week 9 Flashcards
what are innate defences and purpose
surface barriers internal defences eg phagocytes, inflammation, fever • Prevent foreign substances from entering the body • Immobilise and eliminate invaders
what are adaptive defences and purpose
humeral immunity (B cells)
cellular immunity (T cells)
T and B lymphocytes and
protein products
• Tolerant to “self” but react against “non-self”
• Target and destroy specific substances (“antigens”)
what do cytotoxic T cells do
target infected cells, but also affects cells around
what happens in an autoimmune disease
adaptive defences: attack normal body cells antigen cannot be cleared sustained response tissue and organ damage autoimmune disease
define systemic disease
affects multiple organs/system
define organ specific disease
affects one organ/tissue
mechanisms of autoimmune disease
combination of genetic and evironemtnal factors
whats genetic factors autoimmune disease
type of “self proteins” a person has (HLA proteins)
• Women (75% of patients)àrole for estrogen? • Ethnicity
whats environemental factors autoimmune disease
Chemicals
• Viral and bacterial infections (e.g. EBV, streptococcus)
how does breakdown of self tolerance occur
- failure to destroy self reactive T and B lymphocytes during development
- failure of regulatory T cells to control immune response
- antigen mimicry (foreign antigens resemble self antigens)
how does autoimmune disease cause tissue damage 3 ways
mmune complex mediated inflammation
cell mediated cytotxicity
antibody reactions
immune complex mediated inflammation tissue damage
immune complex mediated inflammation eg rheumatoid arthritis:
- autoantibodies are common marker of autoimmune disease eg rheumatoid factor.
- immune complexes go into the blood which attract phagocyte which realease digestive enzymes into extracellular space which leads to tissue damage
cell mediated cytotoxicity tissue damage
- Cytotoxic T cells lyse target cells, e.g. insulin-producing pancreatic b cells in Type I diabetes
- Phagocytesdamage/kill cells by releasing digestive TC cell
enzymes, e.g. rheumatoid arthritis, multiple sclerosis - T cells release enzymes that damage target cells membranes and degrade DNA
antibody reactions tissue damange
against cell surface antigens (act as agonists) eg graves disease
whats rheumatoid arthritis
systemic disease with prominent joint involvement. Immune-mediated chronic inflammationàjoint
destruction, i.e. autoimmune disease
• Inflammatory arthritis involving pain, swelling and stiffness of symmetrical joints
• Heart, lungs, skin, eyes, central nervous system may be affected/damaged by inflammatory reactions
whats idiopathic means
cause unknown
how are autoimmune disease treated
- relieve symptoms eg anti-inflammatory drugs (NSAID)
- replace vital substances the body can no longer make eg hormone replacement (insulin)
- suppress the immune system: control disease process and preserve organ function
- dietary manipulation eg no gluten in coeliac disease
what is JIA
- onset prior to 16 years old
- idiopathic
- arthritis
- immune mediated chronic inflammation (autoimmune disease)
- affects girls more than boys
genetic components of JIA
Markedly increased risk for close relatives
• Females > males
• Most common in Caucasians
• Emotionalissues/stressmayworsensymptoms
• Roleforsexhormones?
what area of immune system affected JIA
Elevated cytokine levels (TNF, IL-1, IL-6) and auto- reactive antibodies
• Distinct from adult RA, despite many similarities
JIA signs and symptoms
- joints pain and swelling (synovial inflammation, erosion of articular cartilage)
- joint stiffness, flexion contracture: leads to restricted movement and physical activity
- sleep disturbances, fatigue
- period of remission (symptom free) and flareups
the stages the pain cycle
- pain
- tense muscles
- stress
- sleep difficulty
- fear, anger, frsutration
- depression
- fatigue
three major factors that cause pain in JIA patients
inflammation
damage to joints
muscle tension
extra articular manifestations JIA
acute phase response
serositis
uveitis
growth failure
whats acute phase response
Low-gradefever,weakness,malaise,muscle and joint aches, increased BP, lack of appetite, anaemia
whats serositis
autoantibodies lead to rollin pathogenesis via immune complex mediated inflammation leads to damage to:
- pericardium= impaired function. pain
- lung pleura= impaired fonction, pain
- blood vessels= schema, necrosis in skin, heart and nerves
- nerve pain (tingling or burning in hands and feet
whats uveitis
inflammation of the urea membrane Easy to treat but hard to know if they have it
- long term uveitis = permanent eye damage, blindness
whats growth faliue
- overall rate of growth reduced
- uneven limb/joint growth
- low bone mineral density
three major types of JIA
oligoarticular
polyarticular
systemic
whats oligoartuclar JIA
- less than 5 joints
- medium-large joints affected eg knees, ankle
- asymmetric
- non destructive arthritis
- 20% uveitis
what is polyarticular JIA
- more than 5 joints affected
- usually smaller joints
- symmetric
- destructive arthritis
- usually RF positive
what is systemic JIA
- more than one joint
- any join
- symetric
- destructive arthrisic
- daily fever, rash
what is enthesitis associated JIA
- typically knee, ankle
- ethestis: inflation of tendons at muscle insertion ponts
- increase risk of unites
- more communion males
whats psoriatic JIA
- any joint small and large
- increase risk of uveitis
- nail pitting and loss
whats undifferentiated JIA
does not fit into any category or fit into 2 or more categories
diagnosis of JIA
usually by exclusion of other paediatric disorders
• Involving blood tests, imaging studies, clinical presentation
three goals for treatment of JIA
Control pain and prevent joint damage
• Maintain normal growth, joint function and muscle strength
• Control systemic complications
pharmacological treatment of JIA
non steroidal anti-inflammatory drugs (NSAID): eg nurophen, aspirin. (1ST LINE)
- reduce joint pain and swelling but DOES NOT prevent joint destruction or inhibit disease progression
corticosteroids: reduce pain, inflammation and can prevent joint inflammation. (1st LINE)
- short term treatment only
disease modifying antirhumatic drugs (DMARDS): (2ND LINE)
- long term use
- imunosupressent, reduces inflammation, progressive joint destruction
Biologics (when 1st and 2 nd line fail)
- immune suppressants
side affects of corticserotied treatment
immunosupression= increased risk of infetion
grwoth retardation
decreased bone mineral density
weight gain
non pharmacological treamtoer
- exercises, stretching and strengthening
- restnng and functional splints
PAIN MANAGMENT: - breathing and relaxation techniques
- massage
- heat cold application
NUTRITION: - vitamin D and calcium supplements (bones)
- Omega 3 (may help reduce inflammation/pain)
SURGERY
three types of surgery
Osteotomy – removing or inserting a wedge of bone to allow more normal joint alignment
• Epiphysiodesis – removal/impairment of the growth plate to stop bone growth
• Joint replacement – not usually done until growth has stopped
prognosis for JIA
Oligoarticular 50% at 10 y post-diagnosis Polyarticular (RF-) 25% at 10 y Polyarticular (RF+) <10% at 10 y Systemic 10% if single episode (90% will have relapsing or chronic disease) Poor prognosis associated with: • Early hip or wrist involvement • Symmetrical disease, rheumatoid factor (i.e. like adult RA) • Persistent inflammation (> 5-10 years) and/or prolonged systemic disease
side effects of non steroidal antjnflamtory drugs (NSAID)
Generally well tolerated in children
• < 1% experience mild nauseaàloss of appetite, but minimised by taking with meals
• Bruising more common
side effects of disease modifying antirhumatic drugs
mmunosuppressantàincreased risk of infection
• Generally well tolerated in children but …
• ~10% experience nausea and abdominal discomfort
• ~ 3% liver damageàregular blood tests (no alcohol)
• Teratogenàbirth defects
side effects of biologics
Increased frequency and severity of infections e.g. UTI, pneumonia, tuberculosis, fungal infections
• Patients cannot have any live vaccines, e.g. polio, chicken pox, MMR
causes of fatigue in JIA
disease activity
pain (affects sleep)
muscle weakness/ wasting
depression
why is exercise good for JIA
Improve mobility and flexibility of joints, muscle strength, posture and balance
Decrease pain, fatigue (tiredness), muscle tension and stress
should clients exercise a painful or inflamed joint
No. You should stop exercising if it is causing you unusual pain or increases your pain beyond what is normal for you. Exercising through this type of pain may lead to injury or worsening of your arthritis symptoms.
