Respiratory diseases

Question 1

What is the function of the lung?

Answer 1

• Oxygenation of blood
• Removal of waste products (CO2)
• Requires:
  1. Ventilation (movement of air). Movement of air from the environment into our lungs to perform gas exchange - requires airway
  2. Perfusion (movement of blood). Movement of deoxygenated blood to the lungs, then oxygenated blood out of lungs to the rest of the body.

Question 2

What is the structure of the lungs?

Answer 2

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

Question 3

How are diseases of the lung divided?

Answer 3

Diseases of the lung can be divided into infectious and non-infectious diseases, and then non-infectious diseases can be subdivided into non-neoplastic and neoplastic diseases (tumours).

Question 4

Describe airways

Answer 4

Include Trachea, bronchi (main, primary, secondary, tertiary) and bronchioles (no larger than 1mm in diameter) which include the terminal bronchioles and respiratory bronchioles - being below Adam’s apple. Composed of inner epithelial layer, with smooth muscle and cartilage
- Series of branching tubes
- 23 generations (respiratory tree) -branches eventually lead to bronchioles
- Bronchioles have thin linings of smooth muscle and epithelial - no larger than 1 mm in diameter - bronchiole eventually leads to acinus

Question 5

Describe acini

Answer 5

Acini are units supplied by a single terminal bronchiole - termed “terminal respiratory unit”. - end point of bronchiole - all lined by alveolar-capillary membrane.
- 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. All 3 components are lined by interstitial septae

Question 6

Describe the alveolar wall and alveolar-capillary membrane

Answer 6

gas transfer takes place across the alveolar-capillary membrane.
- “Alveolar Septae”
- Site of Gas transfer
- Occurs across the alveolar capillary membrane
- Capillary endothelium
- Basement membrane and surrounding interstitial tissue
- Alveolar epithelium (type 1 and 2 pneumocytes)

Alveolar-capillary membrane - part of alveolar wall:
- Type 1 and 2 pneumocyte
- Sit on Interstitial tissue (connective tissue)
- Interstitial tissue surrounds endothelial cells which make up capillaries
- Where gas exchange occurs - gas passes by all - the components listed until it gets to the capillary lumen - oxygen in, CO2 out

Question 7

What does gas exchange require? describe respiratory failure

Answer 7

1. Ventilation: gas moves from nose and mouth through large airways (trachea/ bronchi/ bronchioles) to lung parenchyma (alveoli) where gas exchange takes place
2. Perfusion: two systems of vessels:
   - Pulmonary - pulmonary artery carries deoxygenated blood from the 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 the left atrium.
   - Bronchial - oxygenated blood from descending aorta and intercostal arteries supplies lung parenchyma.
   * Failure of either of these systems results in respiratory failure

Respiratory failure:
- 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 8

Describe lung injury

Answer 8

Can be injured by 2 pathways: air (exposed to 10,000 L of air/day)- most common- or blood.
1. Inhaled injurious agents (most common way of lung injury):
- Infectious: Bacterial, Viral, Fungal
- Non-infectious: Cigarette smoke, Organic particles, Inorganic particles, Toxic gases
2. Blood borne injurious agents:
- Infectious: Bacteria, Parasites, Viral, Fungal
- Non-infectious: Drugs - amiodarone (used to treat heart murmurs/ arythmias), bleomycin (chemotherapy), Autoimmune diseases (antibodies) - rheumatoid arthritis, lupus. Thromboembolism - most common blood-borne injury. Blocks off blood supply

Question 9

What are the mechanisms of defence in the respiratory tract?

Answer 9

Injury to the lung can be mediated through the airways or through the blood vessel systems
Mechanisms of defence:
- Nasal clearance (cough or sneeze reflex)
- Tracheobronchial clearance by muco-ciliary “blanket” - clears smaller particles to be coughed up. Get trapped in mucosa, then cilia beat the particle out where they can be coughed up, etc. (lined by pseudostratified columnar epithelium - cells produce mucus)
- Alveolar clearance by macrophage system/ immune system. Destroy any agents that get past other defence mechanisms. Have resident macrophages to phagocytose any foreign material.

Question 10

Describe infectious diseases of the lung. example?

Answer 10

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

Question 11

Describe Pneumonia

Answer 11

• Inflammation of the lung secondary to infection is called pneumonia.
• Organisms involved include bacteria, viruses, fungi, protozoa, rickettsia and others.
• Organisms enter the lung most commonly by aspiration of organisms that colonize the oropharynx (organisms are usually in the oral cavity or stomach and are displaced to the lung) and less commonly by inhalation of infected organism from environment, hematogenous dissemination (blood stream - infection in other part of body carried by bloodstream to the lung) and direct inoculation (eg. stabbed by a knife - to the lung- which is infected by an organism - gains direct access to the lung) - penetrated by instrument.
• First response by the body - neutrophils in the acinus
• Factors which determine if infection will occur will depend on:
  1. Dose and virulence of the organisms
  2. Host susceptibility - pneumonia will occur if:
  -> Defence mechanisms are impaired
  -> Impaired resistance (immunocompromised) - e.g. due to chemo, or HIV

Question 12

What are the classifications of pneumonia?

Answer 12

Morphologic:
1. Lobar pneumonia - the entire lung or lobe is involved due to organisms which can spread very rapidly
2. Bronchopneumonia - infection is spread by the airways, therefore, this type tends to be patchy (some normal lung dispersed within diseased lung)

Clinical (most important classification - what doctors use):
1. Community acquired - most common - organisms involved include streptococcus pneumoniae (most common cause), Haemophilus influenzae, and Mycoplasma pneumoniae
-> Once decided that patient has community acquired pneumonia, will give antibiotics against Streptococcus pneumoniae right away.
2. Nosocomial (hospital or nursing home acquired) - organisms involved include enteric gram negative bacilli/ rods (Pseudomonas aeruginosa or e.coli), Staphylococcus aureus and oral anaerobes.
-> Patient in hospital develops pneumonia. Especially severe underlying disease, immunosuppressed, prolonged antibiotic therapy.
3. Pneumonia in immunocompromised patients - organisms involved include viruses (CMV, HSV), fungal organisms (candida sp, aspergillus sp), tuberculosis, pneumocystis. Usually opportunistic infectious agents - rarely causes infection in normal hosts.
-> 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.
-> Immune defences are suppressed by disease. Immunosuppressive therapy for organ transplantation. Chemotherapy. Irradiation.

Type of infectious agents
- Bacterial
- Viral
- Fungal
- Parasitic

Question 13

What is the clinical presentation of pneumonia?

Answer 13

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 14

What is the diagnosis of pneumonia?

Answer 14

based on the clinical presentation, typical x-ray appearance (chest x-ray taken), the finding of neutrophils in the sputum (culture the sputum the patient coughs up + analyse) and identifying the organisms. The important factor in treatment is to identify the organism and treat it with antibiotics to which the organism is sensitive.

Question 15

What are the complications of pneumonia?

Answer 15

1. Lung abscess formation: localized suppurative process with necrosis of the lung tissue - can occur following pneumonia or in the absence of a preceding pneumonia (by itself) as result of aspiration of infective material. Usually associated with a depressed cough reflex. Usually treatment involves removal of the affected lobe.
2. Empyema: spread of infection to the pleural/ chest cavity. Intrapleural fibrinosuppurative reaction (pus in the pleural cavity). Have to try and drain out pleural cavity.
3. Septicemia: the organisms spread beyond the lung via the bloodstream. - effects elsewhere in the body.

Question 16

What are examples of impaired host defences?

Answer 16

• Loss or suppression of the cough reflex (+sneeze) - why ask to not eat before surgery, so do not get aspiration into lungs while we have lost defences. E.g. coma, anaesthetic
• Injury to the mucociliary apparatus. E.g. cigarette smoking (smokers have high incidence of pneumonia), inhalation of hot or corrosive gases, viral diseases
• Interference with alveolar macrophages - decreased function. E.g. alcoholism, malnutrition
• Accumulation of fluid or secretions in alveoli. E.g. pulmonary edema, cystic fibrosis (produce thick, sticky mucus)

Question 17

Describe non-infectious diseases of the lung

Answer 17

Non-infectious diseases of the lung can be divided into non-neoplastic and neoplastic diseases.

Question 18

Describe non-neoplastic lung disease - types?

Answer 18

• The non-neoplastic lung disease may be further divided into obstructive or restrictive diseases. Majority due to inhaled injurious agents.
  1. 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 (e.g. aspiration of a foreign object) or chronic. The chronic diseases are called chronic obstructive pulmonary diseases.
  2. Restrictive lung disease: 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.

Question 19

Describe chronic obstructive lung disease. What are the three most common conditions?

Answer 19

This is a non-specific term which includes a number of conditions/diseases which share a number of features but have distinct anatomic and clinical characteristics. The common features include:
- Patients present with shortness of breath
- Chronic and or recurrent airflow obstruction
- Decreased forced expiratory volume
The three most common conditions include:
1. Bronchial asthma
2. Chronic Bronchitis
3. Emphysema

Question 20

What is bronchial asthma?

Answer 20

This is an inflammatory disorder of the airway characterised by:
- Hyper-reactive airways - secondary to increased responsiveness of the airways to various stimuli - very sensitive
- Episodic (episodes/ attacks) reversible bronchoconstriction which include:
-> Coughing, dyspnea, wheezing, chest tightness. Asymptomatic between attacks.
-> Status asthmaticus - rarely episodes are not irreversible and can lead to sudden death.
- The various stimuli include exposure to an allergen, temperature (cold or heat), infectious agent, exercise, or emotional stress - some cases are idiopathic (unknown)
- Inflammation of the airway - type 1 hypersensitivity reaction. Abnormal narrowing of the airway.
- Don’t know etiology - but there are risk factors including:
-> Family history of allergy and allergic disorders
-> High exposure to airborne allergens in the first year of life
-> Exposure to tobacco
-> Frequent respiratory infections early in life
-> Low birth weight
-> Occupational exposure - when asthma may present in an adult - chronic inflammation

Question 21

What is chronic bronchitis? etiology> pathogenesis?

Answer 21

This condition is clinically defined as follows: a patient with a persistent cough with sputum production for at least three months (most days of the week) of the year, in at least two consecutive years. - irreversible - diff from athsma
- Etiology is cigarette smoke (80% of cases). First hand or secondary. 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 (airways)-> recruit neutrophils -> release granules which contain proteases (elastase, cathepsin - proteases damage the lining of the airways) -> protective changes: 1. Hyperplasia of submucosal glands, 2. Squamous metaplasia (squamous cells lack the cilia meant to clear the airways)
- We have almost all had acute bronchitis - but will not last more than a month generally at most
- Pathogenesis: hypersecretion of mucus -> airway obstruction -> increased risk of infection (increased mucus production - good housing for organisms) + decreased ventilation

Question 22

What is Emphysema?

Answer 22

The condition is characterized by damage to the distal part of the lung (acinus) leading to abnormal and permanent enlargement of the airspaces as well as destruction of the alveolar wall.
- Difference with the other two is that this disorder involves distal part (acinus) rather than airways - more proximal
- This is a common disease affecting 50% of the population over the age of 50. There is a significant association with cigarette smoking. Smokers exhibit more lung destruction than non-smokers.
- Inhaled injurious agent - causes recruitment of neutrophils - releases proteases / granules (elastase - degrades elastic tissue important component of the alveolar-capillary membrane) - damage to elastic tissue -> loss of elastic recoil (exhalation)
- While neutrophils are released while someone has pneumonia as well - they do not get this process and develop emphysema because they normally have A1 (alpha 1) antitrypsin which inhibits/ degrades elastase.
- Smoking contains oxygen free radicals which inactivate A1 antitrypsin - nullifies. There is also a hereditary A1 antitrypsin deficiency which can contribute.
- This will lead to airflow obstruction and impairment with gas exchange. These patients are at risk for pulmonary hypertension.
- Occurs with chronic bronchitis (when patients have both - diagnose them with COPD - chronic obstructive pulmonary disease)

Question 23

Describe bronchogenic carcinoma (lung cancer). What are the four types? etiology?

Answer 23

• Lung cancer accounts for 12.6% of all cancers in humans and 17.8% of all cancer deaths (22% developed, 14.6% in developing). 2 male : 7 female - more common in females than males (due to advertising mostly)
• In males second only to prostate cancer, in females second to breast cancer - but leading cause of death is still lung cancer for both.
• The number one etiology is cigarette smoking. 80% of all lung cancers occur in smokers.
• Other etiologic agents include atmospheric pollution, genetic factors, uranium, radiation (radioactive gases) and asbestos.
  There are four types of lung carcinomas (subtypes):
  1. Squamous cell carcinoma (look like squamous cells)
  2. Adenocarcinoma (glandular)
  3. Small cell undifferentiated carcinoma (cells smaller than squamous and adenocarcinoma)
  4. Large cell undifferentiated carcinoma

Question 24

What is the prognosis of lung cancer?

Answer 24

The overall prognosis of lung cancers is dreadful: 25% survival at five years. Prognosis is dependent on:
- The tumour type (subtype) - small cell carcinoma has the worse prognosis
- Stage at presentation - the stage is the extent of the tumour at the time of diagnosis - how far tumour has spread
Stage 1: tumour is confined to the lung (no metastasis)
Stage 2: tumour is in the lung and spread to parenchymal lymph nodes (regional/ close by lymph nodes)
Stage 3: tumour in the lung and spread to mediastinal lymph nodes (further beyond stage 2)
Stage 4: the tumour has spread to distant sites (metastatic spread)

Question 25

What are the effects of lung cancer?

Answer 25

Effects of lung cancer may be local or distant
1. Local effects:
-> Obstruction of an airway
-> Direct invasion of adjacent structures (chest wall or mediastinum)
2. Distant effects:
-> Metastatic spread via lymphatics or blood
3. Paraneoplastic effects. These symptoms in patients which cannot be explained by local or distant spread of the tumour - may be an effect to hormones, which cause effects

Question 26

Diagnosis of lung cancer

Answer 26

Diagnosis based on:
- History and physical examination: patient 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:
1. Examination of the sputum
2. Bronchoscopy biopsy - fibre optic tube with camera to insert into airways to the lungs to biopsy the tumour
3. Fine needle aspiration biopsy - mass cannot be reached by the fibre optic tube (diameter of bronchioles, etc not permitting) - go through chest wall with needle, x-ray guided, take sample to biopsy

Question 27

What is the treatment of lung cancer?

Answer 27

If the patient is operable (i.e. stage 1 or 2) then formal resection either of a lobe or of a lung is undertaken. Treatment dependent on the stage and subtype of the cancer.
- Inoperable tumours are treated with either radiation or chemotherapy or a combination of the two.
- Since small cell carcinoma has a very bad prognosis these patients are not subjected to operation, but are treated with chemotherapy.

Question 28

Describe metastatic tumours of the lung

Answer 28

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 29

Describe restrictive lung disease

Answer 29

Restrictive lung diseases are also known as interstitial lung diseases. These diseases account for 15% of non-infectious lung diseases.
- This term encompasses a number of diseases which have a number of common features. These include:
1. Patients present with cyanosis (bluish hue to skin), dyspnea (shortness of breath), tachypnea (rapid breathing) and no evidence of airway obstruction
2. Reduced lung volume
3. Reduce lung compliance
4. Reduced oxygen diffusion capacity (measure of the diffusion rate of oxygen from the air spaces into the capillaries) - in the disease, oxygen has to diffuse through dense layers - reduced rate
5. Involvement of the alveolar wall - thus name “interstitial lung disease”