MMB (022) Red Hot Joint 2023-2024 PDF

MMB (022) Red Hot Joint Magda Assaf, PhD Professor of Pathology 2023-2024  Aim To outline the basic causes of inflammation, using the joint as an example. Objectives At the end of the session students should be able to: List the causes of joint inflammation and...

MMB (022) Red Hot Joint Magda Assaf, PhD Professor of Pathology 2023-2024  Aim To outline the basic causes of inflammation, using the joint as an example. Objectives At the end of the session students should be able to: List the causes of joint inflammation and describe the changes occurring in the joint at a basic level Compare and contrast acute and chronic inflammation Indicate which of the various general causes of acute inflammation may apply to the joint. M. Assaf NGU 2  The red hot joint Why is it red and hot? M. Assaf NGU 3  The red hot joint Why should a joint be red and hot? These are two of the signs of acute inflammation M. Assaf NGU 4  Cardinal signs of acute inflammation M. Assaf NGU 5  Cardinal signs of acute inflammation Rubor redness Tumor swelling Aulus Cornelius Described by Celsus Calor heat (30BC-38AD) Dolor pain Functio Rudolph Carl loss of laesa function Added by Virchow (1821- 1902) M. Assaf NGU 6  Cardinal signs of acute inflammation Arteriolar dilatation Rubor redness Engorged capillaries Tumor swelling Edema fluid in extracellular space Calor heat Increased blood flow/ chemical mediators Dolor pain Stretching of tissues due to edema Functio loss of Pain and swelling laesa function M. Assaf NGU 7  Reactions of acute inflammation Vascular Cellular A revisit of I&D, Inflammation M. Assaf NGU 8  A. Vascular changes in acute inflammation 1. Transient, insignificant, vasoconstriction 2. Arteriolar vasodilatation → increased blood flow with engorged capillaries. M. Assaf NGU 9  Vascular changes Normal Acute inflammation M. Assaf NGU 10  Vascular changes in acute inflammation 3. Increased vessel permeability→ SWELLING M. Assaf NGU 11 Vascular changes in acute inflammation 3. Increased vascular permeability What are the characteristic microscopic features of this blood vessel (yellow arrow) M. Assaf NGU 12 Vascular changes in acute inflammation 3. Increased vascular permeability Characteristic microscopic features of this blood vessel A dilated BV Engorged with RBCs Leukocytes at the periphery of the blood stream M. Assaf NGU 13 What are the causes of increased vascular permeability? Immediate: chemical mediators (histamine, bradykinin, NO, C5a, LTB4, PAF) [transient] Immediate: severe direct vessel injury [sustained] Delayed: Endothelial cell injury (e.g. bacterial endotoxins) [prolonged] M. Assaf NGU 14  B. Cellular events # Leukocyte recruitment What is the most important function of inflammatory response? Deliver leukocytes to the site of injury Activate leukocytes What is the function of leukocytes? Ingest the microbe Kill it Eliminate necrotic tissues and foreign substances M. Assaf NGU 15  Sequence of events of Leukocyte recruitment (stimulated by chemical mediators & chemo-attractants) Transmigration Migration Firm adhesion Margination between within to and rolling endothelial interstitial endothelium cells tissue M. Assaf NGU 16 Selectins Integrins GPCR= G- protein coupled receptor On surface of leukocytes 17 What is the type of leukocyte emigrating to the site of infection? This depends on the duration of inflammation and the type of stimulus a. Duration: 6-24 hours → PNLs (short lived, die by apoptosis) 24-48 hours → monocytes (survive longer) b. Type of stimulus: Some infections → continuous PNLs recruitment Viral infections→ lymphocytes Hypersensitivity reactions→ eosinophils M. Assaf NGU 18  Leukocyte activation When? Once they reach site of infection How? Through microbes, necrotic products & mediators M. Assaf NGU 19 Enumerate mediators of acute inflammation Vasoactive amines Complement components Eicosanoids Clotting cascade Kinin cascade M. Assaf NGU 20 Mediators of acute inflammation To be studied in a practical physiology session M. Assaf NGU 21 Mediators of acute inflammation To be studied in a practical physiology session M. Assaf NGU 22 Beneficial effects of acute inflammation Dilution of toxins Entry of antibodies and drugs Cell nutrition and oxygenation Start of immune response M. Assaf NGU 23 Harmful effects of acute inflammation Damage to normal tissues (enzymatic digestion, abscess cavities, vascular damage) Swelling in critical sites (epiglottis, brain) Immune hypersensitivity reactions (causing tissue damage and even life-threatening consequences, e.g. asthma) M. Assaf NGU 24 Outcomes of acute inflammation M. Assaf NGU 25 What are the common causes of a red hot joint? 1. Infection 2. Crystal deposition 3. Flare in activity of chronic arthritis 4. Trauma M. Assaf NGU 26  Causes of red hot joint Septic arthritis Routes of infection: Hematogenous (blood borne infection) Direct extension from a soft-tissue abscess or osteomyelitis Risk factors: Existing joint problems (e.g. osteoarthritis, gout, rheumatoid arthritis, an artificial joint, previous joint surgery) Joint trauma Weak immune system ( diabetes, kidney and liver diseases, drugs suppressing immunity) Increased skin fragility and poor healing of wounds M. Assaf NGU 27  How to diagnose a case of septic arthritis? Examination of synovial fluid for: White cell count, which is usually very high. Culture for bacteria or other organisms X-rays: done only to look for damage or to rule out other causes Blood tests to monitor inflammation MANAGEMENT Antibiotics and drainage Synovial fluid smear rich in leukocytes of fluid to stop injury M. Assaf NGU 28  Causes of red hot joint: Crystal deposition GOUT Gout is a disorder of purine metabolism. Its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating in joints, tendons, and tissues The crystals then trigger a local immune mediated inflammatory reaction Note that “Higher primates lack uricase and so are predisposed to gout” M. Assaf NGU 29  Beneficial effects of URIC ACID +++antioxidant Maintains BP High intelligence Protective to neurons M. Assaf NGU 30  Serum urate concentrations represent the balance of urate production and excretion Gout Renal under-excretion of uric acid accounts for the major cause of hyperuricaemia and gout in the adult population Too much uric acid (disturbed purine metabolism) or Failure of elimination of uric acid by kidneys ↓ Hyperuricemia ↓ GOUT M. Assaf NGU 31  What are the risk factors of Gout? 1. Genetic factors: 20 to 80 percent have a family history 2. Gender: It is more common in men than in women 3. Overweight: Increases the risk of developing hyperuricemia because there is more tissue available for turnover or breakdown, which leads to excess uric acid production 4. Alcohol consumption: Beer contains purines 5. Diet: Eating much food that is rich in purines can cause or aggravate gout in some people 6. Lead: Inhibits purine excretion 7. Drugs: like Niacin (vitamin B3) and diuretics M. Assaf NGU 32 AVOID A PURINE-RICH MEAL Organ meat: Brains, Kidneys, Liver, thymus, pancreas, calves’ tongues, stomach) Some sea food: Anchovies, Sardines, Oysters, Lobster CONSUME Plenty of liquid, low- fat dairy products, coffee, cereals, fruits # cherry juice High Purine diet M. Assaf NGU 33 Clinical stages of hyperuricemia and Gout Asymptomatic disease Symptomatic disease Stage A Stage B Stage C Stage D At high risk MUC deposition MUC deposition Advanced Gout for Gout but without signs and with prior or current requiring specialized without MUC Symptoms of gout episodes of Gout intervention deposition flares Hyperuricemia MUC crystals Acute inflammatory Advanced Gout with tophi Response “Synovitis” & joint damage Dalbeth N, Stamp L. Hyperuricaemia and gout: time for a new staging system? Ann Rheum Dis 2014; 73:1598–600 M. Assaf NGU 34 With modification M. Assaf NGU 35 Gout, clinical presentation Acute gouty arthritis “early phase” is typically mono-articular with the first MTP joint being the most common site of involvement. Patients develop pain, swelling and erythema around the involved joint Repeated attacks: crystals remain within the joint, predisposing to subsequent attacks due to chronic inflammation Chronic gouty arthritis “progressive disease” characterized by deposition of monosodium urate crystals, known as tophi M. Assaf NGU 36  Tophi (white masses of MUC) get deposited in: 1. Joints (appear in the articular cartilage of joints, periarticular tendons, ligaments and soft tissues) 2. Cartilage of nose and ear 3. Interstitial tissue of kidney 4. Cardiac valves. 1 2 37 3 M. Assaf NGU 1 Gout Investigations A serum urate level of approximately 6.8 mg/dl is the concentrate at which the crystals begin to precipitate Radiographic findings AP view demonstrating the radiographic hallmark findings of chronic gout. The classic marginal erosions (red arrow), overhanging cortex (blue arrow), preservation of bone density, and maintenance of the joint space are apparent M. Assaf NGU 38  Case study A 50 year old man with severe pain, redness and swelling of his left big toe is asked by his treating physician to do a plain X-ray Analyze the features seen within this x- ray What is your diagnosis? M. Assaf NGU 39 Answer to the case 4 X-ray shows: 3 1,2 1. Juxta-articular erosive changes around the first MTP joint 5 2. with overhanging edges 3. soft tissue swelling 4. the joint space is maintained 5. No evidence of osteopenia Diagnosis: GOUTY arthritis M. Assaf NGU 40 Radiographic features of gouty lesions in the fingers https://www.rheumtutor.com/rheumtutoring/gout-overview-of-x-ray-findings/ M. Assaf NGU 41 Microscopy: Needle- shaped sodium urate crystals (1) surrounded by a FB granuloma (2) ( fibroblasts, mononuclear cells and giant cells). 2 1 2 1 1 M. Assaf NGU 42 Gout is managed in the following stages Treating the acute attack (NSAIDs, ? Colchicine, corticosteroids, intra- articular injections of steroids, possible combinations according to patient’s health condition and kidney function) Providing prophylaxis to prevent acute flares Lowering excess stores of urate to prevent flares of gouty arthritis and to prevent tissue deposition of urate crystals Treatment of chronic gout: therapy to reduce serum uric acid level to AT LEAST 6mg/dl M. Assaf NGU 43 M. Assaf NGU 44  Causes of red hot joint: Autoimmune disease Rheumatoid arthritis A systemic, chronic inflammatory, autoimmune disease affecting many tissues, mainly the joints. It results in a non- suppurative synovitis frequently progressing to destroy articular cartilage and underlying bone → disabling arthritis Can occur at any age but prevalence increases with age M:F = 1:3 Smokers 2-3x > non-smokers Variable course: remissions and exacerbations (chronic with flare-ups) M. Assaf NGU 45  Pathogenesis of rheumatoid arthritis RA 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. Note that high levels of rheumatoid factor in the blood are most often associated with autoimmune diseases, such as Rheumatoid arthritis Rheumatoid factor is IgM directed to the altered Fc fragment of IgG 46  Pathological lesions of rheumatoid arthritis ❖ Articular lesions ▪ Synovial inflammation - pannus ▪ Destruction of articular cartilage ▪ Erosion of adjacent bone ▪ Fibrous fusion (ankylosis) ❖Extra –articular lesions (systemic) ▪ Rheumatoid nodules ▪ Vasculitis 47  PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS Smoking Genetic factors Bacteria Modification of autoantigens M. Assaf NGU 48  PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS Modified Antigen AP Cells presenting cells CD4 Lymph node activation Circulating T- lymphocytes Homing B cells memory Plasma cells& receptors → joints cells Ig M. Assaf NGU 49  Pathophysiology Homing to the joints @ M. Assaf M. Assaf NGU 50  Role of macrophages Role of T- lymphocytes @ M. Assaf @ M. Assaf M. Assaf NGU 51  Mechanism of bone erosion @ M. Assaf M. Assaf NGU 52 TO SUM UP Macrophages+ T-lymphocytes+ Immune complex → Inflammation of the joint NGU 53 @ M. Assaf  Role of inflammation in final development of cartilagenous erosion @ M. Assaf @ M. Assaf M. Assaf NGU 54 M.@M. AssafAssaf NGU 55 Rheumatoid arthritis, Microscopic features In light of the pathogenesis of rheumatoid arthritis: What are the morphologic changes in a rheumatoid joint? What are the cells found in the synovium of a case of RA? What is a Pannus? M. Assaf NGU 56 M. Assaf NGU 57  Synovial inflammation MP: Increased vascularity Numerous inflammatory cells Synovial cell hyperplasia Osteoclastic activity of underlying bone→ bone erosion. Creeping granulation tissue over and under the articular cartilage within the eroded bone (pannus) Articular cartilage is destroyed by collagenase and other proteases released in the pannus. This is followed by fibrous or bony ankylosis. 58 Rheumatoid Arthritis, microscopic features 1. Synovial cell hyperplasia and proliferation 2. Dense inflammatory infiltrate (+/- lymphoid follicles) (CD4+, B cells, plasma cells, dendritic cells, and macrophages) 3. Angiogenesis→ Increased vascularity 4. Fibrinopurulent exudate on the synovial and joint surfaces 5. Osteoclastic activity in underlying bone→ synovium penetrates bone → periarticular erosions and subchondral cysts. M. Assaf NGU 59 Rheumatoid Arthritis, microscopic features PANNUS (edematous synovium, inflammatory PANNUS cells, granulation tissue, fibroblasts) Gross picture Erosion of articular cartilage Pannus bridges the apposing bones PANNUS fibrous ankylosis microscopic picture ossifies bony ankylosis (fusion of bones) NGU 60  Clinical features of rheumatoid arthritis ▪ Systemic symptoms: low grade fever, weakness, malaise, weight loss ▪ Joints …….. ▪ Rheumatoid nodules (skin nodules) ▪ Positive Rheumatoid factor and anti-CCP ▪ Increased risk of cardiovascular disease; linked to inflammatory vasculitis 61  Clinical features of RA Joints What are the joints commonly affected? Small joints of hand affected first (metacarpophalangeal, proximal interphalangeal joints of hands and feet), then wrist, elbow, knee. RA generally spares the distal interphalangeal joints of the fingers Signs of acute inflammation Joint Pain Joint warmth Joint swelling Morning stiffness Joint symptoms become worse after periods of disuse Joint deformity 62  Clinical features of Rheumatoid arthritis Gross Features: Pannus: fibrovascular tissue or granulation tissue. Irregular surface: synovial hyperplasia. Subchondral cysts: involve the entire head of bone (late stage of disease) M. Assaf NGU 63  Boutoniere deformity: Rheumatoid arthritis The finger is bent toward palm at knuckle (first Interphalangeal joint). One or more than one finger is affected by rheumatoid hand disease Swan- Neck deformity: Observed at distal interphalangeal joint or joint near the tip of the finger. The distal portion of the finger is bent permanently toward palm. The middle joint is bent in opposite direction resulting in finger looking like Swan Neck. M. Assaf NGU 64 X- ray hand of a patient with rheumatoid arthritis What are the radiologic features seen in favor of an advanced lesion? M. Assaf NGU 65  2 1 3 Advanced changes of rheumatoid arthritis widespread joint space loss, periarticular erosions, osteopenia, ulnar deviation, swan neck and boutonniere deformities M. Assaf NGU 66 Case study A 54 year old female with long history of pain in hands. Physical examination: Atrophy of the soft tissues of the hands, ulnar deviation of the proximal phalanges with respect to the metacarpals X- ray: Describe findings M. Assaf NGU 67 X- ray findings Uniform joint space loss of all MCP and PIP joints, erosive changes Osteopenia Ulnar deviation M. Assaf NGU 68 Case study, continued Which of the following best describes the pathogenesis of pannus formation in this patient? A. calcification of the synovium B. chronic inflammation of synovium C. degeneration of cartilage D. dislocation of a portion of bone E. necrosis of fibroadipose tissue 69 Which of the following best describes the pathogenesis of pannus formation in this patient? Which of the following best describes the pathogenesis of rheumatoid arthritis? A. calcification of the synovium B. chronic inflammation of synovium C. degeneration of cartilage D. dislocation of a portion of bone E. necrosis of fibroadipose tissue 70 The red hot joint Outcomes: Resolution Suppuration and severe damage to joint Extension to nearby bone causing osteomyelitis Systemic effects: Pyrexia ( high body temperature) Malaise, anorexia, nausea Lympho-reticular hyperplasia Raised ESR, raised WCC M. Assaf NGU 71 Case study 2 A 55 year old man complains of chronic swelling and pain in the foot with inability to walk on concrete and waking at night, without relief from medication. Examination shows a right red hot metacarpo- phalyngeal joint Describe the X-ray picture Describe the microscopic picture What is your diagnosis? X-ray picture Microscopic picture M. Assaf NGU 72 Suggested readings Robbins basic pathology, ninth edition Chapter 20 Bones Joints and Soft tissue tumors The pathogenesis of Rheumatoid arthritis “Review article” Mclnnes IB and Schett G, New England Journal of Medicine, 2011 M. Assaf NGU 73