Rheumatology

1. Rheumatology Note: Hit me to advance to the next slide Or me to go back Dan Cushman 2007

2. Joints Cartilage & intraarticularfibrocartilage Which parts of the joint are not covered by the synovial membrane (2)? Articular (hyaline) cartilage What type of cartilage are bones covered by? It secretes synovial fluid! What’s special about the synovial membrane? It never fully regenerates How long does it take for the articular cartilage to fully regenerate?

3. Synovial Fluid What types of cells secrete hyaluronic acid? Synovial fibroblasts Low protein Is there a high or a low protein content in synovial fluid (SF)? It provides viscosity What is the point of hyaluronic acid? Yep, if you’re good at it Can arthrocenteses be performed on patients with coagulopathies? What happens to the hyaluronic acid content during a pathological process? It is digested by enzymes  decreased viscosity A vasovagal episode What’s the main risk of arthrocentesis? Because it lacks a true basement membrane Real menbranes don’t cry when you bump your knee Why is the synovial membrane not a real membrane? What are the main three purposes of SF? Immune surveillance, supply nutrients, remove wastes

4. Culture! What else should you test for? When is it “Non-inflammatory?” What would fat globules suggest? WBC <= 2000 A fracture Synovial Fluid • Color • Viscosity • WBC • RBC Clear Yellow Cloudy Yellow Cloudy Yellow Red Cloudy Yellow High Low <200 per uL >50,000 >20,000 = Periph blood >> 20,000 None None Oh yeah None Normal Septic Inflamm Bloody Gouty

5. Acute Phase Reactants Inflammatory states What causes them to increase in the blood? ESR and CRP What are the main two tests? They’re not specific Which disease are APRs specific for? Plasma proteins created by the liver What are they? Cytokines (IL-6, IL-1, TNF-α, IFN-β, TGF-β, etc.) What molecules cause the increase? Fever, neuroendocrine effects, behavioral changes, etc. What can they cause?

6. C-Reactive Protein Bind to phosphocholine? What is the main (presumed) function of CRP? C-Reactive Protein Run C-Reactive Protein Innate Is CRP considered part of the innate or humoral immune system? Because it could be a way to recognize foreign pathogens Why would you want to bind to phosphocholine? To recognize the phospholipid constituents of damaged cells Why else? Activates the complement system and/or bind to phagocytic cells When bound, what does CRP do? Rapid Is it rapid or slow?

7. Erythrocyte Sedimentation Rate Indirect Is it a direct or indirect measure of the acute phase protein concentrations? Fibrinogen What molecule largely is responsible for the ESR? The CRP Which changes more quickly – the ESR or the CRP? By their shape, size, and number How can the red cells affect the ESR?

8. Rheumatoid Factor Yes – it’s a known marker; RF+ patients have more aggressive RA Is it even related to rheumatoid arthritis? An auto-antibody to the Fc portion of IgG What’s RF? Unknown What is its role in the immunopathology of rheumatoid arthritis? IgM Which isotype is most commonly identified by testing?

9. CCP Antibodies It’s seen in the early stages of RA Which is important… why? Antibodies to Cyclic Citrullinated Peptide What’re those? A form of arginine What’s citrulline? It’s seen almost exclusively in RA patients Which is important… why?

10. Gout Serum urate above 6.8mg/dL At what level is someone considered to have hyperuricemia? Adenosine and guanine Which ones are purines again? Purines What type of nucleic acid can lead to increased uric acid levels? What would the crystals look like? Negatively birefringent The first metatarsal phalangeal (MTP) Which joint is most commonly affected? Inflammatory (>2000) – usually between 20,000 and 100,000 What would the WBC count be in in the synovial fluid? Monosodium urate What type of crystals deposit into tissues in gout? Yep Is there inflammation present?

11. The Hyperuricemia Cascade Proximal tubules What is the final enzyme in purine degradation? XanthineOxidase Tissue nucleic acids Endogenous purine synthesis Dietary purines Where does most of the uratereabsorption occur in the kidney? Urate Overproduction Underexcretion Hyperuricemia Associated cardiovascular events and mortality Renal manifestations Gout Silent tissue deposition

12. Gout Too high; obesity is a comorbid condition Which is a worse – a BMI that is too high or too low? >3 attacks/year, tophaceous gout, urate nephropathy, urate > 12 mg/dL Who should get allopurinol? Needle-shaped What shape are the urate crystals? More males or females? Males Lose weight, eat less meat/seafood, drink less alcohol What three lifestyle modifications should be recommended? NSAIDs, low-dose oral colchicine What can be done prophylactically? Beer Which type of alcohol is the worst? Cyclosporines, low-dose aspirin, and diuretics Which three drugs can increase the risk?

13. Gout Where is gout present? Where is the pig who ate roast beef? That is a direct contradiction, because roast beef should cause gout (increased purine intake). You can be sure that this guy is gout-free, though.

14. What are “intercritical segments” Asymptomatic intervals between acute flares Gout Where do monosodium crystals tend to accumulate? Joints and soft tissues Decreased urate excretion How can diuretics cause gout? Meat. What food should be avoided if you don’t want to have gout? Underexcretion of urate What’s the most common general mechanism for contracting gout? Lead  kidneys  decreased urate excretion How is lead associated with gout? Alcohol  lapse of judgement promiscuity  STG (sexually transmitted gout) I mean, underexcretion of urate How can alcohol cause gout? No, there is hidden damage that can occur during those periods Are intercriticalsgements safe? Who told you so? I did. Lower pH, lower temperature What are two mechanisms that could cause decreased solubility? How could tissue underperfusion exacerbate gout? Increased ATP degradation  increased adenosine  increased urate ↓ solubility, joint/soft tissue disturbances, reabsorption of water  supersaturation How can precipitation of crystals occur (3)?

15. Pseudogout – six causes • Hemochromatosis • Hyperparathyroidism • Hypophosphatemia/-magnesemia • Familial Hypocalciuria/-emia • Aging • Thyroid Disease

16. Pseudogout Calcium oxalate, calcium hydroxyapatite What other types are possible? Yep Inflammation present? What type of birefringence do the crystals have? Positive Calcium Pyrophosphate Dihydrate (CPPD) What type of crystals? Pseudo-rheumatoid arthritis What is chronic polyarticular arthritis also called? What’s the treatment (4)? NSAIDs, Colchicine, steroids, underlying disease treatment Is the ROM of preserved? It’s painful Wrist and knee Where does it most commonly occur? >2000 What is the WBC count in the synovial fluid? Negative, but there can be a concurrent infection Is the synovial cell culture usually positive or negative?

17. Osteomyelitis Trauma  contamination; contiguous spread What are two other routes of infection? Staph aureusand Strep pyogenes What are the most common bacteria involved in osteomyelitis? Bacteremia What is commonly apparent before acute osteomyelitis? Hematologic What is the most common route of infection? They harbor different bacteria Why should children be treated differently with osteomyelitis?

18. Osteomyelitis IV antibiotics, surgical debridement & stabilization How is it treated? Bone biopsy & culture What is the definitive diagnostic test for ostemyelitis? Long bones of the extremities Where do children most often present with osteomyelitis? Pott’s disease, TB What are two diseases that can cause spinal osteomyelitis? The vertebrae Where do adults most commonly present with osteomyelitis? Back pain, spine tenderness, low-grade fever What symptoms are present? Fever, chills, malaise, localized pain, erythema, warmth, edema How do they present?

19. Where do adults usually get infectious arthritis? The knee Infectious Arthritis Rapid – it’s a medical emergency! Rapid or slow? What are the main 4 risk factors? Previous damage, prosthetics, IV drug use, immunocompromised patients It can be permanent damage! How long until the joint regains its function? Most common route of infection? Hematogenous Damage can occur within a few hours How fast? Contiguous, direct inoculation How else can it spread? The knee; but the hip is more common than in adults Where do kids usually get infectious arthritis? Yes, but most commonly acute Can it be chronic?

20. Infectious Arthritis Both Are the symptoms localized or systemic? Both Is it considered autoimmune or infectious? Staph aureus, Strep pyogenes, H. influenzae What are the main three bacteria responsible? Gonococcal arthritis What is the most common cause of arthritis in sexually active adults? WBC > 10,000; >80% polys What would the synovial fluid show? Knee, wrist, hand What are the three most common sites affected? Women Is it more common in men or women?

21. Bone Skeletal homeostasis, mineral homeostasis, hematopoiesis What are the three main functions of bone? Yes – without scars Can bone regenerate itself? Is the physis stronger or weaker than regular bone? Weaker Active Is the physis metabolically active or inactive? When can a fracture be a result of another inherent process? Neoplasm, endocrinopathy Infection, compartment syndrome, thrombosis What complications can occur with a fracture (3)? When does bone calcification begin? In utero The physis In which part of the bone does growth occur?

22. Bone Comminuted 1 2 3 2 Simple Open

23. Growing Bone 3 4 1 5 2 6 7 8 9

24. Fractures – identify location Type I Type II Type III Type IV Type V

25. Bone The tissue is calcified Then…? Deposition of new bone across the fracture by osteoblasts What is the primary physiology of bone healing? Hematoma forms What happens first in secondary fracture healing? Precise reapproximation of the fracture & rigid immobilization What are the physician’s two goals of the primary stage of bone healing? Inflammation & angiogenesis Then…? Blood vessels invade  formation of normal bone! Then…? A primitive scar is formed  scar Then…?

26. Bone healing – Steps Early Fracture Inflammation Repair Remodelling

27. Bone Healing – Three Processes • Inflammatory • Reparative • Remodelling

28. When does each stage occur? Bone Healing – Six Stages Hours – days • Hematoma • Inflammatory • Formation of granulation tissue • Soft callus formation • Hard callus formation • Remodelling Begins < 48 hours 2-12 days 1 week – months 1 week – months Several months

29. Name the tumor! Ewing sarcoma DIAPHYSIS Chondrosarcoma Chondroma Osteochondroma METAPHYSIS EPIPHYSEAL PLATE EPIPHYSIS Osteosarcoma Giant cell tumor

30. Bone Tumors Myeloma, lymphoma, metastatic carcinoma What are the three most common bone tumors? Malignant neoplasm of mesenchymal tissue What is a sarcoma? Lome What’s the capital of the country of Togo? Osteosarcoma What’s the most common type of sarcoma? Multiple lytic lesions What do the lesions of multiple myeloma look like?

31. Bone Tumors ? ? ? ? ?

32. Osteosarcoma ? Age? 10-20 Body location? Knee Bone location? Metaphysis Level of malignancy? High-grade Radiologic findings? Sunburst, Codman Triangle Produces? Osteoid

33. Osteoma Age? 60 ? Body location? Skull and facial bones Level of malignancy? Benign

34. OsteoidOsteoma ? Body location? Long bones Bone location? Cortex, <2cm Treatment Aspirin at night Osteoblastoma Body location? Spine Size? >2cm in diameter

35. Chondro-sarcoma ? Age? 50-70 Body location? Pelvis, proximal femur, shoulder, ribs Level of malignancy? Low-grade Notable finding? Dedifferentiation

36. Chondroma Age? 30-50 Body location? Hands/feet, humerus, femur Level of malignancy? Benign ? Radiologic importance? X-rays must be reviewed

37. Osteo-chondroma ? Age? 10-30 Body location? Femur, humerus, tibia, fibula Bone location? Metaphysis Level of malignancy? Benign (may convert to malignant) Radiologic importance? MRI shows medullary connection

38. Ewing sarcoma ? Age? 10-20 Body location? Long bones, ribs, pelvis Bone location? Metaphysis or diaphysis Level of malignancy? Highly aggressive Notable finding? CD99 stain

39. Chordoma ? Age? 27-80 Body location? Sacrum, clivus, vertebrae Origin? Notochord Level of malignancy? Slow-growing

40. Giant Cell Tumor ? Age? 25-40 Body location? Distal femur Bone location? Epiphysis Level of malignancy? Benign Notable finding? Easily confused with tendon sheath tumor

42. Joint Hypermobility A failed war on drugs unfairly segregates our society Why are African-Americans much more likely to be jailed for joint hypermobility? Age, gender, family background, ethnic background Joint hypermobility depends on which four factors? By the extensibility of the joint capsule, ligaments, and tendons How is joint mobility limited, generally speaking? Skin striae, lax upper eyelids, weakness of pelvic floor Name three extraarticular features involved in hypermobility syndrome. Polygenic, of course Is the genetic trait mono- or polygenic? Both Is it determined by genetics or the environment?

43. Ehlers Danlos Syndrome What is the main skeletal abnormality on X-ray? The X-rays are normal Does musculoskeletal pain present early or late in the syndrome? Early Shoulder, patella, TMJ Which joints are particularly susceptible? Hypermobility type What’s the most prevalent form of EDS? Chronic, of course Is this chronic or acute? What is EDS? A heterogenous group of heritable connective tissue disorders Bruising, scarring, tissue fragility, skin hyperextensibility What other four presentations can occur? What generally happens with this type of EDS? Joint sublaxations & dislocations Pesplanus (flat foot) How can EDS present in the lower extremities?

44. Vascular EDS Arterial, intestinal, and uterine fragility/rupture What internal damage can occur? Arterial rupture What’s the most common cause of sudden death for vascular EDS? The face and limbs, particularly Where can adipose deposition be limited? Large eyes, thin nose, lobeless ears What facial characteristics can be seen in this type of EDS? Autosomal dominant What’s the genetic inheritance in this disorder?

45. Marfan Syndrome Arm span Which is longer for Marfan patients – arm span or body height? Fibrillin-1 What is the mutation? Dilation of the aorta, involving the sinuses of Valsalva …due to? What is another associated symptom? Ectopialentis Aortic regurgitation What cardiac symptom can be associated? It’s a major protein building block What does fibrillin do? Autosomal dominant What’s the genetic inheritance in this disorder? Aortic dissection What is the most severe associated cardiovascular complication?

46. Arthritis Osteoarthritis It can be Is joint effusion present? It can be Is local inflammation present? Women More common in men or women? No Are systemic effects present? Osteoarthritis! What’s the most prevalent form of arthritis? Radiographic findings are far more common in the hands than symptoms Why shouldn’t the hands be X-rayed for screening?

47. Osteoarthritis It gets worse throughout the day When is pain the worst? What happens to proteoglycan concentration? It’s decreased Very irregular What is the pattern of cartilage loss? What happens to metabolic activity in the joint? It’s increased Can joint instability be present? Sure Is chondrocyte proliferation increased or decreased? It’s increased It’s decreased What happens to the joint space in an X-ray? What is the level of stiffness in the morning? Low What can happen below the cartilage? Subchondral cysts and/or sclerosis

48. Osteoarthritis How can hip OA present? Deep groin pain radiating into medial thigh Radiographic evidence appears late in the disease What’s the problem with this? Yes Typically, should the pain be recreated with passive motion? What is the gold standard for diagnosis? Radiograph MTP joints with excessive destruction seen in X-ray How does diabetic neuropathy usually present on X-ray? Short-term stiffness (<1 hr) Is OA associated with short- or long-term stiffness (> or < 1 hour)? Previous trauma, NM disease (e.g. diabetes), metabolic disorders What are three secondary causes of OA? Not useful How good are ESR and CRP as markers for OA? Which five joints are typically not involved? MCP, wrist, elbow, ankle, or shoulder Pain relief, exercise regiment, patient education What are the three main points of treatment?

49. Osteoarthritis Risk Factors • ereditary • ge • etabolic disorders • ex (female) • euromuscular disease • besity • rauma • H • A • M • S • N • O • T

50. Osteoarthritis – Joints Involved Neck Spine Hip PIP, DIP, CMC Knee 1st MTP