Understanding the Pathophysiology of Lung Cancer

This article provides an in-depth understanding of the pathophysiology of lung cancer, including the development of tumors and their effects on lung function. It explores the causes and mechanisms behind shortness of breath and other symptoms associated with lung cancer.

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Nursing Assignment
Student’s Name
Institutional Affiliation
Professor’s Name
City
Date

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Q. 1
Pathophysiology is the study of the operational changes which accompany a particular
disorder. The pathophysiology of lung cancer is complicated and still not entirely clear;
nonetheless, the comprehension of lung cancer pathophysiology has advanced over time. As with
other epithelial tumours, lung cancers are believed to develop from precursor lesions or
preneoplastic in the respiratory mucosa (Scarlata et al. 2017, p.2619).
In the lungs, the tumor cells move into the close tissue via the walls of the close lymph
vessels along with the blood vessels and reach the liver tissue (Popper 2016, p.77). The tumor
cells develop at a distant site creating minor tumours known as micrometastases that stimulates
the production of new blood vessels that supply oxygen along with the nutrients required for the
development of tumours. This results in the growth of cancer cells in the liver, which is known
as liver metastases.
Since the lungs are not getting enough oxygen as the tumour cells use the oxygen
available for their growth, the trouble in moving air in and out of the lungs causes shortness of
breath or dyspnea. The shortness of breath due to lung cancer is as a result of lung tumours
which block the airways in the lungs. Furthermore, it is as a consequence of blood clots and
tumor cells blocking blood vessel in the lungs along with tumor that spreads and obstructs a
nerve leading to paralysis of all or part of the diaphragm hindering the role of the diaphragm of
creating a vacuum effect which pulls air into the lungs causing dyspnea (Grapatsas et al. 2017,
p.15).
Q. 2
Secondary liver cancer is a tumour which began in another part of the body like the lungs
as with Nigel but has now metastasized to the liver, which means it is advanced cancer. This
means that advanced cancer will influence the pharmacokinetics of chemotherapy drugs taken
(Bocci and Kerbel 2016, p. 659). Pharmacokinetics is described as the movement of medications
into, through and out of the body. Since the existence of tumours influences many parameters in
the body, the chemotherapy pharmacokinetics cannot be inferred from healthy persons to persons
affected by cancer. Therefore, when drugs are administered, the tumour cells develop resistance
in medications through changes in the transportation of medicines leading to declined
intracellular accumulation of drugs.

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The advanced liver cancer can alter the absorption together with the distribution of anti-
cancer drugs in the body resulting in bizarre bioavailability (Pathania et al. 2018, p.55).
Moreover, when the binding of plasma protein is declined, the penetration along with medication
distribution into body tissues is affected. Also, due to secondary cancer in the liver, the bile acids
in the intestines are reduced, decreasing the absorption rate of the anti-tumour drugs. In case of
increases of bilirubin and bile acids in concentrations of plasma, the binding of the protein of
drugs is impacted, which influences the distribution along with metabolism of those drugs
(Wahlström et. 2016, p.41).
The clearance of most chemotherapy medications is profoundly affected by the
metabolism of the drugs, and therefore, it is possible to impact a person’s negative and positive
reactions at a prescribed dose. Reduction in the blood flow and the diversion of blood via
collateral varices reduces the clearance of high clearance drugs. There is capillarization of the
sinusoid in advanced liver cancer which lines the hepatic microcirculation mislays their fenestrae
and generates a basement membrane (Yokomori, Ando and Oda 2019, p.114). The
capillarization creates a barrier to diffusion of oxygen that leads to a critical decrease in hepatic
adenosine triphosphate together with oxidative metabolism.
In drug metabolism, serum albumin might decrease hence changing the disposition of
drugs which are substantially bound to albumin (Yousefpour et al. 2018, p.7784). Cationic anti-
cancer drugs may be preferably linked to alpha1-acid glycoprotein, which is frequently escalated
in individuals with cancer rather than it is to albumin. The considerable replacement of liver
tissue might result in a decrease in metabolic capacity. Furthermore, when the bile flow is
disrupted by the obstruction of extrahepatic biliary or through tumour invasion of intrahepatic
bile ductules, it minimizes the elimination of drugs which are principally excreted into the bile.
Q. 3
The effectiveness of chemotherapy is based on the cancer type along with the phase. The
complete efficiency ranges from being therapeutic for few cancers like leukemia’s to being
ineffectual to some like brain tumour, to being needless in others such as most non-melanoma
skin cancers. The potentiality of anti-cancer medications to destroy cancer cells is based on its
capability to interrupt cell division (Farkona, Diamandis and Blasutig 2016, P. 73). If the cells
are not able to divide, they die, and the quicker the cells are splitting, the more probable it is that
medications will destroy the cells causing the malignancy to shrink. The leading cause of deaths

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is lung cancer, of which 75% of persons with the disease are dire at the discovery and the
universal type being non-small cell of whose cases are almost 90% of lung cancers. Medications
which include cisplatin in combination with other drugs of which Mr Nigel is currently using
docetaxel are the most primarily used drug combinations (De Castria et al. 2013). From the case
study of Nigel, he is presently taking cisplatin and docetaxel.
The amount of cisplatin imported into the cell affects the amount of cell damage that
happens; the higher the intake, the more DNA damage meaning more often cellular apoptosis.
Cisplatin is in a category of alkylating agents and is most operational during the resting stage of
a cell. In the cell, cisplatin ousts its two chloride ions, generating a sensitive species which form
a link with the DNA bases (Bruno et al., 2017, p.461). Cisplatin offers a better example of how
minor adjustments in molecular structure could bring forth significant disparity in biological
action. Moreover, cisplatin creates crosslinks amid bases immediately and interferes with the
multiplication of DNA or DNA repair mechanism bringing about the distortion of DNA and then
triggering apoptosis in tumour cells.
On the other hand, docetaxel is in a category of drugs called mitotic inhibitors (Whitaker
and Placzek 2019, p.346). It is a cytotoxic anti-microtubule agent which clings to the beta-
tubulin subunit of microtubulin (Hardin et al. 2017, p.701) bringing forth microtubules
preservation and hindering depolymerisation which contributes to impeding of microtubule
dynamics together with cell cycle arrest and eventually the death of the apoptotic cell.
Microtubules belong to the cell's apparatus for dividing and replicating itself and therefore
hindering these structures conclusively brings about the cell death and also ceases the tumour
cells from multiplying (Hardin et al. 2017, p.701). Docetaxel also has a function in preventing
the body from generating the proteins required by the tumour cells to thrive, which effectively
treats the disease.
Q. 4
Docetaxel is derived from taxane, and it clings to a protein element of microtubules,
which is tubulin and synchronously encourages assembly and impedes disassembly of them
(Whitaker and Placzek 2019, p.346). The stabilisation of these microtubules results in the
hindrance of the division of the cell, which is called mitosis, along with cancer inflammation
leading to death. This chemotherapy drug halts their role by having the opposite effect by hyper-

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stabilising their framework, which distorts the possibility of the cells to use their cytoskeleton
compliantly.
Typically, this drug clings to the beta-tubulin subunit of which its clinging locks the
tubulin in place. The emanating microtubules are not able to dismantle which adversely impacts
the cell role because the shortening along with the lengthening of the microtubules is accurate for
their function as a transportation highway for the cell (Hardin et al. 2017, p.701). Docetaxel
triggers programmed cell death in cancer cells via clinging to apoptosis halting B-cell leukaemia
2 proteins and stopping its operation.
Cisplatin on the hand clings solidly to plasma proteins, which are the transferrin and
albumin bringing forth the inactivation of a large amount of the administered cisplatin (Gouveia
et al. 2018, p.1471). What counter this chemotherapy drug in the cytoplasm are the various
cellular components which include the thiol-containing peptides and proteins along with RNA.
Cisplatin aims at genomic DNA while a percentage of one of the cellular cisplatin is cling to
nuclear DNA. Cisplatin works by clinging with the DNA to develop adducts along with
intracellular crosslinks (Espina et al. 2017, p.564). These DNA adducts then hinder the
replication of DNA together with its transcription and then trigger various signal transduction
pathways terminating in the triggering of the apoptosis resulting in the cancer cells death.
The mechanism of action of Nivolumab is different from that of the combination of
cisplatin and docetaxel. T cells protect the body from cancer via damaging specific tumour cells,
but because cancer cells produce proteins, they shield those tumour cells from the T cells. The
work of the nivolumab is to obstruct the defensive proteins so that the T cells can damage the
tumour cells (Pluvy et al. 2019, p.12). Apparent of the triggered T cells, there is a PD-1 protein,
and in case a programmed cell death 1 ligand 1 or programmed cell death 1 ligand 2 molecules
clings to PD-1 the T cells become unfunctional. Through this, the body controls the immune
system to avoid reactivity, and many tumour cells generate PD-1, which hinders T cells from
invading the tumour. Therefore, the chemotherapy blocks the programmed cell death 1 ligand
1from clinging to PD-1, helping the T cells in doing their work hence effectively treating cancer
(Fandi et al. 2016, p.570).
Q. 5
Nausea and vomiting can be prompted by taste, pain or smell. Nausea happens when the
chemotherapy drugs destroy the cells which line in the gastrointestinal tract. When cisplatin,

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docetaxel along with nivolumab is administered, a specific part of the brain is prompted and a
particular part of the oesophagus which is a tube linking the mouth, the stomach and intestines is
also triggered. These chemotherapy medications cause nausea and vomiting due to the activation
of the chemoreceptor trigger zone by the afferent and the efferent reflexes (Cangemi and Kuo
2019, p.170). This adverse reaction is regulated in the brain and vomiting is triggered by the
vomiting centre, which is a spot in the brain. The decision of inducing an emetic response to
result in vomiting depends on the higher order centres positioned in the cortex, the input directed
to the vomiting centre by the vestibular system together with the contribution the chemoreceptor
trigger zone imparts to the remaining vomiting centre and the chemoreceptors in the GI tract.
The vomiting centre is situated in the medulla oblangata and consists of the blood-brain
barrier (Sarnat et al. 2019, p.21). Again, the vomiting centre being a diverse interlinking neural
network rather than a formal anatomical structure, it obtains afferent input from the
chemoreceptor trigger zone. Moreover, it gets afferent input from the cerebral cortex, the vagus
nerve, thalamus, hypothalamus, along with the glossopharyngeal through the provocation
mechanoreceptors stretch along with the actuation of serotonin receptors in the GI tract.
However, the chemoreceptor trigger zone contains acetylcholine, serotonin, and dopamine, along
with opioid receptors. The different routes leading to emesis is because of the involvement of the
stimulation of distinct receptors.
The inputs of the enteric nervous system along with the vagal, transmit information
regarding the GI tract status. Moreover, serotonin clings to the intestinal vagal afferent nerves via
serotonin receptors which prompt the vomiting reflex via the solitary tract nucleus and the
chemoreceptor trigger zone in the central nervous system (Sarnat et al. 2019, p.21). However, the
irritation of the GI mucosa by the medications triggers the serotonin receptors of the inputs. The
vomiting reflex that brings forth the relaxation of the oesophagus along with the pylorus,
contraction of the diaphragm and the abdominal walls, peristalsis of the upper GI tract, along
with the intercostal muscles culminating in the forced ejection of gastric elements through the
mucosal pasta closed glottis is the emetogenic pathway.
Q. 6
Morphine is in a category of medications called narcotic or opioid analgesics (Corder et
al. 2017, p.164). It is used in treating severe pain and works in the brain to modify the way the
body feels and react to the discomfort. The principal adverse reaction of this medication is

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respiratory depression (Kong, Wang and Du 2018, p.295). Respiratory depression, also known as
respiratory suppression is a decline in the ability to inhale and exhale. The typical morphine
dosage results in an increased concentration of CO2 and respiratory depression. The respiratory
centre in the brain becomes less sensitive to the level of CO2 and fails to signal for more deep
breathing. Its key influence is clinging to and triggering the μ-opioid receptor in the central
nervous system, and the activation of the receptor is related to physical dependence, respiratory
depression, analgesia and sedation.
Morphine is metabolised in the liver into morphine-3-glucuronide and morphine-6-
glucuronide (Malan, Lundie and Engler 2019, P. 21) and it uses its pharmacological impact on
the central nervous system along with the gastrointestinal tract. Opioids such as morphine
generate respiratory depression through triggering of u-opioid receptors at particular parts in the
central nervous system, inclusive of the pre-Botzinger complex along with respiratory rhythm
making area in the pons. Morphine impacts breathing with the onset and offset profiles, which
are mainly ascertained by opioid transfer to the receptor site (Boom et al., 2012, p. 5994).
The adverse reaction of morphine needs to be managed to prevent deaths. It can be
controlled by using a co-treatment with non-opioid respiratory stimulants since effective
stimulants avoid respiration depression without influencing the reaction of the opioid medication
(Dahan et al. 2018, p.1027). The non-opioid stimulants function in the brainstem respiratory
network containing drugs which work at 5-hydroxytryptamine receptor agonists, ampakines
(alpha –amino-3-hydroxy-5-methyl-4-isoxalepropionic acid receptors), along with the
thyrotropin-releasing hormone.
In managing respiratory depression, the thyrotropin-releasing hormone instigates
rhythmic bursting in breathing neurons of the tractus solitarius nucleus via regulation of
membrane indiscretion (Dahan et al. 2018, p.1027). On the other hand. Alpha –amino-3-
hydroxy-5-methyl-4-isoxalepropionic acid receptors sustains the rhythmogenesis along with the
inspiratory drive and sites out the pre-Botzinger complex. Lastly, when the 5-hydroxytryptamine
receptors are stimulated, they enhance the activity of the respiratory neurons leading to a
decrease in the variability of respiratory rhythm.

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