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Applied Pathophysiology > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

What does Arthritis mean?

A

“Arthro” - joint

“itis” - inflammation

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2
Q

What is arthritis? & how many types are there?

A

inflammation of one or more joints

There are over 100 types of arthritis including rheumatoid arthritis, osteoarthritis, and gout

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3
Q

What is Arthritis caused by?

A

several factors including physical (damage), bacterial, viral, and immune factors (either by: formation of immune complexes (antigen-antibody complexes) which precipitate in the joints, therefore causes damage or immune system can be activated against components of the joints & result in damage to joints

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4
Q

Rheumatoid Arthritis (RA) definition:

A

RA is a CHRONIC SYSTEMIC inflammatory disorder that mainly attacks joints often leading to JOINTS destruction, deformity, and loss of function.

implying: happens over months/years & are manifestations of disease (symptoms) all over body
- caused by continuous inflammation in the joints

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5
Q

What is the hallmark of RA?

A

The characteristic feature of RA is persistent inflammatory synovitis that usually involves the PERIPHERAL joints in a SYMMETRIC (ex: both shoulders) distribution.

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6
Q

Where does RA attack?

A
  • shoulders
  • elbows
  • wrists
  • knuckles & MIDDLE joints of fingers
  • knees
  • ankles
  • MIDDLE joints of toes
  • balls of feet
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7
Q

Where does RA usually affect?

A

• RA usually affects joints symmetrically (on both sides equally)

• RA may initially begin in a couple of joints

• RA most frequently attacks the wrists, hands, elbows, shoulders, knees, and ankles

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8
Q

What is the epidemiology of RA?

A

• The PREVALENCE of RA is about 1-2% of the worldwide population.
• WOMEN are affected about 2-3 TIMES more than men
• The prevalence increases with AGE
• Peak: 35-50 years of age (mid-age)
- as age increases, risk of disease increases

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9
Q

What is the etiology of RA?

A

• The cause of RA is unknown
• Both GENETIC and ENVIRONMENTAL factors are known
to be important in the etiology of RA

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10
Q

What are the environmental factors of RA?

A
  • climate (changes in climate - it increases symptoms)
  • ex: cold or humid weather isn’t good for them (increase temp/warm or drier temp is better for them)
  • cigarette (clearly important)
  • most patients have history of smoking or are currently
  • infectious factors
  • both bacterial & viral infections can lead to RA by activation of the immune system
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11
Q

What are the genetic factors of RA?

A

• Some class II MHC alleles such as HLA-DR4 (DRβ1*0401) are shown to be risk factors for RA

• FIRST DEGREE relatives of RA patients have a HIGHER risk of developing the disease

• MONOZYGOTIC twins MORE likely to be concordant for RA than dizygotic twins

• RA might be a manifestation of the response to an INFECTIOUS AGENT in a GENETICALLY SUSCEPTIBLE HOST

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12
Q

Infectious agents that are thought to be important in the pathogenesis of RA include:

A
  • Mycoplasma
  • Epstein-Barr virus (EBV)
  • Cytomegalovirus
  • Parvovirus
  • Rubella virus
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13
Q

What are the proposed mechanisms by which an infectious agent may cause RA?

A
  1. Persistent INFECTION of articular structures or retention of microbial PRODUCTS in synovial tissues leads to CHRONIC inflammatory response.
  2. MICROORGANISM or RESPONSE TO IT might induce IMMUNE RESPONSE to JOINT components by altering its integrity and revealing antigenic peptides.
  3. Infection might prime the host to cross-reactive determinants expressed within the joint as a result of “MOLECULAR MIMICRY”.
    - & then body starts making antibodies against these microorganisms/their products - these antibodies contribute to damage of their joints (check slide 11)
  4. PRODUCTS of infecting microorganisms such as SUPER- ANTIGENS may induce the disease.
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14
Q

What is the pathogenesis of RA?

A

RA is an AUTOIMMUNE disease TRIGGERED by exposure of a GENETICALLY susceptible host to an unknown ANTIGEN

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15
Q

Pathologic changes of joints in RA include:

A
  1. Increase in the NUMBER of SYNOVIAL LINING CELLS and
    microvascular injury
    - becomes thicker (normally is thin layer)
  2. Perivascular INFILTRATION with MONONUCLEAR cells (mainly CD4+ T cells)
    - type of lymphocytes
    - normally shouldn’t see lymphocytes or would be low #
  3. EDEMATOUS SYNOVIUM that protrudes into the joint cavity as villous
    - inflammation process
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16
Q

What do we notice from the Microscopic Section of Synovitis in RA?

A

normal:
- synovial membrane is v. thin –> 1-2 layers
- no lymphoid aggregates

RA:
- lymphoid aggregate (lots of black cells –> increase of lymphocytes)
- hyperplastic synovial membrane (v. thick)

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17
Q

What are the Major processes involved in pathogenesis of RA?

A

2 pathways:

  1. Susceptibility genes (HLA, other) or 2. Environmental factors (ex: infection, smoking)
    - Failure of tolerance, unregulated lymphocyte activation or Enzymatic modification of self-protein
    - T & B cell responses to self antigens
    - Fibroblasts, chondrocytes, synovial cells
    - Proliferation
    - Pannus formation; destruction of bone, cartilage; fibrosis; anklyosis
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18
Q

What are molecular mechanisms underlying synovitis in RA?

A

•step 1. EXPOSURE of GENETICALLY susceptible host to an UNKNOWN ANTIGEN triggers the immune reaction.

• step 2. CONTINUED autoimmune reaction, with ACTIVATION of CD4+ T-HELPER CELLS and local release of CYTOKINES ultimately destroys the joint.

• step 3. T-CELLS stimulate MACROPHAGES and synovial LINING CELLS in the joint to produce CYTOKINES (TNF & IL-1) causing synovial reaction.

•step 4. TNF and IL-1 stimulate SYNOVIAL CELLS to PROLIFERATE and PRODUCE inflammatory factors (eg PROSTAGLANDINS) and MATRIX PROTEINASES that contribute to cartilage destruction.

•step 5. Activated T-CELLS and synovial FIBROBLASTS also produce factors that ACTIVATE OSTEOCLASTS and promote bone destruction.

• step 6. Formation of PANNUS produces sustained irreversible cartilage destruction and erosion of sub- chondrial bone.

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19
Q

What is the structure of normal & rheumatoid joint?

A
  • v. thick synovial mem. b/c of process of inflammation & increase of lymphocytes
  • damage to bone
  • damage to cartilage (edges of rough)
  • increase in lymphocytes (increase in synovial membrane)
  • increase in synovial fluid
  • antibody-antigen binding which form complexes & will precipitate in tissue & lead to gradual damage of tissue
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20
Q

Describe pannus formation

A

Pannus is a mass of synovial stroma consisting of INFLAMMATORY CELLS, GRANULATION TISSUE, and FIBROCYTES (tries to recover tissue but won’t help with real recovery) which grows over the articular cartilage and causes its erosion resulting in BONY ANKYLOSIS (patient starts losing joint function)
- when bones touching/bones fuse together not as flexible as cartilage so can’t move joint anymore
- irreversible

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21
Q

Describe Rheumatoid Arthritis of hands and wrist

A

*normally MIDDLE joints of fingers & toes

  • in wrist (severe) can lead to bone loss & lots of alignment in the bones, therefore patient can’t use wrist
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22
Q

Signs and symptoms of RA

A

RA is a SYSTEMIC disease with a variety of ARTICULAR and EXTRA-ARTICULAR manifestations.

(non-specific & specific symptoms/manifestations)

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23
Q

A) Non-specific symptoms:

A

Early symptoms that may last weeks to months:
• fatigue
• anorexia (loss of appetite)
• generalized weakness
• vague musculoskeletal symptoms • mild fever

24
Q

B) Specific manifestations:

A

Later symptoms that are progressive:
• symmetric polyarthritis (more than 1 joint is involved)
• pain (2 or more joints)
• morning stiffness (difficulty moving (using their joints) after rest)
• synovial inflammation (swelling (in area of joint), tenderness (painful & sensitive to it),
limitation of motion)
• warmth (especially in large joints e.g. knee)

25
Q

Describe Rheumatoid Arthritis of hand

A

Characteristic features include DIFFUSE OSTEOPENIA (area where loss of bone has begun), marked LOSS OF JOINT SPACES of carpal, metacarpal, phalangeal, and interphalangeal joints, PERIARTICULAR BONY EROSIONS, and ULNAR DRIFT of the FINGERS

normal: bones look wide b/c increase density

RA: density is lower, space b/t bones is lost indicates loss of cartilage

RA in more adv. stages: bone erosion & bone displacement (bone alignment is lost –> can’t use joint anymore & are more susceptible to breaking their bone if even lightly hit)

26
Q

What are Extra-articular symptoms of RA?

A
  • Cutaneous manifestations (most common)
    – subcutaneous nodules, palmar erythema (red palm), vasculitis (damage to surrounding soft tissue)
  • Ocular: eye inflammation (episcleritis, scleritis), retinal nodules, dry eyes
    – can lead to blindness
  • Pulmonary: chronic cough, COPD
  • Cardiac: pericarditis and myocarditis
  • Neuromuscular: carpal TUNEL syndrome (get painful in that area), peripheral neuropathy
  • Hematologic: lymphadenopathy, anemia
  • Osteoporosis
  • secondary to RA
    -aggravated by glucocorticoid therapy (group of drugs that reduce act. of immune system but side effect is osteoporosis (patients are already prone to it so be careful putting them on it)
  • Other
    Felty’s syndrome (they have chronic RA, splenomegaly (has enlarge spleen), neutropenia (reduced levels of neutrophiles), +/- thrombocytopenia (reduced platelet levels) and anemia (reduced RBC levels))
  • & changes in blood cells
  • Extra-articular symptoms are usually observed in patients with HIGH titers of RHEUMATOID FACTOR.
    – indicates a severe systemic form typ.
27
Q

What are diagnostic tests for RA?

A

*NONE ARE SPECIFIC for diagnose of RA; only helpful alongside the clinical symptoms & findings in a patient

Blood tests:
1. RF
2. CBC
3. ESR
4. CRP
5. ANA

Synovial Fluid Analysis

Radiologic Evaluation

28
Q

Describe the blood test: Rheumatoid Factor (RF)

A

• RF is an IgM auto-antibody reactive with the Fc region of the patient’s own IgG
• RF is detectable in ∼70% of PATIENTS with RA
Fab Fc
- therefore, test is (+) but doesn’t confirm, if (-) it doesn’t mean you don’t have it
• The presence of RF is NOT SPECIFIC for RA so CAN NOT be used for DIAGNOSIS or screening of RA
• RF is present in 5% of HEALTHY people (e.g. elderly)
- may have RF (-) test
• RF may be POSITIVE in OTHER diseases (e.g. tuberculosis, leprosy, hepatitis B, systemic lupus erythematosus).

29
Q

When RF test is used?

A
  • RF test is used to CONFIRM the DIAGNOSIS in individuals with a suggestive CLINICAL presentation.
  • The presence of RF in HIGH titer designates patients at RISK for SEVERE systemic disease.

commonly used for RA but isn’t a specific test

30
Q

Describe the blood test: Cell Blood Count (CBC)

A

simple & cheap; used often

• Normochromic (normal colour) normocytic (normal size) anemia is usually present in active RA
- only diff. is # of RBC’s is lower

• White blood cell (WBC) count is usually normal
- unless severe cases

• Eosinophilia reflects severe systemic disease

31
Q

Describe the blood test: Erythrocyte Sedimentation Rate (ESR)

A

• INCREASED in nearly all patients with RA
- b/c they have inflammation
- shows if there is inflammation in the body; but doesn’t tell you where or what is the cause of inflammation (gives idea if their is inflammation or not)
- RBC faster precipitates of RBCs, therefore ESR increase

32
Q

Describe the blood test: C-Reactive Protein (CRP) test

A

• CRP is an acute phase protein of hepatic (liver) origin

• It is typically increased during acute inflammation
- not-specific to RA but says there’s inflammation

33
Q

Describe the blood test: Anti-nuclear antibody (ANA) test

A

• An antibody that targets content of cell nucleus

• ANA-positive test is indicator of autoimmune disease

• Many people with RA have positive ANA test

• It is NOT a specific test for RA

34
Q

Diagnostic Tests: Synovial Fluid Analysis

A

Confirms the presence of inflammatory arthritis:
• synovial fluid is usually turbid - b/c of increase inflammation & increase inflammation cells
• protein concentration is increased
• glucose concentration is normal or decreased
• WBC number is increased (mainly PMN)
• complements (C3 and C4) are decreased
- b/c involved in formation of antigen-antibody complex

NO SPECIFIC TEST is available for diagnosis of RA

35
Q

Diagnostic Tests: Radiologic Evaluation

A

• Used to support diagnosis and to estimate cartilage damage and bone erosions

• Not useful at early stages of RA

• None of the radiologic findings is diagnostic of RA

Radiologic findings in RA:
1. juxta-articular osteopenia - happens in area of bone adjacent to joint
2. loss of articular cartilage - not regular space b/t; & bones are touching
3. bone erosions - pieces of bones disappearing; damaged areas of bone

36
Q

What is the Criteria for classification & diagnosis of RA?

A

The diagnosis of RA can be made when following clinical features are ALL present:
● inflammatory arthritis involving 3 or more joints
● positive Rheumatoid Factor (RF)
● elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)
● other diseases with similar clinical features have been excluded
● duration of symptoms is more than six weeks

37
Q

What is the prognosis of RA?

A

The presence of one or more of the following implies more aggressive disease:
• inflammation in several joints
• markedly elevated ESR rate
• high titers of RF
• radiologic evidence of bone erosions
• rheumatoid nodules
• HLA-DR4 (DRβ1*0401)
• functional disability

38
Q

What is the treatment goal for RA?

A

• There is NO CURE for RA

• The main goal is to LIMIT synovial INFLAMMATION to SLOW
DOWN DESTRUCTION of cartilages & bones

• Remission of symptoms is more likely when treatment begins EARLY with disease-modifying anti-rheumatic drugs (DMARDs)

• Type of recommended medication depends on the SEVERITY of symptoms and DURATION of RA

39
Q

What is the Non-steroidal anti-inflammatory drugs (NSAIDs) treatment goal for RA?

A
  • relieve pain and reduce inflammation
  • over-the-counter NSAIDs: ibuprofen (Advil), naproxen sodium (Aleve)
  • prescribed (stronger) NSAIDs
40
Q

What is the Steroids for RA?

A
  • reduce inflammation, pain, and slow joint damage used to
  • relieve acute symptoms, with the goal of gradually tapering off the medication (using during acute stage)
  • example: corticosteroids (prednisone)
41
Q

What is the Disease-modifying anti-rheumatic drugs (DMARDs) for RA?

A
  • slow progression of RA and save joints from permanent
    damage
  • example: methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo)
42
Q

What is the Cytokine antagonists for RA?

A
  • biologic response modifiers
  • target parts of the immune system that trigger process of inflammation and cause joint damage
  • e.g. IL-1 receptor antagonist: anakinra (Kineret)

(newer category of drugs)
- cytokines play a role in the destruction of the joint
- doesn’t have major side-effects

43
Q

What is the treatment goal for RA in terms of surgery?

A

Synovectomy, Tendon repair, Joint fusion, Total joint replacement

(in later stages when it is irreversible, therefore drugs wouldn’t be helpful)

44
Q

Synovectomy

A

Surgery to remove inflamed lining of joint
(synovium) e.g. knees, elbows, wrists, fingers and hips.
- to remove pain
- usually for larger joints, but it can be done for smaller ones

45
Q

Tendon repair

A

Surgery to repair the tendons around the joint. Inflammation and joint damage may cause tendons around joint to loosen or rupture.
- ruptured/damaged

46
Q

Joint fusion

A

Surgically fusing the joint to stabilize/realign it for pain relief when joint replacement is not an option.
- reduces pressure

47
Q

Total joint replacement

A

Surgery to remove damaged part of joint and insert a prosthesis made of metal and plastic.

48
Q

What is Juvenile Rheumatoid Arthritis (JRA)?

A

JRA is characterized by immune-mediated joint inflammation observed at early ages (<16 years)

49
Q

What are the differences between JRA and RA?

A
  • JRA is usually observed in children
  • oligoarthritis is more common in JRA
  • systemic onset is more frequent in JRA
  • large joints are affected more than small joints
  • usually 1 & it’s usually large
  • rheumatoid nodules and RF are usually absent
  • therefore most are RF (-)
  • anti-nuclear antibodies are usually present
50
Q

RA is an ______ disease triggered by exposure of a ______ susceptible host to an _____ ____.

A

autoimmune

genetically

unknown antigen

51
Q

RA is a _____ disease with a variety of articular and extra-articular manifestations.

A

systemic

52
Q

In RA, ______ synovitis caused by continuous _____ response leads to cartilage ______.

A

reactive

immune

destruction

53
Q

The major pathologic changes in RA synovitis include increased _______ of synovial ____ ___, infiltration of ________ cells, and _______ synovium.

A

number

lining cells

mononuclear

edematous

54
Q

_____ of RA is based on the _____ symptoms, ___ tests and _____ evaluation (other inflammatory disease should be excluded).

A

diagnosis

clinical

lab

radiologic

55
Q

There is __ ___ for RA, the main ______ ___ is to ____ destruction of the cartilages and bones by ___- ______ drugs.

A

no cure

treatment goal

limit

anti-inflammatory

Applied Pathophysiology (34 decks)

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