limbs and back week 4 Flashcards
describe the joint capsule
it is connected to the periosteum
lined with synovium
Describe synovium
a few cells think vascular smooth and non-adherent surface permeable to proteins and crystalloids no microscopic gaps able to maintain normal joint fluid under pressure
Describe synoviocytes
macrophage and fibroblast like
cell to cell interactions mediated by cadherin-II
What do synoviocytes do?
secrete hyaluronic acid into the joint same to retain fluid in the joint
Describe synovial fluid
highly viscous, similar consistency to plasma
glycoproteins ensure a low coefficient of friction between the cartilaginous surfaces
What are also lined by synovium?
tendon sheaths and bursae
Does hyaline cartilage have a blood supply?
no it is avascular
where does hyaline cartilage receive its nutrients from?
diffusion of molecules from the synovial fluid
why type of collagen is in cartilage?
type II
what is the structure of hyaline cartilage?
the type II collagen forms a meshwork enclosing giant macromolecules such as keratin and chondroitin sulphate (aggrecans).
These molecules have a negative charge and retain water om the structure
Why is “loading” essential for healthy cartilage?
it encourages the movement of water, minerals and nutrients between the cartilage and the synovial fluid.
What do chondrocytes secrete?
collagen and proteoglycans
What is rheumatoid arthritis?
a progressive inflammatory autoimmune disease with articular and systemic effects
What are common symptoms of RA?
pain and stiffness of the small joints of the hands and feet
the wrists, elbows, shoulders, knees and ankles are also affected
In most cases many joints are involved
When is the pain of RA worse?
significantly worse in the morning
sleep is often disturbed
what do joints with RA look like?
warm and tender with joint swelling
deformities and non-articular features if disease can not be controlled
Describe presentations of RA
palindromic transient remitting chronic persisting - most common rapidly progressive
what are some of the complications of RA?
ruptured tendons ruptured joints (baker's cysts) spinal cord compression joint infection amyloidosis (rare)
What are some of the non-articular manifestations of RA?
soft tissues surrounding the joints can be affected lung problems vasculitis heart and peripheral vessels the nervous system the eyes the kidneys
What are the investigations for RA?
blood count
the ESR and or CRP are raised in proportion to the activity of the inflammatory processes
serology - ACPA is present earlier in the disease (and may predate it by years)
X-rays show soft tissue swelling in early disease
MRI indicates synovitis and early erosions
aspiration - if effusion is present. Aspirate looks cloudy due to presence of leukocytes
doppler ultrasound is a very good way of demonstrating persisting synovitis when deciding on the need of DMARDs or their efficacy
What is the cause of RA?
its exact cause is unknown
genetic and environmental factors contribute
What inflammatory cells are involved in the pathophysiology of RA?
Differentiation of T cells into Th17 - production of Il17
B cells - antibody and cytokine production
mononuclear cells
What are the main cytokines involved in RA?
IL-17, TNF alpha, IL6, IL1
What is the pannus and what does it do in RA?
the osteoclast rich portion of the synovial membrane destroys the bone
What do enzymes secreted by the synoviocytes do?
Degrade the cartilage
What is rheumatoid factor?
the autoantibody that was first found in RA
the antibody against the Fc portion of IgG (an antibody against an antibody)
RF and IgG join to form an immune complex that contributes to the disease pathogenesis
What are the physical measures for the treatment of RA?
constant advice and support from physiotherapists and nurses combination of rest and exercise exercise in hydrotherapy pool advice on managing daily living shoe-wear psychosocial support
What are the surgical options for the treatment of RA?
useful role in long term management
less needed as therapeutics improve
prophylactic objectives - prevent joint destruction
reconstructive -restore function
Describe the drug therapy of RA
There is no curative agent available for RA but drugs are now available that prevent the disease deterioration.
Symptoms are controlled with analgesia and NSAIDs
Describe the use of corticosteroid therapy in RA
there is evidence to suggest that the early use of corticosteroids slows down the course of the disease
corticosteroids are the most common cause of secondary osteoporosis
when treating for extended periods calcium and vitamin D supplements as well as biphosphonates are required
Describe the use of DMARDs in RA treatment
Disease-modifying anti-rheumatic drugs
mainly act through cytokine inhibition reduce inflammation
their beneficial effect is not immediate and may be partial or transient
When are DMARDs used in RA?
As early as possible
Give examples of DMARDs
Sulfasalazine
methotrexate
hydrochloroquine
leflunomide
What drugs have recently become available for the treatment of RA?
Cytokine modulators
What do cytokine modulators do?
block TNF alpha
Why are DMARDs still usually tried before DMARDs?
The cost
What are examples of cytokine modulators
etanercept adalimumab infliximab certolicumab retuximab abatacept
Name the carpal bones of the hand
scaphoid trapezium trapezoid capitate hamate pisiform triquetral lunate
Describe the intrinsic muscles of the hand
All For One And One For All
abductor pollicis brevis, flexor policis brevis, opponens pollicis, adductor pollicis brevis, opponens digiti minimi, flexor digiti minimi, abductor digiti minimi
PAD, DAB
Palmar interossei Adduct
Dorsal interossei ABduct
Name the 10 structures that pass through the carpal tunnel
median nerve
flexor digitorum profundus (4 tendons)
flexor digitorum superficialis (4 tendons)
flexor policis longus
What is the carpal tunnel covered by?
the flexor retinaculum
What does the radial nerve innervate in the dorsum of the hand?
skin of dorsum of thumb, index, middle and radial half of ring fingers as far as the distal interphalangeal joints
What does the ulnar nerve innervate in the dorsum of the hand?
ulnar half of ring finer and adjacent part of the dorm of the hand
What does the ulnar nerve innervate on the palmar side of the hand?
sensory to skin of ulnar digits motor to muscles of the hypothenar eminence motor to ulnar 2 lumbricles motor to 7 interossei muscles motor to adductor policis
What does the median nerve innervate on the palmar side of the hand?
sensory aspect of the thumb, index, middle and radial half of ring fingers including skin on the dorsal aspect of the phalanges
motor on thenar eminence
motor to two radial lumbricles
What are some examples of autoimmune diseases?
rheumatoid arthritis
psoriasis
systemic lupus
cardiovascular disease
What is autoimmunity?
the immune system mistakenly attacks self, targeting cells, tissues, and organs of a person’s body
What is organ specific autoimmune disease?
autoimmune attack on self antigens in specific organ
Give examples of organ specific AI disease
hashimoto thyroiditis thyrotoxicosis addison's disease juvenile diabetes mellitus Multiple sclerosis Guillain - Barre syndrome
What is non-organ specific IA?
widespread self antigens are target for autoimmune attack
Give examples of non-organ specific IA
systemic lupus
rheumatoid arthritis
mixed connective tissue disease
sjogren’s syndrome
What are some ways the AI is thought to occur?
infections trigger autoimmune reactions
autoimmunity prevented by infection (type 1 diabetes, MS) “the hygiene hypothesis”
What is the target of the autoantibodies in Grave’s disease?
TSH receptor
What is the target of the autoantibodies in Myasthenia graves?
ACH receptor
What is the target of the autoantibodies in idiopathic thrombocytopenia purpura (ITP)
PLatelets
What is the target of the autoantibodies in Guillain-BArre syndrome?
gangliosides
What are some of the autoimmunity theories?
leak theory cryptic self hypothesis self ignorance molecular mimicry modified self theory defective apoptosis polyclonal activators NO overriding theory!!!
What are the main signs of inflammation?
heat redness swelling pain loss of function
what is septic arthritis?
septic infection of the joint
what do neutrophils contain?
reactive oxygen intermediates, extremely toxic to bacteria however can cause damage to tissue when released
What do neutrophils do to get to the site of infection?
They roll, adhere to the epithelial surface then undergo diapedesis to allow them to get to the site of infection
What is the standard response to a bacterial infection?
increased production of neutrophils from the bone marrow
stimulating factors; granulocyte colony stimulating factor
increase the number of circulating neutrophils
What is opsonisation?
bacteria coated with activated compliment component c3b
neutrophil has C3b receptor
encourages phagocytosis
What are the principle mechanisms of innate immunity against viruses?
inhibitions of infection of other cells by type 1 interferons and NK-cell mediated killing of infected cells
What are the the principle mechanisms of the adaptive immune response to viruses?
mediated by antibodies, which block virus binding and entry into host cells and by cytoxic T lymphocytes which eliminate the infection by killing infected cells
Describe the role of antibodies in the fight against viral infections
antibodies are only effective against visions - the extracellular virus
bind to virus capsids or envelope proteins to neutralise them by changing the receptor shape and prevent them from binding to and infecting other cells
can opsonise virus particles - phagocytic clearance
How do cytoxic T lymphocytes control viral infection?
kill cells
triggered by T cell recognition of infected cell expressing MHC viral peptide complex
perforin and granzyme molecules destroy infected cell
What are some viral evasion strategies?
disarm innate immunity regulate MHC molecules responsible for antigen presentation alter antigen presentation interfere with CTL and NK cells Go and hide
What is immunodeficiency?
a time when the immune response fails
what are primary immune deficiencies?
congenital, resulting from genetic defects, inherited, deficiency causing disease
What are secondary immune deficiencies?
acquired - result of other diseases or conditions - HIV, malnutrition, immunosupression
How are the genetics of most immunodeficiencies?
most are recessive
many are X-linked
how do primary immunodeficiencies usually present?
recurrent infection in young and allergy autoimmunity abnormal lymphocyte proliferation cancer
What different immune cells are involved in immunodeficiencies?
humoral defect (B cells and antibodies) combined humeral and cellular defences (t and b) defects in cell-mediated immunity (T) phagocytic dysfunction complement deficiency cytokines / receptors can be at fault
What do NSAIDs do?
inhibit the COX1 and COX2 pathways which stops the release of prostaglandins thereby reducing inflammation
What does aspirin do?
Irreversibly blocks COX pathways
permanently stops platelets from producing thromboxane
What does paracetamol do?
no significant anti-inflammatory effect
mild analgesic effect
antipyretic action
high doses severe hepatotoxitcity
what are common side effects of NSAIDs?
GI problems due to the inhibition of prostaglandins normally stimulated by COX1 which stimulates the mucosal cells to produce the mucosa of the stomach
What are some of the therapeutic uses of corticosteroids?
RA lupus asthma fibrosis interstitial lung disease sarcoidosis anaphylaxis rhinitis transplantation Chrohns ulcerative colivitis acute leukaemia psoriasis
What are some of the side effects of corticosteroids?
euphoria buffalo hump hypertension thinning of the skin thin arms, legs, muscle wasting poor wound healing easy bruising increased abdominal fat osteoporosis
What are biological agents?
Usually antibodies against specific targets
extremely expensive