KIN 3304 1nd Edition Lecture 29Outline of Last Lecture I. PressureII. DCIIII. DCSIV. AGEV. Lung Overexpansion InjuriesVI. Patent Foramen OvaleVII. Nitrogen NarcosisVIII. O2 ToxicityIX. CNS O2 ToxicityX. HypocapniaXI. HypercapniaXII. Carbon Monoxide PoisoningXIII. High Pressure Nervous SyndromeOutline of Current Lecture I. Why Asthma Makes it Hard to BreathII. What is AsthmaIII. The Plugged Garden Hose AnalogyIV. Asthma-Related SymptomsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.V. Asthma StatisticsVI. Causes of AsthmaVII. Triggers includeVIII. The “Hygiene Hypothesis”IX. The Couch Potato HypothesisX. Hallmarks of Asthma PathogenesisXI. The Asthmatic LungXII. Asthma: A Two-phase Inflammatory Trigger ResponseXIII. What are the cell types implicated in the phases of asthmaXIV. Role of Mast Cells and IgE in AsthmaXV. Association of Atropy with AsthmaXVI. T-helper cells: Th1, Th2XVII. Asthma Susceptible GenesXVIII. FEV1/FVC Measurements in Asthma LungXIX. Therapeutic Side EffectsCurrent LectureI. Why Asthma Makes it Hard to Breatha. It’s like breathing through a strawb. Bronchial tubes are inflamed (more narrow)II. What is Asthmaa. A heterogeneous disorder of the air ways with reversible inflammation of the bronchial mucosa accompanied by increased responsiveness of the bronchi to a wide variety of stimulusIII. The Plugged Garden Hose Analogya. Airways become inflamed and constricted b. Bronchial walls become thickerc. And a lot of mucus congestionIV. Asthma-Related Symptomsa. Chest tightnessb. Persistent coughc. Wheezing d. Shortness of breathe. Reduced activityV. Asthma Statisticsa. Asthma keeps increasing since 1982b. More people going to caregiversVI. Causes of Asthmaa. Asthma is caused by environmental factors in genetically predisposed individualsi. Puerto Rico and AfricaVII. Triggers include:a. Allergensb. Virusesc. Aspirind. Diet e. Cold airf. Stressg. Exerciseh. Antibiotic usei. Animal dandruffj. Cigarette smokek. Moldsl. Bird feathersVIII. The “Hygiene Hypothesis”a. 5th born is least susceptible to asthma than 1st bornb. If you live on a farm, characteristics of asthma are greatly reducedc. In a horrible environment, bad stuff keeps the immune system busyd. “Improved hygiene and public health measures in industrialized societies have decreased the incidence of infections that would otherwise alter the immune system in some way to mitigate against asthmaIX. The Couch Potato Hypothesisa. A sedentary lifestyle coupled with a high-fat diet in industrialized society has decreased immunological tolerance that would otherwise alter the immune system in some way to mitigate against asthmab. Increasing evidence indicates that decreased physical activity may play a role in development of asthma*Read papers on bbX. Hallmarks of Asthma Pathogenesisa. Characteristics inflammatory cell infiltrate within the large and small airwaysb. Damage to the ciliated stratified epitheliumc. Hyperplasia and remodeling of the airwaysd. Hyperresponsiveness to a variety of inhaled bronchoconstriater stimuliXI. The Asthmatic Lunga. As inflammatory response superimposed upon remodeled activityXII. Asthma: A two-phase inflammatory Airway Responsea. First/Early Phase:i. Immediate reaction with trigger ii. If allergen trigger, IgE-mediated mast cell degenerationiii. Increased vascular permeability, mucus production, smooth muscle contractionb. Second/Late Phase:i. Delayed, sustained inflammatory responseii. Release of inflammatory molecules iii. Recruitment of leukocytes, T-cells and eosinophils*TQ: Mast cells degenerate to histamineXIII. What are the cell types implicated in the phases of asthma?a. First phasei. Mast cellsii. Airway epithelial cellsiii. Airway smooth muscle cellsb. Second phasei. T-cells/Dendritic Cellsii. EosinophilsXIV. Role of Mast Cells and IgE in Asthmaa. Granulocyte-contains cytoplasmic granulesb. IgE/FcR binging triggers mast cell degenerationc. Release of histamine causesi. Increased vascular permeabilityii. ASM contractioniii. Increased mucus productionXV. Association of Atropy with Asthmaa. Atropy – the genetic susceptibility to generate allergen-specific IgEb. Approximately 50% of asthma can be linked to immunological mechanisms associated with atropyc. Atropy alone is insufficient for the development of variable airflow obstruction and accompanying systems of chronic asthmaXVI. T-helper Cells: Th1, Th2a. T helper cells “help” B cells produce antibody, inducing IgEb. Classified according to interleukin/cytokine production:i. Th1: IFNg, IL-2ii. Th2- IL-4,IL-5,IL-10, IL-13c. Because Th2 cells produce both IL-4 and IL-5, asthma is considered a “Th2-driven” inflammatory diseaseXVII. Asthma Susceptible Genesa. Tim-1 – encodes the cellular receptor for the hepatitis virusi. Expressed on T cellsii. Polymorphisms appear to regulate allergen-mediated Altn and TH2 responsesb. ADAM33 – encodes metalloproteasei. Appears to regulate epithelium response to injuryXVIII. FEV1/FVC Measurements in Asthma Lunga. Cant blow out as much b. Know the charts comparing normal lung versus asthma lungXIX. Therapeutic Side Effectsa. Steroidsi. Skeletal muscle wastingii. Osteoporosisiii. Glancomab. Beta2 Agonistsi. Cardiac arrhythmiasii. Reflex tachycardia iii.