Rheumatoid arthritis - causes, symptoms, diagnosis, treatment, pathology
Summary
TLDRThis video provides an in-depth explanation of rheumatoid arthritis, a chronic autoimmune disorder that primarily affects the joints. It covers the disease's mechanism, where the immune system mistakenly attacks joint tissues, leading to inflammation, cartilage damage, and bone erosion. The script explores genetic and environmental triggers, the role of immune cells, and how antibodies contribute to joint destruction. It also highlights common symptoms, joint deformities, extra-articular complications, and diagnostic methods. Finally, it outlines treatment options, including disease-modifying drugs, biologics, and anti-inflammatory medications for managing flares.
Takeaways
- 🦠 Rheumatoid arthritis is a chronic, autoimmune inflammatory disorder that mainly affects joints but can also involve other organs like the skin, lungs, and heart.
- 🦴 Healthy joints are protected by articular cartilage and synovial fluid, which help bones glide smoothly and reduce friction.
- 🧬 Rheumatoid arthritis is triggered by a genetic predisposition and environmental factors, leading to an autoimmune response that attacks the body's own tissues.
- 🧪 The immune response involves proteins like citrullinated vimentin and collagen, causing the immune system to target these as foreign antigens.
- 🔬 Activated immune cells produce cytokines that cause inflammation in the joints, leading to the formation of a pannus that damages cartilage and bone.
- 🧫 Antibodies like rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) form immune complexes that contribute to joint inflammation.
- 💉 The condition also causes extra-articular symptoms such as fever, muscle weakness, rheumatoid nodules, and increased risk of heart disease and lung problems.
- 🖐️ Rheumatoid arthritis typically affects multiple joints symmetrically, particularly the small joints in the hands and feet, leading to deformities over time.
- ⚕️ Diagnosis is based on blood tests for antibodies (RF and CCP) and imaging that shows joint damage and bone erosion.
- 💊 Treatment includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate and biologics, along with anti-inflammatory medications for acute flares.
Q & A
What is rheumatoid arthritis?
-Rheumatoid arthritis is a chronic, inflammatory autoimmune disorder that primarily affects the joints but can also involve other organs such as the skin and lungs.
How does rheumatoid arthritis affect a healthy joint?
-In a healthy joint, two bones are covered with articular cartilage, which acts as a cushion for smooth movement. Rheumatoid arthritis causes inflammation of the synovial membrane, leading to joint damage, cartilage breakdown, and bone erosion.
What is the role of the synovial membrane in joints?
-The synovial membrane lines the joint capsule, produces synovial fluid to lubricate the joint, and helps remove debris from the joint space.
What triggers rheumatoid arthritis?
-Rheumatoid arthritis is typically triggered by a combination of genetic susceptibility, such as the presence of HLA-DR1 and HLA-DR4 genes, and environmental factors like smoking or bacterial infections, which can cause modifications to proteins in the body.
What is citrullination and how is it related to rheumatoid arthritis?
-Citrullination is a process where the amino acid arginine is converted into citrulline in certain proteins. In rheumatoid arthritis, this modification confuses immune cells, leading to an autoimmune response against these proteins.
How does the immune system contribute to joint damage in rheumatoid arthritis?
-Immune cells like T-helper cells and antibodies enter the joint, releasing cytokines that recruit inflammatory cells. This leads to the formation of a pannus, which is a thickened synovial membrane that damages cartilage and bone over time.
What is the role of rheumatoid factor (RF) and anti-CCP antibodies in rheumatoid arthritis?
-Rheumatoid factor (RF) is an IgM antibody that targets altered IgG antibodies, and anti-CCP antibodies target citrullinated proteins. Both antibodies form immune complexes in the joint, contributing to inflammation and joint damage.
What are some common deformities seen in rheumatoid arthritis?
-Common deformities include ulnar deviation of the fingers, boutonniere deformity, and swan neck deformity, which affect the metacarpophalangeal and interphalangeal joints.
How is rheumatoid arthritis diagnosed?
-Rheumatoid arthritis is diagnosed using blood tests that detect rheumatoid factor and anti-citrullinated peptide antibodies. Imaging studies like X-rays show joint damage, soft tissue swelling, and bone erosions.
What treatments are available for rheumatoid arthritis?
-Long-term treatment includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate, biologics such as abatacept and adalimumab, and medications that block inflammatory cytokines. Acute flares are treated with NSAIDs and short-term glucocorticoids.
Outlines
🧠 Understanding Rheumatoid Arthritis and Joint Function
This paragraph introduces rheumatoid arthritis as a chronic inflammatory disorder primarily affecting joints but also potentially involving other organ systems like the skin and lungs. It explains the structure of a healthy joint, focusing on the role of articular cartilage in providing a lubricated surface for bones to glide against. The synovial joint, particularly in areas like the knee, is highlighted with an emphasis on the fibrous joint capsule, synovial membrane, and synovial fluid, which help in joint lubrication. Rheumatoid arthritis is described as an autoimmune process triggered by genetic and environmental factors, such as cigarette smoke or bacterial infections, leading to changes in proteins like type II collagen and vimentin.
🔬 Autoimmune Response and Inflammatory Cascade
This paragraph dives deeper into the autoimmune mechanism of rheumatoid arthritis. It explains how genetic susceptibility (such as having the HLA-DR1 and HLA-DR4 genes) may cause the immune system to mistakenly recognize altered proteins as foreign. It describes the activation of T-helper cells, B-cells, and the production of autoantibodies like rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (CCP). The paragraph further explains the inflammatory cascade, where cytokines like TNF-α, IL-1, and IL-6 drive synovial cell proliferation, leading to the formation of pannus (inflamed, scar tissue in the joints) and the breakdown of cartilage and bone. The role of T-cells in activating osteoclasts to break down bone is also highlighted.
⚖️ Joint Damage, Deformities, and Extra-Articular Effects
This section discusses the extensive damage caused by rheumatoid arthritis to joints and other organs. Over time, the inflammatory process leads to joint deformities, such as ulnar deviation and boutonniere and swan neck deformities in the fingers. Rheumatoid arthritis also affects large joints, causing swelling, pain, and stiffness, especially during flares. The paragraph further outlines extra-articular manifestations, including systemic symptoms like fever and muscle weakness, as well as organ-specific issues such as rheumatoid nodules, vasculitis, lung fibrosis, pleural effusion, anemia, and the serious condition known as Felty syndrome, which can lead to life-threatening infections.
🩺 Diagnosing and Managing Rheumatoid Arthritis
The final paragraph explains the diagnosis and management of rheumatoid arthritis. Blood tests are crucial for confirming the disease, particularly looking for rheumatoid factor and anti-citrullinated peptide antibodies. Imaging studies like X-rays reveal typical joint damage signs, such as soft tissue swelling and bony erosions. For long-term treatment, disease-modifying antirheumatic drugs (DMARDs), like methotrexate, hydroxychloroquine, and sulfasalazine, are used to suppress inflammation. Biologic drugs, such as abatacept and rituximab, target T-cells and B-cells, while others like adalimumab and infliximab inhibit specific cytokines. Treatment of acute flares involves anti-inflammatory medications and glucocorticoids. The summary recaps that rheumatoid arthritis is an autoimmune systemic disorder with joint destruction and extra-articular involvement.
Mindmap
Keywords
💡Rheumatoid Arthritis
💡Synovial Joint
💡Cytokines
💡Pannus
💡Autoimmune Disease
💡Citrullination
💡T-helper Cells
💡Rheumatoid Factor (RF)
💡Anti-cyclic Citrullinated Peptide (CCP) Antibodies
💡Biologics
Highlights
Osmosis offers personalized study plans with exclusive videos, practice questions, and flashcards, making learning medicine easier.
Rheumatoid arthritis is a chronic inflammatory disorder that primarily affects the joints but can involve other organ systems like the skin and lungs.
Healthy joints have two bones covered with articular cartilage, which acts as a cushion for smooth movement.
A synovial joint is lined with a synovial membrane that produces synovial fluid, lubricating the joint and removing debris.
Rheumatoid arthritis is an autoimmune disease, often triggered by genetic and environmental factors, such as cigarette smoke or certain pathogens.
Citrullination, a process where arginine is converted to citrulline, plays a role in rheumatoid arthritis, confusing immune cells into attacking self-proteins.
T-helper cells stimulate B-cells to produce autoantibodies, which attack the joints and trigger chronic inflammation.
The pannus, a thickened synovial membrane formed by immune cells and scar tissue, damages cartilage and erodes bone.
In rheumatoid arthritis, macrophages and T-cells release inflammatory cytokines, worsening joint destruction.
Antibodies like rheumatoid factor and anti-CCP antibodies bind to their targets in the joint, triggering immune complexes and further inflammation.
Chronic inflammation from rheumatoid arthritis affects other organs, causing fever, muscle wasting, vasculitis, and rheumatoid nodules.
Rheumatoid arthritis can lead to joint deformities, such as ulnar deviation, boutonniere deformity, and swan neck deformity.
The disease also causes extra-articular symptoms like anemia, interstitial lung disease, and cardiovascular complications.
Treatment for rheumatoid arthritis includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate and biologics targeting specific immune pathways.
During acute flares, anti-inflammatory medications like NSAIDs and glucocorticoids are used to reduce inflammation and manage symptoms.
Transcripts
Learning medicine is hard work!
Osmosis makes it easy.
It takes your lectures and notes to create a personalized study plan with exclusive videos,
practice questions and flashcards, and so much more.
Try it free today!
In rheumatoid arthritis, “arthr-“ refers to joints, “-itis” means inflammation,
and “rheumatoid” comes from rheumatism, which more broadly refers to a musculoskeletal
illness.
So, rheumatoid arthritis is a chronic, inflammatory disorder that mostly affects the joints, but
can also involve other organ systems like the skin and lungs as well.
Alright, so a healthy joint typically has two bones covered with articular cartilage
at the ends.
Articular cartilage is a type of connective tissue that acts like a protective cushion
- a lubricated surface for bones to smoothly glide against.
One type of joint, like the knee joint is called a synovial joint.
A synovial joint connects two bones with a fibrous joint capsule that is continuous with
the periosteum or outer layer of both bones.
The fibrous capsule is lined with a synovial membrane that has cells that produce synovial
fluid and remove debris.
The synovial fluid is normally a viscous fluid like the jelly-like part of a chicken egg
and it helps lubricate the joint.
To help serve these synovial cells, the synovial membrane also has blood vessels and lymphatics
running through it.
Together, the synovial membrane and the articular cartilage form the inner lining of the joint
space.
Rheumatoid arthritis is an autoimmune process that is typically triggered by an interaction
between a genetic factor and the environment.
For example, a person with a certain gene for an immune protein like human leukocyte
antigen, or HLA- DR1 and HLA–DR4, might develop rheumatoid arthritis after getting
exposed to something in the environment like cigarette smoke or a specific pathogen like
a bacteria that lives in the intestines.
These environmental factors can cause modification of our own antigens, such as IgG antibodies
or other proteins like type II collagen or vimentin.
Τype II collagen and vimentin can get modified through a process called citrullination.
That’s when the amino acid arginine found in these proteins is converted into another
amino acid, citrulline.
Meanwhile, due to the susceptibility genes HLA- DR1 and HLA–DR4, immune cells sometimes
are not “clever” enough, so they get confused by these changes and they no longer recognize
these proteins as self-antigens.
The antigens get picked up by antigen- presenting cells, and get carried to the lymph nodes
to activate CD4+ T-helper cells.
T-helper cells stimulate the nearby B- cells to start proliferating and differentiate into
plasma cells, which produce specific autoantibodies against these self- antigens.
In rheumatoid arthritis, T- helper cells and antibodies enter the circulation and reach
the joints.
Once there, T- cells secrete cytokines like interferon- γ and interleukin- 17, to recruit
more inflammatory cells like macrophages, into the joint space.
Macrophages will also produce inflammatory cytokines, like tumor necrosis factor, or
TNF- α, interleukin- 1 and interleukin- 6, which together with the T-cell’s cytokines,
stimulate synovial cells to proliferate.
The increase in synovial cells and immune cells creates a pannus, which is a thick,
swollen synovial membrane with granulation or scar tissue, made up of fibroblasts, myofibroblasts
and inflammatory cells.
Over time, the pannus can damage cartilage and other soft tissues and also erode bone.
Activated synovial cells also secrete proteases which break down the proteins in the articular
cartilage.
Without the protective cartilage, the underlying bones are exposed and can directly rub against
one another.
In addition, inflammatory cytokines increase a protein on the surface of T- cells, known
as RANKL or receptor activator of nuclear factor kappa-B ligand.
RANKL allows the T-cells to bind RANK, a protein on the surface of osteoclasts, to get them
to start breaking down bone.
Meanwhile, antibodies also enter the joint space.
One antibody is called rheumatoid factor, or RF, which is an IgM antibody that targets
the constant Fc domain of altered IgG antibodies.
Another antibody is anti-cyclic citrullinated peptide antibody, or CCP, which targets citrullinated
proteins.
When these antibodies bind to their targets, they form immune complexes which accumulate
in the synovial fluid.
There, they activate the complement system, a family of 9 small proteins that work in
an enzymatic cascade to promote joint inflammation and injury.
Finally the chronic inflammation causes angiogenesis, or the formation of new blood vessels around
the joint, which allows even more inflammatory cells to arrive.
As the disease progresses, multiple joints on both sides of the body get inflamed and
gradually destroyed.
But these inflammatory cytokines don’t just stay within the tight joint space.
Instead, they escape through the bloodstream and reach multiple organ systems causing extra-articular
problems, meaning problems beyond the joint space.
For example, interleukin-1 or -6 travel to the brain, where they act as pyrogens, inducing
fever.
In skeletal muscle, they promote protein breakdown and in the skin, as well as in many visceral
organs, they lead to the formation of rheumatoid nodules, which are round- shaped collections
of macrophages and lymphocytes with a central area of necrosis, or tissue death.
Blood vessels can also be affected.
Their walls get inflamed, resulting in various forms of vasculitis and make them prone to
developing atheromatous or fibrofatty plaques.
In response to inflammatory cytokines, the liver also starts producing high amounts of
hepcidin, a protein that decreases serum iron levels by inhibiting its absorption by the
gut and trapping it into macrophages or liver cells.
Meanwhile, within the lung interstitium, fibroblasts get activated and proliferate, causing fibrotic
or scar tissue that makes it harder for the alveolar gas exchange, while also the pleural
cavities surrounding the lungs can get inflamed, filling up with fluid, known as pleural effusion,
and this can sometimes mess with lung expansion.
Rheumatoid arthritis typically involve multiple joints, usually five or more, symmetrically,
meaning the same joint groups on both sides of the body, like both hands for instance.
Commonly affected joints are the small joints like metacarpophalangeal and proximal interphalangeal
joints of the hands, and the metatarsophalangeal joints of the feet.
As the disease worsens, it can start to affect large joints like the shoulders, elbows, knees
and ankles.
During “flares” or sudden worsening of the disease, the affected joints get extremely
swollen, warm, red, and painful.
Over time, they become stiff, especially in the morning or after being inactive for a
prolonged period of time.
People with rheumatoid arthritis may develop specific deformities, usually of the metacarpophalangeal
joints in the hand, such as ulnar deviation of the fingers.
Deformities are also common in the interphalangeal joints, such as the so- called boutonniere
or buttonhole deformity.
This occurs when the extensor tendon in the back of the finger splits and the head of
the proximal phalanges pokes through like a button through a buttonhole, causing flexion
of the proximal interphalangeal joint and hyperextension of distal interphalangeal joint.
Another finger deformity is the swan neck deformity, which is the opposite, so there’s
hyperextension of the proximal interphalangeal joint and flexion of the distal interphalangeal
joint.
Now, in the knee joint, a one-way value can form, with fluid from the swollen knee filling
the semi-membranous bursa.
When that happens, the synovial sac can get so swollen that it bulges posteriorly into
the popliteal fossa, creating a synovial fluid-filled cyst, called a Baker or popliteal cyst.
Now, extra- articular manifestations include non-specific symptoms of inflammation, such
as fever, low appetite, malaise or muscle weakness, and organ- specific, manifistations
include rheumatoid nodules or firm bumps of tissue, and these most commonly in the skin
around pressure points, such as the elbows.
More rarely, in the lungs, the heart, or the sclera of the eye.
There’s also an increased risk of atherosclerosis and therefore, heart attack or stroke.
There’s also anemia, interstitial lung fibrosis and pleural effusions, which can present as
progressive shortness of breath.
One particularly serious condition that’s associated with rheumatoid arthritis is Felty
syndrome which is a triad of rheumatoid arthritis, splenomegaly, and granulocytopenia, and it
can lead to life-threatening infections.
Diagnosis of rheumatoid arthritis usually involves confirmatory blood tests, like looking
for the presence of rheumatoid factor and anti-citrullinated peptide antibody.
Additionally, imaging studies, such as X- ray, usually reveal decreased bone density
around affected joints, soft tissue swelling, narrowing of the joint space, and bony erosions.
The long term management of rheumatoid arthritis is use of disease-modifying antirheumatic
medications like methotrexate, hydroxychloroquine, sulfasalazine, and which can help to suppress
the inflammation.
In addition, there are a variety of medications called biologic response modifiers or biologics.
Some biologics, such as abatacept, work by suppressing the activity of T cells, or others,
such as rituximab suppress B cells.
There are also biologics such as adalimumab, etanercept, and infliximab, that block various
chemokines like tumor necrosis factor.
Anakinra blocks interleukin 1 which is blocked by, and tocilizumab blocks interleukin 6.
Treatment of acute flares can be done with anti- inflammatory medications like NSAIDS
as well as short term use of glucocorticoids.
All right, so as a quick recap, rheumatoid arthritis is a systemic inflammatory disorder
of autoimmune origin that is primarily characterized by progressive, symmetric joint destruction,
especially in the wrists and fingers, but may also affect other joints and many organs,
such as the skin, heart, blood vessels and lungs.
It’s marked by elevated rheumatoid factor and anti- cyclic citrullinated peptide antibodies.
浏览更多相关视频
Rheumatoid Arthritis Animation
Rheumatoid Arthritis Pathophysiology (signs and symptoms)
Ankylosing spondylitis - causes, symptoms, diagnosis, treatment, pathology
Sjogren's Syndrome | Causes, Clinical features, Diagnosis & Treatment
Sickle Cell Disease | Pathophysiology, Symptoms and Treatment
Asthma - causes, symptoms, diagnosis, treatment, pathology
5.0 / 5 (0 votes)