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emm64
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How is histamine synth?
Decarboxylation of histidine
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Which cells have Histamine and when is it released?
- Mast and basophils exocytosis or degranulation, injury, IgE (allergy), drugs
- Skin, bronchial & intestinal mucosa
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What are physiologic effects of histamine?
- Relax vascular smooth muscle
- Large vessel constriction, contract non vascular smooth muscle
- Stimulate exocrine esp gastric
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What are the types of H receptors?
- H1: vasodilation, bronchoconstriction, pain & itching (GCPR)
- H2: stimulate gastric acid
- H3: decrease neurotransmitter (NE, Ach, 5HT) rls
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What are alkylamines?
- H antagonist, 1st gen, cold symptoms
- Chlorpheniramine maleate
- Bromopheniramin maleate
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What are ethanolamines?
- Anti-cholinergic and sedation H antagonists
- Benadryl, (diphenhydramine HCl)
- Dimenhydrinate (Dramamine) anti-emetic
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Which H antagonist is a good anti emetic?
Dimenhydrinate (Dramamine)
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Which H antagonist is used for allergic rhinitis, conjunctivitis?
Phenothiazines: promethazine HCl
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What is the significance of piperidines?
- 2nd gen antihist devoid of CNS effects
- terfenadine (seldane)
- fexofenadine HCl(allegra
- Loratadine (Claritin)
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What is the action of antihistimines?
- Inhibit GI/bronchial smooth muscle contraction
- Inhibit capillary permeability
- Antagonize salivary, lacrimal secretions
- Relatively ineffective for bronchospasms (asthma & anaphalaxis)
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What are the side effects of antihistamines?
- CNS depression (not H1 and anti-cholineric specific)
- GI
- Arrhythmia(rarely astemizol terfenadine)
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What antihistamine is dangerous with antibiotics?
Astemizole and erythromycin
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How are antihistamines used in dentistry?
- Adjuncts for angioedema
- Hydroxyzine and diphenhydramine for sedation
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How do autoimmune diseases develop?
- Problem w/negative selection in thymus
- Infection (mimicry, super antigens)
- Genetics(HLA)
- T cell peripheral suppression
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What does every reactive Tcell express?
FasL (eyes have Fas receptors-> Tcell death)
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What are the systemic autoimmune diseases(others organ-specific)?
RA, SLE, primary sjogrens, scleroderma
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What is the only type I hypersensitivity that causes disease?
Chronic urticaria: persistent itchy rash IgE
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What are the features of graves disease?
- Type II stimulating thyroid antigen
- 30’s, women, bug eyed
- diffuse goiter and hyperthyroidism
- HLA DR3 class II
- ID: TSI(thy, stim Ig), TGSI(thy growth stim Ig), TBI (thy-binding inhibitory Ig)
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What is autoimmune hemolytic anemia?
- Type II Rh Ag, I Ag, destroys RBC by FcR, phag -> anemia
- IgM: kupffer (liver)
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What is thrombocytopenic purpura?
Autoimmune, platelet integrin, abnormal bleeding
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What is goodpastures?
- Non collagenous domain of BM col IV
- Leads to glomerunephritis and pulmonary hemmrhage
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What is pemphigus vulgaris?
- Epidermal cadherin autoantigen
- Blisters
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What is acute rheumatic fever?
- Strep cell wall antigens cross react w/ cardiac muscle
- Arthritis, myocarditis
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What is cryoglobulinemia?
- Type III Rheumatoid factor IgG complexes-> systemic vasculitis
- Form when hypothermic
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What is SLE
- Type III hypersensitivity
- Autoantigen DNA, histones, ribosomes, snRNP, scRNP
- Leads to glomerulonephritis, vasculitis, arthritis
- Malar butterfly rash
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What is the dental presentation of SLE?
Oral lesions on buccal mucosa and roof
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Which molecules do mycoplamic ones mimic?
- RBC mb Ags (create rxn aginst host glycophorins
- Autoimmune hemolytic anemia
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Explain type I diabetes.
- Type IV hypersensitivity
- TH1 (stim by IFN-gamma) attack Beta pancreatic cells
- Glucogon and somatostatin still ok
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What gene puts you at risk for type I diabetes?
HLA DR3/4
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What is rheumatoid arthritis?
- Chronic type IV hypersensitivity w inflammatory polyarthritis of joints
- Pannus: rheumatoid synovial mb
- Erode joint and activate osteoclasts
- Autoreactive CD4 T produce (TNF-a & IL-6) MMP and RANK by fibroblasts
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What do RA joints look like histologically?
Hypercellular, not a lot of eosin (proteins, pink)
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What is MS?
- Tcell activation against CNS (microglia or dendritic cells of brain)
- Inflammatory reaction via mast cells degrades myelin
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Which dye to they use to diagnose MS?
Gadolidium: binds myelin (show up as white plaques in CT)
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What is the pathophys of scleroderma?
- Type IV (CD4+) Systemic sclerosis: excessive fibrosis (fibroblasts) CD4+ mainly in GI, muscles (diffuse or limited)
- No elasticity
- What is a suggested pathogensis of SLE?
- Failure of T and B cell tolerace to defective clearance of nuclear antigens during apoptosis
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What is Sjogren’s syndrome?
- Lymphocytic (CD4+ and B cells infiltration of exocrine glands
- Ductal epithelial target
- Xerostomia
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What is amyloidosis?
- Secondary to autoimmune (never primary)
- Proteinaceous materials in tissue interstitum (congo red)
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What are the 2 types of BMT?
- Bone marrow transplant
- Autologous: chemosensitive
- Allogenic: leukemia
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What is a major hemostasis side effect of chemo?
- Bone marrow suppression
- Oral mucositis
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What are the main dental concerns for chemo?
- Bone marrow: bleeding, infection, anemia
- Mucositis: nutrition, hydration
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What is oral mucositis and the phases?
- Mucosal inflammation ulceration (from chemo typically)
- PHASES
- 1: initiation (DNA injury)
- 2: signaling (messengers)
- 3: amplification (apoptosis)
- 4: ulceration (pain)
- 5: healing
- Grades:
- 0: no symptoms
- 1: soreness
- 2: ulcers, eat solids
- 3: ulcers, liquids
- 4: ulcers: alimentation not possible
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Which areas of oral cavity are keratinized?
- Dorsum of tongue
- Hard palate
- Attached gingiva
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What are the early and late presentations of mucositis?
- Early: Erythema, edema, sensitivity, soreness
- Late: ulcerations, pain, infections, nutrition, bleeding
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What is the main goal of dental therapy for chemo?
- Eliminate sources of infection
- Treat between cycles
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What do PGs do?
- Platelet aggregation, vasodilation, vasc permeability, pain sensitivity
- PDX, PGI: vasodilation, antiaggregating
- PGE2: erythema, edema, pain, fever
- PGF2a: vasodilator, uterus contraction
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What do leukotrienes do?
- Immediate hypersensitivity
- LTC4, LTD4: broncioconstriction, mucosal edema
- LTB4: chemotaxis
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Describe the secretions of lymphocytes.
- IL: stimulate T and B cells
- MCP-1: monocyte accumulation
- GM-CSF: granulocyte/macrophace colony
- INF-a: antiviral, macrophage
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What is the difference between COX 1 & 2?
- COX1: constitutive regulate renal, mucosa integrity
- COX2: inducible (inflammation)
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What is prostaglandin role in GI?
Mucosa protective
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What is a hapten?
Protein-free that can combine and elicit immune response
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What does a dentist need to ID in allergy?
- Severity, speed of onset, extent(local/general)
- Know HX: specifics, timing, treatment
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What are manifestations of allergy?
- Skin: Erythema, urticarial, wheals, rash pruritus
- Resp: bronchospasm, laryngeal edema
- GI: nausea, pain
- CV: angioedema, hypotension, lightheadedness, tachycardia, syncope
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What is allergenic in LA?
Sodium bisulfite (antioxidant)
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What is allergenic in dental office?
LA(Na bisulfite antioxidant), Antibiotics, latex, pain meds
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Which allergic reaction is faster IV or PO?
IV
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What should you prescribe for suspected generalized allergy?
- Diphenhydramine (Benadryl) 25-50mg PO TID 3x
- (can be given IV/IM should be escored home)
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What if respiratory or CV allergy?
- Stop, 911, upright if breathing problems, supine/trendelenberg if hypotensive
- Oxygen, bronchodilator
- EPI: .3-.5mg SC/IM (every 5 minutes)
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What is the common factors of CT?
- Cells (fibroblasts, chondrocytes
- ECM(collagens, proteoglycans
- CD44, integrins
- Enzymes
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What is ANCA?
- Anti-neutrophil cytoplasmic antibody
- Seen in systemic vasculitis
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Which autoantibodies found in Sjogrens?
RNA-assosciated (Ro & La)
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Which autoantibodies seen in scleroderma?
Anticentromere, antitopoisomerase
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What is a bursa?
Synovial lined sac separate bone and muscle/skin
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What is enthesis?
Attachement of muscle tendon and ligaments
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What is the characteristic feature of RA?
- Persistent inflammatory synovitis (slows down with advanced AIDS and pregnancy)
- What is a rheumatoid pannus?
- Early formation of granulation tissue w proliferating fibroblasts and some inflammatory cells
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What are early signs of RA?
- Morning stiffness > 1 hour
- Swelling of 3 or more joints
- Leads to swan neck deformities
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What are x-ray differences of OA and RA?
- Osteo: no cartilage, bone spurs
- RA: synovial inflammation w bone erosion
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What is a complication of RA in dental setting?
Subluxation of C1 and C2 cant’ move head, may need to be ligated
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What is felty’s syndrome?
RA, splenomegaly and neutropenia
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How is RA dignosed?
- No specific, RF in 80%
- ESR and eanemia
- Variable
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How is RA treated?
- Drugs: NSAIDS, corticosteroids (disease modifying antirheumatic drugs (DMARDs)
- Surgery
- Immunologic: entanercept or infliximab (TNF-a inhibitors)
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How is SLE diagnosed?
- ANA (antinuclear Ab)
- Anti-dsDNA & anti-Sm MORE specific, LESS sensitive
- Lupus band test: Ig & complement in dermal epidermal junction
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What is the lupus band test?
Looks for Ig and & complement in dermal-epidermal junction
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Describe the various lesions of scleroderma.
- Plaques(morphea)
- Streaks(linear) (en coup de sabre)
- Nodules(nodular)
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What is CREST syndrome?
- Type of systemic slceroderma
- Cutaneous calcinosis
- Raynaud’s
- Esophageal dysfunction
- Sclerodactyly
- Telangiectasias (dilated suface vessels)
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What does schrirmer’s test measure?
Tera production (confirm sjogrens w/biopsy of salivary glands of lower lip
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Drugs with negative log ratio are selective for?
COX2
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What is Burton’s x-linked agammaglobulinemia?
- Males w/o Ig’s
- No mature B cells, germinal centers, plasma
- Tx: Ig replacement
- Defective bTK stops development from pre-B to immature B
- Dx: NO CD19+ cells
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What are the 3 ways Ig work?
- 1. neutralized
- 2. Opsonized
- 3. Complement activation
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What is isolated IgA def?
- Intrinsic B cell defect (TH dystfunction, suppressor T cells) may have anti-IgA Abs
- Asymptomatic, may have some sickness
- Other Ig levels are normal
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What is often associated w/ IgG subclass deficiency?
- Ataxia-telangiectasia
- Tx: IV IgG
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What is Hyper IgM def?
- X linked mutation in CD40L-> high IgM low other Ig
- Pyogenic bacteria infections
- Dx: hypercellular node w/ no distinguishable germinal center
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What is DiGeorge syndrome?
- 3rd and 4th branchial arch, no thymus, no mature T Cells -> no active B cells
- ears/eyes lower, eyes spaced apart
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What happens in the thymus?
T cells mature: cortex=education
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What is CVID?
- Umbrealla for impared B cells
- High infection, autoimmune
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What is SCID?
- Severe combined immunodeficiency
- Variable forms most commonly x-linked (IL-2 receptor)
- Defective T and B cell function
- Tx: antimicrobial & BMT
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What does a mutated IL-2 receptor cause?
No activation of T cells (gamma chain)
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What does a SCID thymus look like?
No germinal centers, no clonal expansion, different architecture
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What is Wiskott-Aldrich?
- X linked: eczema, bacterial infections thrombo-cytopenia (WASp)
- Decreased T cell, defective NK-cells, increased autoimmune/cancers
- WASp expressed in lymphocytes and megakaryocytes
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What is CGD?
- Defect in monocyte and neutrophil respiratory burst (H2O2, O2, NO, myeloperoxidase)
- Cannot kill CATALASE+ bacteria
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What is the respiratory burst?
NADPH + 2 O2 -> NADP+ 2O- -> SOD-> H2O2
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What does myeloperoxidase do?
Creates chloramines (bleach)
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What is hereditary angioneurotic Edema?
- HAE C1 defect (lacks inhibition)
- Prevented immune complex formation
- Alternative pathway: C3
- Classical pathway: C1qrs, C4 C2
- Terminal Complement: C5-9
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Chemo regimen of induction, consolidation and maintenance/conditioning.
- Induction: 1st cycle, decrease the number of malignant cells.
- Consolidation – once the cells are no longer detectable another cycle is given to further reduce the ones that are not seen. (once the numbers get below 5% of the cells seen on a smear/biopsy, then it is considered undetectable)
- Maintenance – done to keep the cells undetectable
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What is non-myeloablative?
Chemo then TBI(radation) on day of transplant-> mild pancytopenia, delays GVHD
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What is critical to prevent infections for oral mucositis?
Depressed immune, open sores, different oral flora
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How are Fl trays used?
Daily, 1-3 drops, 4-10 minutes at night when less salivary flow
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What does GVHD increase risk for?
Cancer (graft v host)
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