Salehi I.

In the Name of God The merciful The compassionate

General concepts in Rheumatology
I. Salehi A. M.D., Rheumatologist

Salehi I. 

Introduction:

What is Rheumatology?  Rheumatic diseases?  Musculoskeletal disorders  Diffuse collagen disease  Collagen-vascular disease  Connective tissue diseases  Rheumatologist?  Over 120 rheumatic diseases 

General Concepts

Salehi I.

ARA Classification of Rheumatic diseases: 
        

Systemic connective tissue d. Vasculitides Seronegative spondyloarthropathies Infectious Arthritis Metabolic, Endocrine, Hematologic Arthropathies Bone & Cartilage disorders Hereditary, Congenital rheumatic d. Soft tissue rheumatism Musculoskeletal benign & malignant tumor Miscellaneous rheumatic diseases
General Concepts

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Prevalence: 30% of population  Seek medical care: 20% of popul.  About 1 / 5 of general office visits  The most common problems: 

Osteoarthritis  Low Back Pain  Gout  Soft tissue rheumatism  Fibromyalgia 

General Concepts

Salehi I.  Three major functions of the musculoskeletal system:    Structural support Motion Metabolic  The five components of the musculoskeletal system:      Muscles Tendons Ligaments Cartilage Bone General Concepts .

 The macromolecular ··building blocks·· of connective tissue:     Collagen Elastin Adhesion molecules Proteoglycans General Concepts .Salehi I.

Network. Y: Hydroxyproline   Biosynthesis: Degradation:   MMP: Collagenase.Salehi I. Gelatinase. Stromelysin TIMP & a2-macroglobulin General Concepts . Collagen     The most abundant body proteins The principal structural component Over 20 types: Fibrilar. FACIT. « Structure of collagen fibrils:     Triple helix 3 a-chains Gly-X-Y sequence X: Proline.

Intestine. Placenta Type XVI: Several tissues Type XVII: Skin. Cornea Type XVIII: Many tissues. Oral mucosa. Skeletal & Heart muscle. Liver.  Type I: 2 a1 + 1 a2 : Bone. Skin. Disk. Vessels Type IV: Basement membranes Type VI: Most connective tissue Type VII: Skin. Meninges Type XV: Many tissue.Salehi I. Perichondrium. XII. Lung. Tendon  Also V. Kidney. Lung General Concepts . Cervix. Endothelium Type X: Hypertrophic cartilage Type XIII: Endomysium. XIV  Type II: 3 a1: Cartilage. Cornea Type VIII: Several tissues. Vitreous  Also XI & IX            Type III: 3 a1: Skin. Placenta.

Proline. Glycine. leukocytes. Macrophage. Platelet    Polymer of tropoelastin monomers   Degrading by Elastase Fibrillin General Concepts . Alanine Tissues.Salehi I. Elastin:   Fibers with elastic properties They comprise:     Ligaments: 70 ² 80% Lung Larger blood vessels: 30 ² 60% Skin: 2 ² 5% Valine.

G2. G3 100 CS (C6S. Proteoglycans   Elasticity of cartilage Aggrecan: 80 ² 90%  Monomer of PGs  Core protein  G1. C4S) 30 KS  Side chains of GAGs    Hyaluronan General Concepts .Salehi I.

Salehi I. Classification of Joints   Synarthrosis: Fibrous     Skull Pubic symphysis Sacroiliac joint Intervertebral discs Ball and socket (Hip) Hinge (IP joint) Saddle (CMC1) Plane (PF joint) General Concepts Amphiarthroses: Fibrocartilage  Diarthroses(Synovial joint): Hyaline     .

Diarthrodial Joint The most common joints  The most mobile joints  Hyaline cartilage  Capsule lined by Synovium  + Menisci  Negative joint pressure(-5.7cmH2o) pressure( General Concepts .Salehi I.

Salehi I.like Type C   Dendritic cell Mast cell  Bare area General Concepts . Synovium  Synovial lining cells:   1-3 layers Three main types    Type A: Macrophage .like Type B: Fibroblast .

Lu/Opaque Opaque Opaque Low Friable >100000 Not applicable Not applicable Not applicable Not applicable High <200 <25%PMN High Firm <2000 <25%PMN Variable Variable 20002000-100000 Mucin clot Firm WBC Diff. Clear/yl. Transpra. Synovial Fluid Normal Color Clarity Viscosity Noninflam Inflam.Salehi I./White Red Transpra. Septic Hemo./White Yl. Tr. Culture >50%PMN >95%PMN NegNeg- NegNeg- NegNeg- Positive Variable . Clear/yl. Yl.

of cartilage Bottle brush with neg.charge negElastic forces  Proteoglycans:       Membrane proteins Other Molecules  Minerals: HA: 5% Of dry General Concepts . Articular Cartilage     Avascular. of cartilage Tensile forces Aggrecan Up to 40% of dry Wt. Aneural Water: Up to 80% of wet Wt.Salehi I. minor Up to 60% of dry Wt. of cartilage Chondrocytes Matrix:  Collagen:    Type II > 90%.

Articular cartilage  Four zones: from top to bottom  Superficial (tangential) zone: 10%    Lamina splendens Horizontal thin collagen fibers Low GAG content Oblique radial thick collagen fibers High PGs & water content Perpendicular radial collagen fibers Many chondrocytes Anchor the cartilage to the bone General Concepts  Middle (Transitional) zone: 50%    Deep (radial) zone: 20%    Calcified zone  .Salehi I.

Salehi I. Lubrication of diarthrodial joint  Hydrodynamic Lubrication  Liquid film Lubricin Lubrication between synovium & cartilage  Boundary layer lubrication   Hyaluronic acid  General Concepts .

Salehi I.  Ligament:   Attaching one bone to another Type I collagen  Tendon:   Attaching a muscle to a bone Type I collagen General Concepts .

Bone Compact bone Comprises 80% of the skeleton Long bone shafts  Cortical bone     Cancellous bone    Trabecular bone Contact with BM cells Vertebral bodies.Salehi I. proximal ends of femora General Concepts . Pelvis.

 Three cell types:    Osteoclasts Osteoblasts Osteocytes  Composition of trabecular bone  HA Mineral: 62%    99% of the total calcium 8080-85% of the phosphorus 66% of the magnesium   Collagens: 31% Noncollagens proteins: 6% General Concepts .Salehi I.

. Bone Remodeling Unit  Activation: Retraction  TRANCE ..Salehi I. Activ.RANK  Diff. Migr. of osteoclasts  Resorption: 2 weeks  Reversal: 4 weeks   ´Cement lineµ: Osteopontin  Formation: 4 months General Concepts ..

Muscles       About 640.Salehi I. up to 40% of body mass Fascicles Muscle fibers Plasma membrane: Sarcolemma Fibrils Myofilaments:     Actin Troponin Tropomyosin Myosin A network of pores & channels communicate the sarcolemma & sarcoplasmic reticulum General Concepts  T-tubule system:  .

Sarcoplasmic reticulum TRelease of calcium Actin is released from a state of inhibition ActinActin-myosin cross-linkage crossShortening of myofilaments. Contraction Calcium is actively pumped back.Salehi I. T-tubule system. Action potential Sarcolemma. Relaxation General Concepts .  Three types of muscle fibers    Type 1: Respond slowly Type 2a: Respond intermediately Type 2b: Respond rapidly  Muscle contraction & relaxation        Stimulation.

Salehi I. Biomechanics of Joints         Joint Structure Joints Motions Joints Forces: Torque Joint minimization of frictional forces Joint resistance to compressive tensile forces Maximization of contact area Joint Stability Joint Control General Concepts & .

Salehi I. Immune System  Natural immune system   Innate Pathogen recognition & elimination  Adaptive immune system   Acquired Specific Ag recognition by receptors General Concepts .

Bas..Salehi I. NK. Eos... Dend.. PMN. Cells Classic & Alternative pathway  Complement:  Cytokines  Pattern recognition receptors(PRR)  Antimicrobial peptides  General Concepts .... NK-T. Innate immune system  Cells:  Mac. NKMast. Epith.

Adaptive immune system  Cellular:  ThymusThymus-derived (T) lymphocytes     Naïve mature T cell Memory T cell Helper T cell Cytotoxic T cell  Humoral:  Bone marrow-derived (B) lymphocytes marrow   Naïve B cell Memory B cell Plasma cell  Cytokines General Concepts .Salehi I.

Salehi I.    Antibody Antigen Antimicrobial peptides    Small peptides < 100 AA Produced by cells of the innate immune system AntiAnti-infectious agent activity Programed cell death General Concepts  Apoptosis  .

Antiviral. AMP. AMP General Concepts .  Adhesion molecule    Selectin Integrins ImmunoglobulinImmunoglobulin-like       Macrophage: Phagositosis. APC Myeloid dendritic cells: APC NK cells: Kill foreign & host cells that have low levels of MHC + self peptides NKNK-T cells Neutrophils: Phagocytosis. Antitumor. APC Plasmacytoid dendritic cells  INFINF-a.Salehi I.

  Eosinophils: Kill invading parasites T lymphocyte   Helper1. INF. M-CSF GGMMType Type Type Type I: IgE-mediated immediate hypersensitivity IgEII: Ab-mediated tissue injury AbIII: Immune complex IV: Delayed-type hypersensitivity DelayedGeneral Concepts  Classification of Immune responses     .Salehi I.2 / Inducer : CD4+ Suppressor / Cytotoxic : CD8+   B lymphocyte Cytokine:  ILs. G-CSF. TNF. GM-CSF.

DR: APC  Class III  General Concepts . DQ.. Dend.. C: All nucleated cell  Class II: DP. B cell   MHC (HLA): Major histocompatibility complex  Human leukocyte antigen  A group of genes located on human chromosome 6  Class I: A. B.. Langerhans.  APC: Ag presenting cell  Ag processing cell  Mac.Salehi I.

IgM.Salehi I. IgA.  T cell Ag recognition    TCR MHC I: CD8 T cell MHCII: CD4 Tcell  B cell: Immunoglobulins  IgG. IgD. IgE General Concepts .

Laboratory test: Why. LBP: nonsurgical Primary OA does not occur in MCPs. Rheumatology·s Ten Golden Rules           Hx. Wrist. Ankle Primary FMS does not occur for the first time in > 55 y/o No RF # RA & No ANA # SLE With fever Rule out infection General Concepts . & PE. Gout is unusual in young women Shoulder pain: periarticular. What time Acute Monoarthritis: Joint aspiration Chronic Monoarthritis: Synovial Bx. Elbow. Shoulder.Salehi I.

Arthritis Swelling :2p  Tenderness :T  Warmth :1p  Limitation of Motion : 1 p  Redness :1P   Arthritis > T + 2 p General Concepts .Salehi I.

Salehi I. Approach to Joint pain Mechanical / Inflammatory  Joint pain:  Articular  Periarticular  Extra-articular Extra  Articular pain: Arthralgia  Arthrosis  Arthritis  General Concepts .

Oligo.Salehi I. Arthritis  Acute / Chronic  Mono. Migr. Polyarthritis  Symmetric / Asymmetric  Pattern: Additive.  Upper / Lower limb  Small / Large joint  + Muscle involvement  + Axial involvement  + Systemic manifestation  General Concepts . Synch.

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