Obstructive Lung Disease Flashcards Preview

CAM201 Pathology > Obstructive Lung Disease > Flashcards

Flashcards in Obstructive Lung Disease Deck (38):

Pulmonary function test findings for obstructive lung disease.

FEV1 reduced <70%


Pulmonary function test findings for restrictive lung disease

FVC reduced <80% FEV1 reduced FEV1% normal


TLC in obstructive lung disease

TLC increases (through gas trapping), although the ability of the lung to exchange oxygen and CO2 is reduced.


The two situations in which restrictive lung disease occurs

1. Chest wall disorders in the presence of normal lungs (e.g. polymyelitis, severe obesity, pleural disease and kyphoscoliosis) 2. Acute (diffuse alveolar damage) or chronic interstitial and infiltrative diseases (e.g. pulmonary fibrosis)


TLC in restrictive lung diseases



Disorders associated with airflow obstruction

1. Chronic bronchitis 2. Bronchiectasis 3. Asthma 4. Emphysema 5. Bronchiolitis


Chronic Obstructive Pulmonary Disease

Emphysema and chronic bronchitis occurring together. Often occur together because of common aetiology: cigarette smoking. In most patients COPD is the result of cigarette smoking but about 10%.



Characterised by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis. It is usually associated with chronic bronchitis and follows a chronic progressive course.


Classification of emphysema

Classified according to the anatomical distribution within the lobule. 1. Centriacinar (centrilobular) 2. Panacinar (panlobular) 3. Distal acinar (paraseptal) 4. Irregular The first two types cause significant airflow obstruction. Centriacinar emphysema constitutes more than 95% of cases.


Cenriacinar (centrilobular) emphysema

The central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared. This form tends to be worse in the upper lobes and is strongly associated with smoking. Carbon pigment is often seen in the alveolar walls.


Panacinar (panlobular) emphysema

The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli. This is usually associated with alpha-1 antitrypsin deficiency and is worse at the lung bases.


Distal acinar (paraseptal)

The proximal portion of the acinus is normal, but the distal part is predominantly involved. It is worst adjacent to the pleura, along the lobular CT septa, and at the margins of the lobules. It occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs. It is associated with spontaneous pneumothorax in young adults.


Irregular emphysema

The acinus is irregularly involved, is almost always associated with scarring. It may be the most common form of emphysema because careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process. These foci of irregular emphysema are asymptomatic and clinically insignificant.


COPD pathogenesis

Characterised by mild chronic inflammation throughout the airways, parenchyma and pulmonary vasculature. The best explanation for the development of emphysema is the protease-antiprotease theory which holds that alveolar wall destruction results from an imbalance between proteases (mainly elastase) and antiproteases in the lung. Chronic irritation and inflammation (e.g. in cigarette smoking) causes increased neutrophils (the principal source of cellular proteases (which include elastase) into the lung and these release their protease granules. Protease activity and deficiency of protease inhibitors causes overall decreased antiprotease activity resulting in elastic tissue destruction. Macrophages, free radicals (oxidants)/antioxidant imbalcne, elastases and metalloproteinases are also imporant.


Whats the most commonly deficient protease inhibitor?

alpha-1 antitrypsin (alpha1-AT). This is a anti-protease usually present in serum, tissue fluids and macrophages and is a major inhibitor of neutrophil elastase. An inhereted deficiency of alpha1-AT occurs secondary to mutations in the protein inhibitor (Pi) gene which determine the type and amount of alpha1-AT. Those with two Z alleles have 15-20% of normal alpha1-AT. 80% of these individuals are clinically diagnosed with emphysema by the age of 40. The alpha1-AT accumulates in the liver and can lead to cirrhosis.


Morphology of emphysema

Regardless of the histological subtype, emphysema causes hyperinflation of the lung. This is most dramatic in panacinar emphysema. In advanced emphysema, the development of large bullae (blisters) occurs, usually in areas of scarring. There is often an associated bronchitis and bronchiolitis. Changes seen int he bronchioles include goblet metaplasia, with mucus plugging, inflammatory cell infiltrate, wall thickening due to smooth muscle hypertrophy and peribronchial fibrosis. Loss of elastic recoil and bronchiolitis contribute to airways obstruction. The process may continue for decades despite smoking cessation.


Chronic bronchilitis

Is defined clinically. It is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years, int he absence of any other identifiable cause.


Chronic bronchitis aetiology

Long standing irritation with tobacco smoke (most commonly) or polluted air(smog/dust).


Pathogenesis chronic bronchitis

The earliest feature is hypersecretion of mucus associated with mucus gland hypertrophy and an increased Reid index in the trachea and bronchi. Proteases from neutrophils stimulate mucous hypersecretion. As chronic bronchitis persists there is a marked increase in goblet cells in the small bronchi and bronchioles. This goblet cell metaplasia, leads to increased numbers of goblet cells resulting in increased mucous and mucous plugging. Often there is secondary bacterial or viral infection.


Reid index

Thickness of mucous gland layer/thickness between the epithelium and cartilage; N is 0.4


Macroscopic morphology of chronic bronchitis

Hyperemia, swelling and oedema of the mucous membranes frequently associated with mucous/mucopurulent secretions.


Microscopic morphology of chronic bronchitis

Major change is the presence of chronic inflammation of the airways and mucous gland hyperplasia resulting in an increase in the Reid index. The bronchial epithelial may exhibit squamous metaplasia and dysplasia.


Clinical course of COPD

Dyspnoea is usually the first symptom. In some patients, cough or wheezing is the chief complaint, this may be confused with asthma. Cough and phlegm production are extremely variable and depend on the extent of the associated bronchitis. Weight loss is common. Classically in emphysema, the patient is barrel-chested and dyspnoeic, with prolonged expiration. As the disease progresses patients compensate by hyperventilating and remain well oxygenated (pink puffers). With further progression or acute infective exacerbation or chronic bronchitis, they retain CO2, become cyanosed and develop fluid retention secondary to right heart failure (blue bloaters).


Cause of death in COPD

1. Respiratory acidosis and coma 2. Right sided heart failure; and 3. Massive collapse of the lungs secondary to pneumothorax



Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and/or in the early morning. These symptoms are usually associated wit widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment. It is thought that inflammation causes an increase in airway responsiveness (bronchospasm), inflammation of the bronchial walls and increased mucous production to a variety of stimuli.


Categorisation of asthma

Typically categorised into: - atopic (extrinsic) - non-atopic (intrinsic) Clinically classified as mild, moderate and severe.


Atopic asthma

Initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigen.


Non-atopic (intrinsic) asthma

Initiated by diverse, non-immune mechanisms, including ingestion of aspirin; pulmonary infections, especially viral; cold; inhaled irritants; stress; and exercise.


Pathogenesis of atopic asthma.

Example of a type I hypersensitivity response. Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macrophages, T lymphocytes, neutrophils and epithelial cells. Serum IgE levels are often raised and a family or personal history for allergic reactions is often associated.


1. Sensitisation

Inhaled allergencs (antigen) alicit a TH2-dominated response favouring IgE production and eosinophil recruitment. 

2. Re-exposure

Early Phase

Late phase


Early phase of re-exposure in asthma

On re-exposure to antigen (Ag) the immediate reaction is triggered by Ag-induced cross0linking of IgE boung to IgE receptors on mast cells in the airways. These cells release preformed mediators (including histamine) that open tight junctions between epithelial cells. Antigen can then enter the mucosa to activate mucosal mast cells and eosinophils, wich in turn release additional mediators. The mediators induce bronchospasm, increased vascular permeability, and mucous productiona nd recruit additional mediator-releasing cells from the blood. 


Late phase re-exposure in asthma

The arrival or recruited leukocytes (neutrophils, eosinophils and basophils, also lymphocytes and monocytes) signals the initiation of the late phase of asthma and a fresh round of mediator (incuding prostaglandins, platelet activating factor (PAF), leukotrienes) release from leukocytes, endothelium and epithelial cells. These cause damage to the epithelium and may trigger further inflammation, increasing the response. 


Pathogenesis of non-atopic asthma

Has similar features to atopic asthma at a cellular level, however the trigger is not an allergen e.g. respiratory viruses or pollutants (in occupational asthma). There is usually no associated allergy. 


Macroscopic features of asthma

Lungs are distended secondary to over-inflation and there may be small areas of atelactasis. Thick tenacious mucous plugs may be identified in the bronchi and bronchioles. 


microscopic features of asthma

Mucous plugs contain whorls of shed epithelium known as Curshmann spirals. Numerous eosinophils and Charcot Leyden crystals are present - crystalloid made of eosinophil lysophospholipase. Airway remodelling is evidenced by - thickening of the B< of the bronchial epithelium, oedema, an inflammatory infiltrate in the brocnhial walls with a prominence of eosinophils and mast cells, an increase in size of the number of submucosal glands and hypertrophy of the bronchial wall muscle. 


Clinical course of asthma

Clinically, asthma is managed according to severity, with the aim of reducing attacks by use of preventer and reliever mediation. Prevention of severe asthma ttacks (at the extreme end manifested by status asthmaticus) is the aim. 



Characterised by permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue, resulting from, or associated with, chronic necrotizing infections. 


Bronchiectasis clinical manifestations

  • Cough
  • Fever
  • Expectoration of copious amounts of foul-smelling, purulent sputum. 


What conditions is Bronchiectasis associatied with?

  • Congenital or hereditary conditions, including CF, sequestration of the lung, immunodeficiency states, and primary ciliary dyskineasia and Kartagener syndromes (bronchiectasis, sinusitis, and situs inversus or partial lateralizing abnormality). 
  • Post-infectious conditions including necrotising pneumonia caused by bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas), viruses (adenovirus, influenza virus, HIV) and fungi (Aspergillus sp)
  • Bronchial obstruction, owing to tumour, foreign bodies, and occasionally mucus impaction, in whcih the bronchiectasis is localised to the obstructed lung segment. 
  • Other systemic inflammatory conditions including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and post-transplantation (chronic lung rejection, and chronic graft-versus-host disease after bone marrow transplantation)