5. BONE STRUCTURE
1. It consists of a diaphysis or shaft and two
epiphysis or extremities.
2. The diaphysis is composed of central
medullary canal containing yellow bone
marrow.
3. Periosteum is a vascular membrane which
covers the bone & it has two layers
4. The outer layer is tough and fibrous and the
inner layer consists of osteoblasts and
osteoclasts.
5.The epiphysis consists of cancellous or
spongy bone made of red bone marrow.
6. Epiphysis also consists of articular (hyaline)
cartilage.
6. MICROSCOPIC
STRUCTURE OF BONE
Large number of tube shaped
units – OSTEONS, containing a
central canal.(cc)
The central canal consists of
BV, nerves & each CC is linked
with other CC through
PERFORATING CANAL
Cylindrical plates arranged
around each central canal –
LAMELLAE
Between the lamellae string like
cavities called LACUNAE
are present containing an
osteocyte
The lacunae are interconnected
by CANALICULI which allows
the circulation interstitial fluid
7.
8.
9. Functions of bones
1.
2.
3.
4.
5.
6.
Haemopoiesis, the
production of blood cells.
Forming the boundaries of
the cranial, thoracic and
pelvic cavities, protecting the
organs they contain.
Giving attachment to the
muscles and tendons.
Mineral storage, especially
cal. Phosphate
Allowing movements of the
body.
Giving particular shape to
the body.
10. TYPES OF BONES
Bones are classified as:
1. Long bones: consist of a shaft
and two extremities
e.g. femur, tibia and fibula.
2. Short bones: carpals (wrist)
3.Irregular bones: vertebrae &
some skull bones.
4. Flat bones: sternum, ribs &
most skull bones.
5. Sesamoid bones: patella (knee cap)
12. Synovial joint
1. It is characterised by the presence of capsule
between the articulating bones and the
capsule is lubricated with synovial fluid.
2. Synovial membrane forms the lining of
capsule.
3. Synovial fluid is a thick sticky fluid secreted
by synovial membrane into the synovial cavity.
1. it contains phagocytes which removes
microbes and cellular debris.
2. acts as lubricant.
3. maintains joint stability.
4. Synovial fluid act as cushion by preventing
the friction between the bones.
13.
14. 1. This is a chronic progressive inflammatory
autoimmune disease mainly affecting synovial
joints.
2. It is more common in females than in males.
3. It is a systemic disorder where it affects not only
joints but also other sites including the heart, blood
vessels and skin.
4. Immune complexes composed of IgM activate
and release cytokines (mainly TNF alpha and IL1)
5. These TNF & IL1 are chemotactic to neutrophils
and secrete lysosomal enzymes which damage
cartilage and erode bone, while the PG’s produced
in the process cause vasodilation and causes pain.
15. Other variant forms of RA:
1. FELTY’S SYNDROME:
It is a combination of rheumatoid arthritis along with splenomegaly &
consequent haematologic derangements.
2. JUVENILE RA:
occurs below 16 years of age
characterised by acute onset of fever & pain at the site of knees & ankles.
16. Osteoarthritis
Type of disease degenerative
Tissue affected articular cartilage
Age of onset
late middle age
Joints affected
weight bearing areas
e.g. hip, knee; often
only a single joint
Rheumatoid Arthritis
inflammatory and autoimmune
synovial membrane
any age, mainly 30 to 55 years
occasionally children
small joints e.g. hands, feet
often many joints
17.
18. EPIDEMIOLOGY
1. The prevalence rate is 1%, women are affected three to five times
as often as men.
2. It is 4 times more common in smokers than non smokers.
3. The incidence of rheumatoid arthritis is 3 cases per 10,000
population per annum.
19. ETIOLOGY
1.
2.
3.
4.
The exact causes of rheumatoid arthritis are unknown.
Abnormal autoimmune response.
Genetic susceptibility.
Environmental factors.
20. RISK FACTORS
According to National Rheumatoid Arthritis Society (NRAS), RA affects about
1.3 million Americans.
AGE : RA can occur at any age from childhood to old age, onset usually begins
between the ages of 30-50.
GENDER : Women are more likely to develop RA than men.
SMOKING : Heavy long-term smoking is a very strong risk factor for RA.
21. Symptoms
1. Morning stiffness
2. Joint pain
3. Fatigue
4. Low grade fever
5. Loss of appetite
6. Presence of rheumatoid nodules
7. Myalgia and synovitis
22.
23. DIAGNOSIS
1. Anti-CCP Antibody Test :
The presence of antibodies to cyclic citrullinated peptides (CCP) can identify
RA years before symptoms develop.
2. C-Reactive Protein :
High levels of C-reactive protein (CRP) are also indicators of active
inflammation.
3. Rheumatoid Factor :
In RA, antibodies that collect (anti IgG antibodies) in the synovium of the joint
are known as Rheumatoid factor. In about 80% of cases of RA, blood tests
reveal rheumatoid factor.
24.
25.
26. PATHOGENESIS OF RHEUMATOID ARTHRITIS
Genetic susceptibility
(MHC Class –II)
Joint deformities
Antigenic stimulation
CD4+ T- cells
Destruction of bone, cartilage
fibrosis, ankylosis
Cytokines
(TNF-α, INF-γ, IL-1)
activate
B-cells
anti-IgG
antibody
activate
activate
Endothelial
cells
Macrophages
release of
adhesion
molecules
cytokines,
proteases
Inflammatory damage to synovium,
small vessels, collagen
Formation of immune complex,
inflammatory cells, pannus
27. PATHOGENESIS OF RHEUMATOID ARTHRITIS
1. due to antigenic exposure ( e.g. infectious agent ) CD4 T-cells , MHC class II ( HLA-DR) cells
are activated.
2. now the cytokines are activated , which results in the formation of TNF-α, interferon γ, IL-1 &
IL-6.
3. these cytokines activate endothelial cells, B lymphocytes and macrophages.
4. activation of B-cells releases IgM antibody against IgG (i.e., anti- IgG); this molecule is termed
as Rheumatoid Factor (RF)
5. IgG & IgM immune complexes trigger inflammatory damage to the synovium, small vessels and
collagen.
6. endothelial cells stimulate adhesion molecules which stimulate the inflammatory cells.
7. activation of macrophages releases proteases which causes damage to the joint tissues leading to
Pannus formation., which causes destruction of bone & cartilage
28. PANNUS FORMATION
Activation of macrophages releases
proteases , collagenase, acid
hydrolases, which causes
degradation of cartilage by the
formation of Pannus
The restriction in the movements of
synovial joints is due to the
formation of fibrous tissue a
condition known as Ankylosis
31. DMARD’s
Methotrexate: (Mtx) immunosuppressant
Mechanism of action:
Mtx in RA mainly acts by inhibiting the enzyme Aminoimidazole carboxamide
ribonucleotide transformylase (AICAR) & thymidylate synthetase
enzyme, which results in the inhibition of cytokine production.
Pharmacokinetics:
Oral absorption : 70%
Half life : 6-9 hours
Excretion : urine (70%) & bile (30%)
Adverse effects:
nausea and mucosal ulcers.
In some patients liver damage leading to cirrhosis.
32. Azathioprine : (purine antagonist)
Mechanism of action:
Azathioprine
Thiopurine methyl transferase (TPMT)
6- thioguanine ( active metabolite)
It acts by suppressing B-cell and T-cell function, immunoglobulin production
& IL-2 secretion.
Adverse effects:
Bone marrow depression
G.I disturbances
Acute allergic reactions
33. Cyclosporine:
Sulfasalazine:
Mechanism of action:
Mechanism of action:
It inhibits IL-1 & IL-2 production.
It is metabolised in the body to sulfapyridine
& 5-Aminosalicylic acid.
Pharmacokinetics:
Bioavailability : 20-30%
Metabolism : CYP3 enzymes
sulfapyridine is the active moiety which
suppress the superoxide radicals and
cytokine production.
Adverse effects:
Adverse effects:
Hypertension
Hyperkalemia
Hirsutism
Reversible infertility occurs in men
nausea, vomiting, headache & rashes
34. Leflunomide:
Mechanism of action Leflunomide
body
A77-1726 (act. Metabolite)
This metabolite inhibits the enzyme Dihydro orotate dehydrogenase &
pyrimidine synthesis.
hence there is no T-cell proliferation
Pharmacokinetics:
adverse effects:
completely absorbed orally
Half life is 19 days
loss of hair
leucopenia
35. GOLD:
Mechanism of action:
It reduces the chemotaxis, phagocytosis , macrophage & lysosomal activity.
It prevents the joint destruction, may induce the healing of bony erosions.
Gold is heavily bound to plasma & tissue proteins ; it stays in the body for
years.
It is rarely used now because it causes
kidney & liver damage,
bone marrow depression &
hypotension
36. d- penicillamine:
It is copper chelating agent with gold like action.
It is having adverse effects similar to gold, hence its use is obsolete now.
Corticosteroids:
They have immunosuppressant and anti inflammatory activity.
They are often administered with NSAIDS to have better action.
Long term use of corticosteroids causes serious adverse effects, hence low doses
(5-10mg prednisolone) are used.
37. Biological response modifiers (BRM):
TNFα inhibitors: ( etanercept, infliximab & adalimumab)
Mainly suppress macrophage & T-cell function.
Inflammation in the joints gradually decreases.
New bone erosions are slowed.
Quick response than DMARDS.
BRM are often combined with methotrexate for better action.
All are very expensive drugs.
IL-1 antagonist:
Anakinra:
it is less effective than TNFα inhibitors.
dose : 100mg S.C. daily.
38. Etanercept :
Route & dose: S.C. injection 50mg weekly.
S/E: pain, redness, swelling & itching occurs at the site of infection.
Infliximab:
Route & dose: I.V. 3-5mg is infused for every 4-8 weeks.
S/E: increasing respiratory infections, worsening CHF.
Adalimumab:
Route & dose: S.C. injection 40mg for every 2 weeks.
S/E: pain, redness, swelling & itching occurs at the site of infection.
44. OSTEOTOMY
The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to
eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.
45. conclusion
There is no cure for rheumatoid arthritis.
Maintaining proper diet with regular medication is
the only way to avoid the progression of the disease.
46. References
• 1. Ross & Wilson's., Anatomy & physiology
• 2. Harsh Mohan’s., Textbook of pathology
• 3. Rang and Dale’s., Pharmacology
• 4. K.D. Tripathi., Essentials of medical pharmacology
