Download PATH 417 Case 3 Week 1: The Body System- Hasrit

PATH 417 Case 3 Week 1: The Body System- Hasrit Sidhu
Overview of the Case
Based on the signs and symptoms presented, it is likely that Robert will be
diagnosed with pneumonia or tuberculosis. Pneumonia is an infection of the lungs, which
results in the inflammation of the air sacs (MayoClinic, 2015). In this condition, the air
sacs are filled with fluid or pus and, as a result, the patient experiences cough with
excessive sputum production, fever, chills and difficulty in breathing (MayoClinc, 2015).
Pneumonia can be divided into two forms: 1) Bronchial Pneumonia: This involves the
alveoli contiguous to the larger bronchioles of the bronchial tree and occurs in infants,
young children and aged adults. 2) Lobar Pneumonia: This involves only a single lobe of
the lung and is prevalent in young adults (Todar, 2012). Pneumonia can be caused by a
variety of organisms, including bacteria, viruses and fungi (MayoClinic, 2015). For the
purposes of this course and Robert’s case, we will focus on bacterial causes. The primary
bacterial cause of pneumonia is Streptococcus pneumonia (Figure 1), which forms a
component of the normal flora in the nose and throat (Healthline, 2015). When the
immune system is weakened or the respiratory system is damaged, possibly by the
inflammatory immune response, the bacteria are able to enter the lungs by inhalation
(Healthline, 2015). It is important to note that there are other bacterial causes of
pneumonia; however, for the purposes of this report, we will limit our discussion to S.
pneumoniae, which is the most common cause of pneumonia. These signs and symptoms
can also be associated with tuberculosis. Tuberculosis is an infectious disease that affects
the lungs and is usually caused by the bacterium, Mycobacterium tuberculosis (Figure 1)
(Tuberculosis, 2016). Throughout this report, we will discuss the signs and symptoms,
the affect on normal physiological functioning and the secondary infections associated
with both of these bacteria.
Figure 1: A scanning electron micrograph of S. pneumoniae (left) and M. tuberculosis
(right) (Todar, 2012).
Signs and Symptoms
A sign is an objective characteristic that is identified by a healthcare professional,
such as a physician (Niamh and Lowe, 2016). Patients may or may not be aware of the
signs that are associated with their illness (Niamh and Lowe, 2016). In contrast, a
symptom is a characteristic that the patient observes or feels (Niamh and Lowe, 2016).
Based on this, there are some characteristics of the disease, which are detected, by the
physician and not the patient and there are some characteristics that are detected by
patient and not detected by the physician. Finally, there are also some disease
characteristics that are both signs and symptoms.
Please consult the following table for Robert’s signs and symptoms:
-
-
-
-
Signs
A fever of 38.5 degrees Celsius
The presence of crackles in the right
lung. These crackles usually reflect
a build up of fluid in the lungs.
Fluid buildup may be due to the
congregation of white blood cells in
response to the infection in the lung
(LiveStrong, 2015)
There are decreased breath sounds
in the right lower lung field. Breath
sounds are the noises produced by
the structures of the lungs during
breathing. Decreased breath sounds
can mean that there is fluid in the
lung as a result of the immune
response to bacterial infection
(MedlinePlus, 2015).
Lab identification of the pathogen
via X-Rays and the deep sputum
tests.
A chronic productive cough, which
may result in the coughing up of
mucous/sputum from the lung. The
mucous may be green or it may
contain some blood (WebMD,
2014).
Increased heart rate (WebMD,
2014).
Symptoms
-
-
A fever
Chills
Night Sweats
A chronic productive cough, which
may result in the coughing up of
mucous/sputum from the lung. The
mucous may be green or it may
contain some blood (WebMD,
2014).
Shortness of breath (WebMD,
2014).
Chest pain that worsens with
coughing and breathing (WebMD,
2014).
Increased heart rate (WebMD,
2014).
Feeling tired or weak (WebMD,
2014).
Based on this chart, it is clear that some of the signs and symptoms are similar;
however, Robert’s family doctor is able to identify some signs that are not objective or
noticeable symptoms for Robert, such as the lung crackles and the decreased breath
sounds. These signs are primarily associated with defects in the lung. Additionally, I have
included some signs and symptoms that are not directly listed in Robert’s case, but are
generally present during cases of pneumonia and/or tuberculosis. These signs and
symptoms are highlighted in red in the chart above to indicate that they may not
necessarily be associated with this specific case. It is important to note that a key history
finding is that Robert has emigrated from India about a year ago. This is relevant because
India presents a different environment with different potential pathogens than Canada. It
is important for the physician to consider this when ordering and evaluating the tests and
prescribing any type of medication and treatment.
Normal Physiological Function of the Affected Body System
Based on the signs and symptoms presented – lung crackles, decreased breath
sounds, chronic cough, sputum production – it is likely that the primary body system that
is affected is the respiratory system. Specifically, the lungs, which make up the lower
respiratory system, are affected. In this section, we will discuss the regular physiological
function of the lungs and the entire respiratory system.
The respiratory system is made up of four main components: 1) Airways 2) Lungs
3) Blood Vessels 4) Respiratory Muscles (How the Lung Works, 2012). The airways
include the following: 1) Nose and linked air passages, which are termed nasal cavities 2)
The mouth 3) Larynx 4) Trachea 5) Bronchial tubes and the resulting bronchial branches
(How the Lung Works, 2012). During inhalation, air enters the mouth and flows to the
trachea. The trachea splits into two bronchi, which enter the lungs (CDC, 2014). It is
important to note that the bronchi will branch into conducting and respiratory
bronchioles, which eventually terminate in alveolar sacs in the lungs, where gas exchange
takes place (CDC, 2014). These airways facilitate the delivery of fresh air from the
atmosphere through the trachea and bronchioles to the alveolar sacs (Figure 2) (CDC,
2014). This continuous delivery and removal of air allows the process of gas exchange to
take place at the lungs, so that oxygen can be transported into the blood and carbon
dioxide can be transported from the blood into the lungs and expired out into the
atmosphere (CDC, 2014). It is also important to note that the airways are composed of a
mucous epithelium, which heats and humidifies inspired air (How the Lung Works,
2012). This contributes to gas exchange at the alveolar sacs. Additionally, the mucous
epithelium of the bronchial and tracheal tubes contains small hair-like particles, called
cilia, which can trap and eliminate pathogens and foreign particles (How the Lung
Works, 2012). This forms a component of the anatomical immune system.
Figure 2: A diagrammatical representation of the respiratory system. Fresh air will enter
the mouth into the upper airways, which is composed of the larynx and the trachea. Air
will then move into the lower airways, which are composed of the bronchus and
bronchioles. Air will finally terminate in the alveolar sacs, which are found in both the
left and right lung. Gas exchange takes place at the alveoli (CDC, 2014).
As mentioned above, bronchioles terminate in small round air sacs called alveoli.
These alveoli are situated in both the right and left lungs. They are covered in a mesh of
blood vessels, called capillaries (CDC, 2014). These capillaries connect the pulmonary
arteries coming from the right heart carrying deoxygenated blood to pulmonary veins,
which carry oxygenated blood back to the left heart, so it can be pumped out to the rest of
the body (CDC, 2014). At the capillaries, carbon dioxide from the deoxygenated blood in
the pulmonary arteries diffuses into the alveolar sacs and oxygen diffuses from the
alveoli into the blood vessels (CDC, 2014). This functions to oxygenate the blood that is
travelling back to the heart, so that it can sufficiently oxygenate tissues when it is pumped
out to the rest of the body (CDC, 2014). Following gas exchange, exhalation results in the
expiration of carbon dioxide rich air.
Figure 3: This represents an alveoli situated adjacent to a capillary. There is a thin airblood barrier, which separates the blood in the capillary from the air in the alveolus.
Oxygen and carbon dioxide are able to diffuse across this barrier. This diffusion process
is termed gas exchange. This process is essential for all tissues of the body because they
require oxygen for their normal metabolic functions. Dysfunctions in this gas exchange,
as seen in pneumonia and tuberculosis, result in severe deficiencies in blood oxygenation
(CDC, 2014).
The final component of the respiratory system, the respiratory muscles, are
responsible for generating the necessary thoracic pressures, which allow inspiration and
expiration to take place (CDC, 2014). These muscles include the diaphragm, intercostal
muscles, abdominal muscles and accessory muscles in the neck and collarbone area
(Figure 4) (CDC, 2014). The diaphragm is the primary muscle used in inspiration. Its
contraction generates the necessary negative thoracic pressure that allows air to flow into
the airways and the alveolar sacs (CDC, 2014). During normal breathing, expiration is
passive because the relaxation of the diaphragm and the accessory muscles returns
respiratory pressures to normal levels; however, during rapid breathing, abdominal
muscles play an important role in active expiration (CDC, 2014). Ultimately, the muscles
of the respiratory system play an essential role in gas exchange because they allow for the
inspiration of fresh air and the expiration of carbon dioxide rich air.
Figure 4: An overview of the respiratory muscles responsible for inspiration and
expiration (Respiratory Muscles, 2012).
Based on this, it is clear that the airways, lungs, blood vessels and respiratory
muscles all play an important role in regulating airflow and coordinating gas exchange
between the blood and alveolar sacs. Defects in any of these components results in the
dysfunction of the overall respiratory system. In the following section, we will discuss
the damage assessed to the lung as a result of pneumonia and tuberculosis and how this
affects the normal physiological functioning of the lung.
Disruption of Normal Physiological Function of the Respiratory System
As mentioned earlier, the bacteria that are the most prevalent causes of
pneumonia, S. pneumoniae, are members of the human normal flora and colonize the
nasopharynx and other regions of the throat (Todar, 2012). S. pneumoniae and other
pneumonia-causing bacteria are able to infect the upper respiratory system and gain
access to the lower respiratory system, through inhalation, when specific risk factors are
present (Eddy, 2005), including pre-existing infection, smoking, chronic obstructive
pulmonary disease and asthma (Nair and Niederman, 2011). Therefore, pneumonia starts
off as an upper respiratory inflammatory condition and migrates to the lower respiratory
system to the alveolar sacs, which are located in the lung (Nair and Niederman, 2011). As
this bacterial infection progresses, both the bacteria and the host immune response
contribute to the inflammatory condition of the lung and the steady progression of
pneumonia (Nair and Niederman, 2011). This results in a disruption of the normal
physiological functioning of the lungs and the entire respiratory system. It is important to
note that M. tuberculosis initiates a similar inflammatory response and results in similar
changes to the respiratory system’s normal physiological function. Therefore, the
following discussion on how S. pneumoniae affects the normal physiological function of
the respiratory system is also applicable to the M. tuberculosis infection.
As the pneumonia-causing bacteria enter the respiratory system, the body initiates
a hyperactivation of the inflammatory immune response against the bacteria (Singh,
2012). Neutrophils, macrophages and epithelial cells of the respiratory system mediate
this inflammatory immune response (Singh, 2012). The initiation of the inflammatory
immune response requires large quantities of blood to be transported to the site of
infection, so that neutrophils, macrophages and other cells of the innate immune system
can be mobilized (Singh, 2012). This results in vascular congestion of the blood vessels
surrounding the alveoli (Singh, 2012). Considering that the air-blood barrier is thin to
allow for sufficient gas exchange, engorgement of the blood vessels allows fluid to move
through the blood vessel epithelium and into the alveoli (Steel, 2013). Starling’s forces
govern this movement of fluid (Steel, 2013). Ultimately, the inflammatory response
results in the lung becoming inflamed and consisting of high levels of bacteria, innate
immune cells and fluid (Singh, 2012). This excess amount of fluid will adhere to the
lining of the chest wall, the alveoli and the space between the chest wall and alveoli,
which is termed the interpleural space (Boehlke, 2015). In addition to vascular engorging,
this excess fluid is also secreted by the pleural layer (Boehlke, 2015). The overall
accumulation of the fluid results in pleural effusion, which impairs breathing by limiting
the expansion of the lungs (Boehlke, 2015). This means that the diaphragm and other
muscles of inspiration are unable to expand the thoracic cavity enough to generate the
negative pressures that are required for inspiration (CDC, 2014). This is termed
ventilatory failure (Boehlke, 2015). This results in the alveoli failing to become
sufficiently oxygenated, which impairs gas exchange. Additionally, the accumulation of
fluid in the alveoli serves to thicken the blood-air barrier, which impairs the process of
gas transport (Figure 5) (Boehlke, 2015). This further limits the ability of the lung to
oxygenate the blood (Boehlke, 2015). Finally, the inflammatory immune response also
results in the severe inflammation and thickening of the walls of the lung and bronchial
tubes (Boehlke, 2015). This results in hypoxemic respiratory failure through
bronchoconstriction, which limits airflow into the alveolar sacs for gas exchange
(Boehlke, 2015). Combining this with the fact that the inspiratory respiratory muscles are
impaired and that the blood-gas barrier impairs gas exchange, there are severe limitations
in blood oxygenation and carbon dioxide elimination due to the inflammatory immune
response.
Figure 5: This shows how the alveoli are specifically affected during pneumonia. They
are filled with fluid, which prevents normal gas exchange and also has mechanical effects
on ventilation (Pneumonia, 2016).
Ultimately, the complications of pneumonia including ventilatory failure,
hypoxemic respiratory failure and pleural effusion are associated with the symptoms that
Robert experiences and the symptoms that are associated with pneumonia and
tuberculosis in general. The following is a description of how some of the
pathophysiological complications correlate with the symptoms of pneumonia:
1) Fever, chills and night sweats: These symptoms are associated with the general
inflammatory immune response. They are mediated by inflammatory substances,
such as cytokines in response to both the S. pneumoniae and the M. tuberculosis
infections (WebMD, 2014).
2) Chronic productive cough with mucous/sputum and possibly some blood: The
cough and the resulting sputum is also a result of the innate inflammatory
response (WebMD, 2014). Sputum results because there is an upregulation of
mucous generated by the mucous epithelium to eliminate the infection. Blood
may also be coughed out because of the damage to the airway epithelium by the
inflammatory immune response (Singh, 2012).
3) Shortness of breath: Considering that the airways are constricted and the blood is
not sufficiently oxygenated due to the impaired air-blood barrier, there is a
sensation of a shortness of breath even though ventilation rate and depth of
breathing may be adequate. Shortness of breath is termed dyspnea and it is sensed
by chest wall mechanoreceptors, chemoreceptors, lung receptors, and central
nervous system mechanisms (Burki and Lee, 2010). These mechanisms stimulate
the sense of dyspnea.
4) Increased heart rate: During pneumonia, blood may not be sufficiently
oxygenated, so heart rate must increase to mediate the sufficient delivery of
oxygen to tissues for essential metabolic functions (WebMD, 2014).
5) Feeling weak or tired: Again, the insufficient oxygenation of blood prevents
tissues from being sufficiently oxygenated. As a result, the patient feels weak and
tired (WebMD, 2014).
6) Crackles in the lung: This is due to a build up of fluid in the lung, as a result of
the inflammatory immune response (LiveStrong, 2015).
7) Decreased breath sounds: Again, this is a result of the fluid accumulation in the
lungs (MedlinePlus, 2015).
Secondary Sites of Infection
Considering that S. pneumoniae and M. tuberculosis are the most common
bacterial pathogens associated with pneumonia and tuberculosis, we will consider their
ability to spread from the lungs to secondary sites of infection. Although Robert does not
display any signs of a secondary infection, as his symptoms are limited to defects in the
respiratory system, S. pneumoniae and M. tuberculosis are certainly able to spread to
secondary sites.
For S. pneumoniae, the secondary sites of infection include the following:
1) Ear: This results in otitis media, which is an ear infection (Todar, 2012).
2) Sinuses: This results in sinusitis, which is an infection of the sinus (Todar, 2012).
3) Peritoneum: This results in peritonitis, which is an infection of the thin tissue,
which lines the walls of the abdomen (Todar, 2012).
4) Central Nervous System: This results in meningitis, which is an infection of the
brain and spine (Todar, 2012).
Various factors are important in the ability of S. Pneumoniae to travel to these
secondary sites and infect these areas (Figure 6). The first step in this process is initiating
the respiratory infection. This is done through the following steps:
1)
The bacteria adhere to the mucosal epithelium of the nasopharynx (Koedel,
Scheld and Pfister, 2002). S. pneumoniae express various surface molecules
which help them facilitate this adherence. It has been shown that pili proteins
facilitate this initial attachment of bacterial cells to the mucosal epithelium
(Todar, 2012). Additionally, specific surface proteins, called choline-binding
proteins (CBPs) also help to facilitate this attachment (Todar, 2012).
2)
Following successful infection of the mucosal epithelium and spread into the
lower respiratory system, the bacteria are able to gain entry into the blood by
invading the mucous epithelium (Koedel, Scheld and Pfister, 2002). They are
then able to initiate bacteraemic spread (Koedel, Scheld and Pfister, 2002). The
ability of S. pneumoniae to infect and survive in the blood is crucial to the
development of infections in secondary sites because blood provides a route of
travel between these sites. The survival of these bacteria in the blood is aided
by the presence of a capsular polysaccharide, which prevents phagocytosis by
interfering with the biding to complement C3b to the bacterial surface (Todar,
2012). Additionally, the bacteria also produce IgA protease, which cleaves IgA
antibodies (Todar, 2012). These structures and proteins allow the bacteria to
successfully evade the immune system and enter the secondary sites of
infection.
3)
Meningitis: The bacteria are able to travel to the CNS, via the blood, and cross
the blood-brain barrier into the sterile CNS (Cundell et al., 1995). The blood
brain barrier prevents pathogens and other materials from getting into the CNS;
however, S. pneumoniae are able to enter the CNS through the brain
endothelium (Cundell et al., 1995). To enter the CNS, they must first attach to
the endothelial cells (Cundell et al., 1995). Upon contact, S. pneumoniae
activate the endothelial cells, which induces their cellular expression of
platelet-activating factor (PAF). This binds to bacterial phosphorylcholine
expressed on the cell wall (Cundell et al., 1995). Following this, the bacteria
are able to enter the CNS and induce inflammatory defenses. The inflammatory
immune response is initiated in response to the bacterial DNA, which is
released following autolysis, or in response to bacterial cell wall components
(Lewis, 2000). Consequently, most of the damage that occurs in the brain in
Meningitis is associated with the inflammatory response (Todar, 2012). This
damage is induced by the release of host cell proteolytic enzymes, such as
matrix metalloproteinases (MMPs), which disrupt the blood-brain barrier, and
radical oxygen species, which attack fatty acids and damage neuronal cell
membranes (Lukes et al. 1999). This is associated with the loss of brain
endothelial cells, which can result in the loss of cerebrovascular autoregulation
and loss of blood-brain barrier integrity (Koedel, Scheld and Pfister, 2002).
This can lead to severe brain damage and this is the most severe outcome of
secondary infection associated with S. pneumoniae (Koedel, Scheld and Pfister,
2002).
4)
Other sites of infection: The same characteristics of the bacteria are also
important in reaching other secondary sites, including the ear, peritoneum and
sinuses (Todar, 2012). These characteristics include their cell wall proteins,
such as pili and CBPs, which facilitate their attachment to secondary sites and
initiate infection (Todar, 2012). Additionally, the autolysin, LytA, is also
important in initiating autolysis of the bacteria, which ultimately induces the
inflammatory immune response (Todar, 2012). As mentioned in the case of
meningitis, the inflammatory immune response is primarily responsible for
inducing the damage at these sites as well; however, the release of hemolysins,
such as pneumolysins, also results in bacteria-dependent host cell lysis (Todar,
2012). Additionally, the release of pneumolysins can also induce the further
release of cytokines, which contribute to the inflammatory immune response
and increase the amount of damage to the site of infection (Todar, 2012). It is
important to note that the release of pneumolysins and autolysins also plays a
role in the CNS infection (Todar, 2012). Based on this, it is clear that these
factors utilized by S. pneumoniae are crucial in establishing the initial infection
in the respiratory system, evading the immune response in the blood and
establishing a secondary infection at another site, such as the CNS, the ear,
sinus or peritoneum.
Figure 6: This shows a more extensive overview of how S. pneumoniae spreads to
secondary sites and induces infections at those sites (Koedel et al., 2002).
Although S. pneumoniae is able to spread beyond the initial infection site and affect
secondary infection sites, Robert does not experience any symptoms associated with
secondary site infection, which likely means that his infection is isolated to the initial
infection site, the lungs.
In the case of M. tuberculosis, the secondary sites of infection include the kidney,
brain, bones and lymph nodes (Todar, 2012). The bacteria travel to the kidney, brain and
bones via the blood and to lymph nodes via the lymphatic system (Todar, 2012). Their
ability to travel to these various sites of infection via the blood or lymphatic system
depends on their capacity to evade the immune system. They use the following
mechanisms to evade the immune system:
1)
Intracellular growth: They grow intracellularly in phagosomes, which allows
them to evade the immune response (Todar, 2012). Antibodies and
complement are ineffective when these bacteria are inside host cells (Todar,
2012). Their ability to grow within phagocytes depends on their capacity to
inhibit phagosome-lysosome fusion (Todar, 2012). This is due to a secreted
bacterial protein that modifies the phagosome membrane (Todar, 2012). They
are also able to inhibit reactive oxygen species, which are essential to the
phagocytic process. Enzymes that combat radical oxygen species include
AhpC, SodA and SodC (Todar, 2012).
2)
Antigen 85 complex: This complex is a secreted group of proteins, which binds
fibronectin and walls off the bacteria from the immune response (Todar, 2012).
This further facilitates the immune evasion capability of M. tuberculosis.
3)
Slow generation time: These bacteria have a slow generation time, which
means that the immune system may not recognize them or may not be triggered
by them (Todar, 2012).
4)
High lipid concentration in cell wall: This high lipid concentration accounts for
impermeability and resistance to antimicrobial products (Todar, 2012). It also
promotes resistance to osmotic lysis and attack by lysosomes (Todar, 2012).
Based on the above factors, it is clear that M. tuberculosis possesses the necessary factors
to evade the immune system in the blood and lymphatic system. This allows the bacteria
to transit to secondary sites of infection, where they can mediate infection using the
following virulence factors:
1) Cell Entry/Adhesion: Once they arrive at these secondary sites of infection, the
bacteria are able to adhere and enter host cells, such as macrophages, by binding
directly to mannose receptors on macrophages via cell-wall associated
mannosylated glycolipid (LAM) (Todar, 2012). Additionally, they are also able to
adhere to epithelial cells by utilizing HbhA, which is a surface bacterial protein
that binds fibronectin (Todar, 2012). Additionally, M. tuberculosis also utilizes
pili proteins to facilitate adherence (Todar, 2012).
2) 19-kDA protein: Once the bacteria are internalized into macrophages at these
secondary sites, 19-kDA, which is present on the cell wall, binds to TLR-2
(Todar, 2012). TLR-2 stimulates signaling events, which results in the activation
of neutrophils (Todar, 2012). Consequently, the inflammatory immune response is
initiated, which facilitates much of the damage to these secondary sites.
3) Cord Factor: This is found on the cell wall and forms a toxic factor to
macrophages and other host cells upon initial binding (Todar, 2012).
These virulence factors allow M. tuberculosis to bind to phagocytic and epithelial cells
and initiate the inflammatory immune response (Todar, 2012). The inflammatory immune
response, associated with neutrophil recruitment and cell-mediated hypersensitivity are
responsible for most of the damage induced by the bacteria (Todar, 2012). These immune
responses are responsible for most of the symptoms seen at the secondary sites of
infection. In addition, substances on the bacteria, such as Cord factor, will mediate direct
damage to these sites as well (Todar, 2012). Based on this, it is clear that M. tuberculosis
has the ability to evade the immune system, which allows it to reach secondary sites of
infection through the blood or lymphatic system (Todar, 2012). Additionally, it also has
the ability to adhere to specific host cells, initiate the inflammatory and hypersensitive
immune response and directly damage host cells through the release of various
substances (Todar, 2012). These factors allow the bacteria to reach the secondary sites of
infection and damage these sites. It is important to note that the lung can also be a
secondary site of infection (Todar, 2012). This occurs when the bacteria return to the lung
from the secondary sites of infection and reinitiate the infection years or even decades
after the initial infection (Todar, 2012). This shows the persistent nature of M.
tuberculosis (Todar, 2012). This persistent nature correlates with the signs the doctor
notices and the symptoms that Robert experiences. For example, his chronic productive
cough can be explained by the fact that the bacteria are persistent and difficult to
eliminate. This is also associated with the fact that the bacteria is intracellular, so it is
difficult for the immune response to combat, which results in a chronic infection.
Fortunately for Robert, he does not experience any symptoms at the secondary sites,
which likely means that the bacteria have not spread beyond the initial infection site of
the lungs.
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