RHS05 - Pulmonary Pathology 3 Flashcards
Define what emphysema is. Focus on the characteristics that differentiate it from other similar diseases.
Abnormal permanent airspace enlargement distal to the terminal bronchioles (if proximal it is called bronchiectasis) and accompanied by destruction of airspace walls without fibrosis (if fibrosis is present it is a interstitial lung disease).
What is COPD
A combination of emphysema and chronic bronchitis
What is the general cause of emphysema?
An imbalance between protease-antiprotease activity and oxidant-antioxidant concentration.
Why does smoking cause emphysema?
It irritates and triggers an inflammatory response in the lung parenchyma which causes an increase in protease activity and oxidant stress.
List the important genetic factors to emphysema development we need to know.
- Alpha-1 antitrypsin (A1AT) is a protein that inhibitos both trypsin and elastase activity. A1AT deficiency causes emphysema
- Polymorphisms in transforming growth factor-ß (TGFB) and matrix metalloproteinases (MMP) are also known to cause emphysema
What gene on which chromosome codes for A1AT? What are the wild type and mutant versions of this protein called? What diseases are seen when this gene is mutated?
- A1AT is coded by the Pi gene on chromosome 14
- wild type - PiMM
- mutant type - PiZZ or PiZM
- These proteins are synthesized in the liver. When they are mutated, the liver cannot secrete them into the blood stream. This causes both chronic liver disease and emphysema
What is a lung acinar?
The region of the lung distal to the terminal bronchioles
List the major types of emphysema, what they’re primary causes are, and which regions of the lung they affect.
- Centrilobular (centriacinar) - emphysema of mostly the respiratory bronchioles (the central part of the acinars). Usually caused by smoking (smoke never reaches the alveoli) and usually occurs in the upper lung zones
- Panlobular (panacinar) - emphysema of the entire acinus. Usually caused by A1AT deficiency and occurs in lower lung
- Septal (distal acinar) - emphysema of the distal acinar (septa, margins of lobes, and subpleural regions). Rare and more common in upper lobes
- Irregular (paracicatricial) - emphysema surrounding a scar
What further complications can septal emphysema cause and how?
Septal emphysema can cause several alveoli to merge into a large sacs called bullae. These bullae can rupture through the visceral pleura, causing a pneumothorax.
Describe the gross morphological appearance of centrilobular and panlobular emphysema.
Centrilobular Emphysema - you’ll see areas of dilated tissue surrounded by healthy appearing tissue
Panlobular Emphysema - large sections of the lung appear to be dilated
Refer to image
What clinical findings are associated with emphysema?
- Barrel chest
- Dyspnea
- Prolonged expiration through pursed lips
- Often seated forward in a hunched position
- X-ray reveals a flattened diaphragm dome
- Patients are often weak and skinny due to the excessive puffing and panting
- Blood gases are normal until late progression when hypoxia, hypercapnia, and respiratory acidosis begin.
Define chronic bronchitis
A productive cough which occurs for at least 3 consecutive months in 2 consecutive years.
What is the primary etiology of chronic bronchitis?
Inhalation of irritants (cigarette smoke, SO2, NO2)
What is the pathogenesis of chronic bronchitis?
- Inhaled irritants induce hypertrophy of seromucinous glands and increased goblet cells in the surface epithelium
- Airflow obstruction is distal and results from
- Small Airway Disease - goblet cell metaplasia in the bronchioles accompanied by inflammation, smooth muscle hyperplasia, and peribronchiolar fibrosis
- Infiltration of CD8+ T-cells, macrophages, and PMNs (but not eosinophils)
Describe the gross morphological and histological findings in chronic bronchitis.
Gross Findings - hyperemia, swelling (narrowed airways), and edema of the mucous membranes with increased mucinous secretions
Histological Finding - increase in the number of seromucinous glands (refer to image) and fibrosis of the airway walls
Describe the gross morphology and histology of asthma
- Gross Morphology - airway occlusion by thick mucus, hyperinflation of lungs, edema with patchy epithelial necrosis
- Histology - goblet cell hyperplasia, basement membrane thickening, inflammation with eosinophils, smooth muscle hypertrophy (refer to image). Sputem sample could have curschmann spirals (mucus plug in the shape of a spiral with shed epithelial cells)(refer to image), charcot leyden crystals (eosinophil breakdown product), and eosinophils
