This Post is in Progress/ Pump Failure: The Pathogenesis of Hypercapnic Respiratory Failure in Patients with Lung and Chest Wall Disease Chapter 143:

by Steven G. Kelsen

The ventilatory pump accomplishes bulk transfer of air to and from the alveoli. Accordingly, diseases that perturb the mechanical properties of any component of the ventilatory pump (i.e., the bony rib cage, the extra- and intrathoracic conducting airways, and the respiratory muscles) may interfere with CO₂ elimination and O₂ uptake. If disturbances in the function of the ventilatory pump are sufficiently severe, alveolar hypoventilation and respiratory acidosis may ensue. Hypercapnic respiratory failure is defined as a steady-state Pa_CO2 while awake at more than 45 mm Hg, the upper limit of normal. This definition is somewhat arbitrary but has proved clinically useful. https://accessmedicine.mhmedical.com/content.aspx?bookid=1344&sectionid=81207914

Paula has neural injury affecting the operation of her ventilatory pump. This is why her breathing at rest is too slow, even in health. She is now aware of the compensatory/adaptive mechanisms that help preserve ventilation (e.g., respiratory chemosensitivity, motor responses to alterations in the mechanics of breathing, and intrinsic changes in respiratory muscle strength and endurance) . When she gets ill and experiences long lasting airway mucus dysfunction [see below] then she begins to experience the decompensating/maladaptive responses that predispose to CO₂ retention (e.g., respiratory muscle wasting and fatigue and a rapid, shallow pattern of breathing) that follows.

Airway Mucus Function and Dysfunction

John V. Fahy, M.D. and  Burton F. Dickey, M.D

The lungs are remarkably resistant to environmental injury, despite continuous exposure to pathogens, particles, and toxic chemicals in inhaled air. Their resistance depends on a highly effective defense provided by airway mucus,^1–7 an extracellular gel in which water and mucins (heavily glycosylated proteins) are the most important components. Airway mucus traps inhaled toxins and transports them out of the lungs by means of ciliary beating and cough (Fig. 1). Paradoxically, although a deficient mucous barrier leaves the lungs vulnerable to injury, excessive mucus or impaired clearance contributes to the pathogenesis of all the common airway diseases.^1–4 This review examines the normal formation and clearance of airway mucus, the formation of pathologic mucus, the failure of mucus clearance that results in symptoms and abnormal lung function, and the therapy of mucus dysfunction. N Engl J Med. Author manuscript; available in PMC 2014 Jun 8.Published in final edited form as:N Engl J Med. 2010 Dec 2; 363(23): 2233–2247. doi: 10.1056/NEJMra0910061PMCID: PMC4048736NIHMSID: NIHMS567096PMID: 21121836

Open in a separate windowFigure 1Mucus Clearance in Normal Airways

Mucus is continuously swept from distal to proximal airways. In the most distal bronchioles, epithelial cells are cuboidal and do not produce mucin (bottom box), and bronchiolar patency is stabilized by surfactant from adjacent alveoli.⁸ In the adjacent small airways, a thin mucus gel layer is produced by columnar secretory (Clara) cells that do not stain for intracellular mucins because they are produced in low amounts and steadily secreted. In the large airways lined by a pseudostratified epithelium, a thick mucus gel layer (up to 50 µm) accumulates from mucus transported from distal airways and additional mucins are produced by surface secretory cells and glands. After mucus ascends the trachea, it is propelled through the vocal cords by ciliary epithelium in the posterior commissure of the larynx. It then enters the pharynx and is swallowed, with approximately 30 ml of airway mucus eliminated by the gastrointestinal tract daily. The vocal cords are covered by squamous epithelium, so they do not participate in ciliary clearance, although they promote cough clearance by closing while expiratory pressure builds and then opening suddenly so airflow is forceful.Go to:

STRUCTURE AND FUNCTION OF THE NORMAL AIRWAY

Epithelial surfaces in contact with the outside environment are protected by mechanical barriers (e.g., keratinized skin) and chemical barriers (e.g., gastric acid). Mucosal surfaces are wet epithelia that have a mucous barrier as part of their protective mechanism.^1–7 Mucus layers vary widely in composition and structure; for example, they are thick and adherent to the epithelium in the gut, but thin and mobile in the airway.

Mucus dysfunction occurs in virtually all inflammatory airway diseases. Acute viral and bacterial infections and chronic diseases such as primary ciliary dyskinesia, non–cystic fibrosis bronchiectasis (which is often caused by atypical mycobacterial infection), panbronchiolitis, and immunodeficiency states (e.g., hypogammaglobulinemia, human immunodeficiency virus infection, organ transplantation, and hematologic malignant conditions) all have a component of mucus dysfunction. In addition, retained mucus is a problem in intubated patients and those in whom lung mechanics are disrupted as a result of paralysis, immobilization, or surgery; atelectasis and pneumonia are common complications in such patients. Genomic markers in chromosomal region 11p15.5 (which encompasses MUC5AC and MUC5B) have been reported to be associated with asthma severity,⁹⁹ and panbronchiolitis,¹⁰⁰ although mechanisms leading to disease susceptibility have not yet been defined.Go to:

TREATMENT

The development of rationally designed treatments for pathologic mucus has been hindered by a lack of understanding of the mechanisms of mucus dysfunction.

Airway Mucus Function and Dysfunction John V. Fahy, M.D. and  Burton F. Dickey, M.D N Engl J Med. Author manuscript; available in PMC 2014 Jun 8.Published in final edited form as:N Engl J Med. 2010 Dec 2; 363(23): 2233–2247. doi: 10.1056/NEJMra0910061PMCID: PMC4048736NIHMSID: NIHMS567096PMID: 21121836

” Unlike tissue (skin) on the outside of your body, mucous membranes are relatively sheltered from ultraviolet radiation and exposure to the weather. This helps the mucous membranes remain relatively unchanged throughout the aging process. Mucous membranes also replace themselves quite quickly. However, studies have found that oral mucosa becomes increasingly thin with age.⁴ Aging and Your Mucous Membranes 

Mucous membranes protect the inside parts of your body that are exposed to air, in a similar fashion to how your skin protects your external body. Mucous membranes are rich with mucous glands that secrete mucus to help keep the membranes moist..

The human body has four types of tissue with which our organs, bones, cartilage, and other parts of the body are made. One of the types, epithelium, is subdivided into two categories: mucous membranes, and serous membranes. Mucous membranes are made up of epithelial cells that usually covers and protects underlying connective tissue (fibrous and elastic tissue built for supporting other structures of the body).

The oral cavity [and that of the throat, including the larynx] is often referred to as the “mirror of the body” because the mucous membranes in your mouth change depending on many different diseases. ” Oral Mucous Membranes are the Mirror of the Body 

EAR, NOSE & THROAT What Mucous Membranes Do in Your Body By Kristin Hayes, RN  Medically reviewed by Daniel More, MD Updated on April 26, 2020 https://www.verywellhealth.com/what-are-mucous-membranes-1191862

Taste cells are an example, the larynx is made of muccus membraine