Joint pathology
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Joint pathology

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Inflammatory joint diseases

Inflammatory joint diseases

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  • Although the term osteoarthritis implies an inflammatory disease,it is considered to be an intrinsic disease of cartilage in which chondrocytes respond to biochemical and mechanical stresses resulting in breakdown of the matrix
  • Rheumatoid nodules can be associated with the joint or in far off places like lung. <br /> Remember it is a SYSTEMIC auto-immune disease!
  • ULNAR DEVIATION of MP joints is MOST consistent reliable finding. <br /> Bouchard:Rheumatoid (PIP)::Heberden:Degenerative (DIP)
  • Uric acid - an end product of purine metabolism
  • Uric acid - an end product of purine metabolism

Joint pathology Joint pathology Presentation Transcript

  • JOINT PATHOLOGY
  • Aim To discuss pathogenesis, morphology and clinical course of common diseases of joint Osteoarthritis rheumatoid arthritis gouty arthritis infectious arthritis
  • OBJECTIVE Students should be able to: • Define and identify osteoarthritis, rheumatoid arthritis, gouty arthritis and infectious arthritis • Explain the pathogenesis of osteoarthritis, rheumatoid arthritis, gouty arthritis and infectious arthritis • Describe the morphology of osteoarthritis, rheumatoid arthritis, gouty arthritis and infectious arthritis • Outline the clinical course of osteoarthritis, rheumatoid arthritis, gouty arthritis and infectious arthritis
  • SYNOVIAL JOINTS
  • Normal articular cartilage performs two functions: (1) Along with the synovial fluid, it provides virtually friction-free movement within the joint (2) in weight-bearing joints, it spreads the load across the joint surface These functions require the cartilage to be elastic and to have high tensile strength provided by proteoglycans and type II collagen produced by chondrocytes articular cartilage constantly undergoes matrix degradation and replacement Normal chondrocyte function is critical to maintain cartilage synthesis and degradation
  • JOINT DISEASES Joints are subject to a wide variety of disorders  Degeneration  Infections  immune-mediated injury  metabolic derangements  neoplasms
  • JOINT DISEASES ARTHRITIS – Degenerative (OSTEOARTHRITIS) – Rheumatoid – Infectious: Supp., TB, Lyme, Viral – Gout (URATE) – Pseugout (PYROPHOSPHATE) TUMORS – Ganglion (Synovial Cyst) – Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS]) – Synovial Sarcoma
  • OSTEOARTHRITIS (degenerative joint disease) characterized by degeneration of cartilage that results in structural and functional failure of synovial joints an intrinsic disease of cartilage in which chondrocytes respond to biochemical & mechanical stresses resulting in breakdown of the matrix
  • OSTEOARTHRITIS Primary osteoarthritis Onset - insidiously with age and without apparent initiating cause Most commonly affected joints: joints of the hands, knees, hips, and spine
  • Secondary osteoarthritis  strikes in youth  predisposing conditions - previous trauma - developmental deformity - systemic disease : diabetes, ochronosis, hemochromatosis - marked obesity OSTEOARTHRITIS
  • PATHOGENESIS Risk Factors A wear-and-tear phenomenon  Mechanical stresses  Aging  Genetic factors : polymorphisms and mutations in genes encoding components of the matrix and signaling molecules sustained high estrogen levels increased bone density
  • Imbalance in the expression, activity, and signalling of cytokines and growth factors involved in synthesis and degradation of matrix PATHOGENESIS Aging Mechanical Stress Degradation and loss of matrix  degenerating cartilage containing more water and less proteoglycan  diminished type II collagen network
  • MORPHOLOGY early changes in osteoarthritis include alterations in the composition and structure of the matrix Microscopic : vertical and horizontal fibrillation and cracking of the matrix occur as the superficial layers of the cartilage are degraded
  • MORPHOLOGY fibrillation of the articular cartilage
  • Gross morphology Chondromalacia: at early stage - a soft granular- appearing articular cartilage surface bone eburnation: Eventually full-thickness portions of the cartilage are lost and the subchondral bone plate is exposed and is smoothened and burnished by friction, giving it the appearance of polished ivory  underlying cancellous bone becomes sclerotic and thickened  subchondral cyst: fracture gaps allow synovial fluid to be forced into the subchondral regions to form fibrous walled cysts MORPHOLOGY
  • residual articular cartilage subchondral cyst eburnated articular surface exposing subchondral bone Advanced subchondral degenerative cyst in femoral head
  • joint mice: Small fractures can dislodge pieces of cartilage and subchondral bone into the joint, forming loose bodies MORPHOLOGY
  • Osteophytes: Mushroom-shaped bony outgrowths develop at the margins of the articular surface • pannus: a fibrous synovial pannus covers the peripheral portions of the articular surface in severe disease MORPHOLOGY The synovium is usually only mildly congested and fibrotic, and may have scattered chronic inflammatory cells
  • Clinical Course insidious disease predominantly affecting patients beginning in their 50s and 60s Characteristic symptoms and signs 1. deep, aching pain exacerbated by use 2. morning stiffness 3. crepitus (grating or popping sensation in the joint) 4. limitation in range of movement
  • Clinical Course 5. Osteophyte impingement on spinal foramina can cause nerve root compression with radicular pain, muscle spasms,muscle atrophy, and neurologic deficits 6. Heberden nodes in the fingers, representing prominent osteophytes at the distal interphalangeal joints are characteristic in women 7. significant joint deformity
  • 1. Hips 2. Knees 3. lower lumbar 4. cervical vertebrae 5. proximal and distal interphalangeal joints of the fingers 6. first carpometacarpal joints 7. first tarsometatarsal joints of the feet are commonly involved
  • RHEUMATOID ARTHRITIS  systemic chronic inflammatory disorder that  affect many tissues and organs—skin, blood vessels, heart, lungs, and muscles but principally attacks the joints  causing a non suppurative proliferative synovitis  progresses to destruction of the articular cartilage and underlying bone resulting ankylosis of the joints
  • RHEUMATOID ARTHRITIS Pathogenesis RA is an autoimmune disease involving complex interactions of - genetic risk factors - environment - immune system genetic and environmental factors contribute to the breakdown of tolerance to self-antigens
  • Pathogenesis Genetic susceptibility 50% of the risk of developing RA is related to genetic factors Specific HLA-DRB1 alleles have been shown to be associated with rheumatoid arthritis Another gene associated with rheumatoid arthritis is PTPN22 gene which encodes a tyrosine phosphatase that is postulated to inhibit T cell activation RHEUMATOID ARTHRITIS
  • Pathogenesis Environmental factors: Many infectious agents whose antigens may activate T or B cells have been considered Inflammatory and environmental insults such as smoking and infections may induce the citrullination of some self proteins creating new epitopes that trigger autoimmune reactions RHEUMATOID ARTHRITIS
  • Pathogenesis Environmental factors: Cyclic citrullinated peptides are derived from proteins in which arginine residues are converted to citrulline residues post translationally 70% of patients the blood contains anti-CCP antibody (antibodies against cyclic citrullinated peptides) which may be produced during inflammation RHEUMATOID ARTHRITIS
  • Pathogenesis Autoimmunity Pathologic changes are caused mainly by antibodies against self-antigens & cytokine- mediated inflammation (with CD4+ T cells princinpal source of the cytokines) In RA, antibodies to citrullinated fibrinogen, type II collagen, α-enolase, and vimentin immune complexes that deposit in the joints These antibodies are a diagnostic marker for the disease and may be involved in tissue injury RHEUMATOID ARTHRITIS
  • About 80% of individuals with rheumatoid arthritis have autoantibodies to the Fc portion of autologous IgG (rheumatoid factors) Rheumatoid factor, however, is not present in some individuals with the disease (seronegative) and is sometimes found in other disease states and even in otherwise healthy people
  • Pathogenesis RHEUMATOID ARTHRITIS disease is initiated in a genetically predisposed person by activation of CD4+ helper T cells responding to some arthritogenic agent, possibly microbial,or to a self-antigen such as CCP
  • IL-1, IL-8, TNF, IL-6, IL-17, У interferon
  • IL-1, IL-8, TNF, IL-6, IL-17, У interferon
  • Morphology RA typically manifests as symmetric arthritis principally affecting small joints of the hands and feet, ankles, knees, wrists, elbows & shoulders Most often - proximal interphalangeal & - metacarpophalangeal joints distal interphalangeal joints are spared Axial involvement, when it occurs is limited to the upper cervical spine RHEUMATOID ARTHRITIS
  • Morphology Joints Gross synovium becomes  Thickened  Transforming thin, smooth synovial membrane is into lush, edematous, frondlike (villous) projections RHEUMATOID ARTHRITIS
  • Morphology Affected joints show chronic papillary synovitis The characteristic histologic features include 1. synovial cell hyperplasia and proliferation 2. infiltration of synovial stroma by a dense perivascular inflammatory infiltrate composed of lymphoid aggregates (mostly CD4+ helper T cells), B cells, plasma cells, dendritic cells, and macrophages 3. increased vascularity due to vasodilation and angiogenesis - with superficial hemosiderin deposits 4. aggregation of organizing fibrin - covering portions of the synovium and floating in the joint space as rice bodies RHEUMATOID ARTHRITIS
  • 5. accumulation of neutrophils - in the synovial fluid and along the surface of synovium but usually not deep in the synovial stroma 6. osteoclastic activity in underlying bone - allowing the synovium to penetrate into the bone and cause and periarticular bone erosion s, subchondral cysts, and osteoporosis 7. pannus formation - pannus is a mass of synovium and synovial stroma consisting of proliferating synovial lining cells admixed with inflammatory cells, granulation tissue, and fibrous connective tissue - overgrowth of this tissue is so exuberant that thin, smooth synovial membrane is transformed into lush, edematous, frondlike (villous) projections
  • In time, after the cartilage has been destroyed, the pannus bridges the apposing bones to form a fibrous ankylosis which eventually ossifies and results in bony ankylosis Inflammation in the tendons, ligaments, and occasionally the adjacent skeletal muscle frequently accompanies the arthritis
  • Skin Rheumatoid nodules are firm, non tender, and round to oval, in the skin arise in the subcutaneous tissue the most common cutaneous lesion in approximately 25% of affected individuals Sites: arise in regions of the skin that are subjected to pressure, including the ulnar aspect of the forearm, elbows, occiput, and lumbosacral area Less commonly they form in the lungs, spleen, pericardium, myocardium, heart valves, aorta, and other viscera
  • Microscopically A central zone of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes (activated macrophages) and numerous lymphocytes and plasma cells
  • The rheumatoid “nodule” shows “palisading” fibroblasts HANDSWRISTELBOWS
  • Blood Vessels  with severe erosive disease  rheumatoid nodules  high titers of rheumatoid factor are at risk of developing vasculitic syndromes Rheumatoid vasculitis is a potentially catastrophic complication of rheumatoid arthritis, particularly when it affects vital organs
  • Frequently, segments of small arteries such as vasa nervorum and digital arteries are obstructed by an obliterating endarteritis resulting in peripheral neuropathy, ulcers, and gangrene Leukocytoclastic venulitis produces purpura, cutaneous ulcers, and nail bed infarction
  • Clinical Course Symmetric polyarticular arthritis Constitutional symptoms (weakness, malaise, and low-grade fever) Subcutaneous rheumatoid nodules Vasculitic involvement of the extremities may give rise to Raynaud phenomenon and chronic leg ulcers RHEUMATOID ARTHRITIS
  • Symmetric polyarticular arthritis The arthritis first appears insidiously with aching and stiffness of the joints, particularly in the morning As the disease advances the joints become - swollen, painful - Limited movement (minimal or no range of motion) - complete ankylosis characteristic deformities - radial deviation of the wrist - ulnar deviation of the fingers - flexion-hyperextension abnormalities of the fingers (swan neck, boutonnière) Large synovial cysts
  • Hand, acute rheumatoid arthritis This is a classic presentation of acute rheumatoid arthritis It is polyarthritic, affects the proximal interphalangeal joints has produced a fusiform swelling of the soft tissue The lesion is usually symmetric
  • Chronic RA
  • The radiographic hallmarks are  joint effusions juxta-articular osteopenia erosions and narrowing of the joint space loss of articular cartilage
  • Diffuse osteopenia Narrow joint spaces Periarticular bony erosions Ulnar drift of the fingers
  • The disease course may be slow or rapid, and fluctuates over the years, with the greatest damage occurring in the first 4 or 5 years Approximately 20% of affected individuals enjoy periods of partial or complete remission
  • Juvenile Rheumatoid Arthritis  A group of multifactorial disorders with environmental and genetic components  unknown etiology  classified according to their presentation into oligoarthritis, polyarthritis & systemic (Still’s disease) variants  Large joints often are affected  begin before the age of 16 years and persist for more than 6 weeks  Extraarticular inflammatory manifestations such as uveitis also may be present
  • GOUT Crystal-Induced Arthritis  affects about 1% of the population & shows a predeliction for males  caused by excessive amounts of uric acid within tissues and body fluids  Monosodium urate crystals precipitate from supersaturated body fluids and induce an acute inflammatory reaction
  • GOUT Definition Gout is marked by  transient attacks of acute arthritis initiated by crystallization of monosodium urate within and around joints  sometime accompanied by the formation of large crystalline aggregates called tophi, and eventual permanent joint deformity
  • Gout is divided into primary and secondary forms Primary gout - 90% of cases designates cases in which the basic cause is unknown or (less commonly) in which the disorder is due to an inborn metabolic defect that causes hyperuricemia Secondary gout - 10% of cases cause of the hyperuricemia is known, but gout is not necessarily the main or even dominant clinical disorder GOUT
  • PATHOGENESIS  elevated level of uric acid is an essential component of gout, not all such persons develop gout, and genetic and environmental factors also contribute to its pathogenesis  elevated uric acid levels can result from overproduction or reduced excretion of uric acid, or both GOUT
  • Uric acid synthesis -end product of purine catabolism increased urate synthesis typically reflects some abnormality in purine nucleotide production synthesis of purine nucleotides involves two different but interlinked pathways: the de novo - involved in the synthesis of purine nucleotides from nonpurine precursors. salvage pathways - involved in the synthesis of purine nucleotides from free purine bases, derived from dietary intake and by catabolizing nucleic acids and purine nucleotides GOUT
  • PATHOGENESIS Uric acid excretion Circulating uric acid is freely filtered by the glomerulus and virtually completely resorbed in the proximal tubules of the kidney A small fraction of the resorbed uric acid is subsequently secreted by the distal nephron and excreted in the urine GOUT
  • PATHOGENESIS Primary gout - cause of excessive uric acid biosynthesis is unknown in most cases  rare patients have identifiable enzymatic defects [e.g. complete lack of HGPRT in Lesch-Nyhan syndrome] Secondary gout - hyperuricemia can be caused by  increased urate production[e.g.rapid cell lysis during chemotherapy for lymphoma or leukemia)  decreased excretion [chronic renal insufficiency or reduced renal excretion caused by drugs such as thiazide diuretics] GOUT
  • increased levels of uric acid in the blood & body fluids ( synovium) precipitation of monosodium urate crystals chain of events that culminate in joint injury Activation of complement system leading to production of chemotactic and pro-inflammatory mediators Phagocytosis of crystal by macrophages, stimulates the production of the cytokine IL-1 local accumulation of neutrophils & macrophages in the joints & synovial membranes release of chemokines, cytokines, toxic free radicals, leukotriene B & destructive lysosomal enzymes from activated inflammatory cells Cytokines activate synovial cells & cartilage cells to release proteases
  • MORPHOLOGY Major morphologic manifestations of gout are acute arthritis chronic tophaceous arthritis tophi in various sites gouty nephropathy GOUT
  • MORPHOLOGY Acute arthritis : characterized by  a dense neutrophilic infiltrate permeating the synovium and synovial fluid  presence of long, slender, needle-shaped monosodium urate crystals in the cytoplasm of the neutrophils & in small clusters in the synovium  synovium is edematous and congested & contains scattered mononuclear inflammatory cells when the episode of crystallization abates and the crystals resolubilize, the attack remits GOUT
  • MORPHOLOGY Chronic tophaceous arthritis - evolves from  Repetitive precipitation of urate crystals during acute attacks  urates can heavily encrust the articular surfaces and form visible deposits in the synovium  synovium becomes hyperplastic, fibrotic, and thickened by inflammatory cells, forming a pannus that destroys the underlying cartilage, leading to juxtaarticular bone erosions  In severe cases, fibrous or bony ankylosis ensues, resulting in loss of joint function GOUT
  • MORPHOLOGY - Tophi in various sites Tophi are pathognomonic for gout  formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, & foreign-body giant cells, attempting to engulf the masses of crystals  Sites - articular cartilage of joints - periarticular ligaments, tendons, & soft tissues - ear lobes, nasal cartilages, skin of the fingertips [Superficial tophi can lead to large ulcerations of the overlying skin] GOUT
  • MORPHOLOGY Gouty nephropathy  refers to renal complications associated with urate deposition, variously forming medullary tophi, intratubular precipitations, or free uric acid crystals and renal calculi  Secondary complications such as pyelonephritis can occur, especially when there is urinary obstruction GOUT
  • GOUT
  • Clinical Features more common in men than in women not usually cause symptoms before the age of 30 Risk factors : - obesity - excess alcohol intake - consumption of purine-rich foods - diabetes - metabolic syndrome - renal failure GOUT
  • Clinical Features Four stages are classically recognized: (1)asymptomatic hyperuricemia: around puberty in males and after menopause in women (2) acute gouty arthritis (3) “intercritical”gout (asymptomatic intercritical period) (4) chronic tophaceous gout GOUT
  • (2) acute gouty arthritis : after a long interval of years appear as sudden onset, excruciating joint pain with localized erythema & warmth mostly monoarticular 50% occur in the first metatarsophalangeal joint (great toe) & 90% in ankle, heel, or wrist last for hours to weeks & gradually completely resolves, and the patient enters an asymptomatic intercritical period GOUT
  • GOUT (4) chronic tophaceous gout At this stage, radiographs show characteristic - juxtaarticular bone erosion caused by the crystal deposits and loss of the joint space Progression leads to chronic gouty nephropathy - renal colic associated with the passage of gravel and stones
  • Pseudogout calcium pyrophosphate crystal deposition disease (also known as chondrocalcinosis )  crystal deposits first appear in structures composed of cartilage such as menisci, intervertebral discs, and articular surfaces  When the deposits enlarge enough, they may rupture, inducing an inflammatory reaction  typically first occurs in persons 50 years of age or older becoming more common with increasing age, and eventually reaching a prevalence of 30% to 60% in those age 85  no gender or race predilection
  • Infectious Arthritis  Mode of entry: hematogenous dissemination & direct inoculation or by contiguous spread from osteomyelitis or a soft tissue abscess  Infectious arthritis is serious because it can cause rapid joint destruction and permanent deformities
  • Suppurative Arthritis Aetiology (causative agent )  In children < 2 years of age - Haemophilus influenzae  In older children and adults - S. aureus & gonococcus  Patients with sickle cell disease - Salmonella infection at any age  Both genders are affected equally except for gonococcal arthritis, which occurs mainly in sexually active women  In this group, those with deficiency of complement proteins (C5, C6, C7) are particularly susceptible to disseminated gonococcal infections Infectious Arthritis
  • Suppurative Arthritis Clinical presentation  sudden onset with cardinal signs of acute inflammation  Fever, leukocytosis, and elevated ESR  involves only a single joint—usually the knee— followed in order by hip, shoulder, elbow, wrist, and sternoclavicular joints  Joint aspiration typically yields a purulent fluid in which the causal agent can be identified Infectious Arthritis
  • Lyme Arthritis Aetiology - spirochete Borrelia burgdorferi Mode of transmission : arthropod-borne disease deer ticks of the Ixodes ricinus complexin Clinical course - involves multiple organ systems and in its classic form progresses through three successive stages Stage 1 - multiply at the site of the tick bite and cause an expanding area of redness, often with an indurated or pale center (erythema chronicum migrans) with fever &lymphadenopathy last for few weeks’time Infectious Arthritis
  • Stage 2 - early disseminated stage ,spread hematogenously &cause secondary annular skin lesions, lymphadenopathy, migratory joint and muscle pain, cardiac arrhythmias, and meningitis, often with cranial nerve involvement - Diagnostically useful antibodies (usually both IgM and IgG) against Borrelia antigens appear in the serum at this stage of the disease Infectious Arthritis
  • Infectious Arthritis Stage 3 - late disseminated stage, which occurs 2 or 3 years after the initial bite chronic arthritis, with severe damage to large joints, and an encephalitis that ranges in severity from mild to debilitating disease  The arthritis may be caused by immune responses against Borrelia antigens that cross- react with proteins in the joints disease tends to be migratory, with remissions &relapses
  •  involves mainly large joints, especially the knees, shoulders, elbows, and ankles, in descending order of frequency Infectious Arthritis
  • Morphology Histologic examination reveals a Chronic papillary synovitis with synoviocyte hyperplasia fibrin deposition, mononuclear cell infiltrates, onion-skin thickening of arterial walls Infectious Arthritis