Patho Exam 2: Joints 2 Flashcards
Explain Juvenile idiopathic arthritis (JIA)
- age:
- Durration:
- Joints involved:
- _____positive
o Begins before age 16, by definition and persist for a min of 6 weeks
o Generally larger joints than RA
o Often positive Anitnucular antibody
Cause of JIA?
Etiology is unknown, no inciting cause as if prior trauma
7 types of JIA 1: 2: 3: 4: 5: 6: 7:
1: Systemic arthritis: abrupt onset, fever, skin rash, hepatosplenomegaly, serositis ( inflammation of serious tissue)
2: Oligoarthritis: 4 or less joints, absence of psoriasis, HLA-B27 (-), (+) ANA
3: Rh factor positive polyarthritis: similar to adult form
4: Rh factor negative polyarthritis: > 5 joints
5: Enthesitis: Inflammation of a point of attachment of a skeletal muscle to bone B27 (+)
6: Psoriatic arthritis
7: Undifferentiated arthritis
Variety of types based on markers that indicate progression
What are the similarities of adult RA and JIA?
Genetic: HLA (doesn’t have to be, but may be), Environmental Inflammatory synovitis & morphologic changes, abnormal immunoregulation (Immune System gone haywire)
what are some differences of adult RA and JIA?
what is Pauci?
Oligoarthritis more common in JA,
systemic disease more frequent in JA,
larger joints greater than small joints in JIA,
RF nodules and RF factors are usually absent,
ANA seropositivity is common
> 1 joint but less than 5 joints
Seronegative spondyloarthropathies name the three subtypes 1: 2: a b 3:
1: Alkalosing Spondylitis ( AKA Rheumatoid spondylitis or marie stumpell diease ( HLA B27)
2: Reactive arthritis (follows GU or GI infection)
•Reiter syndrome (urethral and conjunctival inflammation too) (HLA-B27)
•Arthritis associated with IBD
3:Psoriatic Arthritis (HLA-B27)
what are some common characteristics of seronegative spondyloarthropathies
Dont have RF \+ HLB 27 Sacroilliac and vertebral Asymmetric Inflammation of the tendons Systemic involvment: Uveitis, carditis and arotitis Perferential onset: young men
ankylosing spondylitis
AKA
rheumatoid spondylitis (Marie Stumpell disease)
what is ankylosing spondylitis
Chronic inflammatory arthropathy of vertebral column and sacroiliac joints
May accompany asymmetric peripheral arthritis and systemic manifestations
who is common to have ankylosing spondylitis?
Young men, peak age is 20
Most are positive for what?
HLA B27
What is the manifestations of Ankylosing Spondylitis?
o Begins at sacroiliac joints bilaterally
o Ascends the spinal column involving small joints of posterior elements
o Destruction of joints: Spine becomes fused posteriorly
o Vertebral bodies: Unburdened and become osteoporotic due to < mechanical force….< osteoblasts (main force is on fused posterior elements)
o Eventually vertebral bodies fuse within articulating area
Reiter Syndrome AKA
Reactive arthritis
what is the reiter syndrome triad?
Seronegative polyarthritis, conjunctivitis/uveitis, non-specific urethritis (nongonococcal) or cervicitis
what is the cause of Reiters syndrome
o Follows venereal exposure or episode of bacillary dysentery (some other bacteria, GI for instance or chlamidia): common in HIV+
o HLA-B27+
After the Venereal exposure how long until Reiters symptoms?
Arthritic symptoms within weeks of inciting bout of urethritis or diarrhea
what are the manifestations of Reiters syndrome?
Low back pain and stiffness most common joints affected are the ankles, knees and feet
Cant pee, can’t see and climb a tree
uvitis
urethritis
arthritis
How long do episodes of Reiters typically last?
6 mo
what percent of Reiters will develop Arthritis?
50%
Enteritis associated arthritis
cause:
GI infections: Salmonella, shigella, campylobacter
The lipopolysaccharide coat causes the autoimmune reaction
UC or Crohns- autoimmune diease
how long after a Gi infection wil the enteritis associated arthritis persist?
about 1 year
How do you treat UC or crohns related Enteritis associated arthritis?
UC you can resect the affected bowl but in crohns since it is a systemic disorder resection will not treat.
what are the affected joints in Enteritis associated arthritis?
Knees and ankles are most common, can affect the wrist fingers and toes, rare to accompany by alkylosing spondylosis
Psoriatic Arthritis
causes
HLA B 27 + –> Linked to psoriatic spondylitis and inflammation of distal interphalangeal joints
HLA DR4 associated with RA pattern involvement ( Hand, wrist and elbows)
Psoriatic Arthritis effects what?
Peripheral and axial joints
can also have conjunctivitis and Iritis
Not as severe as RA but remission more freq.
Infectious arthritis
Often has an predisposing condition which is what?
what does the infiltrate look like?
Osteomyelitis is the predisposing condition the bacteria that are common are similar to those of Osteomyelitis
usually suppurative ( a lot of WBC)
what are the 4 cardinal signs of Infectios Arthritis?
Fever Leukocytosis, ESR, pain
what joints are commonly infected with infectious Arthritis?
Knee, hip, shoulder, elbow, wrist and then Sternoclavicular joints.
what is more common in drug addicts?
Axial articulations
Infectous Arthritis TB
Define:
begins with:
Forms a:
Progressive Monoarticular disease
begins with osteomyelitis
Insidious onset
Forms a Confluent granulomas with central caseosnecorisis
Lyme Disease Infectious Arthritis aka
60-80% of untreated individuals develop
where does is usually affect?
What patten does it follow?
Borrella Burgdoferi
symptoms within a few weeks to years after onset of the disease
Large joints: Knee
A remitting and migratory pattern, can be in one joint one year and then a totally different the next
Few weeks to months
what is the morphology of limes disease?
what does a silver stain show?
cause:
Resembles RA- autoimmune component causing it
Small number of organisms
cause: HLA- DR molecules bind to an epitome of the borrella which Initiates a T cell reaction
Viral Infectious Arthritis
causes
Manifestations:
Parocirus B 19
Rubella
Hep C
Manifestations variable with a range from acute to subacute symptoms
Gout
Define
The endpoints of hyperemia from ANY cause resulting in joint deposition of monosodium urate crystals (Tophi)
How can Gout Present?
Acute or chronic
10% od the population has hyperuricemia but only
1/20 of the 10% has Gout
what is primary v secondary gout?
Primary: Hyperuricemia present with out other disease (33%)
secondary: in association with other dieases (67%) in people with fast growing malignancies such as lymphoma or leukemia due to high DNA turn over
what is the lab value for hyperurcemia?
> 7 mg/dl
what are the causes of increased Uric acid?
Overproduction
Increased catabolism of nucleic acid (greater cell turn over)
Decreased salvage of free purine bases
Decreased urinary uric acid excretion
does increased intake of meat lead to gout?
no
who is affected with Gout more, males or females?
95% is males
what is the normal renal handling of Uric acid?
90% of filtered uric acid is reabsorbed by the irate transporter 1 gene
what is the underlying cause for most primary gout?
Decreased filtration and under excretion of uric acid underlies most cases of primary gout
What medication reduces excretion of uric acid?
Thazide diuretics
What is the purine salvage pathway?
what mutation in the purine salvage pathway can lead to increased gout?
Purine catoblism–> Hypoxanthines–>Uric acid –> Allantion
Usually the Hypoxanthines is recycled and does not turn into uric acid
HGPRT Hypoxanthine transferases- if there is a mutation in this there will not be salvaging of the Purines
what drug works on the purine catabolism pathway and thus works for Gout?
what other med is used for gout?
Allopurinol: inhibits the Xanthine oxiase which is needed to turn Purine catoblism–> Hypoxanthines and therefore there will not be uric acid production.
Probenecid: increases uric acid secretions
What are the causes of Primary gout?
Overproduction of gout with either normal excretion, increased execrations
or
underexcretion with normal production
Or
HGPRT mutation (overproduction of uric acid)
What are the causes secondary Gout
associated with increased nucleic acid turnover, chronic renal disease, Inborn errors of metabolism (HGPRT deficiency - Lesch nyhan syndrome)
what does HGPRT stand for?
Hypoxanthine guanine phospboribosyl transferase
what is Lesh Nyhan syndrome?
is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), produced by mutations in the HPRT gene located on (the) X chromosome.
So how does increased uric acid cause gout?
increased formation leads to formation of monosodium irate crystals that deposit in the joint, this will cause a inflammatory response, which will lead to tissue damage
what is an explanation to why some people have increased uric acid levels but never develop gout?
ApoE Coating: this is made by your body, it actually coats the monosodium crystals and does not cause a immune response.
what are risk factors for developing gout?
Age: age of the individual and the duration of hyperuricemia are factors. Gout is rare before 20’s-30’s
Genetic predisposition: Runs in families and HCPRT mutation
Heavy alcohol : Concentrates the uric acid
Obesity: increase risk of asymptomatic gout
Thiazides:decreased excretion
Lead toxicity: increases the tendency to develop saturnine gout, damages the nephron in kidney
what is Tophaceous arthritis?
A Tophi is a large aggregation of crystals surrounded by forgien giant cells and an associated inflammatory response of mononuclear cells
What is Gouty Nethropathy?
Crystals deposit between the tubules.
what is the patho behind gout
Sodium urate crystals precipitate from supersaturated body fluids
Precipitated crystals absorb fibronectin, complement and other proteins on their surfaces.
Neutrophils that have ingested urate crystals release activated oxygen species and lysosomal enzymes: mediate tissue injury and promote an inflammatory response
WBCs can be found in synovial fluid
Cells die releasing crystals stimulating further inflammatory reaction
Extracelular soft tissue deposit of urate crystals surrounded by foreign body giant cells(macrophages): TROPHUS
explain the spiral of gout?
Attack starts:
Crystals form
WBC attack
Crystals pop the cell
Cell releases protein
Proteins call in more WBC and cause inflammation and pain
Protiesn lower the PH making it possible for more crystals to form…. top of the cycle again.
why is it common to see Gout in the big toe
receives less blood supply, and thus is acidic, more likely to have crystal formation in a acid environment.
what will gout look like on X ray?
Punched out juxta articular lytic lesions (Rat bite)
Minimal reactive new bone
Course of the diease Asymptomatic hyperuricemia: Acute gouty arthritis: Intercritical period: Tophaceous gout:
Asymptomatic hyperuricemia: precedes clinical manifestations -Can last years
Acute gouty arthritis: Painful
Involves one joint: later in course of disease is polyarticular
>50% have podagra: painful redened big toe (metatarsophalageal)
Fever- due to increased cytokins and IL1 IL6 TNF
Intercritical period
Asymptomatic interval between initial acute attack and subsequent episodes: Can last 10 years
Tophaceous gout
Appearance in cartilage, synovial membranes, tendons, and soft tissues
what are the renal manifestations of Gouty nephropathy?
Renal failure: Responsible for 10% of deaths in persons with gout
1/3rd have mild albuminuria, reduced GFR & decreased renal concentrating ability
Urate Stones
10% of all renal calculi in US are urate stones
Urate stones correlates with serum concentatriton of uric acid
Also have increased freuqency of calcium containing stones (uric acid may serve as a nidus)
because crystals may act as a nits central that calcium will deposit on top of
Gout is associated with what other 2 chronic dieases?
ATHEROSCLEROSIS and HTN
what is is Pseudo Gout
Gout:
Pseudo Gout:
Pseudogout is AKA:
Cuase:
1
2:
3:
Secondary cause of Pseudogout:
Gout: Monosodium Urate
Pseudo-GOUT: Calcium Pyrophosphate
PSEUDOGOUT is also called CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease)
IDIOPATHIC, HEREDITARY, SECONDARY
Secondary: joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes
what is ochronosis
the syndrome caused by the accumulation of homogentisic acid in connective tissues.
Pseudogout
Condition age:
Trauma and the aging process in cartilage promote:
Condition of old age: >50 % over age of 85 years
Trauma and the aging process in cartilage promote nucleation of CPPD crystals
