BMS250 - Wk 5

Outcomes

• Discussed are the pathophysiology of restrictive and obstructive lung diseases.
• Obstructive lung diseases include: Bronchial Asthma, Chronic Obstructive Pulmonary Disease (Chronic Bronchitis, Emphysema), and Bronchiectasis
• Restrictive lung diseases include: acute ARDS, which leads to Diffuse Alveolar Damage, and chronic Idiopathic Pulmonary Fibrosis

Ventilatory Impairment

• Diseases are classified by the type of ventilatory impairment, either obstructive or restrictive.
• Pulmonary function tests like spirometry, which measures airflow, and bodyplethysmography, which measures lung volumes, are used

Pulmonary Function Tests

• Pulmonary function tests (PFTs) are used to diagnose and monitor lung diseases.
• Key measurements include:
  • FEV1 (Forced Expiratory Volume in 1 second): The amount of air exhaled in one second.
  • FVC (Forced Vital Capacity): The total amount of air exhaled.
  • FEV1/FVC ratio
• Important lung volumes include:
  • TLC (Total Lung Capacity)
  • RV (Residual Volume)
  • IC (Inspiratory Capacity)

Obstructive vs Restrictive Ventilatory Impairment

• Obstructive lung diseases impair the ability of air to leave the alveoli during expiration, resulting in air trapping.
• Obstructive lung diseases are clinically defined by a decreased FEV1/FVC ratio.
• Obstructive lung diseases lead to increases in residual volume (RV) and functional residual capacity (FRC).
• Total lung capacity (TLC) remains normal in obstructive lung diseases.
• Restrictive lung diseases are clinically defined by a physiological FEV1/FVC ratio.
• Restrictive lung diseases show reductions in residual volume (RV) and functional residual capacity (FRC).
• Total lung capacity (TLC) is reduced in restrictive lung diseases.

Obstructive Lung Diseases

• Obstructive lung diseases include: Bronchial Asthma, Chronic Obstructive Pulmonary Disease, Bronchiectasis, Chronic Bronchitis, and Emphysema

Bronchial Asthma

• Bronchial asthma is characterized by episodic airway obstruction and airway hyperresponsiveness, typically accompanied by airway inflammation.
• In most cases, the airway obstruction is reversible, but in some asthmatics, it may become irreversible.
• Airway inflammation is usually eosinophilic in most patients.
• Some patients might present with differing types of airway inflammation, or no obvious signs of airway inflammation.

Bronchial Asthma Definition

• The definition, also known as the "Trias" Definition, includes:
  • Chronic inflammation.
  • Obstructive ventilatory impairment + bronchial hyperreactivity (symptoms)
  • Reversibility of obstructive ventilatory impairment

Heritable Predisposition to Asthma

• Family and twin studies indicate a 25-80% degree of heritability for asthma.
• Genetic studies suggest complex polygenic inheritance complicated by interaction with environmental exposures.
• Asthma is influenced by epigenetic modifications via environmental exposures.
• Genes related to asthma are associated with a risk for atopy
• Genetic polymorphisms are associated with differential responses to asthma therapies, such as variations in the β-receptor

Symptoms of Atopy

• Atopy symptoms include: allergic rhinitis, allergic conjunctivitis, eczema, and hay fever.
• Allergies (food, contact, inhalation), and positive skin tests (prick tests) are also symptoms

Triggers of Bronchoconstriction

• Allergens (e.g., waste from animals, pets, dust, mites, mold), infections of upper airways, and inhalatory irritants.
• Nonspecific triggers: anxiety, cold air, physical activity, gastroesophageal reflux
• Drugs (nonsteroid anti-inflammatory drugs – Aspirin), and preservatives in grocery items (sulphites).
• Frequently, the trigger remains unknown.

Types of Asthma

• Older classifications included extrinsic (allergic) and intrinsic (non-allergic) asthma.
• Newer classifications distinguish between allergic asthma versus nonallergic asthma.
• Specific types of asthma include: allergic (atopic), nonallergic (nonatopic), drug-induced, occupational, and cardiac asthma

Allergic Asthma

• Allergic asthma is more frequent in children and is associated with other atopic conditions, such as hay fever or eczema.
• The mechanism of allergic asthma is primarily a Type I hypersensitivity reaction.
• Common causes include pollens, dust, and drugs

Pathogenesis of Allergic Asthma

• Hyperreactive airways constrict in response to stimuli, leading to increased airway resistance.
• Type I hypersensitivity
• CD4+ TH2 cells release IL-4 and IL-5.
• IL-4 and IL-5 stimulate eosinophils.
• Production of IgE

Nonallergic Asthma

• Nonallergic asthma occurs more frequently in adults.
• The mechanism is not a Type I hypersensitivity reaction, and IgE levels are normal.
• Causes include exercise, cold air, drugs, gastroesophageal reflux, and viral infections.

Nonatopic Asthma.

• One third of asthmatic patient have this condition
• Allergy and Atopy results are negative with this condition, as is the family history
• viral is a known trigger.

Airway Inflammation

• Characterized by type 2 and non-type 2 inflammations.
• Type 2 invovles Mucus secretion, Antigen activity.
• INvolves smooth muscle proflieration
• Non-type 2 consists of bacteria and pollutants and involves airway hyperresponsive.

Two Stages of Asthma: Early Stage

• Involves mediators that promote bronchoconstriction including lukotrienes, histamine, and Prostaglandin D2

Stages of Astham: Late Stage

• Release of enzymes by eosinophils and neutrophils
  • Neutrophils release proteases
  • Eosinophils release major basic protein that is toxic to epithelial cells.
• The late phase is responsible for the morphologic changes that occur in asthma.

Development of Late Asthma

• Involves interplay between genetic susceptibility, environmental exposure, endogenous development, and age factors

Triggers of Airway Narrowing

• Continued exposure to allergens, irritants, viral infections, exercise, cold air, air pollution, drugs, occupational exposures, hormonal changes, and pregnancy
• The number of exposures can impact the degree of impairment

Mechanisms of AirWay Obstruction

• Hyperresponsiveness, inflammation, and structural chnages also lead to edemas inairways and goblet cells

Pathology of Asthma.

• INcludes Smooth-muscle constriction
• Thickening of the Submucosa, and Mucus production.

Airway Hyperresponsiveness

• Acute narrowing response in reaction to agents that do not elicit airway responses
• Hallmark of asthma
• Excess narrowing response to inhaled agents compared to non-afffected

Two Components of Airway Hyperresponsiveness

• Functional one level of muslce itself as demonstrated through hyerstimulation.
• Structural components assoicated with airway severity or duration
• Smooth Muscle Hypertrophy and Hyperplasis are caused by -subepithelial collagen -airway edema
  • Mucosal inflammation.

Morphology of Asthma

• Lungs become overinflated and mucus plugging airways in gross amounts with eosinophils and increase collegan

Smooth Muscle Over Time with asthma can have...

• Mucus
• Prominent basement membrane
• Smooth Muscle

Eosinophilic Infiltrate

• Asthma is chracterized by this.

Charcot Leyden with asthma can have...

• Charcot-Leyden from basic functions

Symptoms of Spirometry duing an exacerbation includes..

• Fev1/FVC is reduced (as in all obstructive lung diseases) PEF(Peak Errupt Flow) is reduced Resudial voume is increased.

Bronchodilator

• Fev1/FVC is reduced (as in all obstructive lung diseases) PEF(Peak Errupt Flow) is reduced Resudial voume is increased.

Early and Late Astham..

• Early asthma is normal findings
• Late asthma is PEF low and FEv/FVC is decreased.

Arterial Blood gases

• Exacerbation results with rising CO2 levels.
• Range between intervals from 02 to PAC02
• Eosinophilia is noted.

Pathophysiology of clinical symotms

• Includes wheezing and night time cough
• symptoms occur during nights
• Status Asthmatics happen during periods of prolonged asmatic attacks with fatal results.

Other conditions

• Allergic skinners under eyes
• a Dark transverse crease on the nose (".allergic salute")

COPD

• COPD includes a group of Bronchial Asthma.
• COPD involves treatment of the Severity impact in the bodies indevidual systems.
• Airflow is not always versible.
• The airflow is progressive from the infection to gas exposures.

Risk and factors..

• Suspectibility genes
• Alpha-1 antitrypsin deficiencies
• Active or Secondhand Smoke is included Occuptational Dust. Smoking in general Indoor/Outdoor air pollutants

Cumulation of COPD requires

Cigarette smoke Indoor Air Pollution Occupational dusts Outdoor pollution

Pathogenisis

• Four events include

1. Inflantory Immune responses
2. Proteinanse impacts
3. Indued oxygen damage
4. Disordered repairs wwith emphasis on emphaseia.

Imbalance

• Oxidant and antioxident
• Genetic susceptibility, Macrophage activiations Lungs with effective cell repair involved- Ceramide Tgfbelta elastin Inevvfective lung repair.

Cellular Mechanoisms

Apoptosis inflmmation and grwoth factors

• CHronic: airways are air re-modeled and mucus in airway
• Losses occur and elastin

Bronchitus

• COUGH THAT IS MOST 3 MONTHS OVER 2 YRS,
• Airways increases from mucus because high mucus production
• Airways increases also from mucus gland.

Smal airways impacted

• Goblin cell meplatisua also impacts

Emphasia includes

• Alveoli and airways dialste and loss in airway walls

• elastic recoil

E ismphasis of Emphaseia

Respository bronchioli

Alpha antiprotein deficencies is common in...

• the lower Lobes
• Alveoli and ducuts and resposutory bronchioles.

Histology over lungs woth emphsema impacts loss of...

• Pulmonary tissue

CP patterns

• Inolves 4 groups such as Centrolobular :upper Panlobular: diffus in lungs lower Paraseptal- airway inflammation marked Smoking and defiecies can result.

Clinical presentation involves the following

• Blue : Obstructive with Bronchitis
• Pink : emphasizes emphsema and dyspnea.

Diagnois involves

Cough and Risk factors for tobaccop and exposure

Spriometry values

Airflwo is limited.

Spriomentry Obstructive involves

• Less than 0.7

Complicationw

• Lung damage resutling in hypoxemia, heart failure
• mismatched vertrilaitn Respiratory.

Bronicteatis

• Irreversibal dilastions that impact lugn tissure.

Pathology involves

• Obruction
• Infections
• smooth muscle destrcution.

Etiology involves

infectiuos and uninfectous agents

• bronis involves localised areas

Diffuse Bronicstia impacts

• Changes lungs
• Unredyging symptioms

Pathogensis Involves

• Suspetiblity.

Morphology can result in

• Dilated airways

Phatophysiology of clinical presenstaion results from

• Chronic coughs and hemopytus

• Signes: clubbing with lung damage

• Parallel lines occur in x ray with increase thickness

Infections can lead to

• Recurrent of infection

Restrictive lung disease with

• General charestic and acute diffuse damage

Restrictive Lungs involves

• Volume redux

Exrprapymonartes

• obveseity and deromaitres with kyphosis

Intrapulmonary

• Primary of secondafy
• Acute ards

Inrpalmortaey and resrtictive

• Involves ventilation issues.

Pathoogensis and fibroids can result

• from genetics.

Initial and predominance

• Lymohcytpes and infulmtion

Late phase results from

• Pression from fiboris

Acute damaga

• ARDS and damaga resulting in pulmonary infection and trauma with hupoxema.

• Initation of pneumonitis.

Symptoms

• pink frothy can results in an incitning agent.

Chronic Restrictive Lung Diseases

• Impairied Gas exhange DLCO
• Odsftrtuctuve ventiratory

Etiology of internsitail

• Diseasem include immuno response or drug repsoncsce

Restrtuve lung diessse

hamman 1935

###Initial inflammartin can resultin

• Edema

Lat e progresstions

• Honeycumm

Odigapatic PNeukonia

Usual interstitial pneumonia Organising pneumonia

Symtpms for diagnsis with lung and resp

• Involves dry cough tacpmea
• Clubbing and biposy
• Lung bipsy.

###Pulmomorlgosts can be Teamwwork depedneent