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How is histamine synth?
Decarboxylation of histidine
Which cells have Histamine and when is it released?
- Mast and basophils exocytosis or degranulation, injury, IgE (allergy), drugs
- Skin, bronchial & intestinal mucosa
What are physiologic effects of histamine?
- Relax vascular smooth muscle
- Large vessel constriction, contract non vascular smooth muscle
- Stimulate exocrine esp gastric
What are the types of H receptors?
- H1: vasodilation, bronchoconstriction, pain & itching (GCPR)
- H2: stimulate gastric acid
- H3: decrease neurotransmitter (NE, Ach, 5HT) rls
What are alkylamines?
- H antagonist, 1st gen, cold symptoms
- Chlorpheniramine maleate
- Bromopheniramin maleate
What are ethanolamines?
- Anti-cholinergic and sedation H antagonists
- Benadryl, (diphenhydramine HCl)
- Dimenhydrinate (Dramamine) anti-emetic
Which H antagonist is a good anti emetic?
Which H antagonist is used for allergic rhinitis, conjunctivitis?
Phenothiazines: promethazine HCl
What is the significance of piperidines?
- 2nd gen antihist devoid of CNS effects
- terfenadine (seldane)
- fexofenadine HCl(allegra
- Loratadine (Claritin)
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)
What are the side effects of antihistamines?
- CNS depression (not H1 and anti-cholineric specific)
- Arrhythmia(rarely astemizol terfenadine)
What antihistamine is dangerous with antibiotics?
Astemizole and erythromycin
How are antihistamines used in dentistry?
- Adjuncts for angioedema
- Hydroxyzine and diphenhydramine for sedation
How do autoimmune diseases develop?
- Problem w/negative selection in thymus
- Infection (mimicry, super antigens)
- T cell peripheral suppression
What does every reactive Tcell express?
FasL (eyes have Fas receptors-> Tcell death)
What are the systemic autoimmune diseases(others organ-specific)?
RA, SLE, primary sjogrens, scleroderma
What is the only type I hypersensitivity that causes disease?
Chronic urticaria: persistent itchy rash IgE
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)
What is autoimmune hemolytic anemia?
- Type II Rh Ag, I Ag, destroys RBC by FcR, phag -> anemia
- IgM: kupffer (liver)
What is thrombocytopenic purpura?
Autoimmune, platelet integrin, abnormal bleeding
What is goodpastures?
- Non collagenous domain of BM col IV
- Leads to glomerunephritis and pulmonary hemmrhage
What is pemphigus vulgaris?
- Epidermal cadherin autoantigen
What is acute rheumatic fever?
- Strep cell wall antigens cross react w/ cardiac muscle
- Arthritis, myocarditis
What is cryoglobulinemia?
- Type III Rheumatoid factor IgG complexes-> systemic vasculitis
- Form when hypothermic
What is SLE
- Type III hypersensitivity
- Autoantigen DNA, histones, ribosomes, snRNP, scRNP
- Leads to glomerulonephritis, vasculitis, arthritis
- Malar butterfly rash
What is the dental presentation of SLE?
Oral lesions on buccal mucosa and roof
Which molecules do mycoplamic ones mimic?
- RBC mb Ags (create rxn aginst host glycophorins
- Autoimmune hemolytic anemia
Explain type I diabetes.
- Type IV hypersensitivity
- TH1 (stim by IFN-gamma) attack Beta pancreatic cells
- Glucogon and somatostatin still ok
What gene puts you at risk for type I diabetes?
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
What do RA joints look like histologically?
Hypercellular, not a lot of eosin (proteins, pink)
What is MS?
- Tcell activation against CNS (microglia or dendritic cells of brain)
- Inflammatory reaction via mast cells degrades myelin
Which dye to they use to diagnose MS?
Gadolidium: binds myelin (show up as white plaques in CT)
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
What is Sjogren’s syndrome?
- Lymphocytic (CD4+ and B cells infiltration of exocrine glands
- Ductal epithelial target
What is amyloidosis?
- Secondary to autoimmune (never primary)
- Proteinaceous materials in tissue interstitum (congo red)
What are the 2 types of BMT?
- Bone marrow transplant
- Autologous: chemosensitive
- Allogenic: leukemia
What is a major hemostasis side effect of chemo?
- Bone marrow suppression
- Oral mucositis
What are the main dental concerns for chemo?
- Bone marrow: bleeding, infection, anemia
- Mucositis: nutrition, hydration
What is oral mucositis and the phases?
- Mucosal inflammation ulceration (from chemo typically)
- 1: initiation (DNA injury)
- 2: signaling (messengers)
- 3: amplification (apoptosis)
- 4: ulceration (pain)
- 5: healing
- 0: no symptoms
- 1: soreness
- 2: ulcers, eat solids
- 3: ulcers, liquids
- 4: ulcers: alimentation not possible
Which areas of oral cavity are keratinized?
- Dorsum of tongue
- Hard palate
- Attached gingiva
What are the early and late presentations of mucositis?
- Early: Erythema, edema, sensitivity, soreness
- Late: ulcerations, pain, infections, nutrition, bleeding
What is the main goal of dental therapy for chemo?
- Eliminate sources of infection
- Treat between cycles
What do PGs do?
- Platelet aggregation, vasodilation, vasc permeability, pain sensitivity
- PDX, PGI: vasodilation, antiaggregating
- PGE2: erythema, edema, pain, fever
- PGF2a: vasodilator, uterus contraction
What do leukotrienes do?
- Immediate hypersensitivity
- LTC4, LTD4: broncioconstriction, mucosal edema
- LTB4: chemotaxis
Describe the secretions of lymphocytes.
- IL: stimulate T and B cells
- MCP-1: monocyte accumulation
- GM-CSF: granulocyte/macrophace colony
- INF-a: antiviral, macrophage
What is the difference between COX 1 & 2?
- COX1: constitutive regulate renal, mucosa integrity
- COX2: inducible (inflammation)
What is prostaglandin role in GI?
What is a hapten?
Protein-free that can combine and elicit immune response
What does a dentist need to ID in allergy?
- Severity, speed of onset, extent(local/general)
- Know HX: specifics, timing, treatment
What are manifestations of allergy?
- Skin: Erythema, urticarial, wheals, rash pruritus
- Resp: bronchospasm, laryngeal edema
- GI: nausea, pain
- CV: angioedema, hypotension, lightheadedness, tachycardia, syncope
What is allergenic in LA?
Sodium bisulfite (antioxidant)
What is allergenic in dental office?
LA(Na bisulfite antioxidant), Antibiotics, latex, pain meds
Which allergic reaction is faster IV or PO?
What should you prescribe for suspected generalized allergy?
- Diphenhydramine (Benadryl) 25-50mg PO TID 3x
- (can be given IV/IM should be escored home)
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)
What is the common factors of CT?
- Cells (fibroblasts, chondrocytes
- ECM(collagens, proteoglycans
- CD44, integrins
What is ANCA?
- Anti-neutrophil cytoplasmic antibody
- Seen in systemic vasculitis
Which autoantibodies found in Sjogrens?
RNA-assosciated (Ro & La)
Which autoantibodies seen in scleroderma?
What is a bursa?
Synovial lined sac separate bone and muscle/skin
What is enthesis?
Attachement of muscle tendon and ligaments
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
What are early signs of RA?
- Morning stiffness > 1 hour
- Swelling of 3 or more joints
- Leads to swan neck deformities
What are x-ray differences of OA and RA?
- Osteo: no cartilage, bone spurs
- RA: synovial inflammation w bone erosion
What is a complication of RA in dental setting?
Subluxation of C1 and C2 cant’ move head, may need to be ligated
What is felty’s syndrome?
RA, splenomegaly and neutropenia
How is RA dignosed?
- No specific, RF in 80%
- ESR and eanemia
How is RA treated?
- Drugs: NSAIDS, corticosteroids (disease modifying antirheumatic drugs (DMARDs)
- Immunologic: entanercept or infliximab (TNF-a inhibitors)
How is SLE diagnosed?
- ANA (antinuclear Ab)
- Anti-dsDNA & anti-Sm MORE specific, LESS sensitive
- Lupus band test: Ig & complement in dermal epidermal junction
What is the lupus band test?
Looks for Ig and & complement in dermal-epidermal junction
Describe the various lesions of scleroderma.
- Streaks(linear) (en coup de sabre)
What is CREST syndrome?
- Type of systemic slceroderma
- Cutaneous calcinosis
- Esophageal dysfunction
- Telangiectasias (dilated suface vessels)
What does schrirmer’s test measure?
Tera production (confirm sjogrens w/biopsy of salivary glands of lower lip
Drugs with negative log ratio are selective for?
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
What are the 3 ways Ig work?
- 1. neutralized
- 2. Opsonized
- 3. Complement activation
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
What is often associated w/ IgG subclass deficiency?
- Tx: IV IgG
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
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
What happens in the thymus?
T cells mature: cortex=education
What is CVID?
- Umbrealla for impared B cells
- High infection, autoimmune
What is SCID?
- Severe combined immunodeficiency
- Variable forms most commonly x-linked (IL-2 receptor)
- Defective T and B cell function
- Tx: antimicrobial & BMT
What does a mutated IL-2 receptor cause?
No activation of T cells (gamma chain)
What does a SCID thymus look like?
No germinal centers, no clonal expansion, different architecture
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
What is CGD?
- Defect in monocyte and neutrophil respiratory burst (H2O2, O2, NO, myeloperoxidase)
- Cannot kill CATALASE+ bacteria
What is the respiratory burst?
NADPH + 2 O2 -> NADP+ 2O- -> SOD-> H2O2
What does myeloperoxidase do?
Creates chloramines (bleach)
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
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
What is non-myeloablative?
Chemo then TBI(radation) on day of transplant-> mild pancytopenia, delays GVHD
What is critical to prevent infections for oral mucositis?
Depressed immune, open sores, different oral flora
How are Fl trays used?
Daily, 1-3 drops, 4-10 minutes at night when less salivary flow
What does GVHD increase risk for?
Cancer (graft v host)