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Flashcards in Week 3 Deck (60):
1

Mucin clot test
-measures?
-poor clot formation indicates?

-joint viscosity

-increased inflammation due to DECREASED hyaluronic acid = joint lubricator

2

3 components of hyline cartilage matrix and fx

1. Proteoglycans - elasticity and reducing friction

2. Type II collagen - tensile strength

3. Water - normal distention and friction reduction

3

2 types of synoviocytes

Type A
-phagocytic (macrophage like)

Type B
-make hyaluronic acid (GAG)
-make enzymes the degrade cartilage matrix

4

Pathogenesis of osteoarthritis has it's origins in what?

Chondrocytes
-start releasing inflammatory mediators and proteases that lead to net degradation of cartilage matrix

5

List the steps of OA pathogenesis

1. chondrocyte injury
2. cloning
3. release of inflammatory mediators and proteases
4. Proteoglycan and collagen degraded -> matrix weakened
5. fibrillation - superficial clefting + softening
6. Cracking of matrix and breaking off of fragments
7. Chondrocyte death

6

Define:

eburnation

subchondral cysts

Osteophytes

1. smooth bone surfaces due to bone-bone grinding

2. fluid entry into small fractures

3. bony growths at margins of articulate surfaces
-can compress nerves roots

7

OA more common in males or females?

EQUAL

8

RA - males or females?

females 3:1 males

9

What is rheumatoid factor?
Explain it's role in RA pathogenesis

IgM Ab against Fc portion of IgG
-Forms immune complex with IgG which leads to Type III hypersensitivity
-C5a released which attracts inflammatory cells to the joint

10

Describe pannus formation.
How does it relate to ankylosis?

Mass of inflamed, abnormal synovium,
drapes over and causes degradation of cartilage surface

-Pannus may bridge joint surfaces which can lead to tight union = Ankylosis

11

Inflammatory mediators involved with RA have what pathogenic roles?

1. Upregulate degradative enzymes

2. Activate osteoclasts

12

JIA - more common in females or males?

females 2:1

13

Define enthesitis

Inflammation of insertion sites of tendons and ligaments

14

List 4 seronegative spondyloarthrpoathies

1. Ankylosing spondylitis
-SI and intervertebral joints

2. Reiter syndrome
-arthritis, urethritis, conjunctivitis

3. Psoriatic arthritis

4. Arthritis associated w/ inflammatory bowel disease

15

Most gout patients have hyperuricemia as a result of

decreased excretion

16

How to tell the difference b/w gout and pseudogout

Gout
-urate crystals
-negatively birefringent -> yellow when parallel to slow ray

Pseudogout
-calcium pyrophosphate crystals
-positively birefringent -> blue when parallel to slow ray

17

Ganglion cyst

small cyst, can be at joint capsule, arises from degeneration of connective tissue there

18

Synovial cyst

from herniation of synovium through joint capsule (or enlargement of bursa
-example Baker Cyst of knee

19

Tenosynovial giant cell tumor

benign, treated by surgical excision

20

Where does synovial sarcoma arise?

in deeper parts of the muscle

21

Most common cause of inflammatory monoarthritis

GOUT

22

Temporal patterns in polyarthritis

1. Migratory
-Rheumatic fever
-gonococcal
-early phase of lyme disease

2. Additive
-RA
-SLE
-psoriasis

3. Intermittent
-gout
-reactive arthritis

23

Tx for viral arthritis?

None; self resolving

24

Parvovirus B-19 associated with?

kids vs adults

classic presentation in adults
-joints involved?

5th disease - erythema infectiosum (EI)

kids - slapped cheek

adults - joints more involved

Acute onset symmetric polyarthralgia or
polyarthritis with stiffness in young women exposed to kids with E.I.

25

Compare the 2 serological tests for RA

1. RF

2. Anti-CCP
-Autoantibodies to peptidic antigens containing the amino acid citrulline (generated by posttranslational deamination of arginyl residues)
-highly specific for RA and present early in the course of the disease
-marker of bone destructive process

26

NSAIDS for RA
-MoA
-what can and can't they do for patients?
-side effects?

-COX-2 inhibitors

-Not disease modifying drugs
-symptomatic relief of joint pain and swelling
-Do NOT prevent joint damage

-GI bleed is the most concerning risk

27

When should DMARD tx be started? Why?

in most patients, erosive disease occurs w/in 2 years of the onset

start DMARDs ASAP

28

Gold standard DMARD?

MoA?

how long does it take to work?

methotrexate

immunosuppressant - inhibits DHF reductase -> inhibits lymphocyte proliferation (folate antagonist)

3-8 weeks

29

Leflunomide
-brand
-MoA
-adverse effects

-Arava

-pyrimidine synthesis inhibitor
-has anti-proliferative and anti-inflammatory activity

->blocks T cell clonal expansion

-highly teratogenic -> must be stopped 2 years before planned pregnancy

30

TNF antagonists

1. Monoclonal antibody
-sequesters TNF from cells

DRUGS

1. Inflixamab (Remicade)
2. Adalimumab (Humira)
3. Certolizumab
4. Golimumab

2. Soluble TNF receptor
-competes w/ endogenous receptor

DRUGS

1. Entanercept (enbrel)

Think: "intercepts" TNF before it can bind to real TNF receptor

31

Tocilizumab

-brand
-MoA

Actemra

IL-6 inhibitor

32

Rituximab

-MoA

B cell depleting monoclonal anti-CD20 Ab

33

Abatacept

-brand
MoA

-Orencia

-inhibits co-stimulation of T-cell (selective co-stimulation modulator)

34

Dx of JIA requires:

1. onset < 16 y.o.

2. Requires persistent, objective arthritis for min of 6 weeks

35

JIA w/ highest mortality

Systemic JIA

36

Systemic JIA
-pathology
-drugs
-presentation

-autoinflammatory NOT autoimmune
-disease driven by IL-1 and IL-6

DRUGS
1. tocilizumab (actemra) -> IL-6 inhibitor
2. Canakinumab -> IL-1 inhibitor

Presentation
-fever
-adenopathy
-rash
-arthralgia
arthritis -> later on

37

Polyarticular JIA
-definition
-disease driven by
-Drugs

> 4 joints

Driven by TNF

DRUGS
1. Methotrexate
2. Etanercept

38

Which JIA group is at highest risk for uveitis

Oligoarticular JIA

39

Management of oligoarticular JIA

-intra-articular corticosteroid injection

40

What catalyzes the final conversions to uric acid in the purine degradation pathway?

Xanthine oxidase

41

Fx of uricase (uric acid oxidase)

Uric acid -> allantoin
-more soluble, readily excretable form

We don't have this enzyme

42

Most patients with gout have a problem with what?

They have issues with excreting uric acid i.e. UNDERSECRETION

43

Which major class of CV drugs interfere with uric acid secretion?

Diuretics

44

Drugs for managing acute gout?
Usage guidelines?
Side effects?
Contraindications?

1. Colchicine
-must be used w/in 8 - 12 hours of the gout attack to be effective
-Diarrhea can be a major issue
-Can't used if patient is on dialysis
-must be cautious if patient has renal or hepatic disease

2. NSAIDS
-most commonly used drug for gout
-contraindications -> renal insufficiency, PUD, concurrent warfarin tx, liver disease

3. Corticosteroids
-fast acting
-use when above 2 are contraindicated

45

Urate lowering drugs

1. Probenecid
-1st line for lowering SUA
-acts on the proximal tubules to increase excretion of uric acid
-can't be used if patient has nephrolithiasis, renal insufficiency or if using salicylates
-adverse effect -> hepatotoxicity

2. Losartan (Cozaar, Hyzaar) - ACE inhibitor

3. Fenofibrate (Tricor) - antihyperlipidemic agent

-2 birds w/ 1 stone using the above 2 drugs

46

When should Allopurinol (Zyloprim) be used?
MoA?
Adverse effects?

-If probenecid contraindicated -> pt. has kidney stones or renal impairment
-patient is overproducer

-xanthine oxidase inhibitor (precursors much more soluble than uric acid)

-Hypersensitivity rxn can be fatal (1/4000)

47

Febuxostat
-MoA?
-indications?
-benefits over allopurinol?

-non-purine xanthine oxidase inhibitor

-use w/ renal insufficiency

-don't get the hypersensitivity rxn

48

Pegloticase
-MoA
-indications

-pegylated uric oxidase

-can be used in patients who fail standard tx

49

How to differentiate b/w SK and Warts on histology?

Warts (verucca, condyloma)
Kilocytes with warts due to HPV infection
-Nuclear enlargement (two to three times normal size)
-Irregularity of the nuclear membrane contour
-A darker than normal staining pattern in the nucleus, known as Hyperchromasia
-A clear area around the nucleus, known as a perinuclear halo.

50

The only premalignant epidermal neoplasm?
caused by?
risk for which carcinoma?
features?

-Actinic keratosis
-2ndary to sunlight exposure
-SCC

FEATURES
-early -> basal cells large hyperchromatic and pleomorphic
later -> parakeratotic (nuclei in stratum corneum)

51

Most common type to skin cancer?

Basal cell carcinoma
-also most common carcinoma overall

52

Nodular BCC found where in skin?
gross appearance?

-dermis
-smooth red papule

53

Progression of nevi?
Which direction do the melanocytes move?

junctional nevus -> compound nevus -> intradermal nevus

-move into the dermis

54

What characteristics describe acute dermatitis?
subacute?
chronic?

acute -> spongiosis (edema) and exocytosis

subacute/chronic -> progress towards epidermal hyperplasia and hyperkeratosis; decrease in spongiosis

55

Seborrheic dermatitis
-occurs where?
-stimulated by?

-areas of greatest sebum production (head, upper trunk)

-stimulated by androgens
-increased yeast or inflammatory yeast

56

Histological and gross feature of psoriasis

HISTOLOGY
-diffuse parakeratosis
-regular epidermal hyperplasia
-pale papillary dermis because edematous
-loss of granular layer
-neutrophils - UNIQUE

GROSS
-rash on extensor extremities
-Yellow (neutrophils) elevated scales
-well demarcated lesions unlike dermatitis

57

How does clostridium perfringens spread through muscle?

Alpha toxin (phospholipase C)
-degrades sphingomyelin and lecithin

58

What's needed for bacillus anthracis to cause damage?

Toxin - 3 parts
1. PA - protective Ag
2. LF - lethal factor (metalloprotease)
3. EF - edema factor (adenylate cyclase)

Need PA + LF or EF for damage

59

Human vaccine for anthrax contains?

PA

60

Bacillus anthracis capsule characteristics

1. D-Glutamic acid
2. anti-phagocytic
3. Weakly antigenic