Case Introduction Brian, a 21 year old in excellent health, was recently involved in a stunt which involved jumping through a loop of fire. No one is sure what drove him to this crazy act, but it was partly due to his involvement in the television show: Most Extreme Elimination Challenge. He is treated for 2nd and 3rd degree burns on his arms and legs. However, while in ICU he developed a severe bacterial infection because his immune system was compromised. Brian’s systemic over response to the infection resulted in severe sepsis, also known as septic shock. This over-response to the infection disrupted homeostasis through an uncontrolled cascade of inflammation, coagulation, and impaired fibrinolysis. He presented himself to physicians (Phil, Zainab, and Rachel) with severe pain and discomfort. He was shivering with “the chills" and is in obvious respiratory distress evident by his hyperventilation. A blood culture test revealed that bacteria was present in Brian’s blood. Secondary to his infection, Brian has developed systemic edema in his legs. He said that he feels dizzy and was also acting delirious. He complains of an inability to urinate. (You may our video presentation at this link. We hope you enjoy it.) Sepsis Movie Presentation

Data Physical Examination: Temperature: 103.8° (Normal: 98.6°F) Blood Pressure: 90/55 (Normal: 120/80) Heart rate: 100 bpm (Normal: 70 bpm) Respiratory rate: 22 breaths/min (Normal: 12 breaths/min) Lab Results: Creatinine: high Platelet count: low WBC count: 12,500/mm3 pH: 7.34 (Normal: 7.4)

Questions to guide your learning How did Brian develop the severe infecton? Why is there lack of perfusion in his vasculature? What is the cardiovascular's system response to impairment in blood distribution? How does the renal respond to decreased blood flow? How does the respiratory system respond to decrease oxygen delivery?

Learning Objectives To understand how severe infections arise when the body's immune sytem is compromised. To understand the symptoms of an infection to the bloodstream To understand how to diagnose a severe infection To understand how a severe infection affect the cardiovascular, renal and respiration system. To understand how each system responds to such changes. To understand how all the system's are interrelated and disruption to one affects another. To understand what the available treatments are.

Cardiovascular Response to Sepsis The overwhelming infection of the bloodstream is causing low blood pressure and low blood flow due to lack of perfusion in the vasculature. The effect seen in blood pressure and blood flow are caused by blood clots due to coagulation, inflammation and impairment in fibrinolysis. In response to the inflammation, nitric oxide is synthesised by inducible nitric oxide synthase in the vascular endothelium and smooth muscle. The release of nitric oxides leads to vasodilation thus causing a fall in the systemic vascular resistance. Via the Frank-Starling mechanism, the patient will experience an increase in cardiac output to maintain blood pressure. The baroreceptors will mediate the response by increasing heart rate and stroke volume due to decreased afterload, but hypovolemia may decrease preload and thus cardiac output. This is why patients will often exhibit a decrease in blood pressure despite an increase in heart rate. All of these interferences to normal blood delivery will cause an abnormal distribution of systemic blood flow to organ systems causing core organs to not receive appropriate oxygen delivery and thus lead to multiple organ failure. Eventually, the patient will develop biventricular systolic and diastolic dysfunction. Patients will often develop systemic edema as a result of the structural decrease in the permeability of the endothelium allowing inflammatory cells and their products to leave the circulation.

Renal Response to Sepsis The most common complication of the renal system due to sepsis is acute renal failure. Since the renal system maintains renal blood flow and glomerular filtration through the afferent and efferent arterioles, the significant decrease in blood pressure result in renal hypoperfusion. Renal hypoperfusion results in decreased blood filtration and therefore a decreased urine output. The decreased glomerular filtration rate, elevated levels of creatinine, and the decreased oxygen delivery all give rise to acute renal failure.

Respiratory Response to Sepsis Pulmonary dysfunction is common in patients suffering from severe sepsis. The low blood pressure that is common in patients with sepsis lead to a decreased oxygen delivery to the tissues. The lack of gas exchange cause a build up of carbon dioxide, this is why the patient is often hyperventilating and thus in respiratory acidosis. Since the patient is accumulating carbon dioxide, the pH of the patient's blood will thus be acidic. The alteration in gas exchange result in tissue hypoxia and lactic acidosis.

Case Summary Brian's systemic over response to the infection resulted in severe sepsis. Some of his symptoms were decreased blood pressure, increased heart rate, decreased urine output and hyperventilation. The low blood pressure leads to decreased oxygen delivery and hypoxia. The lack of gas exchange cause a build up of carbon dioxide, this is why the patient is hyperventilating. Since the patient is accumulating carbon dioxide, the pH of the patient's blood will be acidic. The most common complication due to sepsis is acute renal failure. Since renal blood flow and glomerular filtration is maintained by the arterioles, the decrease in blood pressure result in renal hypoperfusion and eventually ARF. The overwhelming infection of the bloodstream is causing low blood pressure and low blood flow due to lack of perfusion. Via the Frank-Starling mechanism, the patient will experience an increase in cardiac output. The baroreceptors will mediate the response by increasing heart rate and stroke volume due to decreased afterload, but hypovolemia may decrease preload and thus cardiac output. This is why patients will often exhibit a decrease in blood pressure despite an increase in heart rate. All of these interferences lead to abnormal distribution of blood and thus multiple organ failure. Patient's are treated with antibiotic therapy, oxygen supply, intravenous fluids, and medications that increase blood pressure. The patient will require dialysis in the event of kidney failure and mechanical ventilation in case of respiratory failure. With proper care, patient will resume a healthy lifestyle.

References (used and suggested) Shelton M.D., Ronald. Telephone interview. 29 Nov. 2005. Paterson, R L., and N R. Webster. "Sepsis and the inflammatory response syndrome." Educational Review. June 2000. University of Aberdeen. 1 Dec. 2005 <http://http://www.rcsed.ac.uk/Journal/vol45_3/4530010.htm>. "Sepsis Overview." Sepsis. 2005. Eli Lilly & Company. 12 Nov. 2005 <http://www.sepsis.com>. Bone, Roger. Promoting A Better Understanding of Sepsis. International Sepsis Forum, Nov. 2003, Eli Lilly Corporation. London, 2003. Symeonides, S, and R A. Balk. "Nitric Oxide in the pathogenesis of sepsis." Infectious Disease Clinics of North America 13 (1999): 449-463.