Respiratory Disease

Question 1

FUNCTION of the lung

Answer 1

• oxygenation of blood
• removal of waste products (CO2)

Question 2

STRUCTURE of the lung

Answer 2

Airways, acini and secondary lobules, vasculature, lymphatics, pleura.

Airways: include Trachea, bronchi and bronchioles which include the terminal bronchioles and respiratory bronchioles.

Acini : are units supplied by a single terminal bronchiole. It includes respiratory bronchioles and its distal alveolar ducts and alveolar sacs. Acinus is the basic unit of gas exchange. Alveolar sacs are lined by type 1 and type 2 pneumocytes. Type 2 cells are the progenitor cells for type 1 cells and produce surfactant.

3 lobes on R lung, 2 lobes on L lung

Trachea to main bronchus, then primary bronchi on each of the 5 lobes, then secondary bronchi, then bronchioles (terminal, respiratory)

Respiratory tree has series of branching tubes, with 23 generations of branching
- the branches lead to bronchioles
- bronchioles lack smooth muscle and cartilage that is normally in trachea and bronchi. Instead, they have thin smooth muscle strands with ep lining

Bronchioles lead to terminal respiratory unit, which is made up of:
- respiratory bronchiole
- alveolar ducts
- alveolar sacs
- the above 3 parts have in common the fact that they are lined by an alveolar-capillary membrane aka alveolar-septae

Question 3

Alveolar wall

Answer 3

Gas transfer takes place across the alveolar-capillary membrane. The alveolar capillary membrane consists of:

a) capillary endothelium
b) basement membrane and surrounding interstitial tissue
c) Alveolar epithelium (type 1 and 2 pneumocytes).

Question 4

Gas exchange requires…

Answer 4

1. Ventilation (movement of air)
   - Gas moves from nose and mouth through large airways (trachea/bronchi/bronchioles) to lung parenchyma (alveoli) where gas exchange takes place.
   - movement of air from environment into the lung for gas (CO2) exchange
   - airway begins right below the Adams apple (near voice box). Starts with trachea, then has one main bronchus to each of the R lung and L lung.
   - histologically, airway is surrounded by smooth muscle and cartilage (provides support and protection)

2) Perfusion (movement of deoxygenated blood to the lung to be oxygenated, then it goes to organs)

Two systems of vessels:

a. pulmonary
- pulmonary artery carries deoxygenated blood from right side of the heart to the lungs.
- Intimate contact between air in alveoli and blood in pulmonary capillaries allows gaseous exchange to take place.
- Oxygenated blood returns via pulmonary vein to left atrium.

b. bronchial
- oxygenated blood from descending aorta and intercostal arteries supplies lung parenchyma.

Question 5

Respiratory Failure

Answer 5

Inability to maintain normal oxygen saturation of blood and to remove CO2 from blood entering the lungs.

Could be due to:
- decreased ventilation
- decreased perfusion
- ventilation/perfusion imbalance

Question 6

MECHANISMS OF DEFENCE IN RESPIRATORY TRACT and Inhaled injurious agents

Answer 6

Injury to the lung can be mediated through the airways or through the blood vessel systems.

Most injuries occur as a result of something which is inhaled (i.e. through the airway).

Inhaled injurious agents can be:
1. infectious (virus, bacteria, fungi, etc.)
2. non-infectious (toxic gases, cigarette smoke, organic particles, inorganic particles).

Mechanisms of Defence:
- Nasal clearance
- Tracheobronchial clearance by mucociliary “blanket” - clears smaller particles to be coughed up
- Alveolar clearance by macrophage system/immune system

Question 7

INFECTIOUS DISEASES OF THE LUNG

Answer 7

Pulmonary infections are more frequent than infections of other organ. Account for the largest number of workdays lost. The majority are upper respiratory tract infections caused by viruses.

PNEUMONIA

PULMONARY TUBERCULOSIS

Question 8

What is pneumonia?

Answer 8

Inflammation of the lung secondary to infection is called pneumonia.

Organisms involved include bacteria, viruses, fungi, protozoa, rickettsia and others.

Organisms can enter the lung via:
- aspiraton
- inhalation
- blood
- direct inoculation (as a result of trauma where the lung is penetrated by contaminated object)

Organisms enter the lung most commonly by aspiration of organisms that colonize the oropharynx and less commonly by inhalation of infected aerosols, hematogenous dissemination and direct inoculation.

Question 9

Pneumonia - Factors which determine if infection will occur

Answer 9

Factors which determine if infection will occur will depend on:

1. Dose and virulence of the organisms
2. Host susceptibility - pneumonia will occur if:
   i) defense mechanisms are impaired
   ii) impaired resistance (immunocompromised)

Question 10

Pneumonia - Examples of impaired host defenses

Answer 10

1) Loss or suppression of the cough reflex
- (eg) coma, anaesthetic

2) Injury to the mucociliary apparatus
- (eg) cigarette smoking, inhalation of hot or corrosive gases, viral diseases

3) Interference with alveolar macrophages
- (eg) alcoholism, malnutrition, diabetics

4) Accumulation of fluid or secretions in alveoli
- (eg) pulmonary edema, cystic fibrosis

Question 11

Classification of pneumonia

Answer 11

1) Morphologic

i) Lobar pneumonia - the entire lung or lobe is involved due to organisms which can spread very rapidly.

ii) Bronchopneumonia - infection is spread by the airways, therefore, this type tends to be patchy.

2) Clinical (most important classification)

i) Community acquired (most common) - organisms involved include Streptococcus pneumoniae (most common cause), Hemophilus influenzae, and Mycoplasma pneumoniae

ii) Nosocomial (hospital or nursing home acquired) - organisms involved include enteric gram negative bacilli (E. coli, Pseudomonas aeruginosa, klebsiella sp.), Staphylococcus aureus and oral anaerobes.
- these patients tend to have severe underlying disease, immunosuppressed, and prolonged antibiotic therapy

iii) Pneumonia in immunocompromised patients - organisms involved include CMV, fungal organisms, tuberculosis, pneumocystis.
- is an opportunistic infection, which means that it causes diseases in immunocompromised people, but rarely causes infection in normal hosts
- bacteria (P. aeruginosa, Mycobacterium sp., Legionella, Listeria)
- viruses (CMV, HSV)
- fungi (Candida sp., Aspergillus sp.)
- Immunocompromised patients are more susceptible to infection than healthy patients. Virulent organisms will cause more severe infections than in healthy individuals.
- Organisms which would be unusual in healthy individuals may also cause significant infections in the immunocompromised host.
- these people have immune defences that are suppressed by disease, or immunosuppressive therapy for organ transplantation, or chemotherapy or irradiation

3) Type of Infectious agents

Question 12

Clinical presentation of pneumonia

Answer 12

Pneumonia presents with a sudden onset of fever and chills, malaise, and pain on inspiration (from pleuritis). Cold sores on the lips may flare up. There is still a significant mortality in many forms of untreated bacterial pneumonia.

Question 13

Diagnosis of pneumonia

Answer 13

Based on the clinical presentation, typical x-ray appearance, the finding of neutrophils in the sputum and identifying the organisms. The important factor in treatment is to identify the organism and treat with the antibiotic to which the organism is sensitive.

Question 14

Complications of pneumonia

Answer 14

a) Lung abscess formation: Can occur in the absence of a preceding pneumonia as a result of aspiration of infective material. Usually associated with a depressed cough reflex.
- is a localize suppurative process with necrosis of the lung tissue
- can occur following pneumonia, or can even occur by itself (without preceding pneumonia)

b) Empyema: The infections spreads to the chest cavity or pleural cavity
- intrapleural fibrinosuppurative reaction (pus in the pleural cavity)

c) Septicemia: The organisms spread beyond the lung via the blood stream.

Question 15

PULMONARY TUBERCULOSIS - current issues

Answer 15

caused by Mycobacterium tuberculosis
- is secondary to aerobic bacilli, which is identified by an acid fast stain (Ziehl-Neelsen stain).
- Transmission via inhalation of infected aerosolized droplets

a) A major cause of morbidity and mortality in the world

b) Increased incidence in North America

c) Increased incidence of multi-drug resistant strains.

Question 16

NON-INFECTIOUS DISEASES OF THE LUNG

Answer 16

Non-infectious diseases of the lung can be divided into non-neoplastic and neoplastic diseases.
- The nonneoplastic lung disease may be further divided into obstructive or restrictive diseases.

Nonneoplastic lung diseases are majority due to inhaled injurious agents

Obstructive lung diseases
- involve the airway and are characterized by increased resistance to airflow due to partial or complete obstruction of the airway from the trachea to the bronchioles.
- This condition may be acute (eg. Aspiration of a foreign object) or chronic.
- The chronic diseases are called chronic obstructive pulmonary diseases.

Restrictive lung disease
- is characterized by reduced expansion of the lung.
- Therefore there is a decrease in the total lung capacity.
- This may be due to an abnormality of the chest wall or the lung.

CHRONIC OBSTRUCTIVE LUNG DISEASE

BRONCHOGENIC CARCINOMA

METASTATIC TUMOURS

RESTRICTIVE LUNG DISEASES

Question 17

CHRONIC OBSTRUCTIVE LUNG DISEASE - features and types of conditions

Answer 17

This is a non-specific term which includes a number of conditions which share a number of features but have distinct anatomic and clinical characteristics.

The common features include:
a) Patients present with shortness of breath
b) Chronic and or recurrent airflow obstruction.
c) Decreased forced expiratory volume

The three most common conditions include:
A) Bronchial asthma
B) Chronic Bronchitis
C) Emphysema

Question 18

Bronchial asthma - CHRONIC OBSTRUCTIVE LUNG DISEASE

Answer 18

This is an inflammatory disorder characterized by:
i) hyper-reactive airways - secondary to increased responsiveness of the airways to various stimuli.
ii) Episodic and reversible bronchoconstriction.
- causes coughing, dyspnea, wheezing, chest tightness

The various stimuli include exposure to an allergen, temperature (cold or heat), infectious agent, exercise, or emotional stress, or idiopathic (unknown)

Between attacks, the patients may be asymptomatic. However, but in rare cases, the attacks can be fatal and irreversible as a result of unremitting attacks (status asthmaticus)

Asthma is a type 1 hypersensitivity reaction

Asthma is abnormal narrowing of the airway

Risk factors:
- family history of allergy or allergy disorders
- high exposure to airborne allergens in first year of life
- exposure to tobacco
- frequent respiratory infections early in life
- low birth weight
- occupational exposure

Question 19

Chronic Bronchitis - CHRONIC OBSTRUCTIVE LUNG DISEASE

Answer 19

This condition is clinically defined as follows: A patient with a persistent cough with sputum production for a least three months of the year, in at least two consecutive years.

Bronchoconstriction is irreversible

Etiology is cigarette smoke in 80% of cases. The cigarette smoke will impair ciliary action and cause hypersecretion of mucus. This will lead to airway obstruction and impairment of gas exchange. These patients are at increased risk of pulmonary infections and the development of pulmonary hypertension.

Irritation of airways (like via smoking) causes Recruitment of neutrophils, which causes the Release of proteases (elastase, cathepsin). Proteases damage the lining of airways. Then, there are protective changes:
- hyperplasia of submucosal glands
- squamous metaplasia
Then, there is hypersecretion of mucus and airway obstruction. And then, increased risk of infection, with decreased ventilation

Question 20

Emphysema - CHRONIC OBSTRUCTIVE LUNG DISEASE

Answer 20

This is a common disease affecting fifty percent of the population over the age of fifty. There is a significant association with cigarette smoking. Smokers exhibit more lung destruction than non-smokers. The condition is characterized by damage to the distal part of the lung (acinus) leading to abnormal and permanent enlargement of the airspaces, and destruction of the alveolar wall

Inhaled injurious agents via smoking causes recruitment of neutrophils. Then the neutrophils go to the airways and release proteases (like elastase). Elastase is an enzyme that degrades elastic tissue, which is an important component of the interstitial tissue that make up the supporting network of the alveolar capillary membrane.
- Also, neutrophils are major component to help fight pneumonia. People with pneumonia do not get emphysema because there is alpha1-antitrypsin within our alveoli that inhibits elastase, so there is no degradation of the elastic tissue
- Also, there is a hereditary condition called alpha1-antitrypsin deficiency, so these people have lots of elastase

There is damage to elastic tissue due to overwhelming elastase activity. Then, there is loss of elastic recoil. Then, there is airflow obstruction and air trapping. Then, there is decreased oxygen and increased CO2.

Irreversible

Impacts distal part of lungs, not the airways (unlike asthma and bronchitis)

Also occurs with chronic bronchitis
- for people with both chronic bronchitis and emphysema, they are diagnosed with COPD (chronic obstructive pulmonary disease)

This will lead to airflow obstruction and impairment with gas exchange. These patients are at risk for pulmonary hypertension.

Question 21

BRONCHOGENIC CARCINOMA

Answer 21

Lung cancer accounts for 13% of all cancers in humans and 17% of all cancer deaths. The number one etiology is cigarette smoking. Eighty percent of all lung cancers occur in smokers. Other etiologic agents include pollution, genetic factors, radioactive gases, uranium, radiation and asbestos.

Lung cancer is more common in females than in males

Question 22

BRONCHOGENIC CARCINOMA - 4 types of lung carcinomas

Answer 22

There are four types of lung carcinomas:
- squamous cell carcinoma
- adenocarcinoma
- small cell undifferentiated carcinoma
- large cell undifferentiated carcinoma.

Question 23

Prognosis of lung cancer

Answer 23

The overall prognosis of lung cancers is dreadful: 25% survival at five years.

Prognosis is dependent on:

• The tumour type - small cell carcinoma has the worse prognosis
• Stage at presentation - the stage is the extent of the tumour at the time of diagnosis:

Stage 1: tumour is confined to the lung (no metastasis)

Stage 2: tumour is in the lung and spread to parenchymal lymph nodes

Stage 3: tumour in the lung and spread to mediastinal lymph nodes

Stage 4: the tumour has spread to distant sites.

Question 24

Effects of lung cancer may be local or distant.

Answer 24

Local Effects include:
i) obstruction of an airway
ii) direct invasion of adjacent structures (chest wall, and mediastinum)

Distant Effects include:
i) metastatic spread via lymphatics or blood
ii) paraneoplastic effects. These are symptoms in patients which cannot be explained by local or distant
spread of the tumour. Such as hormones

Question 25

Diagnosis of BRONCHOGENIC CARCINOMA

Answer 25

History and physical examination.
- Patients may present with cough, weight loss, chest pain, or dyspnea

Radiologic examination
- chest x-ray or CT scan

Tissue diagnosis - biopsy of the tumour to identify malignant cells.
Occur via:
i) Examination of the sputum
ii) Bronchoscopic biopsy (camera inside)
iii) Fine needle aspiration biopsy - use needle, go through chest wall

Question 26

Treatment of BRONCHOGENIC CARCINOMA

Answer 26

If the patient is operable (i.e. stage 1 or 2), then formal resection either of a lobe or of a lung is undertaken.

Inoperable tumours are treated with either radiation or chemotherapy or a combination of the two.

Since small cell carcinoma have a very bad prognosis these patients are not subjected to operation, but are treated with chemotherapy.

Question 27

METASTATIC TUMOURS

Answer 27

The lung has a rich blood supply. Therefore the lung is a common site of metastasis from other sites. These include the breast, stomach, pancreas and colon. Metastatic tumours are often multiple and round.

Question 28

RESTRICTIVE LUNG DISEASES

Answer 28

Restrictive lung disease are also known as interstitial lung diseases. These diseases account for 15% of non-infectious lung diseases.

This term encompasses a number of disease which have a number of common features. These include:

i) Patients present with cyanosis, dyspnea, tachypnea and no evidence of airway obstruction

ii) Reduced lung volume

iii) Reduce lung compliance

iv) Reduced oxygen diffusion capacity

v) Involvement of the alveolar wall

Classification of the diseases:

i) Diseases of known etiology - disease occurs as a result of exposure to an occupational or environmental injurious agent. Inhaled injurious agents enter the air sacs, causing inflammatory reaction. These agents may be inorganic (eg. Coal dust, silica, asbestos) or organic (eg. Moldy hay (farmer’s lung) or bird proteins (bird fancier’s lung))

ii) Diseases of unknown etiology - include sarcoidosis and idiopathic pulmonary fibrosis.

Question 29

Blood borne injurious agents

Answer 29

Blood borne injurious agents
1. Infectious (virus, bacteria, fungi, parasites)
2. Non-infectious
- drugs
— amiodarone, which treats heart arrhythmias, with secondary side effect of lung toxicity
— bleomycin, which is a chemotherapeutic agent used to treat diff cancers, with secondary side effect of injury to the lung parenchyma
- autoimmune diseases
— antibodies circulate and may be deposited upon the lung and cause secondary lung side effects

The most common blood borne injurious agent is thromboembolism
- for instance, thrombus in leg may break off and embolise and circulate to other vessels and cause blockage

Question 30

Cigarettes

Answer 30

Many components make up a cigarette
- some components are carcinogenic agents (agents that will cause cancer)

A 30 year old who smokes 15 cigarettes a day will have a life shortened by 5 years

Cigarettes are associated with:
- lung disease
- CV disease (accelerates atherosclerosis)
- cancer (mouth, pharynx, larynx, lung, esophagus, bladder, pancreas)

It is the most important preventable risk factor for lung disease

Are the leading cause of preventable death