Calcium Crystal Dz's Flashcards
Dysregulated chondrocyte differentiation to hypertrophy and inorganic pyrophosphate (PPi) metabolism are what?
Central in the pathogenesis of Calcium Pyrophosphate Dihydrate (CPPD) crystal deposition disease
Autosomal dominant familial CCPD crystal deposition disease has been linked to mutations in?
Multiple kindreds to certain mutations in ANKH, a gene encoding a PPi transporter
NLRP3 (cryopyrin) inflammasome activation and consequent caspase-1 activation and IL1beta processing and secretion do what?
Drive cell responses to CPPD crystals and CPPD crystal-induced inflammation
Degenerative arthropathy caused by CPPD crystal deposition disease often involves what?
Joints uncommonly affected by primary osteoarthritis such as the metacarpophalangeal, wrist, and elbow
Diagnosis of CPPD deposition dz before age 55, particularly if CPPD deposition is polyarticular, should prompt what?
Differential dx consideration of a primary metabolic of familial disorder, and hyperparthyroidism should always be considered in CPPD deposition disease presenting inpatients older than 55
High resolution ultrasound appears partocularly helpful in dx of CPPD CDD because?
Radiographic chondrocalcinosis is detectable in all joints affected by the dz
Basic calcium phosphate (BCP) crystal deposition in articular cartilage is linked with?
Osteoarthritis, particularly with osteoarthritis of increased severity
BCP crystals (unlike urate and CPPD) do not demonstrate what? What does this mean?
Birefringence; therefore specialized methods are required to conclusively identify BCP crystals in specimens from the joint
The vast majority of CPPD CDD is?
Idiopathic/sporatic but early onset familial also occurs
Linkage of familial CPPD CDD to what gene on what chromosome is well established?
ANKH gene on chromosome 5p; encodes transmembrane protein with functions including PPi transport)
The loose avascular connective tissue matrices of articular hyaline cartilage, fibrocartilaginous menisci, and of certain ligaments and tendons are susceptible to what?
Pathologic calcification
Joint cartilage pathologic calcification reflect complex interplay between what things?
Organic and inorganic biochem of Pi and PPi metabolism, aging, dysregulated chondrocyte growth factor responsiveness and differentiation, and other factors
In the elderly, CPPD deposition can mimic what other conditions?
Gout, infectious arthritis, primary osteoarthritis, TA, or polymyalgia rheumatica, it can also present as fever of unknown origin
Pseudogout is a major cause of acute monoarticular or oligoarticular arthritis in the elderly, what do attacks usually involve?
A large joint, most often the knee, and less often the wrist or ankle and unlike gout it rarely affects the first metatarsophalangeal joint
Chronic degenerative arthropathy in CPPD deposition disease commonly affects certain joints that are typically what? (compared to OA)
Spared in OA, like the metacarpophalangeal, wrists, elbow, and glenohumeral
Unlike urate and CPPD CDD acute synovitis due to HA crystal deposition is unusual and how can it present? How is it described in young women?
Acute inflammatory syndromes including subacromial bursitis and a form of pseudopodagra described in young women may occur in association with periarticular HA crystal deposition in bursae, tendons, ligaments, and soft tissues
Patients with advanced chronic renal failure, particularly on dialysis, may develop what? What could they be associated with
Symptomatic articular and periarticular BCP crystal deposition, which may be destructive to the skeleton, they may resemble or be associated with CPPD CDD.
Presence of radiographic evidence for chondrocalcinosis is a common finding in what group of people, what does not necessarily indicate?
In the aged, it does not necessarily indicate that the patient’s symptomatic articular problem is due to CPPD deposition
The use of compensated polarized light microscopy is essential for CPPD, why?
Confirm the presence of the birefringent CPPD crystals, though it should be noted that some CPPD crystals are NOT birefringent
Patients with arthritis in whom CPPD CDD is part of the DDx can be screened how?
By plain radiographs, but high resolution ultrasound of the affected joint is a useful and sensitive approach
CPPD deposition disease treatment involves what?
Alleviation and prophylaxis of acute arthritic attacks, but therapy to lessen chronic and anatomically progressive sequelae of crystal deposition is not well developed for CPPD disease
The approach to pseudogout treatment is similar to what?
Treatment of normal gout
Uric acid is the biologically active end product of what?
Human Purine metabolism
Serum urate concentrations are determined by what?
Balance between urate production and elimination; hyperuricemia = urate overproduction or underexcretion or both
What has been identified as playing a central role in excretion of urate by the kidney?
Organic Anion Transporters (OATs)
Hyperuricemia is defined as serum urate levels greater than?
6.8 mg/dL, this is the soluble limit
Gout pathogenesis requires the accumulation of monosodium urate at levels sufficient to drive the precipitation of crystals which does what?
Initiation of inflammatory response
Monosodium urate crystals activate what? This is a multimolecular cytosolic complex that processes and generates what?
Activates NLRP3 (NALP3) inflammasome; generates IL-1beta, IL18 and IL33
The initiation of gouty inflammation by local white blood cells induces and influx of what into the joint?
Neutrophils
After the neutrophils get into the joint in gout, what happens?
They encounter urate crystals and become activated and propagate further inflammation
Low level inflammation is present in chronic gout and tophaceous gout, what role do macrophages play?
They continue to produce cytokines and proteases, thereby facilitating cartilage and bone destruction
Hyperuricemia is defined as?
Serum urate > 6.8mg/dL
Acute gout is treated with?
NSAID, colchicine, corticosteroids, or adernocorticotrophic hormone; effectiveness of tx depends on how quickly therapy is initiated
Before starting a specific urate-lowering agent, what should be tried?
Low dose colchicine or an NSAID in an attempt to prevent further attacks
Regardless of whether an XO inh, a uricosic agent, or a uricase is used to treat hyperuricemia, the patient should receive what?
The lowest dose possible that maintains serum urate below 6.8, preferably below 6
In addition to allopurinol, what 2 drugs are available are urate lowering agents for the treatment of gout?
Febuxostat and Pegloticase
Individuals who are hyperuricemic should be screened for what?
HTN, CAD, diabetes, obesity, and alcoholism
Using a specific urate-lowering agent to manage asymptomatic hyperuricemia is note recommended, however what should be managed?
Associated condictions such as HTN, CAD, diabetes, obesity, and alcoholism should be managed in these patients, as well as those with symptomatic gout
Hyperuricemia is common and directly associated with what?
Serum creatinine, BMI, age, BP, and alcohol intake
Serum urate levels are low in childhood and increase when in men and when in women?
In puberty in men and menopause in women
The prevalence of gout ranged from 1-15% in populations with a clear increase in incidence in recent years, why is this?
Perhaps due to the assumption of a western diet and obesity epidemic
Many environmental factors are associated with gout such as?
Alcohol (beer), and diet
What foods promote hyperuricemia and gout?
Alochol, seafood, red meat
Consumption of some foods may be protective, such as?
Milk and yogurt
Rare forms of early hyperuricemia and gout have what basis?
Metabolic and genetic
Gout often runs in families, probably because of inherited factors that do what?
Affect serum urate levels through renal clearance
Recent genome wide association studies have identified polymorphisms in several candidate genes that encode what? What will this tell us?
Urate transporters in the renal prox tubule as determinants of serum urate levels and risk of gout
Three stages of gout are?
Asymptomatic hyperuricemia, acute and intercritical gout, and chronic gouty arthritis
A period of asymptomatic hyperuricemia lasts up to how long and then what happens?
20 years before the initial attack of gout or nephrolithiasis
The first attack of gout generally occurs for when in men and when in women?
40-60 for men, 60 for women
What class of drugs raises serum urate levels?
Diuretics, and many more
Most attacks of gout, especially early in the course are monoarticular, which joint do they go after first?
The first metatarsophalangeal joint (podagra) and have a characteristic abrupt and painful onset
The DDx for acute gout is usually what?
Infectious arthritis or other crystal induced synovitis, particularly pseudogout
Ultrasonography is? (in terms of diagnosis)
A useful adjunct in the dx of acute and chronic gout
In untreated or undertreated individuals chronic gout is characterized by?
Development of tophi and progressive joint damage
Gout is associated with?
Obesity, hypertriglyceridemia, glucose intol, metabolic syndrome, HTN, atherosclerosis, and hypothyroidism
What is frequently also associated with hyperuricemia and gout?
Renal insufficiency
Hyperuricemia is a common cause of what?
Nephrolithiasis and rarely chronic hyperuricemia may cause urate nephropathy and acute hyperuricemia may lead to uric acid nephropathy in tumor lysis syndrome.
Alcohol use, lead into, and cyclosporine can lead to what?
Hyperuricemia and gout
Dx of gout should prompt what?
Search for the coexistence of associated conditions
Primary hyperuricemia and gout are caused by what in 90% and what in 10%?
Decreased renal uric acid excretion; overproduction of urate
2ndary hyperuricemia and gout are usually related to decreased what?
Renal urate clearance as a direct or indirect consequence of the primary disease process
4 known specific inborn errors of purine metabolism with overproduction of urate account for what % of cases?
less than 1
Asymptomatic hypeuricemia is generally not treated but identification should make you do what?
Search for the cause and/or associated conditions
Episodes of acute gouty arthritis can be treated with?
Colchicine, NSAIDs, adrenocorticotropic hormone and systemic or intra-articular steroids
Prophylaxis against acute attacks with colchicine or NSAID can be effect but what doesnt change?
The underlying process in the absence of concaminant urate lowering therapy
Starting urate lowering therapy after a single attack of gout remains debatable, what are the indications for urate lowering therapy?
Recurrent gout, urate nephrolithiasis, tophaceous gout, and/or evidence of gout-induced joint damage
XO inhibitors and uricosurics are effective at?
Lowering the amount of serum urate in most patients
Uricases such as pegloticase should be reserved for?
refractory tophaceous gout
What serum level of urate is targeted in tx?
Less than 6
What is prophylactic treatment and for how long?
Colchicine, NSAID, or (less pref) systemic steroids for at least 6 months after initiation of urate lowering therapy
Is long term compliance a problem in recurrence in gout?
Yes; forming a therapeutic alliance with the patient is critical
What else can help control gout besides medication?
Lifestyle alterations like reduced alcohol consumption but this is more important for management of associated conditions such as obesity and hyperlipidemia
