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