Systemic Response To Injury And Metabolic Support Flashcards
The vagus nerve mediates which of the following in the setting of systemic inflammation?
A. Enhanced gut motility
B. Decreased protein production by the liver
C. Decreased tumor necrosis factor (TNF) production
D. Increased HR to increase CO
A.
The vagus nerve exerts several homeostatic influences, including enhancing gut motility, reducing HR and regulating inflammation. Central to this pathway is the understanding of neurally controlled anti-inflammatory pathways of the vagus nerve. Parasympathetic NS activity transmits vagus nerve efferent signals primarily through the NT acetylcholine. This neurally mediated anti-inflammatory pathway allows for a rapid response to inflammatory stimuli and also for the potential regulation of early proinflammatory mediator release, specifically TNF. Vagus nerve activity in the presence of systemic inflammation may inhibit cytokine activity and reduce injury from disease processes such as pancreatitis, ischemia and reperfusion and hemorrhagic shock. This activity is primarily mediated through nicotinic acetylcholine receptors on immune mediator cells such as tissue macrophages. Furthermore, enhanced inflammatory profiles are observed after vagotomy during stress conditions.
Cytokines are which type of hormone? A. Polypeptide B. Amino acid C. Fatty acid D. Carbohydrate
A.
Cytokines are polypeptide hormones. Humans release hormones in several chemical categories including polypeptides (cytokines, glucagon, and insulin), amino acids (epinephrine, serotonin and histamine) and fatty acids (glucocorticoids, prostaglandins and leukotrienes). There are no carbohydrate hormones.
Which of th following is a function of heat shock proteins?
A. Binding of autologous proteins to improve ligand binding
B. Induction of the white cell oxidative burst
C. Binding to capillary endothelium to prevent fluid extravasation
D. Stabilization of membranes to prevent cell lysis
A.
Heat shock proteins (HSPs) are a group of intracellular proteins that are increasingly expressed during times of stress such as burn injury, inflammation and infection. HSPs participate in many physiologic processes including protein folding and protein targeting. The formation of HSPs requires gene induction by the heat shock transcription factor. HSPs bind both autologous and foreign proteins and thereby function as intracellular chaperones for ligands such as bacterial DNA and endotoxin. HSPs are presumed to protect cells from the deletious effects of traumatic stress and when released by damaged cells, alert the immune system of the tissue damage.
Which of the following is an eicosanoid? A. TNF B. Arachidonic acid C. Thromboxane D. IL-10
C.
Thromboxane is an eicosanoid. Arachidonic acid is one of two precursors of the eicosanoids. TNF and IL-10 are cytokines. Eicosanoids are derived primarily by oxidation of the membrane phospholipid arachidonic acid (eicosatetraenoic acid) and are composed of subgroups including prostaglandins, prostacyclins, hydroxyeicosatetraenoic acids (HETEs), thromboxane and leukotrienes. The synthesis of arachidonic acid from phospholipids requires the enzymatic activation of phospholipase A2. Products of the COX pathway include all of the prostaglandins and thromboxanes. The lipoxygenase pathway generates leukotrienes and HETE. Eicosanoids are produced primarily through teo major pathways: 1. with arachidonic acid (omega-6-fatty acid) as substrate and 2. eicosapentaenoic acid (omega-3 fatty acid) as substrate.
Omega-3 fatty acids have which of the following effects on the inflammatory response?
A. Increased inflammatory response
B. Decreases inflammatory response
C. Delayed inflammatory response
D. No effect on the inflammatory response
B.
Omega-3 fatty acids have specific anti-inflammatory effects including inhibition of NF-B activity. TNF release from hepatic Kupffer cells as well as leukocyte adhesion and migration. The anti-inflammatory effects of omega-3 fatty acids on chronic autoimmune diseases such as rheumatoid arthritis, psoriasis and lupus have been documented in both animals and humans. In experimental models of sepsis , omega-3 fatty acids inhibit inflammation, ameliorate weight loss, increase small bowel perfusion and may increase gut barrier protection. In human studies, omega-3 supplementation is associated with decreased production of TNF, interleukin-1b and interleukin-6 by endotoxin stimulated monocytes. In a study of surgical patients, preoperative supplementation with omega-3 fatty acid was associated with reduced need for mechanical ventilation, decreased hospital length of stay and decreased mortality with a good safety profile.
Which of the following known effects of TNF?
A. Decreases catabolic response
B. Promotes insulin entry into cells
C. Enhances the expression of eicosanoids
D. Delays activation of the coagulation pathway
C.
TNF is a cytokine that is rapidly mobilized in response to stressors such as injury and infection and is a potent mediator of the subsequent inflammatory response. TNF is primarily synthesized by macrophages, monocytes and T cells which are abundant in peritoneum and splanchnic tissues. Although the circulating half-life of TNF is brief, the activity of TNF elicits many metabolic and immunomodulatory activities. TNF stimulates muscle breakdown and cachexia through increased catabolism, insulin resistance ans redistribution of amino acids to hepatic circulation as fuel substrates. In addition, TNF also mediates coagulation activation, cell migration and macrophage phagocytosis and enhances thr expression of adhesion molecules, prostsglandin E2, platelet-activating factor, glucocorticoids and eicosanoids.
Which of the following are adhesion molecules (cells that mediate leukocyte to endothelial adhesion)?
A. Platelet activating factor
B. L-selectin
C. Transforming growth factor beta (TGF-b)
D. Tumor necrosis factor (TNF)
B.
There are 4 families of adhesions molecules: selectins, immunoglobulins, beta (CD18) integrins and beta (CD29) integrins. L-selectin is a member of the selectin family of adhesion molecules. Platelet activating factor is a phospholipid which mediates leukocyte function but does not contribute to adhesion. TGF-b is a polypeptide growth factor which is upregulated in some malignant tumors. TNF is a cytokine which is upregulated in inflammatory conditions but which does not play role in adhesion in leukocyte to endothelium.
The primary physiologic effect of nitric oxide is?
A. Increased platelet adhesion
B. Increased leukocyte-endothelial adhesion
C. Increased microthrombosis
D. Increased smooth muscle relaxation
D. Nitric oxide (NO) was initially known as endothelium-derived relaxing factor due to its effect on vascular smooth muscle and has important function in both physiologic and pathologic control of vascular tone. Normal vascular smooth muscle relaxation is maintained by a constant output of NO and subsequent activation of soluble quanylyl cyclase. NO also can reduce microthrombosis by reducing platelet adhesion and aggregation. NO easily tranverses cell membranes and has a short half-life of a few seconds and is oxidized into nitrate and nitrite. NO is constitutively expressed by endothelial cells, however, inducible NO synthase which is normally not expressed is upregulated in response to inflammatory stimuli which increases NO production. Increased NO is detectsble in septic shock and in response to TNF, IL-1, IL-2 and hemorrhage. NO mediates hypotension observed during septic shock, however a clinical trial of nonselective NOS inhibitor showed incressed organ dysfunction and mortality.
Prostacyclin has which of the following effects in systemic inflammation? A. Inhibition of platelet aggregation B. Vasoconstriction C. Increased adhesion molecules D. Decreased cardiac output
A.
Prostacyclin is a member of the eicosanoid family and is primarily produced by endothelial cells. Prostacyclin is effective vasodilator and also inhibits platelet aggregation. During systemic inflammation, endothelial prostacyclin expression is impaired, and thus the endothelium favors a more procoagulant profile. Prostacyclin therapy during sepsis has been shown to reduce the levels of cytokines, growth factors and adhesion molecules through a cAMP-dependent pathway. In clinical trial, prostacyclin infusion is associated with increased cardiac output, splanchnic blood flow and oxygen delivery and consumption with no significant decrease in mean arterial pressure. However further study is required before the widespread use of prostacyclin is recommended.
How many calories per day are required to maintain basal metabolism in a healthy adult? A. 10-15 kcal/kg/day B. 20-25 kcal/kg/day C. 30-35 kcal/kg/day D. 40-45 kcal/kg/day
B.
To maintain basal metabolic needs (at rest and fasting) a normal healthy adult requires approximately 22-25 kcal/kg/day drawn from carbohydrate, lipid, and protein sources.
The primary source of calories during acute starvation (
A.
In the healthy adult, principal sources of fuel during short-term fasting (
Which of the following is the primary fuel source in prolonged starvation? A. Fat B. Muscle (protein) C. Glycogen D. Ketone bodies
D.
In prolonged starvation, systemic proteolysis is reduced to approximately 20 g/d and urinary nitrogen excretion stabilizes at 2-5 g/d. This reduction in proteolysis reflects the adaptation by vital organs (myocardium, brain, renal cortex and skeletal muscle) to using ketone bodies as their principal fuel source. In extended fasting, ketone bodies become an important fuel source for the brain after 2 days and gradually become the principal fuel source by 24 days.
Which of the following is the primary fuel source after acute injury? A. Fat B. Muscle (protein) C. Glycogen D. Ketone bodies
A.
Lipids are not merely nonprotein, noncarbohydrate fuel sources that minimize protein catabolism in the injured patient. Lipid metabolism potentially as well as the immune respinse during systemic inflammation. Adipose stores within the body (triglycerides) sre the predominant energy source (50-80%) during critical illness and after injury. Fat mobilization (lipolysis) occurs mainly in response to catecholamine stimulus of the hormone-sensitive triglyceride lipase. Other hormonal influences which potentiate lipolysis include adrenocorticotropic hormone (ACTH), catecholamines, thyroid hormone, cortisol, glucagon, growth hormone release, reduction in insulin levels and increased sympathetic stimulus.
Sepsis increases metabolic needs by approximately what percentage? A. 25% B. 50% C. 75% D. 100%
B.
Sepsis inceases metabolic needs to approximately 150-160% of resting energy expenditure or 50% above normal. The magnitude of metabolic expenditure appears to be directly proportional to the severity of insult with thermal injuries and severe infections having the highest energy demands. The increase in energy expenditure is mediated in part by sympathetic activation and catecholamine release, which has been replicated by the administration of catecholamines to healthy human subjects.
What is the most abundant amino acid in the human body? A. Leucine B. Tyrosine C. Glutamine D. Alanine
C.
Glutamine is the most abundant amino acid in the human body comprising nearly two thirds of the free intracellular amino acid pool. Of this, 75% is found within the skeletal muscles. In healthy individuals, glutamine is considered a nonessential amino acid because it is synthesized within the skeletal muscles and the lungs. Glutamine is a necessary substrate for nucleotide synthesis in most dividing cells and hence provides a major fuel source for enterocytes. It also serves as an important fuel source for immunocytes such as lymphocytes and macrophages and is a precursor for glutathione, a major intracellular antioxidant.
