Analysis of Asthma: A Case Study on Pathophysiology and Pharmacology

This case study focuses on a 5-year-old girl named Jessica, who experienced a severe asthma attack requiring emergency department admission. The assignment delves into the pathophysiology of asthma, including airway inflammation, bronchoconstriction, and airflow obstruction. It examines the pharmacological interventions used, such as salbutamol, ipratropium, and prednisolone, detailing their mechanisms of action and effects. The case study also analyzes the patient's symptoms, including shortness of breath, coughing, and tracheal tug, linking them to the underlying disease processes. Furthermore, it explores relevant interventions, including medication administration and their metabolic pathways. The study highlights the impact of factors like preterm birth, eczema, and environmental allergens on the development and exacerbation of asthma symptoms. The assignment aims to provide a comprehensive understanding of asthma management through a patient-centered approach.

Running head: HEALTHCARE
Pathophysiology
Name of the Student
Name of the University
Author Note

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Pathophysiology- The case study involves a five year old girl Jessica, who had been
admitted to the Emergency Department of a hospital, following a sudden asthma attack at
night. She reported shortness of breath and cough initially, and was administered salbutamol
puffer. Nonetheless, after two hours, her situation worsened and she became increasingly
short of breath, with no signs of improvement after salbutamol administration. Therefore, the
major illness in this case that resulted in her hospitalisation is asthma attack. Asthma is
generally defined as a prevalent pulmonary condition that is characterised by inflammation in
the respiratory tract, which in turn results in bronchoconstriction and tightening of the
muscles in the airways. In other words, this variable and heterogeneous inflammatory disease
affects the airways and leads to relapse of symptoms.
The anatomy of human lungs comprises of membranous bronchi, cartilaginous
bronchi, bronchioles and alveolar ducts, which play an important role in exchange of
respiratory gases. The airways of the lungs include basement membrane, mucosa made up of
epithelial cells, and fibrocartilaginous tissues. Cellular elements like mast cells are
responsible for histamine release and the neutrophils, eosinophil, basophils, and macrophages
govern mediator release (Tortora & Derrickson, 2018). The pathophysiology of asthma attack
as involves three components that are inflammation of the airways, hyperresponsiveness of
the bronchioles and intermitted obstruction to airflow. There is mounting evidence for the
fact that inflammation of airway can be subacute, chronic or acute and presence of mucus
secretion and oedema in the airways significantly contribute to bronchial reactivity and
airflow blockade. According to Li et al. (2018) inflammation is generally associated with
neural abnormalities in the noncholinergic and cholinergic bronchopastic tone. Researchers
have identified asthma to be a “T-helper 2 (Th2)-linked disease,” and this is explained by the
generation of immunoglobulin E-mediated activation of mast cells, Th2-type cytokines such
as, interleukin [IL]-4, -13, and release of mediators. Furthermore, an increase in levels of

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prostaglandin D2 and higher proportion of mast cells that are chymase positive have also
been correlated asthma (Sverrild et al., 2016). Airway inflammation can also be explained by
the hygiene hypothesis that highlights the fact that there occurs an imbalance in control of Th
cells, thus casing prolonged domination of cells that bring about allergic response. The
immune system present in an infant remains aligned towards the production of Th2 cytokine,
which mediates allergic inflammation. After birth of an infant, infections result in activation
of the Th1 responses, thereby striking a balance between the Th1/Th2 associations (Zhu et
al., 2016).
Bronchoconstriction in asthma can be explained by the fact that the normal
functioning of bronchus is controlled by a balanced operation of the autonomic nervous
system. There are several afferent nerve endings present in the parasympathetic reflex look
that develop near the bronchus linings (Larson & Jaffe, 2017). Upon stimulation of the
aforementioned nerve endings due to cold air, dust or fumes, there occurs transmission of
nerve impulse to the vagal centre at the brain stem, following which the impulse reaches the
small airways of the bronchus, while passing through the vagal efferent pathway (Khosravi,
Lin & Lee, 2018). This leads to the release of the neurotransmitter acetylcholine from the
efferent nerve endings, which in turn stimulates the production of inositol 1,4,5-trisphosphate
(IP3) in the smooth muscle cells of the bronchus, thereby causing shortening of the muscles
and subsequent bronchoconstriction (André-Grégoire et al., 2018).
It has often been found that hyperinflation acts as a compensation mechanism of
obstruction of airflow. However, this compensation is typically restricted when the tidal
volume becomes near or almost equal to the pulmonary dead space, thereby causing alveolar
hypoventilation (Ostrovskyy et al., 2020). During the early phases, when there occurs a
mismatch in ventilation-perfusion patients generally suffer from hypoxia, thus preventing
hypercarbia by the immediate diffusion of carbon dioxide gas across the capillary membranes

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of the alveoli. In addition, hyperventilation during asthma attack might also get stimulated by
the hypoxic drive that brings about a reduction in the amount of PaCO2. With worsening of
obstruction in the airways and an augmentation in the ventilation-perfusion mismatch, asthma
attack is characterised by retention of carbon dioxide. During the initial phases of an acute
asthma episode, hyperventilation leads to the onset of respiratory alkalosis (Reddi, 2020).
This is soon followed by greater oxygen consumption, high work of breathing, and an
increase cardiac output that eventually causes metabolic acidosis. Asthma attack is also
characterised by sudden respiratory failure that gradually leads to the onset and progress of
respiratory acidosis owing to carbon dioxide retention, with a decrease in alveolar ventilation.
Research evidences have also established a correlation between preterm birth and
asthma in children. A probable mechanism for explaining this correlation is that preterm birth
amid babies is characterised by a deficit in the functioning and structure of the lungs, the
principle respiratory organs, which in turn augments the risk of gradual asthma development
(Zhang et al., 2018). Furthermore, scientists are of the opinion that risk factors that trigger the
onset of eczema in children often progress and lead to development of asthma. Symptoms of
asthma typically get triggered by the production and circulation of thymic stromal
lymphopoietin (TSLP) that is formed from damaged skin (Tidwell & Fowler Jr, 2018). This
compound has the capability of eliciting significant immune response and owing to the
efficacy of the skin in secreting this protein in circulating bloodstream, it travels throughout
the human body. On reaching the lungs, it triggers hypersensitive reactions and causes
asthma. Furthermore, proteins present in pet dander, saliva, urine and skin flakes stimulate
allergic reactions and aggravate symptoms of asthma in several people. This can be further
accredited to the fact that pet hair often collects mold spores, pollen and outdoor allergens, all
of which lead to hypersensitivity (SIJU, 2016). Hence, preterm birth of Jessica, eczema
symptoms and presence of two dogs and a cat triggered her asthma attack.

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Pharmacology- The three major drugs that had been prescribed to the patient Jessica
were salbutamol, ipratropium and prednisolone. Salbutamol contains a tertiary butyl group
that increases its selectivity for the β2 receptors that are present on the smooth muscles of the
bronchi. Receptor activation leads to conversion of ATP to cAMP, by adenylyl cyclase, thus
triggering a signalling cascade, which terminates with myosin phosphorylation inhibition and
decreases the intracellular calcium ion concentration (Gaugg et al., 2017). An increase in
cAMP concentration leads to inflammatory cell inhibition in airways like the mast cells,
eosinophils and basophils, thus preventing cytokine and inflammatory mediator release.
In contrast, ipratropium bromide is derived from atropine and manifests broncholytic
action by decreasing the cholinergic effect on the muscles. This in turn leads to blockage of
the muscarinic acetylcholine receptors, thus degrading the cyclic guanosine
monophosphate (cGMP), and decreasing its intracellular concentration (Saab & Aboeed,
2019). The drug also brings about a reduction in smooth muscle contractility in lungs, hence
preventing excess mucus secretion and bronchoconstriction.
The third prescribed medication prednisolone acts in the form of a glucocorticoid and
its lipophilic structure facilitates easy movement through the plasma membrane, following
which it binds to the glucocorticoid receptor (GCR) present in the cytoplasm. Following this
attachment, GC/GCR complex forms and dissociates the chaperone proteins from receptor,
thus helping translocation of the complex to the nucleus (Karthikeyan, 2016). Inside the
nucleus, the complex attaches to glucocorticoid response elements (GREs), and synthesises
anti-inflammatory proteins, thereby managing asthma.
Three signs and symptoms- Three major symptoms presented by the patient Jessica,
were namely, (i) shortness of breath, (ii) coughing, and (iii) tracheal tug, in addition to
moderate intercostal and subcostal recession. Shortness of breath can be accredited to an

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exposure of the patient to allergens like animal dander or dust mites. This symptom might
have occurred since asthma resulted in narrowing of the airways present in the lungs, thereby
preventing air to enter the lungs and leading to breathing difficulties (Tierney & Bhagra,
2018). Cough-variant asthma is characterised by a non-productive and dry cough and
generally occurs following an exposure to allergens to cold temperature (Corrao, 2018). Signs
of tracheal tug in the patient can also be associated to a downward pulling of the larynx and
the trachea that might have occurred owing to the anatomic location of the aortic arch. An
obstruction in the airways might have resulted in chest retractions, thereby causing tracheal
tugging (Otani, Iio & Ihara, 2020).
Interventions- Three relevant pharmacological interventions related to this case study
were inhaled salbutamol, inhaled ipratropium and PO prednisolone. Following its inhalation,
the drug topically acts on the bronchial smooth muscles and after 2-3 hours, low drug
concentrations are observed in blood. Immediately following inhalation, the drug cannot be
detected in circulating bloodstream. Systemic salbutamol levels are less following
recommended dosage inhalation. It has often been found that volume of distribution of this
intravenously administered drug is 156 +/- 38 L. Metabolism of salbutamol occurs in the
liver, predominantly by conjugation of the drug to salbutamol-4'-0-sulphate, an inactive
compound. The half-life of the drug is an estimated 2.7-5 hours, following its oral
administration (NCBI, 2020). After orally administering the drug, around 58-78% dosage
gets excreted in urine within 24 hours and roughly 60% gets excreted in the form of
metabolites. Moreover, small amount of the drug also gets excreted in faecal matter.
However, it does not get metabolised inside the lungs (Drug Bank, 2020). Salbutamol is a
selective beta (2)-receptor agonist that has a similar structure like terbutaline, therefore has
been prescribed owing to its widespread usage in the form of a bronchodilator for the
management of asthma and additional chronic obstructive airway diseases.

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The drug ipratropium is topically active, nonetheless it gets absorbed in a poor
manner. Absence of proper absorption potential of the drug at or near the mucosal regions is
correlated with the presence of 5-valent nitrogen charge. The drug also presents increased
topic efficacy, nonetheless, fails to generate noticeable blood levels nor systemic impacts.
Low serum levels of the drug are observed following inhalation or oral administration, and
correlated to around 1-2% of the dosage administered. Volume distribution of ipratropium
has been found to be an estimated 4.6 L/kg. Thus, it can be stated that the drug gets
distributed to a large extent in the cells and tissues (NCBI, 2020). The primary metabolism of
the drug occurs in the gastrointestinal tract, and this is mediated by cytochrome P-450
isoenzyme activity. From the drug dose that is orally administered, around 90% of the drug
gets excreted in an unchanged manner, and the absorption drug gets metabolised partially to
inactive metabolites, tropane and tropic acid, by the action of ester hydrolysis. Roughly 80-
100% of the drug administered gets excreted in urine, and as less as 20% gets eliminated
through faecal matter (Drug Bank, 2020). Almost the entire drug remains unchanged in the
urine eliminated portion. Taking into consideration the fact that orally administered
ipratropium has low absorption, majority of the dosage gets recovered in faecal matter with
minimum traces in urine. This drug is appropriate for addressing pathophysiology of the
patient owing to the fact that it will prevent activity of the neurotransmitter acetylcholine in
the bronchial smooth muscles, and will avert constriction of the airways, thereby bringing
about relaxation of the respiratory passages, and preventing shortness of breath and coughing.
Hence, the drug was administered based on its inhibitory action on the parasympathetic
nervous system that helps in bronchodilatation and relief from the exacerbating symptoms.
Oral prednisolone has been found to reach Cmax near 113-1343ng/mL that corresponds
to a Tmax of an estimated 1.0-2.6 hours. There is approximately 70% bioavailability of oral
prednisolone. A volume distribution of around 29.3L has been associated to 0.15mg/kg

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dosage of the drug prednisolone, in contrast to a volume distribution of around 44.2L for
0.30mg/kg drug dose. It has been identified that around 98% prednisolone gets eliminated in
urine. The drug generally gets reversibly metabolised to prednisone that is converted to
several intermediate compounds, at the end of which MXIV is obtained. All the intermediate
metabolites, in addition to their gluconide conjugates get predominantly excreted in the urine.
Moreover, the plasma half-life of the drug is nearly 2.1-3.5 hours, and is generally smaller
amid children, with greater half-life amid patients who suffer from liver disease (NCBI,
2020). This drug was administered to the patient since apart from providing anti-
inflammatory effects, the drug also inhibits neutrophil demargination and apoptosis, thus
inhibiting phospholipase A2, which eventually reduces arachidonic acid derivative
production. It will also prove effective in promoting anti-inflammatory signals (Drug Bank,
2020). However, there is a need to counsel the patient Jessica and her family members about
the risk of suppression of hypothalamic-pituitary-adrenal axis and the augmented
susceptibility to infections.

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