Pulmonary Disease I

Lung Basic Anatomy

Trachea → bronchi → bronchioles → terminal bronchioles → acini (respiratory bronchioles, alveolar duct, alveolus)

Dual blood supply (pulmonary/bronchial)

Gas exchange

Microscopic Structure of Alveolar Wall

Capillary endothelium

Pulmondary intersitium

Alveolar epithelium

Pneumocyte I

Pneumocyte II

Pneumocyte I

Lines most of alveolar surface

Pneumocyte II

Synthesize surfactant

Repairs alveolar epithelium

Upper Respiratory Tract Defense

Filtering

Lower Respiratory Tract Defense

Mucociliary units

Lymphoid Tissue Defense

Upper and lower

Cellular immunity

Humoral immunity - mucosal IgA

Pulmonary defenses

Upper respiratory tract - filtering

Lower respiratory tract - mucociliary units

Lymphoid tissues - cellular and humoral immunity

Alveolar macrophages

Types of Pulmonary Diseases

Affect airway

Affect interstitium

Affect pulmonary vascular system

Hemoptysis

Coughing up blood

Dyspnea

Difficulty breathing

Perception of needing to breathe deeper and faster (shortness of breath)

Atelectasis (Collapse)

Loss of lung volume caused by inadequate expansion of air spaces

Pneumothorax

Air in pleural space of cavity, leads to collapse of the lung

Hemothorax

Blood in lung and pleural space or cavity

Decrease ventilation

Empyema

Suppuration in pleural cavity

Pleural Effusion

Fluid in the pleural space (water on lungs)

Transduate or exudate

Transudate

Low protein fuid

Caused by increased venous pressure (CHF)

Exudate

High protein fluid

With or without inflammatory cells

Caused by increased vascular permeability (damage)

Pneumonia

Pulmonary Edema

Accumulation of fluid in lungs

First in interstitial tissues

Ultimately filling up the distal air spaces

Causes of Pulmonary Edema

Increased intravascular pressure (CHF)

Hypoproteinemia (low protein)

Vascular drainage (infections, autoimmune disease)

Issues with Pulmonary Edema

Inhibits normal oxygen exchange

Presdisposes to infection

Acute Respiratory Distress Syndrome (ARDS)

Rapidly developing pulmonary condition

Graded by severity of change in arterial blood oxygenation

Increased endothelial permeability

Same histologic features as interstitial pneumonia

Causes of ARDS

Shock

Infections

Trauma

Drug overdose

Toxins

Toxic gas inhalation

Ionizing radiation

O2 toxicity

Pathogenesis of ARDS

Alveolar-capillary membrane is compromised due to endothelium and alveolar epithelium injury

ARDS Trigger

Inflammatory reaction initiated by pro-inflammatory mediators

Occurs as early as 30 min after acute insult

Neutrophils play a role

Balance between destructive and protective factors determine tissue injury and clinical severity

ARDS Poor Prognosis

Advanced age

Bacteremia

Multiorgan failure

ARDS Complication

Chronic respiratory insufficiency from diffuse interstitial fibrosis

Acute Stage ARDS

Alveolar edema

Epithelial necrosis

Neutrophils

Hyaline membrane in wall and ducts

Healing Stage of ARDS

Thickening of alveolar septa

Many type II pneumocytes

Pulmonary Disease of Vascular Origin

Pulmonary embolism

Hemorrhage

Infarction

Pulmonary Hypertension

Diffuse Alveolar Hemorrhage Syndromes

Granulmatosis with polyangiitis - vasculitis disease

Goodpasture syndrome - autoimmune

Idiopathic pulmonary hemosiderosis - unknown some celiac disease

Pulmonary Thromboemboli

Usually from deep veins of legs or pelvic veins

Pulmonary Thromboemboli Risk Factors

Prolonged bed rest

Surgery

Severe trauma

CHF

Pregnancy and parturition

High estrogen oral contraceptives

Disseminated cancer

Hypercoagulopathy disorders

COVID-19 peneumonia - hypercoagulation

Deep Vein Thrombosis (DVT)

Unilateral swelling and erythema of the lower extremity

Pulmonary Embolism

Venous thrombus from lower extremities, much less likely effects upper extremities or right heart (mural thrombus)

Small emboli may cause minimal damage or are silent

Larger emboli can cause hemorrhage or infarction

Clinical Pulmonary Embolism

Acute onset of chest pain and shortness of breath

Diagnostic Options of Pulmonary Embolus

D-dimer

Spiral CT or VQ scan

Angiography

Lower extremity ultrasound

Autopsy

Saddle Pulmonary Embolism

Thromoboembolus that occurs at the bifurcation of the main pulmonary a.

Large clot associated with sudden hemodynamic collapse, including sudden cardiac death

Pulmonary Embolus Survival

Infarct of pulmonary tissue can occur

Especially if bronchial blood supply is compromised

Complications & Prognosis of Pulmonary Embolism

Chronic dyspnea

Pulmonary hypertension

Acute right sided heart failure

Shock

Death

30% risk for 2nd embolism

Pulmonary Hypertension Causes

Chronic obstructive or interstitial lung disease

Antecedent heart disease - mitral valve stenosis

Recurrent thromboembolic

Autoimmune disease, systemic sclerosis

Obstructive sleep apnea

Idiopathic or genetic

Pathogenesis of Pulmonary Hypertension

Medial hypertrophy of pulmonary arteries

Pulmonary arterial atherosclerosis

Right ventricular hypertrophy

Obstructive Respiratory Diseases

Family of diseases that cause reduced air flow somewhere between trachea and alveoli

Inflammation of the trachea and major bronchi and/or bronchioles

Destruction of alveoli

Obstructive Disease

Increase in resistance to air flow caused by partial or complete obstruction at any level

Obstructive Disorders

Emphysema

Chronic bonrchitis

Bronchiectasis

Asthma

Restrictive Disease

Decrease expansion of lung parenchyma and decrease total lung capacity

Restrictive Disorders

Chest wall disorders with normal lungs - obesity, neuromuscular diseases

Acute or chronic interstitial lung disease - ARDS, pneumoconiosis, sarcoidosis

Chronic Obstructive Pulmonary Disease (COPD)

Irreversible airflow obstruction

Emphysema

Permanent enlargement of the air spaces distal to the terminal bronchioles

Smoking is a major cause of imbalance - also inhaled pollutants

Most patients have concurrent chronic bronchitis due to cigarette smoking - risk factor for both diseases

Emphysema Clinically

Dyspnea

Cough

Prolonged exhalation

Normal O2 at rest

Pathogenesis of Emphysema

Imbalance between protease and anti-protease enzymes

Inflammatory cells - release of inflammatory mediators

Oxidative stress - increased apoptosis and senescence

Airway Infection

Does not initiate the destruction but causes acute exacerbation of the disease

Chronic Obstructive Pulmonary Disease

Inflammation and excess mucus

Chronic Bronchitis Clinical Diagnosis

Cough and mucois sputum production for 3 consecutive months in 2 consecutive years

May have hypoemia, cyanosis (blue bloaters) - often obese

Chronic Bronchitis Pathogenesis

Chronic irritation (smoking)

Air pollutants in smog

Infections (secondary role)

Chronic Bronchitis Pathology

Increased mucus gland layer

Chronic inflammation

Fibrosis and narrowing of the airways

Predisposing Factors of Obstructive Disease

Cigarette smoking

Atmosphere pollutants

Infection

Genetic factors - cystic fibrosis

Cigarette Smoking

Causes mucus gland hypertrophy

Increase smooth muscle tone

Inhibits cilia

Inhibits phagocytosis

Induces squamous metaplasia

Chronic Bronchitis

Edema

Mucous gland hyperplasia

Vascular congestion

Fibrosis

Goblet cell hyperplasia

Squamous cell metaplasia

Chronic inflammation

Excessive secretions (mucinous or mucopurulent) leading to narrowing of airways

Cor Pulmonale

Alteration in the structure/function of the right ventricle caused by a primary disorder of the respiratory system

COPD Management

Discuss smoking and tobacco cessation

Evaluate for tobacco-associated oral lesions

Increased risk for aspiration pneumonia and acute excerbation of lung disease with poor oral hygiene, periodontitis

Anxiety management is important

Monitor oxygen saturation with pulse oximetry

Semisupine or upright chair position to prevent orthopnea

Pink Puffer

Emphysema

Blue Bloater

Chronic bronchitis

Asthma

Characterized by reversible bronchoconstriction caused by airway hyper-responsiveness to a variety of stimuli

Increased irritability and prominence of SM in bronchi and bronchioles

Leads to marked, reversible episodes of contraction and airway constriction

Small airway obstruction due to inflammation and mucus secretion

Initiating Factors of Asthma

Allergies

Infections

Exercise

Drugs

Emotions

Genetics

Asthma Hygiene Hypothesis

Due to lack of exposure to infectious and nonpathogenic microorganisms in early childhood results in defects in immune tolerance

Subsequent hyperactivity to immune stimuli later in life

Asthma vs Chronic Bronchitis

Usually transient

Type I hypersensitivity (allergic)

Most of the inflammatory cells are eosinophils

Significant bronchospasm (SM)

Types of Asthma

Atopic

Non-atopic

Drug-induced

Occupational

Atopic Asthma

Type I IgE hypersensitivity reaction

Classic reaction to dust, pollen, food, and animals

Non-Atopic Asthma

Respiratory viruses and inhaled air pollutants

Drug Induced Asthma

Pharmacologic agents such as aspirin

Occupational Asthma

Triggered by fumes (epoxy resin, plastics)

Dusts (cotton, wood, platinum),

Gases (toluene)

Chemicals

Atopic Asthma Phases

Early - bronchoconstriction, mucucs, vasodilation, vagal nerve stimulation and late phase reactions (inflammation)

Airway Remodeling Atopic Asthma

Hypertrophy of bronchial SM

Increase mucus glands and vascularity

Fibrosis

Asthma Pathology

Increased mucus glands

SM hypertrophy

Inflammation with eosinophils and type 2 T-helper lymphocytes

Asthma Pathogenesis

Antigens bind to surface IgE on mast cells releasing a large number of mediators

Including histamine and leukotrienes

Triggering Asthma

TH2 cell activation and cytokines IL-4, IL-5, IL-13

Cause IgE production (coats mast cels)

IL-5 activates eosinophils

IL-13 stimulates mucus

IL-5

Activates Eosinophils

IL-13

Stimulates mucus