Rheumatic Disorders (Pathophysiology) - Block 1 Flashcards
1
Q
What is rheumatoid arthritis?
A
Chronic systemic inflammatory autoimmune disease characterized by:
1. Synovial inflammation and hyperplasia
2. Auoantibody production
3. Cartilage and bone destruction
4. Systemic involvement
2
Q
What is the cause of RA?
A
Genetic susceptibility (HLA-DRB1, PTPN22, PADI4) + environmental trigger (smoking, silica, air pollution, estrogen) + Infectious agents (EBV, CMV, E coli, mycoplasmas, P. gingivalis) -> loss of tolerance -> RA
3
Q
What are the sx of RA?
A
- Joint
- Chronic, erosive polyarthritis: Symmetrical, bilateral inflammation in joints
- Metabolic manifestations: fatigue, anorexia, weight loss, weakness, low grade fever
4
Q
What are the joint sx of RA?
A
- Join swelling
- Stiffness (morning stiffness, inactivity)
- Warmth
- Tenderness
- Pain
5
Q
What is polyarthritis?
A
arthritis affecting 4 or more joints
6
Q
What is polyarthralgia?
A
Pain in more than 4 joints
7
Q
What is joint swelling caused by?
A
Fluid accumulation in joint capsule
8
Q
What are the small joints in the hands and feet?
A
Proximal interphalangeal (PIP)
Metacarpophalangeal (MCP)
Distal interphalangeal (DIP)
Metatarsalphalangeal joints (feet)
9
Q
What are the types of RA joint deformities?
A
- Ulnar deviation deformity of the fingers
- Mallet finger deformity of the distal interphalangeal joint
- Swan-neck deformity of the proximal interphalangeal joint
- Boutonniere deformity due to extension of distal interphalangeal joint
10
Q
What are rheumatoid nodules?
A
- Most common cutaneous manifestation of RA
- Found on pressure points such as forearm and joints of the hands and toes
- Asymptomatic but may ulcerate that must be surgically removed
11
Q
What is the hallmark of RA?
A
Bone erosion
12
Q
What are the systemic sx of RA?
A
Pulmonary and cardiac disease
13
Q
Describe the progression of RA?
A
14
Q
What are cryptic epitopes?
A
When molecule is denatured or altered, Hidden epitopes are exposed and recognized by the immune systme generating autoantibodies
15
Q
What is RF?
A
IgM against IgG
When IgG antibodies bind, they undergo a conformational change than exposes cryptic epitopes that are recognized by RF
16
Q
What is used to diagnose RA?
A
RF and anticitrullinated protein antibodies (ACPA)
17
Q
What are Citrullinated peptides (CCPs)?
A
Foreign proteins that mount an immune response
18
Q
How does autoantibodies contribute to RA?
A
- Forming immune complexes by binding to autoantigens or soluble antigens
- Activation of classical complement
19
Q
What cells produce autoantibodies?
A
Plasma cells in joints
20
Q
Where are autoantibodies found?
A
Serum and synovial fluid
21
Q
What are the prominent autoantibodies associated with RA?
A
- RF (IgM Ab against IgG Fc portion (cryptic epitope))
- Anti-Citrullinated Protein Autoantibodies (ACPA)
22
Q
Describe the structure of the synovial joint?
A
- Found between bones that move against each other
- Cartilagecovers the end of the articulating bones
- Surrounded by a joint capsule
- Dense connective tissue that attached to bones forming a sleeve around the joint (Outer=fibrous, Inner=synovium)
- Synovial membrane produces the lubricating fluid of the joint-synovial fluid
23
Q
How is the synovial joint affected by RA?
A
Formation of a pannus leads to erotion of cartilae and bone destroying surrounding tissue
24
Q
What is a pannus?
A
Synoviocytes undergo hyperplasia and swell, thickening the synovial tissue
25
Describe the immunological components of RA?
1. **APCs** present self-antigen to helper T cells
2. **T cells** secrete inflammatory cytokines and help B cells and Macrophages become activated
3. **B cells** are activated and secrete inflammatory cytokines and differentiate into plasma cells.
4. **Plasma cells** secrete autoantibodies that form immune complexes.
5. **Activates a Type III hypersensitivity response:** Immune complex mediated hypersensitivity
26
Decribe the macrophage and neutrophil action in RA?
Secrete inflammatory cytokines that lead to:
1. Increased vascular permeability (swelling): TNF-a and IL-1
2. Warmth: IL-1, TNF-a and IL-6; IL-6 initiates the acute phase response
3. Macrophages secrete matrix metalloproteases that degrade collagen (pannus expansion and invasion of the joint)
4. Macrophages secrete IL-1 and RANKL, which activates chondrocytes and osteoclasts to degrade of the cartilage and bone of the joint
26
Chronic inflammation leads to ___ and ___?
Scar tissue and bony fusion (ankylosis)
27
Increase pannus formation, leads to ____ and ____ erosion leading to _____?
Joint and cartilage; reduced joint space
28
What is the difference between remission and relapse?
**Remission:** Period of time when symptoms and inflammation is low or non existent
**Relapse:** After remission when symptoms return
29
What is a flare?
Periods of increased disease activity and inflammation
30
Lab tests used to identify acute phase reactants or inflammation?
CRP and ESR
31
According to 2010 ACR/EULAR RA, what is the classification of RA?
Score ≥ 6
32
What is Lupus?
Systemic, chronic, inflammatory autoimmune disease with heterogeneous manifestations
33
What are the causes of lupus?
**Genetic Factors: ** >33 SNPs identified, HLA-DR
**Environmental Factors:** Epigenetic factors leading to DNA hypomethylation, Smoking, UV light exposure, Viral infections (EBV)
**Hormonal Facotors:** Estrogen, pregnancy
34
Normal complement levels?
C3 80 to 160 mg/dL
C4 16 to 48 mg/dL
35
SLE complement levels?
C3 <60 mg/dL
C4 <15 mg/dL
36
What are the CNS sx of SLE?
1. Acute vasculitis impedes blood flow causing strokes or hemorrhage
1. Anti-neuronal antibodies damage neurons
1. Anti-phospholipids damage blood vessels causing clots
1. Seizures, psychosis, delirium
1. Depression and decreased cognitive functioning
37
What are the hematological sx of SLE?
1. Hemolytic anemia
2. Leukopenia, lymphopenia, thrombocytopenia
38
What are the renal sx of SLE?
1. Persistant protein in the urine
2. Nephritis
39
Diagnostic criteria for SLE?
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood (anemia, leukopenia, thrombocytopenia)
Renal (protein)
ANA
Immunologic (DS DNA)
Neurologic (psych, seizures)
Malar rash
Discoid rash
40
According to 2019 American College of Rheumatology what is the classification of SLE?
Score ≥10
41
How is lupus disease activity measured?
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
42
What is considered a lupus flare?
Flare is an increase in SLEDAI of more than 3 and severe flare is increase >12
Remission is SLEDAI of 0
43
What is Spondyloarthropathies?
1. Affects the axial skeleton and peripheral joints
2. Inflammation begins at sites where tendons and ligaments insert into bone
3. Seronegative (lack RH)
44
What is psoriatic arthritis?
Heterogeneous seronegative inflammatory arthritis associated with skin psoriasis
45
What type of arthritis affects women and men equally?
Psoriatic Arthritis (PsA)
46
What are the clincial patterns of PsA?
1. Symmetrical polyarthritis (5-20%)
2. **Asymmetrical oligoarthritis** (70-80%)
3. Psoriatic Spondylitis (axial disease) (5-20%)
4. Predominant Distal Inter-phalangeal (DIP) Involvement (10%)
5. Severe Destructive (rare)
47
What are common signs of PsA?
1. Psoriatic nail dystrophy
* Nail pitting
* Oncholysis
* Hyperkeratosis
2. Dactylitis
3. Enthesitis
4. Arthritis mutilans
48
What is onycholysis?
Nail bed separation leading to infection
49
What is hyperkeratosis?
Debris accumulates under the nail causing the nail to be raised off the nail bed
50
What is dactylitis?
Swollen and painful digits, Inflammation of the entire digit (sausage digits)
* unable to make a fist
51
What is enthesitis?
Inflammation at the tendon, ligament or joint capsule insertion into the bone
52
What is arthritis mutilands?
Osteolysis-resorption of the bone in phalanges and dissolution of the joint
* Telescoping of the skin
53
What is periostitis?
Thickening of the periosteum
54
What is ankylosis?
Boses fuse together
55
What is osteolysis?
Destruction of the bone
56
Describe the classification of PsA
Score ≥3
56
What cytokines are produced by the skin?
TH22, TH17 and TH1 cells produce IL-22, IL-17, TNF-a and IFN-g
57
What cytokines act on the synovial joints?
IL-23, TNF-a and IL-17 to produce RANKL -> activation of osteoclasts -> bone erosion
58
What is the function of IL23?
Polarizing cytokine to induce the differentiation of Helper T cells into inflammatory TH17 cells
* TH17 cells secrete IL-17
59
What is the function of IL12?
Polarizing cytokine for TH1 cells
* TH1 cells secrete TNF-a
60
How does PsA affect the enthesis?
1. Mechanical stress can trigger activation of innate immune cells (macrophages and DCs) due to release of DAMPS.
2. Mechanical stress can trigger activation of innate immune cells (macrophages and DCs) due to release of DAMPS.
3. IL-17 likely acts as an amplifier of enthesitis, inducing several other cytokines by resident mesenchymal cells and can lead to bone erosion
4. IL-22 causes pathologic bone formation.
61
What is gout?
Chronic progressive inflammatory arthritis associated with the build up of urate in the blood (hyperuricemia)
Uric acid crystallizes into monosodium urate (MSU) at a concentration greater than 6.8mg/dL and deposits in the joints causing inflammation
62
What levels is considered hyperuricemia?
>6.8 mg/dL
63
What is the most common form of gout?
Inflammatory arthritis
64
What are the sources of urate
65
How are purine converted into urate?
66
What are the sx of gout?
1. Rapid onset, erythema, swelling -> monoarticular arthritis
2. Gout attacks
3. Podagra (first metatarsophalangeal)
4. Tophi (crystal stone deposits DIP and PIP under the skin, small joints, elbows, and ears)
67
What would a gout x-ray look like?
1. Punched out erosion
2. Overhanging edges
3. Joint space is maintained
68
What would lab for gout look like?
1. Measure serum uric acid levels
2. Aspirate synovial fluid from the joint and using a microscope with a polarizing filter and red compensator filter
69
Describe the stages of gout?
1. Asymptomatic hyperuricemia: elevated serum urate with no clinical manifestations of gout
2. Acute flares: acute inflammation in joint caused by urate crystals
3. Intercritical gout: intervals between acute gout flares
4. Advanced gout: long-term gout complications, trophi
70
What can cause gout flares?
1. Diuretics
2. Alcohol
3. Surgery
71
According to the 2015 ACR/EULAR Diagnostic Criteria, what is the classification for gout?
Score ≥8
72
How does the body initiatet acute inflammation by MSU?
1. Resident macrophages engulf MSU crystals, become activated or the crystals can be membranolytic
1. Macrophages secrete IL-1b, increases vascular permeability and allows for the influx of neutrophils to phagocytize MSU crystals.
1. IL-1b induces vascular activation, fever, and IL-6 production
1. Complement proteins can also bind to MSU crystals and cause classical complement activation.
1. Anaphylatoxins are released and act as chemoattractants to bring in neutrophils.
1. Intense infiltration of neutrophils into both synovial membrane and fluid is the hall-mark of acute gout
1. Sterile inflammation
