A 54-year-old woman comes to the emergency department due to a 2-day history of fevers, chills, and severe fatigue. She has no chronic medical problems and takes no medication. Temperature is 38.9 C (102 F), blood pressure is 80/50 mm Hg, pulse is 130/min, and respirations are 20/min. The patient's left flank is tender to palpation. Cardiovascular examination reveals tachycardia, decreased capillary refill, and an estimated jugular venous pressure of 3 cm H2O above the sternal notch. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 12 g/dL |
| Platelets | 240,000/mm3 |
| Leukocytes | 19,000/mm3 |
| Neutrophils | 90% |
| Eosinophils | 1% |
| Lymphocytes | 9% |
| Serum chemistry | |
| Blood urea nitrogen | 24 mg/dL |
| Creatinine | 1.7 mg/dL |
| Urinalysis | |
| Nitrites | positive |
| White blood cells | 100+/hpf |
Which of the following is most likely decreased in this patient?
This patient with pyelonephritis (eg, flank pain, pyuria) has likely developed sepsis (eg, fever, peripheral blood leukocytosis). Sepsis is a florid host inflammatory response to an infectious pathogen that can lead to widespread dysfunction of multiple organ systems. Cardiovascular manifestations include profound vasodilation resulting in low systemic vascular resistance and hypotension. Refractory hypotension (ie, vasoplegia) despite adequate intravascular volume (ie, normal jugular venous pressure), as in this patient, indicates progression to septic shock.
Septic shock is an extreme manifestation of sepsis, in which vasodilatory mediators overwhelm endogenous vasoconstrictor mechanisms. Key vasodilators include nitric oxide and prostaglandins; their production is upregulated by acute-phase cytokines such as tumor necrosis factor-α, IL-1, and IL-6 released from innate immune cells and endothelium exposed to bacterial cell wall glycoproteins and endotoxins (Choices C and D).
The normal physiologic response to hypotension is compensatory secretion of vasopressin (antidiuretic hormone) by the posterior pituitary. In addition to promoting water retention (via renal collecting duct V2 receptors), vasopressin is one of the most potent vasoconstrictors (via arteriolar smooth muscle V1 receptors). In septic shock, however, vasopressin is suppressed, possibly due to impaired baroreceptor reflexes and/or depletion of endogenous stores.
For this reason, infusion of vasopressin can be helpful during treatment of septic shock, often decreasing the need for other pharmacologic vasoconstrictor agents (eg, norepinephrine).
(Choice A) C-reactive protein is an acute-phase protein produced in the liver in response to inflammation; it activates the classical complement pathway and promotes phagocytosis, thereby facilitating clearance of bacteria and cellular debris. Levels of C-reactive protein are elevated in sepsis.
(Choice B) Endotoxin (lipopolysaccharide) is a cell wall component of gram-negative bacteria that triggers an acute inflammatory response by binding to toll-like receptor 4 on immune cells. The vast majority of urinary tract infections are caused by gram-negative bacteria, and nitrite production is generally exclusive to gram-negative bacteria; therefore, endotoxin concentrations are likely markedly elevated in this patient.
Educational objective:
Septic shock is a dysfunctional host response to an infectious pathogen resulting from massive upregulation of vasodilators. A vasopressin deficit contributes to unbalanced vasodilation and refractory hypotension.