TOXICOLOGY OF THE LUNG (2)

 

 

I. Pulmonary Anatomy and Ultrastructure

The lung is organized into 3 compartments: airways, blood vessels, and conective tissue. We can think of it as 2 systems of tubes (airways and vasculature) cemented together by the third compartment (inteerstitium):

- Airways and airsacs (traqueobronquial tree and alveoli),

- Vasculature (2 systems, bronquial and pulmonary)

- Interstitium (systems: lymphatic, nervous; cellular: fibroblasts, muscle, nerve cells; extracellular: collagen, elastin)

The following slides review the overall gross anatomy and hystology of the lung and its cell types, examine some of its morphometric (quantitative) features, and show some structural features revealed by specialized morphological techniques.

A. Structural schema

Slide 1. Netter, p. 3. Respiratory system. Note the distinction between the upper and lower respiratory systems. The function of the nasal passages: inhaled air is "conditioned", ie, warmed and humidified and it can also be the site of toxic action, e. g., formaldehyde.

Slide2. Netter, p. 16. Bronchopulmonary segments. Lobes of human lung: 3 right lobes with 10 segments and 2 left lobes with 9 segments. Major airways on right are straighter than those on left.

Slide3. Netter, p. 24. Intrapulmonary airways.

Slide4. Intrapulmonary blood circulation.

Slide 5. Drawing of 3 levels of respiratory epithelium - alveolus, bronchiole, bronchi- with continuous airway lining fluid. In: Bergofsky. '91 Am J Med 91: 4s-10s.

 

B. Ultrastructure and morphometry

Slide6. Netter, p. 26. Ultrastructure of respiratory epithelium.

Slide7. E. M. of bronchiolar epithelium.

Slide8. SEM of airway surface of adult monkey.

Slide9. SEM of fetal monkey lung with bronchial displasia.

Slide 10. Netter, p. 29. Ultrastructure of alveolar capillary unit.

Slide 11. Netter, p. 30. Ultrastructure of the type II cell and surfactant secretion.

Slide 12. Drawing of mucocilliary blanket. In: Vander et al '70 Human Physiology. The arrows indicate the upward direction in which the cilia move the overriding layer of mucus, to which foreign particles are stuck.

Slide 13. Low mag SEM of mucous blanket in rat.

Slide 14. Higher mag SEM of mucous blanket.

Slide 15. TEM of mucous blanket.

 

C. Specialized techniques

Slide 16. Airway cast-untrimmed.

Slide 17. Airway cast-trimmed.

Slide 18. Plastic cast of the conducting airways from traquea to terminal bronchioles, different color in each lobe.

Slide 19. Low mag SEM of vascular cast.

Slide 20. Higher mag SEM of vascular cast.

 

 

 

Cell Types in Normal Lung

More than 40 cell types have been identified (Breeze & Wheeldon, Am Rev Resp Dis, '77).

 Airway epithelial cells  Connective tissue cells

 ciliated

 fibroblast

 mucous (goblet)

 contractile interstitial

 serous

 mast

 Clara

 eosinophil

 brush

 lymphocyte

 K (Kultschnitzky-like)

  plasma cell

 basal

 neutrophil

 intermediate

 Cartilage
 Alveoli

 chrondrocyte

 types I, II, III

 Muscle

 alveolar macrophage

 smooth

 Glands  Nervous

 mucous

 preganglionic nerve process

 serous

 parasympathetic gangliocyte

 Vasculature  Pleura

 endothelial

 mesothelial

 pericyte

 



HISTOLOGICAL FEATURES OF LOWER RESPIRATORY SYSTEM

 Trachea & Bronchi:  Epithelium  ciliated cells
 mucous-secreting cells
 basal cells
 Walls  cartilage (cells & ECM)
 smooth muscle
 fibroblasts
 collagen, elastin
 Bronchioles:  Epithelium  ciliated cells
 Clara cells
 basal cells
   Walls  no cartilage
   collagen, elastin
 Alveoli:  Epithelium  type I cells
   type II cells
   Walls  basement membrane
   collagen, elastin
 Terminal bronchiole  the last purely conducting airway
 Respiratory bronchioles, Alveolar ducts are gas exchange airways; that is, have outpocketings of alveoli
 Bronchial vasculature  extends to terminal bronchioles
 Smooth muscle   extends to alveolar openings
 Lymphatics  start at alveolar/respiratory bronchiole junction

 

MORPHOMETRY OF HUMAN LUNG

 

 VL=  VA +  VNP +  VT +  VC +
 5 liters  3800 ml +  500 ml +   450 ml +  250 ml
   (76%)  (10%)  (9%)  (5%)
 where:  VL  = total lung volume
   VA  = alveolar air space
   VNP  = major airways and blood vessels
   VT  = alveolar septal tissue
   VC  = alveolar capillaries

(NP = "non-parenchyma"; versus "parenchyma"the gas exchange portion of the lungmade up of alveoli, capillaries and connective tissue)

Surface Area:

Alveolar Number:    Estimated at 300 million in adult human.
 SA=  with LM  60 m^2 to 80 m^2
 with EM  160 m^2


where: SA = alveolar surface area

 

 




TOXICOLOGY OF THE LUNG (2)
Summary of characteristics of human lung diseases


Inflammation
: Acute or chronic response to cell/tissue injury; accompanied by influx of inflammatory cells (macrophages, neutrophils, lymphocytes) and mediator release (interleukins, cytokines).

Bronchitis/Bronchiolitis: Inflammation of airways; enlargement of mucous glands and increased mucous cells; accompanied by airway narrowing by mucous plugs and air blockage, edema, inflammation, and fibrosis.

Edema: Leakage of fluid from vascular compartment to interstitial and air compartments.

Bronchial asthma: Heightened reactivity of bronchial tree to stimuli leading to bronchial constriction and inflammation. Wheezing, cough, dyspnea, and tenacious sputum may be present.

Emphysema: Destruction of and permanent loss of septal walls of alveoli, alveolar ducts, and respiratory bronchioles.

Allergic alveolitis (hypersensitivity pneumonitis): Tissue reaction to inhaled antigenic organic aerosols; leads to infiltration of lung by inflammatory cells and can result in edema, fibrosis, and emphysema.

Fibrosis: Irreversible thickening of alveolar septa/airways by formation of fibrotic (scar-like) tissue; may be associated with edema, presence of inflammatory cell response.


Acute airway injury

Bronchoconstriction (airway hyperresponsiveness)
 
due to contraction of airway smooth muscle
(example: response of asthmatics to SO2 inhalation)

may also be associated with airway inflammation
Airway inflammation
 
injured epithelial cells: 1) release membrane constituents such as arachidonic acid that generate cyclooxygenase and lipoxygenase products; 2) produce vasoactive mediators; 3) release chemotactic factors that attract other effe ctor cells, e.g., neutrophils

vasoactive mediators increase vascular permeability, leads to edema formation

hypersecretion of mucous and serous fluids into airways
 
Impairment of defense mechanisms
decreased mucociliary clearance, due to injury to ciliated cells or changes in chemical properties and composition of mucous layer

Acute lung (parenchymal) injury

Type I cell injury and cell death
 
repaired by dedifferentiation and mitotic response of type II cells
 
Impairment of alveolar macrophage function
 
may lead in turn to increase in respiratory illness because of lower defense against microorganism
 
antibacterial defense mechanisms impaired by exposures to as little as 0.1 ppm O3 although O3 exposure does not appear to affect antiviral defense
 
Release of mediators, influx and activation of cells
 
quantitation of such mediators and cells the basis for the alveolar lavage assay

General sequence of acute inflammatory response


Chronic obstructive airway disease

Two major obstructive diseases:

1) Bronchi
al asthma

2) Chronic obstructive pulmonary disease (COPD)

A) Chronic bronchitis (clinical state: pink puffers)

B) Emphysema (clinical state: blue bloaters)

 

 

Chronic lung disease (fibrosis)

 

The lung's defense against environmental pollutants

MAJOR PULMONARY OXIDANT SCAVENGERSa

 CATEGORY  ACTIONS

a In: Principles & Practice of Envir. Med. AB Tarcher, ed (1992), p. 113.

Plumonary Function Tests

LINKS OF INTEREST

Link 1: Pulmonary pathology slides; some interesting ones about emphysema, mesothelioma, etc.

Link2.