2.6.4. PATH LAB - Bone Pathology I (Part 3 of 3)

Question 1

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?

Answer 1

-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.

Question 2

Describe Osteoarthritis

Answer 2

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.

Question 3

Where do osteoarthritis lesions come from?

Answer 3

The lesions of OA stem from degeneration of the articular cartilage and its disordered repair.

Question 4

In the earlym orphology of osteoarthritis, what occurs?

Answer 4

In the early stages, chondrocytes proliferate, forming clusters.
Collagen type II fibers are cleaved, yielding fissures and clefts at the articular surface.

Question 5

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?

Answer 5

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).

Question 6

What shape of ostephytes do we see with osteoarthritis?

Answer 6

Mushroom-shaped osteophytes develop at the margins of the articular surface and are capped by fibrocartilage and hyaline cartilage that gradually ossify.

Question 7

Symptoms of osteoarthritis

Answer 7

Symptoms include deep, aching pains that get worse with use, morning stiffness, crepitus, and limitation of range of movement

Question 8

What are the structural abnormalities seen with osteoarthritis?

Answer 8

Heberden nodes are common in women

With time, joint deformity can occur, but unlike in rheumatoid arthritis, fusion does not take place

Question 9

What is Rheumatoid Arthritis

Answer 9

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

Question 10

The most important cytokines that can be isolated from the inflamed joints in Rheumatoid Arthritis are

Answer 10

IFN-γ
IL-17
TNF and IL-1
RANKL

*Note that your go to supported cytokine implicated with RA is TNF

Question 11

The synovium of RA contains germinal centers with secondary follicles and abundant _____ cells which produce what?

Answer 11

The synovium of RA contains germinal centers with secondary follicles and abundant plasma cells which produce antibodies, some of which are against self-antigens.

Question 12

What type of arthritis, symmetrical or asymmetrical, is RA and what does it affect primarily?

Answer 12

Typically manifests as a symmetric arthritis principally affecting the small joints in the hands and feet

Question 13

Hallmark histologically of RA

Answer 13

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

Question 14

Over time, what happens with a joint afflicted with RA?

Answer 14

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).

Question 15

What are the most common cutaneous lesions associated with RA?

Answer 15

Rheumatoid subcutaneous nodules are the most common cutaneous lesions.

Question 16

Describe the clinical course of RA

Answer 16

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

Question 17

How is pain related to activity with Rheumatoid Arthritis?

Answer 17

Pain improves with activity

Question 18

What lab results support RA?

Answer 18

Combination of rheumatoid factor and anti-CCP antibody

Also, IgM autoantibody against Fc portion of IgG (rheumatoid factor)

Question 19

What is Juvenile Idiopathic Arthritis (JIA)?

Answer 19

JIA is a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks

Question 20

When comparing JIA to RA, in JIA: Oligoarthritis is more or less common?

Answer 20

Oligoarthritis is more common

Question 21

When comparing JIA to RA, in JIA: Systemic disease is more or less frequent?

Answer 21

Systemic disease is more frequent

Question 22

When comparing JIA to RA, in JIA: Large joints are affected more often or are small joints?

Answer 22

Large joints are affected more often than small joints

Question 23

When comparing JIA to RA, in JIA: Rheumatoid nodules and rheumatoid factor are usually absent or present?

Answer 23

Rheumatoid nodules and rheumatoid factor are usually absent

Question 24

In JIA, what antibody is usually present?

Answer 24

ANA (antinuclear antibody) is common

Question 25

Like in adult RA, damage by JIA appears to be caused by what cells?

Answer 25

Like in adult RA, damage appears to be caused by Th1 and Th17 cells

Question 26

What mediators are associated with JIA?

Answer 26

IL-1, IL-17, TNF, and IFN-γ

Question 27

What are Seronegative Spondyloarthropathies?

Answer 27

Heterogenous group of disorders that are unified by pathologic changes in the ligamentous attachments rather than synovium. SI joints are often involved.

Question 28

What surface antigen are Seronegative Spondyloarthropathies related to?

Answer 28

HLA-B27

Question 29

What rheumatoid factor is linked to Seronegative Spondyloarthropathies?

Answer 29

Absence of Rheumatoid factor

Question 30

What is Ankylosing spondylitis also called and what is it

Answer 30

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)

Question 31

What surface antigen is positive in Ankylosing spondylitis?

Answer 31

HLA-B27

Question 32

What is Reactive Arthritis also known as and what is it?

Answer 32

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)

Question 33

What arthritis conditions are most common in men?

Answer 33

Reactive Arthritis (Reiter's) and Ankylosing Spondylitis

Question 34

What surface antigen is positive for Reactive Arthritis?

Answer 34

HLA-B27

Question 35

What is Reactive Arthritis or Reiter's typically caused by?

Answer 35

Most likely caused by an autoimmune reaction initiated by a prior infection of the genitourinary system (Chlamydia) or GI tract (Shigella, Salmonella, etc)

Question 36

Common symptoms of Reactive Arthritis?

Answer 36

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

Question 37

What causes Enteritis Associated Arthritis?

Answer 37

Caused by gastrointestinal infection by Yersinia, Salmonella, Shigella, and Campylobacter, among others

Question 38

How does Enteritis Associated Arthritis typically present?

Answer 38

Appears abruptly and tends to involve the knees and ankles Unlike reactive arthritis, it lasts for a year and then usually clears

Question 39

What is psoriatic Arthritis and where does it hit?

Answer 39

Chronic inflammatory arthropathy associated with psoriasis that affects peripheral joints like the hands and axial joints and entheses (ligaments and tendons)

Question 40

What alleles are related to Psoriatic Arthritis?

Answer 40

Genetically determined and related to HLA-B27 and HLA-Cw6 alleles

Question 41

Throwback question: What lab results do we see with osteoporosis?

Answer 41

No real lab values associated

Question 42

What clinical feature is common with psoriatic arthritis?

Answer 42

Synovitis of digital tendon = sausage finger/toe

Question 43

Compare psoriatic arthritis to Rheumatoid Arthritis

Answer 43

Usually not as severe as RA and remissions are more frequent

Question 44

What are we mainly worried about and what causes infectious arthritis?

Answer 44

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.

Question 45

What bacteria are most commonly the problem in Suppurative Arthritis for children, adolescents, and adults

Answer 45

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

Question 46

Clinical presentation of suppurative arthritis

Answer 46

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

Question 47

What causes mycobacterial arthritis?

Answer 47

Chronic progressive monoarticular infection caused by M. tuberculosis

Question 48

Clinical course of mycobacterial arthritis

Answer 48

Usually develops as a complication of adjoining osteomyelitis or after hematogenous dissemination from a visceral (usually pulmonary) site of infection

Question 49

What joints in particular are usually affected mycobacterial arthritis?

Answer 49

Weight-bearing joints

Question 50

What causes lyme arthritis?

Answer 50

Caused by an infection with the spirochete Borrelia burgdorferi, which is transmitted by deer ticks.

Question 51

Histology of lyme arthritis

Answer 51

Onion-skin thickening of arterial walls and mononuclear cell infiltrates

Question 52

Clinical course and treatment of lyme arthritis

Answer 52

Develops in 60-80% of untreated individuals with Lyme disease Majority of patients respond to antibiotic therapy

Question 53

What lab value do we see with Gout?

Answer 53

Hyperuricemia necessary but not sufficient for the development of gout (plasma urate >6.8 mg/dL)

Question 54

What causes Gout?

Answer 54

caused by overproduction of urate, decreased excretion or both

Question 55

What metabolic pathway is at fault for producing the excess uric acid seen in Gout?

Answer 55

Uric acid is the end product of purine metabolism; increased levels reflect an abnormality in purine production

Question 56

What enzyme in the purine metabolism pathway is associated with the defect that causes Gout?

Answer 56

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

Question 57

What causes the edema we see in Acute Arthritis? What happens at the great toe?

Answer 57

dense neutrophilic infiltrate in synovium and synovial fluid (great toe = podagra)

Question 58

What unique feature do we see with the Gout stage of Acute arthritis episodes?

Answer 58

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

Question 59

What do we see with the Gout stage of Chronic Tophaceous Arthritis?

Answer 59

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

Question 60

What are Tophi?

Answer 60

hallmark of gout large aggregations of urate crystals surrounded by an intense inflammatory reaction of foreign body giant cells

Question 61

What is Gouty nephropathy?

Answer 61

renal complications caused by MSU crystals or tophi in the renal medullary interstitium or tubules uric acid nephrolithiasis and pyelonephritis

Question 62

What may precipitate attacks of Gout?

Answer 62

alcohol and meat consumption may precipitate attack

Question 63

What are the "attacks" associated with Gout?

Answer 63

Transient Attacks of acute arthritis initiated by crystallization of monosodium urate within and around joints (MSU)

Question 64

What are the four stages of Gout?

Answer 64

1. Asymptomatic hyperuricemia 2. Acute Arthritis 3. Asymptomatic intercritical period 4. Chronic Tophaceous Gout

Question 65

When does the Gout stage of asymptomatic hyperuricemia appear?

Answer 65

appears around puberty in males and menopause in females

Question 66

When does the Gout stage acute arthritis appear? What does it present with?

Answer 66

after several years as sudden onset with excruciating joint pain

Question 67

What occurs during the asymptomatic intercticial period of Gout?

Answer 67

resolution of acute arthritis leads to symptom free period

Question 68

The final stage of Gout, Chronic Tophaceous gout, does what to the patients?

Answer 68

juxta-articular bone erosion leads to severe, crippling disease

Question 69

What is Pseudo-Gout?

Answer 69

studies suggest articular cartilage proteoglycans (normally inhibit mineralization) are degraded, allowing crystallization around chondrocytes

Question 70

Difference of Psuedo-Gout crystals when compared to Gout crystals and their effect on inflammation response

Answer 70

Crystals are rhomboid and weakly positively birefringence under polarized light Inflammation, if present, is usually milder than in gout

Question 71

Clinical course and treatment for Pseudo-Gout

Answer 71

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

Question 72

What are Joint Tumors and what causes them?

Answer 72

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.

Question 73

Compare Ganglion and Synovial cysts

Answer 73

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

Question 74

How do we know we are looking at a Ganglion Cyst under histology?

Answer 74

Ganglion cyst wall lacks a lining because it arises as a result of myxoid or cystic degeneration of connective tissue.

Question 75

What is the most common synovial cyst?

Answer 75

Common synovial cyst is the Baker’s cyst (forms in popliteal space)

Question 76

What is a Tenosynovial Giant Cell Tumor?

Answer 76

Term for several closely related benign neoplasms that develop in the synovial lining of joints, tendon sheaths, and bursae

Question 77

What causes a Tenosynovial Giant Cell Tumor and what collagen type is involved?

Answer 77

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

Question 78

What do Tenosynovial Giant Cell tumors look like?

Answer 78

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

Question 79

Compare diffuse and localized variants of Giant Cell Tumors

Answer 79

Diffuse type - tends to involve large joints Localized type - usually occurs as a discrete nodule attached to a tendon sheath, commonly in the hand

Question 80

Explain the biochemistry behind how uric acid is made from purines

Answer 80

1. DNA and RNA are degraded to make purines and other metabolites 2. 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.