Flashcards in Week 3 Deck (60):
Mucin clot test
-poor clot formation indicates?
-increased inflammation due to DECREASED hyaluronic acid = joint lubricator
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
2 types of synoviocytes
-phagocytic (macrophage like)
-make hyaluronic acid (GAG)
-make enzymes the degrade cartilage matrix
Pathogenesis of osteoarthritis has it's origins in what?
-start releasing inflammatory mediators and proteases that lead to net degradation of cartilage matrix
List the steps of OA pathogenesis
1. chondrocyte injury
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
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
OA more common in males or females?
RA - males or females?
females 3:1 males
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
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
Inflammatory mediators involved with RA have what pathogenic roles?
1. Upregulate degradative enzymes
2. Activate osteoclasts
JIA - more common in females or males?
Inflammation of insertion sites of tendons and ligaments
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
Most gout patients have hyperuricemia as a result of
How to tell the difference b/w gout and pseudogout
-negatively birefringent -> yellow when parallel to slow ray
-calcium pyrophosphate crystals
-positively birefringent -> blue when parallel to slow ray
small cyst, can be at joint capsule, arises from degeneration of connective tissue there
from herniation of synovium through joint capsule (or enlargement of bursa
-example Baker Cyst of knee
Tenosynovial giant cell tumor
benign, treated by surgical excision
Where does synovial sarcoma arise?
in deeper parts of the muscle
Most common cause of inflammatory monoarthritis
Temporal patterns in polyarthritis
-early phase of lyme disease
Tx for viral arthritis?
None; self resolving
Parvovirus B-19 associated with?
kids vs adults
classic presentation in adults
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.
Compare the 2 serological tests for RA
-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
NSAIDS for RA
-what can and can't they do for patients?
-Not disease modifying drugs
-symptomatic relief of joint pain and swelling
-Do NOT prevent joint damage
-GI bleed is the most concerning risk
When should DMARD tx be started? Why?
in most patients, erosive disease occurs w/in 2 years of the onset
start DMARDs ASAP
Gold standard DMARD?
how long does it take to work?
immunosuppressant - inhibits DHF reductase -> inhibits lymphocyte proliferation (folate antagonist)
-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
1. Monoclonal antibody
-sequesters TNF from cells
1. Inflixamab (Remicade)
2. Adalimumab (Humira)
2. Soluble TNF receptor
-competes w/ endogenous receptor
1. Entanercept (enbrel)
Think: "intercepts" TNF before it can bind to real TNF receptor
B cell depleting monoclonal anti-CD20 Ab
-inhibits co-stimulation of T-cell (selective co-stimulation modulator)
Dx of JIA requires:
1. onset < 16 y.o.
2. Requires persistent, objective arthritis for min of 6 weeks
JIA w/ highest mortality
-autoinflammatory NOT autoimmune
-disease driven by IL-1 and IL-6
1. tocilizumab (actemra) -> IL-6 inhibitor
2. Canakinumab -> IL-1 inhibitor
arthritis -> later on
-disease driven by
> 4 joints
Driven by TNF
Which JIA group is at highest risk for uveitis
Management of oligoarticular JIA
-intra-articular corticosteroid injection
What catalyzes the final conversions to uric acid in the purine degradation pathway?
Fx of uricase (uric acid oxidase)
Uric acid -> allantoin
-more soluble, readily excretable form
We don't have this enzyme
Most patients with gout have a problem with what?
They have issues with excreting uric acid i.e. UNDERSECRETION
Which major class of CV drugs interfere with uric acid secretion?
Drugs for managing acute gout?
-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
-most commonly used drug for gout
-contraindications -> renal insufficiency, PUD, concurrent warfarin tx, liver disease
-use when above 2 are contraindicated
Urate lowering drugs
-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
When should Allopurinol (Zyloprim) be used?
-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)
-benefits over allopurinol?
-non-purine xanthine oxidase inhibitor
-use w/ renal insufficiency
-don't get the hypersensitivity rxn
-pegylated uric oxidase
-can be used in patients who fail standard tx
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.
The only premalignant epidermal neoplasm?
risk for which carcinoma?
-2ndary to sunlight exposure
-early -> basal cells large hyperchromatic and pleomorphic
later -> parakeratotic (nuclei in stratum corneum)
Most common type to skin cancer?
Basal cell carcinoma
-also most common carcinoma overall
Nodular BCC found where in skin?
-smooth red papule
Progression of nevi?
Which direction do the melanocytes move?
junctional nevus -> compound nevus -> intradermal nevus
-move into the dermis
What characteristics describe acute dermatitis?
acute -> spongiosis (edema) and exocytosis
subacute/chronic -> progress towards epidermal hyperplasia and hyperkeratosis; decrease in spongiosis
-areas of greatest sebum production (head, upper trunk)
-stimulated by androgens
-increased yeast or inflammatory yeast
Histological and gross feature of psoriasis
-regular epidermal hyperplasia
-pale papillary dermis because edematous
-loss of granular layer
-neutrophils - UNIQUE
-rash on extensor extremities
-Yellow (neutrophils) elevated scales
-well demarcated lesions unlike dermatitis
How does clostridium perfringens spread through muscle?
Alpha toxin (phospholipase C)
-degrades sphingomyelin and lecithin
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
Human vaccine for anthrax contains?