnosed and treated before this complication develops.
The spirochetes tend to localize in areas of active enchondral ossification (osteochondritis) and in the periosteum (periostitis).
Acquired syphilis bone lesion begin early in tertiary stage, (2 to 5 years) after the initial infection.
Congenital syphilis the bone lesions begin about the 5th month of gestation and are fully developed at birth.

31. SKELETAL SYPHILIS Location: The bones most frequently involved are-
1-Nose 2- Palate, 3-Skull, 4- Extremities (long tubular bones such as the tibia).
The syphilitic saber shin is produced by massive reactive periosteal bone deposition on the medial and anterior surfaces of the tibia.
Morphology:-
1- Syphilitic bone infection -edematous granulation tissue containing numerous plasma cells + Necrotic bone.
2- Typical gummas may also form in both congenital and acquired syphilis.
3-The spirochetes can be demonstrated in the inflammatory tissue with special silver stains

32. INFECTIOUS ARTHRITIS
Microorganisms of all types can seed joints during hematogenous dissemination,
The commonest 4 types are:
1- Bacterial Arthritis
2- Tuberculous Arthritis
3- Lyme Arthritis.
4- Viral Arthritis.
Ways of spread:
1- Hematogenous dissemination.
2- Direct inoculation from adjacent soft tissue abscess or focus of osteomyelitis
Complications:
 Rapid destruction of the joint and produce permanent deformities.

33. BACTERIAL ARTHRITIS Main causative Microorganisms:
Gonococcus, Staphylococcus, Streptococcus, Haemophilus influenzae, and gram-negative bacilli (E. coli, Salmonella, Pseudomonas, others).
a- H. influenzae arthritis predominates in children <2ys.
b- S. aureus- main agent in older children and adults.
c- Gonococcus- late adolescence and young adulthood.
d- Salmonella- pt. with sickle cell disease at any age.
e- Gonococcal arthritis- mainly in sexually active women.
Mode of spread- microorganisms seed joints during:
1- Episode of bacteremia; in neonates
2- Contiguous spread from underlying epiphyseal osteomyelitis- in neonates

34. BACTERIAL ARTHRITIS Predisposing conditions: include
1- Immune deficiencies (congenital and acquired).
2- Debilitating illness.
3- Joint trauma.
4- Chronic arthritis of any cause,
5- Intravenous drug abuse.
The classic clinical presentation:
1- Sudden development of an acutely painful and swollen infected joint that has a restricted range of motion.
2- Systemic findings: fever, leukocytosis, and elevated sedimentation rate are common.
4- 90% of nongonococcal cases- involves only a single joint usually knee,  hip  sholuder elbow.
5- Axial articulations- commonly involved in drug addicts.

35. TUBERCUOLOUS ARTHRITIS
Chronic progressive monoarticular disease that occurs in all age groups, especially adults.
Precipitating factors:
Develops as a complication of osteomyelitis or after hematogenous dissemination from a visceral (usually pulmonary) site of infection.
Morphology:
1- Confluent granulomas with central caseous necrosis.
2-The affected synovium may grow as a pannus over the articular cartilage  erode the bone along the joint margins.
3- Complications: chronic disease severe destruction
a) Fibrous ankylosis b) obliteration of the joint space. The weight-bearing joints usually affected,hips,& ankles.

36. VIRAARL ARTHRITIS Commonest viral infection:
Alphavirus, parvovirus B19, rubella, Epstein-Barr virus, and hepatitis B and C virus.
The clinical manifestations:
Variable and range from (A) acute (B)subacute symptoms
Pathogenesis: unclear, but whether
(a) Direct infection by the virus- e.g. Rubella and Alpha viruses infection.
(b) Viral infection generate auto-immune diseases, HIV.
A variety of different rheumatic conditions, including reactive arthritis, psoriatic arthritis, and septic arthritis, have developed in individuals infected with HIV

37. Lyme ARTHRITIS
Etiology: caused by infection with the spirochete Borrelia burgdorferi,
Transmission-Vector name:-transmitted by the ticks of the Ixodes ricinus complex.
Clinical presentation:
Arthritis-Joint symptoms (few weeks to 2 yrs)- is late presentation-
Primary involve large joint- remitting, migratory in descending manner knees, shoulders, elbows, and ankles.
Morphology:Infected synovium exhibits a chronic papillary synovitis with synoviocyte hyperplasia, fibrin deposition, mononuclear cell infiltrates (CD4+ T cells), and onion-skin thickening of arterial walls.
In severe cases can closely resemble that of rheumatoid arthritis
Silver stains- reveal small numbers of organisms in 25% of cases.

38. Lyme ARTHRITIS
In chronic cases-there is no response to Antibiotic, due to underline development of autoimmune reaction “molecular mimcery”.
The joints in these patients have synovial pannus, which causes articular cartilage destruction and permanent deformities.

40. Osteomyelitis: Note MC organism : Staphylococcus aureus
In patient’s with:
Sickle cell anemia Salmonella paratyphi*
Genitourinary tract infections
E coli, Pseudomonas, Klebsiella
IVDA pseudomonas.
Dog and cat bites Pasteurella multocida (a gram negative rod)
Nail puncture through rubber footwear pseudomonas*.
AIDS: ??**

41. Fracture (#) of bones

42. Fracture (#) Is a complete break in the continuity of bone or
it may be an incomplete break or crack.
CLASSIFICATION:
Closed and open fractures
Closed or simple fracture: no communication between site of fracture and exterior of body.
Open or compound fracture: direct communication between the skin surface and the fracture site through the skin wound.

43. Closed #
Open #

44. Open or compound fracture
It is not difficult in this case to diagnose a fracture in the femur, because the bone is sticking through the lacerated skin, a compound fracture as a result of trauma from a motor vehicle accident.
Open or compound fracture

45. Classification: According to etiology
Fractures caused solely by sudden injury
Most common ; Caused by :
Direct violence, Indirect violence
Fatigue or stress fracture:
Due to oft-repeated stress
Risk group:
Athletes, New military recruits
Bone : metatarsal
Pathological fracture
Fracture through a bone already weakened by disease.
Cause of # :Trivial trauma
Causes of pathological #
Local diseases of bone
Infection
Pyogenic osteomyelitis
Benign tumor
Giant cell tumor
Malignant tumor
Metastatic carcinoma (lung, breast, prostate, thyroid, kidney)
Osteosarcoma
Ewing’s sarcoma
General affections of skeleton
Congenital disorders
Osteogenesis imperfecta
Diffuse rarefaction of bone
Senile osteoporosis
Disseminated tumors
Multiple myeloma
Diffuse metastatic carcinoma
Miscellaneous
Paget’s disease

46. Patterns of fracture Transverse fracture Oblique fracture
Spiral fracture
Comminuted fracture (more than two fragments)
The bone is broken into several pieces
Greenstick fracture (incomplete break)
The bone is cracked, but not broken into two pieces. "Incomplete" fracture.
Compression or crush fracture

48. Healing of fractures Process divided into 4 stages
Hematoma formation and Inflammation
Formation of soft callus or procallus
Formation of Hard callus or bony callus 
Bone Remodeling

49. Stage 1 – Hematoma & Inflammation
Fracture causes hemorrhage and tissue destruction ; blood clot (hematoma) forms (hours).
Swelling and inflammation around the fracture site.
Healing of a fracture.
Soon after a fracture is sustained, an extensive blood clot forms in the subperiosteal and soft tissue, as well as in the marrow cavity.
The bone at the fracture site is jagged.

50. Stage 2- Soft Callus Fibrin mesh of hematoma: Acts as a framework.
inflammatory cells (neutrophils and macrophages) move in ; phagocytize debris.
Fibroblasts and capillary grow into blood clot forming granulation tissue.
Cartilage is formed ( from primitive mesenchymal cells)
Granulation tissue + cartilage = soft tissue callus or procallus (provisional callus)
Soft callus bridges the fractured bone.
Procallus: It provides some anchorage to bony ends but not good enough for weight bearing.
B. The inflammatory phase of fracture healing is characterized by neovascularization and beginning organization of the blood clot. Because the osteocytes in the fracture site are dead, the lacunae are empty. The osteocytes of the cortex are necrotic well beyond the fracture site, owing to the traumatic interruption of the perforating arteries from the periosteum.

51. Stage 3 - Hard Callus Osteoblasts proliferate Form new bone
New bone is mineralized
Soft callus converted into bony callus (or osseus callus.)
This spans across the fracture and fills in the space between broken bone ends.
The fracture is now stable.
C. The reparative phase of fracture healing is characterized by the formation of a callus of cartilage and woven bone near the fracture site. The jagged edges of the original cortex have been remodeled and eroded by osteoclasts. The marrow space has been revascularized and contains reactive woven bone, as does the periosteal area.

52. Stage 4 - Bone Remodeling
Portions of callus that are not under physical stress are resorbed.
continual reduction in the size of callus
Restoration of marrow cavity.
Strengthening of bone along the lines of stress.
D. In the remodeling phase, during which the cortex is revitalized, the reactive bone may be lamellar or woven. The new bone is organized along stress lines and mechanical forces. Extensive osteoclastic and osteoblastic cellular activity is maintained.

53. A, Recent fracture of the fibula.
B, Marked callus formation 6 weeks later.

54. Factors which affect # healing
Age
Type of fracture (Simple Vs. Compound/ comminuted/spiral etc.)
Favorable factors:
Good blood supply
Immobility
Factors that hinder union:
Impaired blood supply
Movement between the fragments
Infection
Interposition of soft tissue
Systemic disorders : DM , vitamin deficiency
Movement at the fracture site:
improper formation of callus
callus may be composed of fibrous tissue and cartilage resulting in delayed or nonunion.
False joints ( pseudoarthrosis) may result if nonunion allows tooo much motion between bony fragments.
the central protion of the callus undergoes cystic change and the luminal surgace may get lined by synovial like cells , creating a false joint.

55. Fracture healing: Complications
delayed union
nonunion
pseudoarthrosis (false joint)

56. Important fractures Femoral neck #: Bleeds into capsule
Compromises Medial femoral circumflex artery  avascular necrosis of femoral head.
Scaphoid bone #:
MC # of carpal bones
Susceptible to avascular necrosis and nonunion
Colles’ #:
Person falls on outstretched hand
# distal end of radius  dinner fork deformity
Supracondylar #:
Distal # of humerus
Compromises brachial artery with danger of Volkmann’s ischemic contracture of forearm muscles

57. # femoral neck

58. Miscellaneous bone disorders
Myositis ossificans

59. Myositis ossificans Is characterized by development of bony tissue in:
Skeletal muscle or soft tissue
Following a blunt trauma.
Favored Locations:
Quadriceps or brachialis muscle
Pathogenesis:
Soft tissue trauma  hematoma formation  bone formation.
Differential diagnosis:
Bone sarcomas ( osteosarcoma)
Definition: Myositis ossificans is an unusual condition that often occurs in athletes who sustain a blunt injury that causes deep tissue bleeding. A typical story is a soccer player who is kicked forcefully in the mid-thigh, and develops pain and significant bruising.
The soft-tissues that were injured in the traumatic event initially develops a hematoma, and subsequently develop the myositis ossificans. The word myositis ossificans means that bone forms within the muscle, and this occurs at the site of the hematoma. No one knows exactly why this occurs in some people.

60. Quiz Q1-Why is Staph the most common pathogen causing osteomyelitis?
Answer 1: it expresses receptors for bone marrow matrix component such as collagen, thereby facilitating its adherence to bone tissue.
Q2:Why is this lesion in the metaphysis? Answer 2: The location of the lesion depends upon the route by which bacteria gain access to the bone.
The most common route is hematogenous. The metaphysis is quite vascular and hence is often the site where infection localizes.