55. Antitussives, Expectorants and Mucolytics or Therapy of Cough
56. Drugs used in Bronchial Asthema
57. Nasal Decongestants and Cold remedies or Therapy of Allergic Rhinitis
58. Chemotherapy of Tuberculosis
59
Physiology
59. Mechanism and Mechanics of Breathing
60. Regulation of Respiration
61. Pulmonary circulation
62. Pulmonary Gas exchange
63. Gas transport and Exchange
64. Lung compliance
65. Pulmonary Function Tests
66. Spirometry
67. Applied Respiratory Physiology
68. Abnormal Breathing
69. Artificial Respiration
70. Lung Defense Mechanism
71
Pathology
52. Pneumoconiosis
INTRODUCTION
Definition
Pneumoconioses encompass a group of fibrosing diseases of the lung resulting from exposure to organic and inorganic particulates, most commonly mineral dust.
Initially it was used to describe the non-neoplastic lung reaction to inhalation of mineral dusts encountered in the workplace.
But, now it has been proved that many pneumoconioses especially asbestosis increases the risk of mesothelioma by 1000 times and that of bronchogenic carcinoma by many times.
So, pneumoconioses are also the pre-cancerous lesions.
CLASSIFICATION
On the basis of Etiology, it is classified into following types.
PATHOGENESIS
The particles greater than 5μm are easily trapped in the upper respiratory passage in the mucus and are expelled out by mucocilliary actions.
The particles lesser than 0.5μm nearly the size of air and thus are inhaled and exphaled along with air causing no damage to cells.
So, the paricles between 1μm and 5μm are the one to get stuck in the lower respiratory passages, especially at the bifurcation of respiratory tree; and alveoli.
These particles are engulfed by the macrophages of the lungs and are taken up to lymph nodes, where it presents the antigen to the lymphocytes.
Thus the inflammatory reaction occurs in the lung parenchyma and along the lymphatic drainage.
graph TD
1["Inhalation"]
2["Particle of size >5μm"]
3["Easily trapped in the upper <br>respiratory passage in the mucus"]
4["Expelled out by mucocilliary actions"]
5["Particle of size <0.5μm"]
6["Nearly the size of air"]
7["Inhaled and exphaled along with air"]
8["Causes no damage to cell"]
9["Particle of size between 1μm and 5μm"]
10["get stuck in the lower <br>respiratory passages, especially at the <br>bifurcation of respiratory tree; and alveoli."]
11["engulfed by the macrophages of the lungs"]
12["taken up to lymph nodes"]
13["presents the antigen to the lymphocytes"]
14["inflammatory reaction occurs <br>in the lung parenchyma and <br>along the lymphatic drainage"]
1 --> 2
2 --> 3
3 --> 4
4 --> 8
1 --> 5
5 --> 6
6 --> 7
7 --> 8
1 --> 9
9 --> 10
10 --> 11
11 --> 12
12 --> 13
13 --> 14
TYPES
Here we will talk many about the following three pneumoconiosis
Coal Workers' Pneumoconiosis
Silicosis
Asbestosis
The general pathogenesis of all of them are given above.
Coal and Silica comes from the ground and affect the upper lobes or upper part of middle lobes of lung, where as Asbestos comes from upper surfaces like roofs of house and it affects the lower lobes of lungs.
Intense blackened scars ranging from 1 cm to 10 cm in diameter.
They are usually multiple.
Microscopic
It consists of dense collagen and carbon pigment.
The center of lesion is often necrotic, most likely due to local ischemia.
Silicosis
Morphology
Gross
Simple nodules
At first tiny barely palpable, discrete pale to blackened (if coal dust is also present) nodules in the hilar lymph nodes and upper zones of the lungs is found.
Collagenous scars
As the disease progresses, these nodules coalesce into hard, collagenous scars.
Centrally softened and cavitary nodules
Some nodules may undergo central softening and cavitation due to superimposed tuberculosis or to ischemia.
Fibrotic lesions
Fibrotic lesions may also occur in the hilar lymph nodes and pleura.
Eggshell calcified nodule
Sometimes, thin sheets of calcification occur in the lymph nodes and are seen radiographically as calcium surrounding a zone lacking calcification.
Progressive massive fibrosis
As the disease continues to progress, expansion and coalescence of lesions may produce progressive massive fibrosis.
Microscopic
Silicotic nodules
It has a characteristic whorled appearance.
Center
It consists of concentric layers of hyalinized acellular collagen surrounded by a dense cellular capsule of connective tissue and collagen.
Periphery
Shows aggregates of mononuclear cells, mostly macrophages, lymphocytes and fibroblasts.
Polarized light microscopy may show birefringent silica particles in the center of silicotic nodule.
Pathogenesis
graph TD
1["Silica"]
2["Amorphous forms <br>- Biologically less active than crystalline silica"]
3["When Heavy lung burdens"]
4["Lesions"]
5["Crystalline forms <br>- They are highly fibrogenic."]
6["Quartz <br>- Quartz is most <br>commonly implicated."]
7["Cristobalite"]
8["Tridymite"]
9["Inhalation of silica particles."]
10["Phagocytosis of the particles by macrophages."]
11["Phagocytosed silica crystals activate the inflammasome."]
12["Release of inflammatory mediators, particularly IL-1 and IL-8."]
13["Formation of Fibrotic nodules."]
1 --> 2
2 --> 3
3 --> 4
1 --> 5
5 --> 6
6 --> 9
5 --> 7
7 --> 9
5 --> 8
8 --> 9
9 --> 10
10 --> 11
11 --> 12
12 --> 13
Asbestosis
Morphology
Gross
Lesions are mostly localized in lower lobes or lower part of upper lobes.
Diffuse pulmonary interstitial fibrosis
Asebestosis is marked by diffuse pulmonary interstitial fibrosis.
Early: Asbestosis begins as fibrosis around respiratory bronchioles and alveolar ducts and extends to involve adjacent alveolar sacs and alveoli.
Later: The fibrous tissue distorts the architecture, creating enlarged airspaces enclosed within thick fibrous walls; eventually the affected regions become honeycombed.
The pattern of fibrosis is similar to that seen in usual interstitial fibrosis, the only difference being the presence of numerous asbestos bodies.
Microscopic
Asbestos bodies
Asbestos bodies are golden brown, fusiform or beaded rods with a translucent center.
It consists of asbestos fibers coated with an iron-containing proteinacous material.
They arise when macrophages phagocytose asbestos fibers; the iron is presumable derived from phagocyte ferritin.
Other inorganic particulates may become coated with similar iron-protein complexes and are called ferruginous bodies.
Rare single asbestos bodies can be found in the lungs of normal people.
Pleural plaques
Pleural plaques are the well-circumscribed plaques of dense collagen that are often calcified.
The develop most frequently on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm.
Pathogenesis
graph TD
1["Asbestos"]
2["Serpentine chrysotile forms <br>- Less danger due to <br>- Accounts for 90% of the asbestos used in industry"]
3["Aerodynamic properties"]
4["More flexible, curled structure"]
5["Impacted in the upper respiratory passages"]
6["Removed by the mucocilliary elevator"]
7["Solubility"]
8["More soluble and thus leach from the tissue"]
9["Amphibole forms <br>- More danger"]
10["Straight, stiff structure"]
11["Align themselves in the airstream"]
12["Delivered deeper into the lungs"]
13["Penetrate epithelial cells"]
14["Reach the interstitium"]
15["Phagocytosed by macrophages"]
16["Activation of inflammasome"]
17["Release of proinflammatory factors and fibrogenic mediators"]
18["Interstitial inflammation and fibrosis"]
1 --> 2
2 --> 3
3 --> 4
4 --> 5
5 --> 6
2 --> 7
7 --> 8
1 --> 9
9 --> 10
10 --> 11
11 --> 12
12 --> 13
13 --> 14
14 --> 15
15 --> 16
16 --> 17
17 --> 18
