The Morphology and Transport of Mucus in Mammalian Airways.

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The mucociliary clearance mechanisms in mammalian pulmonary airways have been re-examined. In this investigation Wistar rats, housed both under specific pathogen free (SPF) and normal animal house conditions, were examined. An intact airway . system from the trachea down to the level of the terminal bronchioles was used. The airway preparation was rapidly isolated and examined under carefully controlled in vitro conditions. Specimens remained viable for at least 10 h. Mucociliary activity was observed through the intact bronchial wall with the aid of incident light. This function could be examined at all levels of the pulmonary tree in the same specimen. In contrast to the previously described presence of a continuous mucous bl~ket, the morphology of mucus in the airways of the rat has been shown to be discontinuous. Mucus is present as discrete particles of varying size. Under the light microscope these particles appeared to fall into three categories: droplets less than 4 μm in diameter; flakes 10-70 μm in diameter; and plaques which are conglomerations of droplets and flakes. Scanning electron microscopy reveals that droplets (i.e. single particles) may be as small as 0,5 μm and that composite particles made up of numerous aggregated droplets may be as small as 5 μm in diameter. Plaques are conglomerations of these particles. In the normal intrapulmonary airways only smaller particles are seen and are transported over the individual metachronal fields. In the larger extralobar airways these particles move together to be transported in well defined streams which may be up to 500 μm wide. These streams may follow a winding course up the trachea and more than one may be in operation at a time. Under conditions of hypersecretion such as occurs with chronic respiratory disease in rats (CRD) the number of particles increase peripherally and plaques may be found in small airways. The transport of mucus is however still intermittent and it never becomes confluent. Acute bronchitis results in wide-spread abnormalities of ciliary activity and mucus transport, which leads to total disorganisation of pulmonary clearance. "Chronic bronchitis" associated with CRD results in more organised abnormalities of mucociliary activity. Cilia may become inactive, reverse the .direction of their effective stroke, beat retrogradely, and exhibit abnormal beat patterns which result in impaired mucus clearance. Squamous metaplastic areas further impede mucus transport. In general mucus transport rates were found to be faster in rats with "chronic bronchitis" than SPF rats, provided that the extent of the damage to the mucous membrane was ( not too great in the "bronchitic" animal. This finding was confirmed by the examination of airway preparations approximately 19 h after the exposure to a charcoal aerosol. While significant amounts of charcoal were retained at the bifurcations of bronchi in SPF rats, most of the charcoal was cleared in "bronchitic rats'.'. The only areas where particles were seen were on bronchitic patches or on whirlpools. The findings of this study indicated that mucus was present in a discontinuous form, and that in both SPF and non-SPF animals no evidence for a mucous blanket was found.
A· Thesis submitted to the Faculty· of Medicine,University of the Witwatersrand, Johannesburg for the degree of Doctor of Philosophy in Medicine Johannesburg.