1

Case Study 3: Disorders of Ventilation and Gas Exchange

Student's Name

University

Course

Professor

Date
 2

Case Study 3: Disorders of Ventilation and Gas Exchange

1. Emmanuel uses a corticosteroid inhaler for the management of his asthma. What is the

mechanism of action of this drug? How is its action different from the β2-agonist

inhalants?

Corticosteroid inhaler is the most effective medication used in asthma management for

airway inflammation suppression. The mechanism of action occurs by pro-inflammatory protein

downregulation (Hossny et al., 2016). Corticosteroids also reverse asthma-induced structural

change components such as the bronchial wall's increased vascularity. Inhaled corticosteroids, at

cellular levels, reduce the amount of airway inflammatory cells, including dendritic cells,

eosinophils, and T lymphocytes. Inhaled corticosteroids' remarkable effects occur through

suppression of chemotactic mediators' production and adhesion molecules as well as the

inhibition of airway inflammatory cells' survival (Hossny et al., 2016). The major cellular target

for inhaled corticosteroids may be epithelial cells, modern asthma management's mainstay.

Corticosteroids' broad anti-inflammatory profile probably accounts for their asthma

management efficacy. The profile's actions are classified into rapid and delayed forms (Hossny et

al., 2016). Rapid actions take minutes or seconds through membrane-bound glucocorticoid

receptor mediation and direct airway vasculature interaction by non-genomic mechanisms

(Hossny et al., 2016). The delayed form takes days or hours through genomic approaches

necessary for protein expression change.

Inhaled corticosteroids' mechanism of action differs from that of β2-agonist inhalants.

Inhaled corticosteroids work by suppressing airway inflammation at relatively low doses. On the

other hand, β2-agonist inhalants affect some pathophysiology aspects such as airway smooth

muscles (Hsu & Bajaj, 2020). β2-agonist inhalants are the preferred relievers in stable asthma,
 3

while inhaled corticosteroids are the preferred controller therapy (Ban et al., 2018). β2-agonist

inhalants work by replicating catecholamines' functions in producing a wide range of autonomic

responses within the body, such as smooth muscle of the airway, intestine, uterus, and systemic

vasculature (Hsu & Bajaj, 2020). β2-agonist inhalants' mechanism of action involves circulating

catecholamines activating adrenergic receptors to produce sympathetic and parasympathetic

physiological responses (Hsu & Bajaj, 2020). The mechanism of β2-agonist inhalant promotes

bronchodilatory effect used in the treatment of a wide range of common respiratory diseases.

2. Why does someone with severe asthma become physically fatigued during a prolonged

attack? What are the physiologic events that occur during an attack?

Physical fatigue in prolonged severe asthma attacks results from low oxygen levels or

oxygen deprivation. Asthma exacerbations lead to hypoxemia or low oxygen levels in the blood,

manifesting as persistent tiredness in asthmatic patients. Physiologic events occurring during a

severe asthma attack includes abnormal gas exchanges (Kostakouet al., 2019).

Perfusion/ventilation mismatch leads to arterial hypoxemia. Severe asthmatic patients have

increased blood flow in alveolar spaces with remarkably low perfusion/ventilation ratios and low

ventilation in a high cardiac output context.

Severe asthma patients have increased airway resistance and reversible

bronchoconstriction with regard to respiratory system mechanics, followed by increased

breathing work, premature small airway closure, low flow rates, pulmonary hyperinflation, and

decreased elastic recoil. Forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF)

decrease substantially, total lung capacity increase, while the functional residual capacity and the

residual volume may increase up to 200% and 400% the normal value, respectively (Kostakouet

al., 2019). The changes in lung volume keep constricted airways open. The elastic forces serve as
 4

the respiratory system's driving forces during the lungs' passive expiration. Resistive forces

increase with reduced elastic forces, increasing the duration for inspired tidal volume full

expiration. Incomplete tidal volume exhalation begins inspiration at volumes in which the

respiratory system demonstrates positive recoil pressure. Positive alveolar pressure present at the

end of expiration promotes the presence of flow at the expiration end, in the process of dynamic

hyperinflation. The process depends on expiratory flow limitation, tidal volume, expiratory time

constant, external flow resistance, and inspiratory muscle activity during exhalation (Kostakouet

al., 2019). Although the dynamic hyperinflation initially works in patients' favor, by reducing

breathing's resistive work, expiratory muscle length-tension relationships shorten, lungs and

thorax increase in volume, and the contraction's strength eventually diminishes. Accessory and

expiratory muscles become active as the severe exacerbation remains unresponsive, increasing

the work of breathing and fatigue becomes severe (Kostakouet al., 2019). Increased resistance

and bronchospasm, mucous, and auto- positive end expiratory pressure peripheral airway

compression lead to lung's significant heterogeneity.

Hemodynamic compromise in severe asthma patients also promotes dynamic

hyperinflation. Positive intrathoracic pressure development decreases the right heart preload that

decreases the right heart output and increases afterload in the right heart (Kostakouet al., 2019).

Output in the right heart decrease in parallel with left heart diastolic dysfunction, and its

incomplete filling significantly reduces pulsus paradoxus sign presence and systolic arterial

pressure in inspiration (Kostakouet al., 2019). Asthmatic patients may be drowsy, agitated, or

confused due to difficulties in treating or controlling dynamic hyperinflation or developing

paradoxical thoracic-abdominal movement with pulsus paradoxus or absence of bradycardia or

wheeze in lung auscultation.

 5

3. One of the complications of respiratory fatigue is the development of hypercapnia. How

does the body compensate for an increase in CO2? What are the effects of hypercapnia

on the central nervous system?

Hypercapnia develops as a result of insufficient carbon dioxide removal from the blood

and alveolar hypoventilation in individuals with chronic and severe acute lung conditions. The

body compensates for carbon dioxide increase by its cells having sensing and response abilities

to gaseous molecule concentration changes through evolutionarily conserved mechanisms.

Carbon dioxide is produced in eukaryotic cells' mitochondria during oxidative phosphorylation

(Shigemura, Homma & Sznajder, 2020). The physiological levels of the gas are higher in

mammalian tissues than in the atmosphere. The gas traverses the body's cell membranes through

diffusion based on its concentration gradient across membranes and water/lipid partition action.

Insufficient carbon dioxide removal increases partial pressure CO2 in the blood, elevates its level

in the cerebrospinal fluid, and results in cerebrospinal fluid acidification (Shigemura, Homma &

Sznajder, 2020). The body responds to the increased CO2 levels by various central nervous

system sites sensing and eliciting the change's rapid adaptive responses, resulting in an alteration

in the depth and rate of breathing.

Mechanisms involved in CO2 compensation include CO2-sensitive connexin protein, pH-

sensitive ion channel, and central carbon dioxide chemosensing. CO2-sensitive connexin protein

mechanism involves the release of adenosine triphosphate in response to carbon dioxide

elevation. The mechanism involves inward rectifying the K+ channel's roles in CO2-dependent

posttranslational modification and hyperpolarization of excitable cells (Shigemura, Homma &

Sznajder, 2020). The pH-sensitive ion channel involves physiological adaptations to reflect the

blood's base/acid balance to sense and respond to elevated carbon dioxide levels. The Twik-
 6

related acid-sensing potassium 3, 2, and 1 channels demonstrate a significant role in the

regulation of CO2-dependent breathing (Shigemura, Homma & Sznajder, 2020). Central carbon

dioxide chemosensing, on the other hand, encompasses the complex process involving multiple

effector channels, brain regions, and molecules. Neurons detect alterations in hydrogen ions and

carbon dioxide and moderate respiration's CO2-chemosensing regulation.

Hypercapnia has adverse impacts on the central nervous system. The condition activates

a wide range of mechanisms in organs such as the heart and brain to preserve tissue perfusion

and oxygenation through intracellular pH defense and preservation (Shigemura, Homma &

Sznajder, 2020). Hypercapnia's impacts on the central nervous system include cerebrovascular

vasodilation that promotes intracranial pressure increase and adjusts the brain's blood volume. A

hypercapnia complication leads to subarachnoid hemorrhage and cerebral edema in some severe

asthma patients (Shigemura, Homma & Sznajder, 2020). The myocardia response to the

condition impairs contractility because of the irreversible acute respiratory acidosis.

 7

References

Ban, A. Y. L., Omar, A., Chong, L. Y., Lockman, H., Zaliza, I. Z., Ali, I. A. H., ... & Zim, M. A.

M. (2018). Management of asthma in adults in primary care. Malaysian Family

Physician, 13(3), 20-26.

Hossny, E., Rosario, N., Lee, B. W., Singh, M., El-Ghoneimy, D., Soh, J. Y., & Le Souef, P.

(2016). The use of inhaled corticosteroids in pediatric asthma: update. World Allergy

Organization Journal, 9(1), 26. https://doi.org/10.1186/s40413-016-0117-0

Hsu, E., & Bajaj, T. (2020). Beta 2 Agonists. StatPearls [Internet].

https://www.ncbi.nlm.nih.gov/books/NBK542249/

Kostakou, E., Kaniaris, E., Filiou, E., Vasileiadis, I., Katsaounou, P., Tzortzaki, E., ... & Rovina,

N. (2019). Acute severe asthma in adolescent and adult patients: current perspectives on

assessment and management. Journal of clinical medicine, 8(9), 1283.

https://doi.org/10.3390/jcm8091283

Shigemura, M., Homma, T., & Sznajder, J. I. (2020). Hypercapnia: An Aggravating Factor in

Asthma. Journal of Clinical Medicine, 9(10), 3207. https://doi.org/10.3390/jcm9103207