Rheumatoid arthritis – causes, symptoms, diagnosis, treatment, pathology

Rheumatoid arthritis – causes, symptoms, diagnosis, treatment, pathology


Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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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.

25 Comments

  • Chaïma Fr says:

    your videos help A LOT, if the premium version was possible in my country i would be the firt to get it <3 so thank you so much for the work, it's ART, i love you

  • Kiruzo Kaguhaya says:

    request for dengue fever pleaser

  • Ziyad Khamis says:

    What are the odds that I get this video when I have an IM exam in 10 days' time, right?.. Thanks! 😁

  • Grace chi says:

    Thank you ,easy to understand.

  • Marce' Nielsen says:

    Another autoimmune disorder

  • التدريس الالكتروني says:

    Please continue making these amazing videos

  • Marissa Perez says:

    I was diagnosed with RA in February and honestly it's horrible some days I'm fine while others I feel like I can't get out of bed.

  • FadeSkywards says:

    I watched this before. Is this a reupload?

  • shifa khan says:

    Otra vez buena video 👍 Gracias….

  • jhorly alvarez says:

    Wow, very clear.

  • Taqua Ahmad says:

    I took RA last year in pathology, but honestly I feel like I understand it a lot better now. Thank you so much for helping us and keep making great videos.

  • T says:

    I find it hard to understand your accent.

  • Rheumatoid Arthritis Eliminators says:

    Right here on YouTube, Doctors Joel Wallach, Joseph Mercola, Katherine Poehlman, Kurt Woeller, Thomas McPherson Brown, and Lonnie Herman, discuss eliminating Mycoplasma Bacteria to help relieve the pain caused by Rheumatoid Arthritis.

  • J Silva says:

    It is such a coincidence. This video was uploaded 8 days ago and I am studying the immune system today. I'm glad I didn't try to study it 9 days earlier.

  • dinesh raja says:

    Thank you guys,great work !!

  • Manuel Peterson says:

    My nerves and my feet are struggling with pain and I also have arthritis (degenerative joint disease) on my lower back. The arthritis treatment solution “Rοngοdο Ruzο” (Google it) helped me cure this! I use this in my elbows, hands, feet, and neck. It continues to amaze me! .

  • Dominic Tayler says:

    My nerves and my feet are suffering from pain and I also have arthritis (degenerative joint disease) in my lower back. The arthritis treatment solution “Rοngοdο Ruzο” (Google it) helped me cure this! I used it for my feet, I have tried it on my neck, elbows and hands. Its amazing results keeps surprising me till right now. .

  • Dean Hocking says:

    Please can someone help urgent – my auntie is 49 African and she has had a b12 level of 1200 come back from doctors… she dislocated her shoulder (10 yrs ago and 2 months ago) and she’s swelling in her ankles, wrist and her knuckles are “screeching”… she’s also been fatigued…..so could her raised b12 levels and these symptoms indicated ra arthritis or lupus? She’s a vegetarian if that helps?!

  • lily monroy says:

    Recently my mom has had a few random pains in certain joints and wasn't specific. We didn't know what it was last doctor said isn't arithis goes to another hospital find out. She has apparently arthritis in her fingers. Took x-ray that's how found out not sure what type tho since it primarily pain she feels in her fingers

  • Rheumatoid Arthritis Eliminators says:

    Mycoplasma Bacteria. Get familiar with it before it gets familiar with you! Rheumatoid Arthritis: The Infection Connection by Dr. Katherine Poehlmann – right here on YouTube.

  • Maharajan s says:

    thanku

  • Waleed Khalid says:

    Who presented this lesson? I noticed you didn’t leave a name.

    Anyway, thanks a lot for sharing this amazing video. It’s really helpful for learning.

  • Tom will says:

    This is a lot better explanation than my doctor telling me , "you got RA" .

  • liltrollbox says:

    Great info, your mic sucks

  • Amritpal singh says:

    This video is very informative. Actually, my friend has suffered from this problem. During this time, He could not even stand on his own. He did not think he would survive. Someone told him about Planet Ayurveda, he went there and took treatment. He realized the improvement in a few days. Now he is fine. So, if anyone is facing such kind of problem or any health-related problem. You should go to Planet Ayurveda.

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