This is the case study of Mr. Jones, a 65 year old male, who was admitted to the emergency department with persistent cough and episodes of chest pain over the last five days. He appeared to be experiencing worsening dyspnoea, fever and feeling unwell. It was also noted that he had a poor urine output over the last 24 hours. An indwelling catheter was inserted which only obtained 20 mLs of amber urine. Mr. Jones clinical assessment revealed that his Glasgow Coma Score was 11/15.
He was opening his eyes to speech, only making inappropriate words and localizes to pain. He was also pyrexial with a temperature of 39. 0 ? C, diaphoretic with hot peripheries, hypotensive BP 90/45 mmHg (MAP 60 mmHg), and tachyopneic at 30breaths/min and tachycardic at 120beats/min. This paper will not only define SIRS/sepsis but will also discuss the clinical manifestations in relation to the pathophysiology of systemic inflammatory response syndrome (SIRS)/sepsis in relation to Mr. Jones. Mr. Jones appeared to be in distressed.
He is now using his accessory muscles to breathe, crackles are heard on auscultation and there is decreased air entry in the left and right bases. Chest X ray revealed consolidation on the left lower lobe and atelectasis in the right lower lobe. After a series of investigation in the emergency department, Mr. Jones was commenced on Normal Saline at 125 mls/hr and he was given oxygen via non rebreather mask at 10L/min. He was then transferred to the intensive care unit for respiratory and circulatory support and a provisional diagnosis of sepsis due to a respiratory source.
Sepsis is a condition characterized by a systemic inflammation response syndrome (SIRS) and the presence of infection (Steen 2009:48). This is the cascade of inflammatory events that are part of the body’s response to an insult in an attempt to maintain homeostasis (Lever and Mackenzie, 2007:879). Systemic inflammatory response syndrome (SIRS) is a systemic reaction to infection as evidenced by two or more of the following symptoms: Temperature > 38? C or < 36? C; Heart rate > 90 beats per minute;
Respiratory rate > 20 breaths per minute; White blood count > 12,000 or < 4000 per ml (Levy et al, 2003:1250). In December 2001, the American College of Chest Physician (ACCP), the Society of Critical Care Medicine (SCCM), American Thoracic Society and European Society of Intensive Care Medicine met and expanded this list of signs and symptoms to include chills, decreased urine output, decreased skin perfusion, poor capillary refill, skin mottling, decreased platelet count, petechiae, hypoglycaemia, and unexplained change in mental state (Urden, et al. 006:1023). When a confirmed systemic response to infection is associated with SIRS, sepsis has developed (Wagenlehner et al. 2007:30). Sepsis can be caused by pathogens other than bacteria, such as fungi, viruses, and protozoa (Munford, 2001:63). Regardless of the causative organism, sepsis can result in systemic complications that occur as circulating chemical mediators released by the inflammatory response compromised the patients cardiovascular system (Cunha, 2003:24).
Severe sepsis occurs when hypoperfusion, hypotension and organ dysfunction develop. If hypotension and perfusion abnormalities, lactic acidosis, oligoria and acute onset of mental deterioration occur despite aggressive fluid resuscitation and inotropic therapy, septic shock is present (Munford, 2001:65). Mr. Jones CX-ray confirmed to have consolidation on the left lower lobe and atelectasis in the right lower lobe. Respiratory infection is the likelihood of the source of sepsis in Mr. Jones’s case.
Once a microbial infection develops, a general but complex inflammatory response develops, resulting in increased capillary permeability and blood flow (Urden et al. 2006:1032). These responses allow immunologic cells to migrate toward the site of infection; phagocytic actions begin and activate the complement system. Munford 2001 states that once the complement system is activated, more WBC’s come to the site of infection and as many as 40 inflammatory mediators are released. Mr. Jones white cell count is elevated and revealed at 1400 mm while his CRP is also raised.
Cytokinines are the one of the primary mediators that signal other cells to release additional mediators such as tumour necrosis factor-a (TNF-a) interleukin (IL)-1, IL-6, IL-8, interferon, leukotrienes, histamine, bradykinin, prostaglandins, thromboxane A2, serotonin, nitric oxide, arachidonic acid, platelet-activating factor (PAF), oxygen free radicals and myocardial depressant factor (Munford, 2001:67). If the invading organism is a gram negative bacterium, endotoxins are also released, which further stimulate the production of these inflammatory mediators (Jones & Bucher, 1999:134).
Tumour necrosis factor (TNF) is responsible for the disruption of the tight junction between endothelial cells which results in an increased permeability to plasma proteins and fluid, which worsens fluid accumulation in the alveoli further impairing gas exchanged (Bersten & Soni, 2009:709). TNF comprises of two different molecules, firstly TNFa which leads to programmed cell death in target cells, and when combined with IL-1 which acts on the central nervous system causing lethargy (Marieb, 2004).
TNFB stimulates granulocyte activity and B cell proliferation which shows an increase in neutrophil count (Jean- Baptise, 2007:63). Monocytes, macrophages, lymphocytes, astrocytes and endothelial cells secrete IL-1 which promotes fever, anorexia, sleep and hypotension (Jean-Baptise, 2007:64). Certain prostaglandins thromboxane A2, a vasoconstrictor, protacyclin, a vasodilator and prostaglandin E2 participate together in the generation of fever, tachycardia, ventilation perfusion abnormalities and lactic acidosis (Porth, 2005).
Leukocytes and macrophages secrete pyrogens which increases body temperature, decreases haemoglobin affinity for oxygen, worsening hypoxia (Marieb, 2004). Sepsis producing endotoxins TNFa and IL-1 or PAF may cause tissue damage by directly activating nitric oxide (NO), a free radical and potent vasodilator. NO can accumulate in high numbers and react with other free radicals leading to endothelial damage, further stimulating the inflammatory response (Edwards, 2003:636). In addition, sepsis causes enhanced coagulation with stimulation of the coagulation cascade.
This produces a reduction a reduction in the level of protein C and antithrombin III which results in the formation of micro emboli, further impairing blood flow and organ perfusion (Porth, 2005). Inflammatory mediators cause activation of intrinsic and extrinsic clotting pathways. Thrombosis, intravascular fibrin deposits and bleeding develop. Inhibitory pathways of protein C and Protein S are impaired and depleted and clotting increases in plasminogen activator inhibitor levels. Coagulation factors are depleted, and bleeding worsens. Disseminated intravascular coagulation (DIC) may result (Munford, 2001).
The three major effects of septic shock within the vascular system are vasodilation, maldistribution of blood volume and myocardial depression. Two interacting factors result in vasodilatation in septic shock (Munford, 2001). First, a loss of vascular reaction to sympathetic nervous system stimulation occurs and second, production of substances from the endothelial lining relaxes the vascular smooth muscle layer of the vessels (Urden et al, 2006:1033). Profound dilation in the arterial and venous circulation results and decreases in SVR and preload develop.
Initially, compensation occurs by an increase in cardiac output. However, tissue perfusion continues to decrease due to maldistribution of blood flow and impaired cardiac function (Parillo, 2001). Maldistribution of blood flow develops as a consequence of blood volume displacement from intravascular areas to extracellular spaces. Although septic shock is usually associated with vasodilation, pulmonary, renal, hepatic, splenic and pancreatic vasoconstriction occurs with associated organ dysfunction. Increased capillary permeability allows serum to migrate into the interstitial spaces.
Parenchymal oedema in the pulmonary, cardiac and renal vascular beds results in functional failure of these organs. The interstitial fluid shift also depletes the circulating volume and increases blood viscosity. Blood flow becomes sluggish, WBC’s accumulate and microemboli develop. Vascular occlusion and inadequate tissue perfusion progress. Anaerobic metabolism with elevations in lactic acid levels lead to metabolic acidosis (Melander, 2004: 378). Cellular stress response during septic shock results in down regulation or hibernation of the cell with a shift to fetal gene expression.
Through these actions the cell reverts to a lower energy using state and avoids death. Unfortunately only enough energy is produced to keep the individual cells alive but not enough to continue whole organ function. Multiorgan failure eventually results (Hotchkiss et al. 1999). Mr. Jones GCS is slowly deteriorating. Difficult to arouse is an early cardinal sign of systemic infection and inflammatory response to circulating endotoxins. In a patient with sepsis, the level of consciousness continues to deteriorate with impending shock as a result of decreased cerebral perfusion (Parillo, 2001).
Those with prior neurologic deficits and who are elderly are more likely to experience more pronounced neurologic effects (Munford, 2001:69). Mr. Jones is showing signs of respiratory distress. He was also tachypnoeic with respirations of 30 breaths/min. and is using his accessory muscles to breath and his oxygen saturations were only 89%. Arterial blood gas showed respiratory acidosis. His lungs have to work hard to maintain an adequate gas exchange with increased demand from the body (Wheeler & Bernard, 1999:5).
The lungs become a target organ as septic shock progresses. Circulating endotoxins cause deterioration of the patient’s pulmonary status, as the initial pulmonary response to endotoxins creates bronchoconstriction. Pulmonary oedema as a result of increased capillary permeability occurs. Tachypnoea is also an early cardinal sign of systemic infection, hypoxemia and physiologic stress (Munford, 2001:69). The increased in respiratory rate arises from the subtle changes in acid-base balance, which excite the medulla oblongata to stimulate respiration.
The acid-base changes occur as a result of hypoxia from reduction in oxygen supply to the cells, resulting in hypoperfusion. This results in anaerobic cellular respiration, which results in the production lactate causing a reduction in pH, known as acidosis (Steen 2009:51). Mr. Jones was also indicating some signs of mild renal impairment which showed on his increasing creatinine and decreasing urine output. As the renal blood flow in the patient with septic shock is reduced, urine output decreases. Anti-diuretic hormone and aldosterone are released to increase ntravascular water and sodium in an attempt to maintain cardiac output and renal blood flow, often with no success. Acute tubular necrosis from capillary injury and hypotension contribute to renal failure (Melander, 2004:379). Sepsis is one of the most common causes of acute renal failure in ICU patients (Abernethy & Lieberthal, 2002: 215). These can be due to fluid redistribution, hypoperfusion and circulating nephrotoxins that are released following cell injury. Renal tubular cells are obstructed as a result of cytokine action and coagulation leading to acute tubular necrosis (Schor, 2002:7).
Renal dysfunction is most often diagnosed by adequacy of urine output and the level of excretion of nitrogen waste product (Bellomo et al, 2001: 1685). Mr. Jones was also diaphoretic with hot peripheries. In the early stages of septic shock, vasoactive mediators create a flushed appearance because of peripheral vasodilation. These early stage is known as hyperdynamic or warm septic shock (Urden et al. 2006:1026). His blood pressure is only 90/45mmHg. Hypotension commonly is caused by the vasodilation when cardiac compensation fails (Melander, 2004:379).
Vincent 2001:80 states that septic shock is characterized by hypotension in which adults generally refers to a mean arterial pressure below 65-70 mmHg. Hypotension is usually accompanied by signs of altered tissue perfusion, for example oligoria, reduced capillary refill and altered mental state. He is also tachycardic with a heart rate of 120 bpm. Tachycardia is another early cardinal sign of a systemic infection and inflammatory response. An increase in heart rate is also a compensatory mechanism to maintain perfusion and cardiac output (Urden et al. 2006:1026). Mr.
Jones white cell count revealed 14000 mm. As his sepsis progresses, the inflammatory response signals the bone marrow to accelerate leukocytes synthesis and release. In addition abnormalities in neutrophils can also develop, inducing toxic granulations (Munford, 2001:70). Septic work-up was also done for Mr. Jones. This includes blood, urine and sputum cultures. Chambers (2003) states that gram negative bacteria are the organisms that account for 60% of sepsis in adults. Gram positive are the causative bacteria are the causative organisms 35% at the time, with fungi nd other organisms at 5%. He also state that three blood cultures from different sites should be obtained before starting antimicrobials. Up to 20% to 40% of blood cultures for sepsis from a single site will be negative. Three different samples increase the chance of finding the organisms by 95% (Chambers, 2003). Not mentioned in Mr. Jones investigation was his blood sugar levels. The reaction of the adrenal cortex to septic shock is to release glucocorticoids. The glucocorticoids release glucagon.
Glucagon stimulates the conversion of glycogen to glucose (glycolysis) and gluconeogenesis in the liver. Therefore, the serum glucose level may be elevated. Regulating glucose levels with insulin infusion can reduce morbidity and mortality (Ely et al. 2003:120). Mr. Jones was commenced on Normal Saline 1Litre at the rate of 125 mls/hr. Restoration of adequate intravascular volume is an important aspect of patient care during episodes of hypotension in sepsis. Vasodilation during sepsis dramatically decreases preload and afterload. The vascular tree is too large for the circulating volume.
The circulating volume is also further decreased because increased capillary permeability allows fluid to escape into the interstitial spaces (Munford, 2001:70). As we have seen, Mr. Jones has multiple pathological processes taking place manifested in his presenting signs and symptoms which lead to the diagnosis of sepsis. This paper had discussed the pathophysiology of SIRS and sepsis and incorporates the changes in the body system involved in the sepsis. It has also provided some rationale for some of the changes in relation to the disease process.
