Inflammation Part 2 PDF

) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Presented by Oluwatobi Ajayi Inflammatory Diseases, Tissue Integrity & Wound Healing ) ) ) ) ) ) ) ) ) Intro ) ) ) ) ) ) ) ) )...

) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Presented by Oluwatobi Ajayi Inflammatory Diseases, Tissue Integrity & Wound Healing ) ) ) ) ) ) ) ) ) Intro ) ) ) ) ) ) ) ) ) AGENDA Review of Acute Inflammatory Process Vascular & Cellular phases Chronic Inflammation Tissue repair Wound Healing Phases Factors affecting healing. Disorders of Immune Response ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ACUTE INFLAMMATION Acute Inflammation is the body’s early protective response to an injurious agent. Its primary function is to contain injury, stimulate immune response, remove debris, protecting the body against infection and promoting healing. Signs: Redness, Swelling, Heat, Pain & Loss of Function ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ACUTE INFLAMMMATION ) ) ) ) ) ) ) Vascular Phase Cellular Phase Affects small blood vessels at the side of injury. Involves the delivery of leukocytes Starts by Momentary vasoconstriction followed (mainly neutrophils) to the site of injury by: Vasodilation: increase capillary blood flow, for phagocytosis. causing heat and redness. Vascular permeability: leakage of fluid (exudate) Involves endothelial activation, adhesion from blood vessels into extracellular space, & margination, transmigration, and causing swelling (edema), pain and impaired chemotaxis. function. Exudate also contains clotting factors, to After extravasation, leukocytes migrate prevent the spread of infectious agents throughout the body. towards site of injury by chemotaxis.  SYSTEMIC MANNIFESTATION OF INFLAMMATION ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Acute Phase Response mediated by the release of Cytokines (IL-1, IL-6, TNF-α) stimulates liver to produce acute-phase proteins (fibrinogen, CRP, etc.) communicates with the hypothalamus to produce fever. Stimulate leukocytosis in the bone marrow (More Neutrophils). Facilitate metabolic changes, such as the breakdown of protein into amino acids that can be used by immune system, or for tissue repair. Systemic Inflammatory Response Syndrome (SIRS) large amounts of microorganism in the blood = dysregulation of inflammatory response = large amount of cytokines released Vasodilation, increased vascular permeability, intravascular fluid loss, circulatory shock. INFLAMMATION ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) )  INFLAMMATORY ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) MEDIATORS Contents ) ) ) ) ) ) ) ) ) INFLAMMATORY ) ) ) ) ) ) ) ) ) MEDIATORS ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) KEY INFLAMMATORY MEDIATORS Contents Histamine Arachidonic Acid Metabolites Causes dilation of blood vessels, smooth muscle Prostaglandin: Present in most tissues and stored and constriction, tissue swelling, and itching. released by mast cells Increases capillary permeability, attracts WBC to site of Principal mediator of immediate transient phase of inflammation, causes pain, potentiates effects of histamine, and promotes platelet aggregation. increased vascular permeability in acute inflammatory phase Leukotrienes: Effects similar to histamine, but more potent. Also causes slow and sustained bronchioconstriction. Found in tissues and also released by mast cells. Plasma Proteins Clotting: aids coagulation in vascular phase Complement system: increase vascular permeability, improves phagocytosis, and causes vasodilation. Bradykinin: increases vascular permeability and causes contraction of smooth muscles.  INFLAMMATORY ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) MEDIATORS Contents cortiosteroids ) ) ) ) ) ) ) ) ) GLUCOCORTICOIDS/GLUCOCORTICOIDS ) ) ) ) ) ) ) ) ) Systemic steroids are synthetic derivatives of the natural steroid, cortisol produced by the adrenal glands. E.g. prednisone, hydrocortisone, dexamethasone, etc. Local route: joint injections, ear drops, topical creams. Systemic route: ONLY USED IN ACUTE TREATMENT. Risk of systemic side effects with: Long-term treatment PO vs IV vs IM systemic Corticosteroids must be weaned off slowly to avoid withdrawal symptoms. Negative feedback decreases/stops adrenal glucocorticoid synthesis => no if we give cortisol for 2 weeks and then stop brain will abrupt stoppage of treatment. try to overcompensate for that  long term effects of ) ) ) ) ) ) ) ) ) GLUCOCORTICOIDS/GLUCOCORTICOIDS ) ) ) ) ) ) ) ) ) Cushing’s Syndrome: Overtreatment with systemic glucocorticoids = Exaggerated side effects leading to dysfunction of affected systems. ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) EXUDATES serosanuinous Serous Exudate Hemorrhagic Exudate Watery fluid, low in protein Aka Sanguineous content. E.g. Blisters 01 02 Occurs with significant tissue Results from plasma entering injury that damages blood inflammation site. vessels, or when there is Serous is a regular part of healing, leakage of RBC from and small amounts are considered capillaries. normal. Purulent Exudate Fibrinous Exudate Thick yellow, brown, green or grey drainage containing pus (degraded Contain large amount of WBC, proteins and tissue debris). fibrinogen to form a thick 04 03 Staphylococcus induces this. and sticky meshwork, like Indicate an active infectious process fibers of blood clot. Abscess: localized inflammation containing purulent exudate, surrounded by neutrophil layer  TYPES OF EXUDATES ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Contents ) ) ) ) ) ) ) ) ) WOUND HEALING ) ) ) ) ) ) ) ) ) PRIMARY INTENTION Edge to Edge healing by approximating wound with minimal tissue loss. E.g. Paper cut, sutured surgical wound Minimal scarring SECONDARY INTENTION Healing from inside out. No closure! Larger wounds with greater loss of tissue and contamination. E.g. burns, large surface wound. Slower healing and scar formation  TISSUE REPAIR AND WOUND HEALING ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Tissue Regeneration: permanant cells will just replace with different cells since they cant regenerate replaces injured tissue with cells of the same type (Parenchymal vs Stromal) Labile Vs Stable Vs Permanent cells only labile and sometimes stable Fibrous Tissue Repair: can regenrate Replacement by connective tissue Generation granulation tissue: red, moist connective tissue containing new capillaries (formed by angiogenesis) and proliferating fibroblast Fibrogenesis: influx of fibroblast to secrete components of ECM such as fibronectin, proteoglycan, collagen, etc. As healing progresses, number of fibroblasts and new blood vessels decrease, while collagen synthesis persists, causing the granulation tissue scaffolding to evolve into scar tissue composed of inactive fibroblast, collagen fibers, and other ECM components. Although scar tissue fills the gap created by tissue death, it does not repair the structure with functioning parenchymal cells. ) ) ) ) ) ) ) ) ) STAGES OF WOUND HEALING ) ) ) ) ) ) ) ) ) Inflammatory Phase Proliferative Phase Remodeling Phase Removes injurious agent and Fibroblasts secrete collagen, growth About 3 weeks post-injury factors, etc. that induce angiogenesis Decrease in vascularity and prepares wound for healing. and endothelial cell proliferation to Hemostasis (formation of clots), continued remodeling of form granulation tissue. scar tissue through vascular phase, and migrations of Wound space is filled by granulation simultaneous synthesis of phagocytic WBC to wound site. tissue which supply oxygen & nutrients, and acts as a scaffold for collagen and lysis by After 24 hours, macrophages join collagenase, to increase new tissue growth. in phagocytosis and also aid Epithelial cells at the wound edges the strength of the scar production of growth factors for proliferate to form a new surface tissue and shrink the scar next phase layer. to make it less visible. ) ) ) ) ) ) ) ) ) STAGES OF WOUND HEALING ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) FACTORS THAT AFFECT WOUND HEALING Blood flow and Oxygen Delivery: ) ) ) ) ) ) ) ) ) Adequate blood flow is needed to supply nutrient and remove waste. Impaired wound healing may be caused by swelling, compression, diabetes and other vascular diseases. Oxygen is also needed for fibroblast to make collagen, and for neutrophils to phagocytose, therefore impaired oxygen delivery slow healing. Hyperbaric oxygen treatment can be used to treat wounds where hypoxia and infection interfere with healing. Malnutrition: Carbs, proteins & vitamins are essential to wound healing. Age: Neonate and small children may have immature immune systems. Older adults have reduced collagen and fibrinogen synthesis. Impaired Inflammatory and Immune Responses: Corticosteroids, Immunocompromise (Immunosuppressive drugs or disease). Infection: Pathogens compete for oxygen/nutrients, and cause ongoing inflammation. COMPLICATIONS OF WOUND HEALING Wound dehiscence= separation of previously approximated wound edges. Evisceration: Dehiscence with protuding organs. Medical Emergency!! Nursing: Place saline soaked gauze on the area, lower head of bed, and call MD immediately!! PRESSURE ULCER ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) CHRONIC INFLAMMATION ) ) ) ) ) ) ) ) ) Acute inflammation < 10 days. Chronic inflammation may last weeks, months, or even years. Chronic inflammation causes tissue destruction by repetitive inflammatory cascade. Caused by persistent irritants, mostly insoluble or resistant to phagocytosis and other inflammatory mechanisms. Agranulocytes (macrophages and lymphocytes) typically present, instead of neutrophils. Secretion of regenerative mediators e.g. tissue growth factors or fibroblasts instead of exudates. Forming scar tissues (Less vascular, flexible, strong) to replace connective tissues. Repetitive inflammatory cycle causes cellular tissue changes. Dysfunction of the tissue Susceptibility to unusual growth and altered cellular division. E.g. Neoplasms ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) INFLAMMATORY DIAGNOSIS Allergic Rhinitis Dermatitis Psoriasis Arthritis Inflammatory Bowel Disease (IBD) Asthma Chronic Obstructive Pulmonary Disease (COPD) ) ) ) ) ) ) ) ) ) ALLERGIC RHINITIS ) ) ) ) ) ) ) ) ) Rhinitis = irritation and inflammation of nasal mucousal, causing nasal congestion, runny nose, sneezing and itching. Allergic Rhinitis (aka Hay Fever): triggered by inhaled allergens leading to hypersensitivity. Seasonal or occasional triggered by pollen, dust, dander, etc. Signs & Symptoms: rhinitis, conjunctivitis (eyes), headache from nasal-sinus congestion. Relevant Bloodwork: Elevated eosinophils. Treatment: Antihistamines, and Intranasal corticosteroids for nasal inflammation. Corticosteroids - Fluticasone, Mometasone, Budesonide. Desensitization ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) 03 YOU UP? You have never heard of the brand name medication, Dymista. You look at the generic name and find that the drug is a mixture of Fluticasone & Azelastine. What drug classes does the drug belong to, and what is the mechanism of action? When do you think it is used?  ATOPIC DERMATITIS ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) Dermatitis = Eczema Atopic Dermatitis Caused by exaggerated immunoglobulin E (IgE)/allergic response. Chronic inflammation of the skin. Deficient innate skin barrier, itching, scar formation (lichenification) Risk of super-infection (bacterial or viral). Treatment: Moisturize, Topical Glucocorticoids, Antihistamines, Antibiotics/Anti-viral for infection ) ) ) ) ) ) ) ) ) PSORIASIS ) ) ) ) ) ) ) ) ) Chronic inflammatory skin disease. Autoimmune Risk factors: Family history Triggered by skin trauma, climate, stress, medications. Skin changes: hyperkeratosis, thinned stratum granulosum, dilated dermal papillae. Signs and Symptoms: Dry scally skin patches, commonly non-pruritic (non-itchy). Treatment: Glucocorticoids (Local to Systemic as needed), moisturizing cream.  ECZEMA VS PSORIASIS ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) RHEUMATOID ARTHRITIS (RA) ) ) ) ) ) ) ) ) ) Rheumatoid Arthritis = chronic systemic rheumatic (inflammatory) disease of the joint. Involves progressive & autoimmune destruction of healthy endogenous tissues. Risk factors: family history, gender. MOA Inflammation of connective tissue, triggered by an immune system attacking joint. Proliferation of WBCs & pro-inflammatory mediators within a tissue Proliferation of granulation tissue (inflammatory cells, fibroblasts, endothelial cells) Dysfunction of the synovial cavity (‘pannus’) Destruction of surrounding tissue (bone, cartilage) More inflammation + pain Thickening & deformity of affected tissue Affects the same joints bilaterally. Video! ) ) ) ) ) ) ) ) ) RHEUMATOID ARTHRITIS (RA) ) ) ) ) ) ) ) ) ) Signs & Symptoms: Swelling, Stiffness worse in AM, Synovial joint inflammation, Soft feeling on joints, Symmetrical symptoms, Systemic effects (fever, Malaise, etc), (ankylosis) Relevant bloodwork: Elevated C-Reactive Protein (CRP). Treatment: No cure! Rest the joint and use NSAIDs, Glucocorticoids (Oral), Immunomodulators to manage symptoms. ) ) ) ) ) ) ) ) ) RA TREATMENT WITH IMMUNOMODULATORS ) ) ) ) ) ) ) ) ) Disease Modifying Anti-Rheumatic Drugs (DMARDS) target the underlying immune processes that contribute to inflammation and joint damage, helping to modify the disease course rather than just relieve symptoms. suppress the overall immune system!! E.g. Methotrexate (1st line treatment for RA), Azathioprine, hydrochloroquine, tacrolimus, and cyclosporine. ?Nursing consideration for immunosuppressants? Biologics Drugs are a subset of DMARDs made up of antibodies derived from living organisms. Inhibit pro-inflammatory cytokines. E.g. Tumor Necrosis Factor-α (TNF) Inhibitors ( Infliximab, Adalimumab), Interleukin inhibitors (Ustekinumab), B-cell inhibitor (Rituximab). Antibodies are made of large molecules, predicting poor oral absorption...therefore biologics are administered parenterally (e.g. SC,IV) ) ) ) ) ) ) ) ) ) OSTEOARTHRITIS ) ) ) ) ) ) ) ) ) Degenerative disorder of articular cartilage. (Wear & Tear Arthritis). Affects fewer joints than RA Risk Factors: Mechanical stress, obesity, age, gender (reduced estrogen levels). Cartilage changes occur due to: Decreased proteoglycans => weakening collagen network => pro/inflammatory mediator release (cytokines, prostaglandins) => further inflammation => ongoing inflammation = cartilage tissue destruction => bone-bone in articulating surface! Treatment: NSAIDs, glucocorticoids (local administration of cortisone is helpful). OSTEOARTHRITIS ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) INFLAMMATORY BOWEL DISEASE (IBD) ) ) ) ) ) ) ) ) ) IBD = Autoimmune Diseases = Crohn’s Disease & Ulcerative Colitis ) ) ) ) ) ) ) ) ) INFLAMMATORY BOWEL DISEASE (IBD) ) ) ) ) ) ) ) ) ) Autoimmune Diseases: Crohn’s Disease & Ulcerative Colitis Symptoms: Diarrhea, Fatigue, Abdominal pain and cramping, Blood in your stool, Reduced appetite, Unintended weight loss. Attack may be triggered when endogenous GI host flora is recognized as an antigen, leading to inflammation. Risk factors: Family History Ulcerative Colitis Inflammation, swelling and sores in large intestine (colon) and rectum Crohn’s Disease Inflammation that commonly affects the small intestine and the upper part of the large intestine. Affect more women than men. ) ) ) ) ) ) ) ) ) IBD ) ) ) ) ) ) ) ) ) Treatment: aim to treat acute attack and prevent relapse Acute attack: Glucocorticoids IV Main stay: Low dose PO glucocorticoids, salicylates, and DMARDs/biologics as recommended. Sulfasalazine (DMARD) is a pro-drug activated by bacteria in colon, resulting in: 5-ASA (mesalamine): produces local anti-inflammatory effects by blocking arachidonic acid metabolites (like NSAIDs). (May be administer PO/PR by itself) Sulfapyridine: causes systemic anti-inflammatory effects with side effects Side effects: photosensitivity, low urine output, kidney stones, dehydration. Contraindicated in Sulfa allergy!! Sulfasalazine is given PO. Also used in RA but not 1st line due to side effects. ) ) ) ) ) ) ) ) ) ASTHMA ) ) ) ) ) ) ) ) ) Chronic inflammatory airway disorder (not autoimmune). Affects up to 10% Canadians Risk factor: family history. Triggers: noxious stimuli (allergens, environmental particles, infection, stress, etc.) Inflammation + pro-inflammatory mediators activating further inflammation! mast cell degranulation WBC signaling: especially T- lymphocytes & interleukins; Eosinophils, Basophils, Neutrophils, Macrophages TH2-helper cells => signal B-cells to synthesize IgE => crosslinks receptors – mast cell degranulation chronic inflammatory mucosal changes => hypersensitivity + high goblet cell activity (mucous) Outcome: bronchial inflammation, bronchoconstriction, mucous production ASTHMA ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ASTHMA ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ASTHMA CLINICAL PRESENTATION ) ) ) ) ) ) ) ) ) Epithelial injury in the bronchi => chronic hypersensitivity ‘reactivity’ of the bronchial airways. risk of attacks: exposure triggers acute ‘attacks’ Asthma Attack S&S: Wheezing, shortness of breath, decreased/no air entry into lung lobes, chest tightness, tachycardia, anxiety, panic, fatigue. Limited inspiration + longer expiration phase => air trapping in alveoli hyper-inflated lungs with limited gas exchange ventilation-perfusion’ mismatch Low O2 & high CO2 Hypoxemia, hypercarbia & high pulmonary pressures => increased RVEDP => low CO ) ) ) ) ) ) ) ) ) ASTHMA CLINICAL PRESENTATION ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ASTHMA TREATMENTS ) ) ) ) ) ) ) ) ) Drugs used to stabilize asthma are called ‘maintenance’ drugs, while those used during acute asthma attack are called ‘rescue’ drugs. Management of asthma focuses on: stabilizing the bronchial inflammation & minimizing the number of attacks. avoidance of triggers (if possible). acquire control of the inflammation with a daily treatment protocol & compliance. proper use of inhaler; proper dose; avoidance of respiratory infections. ) ) ) ) ) ) ) ) ) MAINTENANCE TX OF ASTHMA ) ) ) ) ) ) ) ) ) Inhaled anti-inflammatory drugs exert local effect in bronchioles, causing low systemic=> Low side effects. GLUCOCORTICOIDS MAST CELL STABILIZERS 1st line for maintenance/prophylaxis Inhibit histamine release from mast treatment against asthma attacks cells. Drugs: Budesonide (Pulmicort), Fluticasone (Flovent), Beclomethasone (Qvar) Drug: Cromolyn Inhaler Slow onset of therapeutic level. Frequent dosing: 3-4 times/day Administration: Not common as 1st choice inhalers (metered dose inhalers, dry Synergy with glucocorticoids powder inhalers) nebulizers ) ) ) ) ) ) ) ) ) MAINTENANCE TX OF ASTHMA ) ) ) ) ) ) ) ) ) Maintenance drugs are administered daily, even if not attacks, to control triggers. BIOLOGICS: MONOCLONAL LEUKOTRIENE ANTIBODIES MODIFERS Block leukotriene receptors Drug: Omalizumab (Xolair) Modify inflammatory response pre- e Binds free IgE => decreases antigen exposure (prophylaxis) binding => no degranulation Drug: Montelukast (Singulair) Decreases expression of mast cell- Administered PO bound IgE => no degranulation. Systemic effects Slow onset of action Long-term treatment plan Synergy treatment ) ) ) ) ) ) ) ) ) MAINTENANCE TX OF ASTHMA ) ) ) ) ) ) ) ) ) e  ACUTE TREATMENT OF ASTHMA (RESCUE) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) -Treat bronchoconstriction via inhaler or Nebulizer BETA-2 ADRENERGIC ANTICHOLINERGICS AGONIST Antagonize Parasympathetic NS, Stimulates sympathetic NS’ B2 causing bronchodilation. receptors directly. Less potent & has slower onset of Potent & Fast-acting action. Synergic with Beta-2-Agonists Drugs: Drugs: Atrovent (Ipratopium) Salbutamol/Albuterol (Ventolin) Formoterol ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) 03 YOU UP? What does SNS stimulation cause in asthma treatment? How will you know the patient is improving? ) ) ) ) ) ) ) ) ) STATUS ASTHMATICUS ) ) ) ) ) ) ) ) ) Sever asthma attack (ER admission). Signs and Symptoms: severe SOB,- accessory muscle use, bluish tint to lips, chest tightness, anxiety/panic AHS protocol - https://www.albertahealthservices.ca/frm-21051.pdf Treatment: Oxygen therapy Beta- Adrenergic Agonist (Ventolin) via NEBULIZER Magnesium Sulfate Glucocorticoids IV (Dexamethasone) Anticholinergics via NEBULIZER Sympathomemetics: Epinephrine IV Potent with short half-life. The goal is bronchodilation Side effect: SNS stimulation ) ) ) ) ) ) ) ) ) STATUS ASTHMATICUS ) ) ) ) ) ) ) ) ) Magnesium Sulfate Electrolyte, Calcium Channel Blocker, Enzymatic activator Can be treated to effect for severe bronchoconstriction. Mechanism: inhibition of Ca channels in smooth muscle => reduced cellular excitability => bronchodilation stabilization of mast cells & T-cells => decreased pro/inflammatory mediators. enhanced release of NO => vasodilation, pulmonary vasodilation = improved gas exchange Side effect: hypotension ) ) ) ) ) ) ) ) ) ASTHMA VS ANAPHYLAXIS ) ) ) ) ) ) ) ) ) Both presentations have a trigger, causing inflammation but: Main issues in anaphylaxis is systemic vasodilation & bronchoconstriction. Tx focuses on perfusion & airway/breathing. Main issue in asthma: airway/breathing. Tx focuses on airway/breathing.