2.6.4. PATH LAB - Bone Pathology I (Part 3 of 3) Flashcards
Discuss the blood supply, lymphatics and nerve supply of hyaline cartilage and the general function of it. What type of collagen is it made up of?
-Hyaline cartilage is a connective tissue ideally suited to serve as an elastic shock absorber and wear-resistant surface. It lacks a blood supply and does not have lymphatic drainage or innervation. It is 10% type II collagen.
Describe Osteoarthritis
Osteoarthritis, also called degenerative joint disease, is characterized by degeneration of cartilage that results in structural and functional failure of synovial joints. It is the most common type of joint disease.
Where do osteoarthritis lesions come from?
The lesions of OA stem from degeneration of the articular cartilage and its disordered repair.
In the earlym orphology of osteoarthritis, what occurs?
In the early stages, chondrocytes proliferate, forming clusters.
Collagen type II fibers are cleaved, yielding fissures and clefts at the articular surface.
In osteoarthritis, after chondrocytes proliferate and
Collagen type II fibers are cleaved yielding fissures and clefts at the articular surface, what happens to the chondrocytes and eventually the joint?
Eventually, chondrocytes die and full-thickness portions of the cartilage fall off.
The dislodged pieces fall into the joint, forming loose bodies (“joint mice”).
Friction with the opposing surface smooths and burnishes the exposed bone, giving it the appearance of polished ivory (bone eburnation).
What shape of ostephytes do we see with osteoarthritis?
Mushroom-shaped osteophytes develop at the margins of the articular surface and are capped by fibrocartilage and hyaline cartilage that gradually ossify.
Symptoms of osteoarthritis
Symptoms include deep, aching pains that get worse with use, morning stiffness, crepitus, and limitation of range of movement
What are the structural abnormalities seen with osteoarthritis?
Heberden nodes are common in women
With time, joint deformity can occur, but unlike in rheumatoid arthritis, fusion does not take place
What is Rheumatoid Arthritis
RA is a chronic inflammatory disorder of autoimmune origin that may affect many tissues and organs but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis
The most important cytokines that can be isolated from the inflamed joints in Rheumatoid Arthritis are
IFN-γ
IL-17
TNF and IL-1
RANKL
*Note that your go to supported cytokine implicated with RA is TNF
The synovium of RA contains germinal centers with secondary follicles and abundant _____ cells which produce what?
The synovium of RA contains germinal centers with secondary follicles and abundant plasma cells which produce antibodies, some of which are against self-antigens.
What type of arthritis, symmetrical or asymmetrical, is RA and what does it affect primarily?
Typically manifests as a symmetric arthritis principally affecting the small joints in the hands and feet
Hallmark histologically of RA
Hallmark = Synovitis leading to formation of a pannus - mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblasts that grows over the cartilage and causes its erosion
Over time, what happens with a joint afflicted with RA?
Over time, the cartilage is destroyed and the pannus bridges the apposing bones to form a fibrous ankylosis, which eventually ossifies and fuses the bones (bony ankylosis).
What are the most common cutaneous lesions associated with RA?
Rheumatoid subcutaneous nodules are the most common cutaneous lesions.
Describe the clinical course of RA
Symptoms usually begin in the hands and feet, followed by wrists, ankles, elbows and knees. It is uncommon for the spine to be involved.
Often progresses to destruction of the articular cartilage and ankylosis of the joints
How is pain related to activity with Rheumatoid Arthritis?
Pain improves with activity
What lab results support RA?
Combination of rheumatoid factor and anti-CCP antibody
Also, IgM autoantibody against Fc portion of IgG (rheumatoid factor)
What is Juvenile Idiopathic Arthritis (JIA)?
JIA is a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks
When comparing JIA to RA, in JIA: Oligoarthritis is more or less common?
Oligoarthritis is more common
When comparing JIA to RA, in JIA: Systemic disease is more or less frequent?
Systemic disease is more frequent
When comparing JIA to RA, in JIA: Large joints are affected more often or are small joints?
Large joints are affected more often than small joints
When comparing JIA to RA, in JIA: Rheumatoid nodules and rheumatoid factor are usually absent or present?
Rheumatoid nodules and rheumatoid factor are usually absent
In JIA, what antibody is usually present?
ANA (antinuclear antibody) is common
Like in adult RA, damage by JIA appears to be caused by what cells?
Like in adult RA, damage appears to be caused by Th1 and Th17 cells
What mediators are associated with JIA?
IL-1, IL-17, TNF, and IFN-γ
What are Seronegative Spondyloarthropathies?
Heterogenous group of disorders that are unified by pathologic changes in the ligamentous attachments rather than synovium. SI joints are often involved.
What surface antigen are Seronegative Spondyloarthropathies related to?
HLA-B27
What rheumatoid factor is linked to Seronegative Spondyloarthropathies?
Absence of Rheumatoid factor
What is Ankylosing spondylitis also called and what is it
Ankylosing Spondylitis (aka rheumatoid spondylitis or Marie-Strumpell disease) is a spondyloarthopathy that causes destruction of articular cartilage and bony ankylosis, especially of the sacroiliac and apophyseal joints (between tuberosities and processes)
What surface antigen is positive in Ankylosing spondylitis?
HLA-B27
What is Reactive Arthritis also known as and what is it?
Reactive Arthritis (Reiter syndrome)
Defined by a triad of arthritis, non-gonococcal urethritis or cervicitis, and conjunctivitis.
(Can’t See, Can’t Pee, Can’t Climb a Tree)
What arthritis conditions are most common in men?
Reactive Arthritis (Reiter’s) and Ankylosing Spondylitis
What surface antigen is positive for Reactive Arthritis?
HLA-B27
What is Reactive Arthritis or Reiter’s typically caused by?
Most likely caused by an autoimmune reaction initiated by a prior infection of the genitourinary system (Chlamydia) or GI tract (Shigella, Salmonella, etc)
Common symptoms of Reactive Arthritis?
Joint stiffness and low back pain are common early symptoms
Ankles, knees, and feet are affected most often, most commonly in an asymmetric pattern
Episodes usually “wax and wane” over several weeks to 6 months
What causes Enteritis Associated Arthritis?
Caused by gastrointestinal infection by Yersinia, Salmonella, Shigella, and Campylobacter, among others
How does Enteritis Associated Arthritis typically present?
Appears abruptly and tends to involve the knees and ankles
Unlike reactive arthritis, it lasts for a year and then usually clears
What is psoriatic Arthritis and where does it hit?
Chronic inflammatory arthropathy associated with psoriasis that affects peripheral joints like the hands and axial joints and entheses (ligaments and tendons)
What alleles are related to Psoriatic Arthritis?
Genetically determined and related to HLA-B27 and HLA-Cw6 alleles
Throwback question: What lab results do we see with osteoporosis?
No real lab values associated
What clinical feature is common with psoriatic arthritis?
Synovitis of digital tendon = sausage finger/toe
Compare psoriatic arthritis to Rheumatoid Arthritis
Usually not as severe as RA and remissions are more frequent
What are we mainly worried about and what causes infectious arthritis?
Infectious arthritis can be caused by microorganisms of all types and is potentially serious because it can cause rapid joint destruction leading to permanent deformities.
What bacteria are most commonly the problem in Suppurative Arthritis for children, adolescents, and adults
S. aureus is the main causative agent in older children and adults
Gonococcus is most common cause during late adolescence and young adulthood
H. influenza is most common cause in children younger than two years old
Clinical presentation of suppurative arthritis
Classic presentation: sudden development of an acutely painful and swollen joint that has a restricted range of motion
Systemic findings of fever, leukocytosis, and elevated ESR are common
What causes mycobacterial arthritis?
Chronic progressive monoarticular infection caused by M. tuberculosis
Clinical course of mycobacterial arthritis
Usually develops as a complication of adjoining osteomyelitis or after hematogenous dissemination from a visceral (usually pulmonary) site of infection
What joints in particular are usually affected mycobacterial arthritis?
Weight-bearing joints
What causes lyme arthritis?
Caused by an infection with the spirochete Borrelia burgdorferi, which is transmitted by deer ticks.
Histology of lyme arthritis
Onion-skin thickening of arterial walls and mononuclear cell infiltrates
Clinical course and treatment of lyme arthritis
Develops in 60-80% of untreated individuals with Lyme disease
Majority of patients respond to antibiotic therapy
What lab value do we see with Gout?
Hyperuricemia necessary but not sufficient for the development of gout (plasma urate >6.8 mg/dL)
What causes Gout?
caused by overproduction of urate, decreased excretion or both
What metabolic pathway is at fault for producing the excess uric acid seen in Gout?
Uric acid is the end product of purine metabolism; increased levels reflect an abnormality in purine production
What enzyme in the purine metabolism pathway is associated with the defect that causes Gout?
some have X-linked enzyme deficiency of HGPRT= hypoxanthine guanine phosphoribosyl transferase which interrupts purine salvage pathway so purine metabolites cannot be salvaged and are instead degraded to uric acid
What causes the edema we see in Acute Arthritis? What happens at the great toe?
dense neutrophilic infiltrate in synovium and synovial fluid (great toe = podagra)
What unique feature do we see with the Gout stage of Acute arthritis episodes?
long, slender, needle-shaped MSU crystals in cytoplasm of neutrophils. These needles are negatively birefringent under polarized light
“when crystals lay low (flat)=yellow”
para”ll”el= ye”ll”ow
What do we see with the Gout stage of Chronic Tophaceous Arthritis?
MSU crystals encrusts articular surface and forms visible deposits in the synovium
hyperplastic, fibrotic, and thickened by inflammatory cells; forms a pannus that destroys underlying cartilage
What are Tophi?
hallmark of gout
large aggregations of urate crystals surrounded by an intense inflammatory reaction of foreign body giant cells
What is Gouty nephropathy?
renal complications caused by MSU crystals or tophi in the renal medullary interstitium or tubules
uric acid nephrolithiasis and pyelonephritis
What may precipitate attacks of Gout?
alcohol and meat consumption may precipitate attack
What are the “attacks” associated with Gout?
Transient Attacks of acute arthritis initiated by crystallization of monosodium urate within and around joints (MSU)
What are the four stages of Gout?
- Asymptomatic hyperuricemia
- Acute Arthritis
- Asymptomatic intercritical period
- Chronic Tophaceous Gout
When does the Gout stage of asymptomatic hyperuricemia appear?
appears around puberty in males and menopause in females
When does the Gout stage acute arthritis appear? What does it present with?
after several years as sudden onset with excruciating joint pain
What occurs during the asymptomatic intercticial period of Gout?
resolution of acute arthritis leads to symptom free period
The final stage of Gout, Chronic Tophaceous gout, does what to the patients?
juxta-articular bone erosion leads to severe, crippling disease
What is Pseudo-Gout?
studies suggest articular cartilage proteoglycans (normally inhibit mineralization) are degraded, allowing crystallization around chondrocytes
Difference of Psuedo-Gout crystals when compared to Gout crystals and their effect on inflammation response
Crystals are rhomboid and weakly positively birefringence under polarized light
Inflammation, if present, is usually milder than in gout
Clinical course and treatment for Pseudo-Gout
Frequently asymptomatic, but can produce acute, subacute or chronic arthritis that can be confused with osteoarthritis or RA
Can last from several days to weeks
~50% of patients experience significant joint damage
There is no known treatment that prevents or slows crystal formation
What are Joint Tumors and what causes them?
Reactive tumor-like lesions, such as ganglions, synovial cysts, and osteochondral loose bodies commonly involve joints and tendon sheaths. They usually result from trauma or degenerative processes and are much more common than neoplasms.
Compare Ganglion and Synovial cysts
Ganglion = small (1-1.5 cm) cyst that is almost always located near a joint capsule or tendon sheath (most common around wrist joints)
Synovial cyst = caused by herniation of synovium through a joint capsule or massive enlargement of a bursa
How do we know we are looking at a Ganglion Cyst under histology?
Ganglion cyst wall lacks a lining because it arises as a result of myxoid or cystic degeneration of connective tissue.
What is the most common synovial cyst?
Common synovial cyst is the Baker’s cyst (forms in popliteal space)
What is a Tenosynovial Giant Cell Tumor?
Term for several closely related benign neoplasms that develop in the synovial lining of joints, tendon sheaths, and bursae
What causes a Tenosynovial Giant Cell Tumor and what collagen type is involved?
Reciprocal somatic chromosomal translocation, T(1;2)(p13;q37), resulting in the fusion of the type VI collagen promoter upstream of the M-CSF gene.
Results in overexpression of M-CSF, which stimulates proliferation of macrophages
What do Tenosynovial Giant Cell tumors look like?
Red-brown to orange-yellow
Diffuse tumors are usually poorly circumscribed
Localized tumors are well circumscribed
Both diffuse and localized variants are heavily infiltrated by macrophages
Compare diffuse and localized variants of Giant Cell Tumors
Diffuse type - tends to involve large joints
Localized type - usually occurs as a discrete nodule attached to a tendon sheath, commonly in the hand
Explain the biochemistry behind how uric acid is made from purines
- DNA and RNA are degraded to make purines and other metabolites
- Purines enter the lumen in the form of AMP and GMP which are then turned into Hypoxanthine and Guanine respectively. These two fuse to become Xanthene, which then becomes uric acid via xanthene oxidase. Uric acid then leaves the lumen for the blood, then excretion in urine via the kidneys.
Problems with Gout occur when too much gets pushed into the blood, not enough is removed from the blood, or Hypoxanthene and Guanine are not salvaged by HGPRT, leading to too much uric acid like in the first problem.
