MSK Flashcards
1
Q
Largest type of tissue in human body?
A
Muscle
2
Q
Striated muscles? (2)
A
Skeletal + cardiac
3
Q
What causes striations?
A
Myosin + actin
- Myosin = dark thick filaments
- Actin = light thin filaments
4
Q
Skeletal muscle innervation? Cardiac muscle? Smooth muscle?
A
- Skeletal muscle = somatic NS
* cardiac + smooth = ANS
5
Q
Differences between skeletal and cardiac muscle? (4)
A
Skeletal muscle
- Neurogenic initiation of contraction
- Neuromuscular junction
- No gap junction
- Ca++ entirely from SR
Cardiac
- Myogenic (pacemaker) initiation of contraction
- No neuromuscular junction
- Gap junctions
- Ca++ from ECF and SR (CICR)
6
Q
What is the neurotransmitter at neuromuscular junction?
A
Acetylcholine
7
Q
Skeletal muscle fibres organised into? What is this?
A
Motor units
* Motor unit = single alpha motor neuron + skeletal muscle fibres it innervates
8
Q
Number of muscle fibres per motor unit?
A
- Muscles which serve fine movements (e.g. external eye muscles, facial expression, hand) have fewer fibres per motor unit
- In muscles where power is more important than precision = more muscle fibres
9
Q
Levels of organisation in skeletal muscle?
A
- Whole muscle -> muscle fibre (= one muscle cell) -> myofibril -> sarcomere (functional unit)
Myofibril and sarcomeres made up of myocin and actin
10
Q
How are skeletal muscles attached to skeleton?
A
Tendons
11
Q
Functional units of muscle?
A
Sacromeres
12
Q
Zones of the sarcomere? (4)
A
- A-band = thick filaments along with portions of thin filaments that overlap in both ends of thick filaments
- H-Zone = lighter area within middle of A-band where thin filaments don’t reach
- M-Line = extends vertically down middle of A-band within the centre of H-zone
- I-Band = consists of remaining portion of thin filaments that do not project in A-band
13
Q
What is the definition of a functional unit?
A
the smallest component capable of performing all the functions of that organ
14
Q
Where is sacromere found?
A
Between 2 z-lines
15
Q
Muscle tension?
A
Produced by sliding of actin filaments on myocin filaments
16
Q
Force generation depends on?
A
ATP-dependent interaction between myosin + actin
17
Q
ATP only required for muscle contraction? Ca++?
A
ATP is required for both contraction & relaxation
* Ca++ is required to switch on cross bridge formation
18
Q
Excitation contraction coupling?
A
process where surface action potential results in activation of the contractile structures of the muscle fibre
19
Q
When is Ca++ released in skeletal muscle fibres? What are T-tubules?
A
In skeletal muscle fibres Ca2+ is released from the lateral sacs of the sarcoplasmic reticulum when the surface action potential spreads down the transverse (T)-tubules
* T-tubules are extensions of the surface membrane that dip into the muscle fibre
20
Q
Explain process of muscle contraction + relaxation
A
- Acetylcholine released by motor neurone and binds to receptors
- Action potential generated and travels down transverse T-tubules
- AP in T-tubules triggers Ca++ release from SR
- Ca++ binds to troponin-tropomyosin to reveal cross-bridge binding site
- Cross bridge formed between myosin and actin
- Ca++ actively taken up by SR when AP dissipates
- When Ca++ no longer bound to troponin/tropomyosin, binding site is blocked again and myosin detaches from actin
21
Q
Motor units? Motor unit recruitment? How can muscle fatigue be prevented?
A
- Motor units = allow simultaneous contraction of muscle fibres
- Motor unit recruitment = stronger contraction achieved by stimulation of more motor units
- Muscle fatigue can be prevented via asynchronus motor unit recruitment during submaximal contractions
22
Q
What does tension developed by each contracting muscle fibre depend on?
A
- frequency of stimulation
- length of muscle fibre
- thickness of muscle fibre
23
Q
How are stronger contractions in skeletal muscle brought about?
A
If restimulate muscle fibre before it has relaxed, 2nd twitch added on to first twitch resulting in summation
24
Q
Tetanus contraction? Can this phenomenon occur in cardiac muscle?
A
Muscle fibre stimulated so rapidly that it does not relax at all between stimuli resulting in MAXIMAL SUSTAINED CONTRACTION
- NO, as long refractory period prevents generation of tetanic contractions
25
What is the approximate optimal length of skeletal muscle?
In the body the resting length of skeletal muscle is approximately its optimal length (not the same for cardiac muscle)
26
Contractile component of skeletal muscle? Elastic component skeletal muscle?
* Contractile = sarcomeres
| * Elastic = tendon/connective tissue
27
2 types of skeletal muscle contraction?
* Isotonic contraction: used for (1) body movements and for (2) moving objects. Muscle tension remains constant as the muscle length CHANGES
* Isometric contraction: used for (1) supporting objects in fixed positions and for (2) maintaining body posture. Muscle tension develops at CONSTANT muscle length
28
Differences between different types of skeletal muscle fibres? (3)
* enzymatic pathways for ATP synthesis
* resistance to fatigue - muscle fibres with greater capacity to synthesise ATP are more resistant to fatigue
* activity of myosin ATPase - determines speed at which energy is made available for cross bridge cycling i.e. the speed of contraction
29
ATP production in skeletal muscle? (3)
* Oxidative phosphorylation (main source when O2 present)
* Transfer of high energy phosphate from creatine Phosphate to ADP
* Glycolysis (main source when O2 is not present)
30
3 types of skeletal muscle fibre?
* Slow oxidative type I fibres (also known as slow-twitch fibres) - prolonged, low work aerobic activities e.g. maintenance of posture, walking
* Fast oxidative (Type IIa) fibres (also known as intermediate-twitch fibres) - both aerobic and anaerobic metabolism, prolonged moderate work activities e.g. jogging
* Fast glycolytic (Type IIx) fibres (also known as fast-twitch fibers) - anaerobic metabolism, short-term high intensity activities e.g. jumping
31
Reflex action?
stereotyped response to a specific stimulus - simplest form of coordinated movement
32
Stretch reflex?
simplest monosynaptic spinal reflex
33
What kind of mechanism is stretch reflex?
Stretch reflex is negative feedback that resists passive change in muscle length to maintain optimal resting length of muscle
34
Why is stretch reflex important?
helps maintain posture e.g. while walking
35
Receptor for stretch reflex? Process?
sensory receptor is the muscle spindle and is activated by muscle stretch
* stretching muscle spindle increases firing in afferent neurons
* afferent neurons synapse in the spinal cord with the alpha motor neurons (efferents) that innervate the stretched muscle
* Contraction of stretched muscle
36
What is required for stretch reflex other than contraction of affected muscle?
Relaxation of antagonist muscle
37
Spinal segment and peripheral nerve involved in knee jerk reflex? Ankle jerk? Biceps jerk? Brachioradialis? Triceps jerk?
* Knee jerk (L3, L4) - femoral nerve
* Ankle jerk (S1, S2) - tibial nerve
* Biceps jerk (C5, C6) - musculocutaneous nerve
* Brachioradials (C5, C6) - radial nerve
* Triceps jerk (C6, C7) - radial nerve
38
What are muscle spindles? Other name? Ordinary muscle fibres?
* Collection of specialised muscle fibres
* Intrafusal fibres
* Ordinary = extrafusal fibres
39
Where are muscle spindles found? Features?
Found in belly of muscles and run parallel to extrafusal muscle fibres
* Have sensory nerve endings called annulospiral fibres
40
Efferent supply to muscle spindles? Function?
Gamma motor neurons
* y neurons adjust level of tension in muscle spindles to maintain their sensitivity when muscle contracts
Intrafusal fibres DO NOT contribute to overall strength of contraction!!!
41
Causes of intrinsic muscle disease? (5)
* Genetic e.g. muscular dystrophy, myotonia, congenital
* Inflammatory e.g. polymyositis
* Non-inflammatory e.g. fibromyalgia
* Endocrine e.g. cushing
* Toxic e.g. alcohol
42
Ix neuromuscular disease? (5)
* Electromyography (muscular activity via APs)
* nerve conduction studies
* muscle enzymes
* inflammatory markers
* muscle biopsy
43
Features of skeletal muscle fibres? (3)
* Striated
* Unbranched
* Multinucleate (nuclei are at periphery of fibre)
44
Muscle fibre arrangement? Connective tissue supporting skeletal muscle tissue?
* Muscle fibres grouped into bundles called fascicles (muscle contains several fascicles)
* connective tissue that surrounds the muscle as a whole is called the epimysium
* connective tissue around a single fascicle is the perimysium
* connetive tissue around a single muscle fibre is the endomysium
45
What do thousands of sarcomeres placed end-to-end form? How far does a single sarcomere extend?
A myofibril
| * sarcomere extends from one Z line to the next
46
Why are skeletal muscles striated?
Striations are an optical illusion – myofibril dark and light bands held in registry
47
3 types of skeletal muscle fibres?
* Type I ("RED" fibres): slow contracting fibres that depend on oxidative metabolism -abundant mitochondria and myoglobin, resistant to fatigue and produce less force.
* Type IIA: intermediate - relatively fast contracting, but are also reasonably resistant to fatigue
* Type IIB (WHITE fibres): fast contracting fibres that depend on anaerobic metabolism - few mitochondria and myoglobin, fatigue easily and produce greater force
48
Features of cartilage? (4)
* Semi-rigid and Deformable
* Permeable
* Avascular
* Cells nourished by diffusion through the extracellular matrix
49
Features of bone? (3)
* Rigid
* Not Permeable
* Cells within bone must be nourished by blood vessels that pass thru the tissue
50
Cells found in cartilage? Organisation?
chondrocytes (chondroblasts when immature)
| * Chondrocytes held within extracellular matrix called lacuna
51
Hyaline ECM composed of?
1) 75% water
2) 25% organic material.
* 60% Type II collagen. Type II collagen differs from type I collagen (e.g. tendon) - it is finer and instead of aggregating into linear bundles it forms a 3D meshwork
* 40% proteoglycan aggregates. Proteoglycan aggregates are made up of GAGs (keratan sulfate and chondroitin sulfate) bound to a core protein and hyaluronan
52
Types of cartilage? (3)
* Hyaline cartilage (blue) - most common form of cartilage
* Elastic cartilage (yellow): very flexible
* Fibrocartilage (white): hybrid between tendon and hyaline cartilage i.e. bands of type I collagen + rows of chondrocytes surrounded by ECM
53
Sites of hyaline cartilage? (5)
* Articular surfaces
* Tracheal rings
* Costal cartilage
* Epiphyseal growth plates
* Precursor in fetus to many bones
54
Functions of bone?
* Support
* Levers for movement
* Protection of internal organs
* Calcium store: >95% calcium found in bone + constant exchange of calcium between bone and blood
* Haemopoiesis: only the axial and limb girdle skeleton is involved in blood production
55
Composition of bone? (4)
* 65% bioapatite (form of calcium phosphate - mostly hydroxyapatite)
* 23% collagen
* 10% water
* 2% non-collaged proteins
56
Structure of bone? (2)
* outer shell of dense cortical bone makes up the shaft (diaphysis)
* Cancellous/trabecular bone at ends of bone (epiphyses)
57
How do blood vessels travel through bone?
* Haversian canal + volkman's canal
58
Difference in structure of trabecular and cortical bone?
* bone cells and matrix are similar in compact and trabecular bone
* main difference is the presence of spaces (marrow cavities) adjacent to trabecular bone
BOTH TYPEs aRE LAMELLAR!!! (made up of layers)
59
Cement lines?
lines that are visible surrounding the osteon
60
What does trabecular bone often lack? Why?
lacks Haversian canals
| * the struts are thin so the osteocytes can survive from contact with the marrow spaces
61
Bone cells? (4)
* Osteoprogenitor cells: reserve cells that can differentiate into osteoblasts
* Osteoblasts: bone forming cells (lots of RER and mitochondria)
* Osteocytes: bone cell trapped within bone matrix
* Osteoclasts: large multinucleated cells - bone resorption
62
Process of bone remodelling?
CUTTING CONE
* osteoclasts ‘drill’ into the bone forming a tunnel
* a blood vessel will grow into the tunnel bringing osteoblasts which line the tunnel and begin laying down new lamellar bone
* This process continues until only the space of a Haversian canal remains
63
What is the collection of osteoclasts and osteoblasts that participate in bone remodelling called?
basic multicellular unit or BMU
64
How do osteoblasts produce bone?
Secrete OSTEOID: collagen, glycosaminoglycans (GAGs), proteoglycans
* this then becomes mineralized over time
65
What is the mineral of bone made up of?
calcium phosphate crystals, particularly hydroxyapatite
66
Osteoclast origin and morphology?
* Derived from macrophage line of cells
| * Several will fuse to form a single giant cell
67
Differences between lamellar and woven bone?
During development or following a break, rather than having collagen fibres orientated all in one direction like lamellar bone, the collagen fibres are laid down in a haphazard fashion - WOVEN BONE
68
Adult osteomyolitis?
Inflammation of bone and medullary cavity, usually in long bones
69
Places where osteomyolitis is most common?
* Vertebral osteomyolitis
* Diabetic foot infection
* Post-traumatic infection
* Prosthetic joint infection
70
Most common pathogen in osteomyolitis?
staph aureus
71
Dx osteomyolitis?
GOLD STANDARD is bone biopsy!
| Via percutaneous sample or deep surgical culture
72
Tx osteomyolitis?
Tx: debridement + antibiotics
| Not an emergency, wait for culture results before beginning treatment
73
Risk factors for osteomyolitis? (6)
* Open fractures
* Diabetes/ Vascular insufficiency
* Haematogeneous osteomyelitis
* Vertebral osteomyelitis
* Prosthetic joint infection
* Specific hosts and pathogens
74
s/s osteomyolitis?
Rubor, tumor, dolor, functio laesa
75
How does infection occur in bone?
Bone is highly resistant to infection – infection only occurs with necrosis + high inoculum
76
How long does osteomyolitis tx take?
6 weeks
77
Open fractures? Tx? Clinical clues of osteomyolitis with open fracture? Pathogens?
* Contiguous infection
* Tx: debridement, fixation + soft tissue cover
* Clinical clues = non-union + poor wound healing
* Ax: staph aureus + aerobic gram -ve bacteria
78
Diabetes/venous insufficiency? Dx? Tx?
* Contiguous infection that is often polymicrobial
* Dx: Bone biopsy
* Tx: debridement and antimicrobials
79
Mild diabetic foot ulcer tx?
Moderate? Severe?
How about patients with penicillin allergy?
MRSA?
* Mild: Fluclox
* Mod: fluclox + metronidazole
* Severe: fluclox, gentamicin + metronidazole
Penicillin allergy
* Mild = doxycycline/co-trimoxazole
* Mod = doxycycline + metronidazole OR co-trimoxazole + metronidazole
* Severe = vancomicin, gentamicin + metronidazole
80
Tx acute osteomyolitis (i.e. when cannot wait for culture)? What about for patients with penicillin allergy?
Fluclox + gram -ve and anaerobic cover
| * allergy = sub fluclox for vanco
81
Mild MRSA tx? Mod? Severe?
* Mild = Doxycycline or co-trimoxazole
* Mod = vancomycin
* Severe = vancomycin + gram -ve cover
82
Duration of tx for mild diabetic foot sepsis? Mod? Severe?
| Osteomyolitis?
* mild = 7 days
* mod = 7 days
* severe = 7-10 days (14 days if s.aureus bacteraemia)
* osteomyolitis = 6 weeks
83
Is vancomycin given orally?
NEVER switch a person from IV vancomycin to ORAL vancomycin (unless topical treatment for c.diff) as it is NOT absorbed systemically
84
Why is oral doxycycline normally given as oral switch from fluclox?
fluclox = big pill 4 x a day
85
Likely colonisers in culture i.e. not causative organism?
Pseudomonas, klebsiella, epidermidis
86
Epidemiology haematogenous osteomyolitis? (5)
* Prepubertal children
* PWID
* Central lines
* dialysis
* elderly
87
Organisms involved in PWID haematogenous osteomyolitis? (2)
* Strep + staph
| * unusual pathogens = pseudomonas, candida, eikenella corrodens (needle lickers), mycobacterium
88
Organisms involved in dilaysis patients with haematogenous osteomyolitis? (2)
* Staph aureus (most common)
| * aerobic gram -ve's
89
Most common site for haematogenous osteomyolitis?
| Unusual sites to be aware of?
* most common = femur
| * Unusual sites = osteitis pubis + clavicle
90
Unusual patients that are prone to haematogenous osteomyolitis?
* Sickle cell
* Gaucher's disease
* SAPHO and CRMO
91
Pathogens involved in sickle cell osteomyolitis? Where does it commonly affect?
* Salmonella + staph aureus
| * Long bones
92
Gaucher's disease? Most commonly affects? Pathogens involved?
* Lysosomal storage disorder (can mimic bone crisis)
* Often affects tibia
* Staph aureus
93
S/s SAPHO (adults) + CRMO (kids)? (3) Most common sites? Dx?
* Fever, weight loss, malaise
* Chest wall, pelvis + spine
* Dx = lytic lesions seen on x-ray + raised inflammatory markers
94
Vertebral osteomyolitis? Most common pathogen?
Vertebral osteomyolitis = spondylodiscitis (disc space infection)
* staph aureus
95
Risk factors vertebral osteomyolitis? (6)
Mostly haematogenous
* Epidural abscess/psoas abscess
* PWID
* IV infection
* GU infection
* Skin infection
* post-operative
96
s/s vertebral osteomyolitis? (5)
| Dx? (2)
* <50% have fever, <50% have raised WCC, insidious pain, neurological signs, infammatory markers
* Dx: Can have someone with vertebral osteomyolitis who has no fever, normal WCC – so MRI important!! Also biopsy
97
Biopsy for vertebral osteomyolitis? Why is biopsy carried out?
* First biopsy = 40% yield
* Second biopsy = 80% sensitivity
Important as empiric antibiotics should be avoided
98
Tx vertebral osteo? (2)
| When is MRI repeated in vertebral osteo? (3)
* Drainage of large psoas/epidural abscesses
* Antimicrobials for 6 weeks minimum
MRI repeated only if
* Unexplained increase in inflammatory markers
* Increasing pain
* New signs/ symptoms
99
Vertebral TB also known as? S/s? Why does epidemiology matter?
= Pott's disease
* often NO systemic symptoms i.e. no cough
Epidemiology MATTERS
* In kids, check reduced receptors for IFN-gamma, IL 12
* In adults over HIV test
100
Risk factors for prosthetic joint infection? (4)
| What is a common indication of infection in prosthetic joints?
* Rheumatoid arthritis
* Diabetes
* Malnutrition
* Obesity
Dehiscing of wound
101
Difference between planktonic and sessile bacteria? Pathogens in prosthetic joint infection? (6)
```
Planktonic = bacteraemia
Sessile = biofilm
* Staph aureus, epidermidis, propionibacterium (rarely strep + entero)
* Gram -ve i.e. E.coli
* Fungi
* Mycobacterium
```
102
Tx PVL-producing staph aureus?(3)
Fluclox, clindamycin, linezolid etc
103
Dx prosthetic joint infections? (4)
* Culture - tissue sample
* Blood culture
* CRP
* Radiology
104
Prosthetic joint infection tx? (3)
* removal of prosthesis and cement
* antibiotics at least 6 weeks
* re-implantation of joint after aggressive antibiotic therapy
105
Tx staph epidermidis in prostehtic joint infection?
Vancomycin
106
Septic arthritis?
| Ax septic arthritis? (4)
Inflammation of the joint space caused by infection
* Wound
* Haematogenous
* Spread from osteomyolitis in adjacent bone
* Infection in adjacent soft tissues i.e. cellulitis
107
Bacteria involved in septic arthritis? (5)
* Staph aureus
* Strep
* Coag neg staph - if prosthetic joints
* Neisseria gonorrheae - if sexually active
* Haemophilus influenzae - in young children
108
s/s septic arthritis? Dx?
```
* Severe pain, red, hot, swollen, pus, limited movement
Dx:
* Culture joint fluid
* Blood culture if fever
* exclude crystals (microscopy)
```
109
Septic arthritis tx?
* Presumptive tx to cover staph aureus = fluclox
* If <5 y/o add ceftriaxone for H.influenzae
(adjust when organisms confirmed)
110
Viral arthritis?
* Hep B, alphavirus, rubella, parvovirus
111
Pyomyositis? Ax? (3)
Muscle inflamamtion caused by infection
* Staph aureus!! most common
* Immunosuppressed = psuedomonas, strep, enterococcus
* Clostridial infection contaminated wounds
112
Tetanus? Pathogen?
Toxin-mediated illness caused by clostridium tetani
| * Gram +ve strictly anaerobic rods = produce SPORES that live in soil etc
113
s/s tetanus? Incubation peroid?
Neurotoxin causes spastic paralysis, lock jaw, sadonic smile
| * 4 days - weeks
114
Tx tetanus? (5)
* Surgical debridement
* Anti-toxin
* Supportive measures.
* Penicillin/Metronidazole
* Booster vaccination
115
Ix fresh tissue lesions?
* Cytogenetic studies - karyotyping, FISH
| * Molecular genetic studies
116
Karyotype? Advantages and disadvantages?
Karyotype = culture cells then arrest during cell division
* adv = overview of chromosome structure
* dis = will NOT detect small lesions, issue with quality of cells
117
FISH use?
Useful for known translocations
118
Immunohistochemistry process?
place pigment on antibody with specific target protein - any pigment staining means the protein is present
119
Benign connective tissue lesions? (5)
* common = ganglion cyst, giant cell tumour, fibromatosis
| * rare = fibrous cortical defect, fibrous dysplasia
120
Ganglion cyst? Common site?
| Histo?
Not a true cyst (no epithelial lining), causes degenerative change within connective tissue
* Common site = wrist (found near joint capsule or tendon)
* Histo = space with myxoid (mucous) material, inflammatory changes
121
Superficial fibromatoses e.g.? (4)
* Dupuytren's
* Knuckle pads
* Plantar
* Penile - peyronie's
122
Dupuytren's epidemiology? Ax?
* Older males
| * Idiopathic but associated with alcohol
123
Deep fibromatosis? E.g? Ax?
Different than superifcial fibromatosis
* Mesenteric or pelvic DESMOID tumours
* Associated with Gardner's syndrome (FAP)
124
Giant cell tumour e.g.? (3)
* Pigmented villonodular synovitis – large joints
* Giant cell tumour of tendon sheath – digits
* Giant cell tumour of bone
125
Tx giant cell lesions? (2)
* GC tendon sheath = small nodules that are easily excised (rarely recur)
* PVNS - more destructive and diffuse, more difficult to excise and often recur
126
Angiolipoma? s/s?
* Vascular lipomas
| * Unlike other lipomas they are painful, usually multiple and peripheral
127
benign mesenteric tumours? (5)
ANGEL
* Angiolipoma
* Neuroma (pinched nerve)
* Glomus tumour (nail beds)
* Eccrine spiradenoma (skin adnexal tumour)
* cutaneous leiomyoma (of erector pilae)
128
Leiomyomas?
Smooth muscle tumours (v common)
| * Leiomyosarcomas are uncommon however
129
Rhabdomyomas? Epidemiology?
Skeletal muscle tumours = very rare
| * Cardiac is limited to paediatric age group
130
Types rhabdomyosarcoma? (3)
* Embryonal = childhood (deletion Xp11.15)
* Alveolar = young adults (PAX translocation t2:5)
* Pleomorphic (rarest) = young adults (IHC = positive MYOD1 and myogenin)
131
Cartilage lesions? E.g.?
Benign lesions are common
* Enchondroma - digits
* Chondromyxoid fibroma
132
Benign bone lesions? (3)
* Simple osteoma – cranial bones
* Multiple – Gardner’s syndrome
* Osteoid osteoma and osteoblastoma
133
Osteosarcoma epidemiology? Dx? (2)
* Usually children = long bones
* Radiology = CODMAN'S TRIANGLE
* Any malignant tumour that produces osteoid is an osteosarcoma until proven otherwise
134
Ewing's sarcoma epidemiology? Location? Features? (3)
CHildren + adolescents
* Often long bones but can appear in any bony location
* Destructive, rapidly growing + highly malignant!!
135
Ax Ewing's sarcoma? Histo appearance?
* Genetic abnormalities = t(11;22)(EWs-FLI1)
| * Small round blue cell tumours
136
Nodular fasciitis? Features? (3)
Pseudosarcoma
| * Any age group, rapid growth, small
137
Nodular fasciits histo features? (5)
Hard to differentiate from sarcoma
* Chaotic appearance
* Pseudocytic spaces
* Large atypical cells
* Frequent mitoses
* Haemorrhage
138
Myositis ossificans?Location?
Abnormal bone growth caused by trauma
| * Big muscles - e.g. gluteus, quadriceps
139
Ewing's sarcoma?
A malignant tumour of endothelial cells in the marrow. Most cases occur between the ages of 10 and 20. It may be associated with fever, raised inflammatory markers and a warm swelling and may be misdiagnosed as osteomyelitis
140
Types of joint? (3)
* Synovial - bones separated by cavity containing synovial fluid + unites by fibrous capsule
* Fibrous - doesn't allow any movement e.g. skull
* Cartilaginous - allow limited movement e.g. intervertebral discs, pubic symphysis, costochondral joints
141
Explain structure of synovial joint (3)
* inner aspect of fibrous capsule is lined with synovial membrane
* synovial membrane is vascular connective tissue with capillary networks and lymphatics
* synovial membrane contains synovial cells (fibroblasts) which produce synovial fluid
142
Types of synovial joint? (2)
* Simple = one pair of articular surfaces e.g. metacarpopharyngeal joint
* Compound = more than one pair e.g. elbow joint
143
What extra-articular surfaces support joints? (3)
* Ligament
* Bursa
* Tendon
144
Role of joints during purposeful motion?
* Stress distribution
* Stability (shape of articular surface, ligaments and synovial fluid contribute)
* Joint lubication = cartilage interstitial fluid, synovium, synovium-derived lubricin
145
What is synovium derived from?
Hyaluronic acid (mucin)
146
Functions of synovial fluid? (5)
* Lubricates Joint
* Facilitates joint movement - reduces friction
* minimises wear-and-tear of joints via lubrication
* Aids in nutrition of articular cartilage
* Supplies chondrocytes (cartilage cells) with O2 and nutrients and removes CO2 and waste products
147
Is synovial fluid a static pool?
NO, it is continuously replenished and absorbed by the synovial membrane
148
What gives synovial fluid a high viscosity?
hyaluronic acid (mucin) produced by the synovial cells (viscosity varies with joint movement however)
149
Other than hyaluronic acid, what else synovial fluid contain? (2)
* Uric acid - derived by dialysis of blood plasma
| * Mononuclear leucocytes
150
How does viscosity and elasticity of synovial fluid change during joint movement? When does this become defective?
Rapid movement is associated with decreased viscosity and increased elasticity
* These properties of synovial fluid become defective in a diseased joint e.g. in osteoarthritis
151
Normal colour of synovial fluid? When does it turn red?
* Colourless
| * Red = traumatic synovial tap + haemorrhagic arthritis
152
Normal WBCC of synovial fluid? When does WBC count increase?
* Normal = <200 WBC/mm3, neutrophils <25/mm3
| * Increases in inflammatory and septic arthritis
153
Viscosity, colour, clarity, WCC, and neutrophil count of normal synovial fluid? Inflammatory synovial fluid? Septic synovial fluid?
* Normal = high viscosity, colourless, transparent, <200 WBC, <25 neutrophil
* Inflammatory = low viscosity, straw to yellow, translucent, 2000 - 75,000 WBC, >50 neutrophil
* Septic = variable viscosity, variable colour, opaque, >100,000 WBC, >75 neutrophil
154
Articular cartilage usually?
| ECM made up of?
Hyaline
| * ECM = water (70%), type II collagen (20%), proteoglycans (10%)
155
Function of water in cartilage? Collagen? What happens to % of water and collagen as we age?
* Water = maintains resiliency of tissue, nutrition + lubrication
* Collagen = cartilage architecture + tensile stiffness and strength
* Both collagen and water decrease with age
156
Highest concentration of proteoglycans found? Composed of? Function?
What happens to proteoglycans as we age?
* Highest conc = middle and deep zone
* Composed of glycosaminoglycan e.g. chondroitin sulphate
* Function = load-bearing
* Decreases as we age
157
ECM total cartilage volume?
| What is responsible for the synthesis, organisation, and degradation of ECM?
* ECM = >98% total cartilage volume
| * CHONDROCYTES
158
How does cartilage receive nutrients if it is avascular?
| What is the rate of ECM degradation in normal joints?
* Chondrocytes receive nutrients via SYNOVIAL FLUID
| * In normal joints, the rate of ECM degradation doesn’t exceed the rate at which it is replaced
159
How do chondrocytes degrade ECM?
Metalloproteinase proteolytic enzymes e.g. collagenase and stromelysin
160
Catabolic and anabolic factors of ECM turnover?
Catabolic
* Stimulate proteolytic enzymes + inhibit proteoglycan synthesis via TNF-a and IL-1
Anabolic
* Stimulate proteoglycan synthesis and block effects of IL-1 via tumour growth factor-B and insulin-like growth factor-1
161
Markers of cartilage degradation?
* Serum and synovial keratin sulphate - increased levels indicate cartilage breakdown (level increases with age and patients with osteoarthritis)
* Type II collagen in synovial fluid - increased levels indicate cartilage breakdown, useful in evaluating cartilage erosion e.g. in osteoarthritis and rheumatoid arthritis!!
162
Problems with joint? (4)
* Cartilage and synovial function deteriorate with age and wear and tear causing OSTEOARTHRITIS
* Synovial cell proliferation and inflammation cause rheumatoid arthritis
* Deposition of salt crystals e.g. uric acid can cause gouty arthritis
* Injury and inflammation to periarticular structures causes soft tissue rheumatism e.g. injury to the tendon causes tendonitis
163
Features of osteoarthritic joint? (6)
* Thickened capsule
* Cyst
* Sclerosis in subchondral bone
* Fibrillated cartilage
* Synovial hypertrophy
* Osteophyte formation
164
Processes in the physiology of pain?
* Transduction: translation of noxious stimulus into electrical activity at the peripheral nociceptor
* Transmission: propagation of pain signal as nerve impulses
* Modulation: modification/hindering of pain transmission in the nervous system e.g. by inhibitory neurotransmitters like endogenous opioids
* Perception: Conscious experience of pain (physiological and behavioural responses)
165
Wha are nociceptors? What kind of neurones are they?
* Nociceptors are specific primary sensory afferent neurones normally activated by intense noxious stimuli (e.g. mechanical, thermal or chemical)
* first order neurones that relay information to second order neurones in the CNS
166
Nociceptive pathway?
* Activated by noxious stimuli
* Synapses with second order neurone in dorsal root ganglion
* Second order neurones ascend in spinal cord in anterolateral system to the thalamus
* Spinothalamic tract = involved in pain perception (location, intensity)
* Spinoreticular tract = involved in autonomic responses to pain
* From thalamus, third order neurones carry impulse to primary sensory cortex
167
What neurotransmitters are delivered across synapse by nociceptors?
Substance P + neurokinin A
168
Subtypes of nociceptors? (2)
* a-delta fibres (thinly myelinated) = respond to noxious mechanical and thermal stimuli. Mediate ‘first’, or fast, pain
* C-fibres (unmyelinated) = respond to all noxious stimuli (POLYMODAL). Mediate ‘second’, or slow, pain
169
Sensations caused by a-delta fibres? C-fibres?
* ad-fibres = quick high intensity pain, stabbing sensations
| * C-fibres = slow lower intensity pain, burning, throbbing, aching sensations
170
Inflammatory pain caused by?
| How is pain activated?
Immune system
* mediators released at the site of inflammation - Causes heightened pain sensitivity to noxious stimuli (hyperalgesia) and pain sensitivity to innocuous stimuli (Allodynia)
171
Neuropathic pain caused by? E.g.?
damage to neural tissue
e.g. compression neuropathies, peripheral neuropathies, central pain (following stroke or spinal injury), postherpetic neuralgia, trigeminal neuralgia, phantom limb
172
Dysfunctional pain? E.g.?
| Tx? Difference between pathological pain (neuropathic + dysfunctional) and other types of pain??
In dysfunctional pain there is no identifiable damage or inflammation
* fibromyalgia, irritable bowel syndrome, tension headache, temporomandibular joint disease, interstitial cystitis
* Sometimes tx by drugs not originally developed for pain e.g. antidepressants
* Pathological pain is NOT adaptive!! It is maladaptive
173
What is referred pain caused by?
convergence of nociceptive visceral and skin afferents upon the same spinothalamic neurons at the same spinal level
174
IPEX syndrome? Caused by?
Autoimmune disease
| * mutation in the FOXP3 gene, which is essential for the development of CD4+ regulatory T cells
175
Class I MHC? Class II MHC?
Class I = expressed by all nucleated cells
| Class II - APCs
176
What are most (if not all) autoimmune diseases associated with?
Genetic polymorphisms in HLA region (MHC molecules)
177
Other than genetics, what factors also play a role in autoimmune disease?
Sex hormones!
* Females more at risk of certain autoimmune diseases (alteration of course of some autoimmune diseases during pregnancy)
Environmental factors
* Molecular mimicry - non-self antigens look identical to self
* Intercurrent infections - immune responses can cause autoimmune reactions
* Tissue damage - release of previously hidden self-antigens
* Superantigens - bacterial superantigens can activate auto-reactive T cells (e.g. TSS)
178
What are many autoimmune diseases driven by? E.g.?
Hypersensitivity reactions
* Type II = Goodpasture's syndrome, rheumatic fever, myasthenia gravis
* Type III = SLE
* Type IV = rheumatoid arthritis
179
Examples of autoimmune diseases that affect musculoskeletal system?
* Rheumatoid arthritis
* Myasthenia gravis
* Scleroderma
* Polymyositis
* Lupus
180
Myasthenia gravis? Main cause?
Autoimmune neuromuscular disorder characterized by severe muscular weakness and progressive fatigue
* auto-reactive antibodies (auto-IgG) bind with acetylcholine receptors on muscle cells
181
Epidemiology MG? (3)
* ANy age
* Thymic tumour (10% cases) - 90% unknown cause
* Genetic predisposition i.e. HLA mutation
182
Clinical manifestations MG? (5)
* May first appear during pregnancy, postpartum or after anaesthetic agents
* Fatigue
* Muscle weakness: eyes, face, mouth, throat + neck
* In advanced stage all muscles are weak
183
What is early onset MG with AChR antibodies associated with?
increased adaptive immune responses in the thymus
| thymic follicular hyperplasia with lymphoid follicles and germinal centres
184
Pathophysiology of MG?
* CD4+ T cells activated by AChR subunits expressed by thymic epithelial cells
* Effector TH cells stimulate auto-reactive B cells to produce anti-AChR antibodies
* Thymic myoid cells are attacked by these antibodies, and release AChR-immune complexes
* These complexes activate other antigen presenting cells, perpetuating the response
* AChR antibodies block binding of endogenous ACh to the receptors, leading to defects in nerve impulse transmission at the NMJ
* Complement system activated leading to destruction of muscle endplate
185
What does activation of compliment cascade result in in MG?
formation of the membrane attack complex (MAC) and localized destruction of the postsynaptic membrane
186
MG tx? (4)
* Anti-cholinesterase
* Immunosuppression e.g. corticosteroids, Eculizumab
* Plasmapheresis
* Thymectomy
187
Rheumatoid arthritis clinical manifestations?
* Inflammatory change in synovial membrane
* Fever
* Leukocytosis
* Anorexia
* Hyperfibinogenaemia
188
Pathogenesis rheumatoid arthritis?
* Genetic, epigenetic + environmental factors: HLA-DR4, smoking, increased in post-partum + breastfeeding
* Type IV hypersensitivity
189
Tx RA? (6)
* Methotrexate
* Sulpasalazine
* Hydroxychlorquinine
* Leflunomide
* Gold, penacillamine, ciclosporin A
* Anti-TNF e.g. Infliximab
190
Osteoarthritits?
Articular cartilage loss
191
Risk factors OA? (10)
* Elderly
* Female
* Obesity
* Previous injury
* Muscle weakness
* Acromegaly
* Joint inflammation
* Crystal deposition in cartilage
192
Pathogenesis OA? (5)
* Mechanical damage
* Imbalance of: cytokines, growth factors, PGE2, free radicals, proteolytic enzymes
* Destroction of chondrocytes
* Bone remodelling
* Reduced synovial fluid viscosity
193
Ax OA? (2)
* Idiopathic
| * Secondary - previous injury, rheumatoid arthritis etc
194
Does osteoarthritis affect spine?
Yes can affect whole spine unlike RA which can only affect C1, C2
195
S/s OA? (2)
* Pain - worse on activity, relieved by rest
| * Stiffness - morning stiffness lasts <30 mins
196
o/e OA? (4)
* Crepitus
* Joint swelling -Bony enlargements due to osteophytes
* Joint tenderness
* Joint effusion
197
S/s hands OA? (2)
* Bony enlargements at DIPs (Heberdens nodes) and PIPs (Bouchards nodes)
* Squaring of hand
(RA tends not to affect DIPs!!)
198
s/s knee OA? (3)
* Osteophytes, effusions, crepitus and restriction of movement
* Genu varus or valgus
* Bakers cyst
199
s/s OA hip? (2)
* Restricted movement
| * Pain may be felt in groin or radiating to knee
200
s/s OA spine?
* Cervical – pain and restriction of neck movement
* Lumbar – Pain on standing or walking
* osteophytes can cause spinal stenosis if encroach on spinal canal or pinch the nerve root
201
Radiological features OA? (4)
* Loss of joint space
* Subchondral sclerosis
* Subchondral cysts
* Osteophytes
202
Kellgren-Lawrence Radiographic Grading Scale of Osteoarthritis?
* Grade 0-No radiographic findings of osteoarthritis
* Grade 1- Minute osteophytes of doubtful clinical significance
* Grade 2 - Definite osteophytes with unimpaired joint space
* Grade 3 - Definite osteophytes with moderate joint space narrowing
* Grade 4 - Definite osteophytes with severe joint space narrowing and subchondral sclerosis
203
Tx osteoarthritis?
Non-pharmalogical
* Physio, weight loss
Pharmacological
* analgesia e.g. paracetamol
* NSAIDs
* Pain modulations e.g. tricyclics
* Steroids
Surgical
* Joint replacement
* Arthroscopic washout
204
Gout?
Inflammation in the joint triggered by uric acid crystals
205
>0.42 uric acid?
Hyperuricaemia = no longer soluble
206
Causes of hyperuricaemia? (2)
* Increased urate production - enzyme defects, psoriasis, cancer, ALCOHOL, high dietary purine intake (e.g. red meat, seafood)
* Reduced urate excretion - renal impairment, HF, hypothyroidism, diuretics, cytotoxics e.g. cyclosporin
207
Epidemiology gout?
* Males > females
| * Elderly (rare before menopause in women)
208
Acute gout?
* Usually monoarthropathy:- 1st MTP > ankle > knee
* Settles in about 10 days without treatment
* Settles in about 3 days with treatment
* Abrupt onset, often overnight
* May have normal uric acid during acute attack
209
chronic tophaceous gout?
* Chronic joint inflammation
* Often diuretic associated
* High serum uric acid
* Tophi
* May get acute attacks
210
Ix gout? (5)
* Raised inflammatory markers
* Serum uric acid raised (may be normal during acute attack)
* Synovial fluid - polarising microscopy shows needle shaped NEGATIVELY birefringent crystals
* Renal impairment (may be cause or effect)
* Xrays
211
Tx acute gout? Long term?
Acute
* NSAIDs, colchicine, steroids
```
Long term (2-4 weeks after acute attack)
* allopurinol, febuxostat
```
212
calcium pyrophosphate deposition disease epidemiology? Where does it affect? 2 types?
Commoner in elderly (chondrocalcinosis increases with age)
* Affects fibrocartilage - knees, wrists, ankles
2 types
* Calcium pyrophosphate and calcium hydroxyappatite crystals
213
CPPD attacks due to? Appearance of crystals?
* calcium pyrophosphate crystals (pseudogout)
| * Calcium pyrophosphate crystals- rhmboid shaped, POSITIVELY birefringent
214
Tx pseudogout? (4)
* NSAIDs, colchicine, steroids, rehydration
215
What causes "Milwaukee shoulder"?
Epidemiology?
Tx? (4)
Hydroxyapatite crystal deposition in or around the joint
* Females, 50-60 years
* NSAIDs, steroid injection, physiotherapy, arthroplasty
216
Soft tissue rheumatism? Features?
pain that is caused by inflammation/damage to ligaments, tendons, muscles or nerve near a joint rather than the bone or cartilage
* Pain should be confined to specific site e.g. shoulder, wrist etc (more generalised soft tissue pain – consider fibromyalgia)
217
Commonest area for soft tissue pain? e.g.? (5)
Shoulder!
* Adhesive Capsulitis
* Rotator cuff tendinosis
* Calcific tendonitis
* Impingement
* rotator cuff tears
218
Joint hypermobility syndrome epidemiology? Predisposing conditions?
* F > M
| * Marfan's syndrome, ehlers danlos syndrome
219
Hypermobility s/s? Tx?
* Arthralgia, premature osteoarthritis
| * Tx: physiotherapy
220
Rheumatoid athritis? Epidemiology?
symmetrical inflammatory arthritis affecting mainly the peripheral joints (spine is NOT affected!!! Only C1, C2)
* Women:men 3:1
221
Main structure involved in RA? Effect on structure?
Synovium
| * Synovial inflammation causes bone erosion and damage (due to activation of osteoclasts)
222
Pannus? Pro-inflammatory cytokines involved in RA?
hypervascular inflammed synovium associated with RA
| * TNF-a, IL-1, IL-6
223
Early RA?
<2 yrs since symptom onset
224
Criteria for RA? (4)
* Morning stiffness >1 hr.
* Arthritis of 3 or more joint areas.
* Arthritis of hand joints.
* Symmetric arthritis.
225
Dx RA? (3)
* Bloods - anaemia of chronic disease (normocytic), raised platelets, CRP, plasma viscosity, autoantibodies
* Imaging - xray, US, MRI
* Positive compression test in MCP and MTP joints
226
s/s RA? (7)
* PIP, MCP, wrist, MTP synovitis
* Tenosynovitis (tendinous inflammation)
* Trigger figer
* Bilateral carpal tunnel
* Polymyalgia rheumatica.
* Palindromic rheumatism.
* Poor grip strength
227
Auto-antibodies RA?
* Rheumatoid factor(Rheumatoid IgM)-
* Antibodies to cyclic citrullinated peptide(Anti-CCP antibodies)
228
DAS28 scoring?
For RA
* >5.1 = active disease
* 3.2 - 5.1 = moderate disease
* 2.6 - 3.2 = low disease activity
* <2.6 = remission
229
Tx RA? (3)
Start with aggressive tx then gradually withdraw tx
* NSAIDs
* steroids (NOT used on their own - in combo with DMARDs!!)
* DMARD
230
DMARDs? (5)
DIsease-modifying anti-rheumatic drugs
* Methotrexate (DRUG OF CHOICE)
* Sulfasalazine
* Hydroxychloroquinone (does not prevent erosions!!)
* Leflunomide
* Gold, penicillamine, azathioprine
231
DMARD combo? Risk of methotrexate?
MTX + SASP + HCQ
| * risk of pneumonitis with methotrexate
232
Risks associated with DMARDs? (3)
* Bone marrow suppression = infection
* Impaired liver function
* Pneumonitis in case of methotrexate
233
Biologic agents for RA? (5)
| When should biologic agents for RA be administered?
* Anti TNF = inflixumab
* T cell receptor blocker = abatacept
* B cell blocker = rituximab
* Anti-Il 6 = tocilizumab
* JAK 2 inhibitor = tofacitinib
Failure to respond to 2 DMARDs (inc. methotrexate) + DAS28> 5.1
Methotrexate therapy is co-prescribed!!
234
Spondylarthropathy?
inflammatory arthritides characterized by involvement of both the spine and joints, principally in genetically predisposed (HLA B27 positive) individuals
235
HLA B27?
| Used in dx?
Associated with Ankylosing spondylitis, Reactive arthritis, Crohn’s disease, uveitis
* Not a useful screening or Diagnostic test unless patients also have symptoms
- because 1/5 people have mutation but most don't have disease
236
Types of spondyloarthritis? (4)
* Ankylosing Spondylitis
* Psoriatic Arthritis
* Reactive Arthritis
* Enteropathic Arthritis
237
Mechanical vs inflammatory back pain?
* Mechanical- worsened by activity, typically worst at end of day, better with rest
* Inflammatory- worse with rest, better with activity, significant early morning stiffness (>30 minutes)
238
Features of spondylarthropathies? (4)
* Sacroiliac and spinal involvement
* Enthesitis: inflammation at insertion of tendons into bones eg Achilles tendinitis
* Inflammatory arthritis
* Dactylitis (“sausage” digits)- inflammation of entire digit (not just 1 joint)
239
Extra-articular features of spondylarthropathies? (4)
* Ocular inflammation (uveitis, conjuntivitis)
* Mucocutaneous lesions
* Rare Aortic incompetence or heart block
* No rheumatoid nodules
240
Ankylosing spondylitis?
Hallmark??
Epidemiology?
Chronic systemic inflammatory disorder that primarily affects the spine
* HALLAMRK = sacroiliac joint involvement!! (v rare to have small joint involvement unlike RA)
* Men > women, young adults
241
s/s ankylosing spondylitis? (6)
| Dx? (3)
* Back pain
* Enthesitis
* Uveitis
* Cardiovascular involvement (aortic regurgitation)
* Fibrosis upper lung lobes
* amyloidosis
Dx
* Examination - occiput to wall, chest expansion, schober test
* Bloods - CRP, HLA B27
* X-ray - sacroiliitis, syndesmophytes, "bamboo" spine
242
Ankylosing spondylitis vs osteoarthritis? (5)
AS
* Bone density reduced in late disease
* Shiny corners
* Syndesmophytes
* Fusion (bamboo spine)
OA
* Normal bone density
* Reduced joint space
* Subchondral sclerosis
* Sunchondral cyst
* Osteophytes
243
What is the preferred imaging technique for AS?
MRI - can detect AS earlier than x-rays
Can detect bone marrow oedema and enthesitis!!
244
Psoriatic arthritis? s/s? (5)
Inflammatory arthritis associated with psoriasis (rheumatoid factor negative!)
* Sacroiliitis (often asymmetric)
* Nail pitting/oncholysis
* Dactylitis
* Enthesitis
* Eye disease
245
5 subgroups of psoriatic arthritis? (5)
* Confined to distal interphalangeal joints (DIP) hands/feet
* Symmetric polyarthritis (similar to RA)
* Spondylitis (spine involvement) with or without peripheral joint involvement
* Asymmetric oligoarthritis with dactylitis
* Arthritis mutilans
246
Dx psoriatic arthritis? (2)
* Bloods - CRP, negative RF
| * X-ray - whiskering, "pencil in cup", osteolysis, enthesitis
247
Reactive arthritis? Most common infections? Epidemiology?
Arthritis in response to infection etc characterised by inflammatory synovitis from which organisms CANNOT be cultured!!
* Urogenital e.g. chlamydia
* Enterogenic e.g. salmonella
Epidemiology
* Equal sex distribution
* Young adults
* HLA B27 positive
248
Reiter's syndrome?
Form of reactive arthritis
| Traid: urethritis, conjunctivitis/uveitis, arthritis
249
s/s reactive arthritis?
* fever
* Asymmetrical arthritis
* Enthesitis
* Mucocutaneous lesions: keratodema blenorrhagica, circinate balanitis, painless oral ulcers, hyperkeratotic nails
250
Dx reactive arthritis? (3)
* Bloods - CRP, HLA B27
* Cultures - blood, urine, stool (NOT SYNOVIAL FLUID)
* x-ray
251
Enteropathic arthritis?
| s/s?
Associated with inflammatory bowel disease eg. Crohn’s, Ulcerative colitis
* GI symptoms
* Uveitis
* arthritis in several joints, esp knees, ankles, elbows, and wrists
* pyoderma gangrenosum
* Enthesitis
* Oral- apthous ulcers
252
Dx enteropathic arthritis? (5)
* Upper and lower GI endoscopy with biopsy showing ulceration/ colitis
* Joint aspirate- no organisms or crystals
* Raised inflammatory markers- CRP, PV
* X ray/ MRI showing sacroiliitis
* USS showing synovitis/ tenosynovitis
253
Tx of spondylarthropathies? (look back if cant remember subgroups) - 6
Non-pharmacological tx? (2)
* NSAIDs
* Corticosteroids
* Topical steroid eyedrops
* DMARDs (methotrexate etc)
* Anti-TNFa (biologics) – only in severe disease
* Secukinumab (anti-Il7) only for PSA and AS
Non-pharma
* Physiotherapy
* Occupational therapist
254
Vasculitis?
| Mortality rate of untreated small vessel vasculitis?
inflammation of blood vessels
| * Untreated small vessel vasculitis can have mortality rate of 90% after 2 years
255
Ax vasculitis?
* Primary vasculitis - inflammatory response that targets vessel walls and has no known cause (possibly autoimmune)
* Secondary vasculitis - infection, drug, toxin, inflammatory disorder, cancer
256
Pathogenesis vasculitis?
* Dendritic cells activate T cells and release cytokines that cause vascular inflammation
* T cells activate macrophages
* Macrophages release mediators that cause vascular inflammation, endothelial damage, disruption of elastic lamina, intimal hyperplasia
257
Classifications of vasculitis? (4)
* Medium-vessel vasculitis - Kawasaki disease, polyarteritis nodosa
* Immune complex small-vessel vasculitis - cytoglobunemic vasculitis
* ANCA-associated smell vessel vasculitis - microscopic polyangitis
* Large vessel vasculitis - takayasu vasculitis, giant cell arteritis
258
S/s vasculitis? (5)
* Depends on which vessel it affects
HOWEVER
Systemic symptoms like fever, malaise, weight loss and fatigue are common to ALL vasculitides
259
Ax large vessel vasculitis?
Epidemiology?
Hallmark?
* Takayasu arteritis and giant cell arteritis
* Epidemiology: TA = <40 years, female, Asian
GCA = >50 years, typically causes temporal arteritis
* Granulomatous infiltration of walls of large vessels
260
s/s large vessel vasculitis? (3)
* Bruit (mostly carotid artery)
* Blood pressure difference of extremities
* Claudication
261
Temporal arteritis? Associated with? s/s? (4)
| Biggest risk??
Common in giant cell arteritis
* Associated with polymyalgia rheumatica
S/s
* Unilateral temporal headache
* scalp tenderness
* jaw claudication
* Temporal arteries prominent with reduced pulsation
Risk of blindness due to ischaemia of the optic nerve!!
262
Ix large cell vasculitis? (3)
* Bloods - ESR, plasma viscosity and CRP raised
* Temporal artery biopsy (remember that “skip lesions” occur so biopsy may be negative)
* MR angiogram or PET CT
263
Tx large cell vasculitis?
40 - 60 mg prednisolone
264
Small vessel vasculitis divided into? (2)
| Types of small vessel vasculitis? (3)
* ANCA associated vasculitis (AAV) and ANCA negative
Types
* Granulomatosis with polyangiitis (Wegener's granulomatosis) - granulomatous inflammation of respiratory tract, associated with necrotising glomerulonephritis
* Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) - eosinophilic granulomatous inflammation of respiratory tract, associated with asthma
* Microscopic polyangiitis - necrotising vasculitis with immune deposits, associated with necrotising glomerulonephritis
265
Ax ANCA associated vasculitis? (4)
* Bacteria: Staph aureus, E.coli
* Genetic: HLA, CD226
* Environmental: silica
* Drugs: propylthiouracil, hydralazine
266
Granulomatosis with polyangiitis (GPA) epidemiology?
* Europeans
* Males > females
* Adults
267
s/s GPA? (6)
* ENT = sinusitis, nasal crusting, epistaxis, mouth ulcers, otitis media + deafness, nose bleeds, saddle nose due to cartilage ishaemia
* Resp = pulminary infiltrates, cough, haemoptysis, cavitating nodules on CXR
* Skin = purpura!!! ulcers
* Renal = necrotising glomerulonephritis (microhaematuria)
* NS = mononeuritis multiplex, sensorimotor polyneuropathy, CN palsies
* Eyes: conjunctivitis, uveiis, retinal artery occlusion
268
Difference between Granulomatosis with polyangiitis (GPA) and Eosinophilic granulomatosis with polyangiitis (EGPA)?
EGPA = late onset asthma and a high eosinophil count
269
s/s EGPA? (6)
* Asthma
* Eosinophilia > 10%
* Paranasal sinusitis
* Pulmonary infiltrates
* Purpuric rash
* Mononeuritis multiplex or polyneuropathy
270
Immunology AAV? (3)
| ANCA patterns? (2)
* Anti-Neutrophil Cytoplasmic Antibodies (ANCAs) auto-antibodies against antigens in the cytoplasm of neutrophil granulocytes
* Immunofluoresence used to detect ANCA and can differentiate ANCA patterns i.e. cANCA+ PR3 (GPA) and pANCA + MPO (MPA and EGPA)
271
Tx AAV? (3)
* Localised/early systemic = methotrexate + steroids
* Generalised/systemic = cyclophosphamide + steroids
* Refractory unresponsive to steroids + cyclo) = IV immunoglobulins + rituximab
272
Prognosis AAV? (2)
* Untreated = fatal
| * Treated = 5 yr survival 90%
273
Henoch-schonlein purpura (HSP)?
acute immunoglobulin A (IgA)–mediated disorder
| * vasculitis involving small vessels of skin, GI tract, kidneys, joints (RARELY lungs and CNS)
274
Epidemiology HSP? Ax?
* Children 2-11
>75% patients have preceding URTI, pharyngeal or GI infection
* GAS most common!!
275
S/s HSP? (5)
* Purpuric rash
* Colicky abdominal pain
* Bloody diarrhoea
* Jont pain + swelling
* Renal symptoms (50%)
276
HSP tx?
* Usually self-limiting (tends to resolve in 8 weeks)
| * MUST perform urinalysis to screen for renal involvement!!
277
Main causes of myopathy? (7)
* Inflammatory - polymyositis
* Endocrine disorders - cushing's
* Electrolyte disorders - hypokalaemia
* Metabolic myopathies
* Drugs and toxins
* Infections - pyomyositis
* Rhabdomyolysis
278
Inflammatory myopathies? (2)
Epidemiology?
Risk?
Polymyositis + dermatomyositis
* Female > male, adults
* Increased incidence of malignancy
279
Histology inflammatory myopathy? Ax?
* Histo: necrosis, inflammatory cell infiltrate
| * Ax = idiopathic (unknown)
280
s/s inflammatory myopathies?
MUSCLE WEAKNESS
* usually symmetrical, proximal muscles
* Often specific problems eg difficulty brushing hair, climbing stairs
281
Dermatomyositis? Other organs involved in inflammatory myopathies? (6)
* Cutaneous disease - gottrons sign, heliotrope rash, shawl sign
* ILD
* Dysphagia
* Myocarditis
* Fever
* Weight loss
* Raynauds
282
Risk factors for inflammatory myopathies? (4)
* Other medical problems : thyroid disease, diabetes
* Drugs : steroids, statins
* Family history
* Social : alcohol, illicit drug use
283
Ix inflammatory myopathies?
* Bloods - CK, inflammatory markers, autoantibodies
* Electromyogrphy
* Muscle biopsy (gold standard)
* MRI
284
Tx inflammatory myopathies? (6)
* Glucocorticoids
* Azathioprine
* Methotrexate
* Ciclosporin
* IV immunoglobulin
* Rituximab
285
Polymyalgia rheumatica associated with? s/s? (7)
Temporal arteritis/Giant cell arteritis
* Shoulder and hip ache (usually symmetrical)
* Morning stiffness
* Fatigue
* Anorexia + weight loss
* Fever
* Limited movement
* Muscle strength is normal
286
Tx polymyalgia rheumatica?
Steroids
| higher dose steroids for temporal arteritis
287
Fibromyalgia associated with inflammation? s/s? (6)
NO!!
* Pain (worse with exertion)
* Swelling
* Fatigue and poor sleep
* Pins and needles
* Headaches
* IBS
288
Connective tissue disease? e.g? (7)
NOT diseases of connective tissue!!
Spontaneous over activity of the immune system involving auto-antibodies (can lead to organ failure and death)
* SLE
* Sjogren’s syndrome
* Systemic sclerosis
* Dermatomyositis
* Polymyositis
* Mixed Connective Tissue Disease
* Anti-phospholipid syndrome
289
SLE? Epidemiology? (2)
Systemic autoimmune disease that can affect any part of the body
* Females > males
* Asians, afro-Americans, afro-caribbeans (uncommon in African blacks)
290
Ax SLE? (4)
* Genetic
* Environmental
* Hormonal - oestrogen (HRT)
* Immunological
291
Pathogenesis SLE?
* Increased and defective apoptosis
* Necrotic cells release nuclear material which act as auto-antigens
* B and T cells are stimulated
* Autoantibodies are produced
292
How does SLE lead to renal disease?
Deposition of immune complexes in mesangium (neutrophils attack immune complexes)
293
Clinical criteria SLE?
* Mucocutaneous - oral/nasal ulcers, cutaneous disease, non-scarring alopecia
* Musculoskeletal - arthritis
* Serositis
* Renal
* Neurological
* Haematological - haemolytic anaemia, leukopenia, thrombocytopenia
294
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General s/s SLE? (5)
Mucocutaneous? (6)
Musculoskeletal? (3)
Serositis? (4)
Renal? (2)
Neurological? (4)
Haematological? (5)
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General
* Fever, malaise, anorexia, weight loss, fatigue
Mucocutaneous
* Photosensitivity, malar rash, discoid lupus erythematosus, subacute cutaneous lupus, mouth ulcers, alopecia
MSK
* Non-deforming arthritis (poly), deforming arthropathy (Jaccoud's arthritis), myopathy (weakness, myalgia)
Serositis
* Pericarditis, pleurisy, pleural effusion, pericardial effusion
Renal
* Proteinuria >500mg in 24 hrs, red cell casts
Neurological
* Depression, migrains, seizures, neuropathy (e.g. mononeuritis multiplex is a peripheral neuropathy)
Haematological
* Lymphadenopathy, lymphopenia, leukopenia, haemolytic anaemia, thrombocytopenia
295
Anti-phospholipid syndrome?
| s/s? (5)
Production of antiphospholipid auto-antibodies (associated with other autoimmune conditions esp SLE)!!!
* Venous + arterial thrombosis
* Recurrent miscarriage
* Livido reticularis
* Thrombocytopenia
* Prolonged APTT
296
Ix SLE? (10)
* Antinuclear antibodies - ANA, anti-double stranded DNA, anti-Ro, anti-Sm, anti-RNP
* Anti-phospholipid antibodies = anti-cardiolipid antibody, lupus anticoagulant, anti-beta 2 glycoprotein
* CXR
* Pulmonary function test
* CT chest
* Urine protein quantification
* Renal biopsy
* ECHO
* Nerve conduction studies
* MRI brain
297
In a patient with SLE which of the following features would make you most suspicious of a disease flare?
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A. Increasing fatigue levels
B. Raised CRP
C. Positive ANA
D. Fall in C4 level
E. More frequent headaches
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D. Fall in C4 level
| * C3/C4 levels NEGATIVELY correlate with disease activity
298
How can SLE disease activity be monitored? (5)
* Anti-dsDNA level positively correlates with activity
* C3/C4 levels negatively correlate with activity
* Urine examination
* FBC
* Blood biochemistry
299
Tx SLE? (5)
* NSAIDs
* Anti-malarials e.g. hydroxychloroquine (useful for arthritis, skin manifestations)
* Steroids (low dose for skin rashes/arthritis/serosisits, mod doses for resistant serositis, haematologic issues, high dose for severe haematological issues, renal disease and major organ involvement)
* Immunosuppressants - azathioprine, methotrexate, cyclophosphamide
* Biologics - anti-CD20 (rituximab), anti-Blys (belimumab)
300
When to suspect autoimmune disease? (8)
* Arthralgia/arthritis
* Muscle pain/muscle weakness
* Photosensitivity
* Raynaud`s phenomenon
* Sicca symptoms(dry eyes/mouth/throat/vaginal dryness) in the absence of other causes
* Dysphagia, shortness of breath
* Neurological symptoms
* Recurrent pregnancy losses/unprovoked thrombosis/pregnancy complications
301
When is Raynaud's associated with autoimmune disease?
| Tx?
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Primary = teenagers, no autoimmune disease, benign
Secondary = adults, underlying autoimmune disease (if ulcers or gangrene, usually secondary)
```
Tx
* Vasodilators - CCB
* For ulcers = iloprost, botox injections
302
Systemic sclerosis? Types?
Used to be called scleroderma (skin thickening)
2 types
* Diffuse cutaneous systemic sclerosis (dsCC) - skin involvement on extremities above AND below elbows and knees (plus face + trunk)
* Limited cutaneous systemic sclerosis (lsCC) - skin involvement on extremities ONLY BELOW elbows and knees (plus face)
303
Pathogenesis systemic sclerosis?
Environment + genetics!
* Antigen detected
* Endothelial cell stimulation
* Chronic inflammation
304
Systemic sclerosis symtpoms? (5)
CREST
* Calcinosis - calcium deposits in skin
* Raynaud's
* Esophageal dysfunction - acid reflex and decreased motility
* Sclerodactyly - thickening and tightening of skin on fingers and hands
* Telangiectasias - dilation of capillaries causing red marks on surface of skin
Also pulmonary + Renal complications!!
* Pulmonary fibrosis + pulmonary hypertension
* Scleroderma renal crisis
305
Antibodies in systemic sclerosis? (5)
* Anticentromere
* Antitipoisomerase
* Anti-RNA polymerase
* Anticardiolipin antibodies
* Anti-Scl-70
306
Tx systemic sclerosis? (6)
* Yearly ECHO and PFTs
* Treat Raynaud`s and digital ulcers
* Treat reflux with PPi (ranitadine)
* Immunosuppression
* Pulmonary hypertension- prostacyclin analogues, endothelin receptor antagonists, PDE5 inhibitors.
* Tight control of blood pressure - ACE INHIBITORS
307
Sjogren's syndrome? Main features?
Characterised by lymphocytic infiltration of exocrine glands
| * Keratoconjunctivitis sicca, vaginal dryness, difficulty swallowing, extreme thirst, dry mouth (tooth decay)
308
S/s Sjogren's? (5)
* Blepharitis
* Salivary gland inflammation
* Tooth decay
* Lymphoma
* Dry cough
* Multisystem involvement
309
Dx Sjogren's? (5)
* Usually ANA positive
* If antibodies negative, salivary gland ultrasound and biopsy
* high ESR/plasma viscosity
* Raised IgG
* Cytopaenias
310
Tx Sjogren's?
* Artificial tears, salivary supplements, vaginal lubricants
* Good dental hygiene-strong fluoride toothpaste-e.g.Duraphat
* Hydroxychloroquine for fatigue and arthralgia
* Immunosuppression for major organ involvement.
311
What pattern does psoriatic arthritis normally follow?
an asymmetrical oligoarthritis
312
What are mixed connective tissue diseases?
Mixed connective tissue diseases are conditions which feature symptoms also seen in other connective tissue diseases
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These include:
Raynauds phenomenon
Arthralgia/arthritis
Myositis
Sclerodactyly
Pulmonary hypertension
Interstitial lung disease (ILD)
```
They are associated associated with anti-RNP antibodies!!
313
Difference between polymyositis and dematomyositis?
Polymyositis is an idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness. Dermatomyositis is clinically similar but also has typical cutaneous manifestations
314
How to differentiate between polymyositis and polymyalgia rheumatica?
* Polymyositis = weakness
| * Polymyalgia rheumatica = pain + stiffness
315
Spondylosis?
intervertebral discs lose water content with age resulting in less cushioning and increased pressure on the facet joints leading to secondary OA
316
Once suspect cauda equina syndrome?
Urgent MRI
317
Tx carpal tunnel? (2)
Non-operative treatment
* wrist splints at night to prevent flexion
* Injection of corticosteroid
Surgical treatment
* Carpal tunnel decompression
318
Tests for carpal tunnel? Cubital tunnel?
Carpal
* Tinel’s test (percussing over the median nerve)
* Phalen’s test (holding the wrists hyper‐flexed)
Cubital
* Tinel's test
* Froment's test
319
Cubital tunnel syndrome?
compression of the ulnar nerve (paraesthesiae in the ulnar 1½ fingers)
