BS 2 Flashcards
Articular hyaline cartilage:
How get nutrition
Top 3 components
Diffusion nutrition from synovial fluid
- Avascular (why doesn’t heal)
Components: H2O, PG, collagen (type 2 = car-two-lage)
Describe collagen structure
3 alpha collagen chains in a triple helix
Where do you find type X cartilage
Fracture callus
Hypertrophic zone growth plate
Calcified tidemark of articular cartilage
What are 2 genetic disorders that affect type 2 collagen of cartilage?
Achond - lethal kind
Spondyloepiphyseal dysplasia (SED-C) - congenita
- Mentally normal
- Proportional dwarfism (trunk + limbs)
What is the structure of PG
HA backbone
Protein core
Chondroitin + keratan sulfate
Overall negative charge molecule
Diastrophic dysplasia:
Inheritance
Mutated protein
Clinical presentation
AR
Sulfate transporter mutation - can’t get sulfate into cells to make PG (chondroitin and keratin sulfate)
Presentation
- Dwarfism
- Hitchhiker thumb
- Cauliflower ear
“If your sulfate transporter isn’t working, you have to hitchhike”
What is the only cell in cartilage? What TF controls it?
Chondrocytes - SOX9
What are the layers of cartilage from superficial to deep
Tangential - chondrocytes lay flat
- Most H2O + lubricin, least PG
Transitional/radial
Deep zone
Tidemark - contains Ca2+ cartilage (type X)
Subchondral bone
Cancellous bone
What are the 2 types of cells in synovium
Type A = mArcophAge like cells
- Removes debris from joint
- From bone marrow (hematopoietic)
Type B = fiBroBlast like cells
- Mesenchymal derived
- Make synovial fluid - lubricin, etc
What molecule is responsible for synovial fluid viscosity
Hyaluronic acid
Name molecules in synovial fluid
Hyaluronic acid
Lubricin
HA binds lubricin
Lubricin works via boundary lubrication
How does cartilage change with OA
Wet - increase H2O
Decrease modulus of elasticity (stress strain curve has lower slope)
How does cartilage change with aging
Less H2O - dry
Brittle = increased mod of elasticity
Increased decorin
What signaling molecules are upregulated in OA
IL 1beta
MMPs
ADAMTS
What is an antimicrobial peptide over expressed in psoriasis patients
Cathelicidins
Increased keratin in wound helaing
While interleukin causes the liver to bump CRP + ESR
IL 6
Name the class of drug + specific mechanism
Etanercept
Infliximab
Adalimumab
TNF alpha blockers
Etanercept - receptor fusion protein
Infliximab - chimeric IgG Ab
Adalimumab - mAb
Mechanism of anakinra
IL 1 receptor blocker
Mechanism of tocilizumab
IL6 receptor antibody
Rituximab mechanism
Ab to CD 20 antigen (B cell inhibitor)
What does each nomenclature mean
-mab
-ximab
-zumab
-cept
-mab = mAb
-ximab = chimeric mAb (mouse+human)
-zumab = humanized mAb
-cept = fusion of a receptor to Fc part of IgG
What is the first cell recruited to fracture hematoma?
Neutrophils - “inflam phase”
Why cytokines do macrophages release
IL1/6
TNF alpha
VEGF
M-CSF
What cell mediates osteolysis?
What cytokine is release that stimulates osteoclasts?
Macrophages - osteolysis
RANKL - osteoclasts - dissolve bone
What is tabetic arthropathy? Describe clinical presentation
Tabes dorsalis aka neurosyphilis
Joint changes before neuro diagnosis
XRs look WAY worse than the sx
Will also have unsteady gait, bloody effusion w/ neg infx wu
Diagnose:
Neuropathic arthritis XR
Loss of pain/temp sensation in a capelike distribution
Syrinx causing neuropathic arthritis
Often middle aged
Often shoulder or elbows affected - 1 joint
What is black cartilage disease
Inheritance
Alkaptonuria
AR
Homogentisic acid oxidase
Excess homogentisic acid deposited in joints - tints matrix black
Predisposes to Ca deposition in cartilage (chondrocalcinosis) and early OA (young joint replacement)
Name that arthritis:
Viking heritage
FHx arthritis + liver disease
Hyperpig skin
Chondrocalcinosis on XRs w/ +crystals on aspirate
Screening test
Trt
Hemochromatosis w/ CPPD
- Hereditary excess iron absorption
“Viking curse”
Bronze DM - cirrhosis, DM, skin pigmentation
Screen w/ transferrin + ferratin tests
Trt: blood letting for iron control
Describe the crystals:
Gout
CPPD
Gout - yellow, urate, needle, neg birefringe
CPPD - blue, post birefringe
Tumoral calcinosis:
2 causes
What kind of crystals are deposited
Too much blood PO4
- Renal failure - can’t excrete
- Familial tumoral calcinosis - low FDF23 = can’t excrete
Ca hydroxyapatite
What diseases are these HLAs associated with
HLA B27
HLA DR3
HLA DR4
HLA B27 - ank spond, JRA
HLA DR3 - SLE
HLA DR4 - RA
Describe the pathophys of RA
Genetically susceptible person - HLA DR4/DW4
Some antigen trigger
B cells make auto Abs vs RF, aCCP
CD4 T cells infiltrate around jt tissues
- Release TNFa, IL 1/6
Inflam cells proliferate synovium = pannus
What cells are in RA pannus
CD4 T cells
Macrophages - TNFa, IL1/6
Fibroblast (type B) - MMPs, proteases, RANK-L
What 2 Abs are diagnostic for RA?
RF = IgM to IgG
Anti-CCP = anti cyclic citrullinated peptide Abs
- Most sensitive + specific for RA
HST rxn
Type 1 - cell type and example
Type 2 - “ “
Type 1 - IgE mediated, mast cells release histamine
Ie latex allergy
Type 2 - IgM or IgG mediated
Ie myasthenia gravis, transfusion reaction (ABO mismatch)
SLE:
Pathophys
3 Abs
Ag-Ab immune complex deposition - T3 HST rxn
Sensitive: ANA
Specific:
Anti-dsDNA
Anti-Sm (=RNA)
Sjogren:
Pathophys
2 Abs
Other immune cell involvement
CD4 T cells infiltrate saliva and lacrimal glands
- Dry mouth/eyes
Abs vs ribonucleoproteins: SS-A(Ro) + SS-B(La)
Increased IgA
Scleroderma:
Pathophys
3 Abs
CD4 T cells activate fibroblasts
More type 1 collagen deposition
Calcinosis
ANA+
Localized = CREST = anticentromere Ab
Diffuse = anti-DNA topoisomerase I Ab
What is the triad of reactive arthritis (Reiter’s syndrome)
Cause
Trt
Cant see - conjunctivitis
Cant pee - urethritis
Cant bend the knee - arthralgia
“Red eyes, burning pee, joint effusions and pain”
Chlamydia
Diarrheal causes: Shigella, salmonella
Trt - supportive, treat underlying bug if possible
