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Block 4 AR > Pathophysiology > Flashcards

Pathophysiology Flashcards

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1
Q

What is pseudogout?

A

Aging cartilage degeneration: age related OA - calcium pyrophosphate crystals into joint cavity. Common in the elderly
Mineralisation around chondrocytes
Mainly asymptomatic

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2
Q

What are Seronegative spondyloarthropathies?

A

Inflammatory systemic disease involving axial skeleton (spine and sacroilliac joints), also peripheral joints. Negative to rheumatoid factor
Oligoarthritis commonly involving large joints in lower limbs
Familial clustering, & linkage to HLA-B27
Characterized by inflammation at sites of attachment of ligament, tendon, fascia, or joint capsule to bone (enthesopathy)
Includes Reiter’s syndrome, ankylosing spondylitis, psoriatic arthritis, & arthritis of inflammatory bowel disease
Occurs more third decade, commonly young men
Genetic factors important role in susceptibility
Initial event involves interaction between genetic & environment factors, particularly bacterial infections
Reiter’s syndrome may follow GI/ GU infections
Bowel inflammation implicated in pathogenesis of Reiter’s syndrome, psoriatic arthritis, & ankylosing spondylitis

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3
Q

What is Ankylosing spondylitis?

A

Erosion of sites where ligaments and tendons attach to bone at sacroiliac joint and lumbar spine. Eventual posterior fusion of spine and possible involvement of upper spine and large joints. 5x more common in men. 90% have HLA-B27 antigen

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4
Q

What are Reactive arthropathies?

A

Inflammatory joint disorders with an infective cause but distant in time and place from the infection

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5
Q

What is Psoriatic arthritis?

A

Inflammation of the joints in 5-7% of psoriasis sufferers
Most have extra spinal disease
Silver/grey scaly spots on scalp, elbows, knees and lower spine
Pitting fingernails/toenails
Pain & swelling in one or more joints
Dactylitis of fingers/toes gives “sausage” appearance

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6
Q

What are 3 types of autoimmunity?

A

Organ-specific: type 1 diabetes
Tissue-specific: myesthenia gravis
Systemic: lupus

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7
Q

Which cells mainly mediate autoimmunity?

A

B cells

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8
Q

Why can diagnosis of autoimmunity be difficult?

A

Presence of auto-antibodies in healthy patients

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9
Q

What are the mechanisms underlying autoimmunity?

A

Inappropriate access to self- antigens by antigen presenting cells (normally immuno-priviledged site exposed)
Inappropriate/increased local expression of co-stimulatory molecules (infection or inflammation)
Alterations in way in which molecules are presented to immune system
(MHC changes)
Molecular mimicry (infective agent)

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10
Q

What are the types of arthropathy?

A

Degenerative: OA
Inflammatory: Seropositive e.g. RA, Seronegative e.g. Ank Spond, Psoriatic, Inflammatory bowel disease, Gout, Infection

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11
Q

What are risk factors for rheumatoid arthritis?

A

Genetic predisposition: HLA-DR4 associated
2-3x women than men
Increases with age
Caucasians

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12
Q

What are symptoms of rheumatoid arthritis?

A

Systemic: fatigue, anorexia, weight loss, low grade fever, anaemia
Articular- joint aching and stiffness
Extra-articular: pericarditis, valve problems, atherosclerosis, pleural effusions, rheumatoid nodules, pulmonary fibrosis, anaemia, splenomegaly, osteoporosis, rheumatoid nodules, vasculitis, leg ulcers, C1/C2 atlanto-axial subluxation, nerve compression scleritis, xerophthalmia

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13
Q

What are clinical features in the hands of a rheumatoid patient?

A

Metacarpophalangeal joint & proximal interphalangeal joint arthritis with ulnar deviation

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14
Q

Describe the pathogenesis of rheumatoid arthritis

A

Rheumatic factor autoantibodies attack synovium
Inflammation of synovium: angiogenesis, proliferation
Secondary changes occur in cartilage: enzymes and prostaglandins destroy articular cartilage and underlying bone, pannus invasion destroys cartilage at joint periphery

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15
Q

What can cause ankylosis of joints in rheumatoid arthritis?

A

Reduced movement of joint due to collagen scarring building up in the joint. This can mineralise and fix the joint

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16
Q

Describe visible differences in the joint between RA and OA

A

RA: inflammation, pannus, eroding cartilage, bony & fibrous ankylosis
OA: Osteophytes, bony spur, no ankylosis, subchondral cyst, subchondral sclerosis, thinned fibrillated cartilage

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17
Q

What investigations can be done to diagnose rheumatoid arthritis?

A

Bloods
FBC : anaemia (chronic disease / haemolytic)
ESR : raised
CRP : moderately raised
Immunology: RhF : raised in ~70% of cases (also some healthy people), Anti CCP more specific marker
Radiology :
US, MR or isotope bone scans (early changes)
Radiographs of hands & feet (later changes), soft tissue swelling, juxta-articular osteopenia, joint space narrowing, periarticular erosions, subluxation, deformity

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18
Q

What are treatment options for rheumatoid arthritis?

A

Symptomatic relief: Pain killers, Glucocorticosteroids
Treatment of underlying disease process: DMARDS (Disease modifying anti-rheumatic drugs), Normally at least two
Biological agents after DMARDS have been unsuccessful

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19
Q

How do corticosteroids help to treat rheumatoid?

A

Inhibition of transcription factors
Reduced transcription of many cytokine genes e.g. ↓IL1, IL2 and TNF
Reduced clonal proliferation of T helper Cells

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20
Q

What are DMARDs?

A

Mimic endogenous compounds, Anti-cancer and immunosuppressant effects
Anti-proliferatives: Methotrexate (against folate activity), azathioprine (against purine synthesis)
Suppressive: sulphasalazine (against IL-1 & TNF), penicillamine (against MΦs, T cells, IL-1)
Gold injections = uncertain mechanism

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21
Q

Describe how methotrexate works

A

Folic acid antagonists. Inhibits dihydrofolate reductase activity which prevents conversion of dihydrofolate to tetrahydrofolate which is not all used for the production of purines and amino acids and therefore DNA and protein synthesis
Inhibits S phase
Renal excretion
Side effects - mainly affects tissues which are highly proliferative - Gi tract, liver due to anti proliferative effects

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22
Q

Describe how azathioprine works

A

Anti proliferative effects
Purine analogue
Reduce DNA & RNA synthesis so can’t go through cell cycle
Reduce guanine and adenine synthesis
Adverse effects: cholestasis, liver necrosis

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23
Q

What Biological Agents can be used to treat rheumatoid arthritis?

A

mAbs (monoclonal antibodies): infliximab = anti-TNF cytokine, rituximab = anti-CD20 on B lymphocytes

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24
Q

What is the prognosis for rheumatoid arthritis patients?

A

10% will become severely disabled, majority of damage in first 5 years
70% will have variable symptoms with flair ups requiring drug therapy 20% mild disability and symptoms
Complications: Reduced immunity, Complications of drug treatments

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25
What questions need to be asked in a history addressing lumps and bumps?
``` How long have you had this? Exacerbating/alleviating factors Pain in swelling location or elsewhere History of trauma Any previous or recent treatment/intervention/surgery Site-dependent questions Neurological disturbance/distribution Temporally-associated systemic symptoms ```
26
What additional factors need to be considered when forming a diagnosis on lumps and bumps?
``` Age Gender Social history Occupation Medical history ```
27
What are 2 methods for lump examination?
``` SSSCCATTTT Site, Size, Shape, Consistency, Colour, Auscultate, Tenderness, Tissue layer, Thrills/Fluctuance, Transillumination SPACE TIT Size, Shape, Surface Position Attachments Consistency & Colour Edge Thrills/pulsation/fluctuance Inflammation Transillumination ```
28
What are methods for determining the origin/content of a lump?
Transillumination - fluid filled Fluctuance - fluid filled Auscultate - air, bowel sounds, pulsation, bruits
29
What does annular mean in relation to lumps?
Ring shaped
30
What does arcuate mean in relation to lumps?
Curved
31
What does nodule or papule mean in relation to lumps?
Palpable mass of specific size
32
What does macule mean in relation to lumps?
Flat region of surface colour change
33
What does pustule mean in relation to lumps?
Small pocket of pus
34
What techniques can be used to determine the tissue layer location of a mass?
Bone masses are immobile Muscle/tendon masses can be moved, or have their movement limited, by muscle contraction Neural masses only tend to move left-to-right Pressing on a neural mass can cause pain/tingling/sensory loss Lumps within the skin can be moved with the skin
35
What ways can you describe a skin cancer?
A – Asymmetry B – Borders C – Colour D - Dimensions
36
How does lymphadenopathy present?
Palpable relatively non-mobile mass | Enlargement can be unilateral during cancer or infection
37
What are Sister Mary Joseph Nodules?
Cancer metastasis in umbilicus | Spread up urachus from bladder
38
What needs to be considered with groin lumps?
Can you get above the swelling? Yes: not a hernia, No: likely a hernia Reduce a hernia and test cough impulse Is it solid or fluid-filled? - fluid, hydrocele Where is the lump relative to the testicle? - above: spermatocele, on testicle: Cancer Where is the testicle? - within swelling: hydrocele Does it look/feel like a ‘Bag of worms’? - varicocele
39
What is testicular pain?
Torsion until proven otherwise
40
What is a hydrocele? And how can you diagnose it?
Fluid in tunica vaginalis Will transilluminate and sits at the level of the testicle May not be able to palpate the testicle
41
How would a patent processus vaginalis present?
Young boy Swelling not there in the morning but appears during the day, then disappears when lying down Swelling transilluminates but can’t get hand above it Peritoneal fluid communicating, gravity means it accumulates through the day
42
What is a hernia?
Protrusion of a tissue or organ through its retaining tissue
43
What are the 4 abdominal wall area hernias?
Inguinal: Males more than females, Above & medial to pubic tubercle Femoral: Females more than males, Below & lateral to pubic tubercle Incisional (post operative) Umbilical: Normally in newborn / young
44
What is Lumbar (Petit) triangle?
Site for herniation | Bordered by iliac crest, latissimus dorsi and external oblique
45
What is the inguinal canal?
Passageway through anterior abdominal wall
46
What is the deep inguinal ring?
Invagination of transversalis fascia | Lies between the midpoint of inguinal ligament & the midinguinal point (1cm above the inguinal ligament)
47
What is the superficial inguinal ring?
Lies supero-lateral to the pubic tubercle | Point of emergence of spermatic cord (male) or round ligament of uterus and coverings (female)
48
What are the contents of the female inguinal canal?
Round ligament of uterus Lymphatics from uterus Ilioinguinal nerve Genital branch of genitofemoral nerve
49
What are the contents of the male inguinal canal?
Spermatic cord & contents Ilioinguinal nerve Genital branch of genitofemoral nerve
50
What is a direct inguinal hernia?
Medial to inferior epigastric artery Weakness of conjoint tendon Presses on the superficial inguinal ring
51
What is an indirect inguinal hernia?
``` Lateral to inferior epigastric artery Passes through processus vaginalis via deep & superficial inguinal rings Travels into scrotum Congenital type Common in males ```
52
What is Hesselbach’s triangle?
Region of bulging with a direct inguinal hernia | Bordered by rectus abdominis, inguinal ligament and inferior epigastric artery
53
Describe the examination of an inguinal herniae
``` Patient lying down & standing Observe site and direction Make other regional observations Compare sides Test cough impulse Reducible/irreducible Pressure over alternate inguinal rings May need to stand Auscultate for bowel sounds ```
54
What types of groin swelling can occur in females?
Canal of Nuck (female equivalent of processus vaginalis) Bartholin gland cyst Femoral hernia
55
What swellings can occur in femoral triangle?
Saphenous vein pierces roof (can dilate here saphena varix) Inguinal lymph nodes sit in triangle (lymphadenopathy) Femoral hernia presents as swelling in the triangle
56
Where are superficial inguinal lymph nodes?
Sit in two groups, proximal & distal | Gross lymphadenopathy can present as a groin lump
57
Which structure lies outside femoral sheath & deep to iliac fascia?
Femoral nerve Femoral artery, vein & lymphatics located inside the fascia Artery and vein sit in femoral sheath & lymphatics sit in femoral canal
58
What is the femoral canal?
Fascial compartment for lymphatics (weak spot)
59
Why are women at higher risk of femoral hernia?
Wider pelvic girdle so femoral canal larger
60
What forms the femoral ring?
Lacunar ligament Inguinal ligament Pectineal ligament High chance of hernial sac contents strangulation due to rigid borders of femoral ring
61
What are Branchial cysts?
Remnants of the embryological branchial sinus which should obliterate If it remains open it can form a branchial fistula that opens & discharges onto the lower neck
62
What are rheumatological diseases?
Characterized by pain & inflammation in joints & connective tissues Sometimes referred to as collagen-vascular diseases May affect many different parts of the body Over 200 different conditions
63
What are Non Immunological Inflammatory Diseases?
Osteoarthritis (OA) Gout Pseudogout
64
What form of immunity underlies the non inflammatory rheumatological diseases?
Innate
65
What are Immunologically-Mediated rheumatological Diseases?
``` Rheumatoid Arthritis (RA) Systemic Lupus Erythematosus (SLE/ Lupus) Spondyloarthropathies Ankylosing spondylitis Reactive Arthritis (Reiter’s Syndrome) Psoriatic Arthritis Spondylitis associated with Inflammatory Bowel Disease Sjogren’s Syndrome Polymyositis/Dermatomyositis Behcet’s Syndrome Systemic Sclerosis (Scleroderma) Giant Cell Arteritis ```
66
What is the Function of Normal Synovium?
Maintenance of intact non-adherent tissue surface Lubrication of cartilage Control of synovial fluid volume & composition (plasma & hyaluronan) Nutrition of chondrocytes within joint
67
What is athralgia?
Joint pain
68
What are characteristics of joint Arthritis?
``` Pain Redness Swelling Increased warmth Fluid accumulation (synovial effusion) Stiffness (especially in morning/ inactivity) ```
69
Describe the Pathogenesis of Rheumatoid Arthritis
``` Inflammed synovial tissue (synovitis) Villous hyperplasia Intimal cell proliferation Inflammatory cell infiltration: T & B cells, macrophages & plasma cells Production of cytokines & proteases Increased vascularity Self-amplifying process ```
70
What are Key cytokines in Chronic Inflammatory Arthritis?
``` TNF-alpha IL-1 IFN-gamma IL-6 OPGL (RANK-ligand) IL-17 IL-23 ```
71
What T cell subtypes contribute to pathogenesis of RA?
Synovial naive T cells Regulatory T cells T helper cells: release cytokines to activate leukocytes and mesenchymal cells, recruit B cell help, cytotoxicity CD8 cells, cell contact mediated activation of macrophages, fibroblasts & endothelium
72
What signs of RA can be seen on xray?
Early Arthritis - soft tissue swelling, especially around PIP joints Chronic inflammation in joint leads to bone destruction evident as erosions Prolonged severe chronic arthritis leads to deformity & disability
73
What is the Immune Response Directed Against in RA?
Type II collagen IgG (rheumatoid factor) Citrullinated proteins (arginine residues modified)
74
What is the immune response targeted against in SLE?
Nuclear: Ribonuclear proteins, Histones, dsDNA Leukocyte cell surface antigens Cardiolipin
75
What are Susceptibility genes for rheumatological conditions?
``` MHC class II in RA, HLA DR4 MHC class I in seronegative spondyloarthropathy Complement deficiency genes in SLE Gender due to oestrogen involvement ```
76
Describe Genetic Basis of Rheumatic Diseases
Genotype contributes to rheumatic disease susceptibility Rheumatic diseases are polygenic Genotype predisposes an individual to disease, but does not make disease development certain
77
What Environmental factors may contribute to rheumatological disease?
Viral (hepatitis B and C, mumps, EBV) Bacterial (Streptococci, Salmonella, Shigella) UV light in SLE
78
What factors of Immune System Status are important in the development of rheumatological conditions?
``` Relative state of activation Relative balance of Th1:Th2 cells History of previous immune responses Level of expression of autoantigen Level of expression of MHC Co-stimulatory molecules Ongoing inflammation ```
79
Describe the 3 phases of RA development
Environment and genetics feed into this Pre-articular phase: autoimmunity, anti CCP, RhF, collagen specific response Transition phase: microbial insult, biomechanical events, neurological events, microvascular dysfunction Articular phase: articular localisation, CV disease, osteoporosis, functional decline
80
Describe differences between acute and chronic inflammatory arthritis
Acute Arthritis: Rapid onset (hours/days), Severe symptoms, innate immune response, neutrophils (proteases, leukotrienes, prostaglandins) rapid joint destruction, Can evolve into chronic disease Examples: Gout & Infectious Arthritis Chronic Arthritis: gradual onset (days/weeks), Symptoms more moderate, adaptive immune response, T cells & macrophages, Cytokines & chronic inflammation lead to joint remodeling & destruction via erosion Examples: Rheumatoid Arthritis, Ankylosing Spondylitis
81
Give examples of monoarticular inflammatory arthritis
Gout Infection Reactive
82
Give examples of polyarticular inflammatory arthritis
RA | SLE
83
Which joints are affected in RA and SLE?
PIPs and MCPs
84
Which joints are affected in Osteoarthritis and Psoriatic arthritis?
DIPs
85
Which joint is affected in gout?
MTP - big toe
86
Give examples of symmetrical inflammatory arthritis
RA and SLE
87
Give examples of asymmetrical inflammatory arthritis
Psoriatic and reactive
88
What is the clinical picture of someone presenting with RA?
``` Morning stiffness Arthritis of 3 or more joints Arthritis of hand joints Symmetrical Rheumatoid nodules Anti CCP/RhF Radiographic changes Diagnostic criteria: 4 of 7 present for at least 6 weeks ```
89
What can be complications of RA?
``` Carpal tunnel syndrome Baker’s cyst Vasculitis Subcutaneous nodules Secondary Sjögren’s syndrome Peripheral neuropathy Cardiac & pulmonary involvement Felty’s syndrome Anaemia of chronic disease ```
90
What are therapeutic strategies for RA?
Reduce inflammation: NSAIDs, Steroids (prednisolone) Disease Modifying Anti-Rheumatic Drugs (DMARDs): Sulfasalazine, Methotrexate, Hydroxychloroquine, Steroids, Azathioprine, Cyclosporine, Cyclophosphamide More selective biologics: TNF antagonists, IL-6R antagonists, anti-B cell (CD20) therapy, costimulatory inhibitors (CTLA4-Ig), (IL-1R antagonists)
91
How does etanercept exert its therapeutic effects?
Binding of inflammatory cytokines like TNF to its receptor leads to the production of inflammatory effector molecules. Soluble TNF receptor fusion proteins like etanercept prevent this binding MAbs have similar effect by binding directly to the cytokine
92
What are surgical options for RA treatment?
Removal of inflamed synovium | Arthroplasty
93
What systems can be effected in RA?
``` Joints (arthritis) Vessels (vasculitis) Eyes (scleritis & episcleritis) Haematologic (anaemia, thrombocytosis) Pulmonary (pleurisy, alveolitis) ```
94
Which systems are involved in SLE?
``` Joints (arthritis) Skin (photosensitive rash) Serosa (pericardium & pleura) Haematology (anaemia, thrombocytopenia) Kidneys (glomerulonephritis) Lungs (interstitial disease, alveolitis) CNS (cognitive dysfunction, seizures) ```
95
What is SLE?
Autoimmune connective tissue disease, immune system primarily attacks parts of the cell nucleus Affects tissues throughout body M:F 1: 9 Most often develops between 15 & 40yrs , although can develop any age More common in afrocarribean and Asian populations
96
What risk does pregnancy pose to someone with SLE?
Chances of miscarriage, premature birth, & inter-uterine death high if disease poorly controlled Ro or La positive mother - pass to baby and cause heart problems, baby can be born with malar rash which settles 3-6 months
97
What are treatment options for Seronegative spondyloarthropathies?
Early diagnosis & treatment, pain, stiffness & fusion controlled In women, AS often mild &hard to diagnose Exercise Medications: NSAIDs, Sulfasalazine, MTX, Biologics Posture management
98
What is Reiter's Syndrome?
Inflammatory Arthritis can affect spine, joints of spine & sacroiliac joints Characteristic inflammation of joints, urinary tract, eyes, & ulceration of skin &mouth Fever, weight loss, skin rash Often begins following inflammation of the intestinal or urinary tract. Sets off a disease process involving joints, eyes, urinary tract, & skin. Many people have periodic attacks that last from 3-6 months Some have repeated attacks, usually followed by symptom-free periods
99
What are treatments for psoriatic arthritis?
``` Skin care Light treatment (UVB or PUVA) Corrective cosmetics Medications: NSAIDs, DMARDs Biologics IL- 23 Exercise Splints Surgery (rarely) ```
100
What is Inflammatory Bowel Disease? And how does it link to arthritis?
2 separate diseases: inflammation of bowel & can cause arthritis Crohn's Disease: inflammation of colon or small intestines Ulcerative Colitis: ulcers & inflammation of lining of the colon Severity IBD influences severity of arthritis Other areas affected by IBD include spine, hips ankles, knees, liver, skin, eyes
101
Describe osteoarthrititis
Most common rheumatic disease Progressive loss of cartilage & reactive changes at margins of joint & in subchondral bone Begins at 40/50, increases with age; mainly aged 65 & older Affects weight-bearing joints eg knees, hips, & lumbosacral spine May be consequence of earlier damage or overuse of joint Obesity frequently associated, Genetic factors play a role in development, Dominant in females, incidence 10x greater than in men Final outcome is full-thickness loss of cartilage down to bone
102
What is treatment for osteoarthrititis?
Joint Replacement Surgery -Primarily of knee & hip, also available in hands, shoulders,& elbows Indications: pain at rest, instability, patients benefit from aggressive PT before & after surgery
103
What are treatment options for IBD?
Diet Exercise Medication: Corticosteroids, Immunosuppressants, NSAIDs, Sulfasalazine, Biologics (anti- TNF) Surgery
104
Who would be in the MDT of a rheumatology patient?
``` Consultants & trainees Rheumatology Nurse practitioner Biologics Nurse practitioner Occupational Therapist Physiotherapist ```
105
Why are cutaneous nerve innervation areas different to dermatomes?
Named nerve can carry several root values and innervate parts of several dermatomes
106
What is gout? and what causes it?
Crystal arthropathy, Hyperuricaemia Presents with a acute red swollen joint and soft tissue lesions (similar to septic arthritis) Multiple attacks lead to chronic damage Uric acid is breakdown product of purines, gout if not excreting it or producing too much of it Excreted by kidneys so gout in CKD, Taken in in diet - red meat Acute leukemia - high turnover of cells so high levels of uric acid

Block 4 AR (8 decks)

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