Sub-Acute Phase

Sepsis and Septic Shock have been my personal topic after the life of young Kamil Williams and a 31-year-old Texas man who both contacted a bacterial infection later turn into sepsis. Although I have not formally studied it during my school or university years, I still find the human body, how it can break down and react to certain ailments interesting. The next question would be why does this happen? Well when there is infection or insult upon the body’s immune system normal reacts and causing an inflammatory response. This normally a good thing and it promotes healing and the resolution of the insult, however in Septic Shock the inflammatory response comes explosive and uncontrollable. According to Allison Hotujec, the author of “Severe Sepsis and Septic Shock Protocols,” Sepsis has been called a “malignant intravascular inflammation.” The term malignant is because it is uncontrolled unregulated and self-perpetuating, in the usual immune response here is release of both pro-inflammatory and anti-inflammatory mediators, these balance to promote tissue

According to information published by the Mayo Clinic, sepsis has three stages: sepsis, severe sepsis and septic shock. The mortality rate for septic shock is nearly 50 per cent, and an episode of severe sepsis increases the risk of future infections. Severe sepsis causes blood flow to the vital organs, such as the brain, heart and kidneys, to become impaired. Sepsis can also cause blood clots to form in organs and extremities such as arms, legs, fingers and toes, which can lead to organ failure and tissue death (gangrene).

The systemic inflammatory response is the next step in the continuum and is a nonspecific inflammatory state that may be seen with an infection. Sepsis is the presence of the systemic inflammatory response syndrome (SIRS) with evidence of infection. As the bacteria invade the bloodstream, they release endotoxins that damage the endothelial cell lining and impair the vascular system, coagulation mechanism, and immune system. These endotoxins also trigger the immune and inflammatory responses, which results in the activation of macrophages and CD4 cells that release proinflammatory cytokines to create a systemic inflammatory response to the pathogen. Hospitalized patients may quickly progress from bacteremia to sepsis and finally to septic shock, even with treatment.

The fundamental principle of the phenomenon known as sepsis is an amplified immune response to a pathogen. It is important to note that the insult originates from the excessive host response to, rather than the pathogenicity of, the infective agent1. The upregulation of pro-inflammatory (TNF-α, IL-1α/β, IL-6, IL-12, IFN-γ, and MIF) and anti-inflammatory (IL-10, TGF-β, and IL-4) mediators have been found in various sepsis states2. The exact function, value, and limits of this peculiar, and extravagant, immune response is not fully understood3. Historically, sepsis and processes within the sepsis spectrum have been difficult to truly identify and diagnose1. In 2012, the Surviving Sepsis Campaign identified three major categories of the phenomenon: sepsis, severe sepsis, and septic

The body’s primary reaction to an injury is tissue destruction. The degree of tissue destruction will greatly depend on the injurious force. Secondary damage may occur from cell death. Cell death occurs because of the hypoxia associated with the injured area. The damage done in the primary stage

However, modern technology is helping us to properly identify the physical cause of this injury. Today the diagnosis has changed to blast shock, it properly is named because it is the blast that has been discovered to cause the damage to the brain. An autopsy was done on 8 soldiers who had died after suffering blast shock. In each brain, scare tissue was discovered. This was different from the damage done from suffering a concussion as athletes do. What was once thought o be psychological may be identified as physical. This new discovery can help t properly identify patient diagnosis and

Some area’s affected by neuronal loss are the cerebral cortex, the hippocampus, locus coeruleus, and cerebellum. Even with a single TBI, neuronal loss does occur, and evidence suggests this neuronal loss continues beyond the initial injury phase. White matter degeneration does occur as well, and while this study has little information on this, it is noted that white matter injury as well as axonal pathology has been suggested as a mechanism of rapid Aβ genesis. Also seen in neurodegeneration is neuroinflammation that is beyond repair. This inflammation continues after the initial injury in the white matter region, including the corpus callosum. Finally, changes in the cerebellar pathology are noted, in particular loss of cerebellar neurons. Smith, Johnson, & Stewart (2013) note atrophy and demyelination of the folial white matter present in those affected by

The human body is such an amazing structure that it is able to cope with trauma and destruction at extraordinary levels. We have become immune to hearing about the survivals of horrific falls, terrifying crashes and those who have survived accidents which are life threatening. Although, the survivors of these incidents rarely walk away unchanged, whether that be mentally or physically.

the two pathways and it requires that all factors are present within the blood for clotting

Inflammation normally occurs as a second response when damage tissues. Inflammation can occur immediately however

Several mechanisms explaining the mechanism by which MSCs exert their therapeutic effect in neurological disorders have been proposed. Currently, the must accepted hypothesis is that MSCs exert their neuroprotective action mainly through a paracrine-mediated mechanism. In fact, MSCs have the capacity to secret a plethora bioactive factors (secretome), including neurotrophic growth factors, chemokines, interleukins or cytokines, extracellular proteins and extracellular vesicles, which promote injured tissues repair and regeneration (Caplan and Correa, 2011; Maltman, Hardy and Przyborski, 2011; Paul and Anisimov, 2013).

Melanie Reece presented on Blast induced neurotrauma, which can cause damage to the brain and cause permanent damage. Research regarding Blast induced Neurotrauma started around WW1, most cases were regarding shell shock. Blast induced traumatic brain injury (BINT) can cause damaging effects that linger on, after the initial shock, mainly due to the impact on specific areas in the brain. BINT’s have different types of severity, ranging from mild to severe.

The homeostasis of the brain depends heavily on efficient energy metabolism. A number of studies have shown the role of inflammatory mediators such as nitric oxide, NF-κB, and proinflammatory cytokines play a key role in the impairment central nervous system function, thereby leading to the development of several neuroinflammatory and neurodegenerative disorders. Although not much emphasizes has been made in understanding the role of neural-immune aspect of inflammatory mediators and leukocytes infiltration in the development of glioblastoma. Therefore, understanding the role of choroid plexus and leukocytes infiltration and its association with energy metabolism in cancer will lead us in understanding the role of neural-immune interaction in the development of glioblastoma. Dr. Ellora Sen’s research work has caught my attention with her work on neuroinflammation and metabolism in glioblastoma. I believe my previous research experience in working in the area of neuroimmunology, metabolism and cancer make me a suitable candidate for this position and I would enjoy the opportunity to work in this project

Circulatory shock is a syndrome of widespread cellular hypoxia, triggered by a systemic alteration of perfusion and delivery and/or utilization of tissue oxygen, eventually causing end-organ dysfunction and death [53]. It can be subdivided into 4 distinct categories according to its primary pathophysiological mechanism, namely cardiogenic, hypovolemic, obstructive and distributive [54]. In the first 3 types, perfusion has changed as a consequence of the cardiac output decrease, whereas distributive types of shock are related to a primary dysfunction of the resistive component of the cardiovascular system. In vasoplegia, vascular tone is reduced and there is a noticeably depressed constrictive response of arterioles to vasoconstrictors, and

The neutrophils are attracted by fibronectine and growth factors which leads to them performing their role of phagocytosis. Phagocytosis allows the neutrophils to engulf all the debris and bacteria that are in and surround the site therefore getting rid of foreign particles and allow a clean environment for the inflammation to being to happen. As a result of the phagocytosis happening this then leads to macrophages replacing neutrophils which come from immature monocytes which are stored in spleen, they secrete growth factors and cytokines which lead onto the next phase of the healing response which is the proliferation phase (Frederic H. Martni, Judi L. Natch, Edwin F. Bartholomew, 2014).