Systemic Inflammation and Organ Dysfunction in a Patient with Asthma

Faculty of Health and Life Sciences
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Introduction
An analysis of the case study suggests that the patient X (pseudonym) had a history of asthmatic
symptoms, and had been admitted to the care facility for the treatment of persisting signs and symptoms of
fever, cough and wheezing. It can be suggested that the patient suffered from cough-variant asthma that is
commonly manifested in the form of persistent, non-productive cough, generally without mucus formation.
Upon admission, abnormalities were observed in her vital signs that suggested the presence of tachypnea,
tachycardia, poor oxygen saturation, high body temperature, and hypotension. In addition, it can be stated that
the patient reported gradual reduction in the levels of oxygen saturation, which in turn demonstrated the
presence of hypoxemia that prevented normal functioning of the cells, due to a shortage of oxygen in the
bloodstream. Low urine output and elevated blood urea levels also provided indication for the failure of the
renal system to function effectively, thus leading to accumulation of waste products in the body, and subsequent
death of the patient. This report will discuss the disruption of the immune system, in relation to normal
functioning of physiological system in the patient that ultimately resulted in death.
Innate immune system
The innate immune system is referred to as an evolutionary strategy of defence against a range of
infections. The system gets activated following an attack by any pathogen and is primarily composed of several
barriers that prevent the entry of bacteria, viruses, foreign particles and other parasites inside the human body.
Some of the major functions of the innate immune system comprise of recruitment of immune cells to infection
sites, via the production of chemical factors and mediators like cytokines. Another potential role of the system
can be accredited to the activation of a signalling cascade that facilitates bacteria recognition, thereby promoting
antibody complex clearance (Lackey and Olefsky 2016). Prior to triggering any immune factors, the skin acts as
an impassable, continuous barrier to the pathogens that get inactivated or killed by the acidity of the skin and/or
desiccation (Iwasaki and Medzhitov 2015). Alternate defence mechanisms are present in other regions of the
Module: 212BMS Systemic Physiology
COURSEWORK Proforma
2018-19

body such as the mucus membranes and eyes that secrete mucus and tears for rinsing away the pathogens. Cilia
lining the nasal passages also trap the pathogen, and prevents infection. In addition, low pH present in the
stomach also inhibits pathogen growth and disrupts the cell membrane of the bacteria, thereby preventing
pathogen attack (Martini, Nath and Bartholomew 2014).
Inefficacy of the treatment that was implemented upon X resulted in the onset and development of
systemic inflammatory response syndrome (SIRS), commonly refers to an inflammatory state that affects the
entire human body. According to Kaukonen et al. (2013) the condition manifests in the form of response of the
entire body against a non-infectious or infectious insult and has several anti- and pro-inflammatory components.
Some of the common manifestations of SIRS comprise of an elevated body temperature (higher than 38 °C),
elevated heart rate (>90bpm), high respiratory rate (>20), and reduced WBC count in the blood. Taking into
consideration the fact that the patient X manifested tachycardia, tachypnea, and increased body temperature, it
can be suggested that the treatment administered was not effective in protecting the body against pathogen
attack, thereby leading to systematic inflammation, and subsequent dysfunction and failure of the organs.
SIRS and respiratory system
The respiratory system maintains homeostasis in two different ways namely, gaseous exchange and
blood pH regulation. The lungs participate in gas exchange through the elimination of carbon dioxide, a waste
product that is produced during cellular respiration. Removal of carbon dioxide from the body results in entry of
oxygen in the lungs that is required for cellular respiration (Guyenet and Bayliss 2015). Normal respiration rate
is associated with an estimated 12-25 breaths per minute. Tachypnea typically occurs under circumstances when
the respiratory rate is greater than 20 breaths/minute and is generally manifested in the form of shortness of
breath and retracting chest during breathing. On sensing the presence of an infection in the body, the innate
immune system releases chemicals in the bloodstream that results in an inflammation in the body and interferes
with the flow of blood to the vital organs, thus leading to tachypnea (Censoplano, Epting and Coates 2014).
Taking into consideration the fact that asthmatic conditions reported by the patient resulted in lung damage and
allowed more viruses and bacteria to invade the body, thus causing infection, the innate immune system, X
might have had eosinophilic inflammation in the lungs (Lambrecht and Hammad 2015). However, failure in
restoration of homeostasis resulted in a major systemic reaction where cytokine release promoted destruction of
cellular integrity and end-organ dysfunction.
Furthermore, history of asthma in the patient can be associated with the failure of the innate immune
system that was responsible for chronic inflammation of the airway conducting zone, thus leading to the
development of tachypnea. Furthermore, gradual decrease in the oxygen saturation levels in the patient can be
accredited to the fact that severe attack of asthma lead to hypoxia in the patient (Silverthorn 2013). The
condition is a typical hallmark of infected and inflamed tissue and the adaptation to inadequate tissue
oxygenation is regulated by hypoxia-inducible factors (HIFs) (Semenza 2014). In addition, a characteristic
attribute of the cells of the immune system is to penetrate and operate in cells and tissues that have low levels of
oxygen and nutrients. However, onset of SIRS resulted in failure of expression of hypoxia-inducible
transcription factors HIFs, thereby decreasing the oxygen saturation levels in the patients.
SIRS and cardiovascular system
The major mechanism of the cardiovascular system in homeostasis maintenance depends on the
controlled and continuous movement of bloodstream though the capillaries, permeating the cells and tissues of
the human body (Fox 2013). There is mounting evidence for the association between inflammation and atrial
fibrillation that occurs due to a maladaptive hyperimmune response, which in turn is triggered by pathogen
infection (Harada, Van Wagoner and Nattel 2015). The onset of tachycardia in the patient can be explained by
the fact that multiorgan dysfunction syndrome (MODS) and SIRS result in prognostically pertinent cardiac
autonomic dysfunction. This is generally manifested via strong attenuation of vagally and sympathetically
governed heart rate variability (HRV) (Balk 2014). In addition, the immune mechanisms that underlie the
process of attenuation are not just restricted to the nervous system, and encompass variations in the cells of the
cardiac pacemaker on a cellular level.
According to Ebelt et al. (2015) endotoxin typically interacts with hyperpolarization-activated cyclic
nucleotide-gated (HCN) ion channels that are located in the heart, which in turn mediate the pacemaker current.
This also transmits vagal signals on heart rate and HRV. Failure of the innate immune system also resulted in
abnormal firing of the cardiac electrical signals, thus speeding up the heart rate and causing tachycardia in the
patient. In addition, the decreased pumping efficiency of the left portion of the heart resulted in fluid build-up in
the lungs that was responsible for wheezing, breathlessness, and tachycardia (Widmaier et al. 2011).
Furthermore, the pathologic condition of circulatory shock also occurred due to a mismatch between the demand
and supply of oxygen, and led to inadequate tissue perfusion, thus bringing about multiple organ failure and
dysfunction (Cecconi et al. 2014). In addition, although hydrocortisone is used for treating the inflammation in
asthmatic conditions, the corticosteroid failed to treat the patient, thus deteriorating the patient condition (Rang
et al. 2014).
SIRS and renal system

According to Blaine, Chonchol and Levi (2015) kidneys maintain homeostasis by regulating the
concentration of ions and the amount of water in the blood. The kidneys have been found to largely contribute to
immune homeostasis. There is mounting evidence for the fact that several components of the immune system
play a major role in mediating acute types of renal disease, in addition to controlling the progression of chronic
kidney disease (Fearn and Sheerin 2015). A dysregulated immune system has been found responsible for the
onset of indirect or direct renal impacts. In addition, the loss of immune homeostasis in the kidneys lead to the
perpetual recruitment of immune cells and also brought about a worsening injury to the kidneys.
Owing to the fact that SIRS involves uncoordinated tissue repair attempts, the onset of immune-mediated injury
was primarily responsible for the fibrosis of renal structures that eventually resulted in kidney failure. Time and
again it has been proved that Acute Kidney Injury (AKI) is a recurrent complication of SIRS, which in turn is
correlated with a progressive decrease in sodium concentration (NaU) in the urine and fractional excretion
(FENa) (Garg et al. 2014). The aforementioned events resulted in inactivation of renin-angiotensin-aldosterone
system, thus reducing the urine output and increasing renal dysfunction. Renal function could be monitored by
measuring the glomerular filtration rate (normal=60) that is considered superior to the levels of serum
creatinine, which generally differs with race, age and gender.
Conclusion
To conclude, SIRS has been found to be triggered by inflammation, ischemia, trauma, infection or
several insults that are not generally related to infection. An analysis of the case scenario suggests that previous
history of asthma resulted in the onset and development of SIRS in the patient X, which has been found to use
inflammation as the mode of response of the human body to a plethora of nonspecific insults that developed
from chemical, and/or infectious stimuli. The immune system comprises of a complex inflammatory cascade
that involves cellular and humoral responses. Although the infection resulted in the local production of cytokine
into the circulating bloodstream for improving local response, failure of the immune system in restoring
homeostasis made the cytokine release cause destruction, rather than protection, which resulted in the activation
of several humoral cascades, endothelial system, and subsequent loss of circulatory integrity. The
aforementioned steps led to organ dysfunction and eventual death of the patient.
References
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