KIN 3304 1nd Edition Lecture 29 Outline of Last Lecture I Pressure II DCI III DCS IV AGE V Lung Overexpansion Injuries VI Patent Foramen Ovale VII Nitrogen Narcosis VIII O2 Toxicity IX CNS O2 Toxicity X Hypocapnia XI Hypercapnia XII Carbon Monoxide Poisoning XIII High Pressure Nervous Syndrome Outline of Current Lecture I Why Asthma Makes it Hard to Breath II What is Asthma III The Plugged Garden Hose Analogy IV Asthma Related Symptoms These 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 Statistics VI Causes of Asthma VII Triggers include VIII The Hygiene Hypothesis IX The Couch Potato Hypothesis X Hallmarks of Asthma Pathogenesis XI The Asthmatic Lung XII Asthma A Two phase Inflammatory Trigger Response XIII What are the cell types implicated in the phases of asthma XIV Role of Mast Cells and IgE in Asthma XV Association of Atropy with Asthma XVI T helper cells Th1 Th2 XVII Asthma Susceptible Genes XVIII FEV1 FVC Measurements in Asthma Lung XIX Therapeutic Side Effects Current Lecture I Why Asthma Makes it Hard to Breath a It s like breathing through a straw b Bronchial tubes are inflamed more narrow II What is Asthma a 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 stimulus III The Plugged Garden Hose Analogy a Airways become inflamed and constricted b Bronchial walls become thicker c And a lot of mucus congestion IV Asthma Related Symptoms a Chest tightness b Persistent cough c Wheezing d Shortness of breath e Reduced activity V Asthma Statistics a Asthma keeps increasing since 1982 b More people going to caregivers VI Causes of Asthma a Asthma is caused by environmental factors in genetically predisposed individuals i Puerto Rico and Africa VII Triggers include a Allergens b Viruses c Aspirin d Diet e Cold air f Stress g Exercise h Antibiotic use i Animal dandruff j Cigarette smoke k Molds l VIII Bird feathers The Hygiene Hypothesis a 5th born is least susceptible to asthma than 1st born b If you live on a farm characteristics of asthma are greatly reduced c In a horrible environment bad stuff keeps the immune system busy d 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 asthma IX The Couch Potato Hypothesis a 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 asthma b Increasing evidence indicates that decreased physical activity may play a role in development of asthma Read papers on bb X Hallmarks of Asthma Pathogenesis a Characteristics inflammatory cell infiltrate within the large and small airways b Damage to the ciliated stratified epithelium c Hyperplasia and remodeling of the airways d Hyperresponsiveness to a variety of inhaled bronchoconstriater stimuli XI The Asthmatic Lung a As inflammatory response superimposed upon remodeled activity XII Asthma A two phase inflammatory Airway Response a First Early Phase i Immediate reaction with trigger ii If allergen trigger IgE mediated mast cell degeneration iii Increased vascular permeability mucus production smooth muscle contraction b Second Late Phase i Delayed sustained inflammatory response ii Release of inflammatory molecules iii Recruitment of leukocytes T cells and eosinophils TQ Mast cells degenerate to histamine XIII What are the cell types implicated in the phases of asthma a First phase i Mast cells ii Airway epithelial cells iii Airway smooth muscle cells b Second phase i T cells Dendritic Cells ii Eosinophils XIV Role of Mast Cells and IgE in Asthma a Granulocyte contains cytoplasmic granules b IgE FcR binging triggers mast cell degeneration c Release of histamine causes i Increased vascular permeability ii ASM contraction iii Increased mucus production XV Association of Atropy with Asthma a Atropy the genetic susceptibility to generate allergen specific IgE b Approximately 50 of asthma can be linked to immunological mechanisms associated with atropy c Atropy alone is insufficient for the development of variable airflow obstruction and accompanying systems of chronic asthma XVI T helper Cells Th1 Th2 a T helper cells help B cells produce antibody inducing IgE b Classified according to interleukin cytokine production i Th1 IFNg IL 2 ii Th2 IL 4 IL 5 IL 10 IL 13 c Because Th2 cells produce both IL 4 and IL 5 asthma is considered a Th2driven inflammatory disease XVII Asthma Susceptible Genes a Tim 1 encodes the cellular receptor for the hepatitis virus i Expressed on T cells ii Polymorphisms appear to regulate allergen mediated Altn and TH2 responses b ADAM33 encodes metalloprotease i Appears to regulate epithelium response to injury XVIII FEV1 FVC Measurements in Asthma Lung a Cant blow out as much b Know the charts comparing normal lung versus asthma lung XIX Therapeutic Side Effects a Steroids i Skeletal muscle wasting ii Osteoporosis iii Glancoma b Beta2 Agonists i Cardiac arrhythmias ii Reflex tachycardia iii Tremor