7 - Pulmonary Defense Mechanisms Flashcards
The lung is continuously exposed to the outside environment. Defense mechanisms are necessary to ensure efficient _______ _______ and prevent ________.
Gas exchange
Infection
Lung defense can be divided into two locations, which are…
Upper airways and bronchi
Alveolar spaces
The first defense of the upper airways and bronchi is the removal of particulate matter. Describe which sizes of particulate matter are removed where.
Particle size > 10 um = Removed by tonsils and adenoids
Particle size 2-10 um = Removed by mucokinesis and coughing
Particle size <2 um = Makes it to lungs
What are the steps of the cough reflex?
1) Deep inspiration
2) Trapping of air by shutting off its exit (glottis in the case of cough)
3) Initiation of expiratory effort, raising the intrathoracic pressure
4) Buildup of pressure
5) Sudden release of the trapped air at high pressure
***Cough can be triggered by chemicals, mechanical stimulation, inflammation, or be voluntary
This has a barrier function and a defense function. It releases bacteriostatic molecules and regulates an immune response containing receptors and producing cytokines. Supports microbiome.
Airway Epithelium
Airway epithelium translocates…
IgA
Particles larger than 2-3 um and smaller than 10 um are deposited on the mucus of the upper airways. The mucus contains defense molecules…
IgA
Lysozyme
Lactoferrin
Peroxidases
What is the mucus blanket composed of?
Sol Layer – aqueous
Mucus Layer
Cilia move through the Sol Layer striking the Mucus Layer above and propel it forward (mucus elevator). This is called _________ __________. This mechanism is altered in disease states such as asthma, chronic bronchitis, and cystic fibrosis.
Mucociliary Clearance
These are the first line of defense in the alveoli. They are tissue residents, and are long-lived and self-renewing.
Alveolar (Airway) Macrophages
These proteins are synthesized by Type II Alveolar and Clara cells. They bind to a wide range of pathogens, suppress microbial growth, damage bacterial membranes, and modulate macrophage phagocytosis.
Surfactant Protein A (SP-A)
Surfactant Protein D (SP-D)
What is the acute immune response?
– Activation of immune response by exogenous triggers
– Influx of inflammatory cells from capillaries into air spaces
– Deployment of neutrophil nets
______ and ______ increase expression of P & E Selectins on endothelium (1-2 hours), binds, detaches, binds, “rolling” of leukocyte. End result is the leukocytes slow down.
IL-1
TNF
Slowing down of leukocytes allows cells to respond to chemokines in the area that are produced in response to ______ and ______. Chemokines increase affinity and clustering of integrins for ligand binding. The leukocytes firmly attach, cytoskeleton reorganizes and they flatten on endothelium.
TNF
IL-1
This occurs when plasma proteins come in intimate contact with the damaged area. Due to inflammatory exudate.
Edema
What are the proteins in the inflammatory exudate?
Clotting Proteins
Complement
Kinin Cascade
Fibrinolytic Protein
These proteins form blood clots to prevent further loss of blood.
Clotting Proteins
These proteins stimulate immune responses and destroy bacteria.
Complement
These proteins cause vasodilation and increase the permeability of blood vessels and stimulate pain receptors.
Kinin Cascade
This protein degrades the clot when the wound has healed.
Fibrinolytic Protein
A chronic inflammatory response develops over time due to infiltration of activated ________ and ________. There is mucus hypersecretion and substantial remodeling of tissue leading to fibrosis.
T Cells
M1 Macrophages
What can occur in an early phase (immediate) acute atopic response?
In minutes:
- Cross-linking of mIgE
- Degranulation of Mast cells
- Sneezing, pruritus, rhinorrhea, congestion
- Preformed Mast cell cytokines and inflammatory proteins recruit inflammatory cells to the area
What can occur in late phase chronic atopic response?
Hours 4-12:
– Influx and activation of eosinophils, neutrophils, basophils, and lymphocytes (Th2)
– 10-fold increase in Mast cells present in area
– Increased expression of Fce receptors
– Systemic symptoms: fatigue, myalgias, asthma
In chronic asthma related airway remodeling, these induce bronchospasm, vascular permeability, and mucus production.
Leukotrienes C4, D4, and E4
In chronic asthma related airway remodeling, these induce bronchospasm and vasodilation.
Prostaglandins D2, E2, and F2
In chronic asthma related airway remodeling, the recruitment of smooth muscle cells and fibroblasts lead to deposit of _________ in the submucosa.
Collagen
There is _______ mediated inflammation in COPD. These cytokines induce IL-8 and G/GM-CSF secretion from airway epithelial cells (IL-17, IL-22).
Th17
In COPD there is recruitment of large population of inflammatory…
Macrophages and Neutrophils
Is Asthma or COPD being described?
- Allergens
- Epithelial cells
- Mast cells
- CD4+ cell (Th2)
- Eosinophil
- Bronchoconstriction
Asthma
Is Asthma or COPD being described?
- Cigarette Smoke
- Alveolar Macrophages
- Epithelial cells
- CD8+ cell (Tc1)
- Neutrophils
- Th17
- Small airway narrowing and alveolar destruction
COPD
What type of lung injury is being described?
Physical Damage:
- Over-inflation
- Mechanical stress
Biodamage:
- Hyper-oxygenation
- Free radical production
- Influx of neutrophils into tissue from activation of endothelium
- Neutrophil netosis leading to platelet activation and clot formation
Ventilator Associated Lung Injury
This type of injury is present with ARDS and has bilateral infiltrates on CXR. There is absence of infection. If vaping was used within last 90 days then there is no other plausible cause.
Vaping Associated Lung Injury (VALI)
This type of pneumonia is caused by inhalation/aspiration of lipids. It is usually very rare. There can be a dramatic increase due to vaping CBD/THC and the use of essential oils in large quantities.
Lipoid Pneumonia
