bronchial asthma asthma bronchiale. asthma is characterized by episodic air-flow obstruction in...
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Bronchial Bronchial AsthmaAsthmaAsthma bronchialeAsthma bronchiale
Asthma is characterized by episodic air-flow obstruction in response to a number of stimuli.
Patients typically have paroxysms of wheezing, dyspnea and cough.
Acute episodes of asthma may alternate with asymptomatic periods or be superimposed on a background of chronic airway obstruction.
Severe acute asthma unresponsive to therapy is termed status asthmaticus.
Most asthmatic patients, even when apparently well, have some persistent air-flow obstruction and morphologic lesions.
Asthma
Chronic Chronic iinflammatorynflammatory disorder of disorder of bronchi bronchi
EEpisodicpisodic - - RReversibleeversible bronchospasmbronchospasm Affects 10% of children & 5% adultsAffects 10% of children & 5% adults
Half of cases appear in patients younger Half of cases appear in patients younger than 10 yearsthan 10 years
Initial attack of the disease can occur at Initial attack of the disease can occur at any ageany age
Asthma was classically divided into Extrinsic (allergic) Intrinsic (idiosyncratic)
depending on inciting factors.
Asthma
Extrinsic (allergic) Triggers
Allergic asthma PollensAnimal hair or furHouse dust (with mite)Allergic Bronchopulmonary Aspergillosis
Occupational asthma Cedar woodPlatinum saltsCotton dustAnhydrides (epoxy hardeners)IsocyanatesEpoxy resinsLab animalsVinyl chloride (in meat packing)Flour processingCrab processingOil mistsFormaldehyde and Toluene (path labs)
Intrinsic (idiosyncratic)
Aspirin (and some NSAIDs)Tartrazine yellow Respiratory tract infection viruses (e.g., rhinovirus, parainfluenza virus)
Asthma
ALLERGIC ASTHMA Most common form of asthma and is usually seen
in children TType I hypersensitivityype I hypersensitivity reaction reaction induced by induced by
exposure to an extrinsic antigen.exposure to an extrinsic antigen. One third to one half of all patients with asthma
have known or suspected reactions to such allergens as pollens, animal hair or fur, and house dust contaminated with mites
Allergic asthma is strongly correlated with skin-test reactivity
Half of all children with asthma have a substantial or complete remission of symptoms by age 20 but in many, asthma may recur after age 30
Asthma
Pathogenesis Pathogenesis of of AAllergicllergic Asthma Asthma
Asthma
Primary MediatorsPrimary Mediators
(1) (1) HHistamineistamine
(2) (2) EEosinophilic and neutrophilic osinophilic and neutrophilic chemotactic factorschemotactic factors (e.g., leukotriene (e.g., leukotriene B4)B4)
Secondary MediatorsSecondary Mediators
(1) L(1) Leukotrieneseukotrienes:: ((C4, D4, E4C4, D4, E4))
(2) (2) PProstaglandin D2rostaglandin D2 (PGD2)(PGD2)
(3) (3) PPlatelet-activating factorlatelet-activating factor (PAF)(PAF)
(4) cytokines(4) cytokines ((IL-1, TNF, IL-6IL-1, TNF, IL-6))
Asthma
Mast cells in Asthma PathogenesisMast cells in Asthma Pathogenesis
Asthma
Eosinophils in Asthma Eosinophils in Asthma PathogenesisPathogenesis
Asthma
INFECTIOUS ASTHMA
A common precipitating factor in childhood asthma is a viral respiratory tract infection rather than an allergic stimulus.
In children under 2 years, Human respiratory syncytial virus (RSV) is the usual agent; in older children, rhinovirus, influenza, and parainfluenza are common inciting organisms.
The inflammatory response to viral infection in a susceptible person is believed to trigger the episode of bronchoconstriction.
Asthma
EXERCISE-INDUCED ASTHMA
Exercise can precipitate some bronchospasm in more than half of all asthmatics. In some patients, exercise is the only inciting factor.
Exercise-induced asthma is related to the magnitude of heat or water loss from the airway epithelium. The more rapid the ventilation (severity of exercise)
and the colder and drier the air breathed, the more likely is an attack of asthma.
The mechanisms underlying exercise-induced asthma are unclear.
Asthma
OCCUPATIONAL ASTHMA More than 100 different occupational exposures
have been linked to the development of asthma. In some instances, these substances provoke
allergic asthma via IgE-related hypersensitivity. Examples of those so affected are animal
handlers, bakers, and workers exposed to wood and vegetable dusts, metal salts, pharmaceutical agents, and industrial chemicals.
In other cases, occupational asthma seems to result from direct release of mediators of smooth muscle contraction after contact with an offending agent.
Some occupational exposures affect the autonomic nervous system directly.
Asthma
OOccupational asthmaccupational asthma Industrial asthma is a serious problemIndustrial asthma is a serious problem::
cedar woodcedar wood platinum saltplatinum salt cotton dustcotton dust anhydrides (epoxy hardenersanhydrides (epoxy hardeners)) isocyanatesisocyanates epoxy resins epoxy resins lab animalslab animals vinyl chloride vinyl chloride ((in meat packingin meat packing)) fflourlour processingprocessing crab processing crab processing oil mistsoil mists fformaldehydeormaldehyde and toluene (path labs) and toluene (path labs)
Asthma
DRUG-INDUCED ASTHMA
Drug-induced bronchospasm occurs mostly in patients with known asthma.
The best-known offender is aspirin but other nonsteroidal anti-inflammatory agents also have been implicated.
Aspirin induce arachidonic acid metabolism and elaboration of the bronchoconstrictor leukotrienes.
It is estimated that up to 10% of adult asthmatics are sensitive to aspirin.
Asthma
Immediate hypersensitivity does not seem to be involved, and these patients can be desensitized by daily administrations of small doses of aspirin.
Serum IgE levels are normal. Skin test results are usually negative. Rhinitis and nasal polyps are also frequent
findings in aspirin-sensitive individuals. -Adrenergic antagonists consistently
induce bronchoconstriction in asthmatics and are contraindicated in such patients.
Asthma
AIR POLLUTION and EMOTIONAL AIR POLLUTION and EMOTIONAL FACTORS in Asthma bronchialeFACTORS in Asthma bronchiale
Air pollutionAir pollution SO2 SO2 Oxides of nitrogen Oxides of nitrogen Ozone Ozone
OdorsOdors Foul smelling gasesFoul smelling gases PerfumePerfume
Temperature inversionsTemperature inversions Psychological stress Psychological stress
Vagal efferent stimulationVagal efferent stimulation
Asthma
PathologyPathology
From autopsies on patients who have died in status asthmaticus
Asthma
Gross PathologyGross Pathology The lungs are overdistended because of The lungs are overdistended because of
overinflationoverinflation Small areas of atelectasis Small areas of atelectasis Occlusion of bronchi and bronchioles by Occlusion of bronchi and bronchioles by
thick, tenacious thick, tenacious and adherent and adherent mucous plugsmucous plugs
Asthma
Bronchial Bronchial inflammationinflammation
Edema, Edema, MucouspluggingMucousplugging
BronchospasmBronchospasm ObstructionObstruction Over Over
inflation/Atelectasisinflation/Atelectasis COPDCOPD
Asthma
HyperinflationHyperinflation
Asthma
Mucous plugsMucous plugs
Asthma
Mucous plugMucous plug
Asthma
MicroMicroscopyscopy
Mucous Mucous plugsplugs ((strips of epithelium and many eosinophils) Curschmann spiralsCurschmann spirals ((mucoid exudate casts - may be expelled
with coughing) Charcot Layden crystalsCharcot Layden crystals ((phospholipids of the eosinophil cell
membrane) Creola bodiesCreola bodies (compact clusters of epithelial cells in the
sputum) Patchy Patchy necrosisnecrosis of epithelium of epithelium Submucosal Submucosal glandularglandular hyperplasiahyperplasia Goblet cellGoblet cell hyperplasia hyperplasia Hypertrophy of bronchial Hypertrophy of bronchial smoothsmooth musclemuscle Mixed inflammatory infiltrate: Mixed inflammatory infiltrate: EosinophilsEosinophils (5-50%) + L (5-50%) + Lymphoympho
(T(THH2, CD2, CD44) ) MMastast cellscells
Asthma
Obstructed Inflammed Bronchi
Asthma
Bronchial morphologyBronchial morphology
IInflammation nflammation EosinophilsEosinophils Gland Gland
hyperplasiahyperplasia Mucous plug in Mucous plug in
lumenlumen Hypertrophy of Hypertrophy of
muscle layermuscle layer
Asthma
Bronchial morphologyBronchial morphology
InflammatioInflammationn
Mucous Mucous PlugPlug
EosinophilsEosinophils
Asthma
EosinophilsEosinophils
Asthma
Curschmann's spiralsCurschmann's spirals ((mucoid exudate - may be expelled with coughing)
Asthma
The Reality The Reality Asthma is not yet curable *Asthma is not yet curable * Underdiagnosis & Underdiagnosis &
UndermanagementUndermanagement Therapy is still evolvingTherapy is still evolving
Hope Hope Better understanding of Better understanding of PathologyPathology
New line of Promissing DrugsNew line of Promissing Drugs Proper management Proper management NNormal lifeormal life
Asthma
Asthma Pathology - Modern Asthma Pathology - Modern viewview
Allergen
MucushypersecretionHyperplasia
VasodilatationNew vessels
Edema
BronchoconstrictionHypertrophy/hyperplasia
Cholinergic reflex
Subepithelialfibrosis
Sensory nerve activation
Eosinophil
Mast cell
Th2 cell Neutrophil
Macrophage/dendritic cell
Mucus plugEpithelial shedding
Nerve activation
LeukotrienesC4, D4 & E4
Asthma
An important clinical finding: An important clinical finding: WheezingWheezing Asthma bronchialeAsthma bronchiale Foreign body or tumor in the upper airway Foreign body or tumor in the upper airway Pulmonary edemaPulmonary edema (especially left-sided (especially left-sided
congestive heart failure) congestive heart failure) Pulmonary embolus Pulmonary embolus Chronic bronchitis Chronic bronchitis Carcinoid syndrome Carcinoid syndrome