Synovial joints and rheumatoid arthritis Flashcards
(Hand anatomy too)
What are the 8 carpal bones of the hand
scaphoid
lunate
triquetrum
pisiform
hamate
capitate
trapezoid
trapezium
so long to pinky, here comes the thumb
how many of each type of bone are in the hand
8 carpal bones
5 metacarpals
5 proximal phalanges
4 intermediate phalanges
5 distal phalanges
joints of the hand from proximal to distal
radiocarpal (wrist)
midcarpal
carpometacarpo
metacarpophalangeal
interphalangeal (proximal and distal)
the three grips
power grip, hook grip, precision handling grip
4 groups of muscles in the hand
thenar
hypothenar
lumbricals
interossei
3 divisions of thenar/hypothenar muscles
OAF
opponens (deep)
abductor (most lateral)
flexor (medial)
what does the term pollicis refer to
thumb
what does the term digiti minimi refer to
pinky finger
what does brevis mean
short
where do the lumbricals arise from
flexor digitorum profundus tendon
what are the two groups of interossei
palmar and dorsal
what does PAD stand for
palmar adduct
controlled by palmar interossei
what does DAB stand for
dorsal abduct
controlled by dorsal interossei
how many palmar interossei are there
3
how many dorsal interossei are there
4
what innervates the intrinsic muscles of the hand
the ulnar nerve (and median)
what are the boundaries of the cubital fossa
base = imaginary line between epicondyles
medial = pronator teres
lateral = brachioradialis
floor = brachialis and supinator
what does the cubital fossa contain
radial nerve
termination of brachial artery and accompanying veins
median nerve
tendon of biceps brachii
where are venipunctures placed
superficial veins which lie superficial to the cubital fossa
where is the carpal tunnel
between carpal bones and flexor retinaculum
what ten structures are contained in the carpal tunnel
4 flexor digitorum superficialis tendons
4 flexor profundus tendons
tendon of flexor pollicis longus
median nerve
what is the flexor retinaculum
strong connective tissue which runs between carpal bones at the top - turning carpal arch into tunnel
what structures do not pass through the carpal tunnel
ulnar nerve and ulnar artery, radial nerve and radial artery
function of retinaculum
prevents bow stringing (keeps tendon down in place) as tendons cross joints
where does the dorsal scapular nerve originate
C5 root
where does the phrenic nerve originate
C5 root
where does the suprascapular nerve originate
superior trunk of brachial plexus
C5, C6
where does the lateral pectoral nerve originate
lateral cord of brachial plexus
C5 - C7
where does the long thoracic nerve originate
C5, C6, C7 roots
where does the upper, mid and lower subscapular nerve originate
posterior cord
think that theyre on the back
where does the thoracodorsal nerve originate
posterior cord
where do the medial cutaneous nerves of the arm and forearm originate
medial cord
where does the medial pectoral nerve originate
medial cord
where does the lateral pectoral nerve originate
lateral cord
where does the musculocutaneous nerve innervate
anterior compartment of the arm
where does the axillary nerve innervate
“badge patch” upper posterior arm
where does the radial nerve innervate
lower posterior arm, posterior forearm, lower lateral anterior arm, lateral dorsal hand
where does the median nerve innervate
dorsal fingertips and lateral lumbricals and OAF of thenar (palmar lateral 3.5 digits)
where does the ulnar nerve innervate
palmar medial 1.5 digits, dorsal medial 1.5 digits
What is achondroplasia
A lack of cartilage growth
Autosomal dominant condition that affects endochondral ossification via cartilage. Caused by a mutation in fibroblast growth factor receptor 3.
What are the two cell types within the synovium
Type A - similar to macrophages, remove debris
Type B - similar to fibroblasts, produce extra matrix proteins in synovial fluid (hyaluronic acid, collagen, fibronectin)
What are limbs developed from
small buds of undifferentiated mesoderm cells, which are covered by ectoderm
when does limb morphogenesis take place
between weeks 4 and 8
where is mesenchyme derived from
dorsolateral mesoderm cells of the somites
what is the apical ectodermal ridge
ectoderm at the distal border which is thickened. the AER has an inductive relationship with the mesoderm. Secretes signals that tell the cells next to it not to differentiate? Also promotes mitosis.
What happens in limb development without the AER
limbs fail to develop as the AER is a key signalling centre
What corresponds to the border between the dorsal and ventral ectoderm
the AER
What happens in week 6 og limb development
Terminal portion of buds become flattened (handplates and footplates)
Parts of limb becomes separated from the proximal segments by constriction (wrist and elbow)
How does digit separation occur
Cell death in the AER separates ridges into 5 parts. Mesenchyme condense to form cartilaginous digits
By d56, digit separation = complete
What is developed from the stylopod
humerus and femur
What is developed from the zeugopod
radius/ulna and tibia/fibula
think Z looks like a 2, 2 bones in calf and 2 bones in forearm
What is developed from the autopod
carpels, metacarpals, digits, tarsals/metatarsals
what do HOX genes regulate
positioning of the limbs along the craniocaudal axis
what is polydactyly
extra digits - defect is mesoderm caused by mutation in Hox genes (Shh or Wnt)
when does limb rotation occur
week 7 of development (upper and lower limbs rotate in opposite directions)
where do the upper limbs rotate
90° laterally
extensor muscles lie on the lateral and posterior side
where do the lower limbs rotate
90° medially
extensor muscles lie on anterior surface
what happens in week 6 of bone development
cartilage models of bone form
what happens in week 8 of bone development
ossification begins
what happens in week 12 of bone development
primary centres of ossification in all long bones of limbs
Symptoms of carpal tunnel syndrome
Pain and altered sensation in a median nerve distribution
shaking hand relieves symptoms
can waken patients at night
worse when wrist is flexed
treatment for carpals tunnel
stopping habits
splints
steroid injection
carpal tunnel decompression
what is held in guyon’s canal syndrome
ulnar nerve and artery
symptoms of guyon’s canal
numbness and tingling in an ulna nerve distribution
pain
weakness
symptoms of cubital tunnel syndrome
reduced sensation in ulna nerve distribution in hand, altered sensation in dorsum of hand too
intrinsic muscle weakness and wasting (elbow)
what is tinel’s test
tapping over a nerve to test sensation
what is durkan’s test
pressure over a nerve to test sensation
what is phalens test
holding hands pointed downwards with backs towards each other, flexed at the wrist and seeing how long it takes for fingers to begin tingling
What does a swollen synovium contain
Fibroblasts
macrophages - activated to produce TNFa, IL-1, IL-6
T cells
B cells
what is the use of NSAIDs
used to relieve pain and swelling
no evidence of effect on erosions/progression
what do NSAIDS target
COX-1 and COX-2
this reduces prostaglandins and thromboxane
what are some contraindications of NSAIDs
active bleeding
acute kidney injury
drug interactions ?
what are the mechanisms of action of corticosteroids
Blocks phospholipase A2
decrease in monocytes and macrophages
decrease in T cells
increase in neutrophils
decrease in vessel permeability
decrease in proliferation of endothelial cells
what are some comorbidities of corticosteroids
diabetes, osteoporosis, immunosuppression
what are the three regimes of corticosteroids
oral - prednisolone
intramuscular - triamcinolone
intra-articular - depomedrone or kenalog
three options of DMARDs
conventional, biologic and targeted synthetic
4 most common DMARDs
methotrexate
sulfasalazine
hydroxychloroquine
leflunomide
describe the mechanism of methotrexate
Dihydrofolate reductase inhibitor
increases T cell apoptosis, allowing immune system to settle down
describe the mechanism of sulfasalazine
comprised of sulfapyridine and5-ASA
intact SSz may act like MTX as a folate antagonist, also ihibits TNF binding to membrane bound receptors. Individual components may decrease prostaglandin synthesis.
mechanism of leflunomide
reversible inhibits dihydroorotate dehydrogenase, reducing pyrimidine synthesis and thus exhibiting antiproliferative properties
think anti proLiferative
mechanism of hydroxychloroquine
action is unclear but it decreases prostaglandins, decreases TNFa and decreases IL-6
what is the prevalence of rheumatoid arthritis in the UK
around 1.5 men and 3.6 women developing RA per 10,000 people per year in the UK
Symptoms of RA
Painful joints, stiffness, swelling, affects small joints more than large joints, presents symmetrically, DIP joints not affected, persistent swelling (doesn’t settle)
Non-specific tests for RA
CRP/ESR - often elevated
FBC - anaemia common
Urate - can be falsely low during gout
Specific tests for RA
RhF
CCP
not diagnostic
What is Rheumatoid Factor
IgM antibody, directed against Fc portion of IgG Ab
Sensitivity around 70%
Specificity around 80-85%
%% of population without RA are positive
What is CCP Ab
Inflammation leads to cellular damage
Enzymatic process leads to the conversion of arginine residues to citrulline
Sensitivity 66%
Specificity 90%
positive test for anti-ccp ab normally means RA
First changes in X-Ray imaging for RA
Periarticular osteopenia
Joint space narrowing
Soft tissue swelling
Late changes in X-Ray imaging for RA
Erosions
Joint destruction
Subluxation
oral steroid side effects
Renal impairment, anti-coagulation, liver disease, heart failure, can be hard to get off steroids
4 theories of immune regulatory failure
Loss of central tolerance
loss of peripheral tolerance
molecular mimicry
Inappropriate activation
What does positive selection of the thymus ensure
T cells are functional and well equipped
What does negative selection of the thymus result in
contributes to self-tolerance
What is central regulation of the immune system
The thymus - positive and negative selection
Examples of peripheral regulation of the immune system
Regulatory B and T cells
dendritic cells
costimulation
ignorance and privilege
What causes Autoimmune lymphoproliferative syndrome
A result of a mutation in Fas - uncontrolled lymphocyte proliferation in the absence of infection
What is IPEX (immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome)
A defect in peripheral tolerance leading to dermatitis, diarrhoea and diabetes
What is the hygiene hypothesis
Exposure to microorganisms in early life will improve the immune system
Some autoimmune diseases are prevented by infections
Explain the pathogenesis of autoimmune diseases
Susceptibility genes ->
failure of self tolerance - >
persistence of functional self reactive lymphocytes - >
+Environmental trigger ->
activation of self-reactive lymphocytes ->
immune responses against self tissues
what are immune mediated inflammatory diseases
Chronic diseases with prominent inflammation, often caused by a failure of tolerance or regulation
May result from autoimmunity or microbial agents
May be caused by T cells and antibodies
May be systemic or organ-specific
Describe Grave’s disease
Targets the TSH receptor
Non regulated “activating” auto-antibodies that bind to the TSH receptor, leading to overstimulation of the thyroid hormones
Describe organ specific autoimmune disease
Autoimmune attack vs. self-antigens of given organ, resulting in damage of organ structure and function
Describe non-organ specific autoimmune disease
Widespread self-antigens are targets for autoimmune attack
Damage affects such structures as blood vessels, cell nuclei etc.
Examples of organ specific autoimmune diseases
Hashimoto thyroiditis, Multiple Sclerosis (CNS), Guillain Barre syndrome (PNS)
Examples of non-organs specific
Systemic Lupus (affects skin, kidney, CNS)
Rheumatoid arthritis (affects joints, lungs, vessels/vasculature)
What is a transient auto-immune disease
Transient - does not necessarily result in chronic autoimmunity
Describe Guillain-Barre syndrome
Example of molecular mimicry
Disease of the peripheral nerves
Triggered by infections including Campylobacter jejuni
common cause of acute paralysis
What are the three phases of RA
- Pre-articular or lymphoid phase
- Transition phase
- Articular phase
Loser Takes it All
(think hunger games edit)
Describe the pre-articular/lymphoid phase of RA
The presence of factors that may suggest RA but no clinical presentation yet
Autoimmunity
CCP-specific antibody
Rheumatoid factor
Collagen-specific response
GP39-specific response
Describe the transition phase of RA
Microbial insult?
Bio-mechanical events
Neurological events
Microvascular dysfunction
Describe the articular phase of RA
Articular localisation
cardiovascular disease
osteoporosis
functional decline
