Respiratory Disease

Question 1

Structure of Respiratory System

Answer 1

airways, acini, secondary lobules, vasculature, lymphatics, pleura

airways - trachea, bronchi, bronchioles (terminal + respiratory bronchioles)

Acini - units supplied by single terminal bronchiole - respiratory bronchioles, and its distal alveolar ducts and alveolar sacs.

Acinus - the basic unit of gas exchange
- terminal bronchiole (last order of airway with mucosal lining)
- consists of -> Alveolar sacs, alveolar ducts, and respiratory bronchioles - all lined by interstitial septa
- Alveolar sacs lined by: type 1 and 2 pneumocytes. 1 = produce surfactant, 2 = progenitor cells for type 1

Trachea -> 1 mainstem bronchi to each lung
bronchiole - endothelial lining, surrounded by smooth muscle and cartilage - for support and protection

lung has two lobes - right (upper, middle, lower) and left (upper and lower)

Question 2

Function of Respiratory system

Answer 2

1. oxygenation of the blood
2. removal of waste products (CO2)

Requires:
- ventilation = movement of air
- perfusion = movement of blood
- interference of either = respiratory failure

Question 3

Alveolar Wall

Answer 3

• gas transfer takes place across the alveolar-capillary membrane

it consists of:
- Capillary endothelium
- basement membrane and surrounding interstitial tissue
- Alveolar Epithelium (type 1 & 2 pneumocytes)

Question 4

Gas exchange requires

Answer 4

1. Ventilation
   - gas moves from the nose and mouth through the large airways (trachea/bronchi/bronchioles) to lung parenchyma (alveoli), where gas exchange takes place
   - moves air from the environment to the lungs
   -Bronchi (main, primary, secondary), Bronchioles (terminal, respiratory)
2. Perfusion
   - deoxygenated blood -> lungs, oxygenated blood -> distal organs for oxygenation
   - Two systems of vessels: pulmonary and bronchial

Question 5

Two systems of vessels - that supply the lungs

Answer 5

1.) Pulmonary
- pulmonary artery carries deoxygenated blood from the right side of the heart to the lungs, then oxygenated blood -> heart.
- intimate contact between the air in alveoli and blood in pulmonary capillaries allow gaseous exchange

2.) Bronchial
- oxygenated blood from descending aorta and intercostal arteries supplies lung parenchyma
- lung has a dual blood supply

Question 6

Respiratory Failure

Answer 6

• inability to maintain normal oxygen saturation of blood and remove CO2 from blood entering the lungs

Potential causes:
- decreased ventilation
- decreased perfusion
- ventilation/perfusion imbalance

Question 7

Lung needs of defense

Answer 7

• most injuries are a result of something inhaled through the airway - exposed to 10,000L/day
• Mediated through airways or blood vessel systems

Question 8

Inhaled Injurious Agents

Answer 8

1. infectious
   - virus
   - bacteria
   - fungal
2. Non-infectious
   - Cigarette smoke
   - organic particles
   - inorganic particles
   - toxic gases

Question 9

Blood-borne injurious agents

Answer 9

1. Infections
   - bacterial, fungi, viruses
2. Non-infectious
   - drugs - amiodarone (for the heart arrhythmias are toxic to the lung), bleomycin (chemo drug injures parenchyma)
   - Autoimmune diseases (antibodies) - lupus, rheumatoid arthritis antibodies deposited in lung -> secondary effects
   - Thromboembolism (most common) - breaks off in the peripheral, circulates, cause blockage (major if at lung)

Question 10

Mechanisms of Lung Defense

Answer 10

1.) Nasal clearance
- cough or sneeze reflex to expel injurious agent

2.) Tracheobronchial clearance
- via muco-ciliary “blanket”
- bypassed nasal clearance
- specialized surface epithelial lining - pseudostratified columnar epithelium (more rectangular on the apex of the cell)
- cell produce mucus - mucus vacuoles release mucus on to the surface, and injurious agents get stuck in it
- cilia suppose to be away from the alveolar wall because of nasal clearance

3.) Alveolar Clearance
- via macrophages and immune system
- for agents that small enough to bypass tracheobronchial

Question 11

Diseases of the lung

Answer 11

1.) infectious

2.) Noninfectious
- Non-neoplastic
- neoplastic

Question 12

Mechanisms of Lung Defense

Answer 12

1.) Nasal clearance
- cough or sneeze reflex to expel injurious agent

2.) Tracheobronchial clearance
- via muco-ciliary “blanket”
- bypassed nasal clearance
- specialized surface epithelial lining - pseudostratified columnar epithelium (more rectangular on the apex of the cell)
- cell produce mucus - mucus vacuoles release mucus onto the surface, and injurious agents get stuck in it
- cilia suppose to be away from the alveolar wall because of nasal clearance

3.) Alveolar Clearance
- via macrophages and the immune system
- for agents that are small enough to bypass tracheobronchial

Question 13

Diseases of lung

Answer 13

1.) Infectious Diseases
- Pulmonary diseases are the most frequent of any infection - upper respiratory tract caused by virus
2.) Non-infectious Diseases
- Non-neoplastic
- Neoplastic

Question 14

Pneumonia

Answer 14

• inflammation of the lung secondary to infection
• organisms -> viruses, bacteria, protozoa, fungi, rickettsia, other

Enter the lung by:
- aspiration - infectious agent in the oral cavity or stomach -> lung, then destruction
- Inhalation - infectious agent in the environment -> breathed in
- Blood - infectious agent carried to another part of the body via circulation
- Direct Inoculation - a result of trauma, the lung is penetrated by an object with an infectious agent

body response once in the lung - neutrophils in the acinus

Question 15

Examples of Impaired Host defences

Answer 15

1.) Loss or suppression of host defences
- coma, anesthetic - why not to eat/drink on surgery day, aspiration

2.) Injury to mucociliary apparatus
- cigarette smoke, inhalation of hot/corrosive gases, viral disease (Spanish flu - pneumonia secondary deaths)

3.) Interference with alveolar macrophages
- alcohol, malnutrition, diabetes

4.) Accumulation of fluids or secretion in Alveoli
- pulmonary edema, cystic fibrosis
- thick, sticky mucous that cannot be removed - contains AAs and lipids (fatty acids) that allow overgrowth of bacteria -> secondary pneumonia

Question 16

Classifications of Pneumonia

Answer 16

1.) Morphological
- lobar pneumonia - the entire lung or lobe is involved due to organisms which can spread very rapidly, pus on pleural surface, grayish colouring
- Bronchopneumonia - infection is spread by the airways, this type is patchy

2.) Clinical
- community required - organisms involved include streptococcus pneumonia, Hemophilus influenza, and mycoplasma pneumonia
- Nosocomial (hospital or nursing home required) - include gram-negative bacilli, Pseudomonas aeruginosa, Staphylococcus aureus and oral anaerobes
- Pneumonia immunocompromised patients - CMV, fungi, TB, pneumocytes - are the most susceptible patients, causing more severe infections than healthy people

3.) Types of Clinical Presentation
- Clinical presentation - sudden onset of chills and fever, malaise, pain on inhalation (b/c pleuritis), cold sore flare-up, significant mortality with unknown viruses
-diagnosis - typical x-ray, find neutrophils in sputum and organisms, treat specific organism with antibiotic
- complications - A.) lung abscess formation (necrotic tissue, aspiration of infectious material, depressed cough reflex from comatose or anesthetic agents) - B.) Empyema (infection spreads to the chest cavity, intrapleural fibrinosuppurative reaction, pus in the cavity, blood vessels cannot get into the cavity) - C.) Septicemia (spread from bloodstream to effect other organs)

Question 17

Pulmonary Tuberculosis

Answer 17

• a major cause of morbidity and mortality in the world
• increased incidence in NA
• increased incidence of multi-drug resistant strains

Question 18

Non-infectious diseases of the lung

Answer 18

• can be divided into non-neoplastic and neoplastic diseases
• non-neoplastic diseases can be further divided into obstructive and restrictive diseases
• obstructive lung disease involves the airway and is characterized by increased resistance to airflow due to partial or complete obstruction of the airway from the trachea to the bronchioles - it can be acute (aspirate foreign object) or chronic (chronic obstructive pulmonary diseases)
• restrictive is characterized as a reduced expansion of the lung = decrease in total lung capacity - due to abnormality of chest wall or lung

Question 19

Chronic Obstructive Pulmonary Disease

Answer 19

Common features:
- patients present with shortness of breath
- chronic and or recurrent airflow obstruction
- decreased expiratory volume

Common Conditions
- Bronchial Asthma
- Chronic Bronchitis
- Emphysema

Question 20

Bronchial Asthma

Answer 20

An inflammatory disorder of the lung characterized by:
A.) hyper-reactive airways
- secondary to increased responsiveness to various stimuli
B.) Episodic and reversible bronchoconstriction
- coughing, dyspnea (shortness of breath), wheezing, chest tightness
- asymptomatic between coughs

Triggers
- allergen, cold or heat, infection, exercise, emotional stress, idiopathic

Etiology - genetic or other causes

• Type 1 hypertension of the airway
• abnormal narrowing of the airway

Pathogenesis
- left side = normal
- right side = airway undergoing an asthmatic attack, narrowing secondary to hypertension type 1 rxn

Predisposing factors
- family history of allergies or allergic disorders
- high exposure to airborne allergens year one alive
- tobacco exposure
- frequent respiratory infections
- low birth rate
- occupational exposure

Question 21

Chronic Bronchitis

Answer 21

• patient with productive cough most days of the week for more than three months of the year for two or more years

Etiology - cigarette smoking (80%), impairs ciliary action and causes hypersecretion of mucus, leading to airway obstruction and gas exchange impairment, they develop pulmonary hypertension

Irritation -> recruit neutrophils -> release proteases (elastase, cathepsin) -> protective changes 1. hyperplasia of mucosal glands 2. squamous metaplasia

Morphological changes
- proteases, goblet cells, and underlying mucus glands are released,
- after continuous damage of cilia you get pseudostratified columnar epithelium by squamous metaplasia and squamous cells - squamous cells do not have cilia so mucus is not removed and increased production of mucus

Pathogenesis:
- hypersecretion of mucus -> airway obstruction -> increased risk of infection decreased ventilation
- mucus rich in fatty acid and AAs - helps bacteria multiply
- narrowing of the airway
- difference from asthma - irreversible in nature

Question 22

Emphysema

Answer 22

• damage to the distal part of the lung
• abnormal and permanent enlargement of the airspace and destruction of the alveolar wall
• similar to chronic bronchitis - irreversible in nature - the difference is it involves a distal part of the lung, asinine
• affects 50% of people over 50
• association with smoking
• occurs with chronic bronchitis (COPD)

Question 23

Effects of Smoking

Answer 23

□ Inhale injurious agent, causes recruitment of neutrophils
□ The neutrophils come in along the airways in the airspaces and releases it proteases
□ Elastase (a protease) is an enzyme that degrades elastic tissue
® Which is a major component of the interstitial tissue or supporting network of the alveolar capillary membrane
□ Neutrophils help fight pneumonia, so we do have release of elastase
® We have Alpha 1 antitrypsin (elastase inhibitor) within our alveoli - reason why people with pneumonia do not get emphysema
□ Smoking allows for the intact of injurious agents - the smoke contains oxygen free radicals which inactivate the A1 antitrypsin - nullifying the function of A4 antitrypsin and leading to overwhelming functioning of the elastase
□ There is an inherited condition known as:
® Hereditary A1 antitrypsin deficiency
□ Damage elastic tissue (due to overwhelming elastase activity) –> loss of elastic recoil
□ Alveolar sacs and ducts - like a big balloon
® Elastic tissue role is to cause compression of the alveolar sacs and ducts to allow for exhaling of the air, containing CO2
□ Airflow obstruction, air trapping –> decreased oxygen, increased CO2
® Elastic tissue cannot expel out used up air
Lead to decrease in ventilation, decreased oxygenation in the blood and increasing CO2 in the blood

Question 24

Bronchogenic Carcinoma

Answer 24

• 13% of all cancers, 7% of all cancer deaths - affects females 7:2
• etiologic agents: uranium, asbestos, radiation

Types
- Squamous cell carcinoma
- Adenocarcinoma
- Small undifferentiated carcinoma
- Large cell undifferentiated carcinoma

Prognosis - 25% survival at 5 years
- depends on the subtype (small cell worse) and stage at presentation

Stage
1. Tumor confined to lung (surgical management)
2. Tumor in lung and spread to parenchymal lymph nodes (surgical)
3. Tumour in the lung and spread to mediastinal lymph nodes (nonsurgical followed by surgical)
4. Metastatic spread of tumour to distant sites ( nonsurgical management)

Effects
1. local effects (airway obstruction, invasion of the chest wall or mediastinal - heart, great vessels, airways)
2. Distant effects (metastatic spread)
3. paraneoplastic effects (cannot be explained by distant or local effects)

Diagnosis
- historical and physical examination
- radiologic examination - x-ray, CT scan
- Bronchoscope - fibre optic tube + camera
- Fine needle aspiration biopsy

Question 25

Restrictive Lung Disease

Answer 25

• interstitial lung disease
• 15% of non-infectious lung diseases

common features
- patient presents with cyanosis, dyspnea, tachypnea, and no evidence of airway obstruction
-reduced lung volume
- reduced lung compliance
- reduced oxygen diffusion capacity
- involvement of the alveolar wall

Classification of the disease
1.) diseases known etiology - occurs as a result of exposure to an occupational or environmental injurious agent - inorganic (coal dust, silica, asbestos) or organic (moldy hay or bird proteins)
2.) Diseases with unknown etiology - sarcoidosis and idiopathic pulmonary fibrosis