Ch. 68, 70, 71, 73, 74 Last of Musculoskeletal Flashcards
What are the aggrecanases?
examples are ADAMTS 4 and ADAMTS 5
cleaves the aggrecan protein core in the interglobular domain between G1 and G2
ADAMTS 5 is upregulated in murine OA models
aggrecan is degraded and this disrupts the collagen network
what enzymes degrade the type II collagen triple helix?
MMP 1 and MMP 13
Maybe also MMP8 and MMP4
what is the most abundant non collagenous protein of articular cartialge?
cartilage oligomeric matrix protein
what cells are thought to be the precursors of osteophytes?
mesenchymal stem cells
what cytokine plays a crucial role in the induction of osteophytosis?
TGF beta
what are the validated owner completed questionaires for dogs and cats?
for dogs, the Canine Orthopedic Index (COI) and for cats, there is none
what are the radiologic features of OA?
osteophytosis enthesophytosis effusion soft tissue swelling subchondral sclerosis intra artciular mineralization subchondral cyst
what are two weight loss pharmaceuticals approved for use in dogs?
Mitratapide and Dirlotapide are microsomal triglyceride transfer protein inhibitors that can suppress appetite in dogs
how does acetaminophen have analgesic effect?
- May work on CNS but indirectly activate the cannabinoid (CBI) receptors
- acetaminophen –> deacetylation to p-aminophenol will conjugate with AA to form N-arachidonoylphenolamine, an endogenous cannabinoid
- May play central inhibitory action on COX1 splice variant
- May stimulate inhibitory pain pathway that is mediated by serotonin by activating serotonin receptors
- Has no produced renal or gastric injury in dogs when given at recommended dosages
- Not licensed for use in dogs in most countries
characteristics of carprofen
- propionic acid derived NSAID
- COX 2 selective with COX1:COX2 of 17
- stimulatory effect on sulfated glycosaminoglycans but inhibitory at higher doses
characteristics of Deracoxib
- coxib
- metabolism is primarily in the liver with elimination half life of 3 hours
characteristics of etodolac
- indole acetic acid derivative that inhibits both COX1 and COX2
- may inhibit COX1 preferentially
- affects macrophage chemotaxis
- removed from body primarily through biliary excretion but it does under enterohepatic recirculation –> a long half life
- not approved in patients less than 12 months old
- may cause KCS
characteristics of firocoxib
- a pyridylsulfone
- COX 1: COX2 ratio is 342-430 therefore strongly cox 2 specific
characteristics of ketoprofen
- propionic acid
- recommended treatment of up to thirty days
characteristics of mavacoxib
COX1:COX2 OF 21 –> Prefers to inhibit cox 2
very long administration - may only have to dose once a month
may do a treatment cycle every 2 months
only labeled for use in Europe
characteristics of meloxicam
- cox 2 selective with a ratio of 3
- long half life so give once a day
- currently the only NSAID that is licensed in Europe, Australia, and New zealand for long term treatment of cats with OA
characteristics of phenylbutazone
- licensed in Europe only
- COX1:COX2 ratio of 2.64 - slightly more cox 2 selective
- toxicity can manifest as hemorrhage, biliary stasis, hepatitis, renal failure, blood dyscrasias
characteristics of robenacoxib
- COX1:COX2 of 140 so highly COX2 selective
- extensively metabolized by the liver and has a half life in blood of 1.2 hours
- excretely primarily in the biliary system and some by kidneys
- recommended that liver enzymes are assayed before and after starting liver enzymes
characteristics of tepoxalin
- only labeled in Europe
- inhibits COX (nonselective) and 5-lipoxygenase
- 10% GI adverse event rate
- may ameliorate the degradation of collagen in a canine in vitro model of cartilage catabolism
characteristitcs of tolfenamic acid
- recommended dosage is 4 mg/kg SID for three days and then repeat every 7 days - so give 3 days of meds and then 4 days off and repeat
- not super practical
- labeled in Europe
charactersitics of amantadine for OA pain
- NMDA antagonist
- also used as drug for Parkinson’s –> may act on dopaminergic system too
characteristics of gabapentin for OA pain
- gamma aminobutyric acid (GABA)
- originally developed for the treatment of epilepsy
- not licensed for dogs or cats
- may involve voltage gated N type calcium ion channels
- excreted by the kidneys and so patients with renal insufficiency may require less dosing
- avoid abruptly stopping the drug because that may lead to rebound pain
characteristics of codeine
- codeine, aka methymorphine - natural alkaloid found in opium poppy
- approx 5-10% is converted to morphine
- the remaining free amount may be conjugated to form codeine-6-gluconuride (70%), norcodeine (10%), and hydromorphone (1%)
- schedule II controlled substance
How can intra articular steroids be detrimental to the joint?
repeated use can lead to suppression of the cartilage matrix synthesis
recommend no more than 3-4 injections per year
how do polysulfated glycosaminoglycans aid in OA pain management?
- direct injection may maintain chondrocyte viability
- IM administration may lead to inhibited cartilage oligomeric matrix protein degradation and decreases in serum cartilage oligomeric matrix protein concentrations
how does pentosan polysulfate aid in OA treatment
- semisynthetic GAG prepared from beech hemiscellulose and is structurally similar to heparin
- may retard cartilage degrafation and stimulate syntehtsis of hyaluronan by synovial cells and proteoglycan by chondrocytes
- acts as a fibrinolytic and thrombolytic agent
- approved in Europe, Australia and New Zealand, and canada
How are n-3 essential fatty acids thought to be involved in the OA process?
- reduce mRNa levels for ADAMTS-4 and 5 and MMP-3 and MMP-13 (proteinases that degrade cartilage
- reduce mRNA for COX2 (but not COX1)
- reduce mRNA for TNF alpha, IL-1
what are key factors related to human rheumatoid arthritis
- a genetic link with human leukocyte antigen (HLA)-DR4
- a dramatic response to blockade of TNF alpha suggests that TNFalpha plays big role
- similar response to depletion of B lymphocytes but not T lymphocytes
- presence of autoantibodies to the Fc region of immunoglobulin G (known as rheumatoid factors) and to citrullinated peptides (ACPAs)
- link with tobacco smoking
what is pannus?
In erosive forms of immune mediated polyarthritis like canine rheumatoid arthritis, granulation tissue called pannus will proliferate and invade the margins of articular cartilage and subchondral bone
What is the significance of DLA class II genes?
DLA class II is a highly significant genetic risk factor for antinuclear antibody positive immune mediated polyarthritis
what are rheumatoid factors?
anti-immunoglobulin antibodies for IgM and IgA against the Fc portion
the rheumatoid factor will form a complex with the immunoglobulin
not specific for canine rheumatoid arthritis
type I IMPA
this is a non erosive idiopathic IMPA
most dogs with IMPA will respond to initial immunosuppression but 31% of dogs relapsed, required further treatment, or both
type II IMPA
non erosive
compared ot Reiter’s syndrome in people or called reactive arthritis
may be secondary to infection from Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia
treating the underlying infection can resolve the IMPA but you may have recurrent or chronic IMPA still
type III IMPA
non erosive
most common GI signs are vomiting and diarrhea
may be a source of bacterial and food antigens that can trigger an immune complex disease
type IV IMPA
non erosive
paraneoplastic IMPA - no direct invasion of the neoplasm
Drug induced IMPA - which is the most commonly implicated drug?
sulfonamide
usually withdrawal of the drug results in improvement within 1-3 days
what is polyclonal activation?
non specific reactivation of memory b lymphocytes - may show high levels of many antibodies, which can make it confusing to diagnose what type of IMPA the patient has
feline chronic progressive polyarthritis or periosteal proliferative polyarthritis
erosive and non erosive forms but seems like mostly erosive
may see ankylosis of the joins - tarsi and carpi most commonly affected
marked proliferation of periosteal new bone
negative for rheumoatoid factor
entehesopathies
usually positive for feline syncytial forming virus (FeSV) and FeLV
what are infliximab and adalimumab
TNF alpha antibody treatments for rheumatoid arthritis
what are the typical causes of bacterial polyarthritis in puppies and kittens?
usually secondary to omphalophlebitis, streococcal pharyngitis, or uterine/mammary infection
what are the three criteria for bacterial infective arthritis?
- typical history and clinical signs
- synovial fluid cytology consistent with bacterial infective arthritis
- positive bacteriologic culture
how does Borrelia burgdorferi induce IMPA
induce and activate host proteases such as aggrecanases ADAMTS and matrix metalloproteinases –> cartilage degradation
what is the recommended serodiagnostic test for borrelia burgdorferi
C6 and IR6 peptides that bind to the VlsE protein
the organism is found in low levels in the blood and is difficult to culture
can check PCR but it might be high with only exposure not so much a serologic response
what are bacterial L forms?
cell wall deficient bacteria that revert to their parent cell wall state in culture
an L form of Nocardia was seen in a dog with IMPA
what stains will show mycoplasma organisms?
Giemsa, Wright, or Leishmann
what are the diameters of arthroscopes used in small animal med?
1.9, 2.3, 2.4, 2.7
usually 1.9 for carpi and tarsi
2.7 for shoulders and stifles
1.9 or 2.3/2.4 for elbows
what length is typical for arthroscopes?
short - 8.5 cm
long - 13 cm
what is a direct coupling for an arthroscope?
also called glass on glass, the arthroscope is coupled to the camera using a threaded interface
what is the commonly recommended starting pressure for arthroscopy fluid?
60 mm Hg
what size surgical curette is typically used for arhtroscopy?
size 5-0
what is the typical size of arthroscopic cannulas?
inner diameters of 2.3 to 3.5 and a length of 4-5cm
where are the accepted common locations of OCD in the dog?
humeral head
medial aspect of the humeral condyle
lateral or medial femoral condyle
medial or lateral trochlear ridge of the talus
when does the tibial tuberosity fuse?
6-8 months to the condule
6-12 months to the shaft
saltation and stasis
saltation - short periods of growth
stasis - no growth
growth is not a continuous process, goes back and forth between these states
what is the Hueter Volkmann law?
growth is retarded by increased mechanical compression and accelerated by reduced loading in comparison with normal values - growth usually is occurring during recumbency and not while standing and moving
what are the two main differences between the epiphyseal inner layer and the growth plate?
- inner layer is visually disorganized and does not have the ordered zonal and columnar arrangement of the growth plate
- unlike the proliferative, hypertrophic, and mineralization zones in the [hysis, the chondro-epiphysis has a lot of vasculature
what is kinetic vs kinematic gait analysis
kinetic is the study of forces generated during movement
kinematic is the study of motion irrespective of masses or forces
what are the symmetrical gaits?
trot
walk
pace
what are the components measured with each time a foot makes contact with a measurement device?
force vector - described the direction of force
spatial components - describe the location of the force vector
three orthogonal movements
what shape is Fz (vertical force) during the trot and walk?
trot is a bell shape and walk is an M shape
Braking vs propulsion
both are measurements of the craniocaudal force
braking is deceleration and is positive
propulsion is acceleration and is negative
what is a symmetry index?
using an animal’s own limb to serve as an internal control for comparison
what is parallax error
occurs as the subject moves away from the optical axis of the camera
what is perspective error?
occurs when the subject moves out of the calibrated plane of motion
