Rheumatoid arthritis

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Rheumatoid arthritis by Mind Map: Rheumatoid arthritis

1. Extra-articular manifestation

1.1. Increased risk of infections

1.2. Gi hemorrhage/ perforation

1.3. Vasculittis (Leukocytoclastic vasculitis

1.4. Amyloidosis

1.5. Sublaxation of cervical spine

2. Pathogenesis

2.1. No exact etiology

2.2. due to immune tolerance

2.3. multiple factors

2.3.1. hereditary Increased risk in first degree family members high in monozygotic twins 30% certain alleles present in HLA II predispose to RA DR1 DR4 DR10 DR14 These alleles are part od HLA-DRB1 gene gene PTPN 22 is associated with RA

2.3.2. immune system humoral RF cellular T lymphocytes B-lymphocytes Other leukocytes

2.3.3. Environmental Infectious Agents intiators of disease Viruses Bacteria Smoking citrullinated proteins can cause strong activation of immune system

2.3.4. local Mainly mediated by macrophages synoviocytes cytokines growth factors

3. Morphologic pathology

3.1. Joints

3.1.1. Synovium thickening, edematous and hyperplastic

3.1.2. Infiltration of perivascular inflammatory cells with lymphoid aggregates

3.1.3. Fibrin aggregation covering synovium & present in joint space (rice bodies)

3.1.4. Accumulation of neutrophils on the synovial surface and fluid, but not deep in stroma

3.1.5. Osteoclastic activity

3.1.6. Pannus Formation Mass of synovium, stroma, granulation tissue and inflammatory cells

3.2. Skin

3.2.1. Rheumatoid nodules (Seen in other organs too)

3.3. Heart

3.3.1. Myocarditis

3.4. Blood vessels

3.4.1. Rheumatoid vasculitis

4. A chronic systemic inflammatory disorder that principally affects multiple joint and may affect many tissues and organs

4.1. Joint involvement is characterized by non-suppurative and destructive inflammatory synovitis

5. Clinical Features

5.1. 1-2% of adults

5.2. Female more than male

5.3. 40-70 years old

5.4. Diagnosis

5.4.1. based on criteria

5.4.2. on pattern of joint involvement, duration of symptoms, lab values (ESR, RF, CRP, ACPT)

6. Development of Limbs

6.1. Intraembryonic mesoderm

6.1.1. paraxial mesoderm Most medial Somites at the end of 3rd week differentiate appear as elevations lateral to neural tube develop craniocaudally

6.1.2. intermediate mesoderm

6.1.3. Lateral mesoderm Somatic/ parietal layer body and limbs are formed by the overlying ectoderm visceral/ splanchic wall of GIT with underlying endoderm

6.1.4. Mesodermal cells differentiate into mesenchymal cells fibroblast blood vessels connective tissue chondroblast osteoblast

6.2. Early stages

6.2.1. Week 4 Limb buds (venterolateral region) day 26-27 day 27-29 composed of

6.2.2. Week 5 Hand and foot plates on day 32/36 Mesenchymal condensation form mesenchymal models of the bone chondrification centers appear Motor axons from spinal cord enter limb buds

6.2.3. Week 6 Digital rays appear of the hand Mesenchymal condensation AER at the tips of the digits induce the bone formation (phalenges) regions between the digital rays is loose mesenchymal cartiliginous skeleton appears

6.2.4. Week 7 digital rays appear of the foot osteogenesis of long bones begins (primary ossification centers) Limbs extend ventrally

6.2.5. Week 8 Separate digits day 52/56

6.3. Late stages

6.3.1. Week 12 All long bones have primary ossification centers form diaphysis

6.3.2. 1st year after birth ossification of carpals begin

6.3.3. Synovial joints development begin in the 6th week and appear by the end of the 8th week

6.3.4. After formation of long bones, myoblasts aggregates on the limb buds and form MUSCLE MASS seperated into dorsal (extensor) & ventral (flexor) Upper limb muscles derived from the cervical myotomes Lower limb muscles derived from the lumbosacral myotomes

6.4. Development of Cartilage

6.4.1. Mesenchyme Mesenchymal condensation chondrification centers Mesenchymal cells →chondroblasts

6.5. Bone formation/ ossification

6.5.1. Intramembranous directly from mesenchymal cells osteopregeneritor

6.5.2. endochondral ossification within hyaline cartilage Developing of cartilage model mesenchymal cells form a cartilage model of the bone Growth of the cartilage model In length In width development of primary ossificiation centers perichondriom lies down periosteal long collar nutrient artery penetrates center of cartilage model osteogenic bud brings osteoblasts and osteoclasts to center of cartilage model osteoblasts deposit bone matrix over calcified cartilage forming spongy bone trabeculae osteocyte form medullary cavity development of secondary ossification centers blood vessels enter the epiphyses around time of birth spongy bone is formed but no medullary cavity Formation of Articular Cartilage

6.6. Limb rotation

6.6.1. Limbs extend ventrally Upper limb laterally (90 degrees) Lower Limb medially 90 degrees

6.7. Nerve supply

6.7.1. Motor axons from spinal cord enter limb buds on week 5 & grow as dorsal and ventral muscle masses

6.7.2. sensory axons enter limb buds in guidance by motor axons

6.7.3. Neural crest cells (Schwann cells precursors) surround nerves in limbs & form myelin sheaths & neurolemma

6.7.4. Spinal nerves distribute as bands along the developing buds and migrate distally as the limb elongates (dermatomes)

6.8. Blood supply

6.8.1. Aorta Intersegmental arteries its branches supply the limb buds

6.8.2. in each limb primary axial artery → peripheral marginal sinus → peripheral vein

6.8.3. Primary axial artery Upper limb arm forearm Lower limb thigh leg

6.9. Polarized development

6.9.1. generally craniocaudal direction

6.9.2. transverse plane mid-dorsal region

6.9.3. limbs proximo-distally

6.9.4. amniotic fluid surrounding the embryo in the uterus assist in symmetrical external growth muscular developmen through movement

6.10. Pattern formation in the limbs

6.10.1. HOX gene regulate the cranocaudally development of the limbs

6.10.2. ZPA is a cluster of mesenchymal cells regulates the anterio-posterior pattern development of the limbs produces retinoic acid & Sonic hedgehog ??

6.10.3. forelimb TBX 4

6.10.4. hindlimb TBX 5

6.11. Limb Malformation

6.11.1. Ameila complete absence of limbs suppression in week 4

6.11.2. meromelia partial absence of the limbs disturbance of development in week 5

6.11.3. cleft hand or foot(lowbster claw) absence of central digits problem in msenchymal condensation

6.11.4. congenital abscence of the radius failure of radial premordium to form

6.11.5. brachydactyl y rare shortness of fingers or toes

6.11.6. syndactyly cutaneous failure of web to degenerate between digits osseous failure of notches to develop between digits hereditary

6.11.7. polydactyly extra finger(s) hereditary medial or lateral of the hand but not the middle lateral in the foot

6.11.8. congentical club foot/ talipes abnormal position of the foot Affected child walks on ankle Talipes equinovarus (most common) medial orientation and inversion multifactoral inheritance or movement restriction twice common in male

6.11.9. congenital dislocation of the hip Causes generalized laxity abnormal development of the acetabulum common in female more than males

6.12. Causes of the limb malformations

6.12.1. Genetic factor trisomy 18 environmental thaledomide mutated gene brachydactyly Multifactorial inheritance congenital dislocation of the hip vascular desruption amniotic bands