Salehi I.

In the Name of God The merciful The compassionate

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

Salehi I. 


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 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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