An 85-year-old man is transferred to the hospital from a nursing home due to fever and confusion. On arrival, the patient is admitted directly to the intensive care unit with a presumptive diagnosis of septic shock. Antibiotic therapy is initiated. The patient is unable to provide any history, but his caretakers state that he has had nonspecific symptoms, including fever, for the past few days. The patient has a history of cardiovascular disease, diverticulitis, and dementia. Blood pressure is 60/40 mm Hg despite aggressive intravenous hydration. Intravenous norepinephrine is administered in response to the patient's hypotension. Which of the following cellular changes is most likely to occur in direct response to the medication?

Question

An 85-year-old man is transferred to the hospital from a nursing home due to fever and confusion.  On arrival, the patient is admitted directly to the intensive care unit with a presumptive diagnosis of septic shock.  Antibiotic therapy is initiated.  The patient is unable to provide any history, but his caretakers state that he has had nonspecific symptoms, including fever, for the past few days.  The patient has a history of cardiovascular disease, diverticulitis, and dementia.  Blood pressure is 60/40 mm Hg despite aggressive intravenous hydration.  Intravenous norepinephrine is administered in response to the patient's hypotension.  Which of the following cellular changes is most likely to occur in direct response to the medication?

Quizplus · Accepted Answer

11ec160b_3b9f_75a9_9249_6d7929ce81dc_MD0001_00 Stimulation of adrenoreceptors leads to a change in concentration of a second messenger (eg, cAMP), which mediates the effects on the target organ. Norepinephrine, an adrenergic agonist, is the preferred pharmacologic treatment for septic shock as it predominately stimulates a1, a2, and B1 receptors, with little influence on B2 receptors. This leads to the following clinical effects: Stimulation of α1 adrenoreceptors leads to vasoconstriction in the skin and viscera, resulting in increased systolic and diastolic blood pressure with decreased renal and hepatic blood flow. α1-mediated vasoconstriction occurs via the IP₃-second messenger pathway. Stimulation of β1 adrenoreceptors within the heart increases cAMP concentrations through G_s-mediated receptor coupling, which leads to increased cardiac contractility, conduction, and heart rate. However, the direct effect of norepinephrine on heart rate is counteracted by an indirect, baroreceptor-mediated reflex bradycardia that occurs following the increase in peripheral resistance. The combined result of these effects is often an unchanged or even decreased heart rate. Stimulation of α2 adrenoreceptors causes a decrease in cAMP in pancreatic β cells and in the intestines, resulting in decreased insulin secretion and reduced intestinal motility. Central α2 adrenoreceptors are not stimulated by intravenous administration of norepinephrine as the molecule does not cross the blood-brain barrier. (Choice A) Stimulation of β2 adrenoreceptors in bronchial smooth muscle cells leads to increased, rather than decreased, cAMP synthesis, resulting in bronchodilation. Regardless, norepinephrine does not significantly stimulate β2 adrenoreceptors. (Choices C and D) Norepinephrine-mediated stimulation of α1 adrenoreceptors increases, rather than decreases, IP₃ (increased calcium release) and DAG concentrations in vascular smooth muscle cells. cAMP is increased after β2 adrenoreceptors are stimulated; however, because norepinephrine does not significantly stimulate β2 adrenoreceptors, cAMP concentrations in vascular smooth muscle are not increased. (Choice E) A significant elevation in IP₃ concentration does not occur in cardiac muscle cells following norepinephrine administration. The cardiac effects of norepinephrine are primarily mediated by β1 adrenoreceptors that are linked to a cAMP, rather than IP₃, signal transduction pathway. Educational objective: Norepinephrine stimulates cardiac β1 adrenoreceptors, which increases cAMP concentration within cardiac myocytes and leads to increased contractility, conduction, and heart rate. Peripheral vasoconstriction occurs via stimulation of α1 adrenoreceptors in vascular smooth muscle cells and activation of an IP₃ signaling pathway. __________ References: Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. (http://www.ncbi.nlm.nih.gov/pubmed/20670424)

An 85-Year-Old Man Is Transferred to the Hospital from a Nursing