Rheumatoid Arthritis Pathophysiology (signs and symptoms)

00:15:34
https://www.youtube.com/watch?v=ld8PhyAHov8

概要

TLDRThe video discusses rheumatoid arthritis (RA), a systemic disorder characterized by symmetrical arthritis, particularly affecting the hands. It contrasts RA with osteoarthritis, highlighting the specific joints involved. The pathophysiology of RA is explained, focusing on synovitis, inflammation, and the role of immune cells like macrophages and T cells. Key antibodies, including rheumatoid factor and anti-citrullinated protein antibodies, are discussed for their diagnostic significance. The video also covers extra-articular manifestations affecting various organs, emphasizing the systemic impact of RA. Overall, it provides a detailed understanding of RA's clinical features, causes, and effects.

収穫

  • 🦴 Rheumatoid arthritis is a systemic disorder affecting multiple joints.
  • 🤝 Hand involvement is early and symmetrical in RA.
  • 🔬 Synovitis leads to inflammation and joint damage.
  • 🧬 Key antibodies include rheumatoid factor and anti-citrullinated protein antibodies.
  • 🌍 RA has extra-articular effects on various organs.
  • 🧪 Cytokines play a crucial role in inflammation and disease progression.
  • 🩺 Early diagnosis is important for managing RA effectively.
  • 🧑‍⚕️ Treatment may involve glucocorticoids, affecting immune response.
  • 💔 RA can lead to cardiovascular complications.
  • 🦵 Musculoskeletal involvement can result in osteoporosis.

タイムライン

  • 00:00:00 - 00:05:00

    The video introduces rheumatoid arthritis as a systemic rheumatological disorder characterized by symmetrical arthritis, primarily affecting the hands. It contrasts the joint involvement in rheumatoid arthritis with osteoarthritis, highlighting the specific joints affected and the deformities that can occur, such as swan neck and boutonniere deformities. The video emphasizes the early involvement of the metacarpal phalangeal and proximal interphalangeal joints in rheumatoid arthritis, leading to various hand deformities as the disease progresses.

  • 00:05:00 - 00:10:00

    The video delves into the cellular mechanisms of rheumatoid arthritis, focusing on the inflammation of the synovial membrane (synovitis) and the role of various immune cells, including macrophages, T cells, and fibroblasts. It explains how cytokines like TNF-alpha and interleukin-1 contribute to inflammation and bone erosion through the activation of osteoclasts. The video also discusses the migration of activated fibroblasts and T cells, leading to symmetrical arthritis, and the presence of immune complexes in the synovial fluid that further promote inflammation.

  • 00:10:00 - 00:15:34

    The video concludes by discussing the extra-articular manifestations of rheumatoid arthritis, which arise from systemic inflammation due to cytokines. It covers the impact on various organs, including skin nodules, liver function, cardiovascular risks, and neurological effects such as fatigue and depression. The video also touches on the potential complications from treatment, particularly lung involvement due to glucocorticoids, and summarizes the clinical manifestations, pathophysiology, and causes of rheumatoid arthritis.

マインドマップ

ビデオQ&A

  • What is rheumatoid arthritis?

    Rheumatoid arthritis is a systemic rheumatological disorder that affects multiple joints, causing pain, swelling, and inflammation.

  • How does rheumatoid arthritis differ from osteoarthritis?

    Rheumatoid arthritis primarily affects the proximal interphalangeal and metacarpal phalangeal joints, while osteoarthritis affects the distal interphalangeal joints.

  • What are the main antibodies associated with rheumatoid arthritis?

    The main antibodies are rheumatoid factor (IgM) and anti-citrullinated protein antibodies, which help in diagnosing RA.

  • What are the extra-articular manifestations of rheumatoid arthritis?

    Extra-articular manifestations can include skin nodules, liver inflammation, cardiovascular issues, and lung involvement.

  • What causes the inflammation in rheumatoid arthritis?

    The exact trigger is unknown, but factors like genetics, smoking, and infections may modify autoantigens, leading to an immune response.

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  • 00:00:05
    hello in this video we're going to look
  • 00:00:07
    at rheumatoid arthritis which is a
  • 00:00:09
    systemic
  • 00:00:11
    rheumatological disorder affecting
  • 00:00:13
    multiple joints
  • 00:00:16
    the clinical presentation of rheumatoid
  • 00:00:18
    arthritis is arthritis which is
  • 00:00:20
    symmetrical we have pain swelling as
  • 00:00:22
    well as nodules around the area
  • 00:00:24
    hand involvement is early in the disease
  • 00:00:27
    and affects the metacarpal phalangeal
  • 00:00:29
    and proximal interphalangeal joints
  • 00:00:33
    in rheumatoid arthritis there's also
  • 00:00:34
    extra articular involvement which we'll
  • 00:00:36
    look at later on
  • 00:00:39
    but first let us look at the hand
  • 00:00:41
    involvement in in rheumatoid arthritis
  • 00:00:43
    and see how it differs to osteoarthritis
  • 00:00:48
    so here is rheumatoid arthritis and
  • 00:00:49
    osteoarthritis
  • 00:00:51
    so in osteoarthritis the joints affected
  • 00:00:54
    are the distal interphalangeal joints as
  • 00:00:56
    well as a proximal interphalangeal
  • 00:00:58
    joints
  • 00:00:59
    whereas in rheumatoid arthritis it is
  • 00:01:01
    the proximal interphalangeal joints and
  • 00:01:04
    the metacarpal phalangeal joints
  • 00:01:06
    as well you can have other
  • 00:01:08
    joint involvement such as the wrist
  • 00:01:10
    so so these joints are affected early in
  • 00:01:14
    the disease
  • 00:01:16
    in rheumatoid arthritis but as the
  • 00:01:18
    disease progresses you can have other
  • 00:01:20
    features occurring in the hands
  • 00:01:22
    these are swatness boutonniere
  • 00:01:26
    deformity of the thumb
  • 00:01:28
    so in swan neck what you have is you
  • 00:01:30
    have the distal interphalangeal joints
  • 00:01:33
    flexed
  • 00:01:34
    but the proximal interphalangeal joints
  • 00:01:38
    hyper extended in
  • 00:01:40
    the air it's the opposite you have the
  • 00:01:42
    distal interphalangeal joints
  • 00:01:43
    hyperextended and the proximal
  • 00:01:45
    interphalangeal joints flexed
  • 00:01:48
    the z deformity of the thumb is
  • 00:01:50
    essentially the thumb looking like a zed
  • 00:01:52
    it's
  • 00:01:53
    sort of bent hyper-extended
  • 00:01:56
    in the hands the hands can also deviate
  • 00:01:59
    medially
  • 00:02:00
    this is referred to as ulnar deviation
  • 00:02:04
    so they were the they were the uh the
  • 00:02:08
    hand
  • 00:02:09
    what will the features of the hands in
  • 00:02:10
    rheumatoid arthritis let us actually
  • 00:02:12
    look at what happens inside the joints
  • 00:02:15
    so let us zoom into the this a finger
  • 00:02:18
    here
  • 00:02:19
    and just to recap the anatomy here we
  • 00:02:22
    have the bone
  • 00:02:23
    the joint capsule
  • 00:02:25
    the synovial membrane
  • 00:02:27
    also known as a synovium
  • 00:02:30
    the synovial membrane also known as a
  • 00:02:32
    synovium which produces the synovial
  • 00:02:34
    fluid which helps in lubrication
  • 00:02:38
    as well as supplying nutrients to the
  • 00:02:39
    area then we have the cartilage here in
  • 00:02:42
    blue
  • 00:02:44
    in rheumatoid arthritis you essentially
  • 00:02:46
    have inflammation of the synovium of the
  • 00:02:49
    synovial membrane you have synovitis
  • 00:02:52
    and this causes pain and swelling
  • 00:02:55
    which occurs in rheumatoid arthritis
  • 00:02:58
    this also leads to bone and cartilage
  • 00:03:01
    erosion
  • 00:03:02
    breakdown
  • 00:03:04
    another feature we can see in the joints
  • 00:03:06
    of
  • 00:03:07
    rheumatoid arthritic patients is
  • 00:03:09
    angiogenesis
  • 00:03:12
    so that was the macroscopic view of the
  • 00:03:14
    joint just an overview let's look at it
  • 00:03:17
    in a more deep in a lot more detail at a
  • 00:03:20
    cellular level let us zoom into this
  • 00:03:22
    area
  • 00:03:22
    and
  • 00:03:24
    see what cells are involved
  • 00:03:26
    so just to uh
  • 00:03:28
    just to show where we are here we have
  • 00:03:30
    the bone the synovium
  • 00:03:33
    here's the fluid here in yellow and blue
  • 00:03:35
    is the cartilage
  • 00:03:37
    and again i'm drawing the synovium
  • 00:03:38
    really big because it is inflamed right
  • 00:03:42
    the synovial membrane now the synovial
  • 00:03:45
    membrane is made up of these cells known
  • 00:03:47
    as fibro fibroblasts like synoviocites
  • 00:03:51
    and these guys are very important in the
  • 00:03:53
    pathogenesis
  • 00:03:55
    of
  • 00:03:56
    rheumatoid arthritis
  • 00:03:58
    so again rheumatoid arthritis is where
  • 00:04:00
    we have inflammation of the synovial
  • 00:04:01
    membrane of the synovium
  • 00:04:04
    now the exact trigger of
  • 00:04:06
    the
  • 00:04:08
    the inflammation of the disease is
  • 00:04:10
    really not quite
  • 00:04:13
    not quite known
  • 00:04:14
    however
  • 00:04:15
    we are now looking at what cells we can
  • 00:04:17
    find here and what cells are involved
  • 00:04:20
    so we have macrophages here and they're
  • 00:04:22
    they're normally around here as well but
  • 00:04:24
    they they essentially begin secreting
  • 00:04:26
    cytokines such as tnf alpha
  • 00:04:28
    interleukin-1 and interleukin-6
  • 00:04:31
    which of course leads to inflammation
  • 00:04:35
    the cytokines also stimulate the
  • 00:04:38
    fibroblasts like synoviocytes
  • 00:04:40
    when the fibroblasts like stand over
  • 00:04:42
    your sites are stimulated
  • 00:04:44
    they essentially become activated and
  • 00:04:46
    then they begin to proliferate
  • 00:04:49
    at the same time they also begin
  • 00:04:52
    assisting in rank l expression
  • 00:04:54
    stimulating the rank l expression which
  • 00:04:56
    together with the cytokines here will
  • 00:04:58
    stimulate osteoclast activity which will
  • 00:05:01
    lead to bone erosion what we find in
  • 00:05:04
    rheumatoid arthritis
  • 00:05:07
    when the fibroblasts like synovial sites
  • 00:05:09
    are stimulated and proliferate they also
  • 00:05:12
    begin secreting proteases
  • 00:05:15
    these proteases essentially cause the
  • 00:05:17
    cartilage to break down so we get
  • 00:05:20
    cartilage degradation and the cartilage
  • 00:05:22
    also secrete proteases and it's sort of
  • 00:05:24
    like a feedback loop
  • 00:05:28
    another interesting feature of where of
  • 00:05:30
    the fibroblasts like synovial sites is
  • 00:05:32
    that when it's stimulated when it's
  • 00:05:34
    activated
  • 00:05:35
    these guys can actually migrate from
  • 00:05:38
    joint to join
  • 00:05:39
    so they can migrate from the hand joint
  • 00:05:41
    on one side to the hand joint on the
  • 00:05:43
    other and this is why we get symmetrical
  • 00:05:45
    arthritis in rheumatoid arthritis
  • 00:05:50
    we also can find t cells in the area in
  • 00:05:52
    the synovium t cells make up about fifty
  • 00:05:55
    percent of the uh immune cells in this
  • 00:05:57
    area so they're very important in the
  • 00:05:59
    pathophysiology
  • 00:06:01
    t cells uh promote inflammation
  • 00:06:03
    essentially and they secrete they can
  • 00:06:06
    secrete interleukin-17 which will
  • 00:06:08
    promote macrophage activity as well as
  • 00:06:10
    stimulate
  • 00:06:11
    the fibroblasts like synoviocites
  • 00:06:14
    the t cells also help
  • 00:06:16
    in the expression of rank l which will
  • 00:06:18
    stimulate osteoclast for bone erosion
  • 00:06:23
    we also find plasma cells in the area
  • 00:06:26
    and plasma cells only make up a small
  • 00:06:27
    majority about five percent of the
  • 00:06:29
    immune cells and they essentially assist
  • 00:06:31
    in inflammation through cytokines as
  • 00:06:34
    well as through antibodies
  • 00:06:38
    now in the fluid in the synovial fluid
  • 00:06:41
    not in the synovial membrane in the
  • 00:06:43
    synovial fluid we can find neutrophils
  • 00:06:46
    and neutrophils they they essentially
  • 00:06:49
    produce proteases and reactive oxygen
  • 00:06:51
    species
  • 00:06:53
    which will essentially cause bone and
  • 00:06:55
    cartilage degradation erosion
  • 00:06:58
    so they contribute to inflammation
  • 00:07:01
    in the synovial fluid we also find the
  • 00:07:03
    immune complexes which is a feature of
  • 00:07:07
    rheumatoid arthritis these immune
  • 00:07:08
    complexes are essentially antibodies
  • 00:07:10
    that bind to one another and they
  • 00:07:12
    essentially promote inflammation so
  • 00:07:14
    those are the cells that we can find
  • 00:07:16
    in a inflamed
  • 00:07:18
    joint in rheumatoid arthritis
  • 00:07:20
    again another feature around this area
  • 00:07:23
    is that we see angiogenesis
  • 00:07:25
    also the cytokines that are produced by
  • 00:07:26
    all these cells they help
  • 00:07:28
    increase vascular permeability and
  • 00:07:32
    expression of adhesion molecules on the
  • 00:07:33
    vascular vasculature allowing for these
  • 00:07:36
    immune cells to migrate
  • 00:07:39
    into the joints
  • 00:07:42
    but where do all these cells come from
  • 00:07:44
    why do they migrate into these joints
  • 00:07:46
    and cause rheumatoid arthritis
  • 00:07:49
    well as i mentioned we don't actually
  • 00:07:51
    know but there are a few theories out
  • 00:07:53
    there
  • 00:07:54
    so let's go to the pre-rheumatoid
  • 00:07:57
    arthritis phase before a person has
  • 00:07:59
    rheumatoid arthritis and there are many
  • 00:08:02
    possible things that could contribute to
  • 00:08:03
    the development of rheumatoid arthritis
  • 00:08:05
    these include genetics
  • 00:08:07
    epigenetic modifications
  • 00:08:09
    smoking
  • 00:08:10
    a bacteria called porphyramonas
  • 00:08:13
    gingivalis which can lead to gingivitis
  • 00:08:17
    essentially these things they can cause
  • 00:08:19
    modification of autoantigens
  • 00:08:22
    what do i mean by modifications of
  • 00:08:23
    autoantigens
  • 00:08:25
    it essentially what i essentially mean
  • 00:08:27
    is modification of your own antigens
  • 00:08:31
    to make it seem foreign to the immune
  • 00:08:33
    cells so you're modifying your so these
  • 00:08:36
    things can lead to modifications of your
  • 00:08:38
    own antigens leading
  • 00:08:40
    to an immune response
  • 00:08:42
    and the modifications of autoantigens
  • 00:08:44
    include what's known as citrullination
  • 00:08:48
    so not only this things can occur in the
  • 00:08:51
    joints such as
  • 00:08:53
    you can have a synovial injury or
  • 00:08:55
    hyperplasia or you can have infection
  • 00:08:58
    within the joint and this will trigger
  • 00:09:00
    you know cytokine release and it will
  • 00:09:02
    cause inflammation
  • 00:09:04
    this inflammation that occurs in the
  • 00:09:06
    joints can also lead to modification of
  • 00:09:09
    autoantigens so modification of your own
  • 00:09:13
    antigens making it seem foreign
  • 00:09:16
    and this also includes citrullination
  • 00:09:20
    so because you have modifications of
  • 00:09:22
    your own antigens this will be
  • 00:09:24
    recognized by antigen presenting cells
  • 00:09:26
    and it will essentially activate the
  • 00:09:28
    antigen presenting cells
  • 00:09:30
    to initiate an immune response the
  • 00:09:32
    antigen presenting cell will migrate to
  • 00:09:34
    the lymph nodes where
  • 00:09:36
    here i'm drawing the lymph node
  • 00:09:38
    remember the lymph node here is green
  • 00:09:40
    and within the lymph node we have the
  • 00:09:42
    germinal center where we have b cells
  • 00:09:45
    anyway the antigen presenting cell will
  • 00:09:47
    activate t cells here in the area so we
  • 00:09:50
    can have a cd4 t cell activation
  • 00:09:55
    and when the cd4 when the t cell is
  • 00:09:57
    activated the cd4 t cell it can activate
  • 00:10:00
    then b cells in the germinal center and
  • 00:10:02
    this can be through co-stimulation
  • 00:10:05
    when the b cells are activated they will
  • 00:10:07
    begin to you know proliferate they will
  • 00:10:09
    begin to class switch and they will
  • 00:10:12
    become plasma cells
  • 00:10:13
    then plasma cells will then produce oto
  • 00:10:16
    antibodies they will produce the
  • 00:10:18
    antibodies against your own antigen
  • 00:10:21
    essentially
  • 00:10:24
    so then what well you have now cd4 t
  • 00:10:28
    helper cells and then you have the
  • 00:10:31
    antibodies and the plasma cells and they
  • 00:10:33
    will also have homing receptors and
  • 00:10:35
    stuff like that which will allow them to
  • 00:10:37
    migrate to joint tissue so that is how
  • 00:10:40
    they move into the joints in rheumatoid
  • 00:10:43
    arthritis
  • 00:10:45
    so i hope that made sense now it's
  • 00:10:47
    important to talk about the antibodies
  • 00:10:49
    because they're an important feature in
  • 00:10:50
    rheumatoid arthritis we have two main
  • 00:10:52
    antibodies found
  • 00:10:55
    and these are
  • 00:10:56
    we look at one one one of them at a time
  • 00:10:59
    so the first one is the rheumatoid
  • 00:11:00
    factor which is an igm antibody and it's
  • 00:11:03
    present in 75 percent of people with
  • 00:11:06
    rheumatoid arthritis
  • 00:11:08
    what these guys do is that they target
  • 00:11:09
    fc portion of igg antibodies so the
  • 00:11:13
    constant region
  • 00:11:15
    and they essentially are the ones that
  • 00:11:17
    are that that in that form the immune
  • 00:11:20
    complex and can deposit in the synovial
  • 00:11:22
    fluid
  • 00:11:24
    the rheumatoid fact that not only you
  • 00:11:26
    know
  • 00:11:28
    forms immune complexes with but with
  • 00:11:30
    itself but with the igg as well as
  • 00:11:32
    complement proteins
  • 00:11:35
    so it will promote inflammation
  • 00:11:40
    the second antibody is the anti
  • 00:11:42
    citrullinated
  • 00:11:43
    protein antibody
  • 00:11:47
    now these guys as the name suggests they
  • 00:11:49
    target citrullinated proteins
  • 00:11:52
    these are things such as fibrin and
  • 00:11:55
    filogrin
  • 00:11:56
    now
  • 00:11:58
    they target citrullinated proteins what
  • 00:12:00
    are they well citrulline proteins are
  • 00:12:02
    essentially proteins
  • 00:12:04
    who have arginine residues that have
  • 00:12:07
    been converted to citrullinate
  • 00:12:10
    and
  • 00:12:10
    this sort of change
  • 00:12:12
    deems makes it seem foreign to the body
  • 00:12:15
    and that is why
  • 00:12:17
    when we have modifications of our
  • 00:12:19
    autoantigens such as citrullination our
  • 00:12:23
    body thinks it's foreign
  • 00:12:25
    and unfortunately in our joints
  • 00:12:27
    um we have these sort of tissues so
  • 00:12:30
    therefore um that's how it can so that's
  • 00:12:33
    how this antibody contributes to the
  • 00:12:34
    pathophysiology
  • 00:12:37
    um but essentially there's these
  • 00:12:39
    rheumatoid factor and anti-citrullinated
  • 00:12:42
    protein antibodies they're important for
  • 00:12:44
    in helping diagnose rheumatoid arthritis
  • 00:12:46
    not everyone has rheumatoid factor but
  • 00:12:48
    the anti-citrullated protein antibody it
  • 00:12:51
    is a lot more specific
  • 00:12:53
    for rheumatoid arthritis
  • 00:12:57
    so i hope that all made sense
  • 00:12:59
    now it's important that we talk about
  • 00:13:01
    the extra articular involvement
  • 00:13:04
    within rheumatoid arthritis so what i'm
  • 00:13:06
    talking about is involvement of other
  • 00:13:07
    organs around the body and how
  • 00:13:09
    rheumatoid arthritis causes problems
  • 00:13:11
    there too
  • 00:13:13
    so these extra articular involvement is
  • 00:13:16
    a result of the cytokines produced
  • 00:13:18
    within the joints and stuff and these
  • 00:13:20
    are mainly tnf alpha interleukin-1 and
  • 00:13:22
    interleukin-6 so within the blood we
  • 00:13:24
    have increasing inflammatory cytokines
  • 00:13:27
    and they essentially contribute to many
  • 00:13:30
    things around the body
  • 00:13:32
    for example in the skin they contribute
  • 00:13:34
    to the nodule formation in the liver
  • 00:13:37
    because of the cytokines the liver will
  • 00:13:39
    begin
  • 00:13:40
    producing more crp or ecr proteins which
  • 00:13:42
    are inflammatory markers as well as the
  • 00:13:45
    liver will produce a lot more hepatin
  • 00:13:47
    which will contribute to anemia
  • 00:13:50
    in rheumatoid arthritis cardiovascular
  • 00:13:52
    involvement well these cytokines and
  • 00:13:54
    this inflammation that's occurring will
  • 00:13:56
    actually promote
  • 00:13:57
    arthrogenesis so plaque formation and it
  • 00:14:00
    can also lead to promote you know
  • 00:14:02
    myocardial infarction as well as stroke
  • 00:14:05
    neurological involvement include
  • 00:14:08
    fatigue
  • 00:14:09
    and depression and these can be
  • 00:14:11
    attributed to anemia
  • 00:14:13
    um bone involvement is very serious in
  • 00:14:16
    rheumatoid arthritis
  • 00:14:18
    sorry musculoskeletal involvement so
  • 00:14:20
    these these include osteopenia which can
  • 00:14:22
    lead to osteoporosis
  • 00:14:25
    in the muscles the inflammation causes
  • 00:14:28
    can lead to insulin resistance which
  • 00:14:30
    which can result in muscle weakness
  • 00:14:34
    and also bone marrow involvement we can
  • 00:14:36
    have thrombocytosis
  • 00:14:39
    which is a lot of platelet which can
  • 00:14:41
    contribute to you know to the
  • 00:14:43
    plaque from a uh the thrombus formation
  • 00:14:46
    as well as we have anemia
  • 00:14:48
    so i hope that made sense and i hope you
  • 00:14:50
    enjoyed this video we look
  • 00:14:54
    so those are the extra articular
  • 00:14:56
    involvement of rheumatoid arthritis you
  • 00:14:58
    also have lung involvement
  • 00:15:00
    such as
  • 00:15:01
    pleural effusion and lung infection but
  • 00:15:04
    this can be attributed to the treatment
  • 00:15:06
    used for rheumatoid arthritis which
  • 00:15:08
    involves glucocorticoids and as we know
  • 00:15:11
    glucocorticoid suppresses the immune
  • 00:15:12
    system
  • 00:15:14
    um i hope you enjoyed this video we
  • 00:15:16
    looked at the clinical manifestations
  • 00:15:18
    the hand involvement the pathophysiology
  • 00:15:21
    the causes potential causes as well as
  • 00:15:23
    the articular manifestations of
  • 00:15:25
    rheumatoid arthritis thank you for
  • 00:15:26
    watching bye
タグ
  • Rheumatoid Arthritis
  • Pathophysiology
  • Immune Response
  • Extra-Articular Manifestations
  • Antibodies
  • Synovitis
  • Cytokines
  • Hand Involvement
  • Diagnosis
  • Osteoarthritis