Defense Mechanisms of the Lungs Flashcards Preview

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Flashcards in Defense Mechanisms of the Lungs Deck (41)
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1
Q

What has the largest epithelial surface exposed to the environment?

A

Lungs=largest epithelial surface

  • Lungs=85m
  • GI=32 m
  • Skin=1-2m
2
Q

Is our air clean?

A
  • Particles in the air:
    • smoke
    • exhaust
    • soil
    • dander
    • viruses
    • fungi
    • bacteria
  • 600,000 bacteria inhaled/day
3
Q

What are the particles that we breathe in, what is their fate, and where do they land?

A
  • >10 um=large particles
    • impact in mucous of upper respiratory tract
    • pollen, Pin(limit of vision=50um), Hair
  • 2.5-10 um: Course ambient particles (PM10)
    • Impact in large airways-where trachea divide into bronchi
    • Cells, RBC
  • .1-2.5:
    • sedimentation interception into distal small airways
      • they just fall out of the air
        • interception: fibers spear airway at an angle
    • Bacteria, Fine ambient particles (PM2.5)
  • .01-.1:
    • diffusion into alveoli
    • nanoparticles=man made
    • viruses
    • ultrafine PM
    • Molecules
4
Q

Factors in particle deposition:

A
  • Particle characteristics:
    • size, shape, density, charge, and hygroscopicity (growth in humid enviroment)
  • Respiratory tract geometry
    • airway diameter
    • branching pattern
  • Ventilation characteristics:
    • nasal or oral breathing
    • respiratory rate
    • tidal volume
    • flow rate/velocity
    • length of respiratory pauses
    • distribution of ventilation
  • Host factors:
    • existing lung disease
    • irritant exposure (smoking)
      • body takes shallower breathes
    • age
    • gender
      • males have larger air ducts
5
Q

Defense of the Airways

A
  • Physical barrier
    • epithelium and mucus
  • Chemical barriers:
    • antimicrobial factors secreted by submucosal gland cells, epithelial cells, and inflammatory cells (PMNs) into periciliary fluid
  • Neural reflexes
    • innate immunity:
      • inflammation
    • Adaptive (aquired) immunity
      • cell-mediated
      • humoral (antibody-mediated)
6
Q

Major innate barrier of the immune system in the lungs:

A
  • Mucocilliary escalator
    • primary clearance mechanism for inhaled substances that deposit in the airways
    • prevents mucus obstruction of the airways
    • line the nasal cavity, larynx, pharynx, and conducting airways
  • Cellular components:
    • ciliated epithelial cells
    • goblet cells-secrete mucus
      • or clara cells in the bronchioles
    • submucosal glands-secrete mucus
      • serous glands
        • and antimicrobial factors
      • mucous glands
7
Q

What 3 defense mechanisms support the lungs?

A
  • Physicall barrier
    • epithelium and mucus
  • Chemical Barrier
  • Neural Reflexes
8
Q

What chemical barriers are in the lungs?

A
  • Antimicrobial factors secreted by submucosal gland cells, epithelial cells, and inflammatory cells (PMNs) into periciiary fluid (fluid around ciliarly)
9
Q

What are the cells of the mucociliary transport?

A
  • ciliated epithelial cells
  • Goblet cells
    • or clara cells in the bronchioles
  • Submucosal glands
    • serous and mucous glands
10
Q

What are the components of the airway surface fluid (ASF)?

A
  • Fluid above epithelium
  • particles get trapped in mucous/gel layer
  • Gel layer=mucus layer
    • next to airway lumen
    • made of carbohydrates, proteins, and lipids
    • viscious
    • elasticitiy
    • propelled by cilia (MUC5AC, and MUC5B)
  • Sol Layer=periciliary fluid layer
    • watery airway surface fluid next to cell surface
    • allows cilia to move freely to establish upward flow
  • The depth of the periciliary fluid is critical for cilia to beat and move the gel layer effectively
11
Q

Describe the masses of cilia used in respiratory transport

A
  • Cilia
    • 200 cilia per cell
    • beat asymetrically 600-1000 times per minute
    • effective power stroke
      • cilia moves into upright positioino and contact the gel layer to move it
    • Recovery stroke:
      • cilia swing back through the sol layer
12
Q

What regulates Mucociliary clearance

A
  • Dependent on the depth and viscosity of the ASF and ciliary beating
  • epithelial cells secrete Cl- to the luminal side of the airway to form a electrolyte layer
    • ​Cl- out: via CFTR and Ca2+ activated Cl- Channels
    • Na+ in: ENaC-epithelium Sodium Channels
  • electrolyte secretion
    • Goblet Cells/Clara cells
      • stimulated by B-adrenergics
      • inhibited by bumetanide diuretic
    • Submucosal glands: stimulated by:
      • serous glands: a-adrenergic
      • mucous glands: B-adrenergic
  • Basal Na+ absorption
    • amiloride diuretic inhibits
  • Mucus secretion:
    • Cholinergic-mucarinic M3 (parasympathetic)
13
Q

Clearance mechanisms:

A
  • Upper respiratory tract
    • mucociliary transport
      • sneezing, nose blowing
      • dissolution of soluble particles
  • Tracheobronchial tree
    • mucociliary transport
      • coughing
  • Gas exchange zone (Alveoli)
    • Phagocytosis (alveolar macrophages) move to mucociliary escalator, interstitium, lymphatics, or blood
      • dissolution of soluble particles
14
Q

Effect of disease on mucociliary clearance:

A
  • Direct effect on movement of cilia
    • ciliary dyskinesia
      • primary-genetic defect
      • secondary- enviromental (temporary) pollutants/toxins, virus, bacteria
        • ex: Cigarette smoke
  • Changes in mucus (increased viscosity)
    • Dehydration-cystic fibrosis
    • Hypersecretion-chronic bronchitis, asthma
15
Q

Antimicrobial agents secreted into the airways

A
  • Lysozyme and phospholipase A2
  • Antimicrobial peptides- defensins and cathelicidins
  • Opsonins: surfactant proteins, complement
  • Lactoferrin
  • Antibodies: Secretory IgA
16
Q

Describe CFTR

A
  • CF transmembrane regulator
    • chloride channel
    • normal-inhibits ENaC,so water is not excessively absorbed
  • In Cystic Fibrosis
    • genetic varient of CFTR causes dysfunciton of the cAMP-dependent chloride channel
    • reduction in the volume of the periciliary fluid
17
Q

What stimulates mucus secretion in the lungs?

A

Cholinergic-Muscarinic M3

18
Q

What do lysozyme and phospholipase A2 do:

A

Break cell wall of bacteria

19
Q

What do antimicrobial peptides-defensins and cathelicidins do

A
  • ​from epithelial cells, macrophages, and neutrophils
  • act against bacteria, fungi, and enveloped virsues
  • can mediate inflammation
20
Q

What do Opsonins (surfactant proteins, complement) do

A

Promote phagocytosis

21
Q

What does lactoferrin do

A

binds free iron so its not availabe for bacterial growth

22
Q

What does Antibodies: IgA do:

A
  • bind viruses
  • facilitate removal
23
Q

How does the lungs metabolic activity impact its defense mechanisms:

A
  • Many foreign substances must be activated to exert their toxic effect
  • Distribution of the drug-metabolizing enzymes determine the cellular specificity of many pulmonary toxins
    • Clara cells:
      • high in cytochrome p450 (CYP genes)
      • can make toxins more toxic as radicals
    • Different cell types have different enzymes
  • Enviromental factors such as air pollution, cigarette smoke, and diet affect pulmonary metabolism of some chemicals and affect their toxicity
24
Q

Lung Defense Reflexes

A
  • Nasal Receptors:
    • sneeze reflex
    • diving reflex
  • Epipharyngeal receptors:
    • aspiration reflex
  • Pharyngeal receptors:
    • swallowing reflex
  • Laryngeal receptors:
    • cough reflex
    • Apnea Reflex
  • SARs-slow adapting receptors
    • Hering-Breur inflation reflex
    • Hering-Breur deflation reflex
    • bronchodilation
    • tachycardia
  • RARs-Rapid adapting receptors
    • Hering-breur deflatioin reflex
    • cough
    • bornchoconstriction
    • mucus secretion
  • J Receptors-C-fiber endings
    • pulmonary chemoreflex
    • rapid shallow breathing
    • bronchoconstriction
    • mucus secretion
    • bradycardia
    • hypotension
25
Q

Sneeze reflex

A
  • mechanical stimulation, inhalation of gases, and irritation of nasal passages induce strong inspiration followed by vigorous exhalation
  • most of the exhaled gas passes through nasal passages
  • result-forceful clearing of nasal passages
26
Q

What is the diving reflex?

A
  • water in the nose or on the face induces:
    • apnea (cessation of breathing)
    • closure of the larynx, bronchoconstriction
    • slowing heart rate
    • vasoconstriction of vascular beds other than the brain and coronary circulation.
  • result: is prevention of water from entering the airways, and protection of the brain and heart from hypoxia.
27
Q

Aspiration reflex:

A
  • mechanical stimulation of the epipharynx induces rapid strong inspiratory effort, which will dislodge material in epipharynx and move it to the pharynx where it can be coughed-up or swallowed.
28
Q

Swallowing reflex

A
  • material in the pharynx inhibits inspiration, closes the larynx, and induces muscle contraction which moves the material to the esophagus, thereby forcing the material into the GI tract and away from the airways.
29
Q

Upper airway dilation reflex

A
30
Q

Cough and Apnex reflex:

A

Irritants and water in the larynx can induce cough and apnea. The apnea coincides with the absence of rhythmic integrated phrenic nerve activity, and has been alleged to play a role in sudden infant death syndrome (SIDS).

31
Q

Slow Adapting Receptors reflex:

A
  • located in the lower airways and are activated by stretch of the airway as occurs during lung inflation. The SARs are responsible for the Hering-Breuer inflation reflex in which inspiration is inhibited by lung inflation. When the vagus is severed, and output from the SARs does not reach the brainstem, tidal volume increases and breathing rate slows. This reflex is not seen in humans during tidal breathing, but is active at higher lung volumes. A Hering-Breuer deflation reflex is also observed. Lung deflation from FRC reduces firing of the SARs, and increases inspiratory drive. Firing of the SARs also relaxes airway smooth muscle, thereby reducing tension in the airway wall as the lung expands, and increases heart rate, which facilitates uptake of O2 from the additional air entering the alveoli.
32
Q

Rapidly Adpating Receptors:

A

RARs located in the lower airways fire in response to noxious stimuli, including excessive lung inflation. RAR’s also fire in response to chemicals, such as histamine, which are released in inflammation and tissue damage. RAR’s in the trachea and bronchi induce coughing, mucus secretion and bronchoconstriction. These receptors may play a role in the asthmatic response.

33
Q

C-Fiber ending reflex

A

C-fiber endings located in the airways and bronchial circulation give rise to the pulmonary chemoreflex. Stimulation with capsaicin (from red peppers and paprika), or serotonin produce bradycardia, hypotension, and apnea followed by tachypnea (shallow breathing). Release of neuropeptides, such as substance P, from C-fibers can cause bronchoconstriction and increased vascular permeability.

34
Q

What are the types of cells underlying the lungs innate immunity

A
  • Macrophages
  • Neutrophils
  • Natural Killer cells
  • Epithelial cells
35
Q

Macrophages:

A
  • Resident alveolar and interstitial
  • Engulf particles, viruses, bacteria
  • release toxic oxygen radical to kill microbes
  • can act as Antigen Presenting cells
36
Q

Neutrophils

A
  • recruited to help phagocytize and kill microbes if needed
37
Q

Natural Killer cells

A
  • Cytotoxic lymphocytes
  • recognize viruse-infected and tumor cells
  • release perforins, serine-esterases
38
Q

Epithelial Cells

A
  • Pattern recognition receptors for microbes
  • release cytokines to mount inflammatory response
39
Q

Adpative Immunity: Humoral immune response to allergic reaction

A
  • Allergic reaction: IgG bind to mast cells
    • degranulation
    • causes allergy symptoms
  • Mechanism:
    • exposure to an allergen activates B cells to form IgE-secreting plasma cells
    • IgE bind to IgE specific Fc receptors on mast cells and basophils
    • Second exposure to allergen
    • bound IgE is cross-linked and triggers the release of histamine
    • histamine causes:
      • smooth muscle contraction
      • increased vascular permeability
      • vasodilation
40
Q

What can mast cells secrete:

A
  • Histamine
    • SM contraction
    • vascular permeabiity
  • Leukotrienes
    • SM contraction
    • vascular permeability
    • mucus
  • Cytokines:
    • TNF-a
      • pro-inflammatory
    • IL-13
      • promotes mucus cells
      • airway remodeling
    • IL-4
      • B-Cell growth
      • IgE
    • IL-5
      • eosinophil growth
41
Q
A