Chronic Obstructive Pulmonary Disease

Question 1

What process is hindered in Chronic Obstructive Pulmonary Disease? What values are affected? What happens to Total Lung Capacity (TLC)?

Answer 1

Airway obstruction. Lung does not empty and air is trapped. FVC is lowered, FEV1 is lowered even more, results in a decrease in FEV1:FVC ratio. Total lung capacity is usually increased due to air trapping.

Question 2

What is the presentation of chronic bronchitis? What is it associated with? What is seen on histology? What measurement scale is used to assess the damage of the disease?

Answer 2

Chronic productive cough lasting at least 3 months over a minimum of 2 years. Highly associated with smoking. Hypertrophy of bronchial mucinous glands. Reid index (thickness of mucus glands relative to bronchial wall thickness) which increases to > 50% (normal is 40%).

Question 3

What are the clinical features of chronic bronchitis?

Answer 3

1. Productive cough due to excessive mucus production
2. Cyanosis (‘blue bloaters’) - Mucus plugs trap CO2 which increases PaCO2 and decreases PaO2. 3. Increased risk of infection and cor pumonale

Question 4

What is emphysema?

Answer 4

Destruction of alveolar air sacs. Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping.

Question 5

What structures are involved in emphysema?

Answer 5

Destruction of alveolar air sacs. Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping.

Question 6

What process is disrupted in emphysema? What happens?

Answer 6

Imbalance of proteases and antiproteases. Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages. alpha1-antitrypsin (A1AT) neutralizes proteases. Excessive inflammation or lack of A1AT leads to destruction of the alveolar air sacs.

Question 7

What process is disrupted in emphysema? What happens?

Answer 7

Imbalance of proteases and antiproteases. Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages. alpha1-antitrypsin (A1AT) neutralizes proteases. Excessive inflammation or lack of A1AT leads to destruction of the alveolar air sacs.

Question 8

What is the most common cause of emphysema? What does it cause and which part of the lungs does it affect?

Answer 8

Smoking. Pollutants in smoke lead to excessive inflammation and protease-mediated damage. Results in CENTRIACINAR emphysema that is most severe in the upper lobes.

Question 9

What does alpha1-antitrypsin (A1AT) deficiency lead to ? What does it cause and which part of the lungs does it affect? What other organ is affected?

Answer 9

Lack of antiprotease leaves the air sacs vulnerable to protease-mediated damage. Results in PANACINAR emphysema that is most severe in the lower lobes. Liver cirrhosis may also be present.

Question 10

How is the liver damaged in alpha1-antitrypsin (A1AT)? What is seen on biopsy?

Answer 10

A1AT deficiency is due to misfolding of the mutated protein. Mutant A1AT accumulates in the endoplasmic reticulum of hepatocytes, resulting in liver damage. Biopsy reveals pink, PAS-positive globules in hepatocytes.

Question 11

What is the normal allele in A1AT (alpha1-antitrypsin) deficiency? How many copies are expressed?

Answer 11

PiM. 2 copies.

Question 12

What is the most common clinically relevant mutation in A1AT (alpha1-antitrypsin) deficiency?

Answer 12

PiZ

Question 13

Which mutations are usually asymptomatic with decreasing levels of A1AT (alpha1-antitrypsin)? How is the risk level increased for emphysema?

Answer 13

PiMZ heterozygotes. When Smoking is present.

Question 14

Which mutations are at significant risk for panacinar emphysema and cirrhosos?

Answer 14

PiZZ

Question 15

Which mutations are at significant risk for panacinar emphysema and cirrhosis?

Answer 15

PiZZ homozygotes

Question 16

What are the 5 clinical features of emphysema?

Answer 16

1. Dyspnea and cough with minimal sputum 2. Prolonged expiration with pursed lips (‘pink puffer’) 3. Weight loss 4. Increased anterior-posterior diameter of chest 5. Hypoxemia and cor pulmonale

Question 17

What is asthma? What causes it and when does it present?

Answer 17

Reversible airway bronchoconstriction, most often due to allergic stimuli (atopic asthma). Presents in childhood, often associated with allergic rhinitis, eczema and a family history of atopy.

Question 18

What is the pathogenesis of Asthma? What type of hypersensitivity is it?

Answer 18

Type I.

1. Allergens induce TH2 phenotype in CD4+ T cells of genetically susceptible individuals.
2. TH2 cells secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils) and IL-10 (stimulates TH2 cells and inhibits TH1).
3. Reexposure to allergen leads to IgE mediated activation of mast cells.

Question 19

How is the damage done via IgE mediated activation of mast cells in asthma?

Answer 19

1. Release of preformed histamine granules and 1. generation of leuktrienes C4, D4, and E4 lead to bronchoconstriction, inflammation and edema (early-phase reaction)
2. Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late phase reaction).

Question 20

How is the damage done via IgE mediated activation of mast cells in asthma?

Answer 20

1. Release of preformed histamine granules and 1. generation of leuktrienes C4, D4, and E4 lead to bronchoconstriction, inflammation and edema (early-phase reaction)
2. Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late phase reaction).

Question 21

What is the pattern of the clinical features of asthma? What is it related to? What are the three features?

Answer 21

Episodic and related to allergen exposure.

1. Dyspnea and wheezing
2. Productive cough, clasically with spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals)
3. Severe unrelenting attack can lead to status asthmaticus and death

Question 22

What are non allergenic causes of asthma?

Answer 22

Exercise, viral infection, aspirin (aspirin intolerant asthma) and occupational exposures.

Question 23

What are non allergenic causes of asthma?

Answer 23

Exercise, viral infection, aspirin (aspirin intolerant asthma) and occupational exposures.

Question 24

A patient comes in with cough, dyspnea and foul smelling sputum. What does he have? What are some complications?

Answer 24

He has Bronchiectasis which is a permanent dilatation of bronchioles and bronchi. Loss of airway tone results in air trapping. Complications include hypoxemia with cor pulmonale and secondary AA amyloidosis

Question 25

What are the 5 causes of bronchiectasis?

Answer 25

1, Cystic fibrosis 2. Karatagener syndrome 3. Tumor or foreign body 4. Necrotizing infection 5. Allergic bronchopulmonary aspergillosis

Question 26

What is Kartagener syndrome and what diseases is it associated with?

Answer 26

Inherited defect of the dyenin arm which is necessary for ciliary movement. Associated with sinusitis, infertility, situs inversus.

Question 27

What two diseases is allergic bronchopulmonary aspergillosis usually seen?

Answer 27

Asthmatics and Cystic Fibrosis