Msd 1 (Gout, Ra, Ifxn Oa, Sa, Sle)

Front 1

What causes gout?

Back 1

An inflammatory response to uric acid crystals that are deposited in the joint

Front 2

Epidemiology of gout (men vs women)

Back 2

Men get a large increased in uric acid levels after puberty. In women, estrogen appears to be protective agains uric acid so levels do not rise until after menopause.

Front 3

saturation point of uric acid

Back 3

~ 7 mg/100 ml

Front 4

Stage 1 of gout

Back 4

uric acid pool is in a delicate balance of formation and excretion.

Front 5

source of purines and means of excretion

Back 5

Sources of adenine and guanine are from diet (0.33) and cellular necleotides (0.66). A thrid of uric acid pool is ecreted by gut (bacterial degredation, and two-thirds, by renal excretion.

Front 6

General Mechanisms of Uric acid overproduction (2)

Back 6

Abnormal Purine metabolism ( increased PRPP synthase , defective HGPRT). Increased cell and purine turnover (Myelo- and Lymphoproliferative malignancies, hemolytic anemias, Chemotherapy with tumor lysis.

Front 7

Good foods and Bad foods (purine content)

Back 7

Increased consumption of meat --> bad. Increased dairy --> good.

Front 8

important enzyme in de novo purine synthesis

Back 8

PRPP synthase. Overactive PRPP synthase can lead to increased purine synthesis and gout.

Front 9

important enzyme in purine salvage pathway

Back 9

HGPR transferase. Deficiency of this enzyme results in elevated xanthines and hence elevated uric acid. Purine salvages fails (lysch-neyan syndrome)

Front 10

General mechanisms of uric acid undersecretion (3)

Back 10

Renal Tubular defects. Glomerular insufficiency, competitive inhibition of excretion by lactic acid and ketoacidosis or drugs

Front 11

Risk of hyper uricemia

Back 11

for most patients, there are no consequences of hyperuricemia so its not treated.

Front 12

Stage 2 of gout

Back 12

acute gout

Front 13

Most common site of first attack

Back 13

great toe (Podagra)

Front 14

pathogenesis of acute gout

Back 14

urate crystal is offending antigen. Upregulation of inflammatory cascade in two ways: 1. activation of complement C5a (direct and indirect pathways) leading to an upregulation of PMN integrins --> PMN activation. 2. Activation of synovial macrophages (IL-1, TNF-alpha, IL-8) --> upregulation of Endothelial cell ICAMs and Selectins

Front 15

Effect of crystal on neutrophils in the gouty joint

Back 15

Neutrophil actiavtaion leads to production of leukotrienes, superoxides and preoteases. Neutrophil lyses releases inflammatory cytokines. Essentially, neutrophil infiltration leads to a constant cycle of inflammation and joint damage.

Front 16

Lab values in acute gout

Back 16

Elevated ESR, elevated WBC, elevated Uric acid, X-ray will show just swelling of tissue.

Front 17

How is a definite diagnosis made?

Back 17

Joint aspiration. This will show: uric acid crystals (both extracellular and intracellular), other crystals, synovial fluid leukocytosis, culture and gram tain to rule out infection.

Front 18

Pseudogout

Back 18

Caused by calcium pyrophosphate crystals

Front 19

characteristics of pseudogout

Back 19

A bit less inflammatory than gout. Less podagra. Postively Birefringement crystals. Seen in hyperparathyroidism, familial hypocalciuric hypercalcemia, hypophosphatasia, hypomagnesemia and hypthyroidism

Front 20

treatment of acute gout and acute pseudogout (4)

Back 20

No treatment --> will self resolve after 2 weeks however very painful though. NSAIDS or COX-2 inhibitors. Glucocorticoids.Colchicine

Front 21

Stage 3 of gout

Back 21

intercritical gout

Front 22

treatmetn of stage 3 gout

Back 22

nothing if rare attacks. Low purine diet. Low dose colchicine. NSAID or cox-2 inhibitor. Probenicid (URAT inhibitor). Allopurinol (decreases urate production). Febuxostat (a non-purine xanthine oxidase inhibitor

Front 23

stage 4 of gout

Back 23

chronic tophaceous gout. These can occur anywhere in the body

Front 24

Lecture 2

Back 24

Rheumatoid Arthritis

Front 25

Epidemiology of Rheumatiod arthritis (gender prevalence, age range)

Back 25

There is an increase on female prevalence. Peak onset of the disease is between the 4th and 6th decades of life

Front 26

Pathogenesis of RA (3)

Back 26

1: Primary T cell reaction (Th1 response) to some unkown antigen. 2: mesenchymal inflammatory response. 3: Erosive process at the joint margin. (all three processes go on simultaneously)

Front 27

Stage 1 - 5 of RA pathophysiology

Back 27

1: presentation of antigen (asymptomatic phase). 2: Initiation of perpertuation of inflammatory response. 3: Infiltration into synovium leading to synovial proliferation (symptomatic --> Joint pain, swelling, stiffness). 4: X-ray shows articular bone loss. 5: Erosion of subchondral bone, pannus invasion, distortion of articular architecture. (symptoms of Pain, Joint instability, Extra-articular manifestation)

Front 28

Clinical features of RA(7)

Back 28

Symmetrical Polyarthritis. Positive Rheumatoid Factor and Anti-CCP Antibodies. Acute phase reactants. Morning Stiffness > 1 hour in duration. Limited function. Extra-articular manifestation. Constitutional symptoms.

Front 29

Most common joints affected in RA (2)

Back 29

PIP (90% of patients) and MTP.

Front 30

Joints that are not affected in RA (2)

Back 30

DIP. Lumbar spine is also not a likely site.

Front 31

Critera for diagnosing RA

Back 31

At least 4 out of 7 criteria must be present for more than 6 weeks.

Front 32

7 criteria for diagnosing RA

Back 32

Arthritis of the hands. Symmetric Arthritis. Rheumatoid nodules. Morning stiffness. Serum Rheumatoid Factor. Radiographic changes (later finding). Arthritis of three or more different joint areas.

Front 33

Physical exam of RA (nature of the joint)

Back 33

Tender and boggy joint. Deformity as well as reduced range of motion. Significant muscle wasting. Low grade fever. Nodules. MCP subluxation. Swan-neck deformity. Boutonniere deformity (--> PIP hyperflexion with DIP hyperextension) Ulnar deviation

Front 34

Effect on synovial membranes (RA)

Back 34

hyperplasia of synovial membranes because of neutrophilic infiltration, capillary formation and hypertrophic synoviocytes.

Front 35

Extraarticular Manifestations of RA (7)

Back 35

Rheumatoid Nodules. Serositis. Interstitial Lung disease. Scleritis. Vasculitis. Felty's Syndrome. Sjogren's Syndrome

Front 36

Felty's Syndrome (3)

Back 36

RA, Splenomegaly, Neutropenia

Front 37

Sjogren's Syndrome

Back 37

Autoimmune attack of the exocrine glands that produce tears and saliva.

Front 38

Secondary Sjogren's Syndrome (4)

Back 38

Keratoconjunctivitis sicca (inflammation of cornea and conjunctivia). Xerostomia (dry mouth_. Lack of extraglandular involvment. Evidence of systemic autoimmune disease

Front 39

Lab findings in RA (5)

Back 39

Rheumatoid Factor (+ in 80 %). Anti-CCP (+ in 78 %). ANA (+ in 40 %). Normocytic Anemia. Elevated acute phase reactants.

Front 40

HLA associated with RA (2)

Back 40

HLA DR4 and HLA DR1 (these HLAs are expressed on B cells and macrophages. They play a part in peptide binding. Severe disease has the strongest HLA DRB1 association).

Front 41

Treatment (Disease Modifying Anti-RA drugs -- DMARD) (7)

Back 41

Methotrexate. Leflunomide. Slfasalazine. Azathioprine. Hydroxychloroquine. Cyclosporine. IM Gold.

Front 42

Treatment (Biological Agents against RA) (5)

Back 42

Anti-TNF agents. IL-1 receptor antagonists. Anti-CD20. CTLA4-Ig. Anti-IL-6

Front 43

Other treatment of RA

Back 43

Reduce exposure to inciting agents. Prevent neovascularization. Modulate inflammatory process and proteases

Front 44

Lecture 3

Back 44

Septic arthritis and Osteomyelitis

Front 45

Primary risk factors for infectious joints (5)

Back 45

RA (10x risk). SLE. Osteoarthritis. > 60 yrs. Previous trauma to the joint.

Front 46

Secondary risk factors for infectious joints

Back 46

Diabetes. Malignancies. Renal Disease. Liver Diseae. Immunosuppression. IV drug abuse.

Front 47

Staph epidermidis infection of joint

Back 47

Joint Implant surgery

Front 48

Salmonella infection of joint (2)

Back 48

Sickle cell disease. Reptile owner

Front 49

Pseudomonas infection of joint (2)

Back 49

Wet Sneaker Puncture Wound. IV drug users

Front 50

Different ways bacteria can enter a joint and be deposited in the synovium (3)

Back 50

1: Hematogenous spread. 2: Direct Inoculation. 3: Peri-articular spread.

Front 51

Pathophysiology of Septic arthritis

Back 51

Bacterial infection of joint (synovial membrane) --> inflammatory response with release of cytokines --> cartilage degradation and inhibition of cartilage synthesis --> complications (eg: osteonecrosis of the hip joint)

Front 52

Clinical presentation of Septic arthritis (7)

Back 52

Single swollen and painful joint. Decreased range of motion. Large effusion. Warm. Erythema. Systemic signs. Knee involvement (50 % of cases)

Front 53

Best way to diagnose septic arthritis

Back 53

Synovial fluid culture.

Front 54

Cystalline Arthropathy

Back 54

Gout or pseudogout (may co-exist with septic arthritis)

Front 55

Reactive synovitis/Viral Synovitis

Back 55

History of GI symptoms. conjunctivitis. Mucus membrane lesions

Front 56

Bursitis

Back 56

Red-herring. This is inflammation around the joint, not in the joint.

Front 57

Acute inflammatory arthritis

Back 57

RA or lyme disease

Front 58

Which type of septic arthritis is a medical emergency?

Back 58

bacterial septic arthritis. Also the most common and most clinically significant

Front 59

Treatment goals of septic arthritis (3)

Back 59

Permanently resolve infection (remove fluid and wash the joint. Use Abx). Prevent joint/articualar cartilage destruction. Maintain normal joint function.

Front 60

Antibiotic choice in Septic arthritis (2)

Back 60

Vancomycin and a 3rd generation cephalosporin, then culture sensitive treatment once cultures are ready.

Front 61

Risk factors for gonoccal Arthritis (5)

Back 61

females more than males. SLE. Menstruation and pregnancy. Male homosexuality. Promiscuity.

Front 62

How do gonococcal arthritis present (monoarticular arthritis)

Back 62

No systemic signs, no sign lesions

Front 63

How do gonococcal arthritis present (systemic disease) (3)

Back 63

Fevers, Migratory arthralgias, Asymmetric involvement of distal joint. Teneosynovitis (inflammation of synovium). Multiple skin lesions (Dermatitis-Arthritis syndrome)

Front 64

Dermatitis-Arthritis syndrome

Back 64

Small pustular lesions that can occur on palms and soles.

Front 65

Diagnosis of Gonococcal arthritis (5)

Back 65

Sexually active. Synovial fluid analysis (has low % of + cultures). Endocervical culture/Male urethral culture. Urine PCR. Look for rectal, pharnx, skin lesions.

Front 66

Treatmetn of gonococcal infection

Back 66

3rd generation cephalosporin + concommitant treatment for chlamydia infection as well

Front 67

Common causes of viral arthritis

Back 67

Parvovirus. Hepatitis B and C. Rubella. Alphavirus. Lyme disease. HIV. Enteroviruses. Mumps. Adenovirus. Varicella. HSV. CMV. EBV

Front 68

Viral arthritis of Parvovirus B19 (common sites and epidemiology)

Back 68

Affects MCPs and PIPs and knees. Occurs in 8% of children but in 60 % of adults

Front 69

Systemic signs if viral arthritis of Parvovirus B 19

Back 69

fifths disease (erythema infectiousum)

Front 70

Diagnosis of Parvovirus B 19 abd treatment

Back 70

Diagnosed by clinical pictuer and + IgM serology. Supportive tratment with NSAIDS because it resolves on its own in weeks to months.

Front 71

Lyme disease of the joint (common signs, diagnosis & treatment)

Back 71

Migratory arthralgias. Screen with ELISA, confirm with Western blot. Treat with Doxycline. (About 10 % of patients may develop chronic arthritis.

Front 72

Tuberculosis of the joint (eipidemiology)

Back 72

Single joint (weight bearing joint). Hematogenous spread. Older patients. May spread from osteomyelitis.

Front 73

Most common offending agent in osteomyelitis

Back 73

Staphylococcus

Front 74

Risk factors for osteomyelitis (2)

Back 74

systemically compromised host (Transplant pt). Local tissue compromise (vascular disease in diabetics)

Front 75

osteomyelitis in infant

Back 75

S. aureus. Strep Agalactia. E. coli

Front 76

osteomyelitis in children > 1

Back 76

S. aureus. Strep pyogens. H. flu

Front 77

osteomyelitis in adult

Back 77

S. aureus

Front 78

osteomyelitis in diabetics

Back 78

pseudomonas

Front 79

ostemyelitis in sickle cell pt

Back 79

salmonella

Front 80

pathogenesis of osteomyelitis

Back 80

typically hematogenous spread of bacteria. Exudate in marrow leading to increased pressure. extension of pressure into bone coretex leading to ruprues through periosteum. interruption of blood supply leads to necrosis.Commonly affects children because their bones are more vascularized. In older pts, tend to happen in verterbral bodies (classic presentation = elderly pt comes in with new onset back pain and fever)

Front 81

Piece of dead bone? New bone formation?

Back 81

Sequestra. Involcrum

Front 82

Diagnosis of osteomyelitis

Back 82

Postive culture from bone + a CBC, ESR, CRP.

Front 83

Treatment of osteomyelitis

Back 83

Specific abx (IV) for 6 weeks. Surgical decompression of bone. Hyperbaric oxygen

Front 84

Presentation and treatment of chronic osteomyelitis

Back 84

chronic draining ulcers. Exarcebations (with fever etc) separated by quiescent periods. Treat with combined surgical and medical management.

Front 85

Lecture 4

Back 85

Osteoarthritis

Front 86

osteoarthritis

Back 86

clinical syndrome which is characterized by cartilage damage and disordered reparative damage response of cartilage synovium and bone.

Front 87

Diagnosis of osteoarthritis (radiographic appearance)

Back 87

Laterally projecting osteophytes. Narrowing joint spaces. Subchondral changes (cyst ands sclerosis), malalignment. Sclerosis of adnacent bony margins.

Front 88

Common sites affects in osteoarthritis

Back 88

hands, Hips, Knees, Spine.

Front 89

Physical signs of osteoarthritis

Back 89

Bony enlargement (Heberden's Nodes--> DIP joints; Bouchard's Nodes --> PIP joints), brief morning stiffness, joint pain is worse with use. Limited range of motion. Joint crepitus (Creaking sound with use). No inflammatory effusions.

Front 90

Epidemiology of osteoarthritis

Back 90

highest prevalence of joint diseases. Most common in femaleas after menopause. Rare familial forms (type II procollagen gen mutation.

Front 91

Risk factors for osteoarthritis

Back 91

increased age. Inflammation. High bone mineral density. Hormonal status. Prolonged immobilization. Hypermobility syndromes. Obesity. Occupational stress.

Front 92

Function of collagen in cartilage

Back 92

provides tensite strenght and prevents cartilage from over stretching

Front 93

Stage 1 of osteoarthritis

Back 93

Increased matrix water content. Decreased aggrecan. Damaged collagen Network. Reduced stiffness of the Cartilage.

Front 94

Stage 2 of osteoarthritis

Back 94

Chondrocyte compensation by enhanced proliferation ane metabolic activity. Cell clusters form, surrounded by newly formed matrix

Front 95

Stage 3 of osteoarthritis

Back 95

chondrocyte aplptosis. Loss of cartilage. Subchondral bone fibrillation and cyst formation. Osteophyte and subchondral sclerosis

Front 96

Non-pharmacological treatment of osteoarthritis

Back 96

Patient education and Self-management programs. Social support. Weight-loss. Aerobic excerise. Physical therapy. Muscle strengthening exercise. Assisted devices for daily living. Joint protection.

Front 97

Pharmacological treatment of osteoarthritis

Back 97

Pain modulators. Disease modifying agents (anti-inflammatory agents). Surgical treatment (osteotomy, joint replacement, chondrocyte transplantation).

Front 98

Lecture 5

Back 98

Sero-negative spondyloarthropathies

Front 99

What is reactive arthritis (Reiter's syndrome)

Back 99

sterile synovitis that develops during or after a genital or enteric infection

Front 100

offending agents of reactive arthritis

Back 100

Post enteric: Shigella, salmonella, yersina, campylobactor. Post Veneral: Chlamydia, Mycoplasma

Front 101

Manifestation of reactive arthritis

Back 101

Arthritis. Urethritis. Conjunctivitis. Mucocutaneous lesions.

Front 102

Treatment of reactive arthritis

Back 102

Antibiotic and NSAIDS.

Front 103

Ankylosing spondylitis (gender? Bacterial? Familial?)

Back 103

Male predominance. No bacterial trigger. Tends to be familial

Front 104

Clinical feature of Ankylosing spndylitis

Back 104

Spinal manifestation: Back pain, sacroilitis, Fractures, Atlanto-axial subluxation. Other MS involvement: Peripheral arthritis, Tendintis, Almost always involves the hip. Extra-articular manifestation: Acute anterior uveitis, Heart Block, Apical Pulm Fibrosis, Cauda Equina syndrome, Secondary amyloidosis

Front 105

Treatment arthritis

Back 105

Drugs: NSAIDS, Sulfasalzine, Bisphosphonates. TNF-alpha blockers (as early as possible). Surgery: joint replacement, wedge oseotomy

Front 106

Psoriatic Arthritis

Back 106

autoimmune disease that involves the skin (psoriasis) with arthritis of hands and toes.

Front 107

Clinical presentation of psoriatic arthritis

Back 107

Asymmetric distribution. DIP involvement only. Sausage digits. Bamboo spine

Front 108

Treatment of psoriatic arthritis

Back 108

NSAIDS, physical therapy, methotrexate, lefunomide

Front 109

Arthritides associated with IBD

Back 109

Ankylosing spondylitis and Enteropathic arthritis

Front 110

HLA association btn IBD and arthritis

Back 110

HLA B27

Front 111

Lecture 6

Back 111

Systemic Lupus Erythematous

Front 112

Genetic associations in SLE

Back 112

Over-reacting immune system. HLA-A1, B8, DR3

Front 113

Hormonal factors in SLE

Back 113

Abnormal estrogen metabolism or elevated prolactin + low androgen levels

Front 114

Environmental factors in SLE

Back 114

Drugs: Procainamide, INH, sulfa drugs, Penicillamine, Methyldopa, Anticonvulsants, Beta-blockers. UV light. Infections. Smoking. Surgery.

Front 115

Pathogenesis of SLE

Back 115

antinuclear Abs trigger Apoptosis of cells that are poorly cleared. Phagocytosis of this material stimultes the immune activation and tissue damage.

Front 116

3 things to know about etiology of lupus

Back 116

Autoantibody production. Generation of Circulating Immune complexes, Episodic complement activation.

Front 117

SLE diagnosis

Back 117

4 our of 11 criteria

Front 118

criteria for diagnosing SLE

Back 118

Malar Rash. Discoid rash. Photosensitivity. Oral ulcers. Arthritis. Sserositis. Renal disorder.Neurological Disorder. Hematological disorder. Immunologic disorder (Anti-DNA or Anti-smith or antiphospholipid Abs). Anti nuclear Abs (ANA is sensitive, but not specific for lupus)

Front 119

Cardiac disease in Lupus

Back 119

Myocarditis. Valvular disease. Accelerated atherosclerosis (9 times the mortality of normals)

Front 120

Mortality data of SLE

Back 120

90% 5 yr mortality, 80% 10 year mortality. Worse if: renal disease, Males or children. Worse in Aas. Worse in pts with antiphospholipid Abs

Front 121

Antiphospholipid Ab syndrome

Back 121

A vascular thromboss and/or pregnancy morbidity developing in persistenly anti-phospholipid antibody positive pts

Front 122

Treatment of SLE

Back 122

Sunscreen. Topical steroids. NSAIDs. Calcium and vit. D. Anti-malarials. Steroids. Cytotoxics (methotrexate, etc). Mycophenalate mofetil. Vaccines and anti-depressants if needed.