Increasing evidence has implicated gram-negative bacterial lipopolysaccharide (LPS endotoxin) as the portion of the gram-negative bacterial cell membrane responsible for many, if not all the toxic effects that occur during gram-negative bacterial sepsis. The following statement(s) is/are true concerning LPS and the host response. a. The LPS molecule can in itself cause physiologic responses similar to that seen during gram-negative bacterial sepsis b. LPS triggers host macrophages to release a variety of cytokines including TNF-a, IL-1a, and IL-1b, IL-6, and IFN-a c. Excessive cytokine production is not associated with detrimental consequences d. TNFa and IL-1b appear to be the primary mediators within the host, exerting deleterious effects on the host when excessive amounts reach the syst

Increasing evidence has implicated gram-negative bacterial lipopolysaccharide (LPS endotoxin) as the portion of the gram-negative bacterial cell membrane responsible for many, if not all the toxic effects that occur during gram-negative bacterial sepsis. The following statement(s) is/are true concerning LPS and the host response. a. The LPS molecule can in itself cause physiologic responses similar to that seen during gram-negative bacterial sepsis b. LPS triggers host macrophages to release a variety of cytokines including TNF-a, IL-1a, and IL-1b, IL-6, and IFN-a c. Excessive cytokine production is not associated with detrimental consequences d. TNFa and IL-1b appear to be the primary mediators within the host, exerting deleterious effects on the host when excessive amounts reach the systemic circulation
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Answer: a, b, d  The LPS molecule exerts diverse effects on the mammalian host. Immunologic responses to LPS include nonspecific polyclonal B-cell proliferation, macrophage activation and cytokine secretion, tolerance to subsequent LPS or bacterial challenge, and production of antibody directed against various portions of the LPS molecule after repeated challenge. Physiologic responses similar to those seen during gram-negative bacterial sepsis occur during LPS administration alone and include hypotension, hypoxemia, acidosis, bacterial translocation across the gut, complement and coagulation cascade activation, white blood cell and platelet margination, and death. Indirect effects result from LPS-triggering of host macrophages. Activated macrophages secrete a wide array of cytokines that include TNF-a, IL-1a, and IL-1b, IL-6 and interferon-a (IFNa). Excessive secretion of cytokines produce substantial systemic effects in the mammalian host. TNFa and IL-1b appear to be the primary mediators within the local host milieu, exerting deleterious effects on the host only after large amounts are secreted and reach the systemic circulation
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Cytokines are low-molecular-weight polypeptides exerting a wide variety of biologic effects at both local and systemic levels. Which of the following statement(s) is/are true concerning the production and actions of cytokines? a. Cytokines are produced solely by macrophages b. Cytokines act only on other cells within the same local environment c. Cytokines may have both protective and deleterious effects on the host d. Each specific cytokine is produced by a single cell type

Description : Cytokines are low-molecular-weight polypeptides exerting a wide variety of biologic effects at both local and systemic levels. Which of the following statement(s) is/are true concerning the production and ... effects on the host d. Each specific cytokine is produced by a single cell type

Last Answer : Answer: c Macrophages, endothelial cells, lymphocytes, and other cells secrete a large number of different compounds, termed cytokines, that are most probably evolved for the purpose of ... host defenses, exerting both salutatory and deleterious effects on the host, has become increasingly evident

Which of the following statement(s) is/are true concerning tumor necrosis factor (TNF)? a. TNF is a product of activated macrophages secreted in response to contact with endotoxin or lipopolysaccharide, antibody complexes, or inflammatory stimuli b. The liver and gut appear to be a major source of TNF following hypoperfusion c. Circulating levels of TNF correlate well with severity of tissue injury in shock d. Recently completed clinical trials of anti-TNF antibody in septic patients shows a marked improvement in survival

Description : Which of the following statement(s) is/are true concerning tumor necrosis factor (TNF)? a. TNF is a product of activated macrophages secreted in response to contact with endotoxin or ... completed clinical trials of anti-TNF antibody in septic patients shows a marked improvement in survival

Last Answer : Answer: a, b Tumor necrosis factor (TNF), a protein product of activated macrophages, is secreted in response to contact with endotoxin or lipopolysaccharide, antibody complexes, or ... patients utilizing infusion of monoclonal antibodies to the TNF molecule have shown no overall survival benefit

Which of the following statements regarding cytokines is incorrect? A. Cytokines act directly on target cells and may potentiate the actions of one another. B. Interleukin 1 (IL-1) is a major proinflammatory mediator with multiple effects, including regulation of skeletal muscle proteolysis in patients with sepsis or significant injury. C. Platelet-activating factor (PAF) is a major cytokine that results in platelet aggregation, bronchoconstriction, and increased vascular permeability. D. Tumor necrosis factor alpha (TNF-a), despite its short plasma half-life, appears to be a principal mediator in the evolution of sepsis and the multiple organ dysfunction syndrome because of its multiple actions and the secondary cascades that it stimulates.

Description : Which of the following statements regarding cytokines is incorrect? A. Cytokines act directly on target cells and may potentiate the actions of one another. B. Interleukin 1 (IL-1) ... organ dysfunction syndrome because of its multiple actions and the secondary cascades that it stimulates.

Last Answer : Answer: C DISCUSSION: Cytokines are soluble peptide molecules that are synthesized and secreted by a number of cell types in response to injury, inflammation, and infection. Cytokines, which ... is thought to play a central role in the stress response, particularly in response to endotoxemia

The complement system consists of a series of serum proteins that exist in a quiescent or very low-level state of activation in the uninfected host. Which of the following statement(s) is/are true concerning complement activation? a. The alternate (properdin) pathway of complement activation can occur directly through contact with fungal or bacterial cell wall compounds b. Complement component fragments may serve to decrease vascular permeability c. Excessive complement activation can produce deleterious effects d. Fragments of certain complement components serve as chemoattractants to additional cellular components of the host defense mechanism

Description : The complement system consists of a series of serum proteins that exist in a quiescent or very low-level state of activation in the uninfected host. Which of the following ... certain complement components serve as chemoattractants to additional cellular components of the host defense mechanism

Last Answer : Answer: a, c, d Complement activation can occur through either classic or alternate (properdin) pathways, both of which eventuate in deposition of terminal complement pathway components on the ... and release of lysosomal enzymes that can directly damage certain target tissues, such as the lung

Interleukin-6 is recognized as the cytokine primarily responsible for the alteration in hepatic protein synthesis recognized as the acute phase response. Which of the following statement(s) is/are true concerning acute phase protein response to surgical stress? a. Glucocorticoid hormones inhibit this response b. Proteins such as albumin and transferrin which serve in serum transport are generally increased in this response c. Examples of acute phase proteins include fibrinogen and C-reactive protein d. In general, the physiologic role of acute phase proteins are to reduce the systemic effects of tissue damage

Description : Interleukin-6 is recognized as the cytokine primarily responsible for the alteration in hepatic protein synthesis recognized as the acute phase response. Which of the following statement(s) is/are true ... physiologic role of acute phase proteins are to reduce the systemic effects of tissue damage

Last Answer : Answer: c, d IL-6 is now recognized at the cytokine primarily responsible for the alteration in hepatic synthesis recognized as the acute phase response. Glucocorticoid hormones augment ... that generally inhibit the tissue destruction that is associated with the local initiation of inflammation

The neurohormonal arm of the stress response is well defined. Less is known about the inflammatory arm mediated primarily by cytokines. Which of the following statement(s) is/are true concerning this arm of the surgical stress response? a. Cytokines primarily work locally via direct cell-to-cell communication b. Cytokines are never detectable in the systemic bloodstream c. Cytokines are produced only by immune cells attracted to the site of injury d. Cytokine release may stimulate the release of other cytokines leading to an important cascade of events

Description : The neurohormonal arm of the stress response is well defined. Less is known about the inflammatory arm mediated primarily by cytokines. Which of the following statement(s) is/are true ... Cytokine release may stimulate the release of other cytokines leading to an important cascade of events

Last Answer : Answer: a, d Cytokines, which are produced at the site of injury by endothelial cells and by diverse immune cells throughout the body, also occupy a pivotal position in the stress response ... act as hormones and spill over into the systemic circulation and become detectable in the bloodstream

Which of the following statement(s) is/are true concerning the neuroendocrine responses to shock? a. Sympathetic nerve endings release epinephrine which is responsible for greater than 80% of systemic vascular resistance b. Endogenous epinephrine is the primary contributor to systemic vascular resistance c. Increased pancreatic secretion of glucagon contributes to glucose intolerance associated with injury and sepsis d. The renin-angiotensin axis further augments the sympathetic-mediated vasoconstriction

Description : Which of the following statement(s) is/are true concerning the neuroendocrine responses to shock? a. Sympathetic nerve endings release epinephrine which is responsible for greater than 80% ... injury and sepsis d. The renin-angiotensin axis further augments the sympathetic-mediated vasoconstriction

Last Answer : Answer: c, d The neuroendocrine response to shock attempts to achieve restoration of effective blood volume, mobilization of metabolic substrates, and maintenance of central ... . Angiotensin II is an extremely effective vasoconstrictor that further augments sympathetic-mediated vasoconstriction

The initiation of a humoral immune response involves a complex interaction of the antigen, cells and intercellular messengers. Which of the following statement(s) concerning the initiation of the humoral immune response is/are correct? a. Helper T lymphocytes stimulate B lymphocytes through secretion of cytokines such as interleukin 4 and 6 b. A number of cells can aid in presenting the antigen to the helper T cell including B lymphocytes and macrophages c. All antigens require coordinated efforts of the various cellular components of the immune system d. An antigen must be a living microorganism

Description : The initiation of a humoral immune response involves a complex interaction of the antigen, cells and intercellular messengers. Which of the following statement(s) concerning the initiation of the ... various cellular components of the immune system d. An antigen must be a living microorganism

Last Answer : Answer: a, b Stimulation of the immune system occurs after a variety of antigen-presenting cells (B lymphocytes, macrophages, dendritic cells, and Langerhans cells) act to engulf ... polysaccharides), most antigens require coordinated efforts of the various cellular components of the immune system

The following statement(s) is/are true concerning gram-negative bacterial sepsis. a. Mortality due to this condition has almost been eliminated due to therapeutic intervention with antibiotics, aggressive hemodynamic monitoring and fluid resuscitation b. Recent series have noted a decrease in the incidence of this condition c. Predisposing factors include old age, malnutrition, and immunosuppression d. Pseudomonas bacteremia is the most common cause of gram-negative sepsis e. Polymicrobial sepsis is generally considered a more serious problem than sepsis due to a single organism

Description : The following statement(s) is/are true concerning gram-negative bacterial sepsis. a. Mortality due to this condition has almost been eliminated due to therapeutic intervention with antibiotics, aggressive ... sepsis is generally considered a more serious problem than sepsis due to a single organism

Last Answer : Answer: c, e Gram-negative bacterial sepsis is a serious disease process that produces substantial morbidity and mortality in both normal and immunocompromised patients (10% to 20% and ... and most investigators agree that polymicrobial sepsis is more lethal than infection with a single organism

Which of the following statements are true of oxidants? A. In addition to their pathophysiologic roles in inflammation, injury, and infection, oxidants also have physiologic roles. B. Oxidants may be generated from activated neutrophils and during reperfusion following a period of ischemia. C. The deleterious effects of oxidants include lipid peroxidation and cell membrane damage, oxidative damage to DNA, and inhibition of adenosine triphosphate (ATP) synthesis. D. The mechanism of ischemia-reperfusion injury involved the catalytic production of superoxide anion (O 2•) by the enzyme xanthine oxidase.

Description : Which of the following statements are true of oxidants? A. In addition to their pathophysiologic roles in inflammation, injury, and infection, oxidants also have physiologic roles. B. Oxidants may ... involved the catalytic production of superoxide anion (O 2 ) by the enzyme xanthine oxidase.

Last Answer : Answer: ABCD DISCUSSION: Oxidants are reactive oxygen metabolites that have both physiologic and pathophysiologic roles. As potent oxidizing agents, oxidants are involved in cytochrome P ... leukocyte infiltration and activation, causing further tissue damage by the release of cytotoxic proteases

Cytokines which play an important role in the metabolic response to injury include: a. Tumor necrosis factor—a (TNF) b. Interleukin-1 (IL-1) c. Interleukin-6 (IL-6) d. Interferon-g

Description : Cytokines which play an important role in the metabolic response to injury include: a. Tumor necrosis factor—a (TNF) b. Interleukin-1 (IL-1) c. Interleukin-6 (IL-6) d. Interferon-g

Last Answer : Answer: a, b, c, d TNF or cachetin is considered the primary mediator of the systemic effects of endotoxin, producing anorexia, fever, tachypnea, and tachycardia at low doses and hypotension, ... infected sells. IFN-g has the ability to upregulate the number of TNF receptors on various cell types

Which of the following statements are true of the multiple organ dysfunction syndrome (MODS)? A. The “two-hit” model proposes that secondary MODS may be produced when even a relatively minor second insult reactivates, in a more amplified form, the systemic inflammatory response that was primed by an initial insult to the host. B. The systemic inflammatory response syndrome (SIRS), shock due to sepsis or SIRS, and MODS may be regarded as a continuum of illness severity. C. Prolonged stimulation or activation of Kupffer cells in the liver is thought to be a critical factor in the sustained, uncontrolled release of inflammatory mediators. D. The incidence of MODS in intensive care units has decreased owing to increased awareness, prevention, and treatment of the syndrome.

Description : Which of the following statements are true of the multiple organ dysfunction syndrome (MODS)? A. The two-hit model proposes that secondary MODS may be produced when even a relatively ... intensive care units has decreased owing to increased awareness, prevention, and treatment of the syndrome.

Last Answer : Answer: ABC DISCUSSION: MODS is part of a clinical continuum that begins with the systemic inflammatory response syndrome, which is the host's stress response to any major insult such ... pathogenesis of MODS, the incidence of MODS continues to increase without a significant improvement in outcome

Although TPN has major beneficial effects to the patient and specific organ systems, TPN has a downside which is related to intestinal disuse. Which of the following statement(s) is/are true concerning the effects of TPN on the GI tract? a. Patients receiving TPN have an accentuated systemic response to endotoxin challenge compared to enterally fed volunteers b. TPN can result in disruption of intestinal microflora c. In experimental models, bacterial translocation from the gut is increased d. Effects of TPN on the gut may lead to multiple organ failure

Description : Although TPN has major beneficial effects to the patient and specific organ systems, TPN has a downside which is related to intestinal disuse. Which of the following statement(s) is/are true concerning the ... from the gut is increased d. Effects of TPN on the gut may lead to multiple organ failure

Last Answer : Answer: a, b, c, d A number of studies have examined the effects of TPN on intestinal function and immunity. Although most of these studies have been done in animal models, ... the release of bacteria and/or cytokines leading to pronounced systemic responses and possibly multiple organ failure

Which of the following statements about septic shock are true? A. A circulating myocardial depressant factor may account for the cardiac dysfunction sometimes seen with shock due to sepsis or SIRS. B. A cardiac index (CI) of 6 liters per minute per square meter of body surface, a pulmonary capillary wedge pressure of 15 mm. Hg, and a systemic vascular resistance index (SVRI) of 800 dynes-sec/(cm 5-m 2) is a hemodynamic profile consistent with septic shock. C. An increase in SvO 2 in septic patients may be explained by the finding of anatomic arteriovenous shunts. D. Results of human trials employing antimediator therapy, such as antiendotoxin antibodies, IL-1 receptor antagonist, and tumor necrosis factor (TNF) antibodies, have confirmed animal studies that demonstrate a significant im

Description : Which of the following statements about septic shock are true? A. A circulating myocardial depressant factor may account for the cardiac dysfunction sometimes seen with shock due to sepsis or ... animal studies that demonstrate a significant improvement in survival with the use of such agents.

Last Answer : Answer: AB DISCUSSION: Shock due to sepsis or SIRS frequently manifests as a hyperdynamic cardiovascular response, consisting of an elevated CI and a decreased SVR or SVRI. Occasionally, ... been encouraging thus far in human clinical trials, despite the promising results from many animal studies

Which of the following statement(s) is/are true concerning the pulmonary response to shock? a. The acute pulmonary vascular response to shock differs markedly from that of systemic vasculature b. The pulmonary edema of ARDS occurs in the face of elevated left heart pressures c. The initial physiologic changes of ARDS involve the capillary endothelial cells and the type I pneumocyte d. Mechanisms proposed in the pathogenesis of ARDS include injury from mediators of inflammation elsewhere and from activated cellular elements e. A decrease in lung compliance may result from the loss of type I pneumocytes

Description : Which of the following statement(s) is/are true concerning the pulmonary response to shock? a. The acute pulmonary vascular response to shock differs markedly from that of systemic vasculature b. The ... elements e. A decrease in lung compliance may result from the loss of type I pneumocytes

Last Answer : Answer: c, d, e Contributing pathophysiologic processes to the pulmonary manifestations of shock include the pulmonary component of the cardiovascular response, disruption of the normal ... injury from mediators of inflammation elaborated elsewhere, and from activated cellular blood elements

Which of the following statement(s) is/are true concerning the vascular response to injury? a. Vasoconstriction is an early event in the response to injury b. Vasodilatation is a detrimental response to injury with normal body processes working to avoid this process c. Vascular permeability is maintained to prevent further cellular injury d. Histamine, prostaglandin E2 (PGE2) and prostacyclin (PGI2) are important mediators of local vasoconstriction

Description : Which of the following statement(s) is/are true concerning the vascular response to injury? a. Vasoconstriction is an early event in the response to injury b. Vasodilatation is a ... Histamine, prostaglandin E2 (PGE2) and prostacyclin (PGI2) are important mediators of local vasoconstriction

Last Answer : Answer: a After wounding, there is transient vasoconstriction mediated by catecholamines, thromboxane, and prostaglandin F2 (PGF2a). This period of vasoconstriction lasts for only five to ten minutes. Once ... and mast cells and enhance the egress of cells and substrate into the wound and tissue

The following statement(s) is/are true concerning cellular defense mechanisms. a. Macrophages function solely as antigen processing cells in the initial reaction to exposure to an antigen b. Macrophages may become activated and secrete cytokines c. Macrophages serve as phagocytic cells in the tissues but not within the bloodstream d. Polymorphonucleocytes (PMNS) are normally present in only small numbers within the tissue and enter an area of infection through diapedesis

Description : The following statement(s) is/are true concerning cellular defense mechanisms. a. Macrophages function solely as antigen processing cells in the initial reaction to exposure to an antigen b. Macrophages ... in only small numbers within the tissue and enter an area of infection through diapedesis

Last Answer : Answer: b, d A wide variety of cell types serve to provide host defense at several levels. Macrophages act as the initial antigen processing cell that serves to ... through diapedesis after chemotactic stimuli are excluded by macrophages, bacterial breakdown products, and complement activation

Neutrophil chemotaxis is a fundamental aspect of inflammatory injury in conditions such as the Adult Respiratory Distress Syndrome (ARDS). Neutrophil chemotaxis is directly attributable to which of the following molecules? a. C5a b. TNFa c. LPS d. IL-1 e. ENA-78 (Epithelial Neutrophil Activating Protein)

Description : Neutrophil chemotaxis is a fundamental aspect of inflammatory injury in conditions such as the Adult Respiratory Distress Syndrome (ARDS). Neutrophil chemotaxis is directly attributable to which of the following molecules? ... TNFa c. LPS d. IL-1 e. ENA-78 (Epithelial Neutrophil Activating Protein)

Last Answer : Answer: a, e There is a large collection of peptide, polypeptide and lipid mediators which have chemotactic properties. Although TNF a, IL-1 and LPS were initially reported to have direct ... are several complement-derived peptides. Perhaps, the most potent of these is the short-lived C5a peptide

Cytokines with clearly defined actions in acute inflammation and early tissue injury include which of the following? a. Cysteine-X-Cysteine (C-X-C) chemokines b. Tumor Necrosis Factor (TNFa) c. Transforming Growth Factor-b (TGF-b) d. Interleukin-6 (IL-6) e. Platelet Derived Growth Factor (PDGF)

Description : Cytokines with clearly defined actions in acute inflammation and early tissue injury include which of the following? a. Cysteine-X-Cysteine (C-X-C) chemokines b. Tumor Necrosis Factor (TNFa) c. Transforming Growth Factor-b (TGF-b) d. Interleukin-6 (IL-6) e. Platelet Derived Growth Factor (PDGF)

Last Answer : Answer: a, b, c, d, e Polypeptide mediators, such as TNFa and IL-1, are considered early response cytokines and are actively involved in the initiation of the ... of tissue repair. Thus, coagulation and platelet activation provide the initial foundation for subsequent cellular recruitment

Eicosanoids mediate inflammation in a variety of ways. Of the following statements, which are true with regard to this? a. Eicosanoids are stored in cytoplasmic granules for release after receptor mediated signaling b. Eicosanoids include prostaglandins, thromboxanes, leukotrienes and lipoxins c. Eicosanoids generally have a plasma half-life measured in hours d. Physiologic responses to eicosanoids include vasodilatation, vasoconstriction, increased vascular permeability and both chemotaxis and chemoattractant inhibition

Description : Eicosanoids mediate inflammation in a variety of ways. Of the following statements, which are true with regard to this? a. Eicosanoids are stored in cytoplasmic granules ... include vasodilatation, vasoconstriction, increased vascular permeability and both chemotaxis and chemoattractant inhibition

Last Answer : Answer: b, d The eicosanoids are derived from arachidonic acid (eicosatetraenoic acid) and consist of prostaglandins, thromboxanes, leukotrienes and lipoxins. The eicosanoids are not ... nervous system d. Mononuclear phagocytes release a variety of proinflammatory cytokines and growth factors

Which of the following statements regarding TNFa are true? a. TNFa has a marked procoagulant effect b. Passive immunization of patients with neutralizing antibodies to TNFa improves survival from multi-organ system failure c. TNFa upregulates E-selectin expression d. The most potent known stimulus for TNFa production and release is IL-1

Description : Which of the following statements regarding TNFa are true? a. TNFa has a marked procoagulant effect b. Passive immunization of patients with neutralizing antibodies to TNFa improves survival from multi-organ ... expression d. The most potent known stimulus for TNFa production and release is IL-1

Last Answer : Answer: a, c TNFa has a marked procoagulant effect on endothelial cells, precipitating intravascular thrombosis. TNFa causes endothelial cells to release procoagulant activity (tissue factor), ... to produce TNFa, however the most potent stimulus for TNFa production and release is endotoxin

New treatment modalities designed to modulate host defense mechanisms that have been demonstrated conclusively to be of benefit include: a. Gut decontamination b. Anti-LPS antibody c. Anti-TNF antibody d. Thymopentin e. None of the above

Description : New treatment modalities designed to modulate host defense mechanisms that have been demonstrated conclusively to be of benefit include: a. Gut decontamination b. Anti-LPS antibody c. Anti-TNF antibody d. Thymopentin e. None of the above

Last Answer : Answer: e Selective gut decontamination involves the use of orally administered antibiotics that achieve a high intraluminal level directed against gram-negative aerobes and yeast, leaving ... but conclusive evidence that concurrent reduction of infection-related mortality occurs is not available

Which of the following statements regarding IL-1 are correct? a. While IL-1 and TNFa share many biologic effects, IL-1 appears to be more potent b. IL-1 expression is in part autoregulated c. IL-1 inhibits prostaglandin production d. The ability of IL-1 to upregulate endothelial cell-neutrophil adhesion molecules is relatively limited

Description : Which of the following statements regarding IL-1 are correct? a. While IL-1 and TNFa share many biologic effects, IL-1 appears to be more potent b. IL-1 expression is in part ... production d. The ability of IL-1 to upregulate endothelial cell-neutrophil adhesion molecules is relatively limited

Last Answer : Answer: b IL-1 and TNFa share many biologic properties. In addition, each potentiates the effects of the other one when given concurrently. Overall, IL-1 alone probably has weaker effects than ... IL-1 provides a key step in the extravasation of leukocytes to sites of local inflammation and injury

Which of the following statement(s) is/are true concerning metabolic derangements in sepsis and the systemic inflammatory response syndrome which may follow progressive shock? a. Alterations in glucose metabolism lead to the development of efficient substrate utilization b. A progressive rise in serum triglyceride levels result from less efficient clearance and increased hepatic lipogenesis c. A net negative nitrogen balance occurs due to the oxidative metabolism of proteins to meet energy needs d. The serum aromatic amino acids fall rapidly as they are actively used in oxidative metabolism

Description : Which of the following statement(s) is/are true concerning metabolic derangements in sepsis and the systemic inflammatory response syndrome which may follow progressive shock? a. Alterations in glucose ... The serum aromatic amino acids fall rapidly as they are actively used in oxidative metabolism

Last Answer : Answer: b, c A broad spectrum of metabolic abnormalities become apparent in sepsis and the systemic inflammatory response syndrome following shock. Disruption of the normal cycles of carbohydrate, ... acetyl coenzyme A. This results in reduced serum level of leucine, isoleucine and valine

Cell regulation can be thought of as the effector side of cell communication. Most commonly cell regulation occurs by means of extracellular chemical messengers. Which of the following statement(s) is/are true concerning these messengers? a. Paracrine regulation involves a messenger which is produced and acts systemically b. The extracellular signal or stimulus is received by a receptor on or in the target cell c. Neurocrine regulation depends on a physical connection between the neuron and the target cell d. Most hormones, local mediators, and neurotransmitters readily cross the cell plasma membrane

Description : Cell regulation can be thought of as the effector side of cell communication. Most commonly cell regulation occurs by means of extracellular chemical messengers. Which of the following statement(s ... d. Most hormones, local mediators, and neurotransmitters readily cross the cell plasma membrane

Last Answer : Answer: b, c Depending on how the extracellular messenger arrives, cell regulation can be classified as paracrine, endocrine, or neurocrine. In paracrine regulation, a chemical messenger ... , local mediators, and neurotransmitters are water-soluble and cannot readily cross the plasma membrane

A 65-year old patient has colon carcinoma metastatic to the liver and lungs. He has had a weight loss of 10 kg. Cytokine-dependent tumor cachexia is attributable to which of the following? a. Increased glucose uptake and increased glycogen breakdown occur in this circumstance. b. Suppressed activity of lipoprotein lipase results from TNFa c. TNFa stimulates lipolysis d. The differentiation process of pre-adipocytes is impaired e. Partial reversal of differentiated adipocytes to pre-adipocyte morphology and gene expression occurs

Description : A 65-year old patient has colon carcinoma metastatic to the liver and lungs. He has had a weight loss of 10 kg. Cytokine-dependent tumor cachexia is attributable to which of the ... is impaired e. Partial reversal of differentiated adipocytes to pre-adipocyte morphology and gene expression occurs

Last Answer : Answer: a, b, c, d, e Tumor cachexia appears to be mediated by TNFa. Lipopolysaccharide (LPS), as well as other cytokines, activate a variety of inflammatory cells, most ... chronic syndromes of anorexia, weight loss, and cachexia that are associated with both chronic infection and malignancy

Which of the following is exposed on the outer surface of a gram-negative bacterium?A- O-antigen of lipopolysaccharide (LPS) B- Polysaccharide portion of lipoteichoic acid (LTA) C- Braun lipoprotein D- .Electron transport system components

Description : Which of the following is exposed on the outer surface of a gram-negative bacterium?A- O-antigen of lipopolysaccharide (LPS) B- Polysaccharide portion of lipoteichoic acid (LTA) C- Braun lipoprotein D- .Electron transport system components

Last Answer : O-antigen of lipopolysaccharide (LPS)

Which of the following statement(s) is/are true concerning septic shock? a. The clinical picture of gram negative septic shock is specifically different than shock associated with other infectious agents b. The circulatory derangements of septic shock precede the development of metabolic abnormalities c. Splanchnic vascular resistance falls in similar fashion to overall systemic vascular resistance d. Despite normal mechanisms of intrinsic expansion of the circulating blood volume, exogenous volume resuscitation is necessary

Description : Which of the following statement(s) is/are true concerning septic shock? a. The clinical picture of gram negative septic shock is specifically different than shock associated with ... mechanisms of intrinsic expansion of the circulating blood volume, exogenous volume resuscitation is necessary

Last Answer : Answer: d The clinical findings in sepsis and septic shock represent the host response to infection. Gram-positive and gram-negative bacteria, viruses, fungi, rickettsiae, and ... intravascular volume, exogenous volume resuscitation must be provided to restore venous return and ventricular filling

A 67-year-old male with advanced cholangiocarcinoma develops gram-negative sepsis. Excessive bleeding is noted around vascular catheters and from needle puncture sites. The diagnosis of disseminated intervascular coagulation (DIC) is considered. Which of the following laboratory test(s) is/are indicative of DIC? a. Decreased platelet count b. Decreased fibrinogen level c. Normal prothrombin time d. Elevated fibrin split products

Description : A 67-year-old male with advanced cholangiocarcinoma develops gram-negative sepsis. Excessive bleeding is noted around vascular catheters and from needle puncture sites. The diagnosis of disseminated ... b. Decreased fibrinogen level c. Normal prothrombin time d. Elevated fibrin split products

Last Answer : Answer: a, b, d Disseminated intravascular coagulation (DIC) is the primary form of acute thrombosis. Causes of this syndrome include abruptio placenta, gram-positive and gram-negative sepsis, ... decline in the platelet count and fibrinogen level, along with an elevation of fibrin split products

Answer: a, b, c, d Free oxygen radicals are chemical species that are intermediates in the normal process of cellular respiration. Oxidants that are free radicals have been implicated as initiators of reactions which lead to a variety of cellular injuries. Oxidants are derived from several sources, notably phagocytes. Among the effects of oxygen free radicals are membrane lipid peroxidation, DNA strand breaks, cytoskeletal disassembly and inhibition of glucose metabolism leading to decreased cellular ATP concentrations. (Figure 6-16) 187 Which of the following acute-phase protein levels are increased in human plasma following acute inflammation? a. C-reactive protein b. Serum amyloid c. a -Proteinase inhibitor d. Fibrinogen e. Albumin

Description : Answer: a, b, c, d Free oxygen radicals are chemical species that are intermediates in the normal process of cellular respiration. Oxidants that are free radicals have been implicated as initiators of ... a. C-reactive protein b. Serum amyloid c. a -Proteinase inhibitor d. Fibrinogen e. Albumin

Last Answer : Answer: a, b, c, d The acute-phase response is a series of homeostatic responses of the organism to tissue injury in infection and inflammation. After an inflammatory stimulus occurs, a number ... 30% to 50% of the level before injury. The reason for the decrease in production is poorly understood

The use of antibiotics can be based on either the clinical course of a patient without the benefit of well-defined microbiologic data (empiric therapy), or targeted at specific identified pathogens once sensitivity reports are available (directed therapy). The following statement(s) is/are true concerning these therapies. a. The issue of toxic side effects of antibiotics is only important in dealing with emperic therapy b. Single agent therapy is generally inferior to specific multi-drug therapy (aminoglycoside plus an antianaerobic agent) for the treatment of secondary bacterial peritonitis due to appendicitis, diverticulitis, penetrating gastrointestinal injury, or anastomotic leak c. With the empiric use of antibiotics, a diligent search for the septic source should be undertaken and co

Description : The use of antibiotics can be based on either the clinical course of a patient without the benefit of well-defined microbiologic data (empiric therapy), or targeted at ... which polymicrobial infection is identified, specifically-directed treatment for the predominant organism is satisfactory

Last Answer : Answer: c The use of empiric therapy without the benefit of well-defined microbiologic data is appropriate when there is sufficient clinical evidence to support the diagnosis such that it would ... components of the infection if the body site is such that these microorganisms may be present

Which of the following statements regarding fibroblasts and their function in wound healing are true? a. IL-1 has both inhibitory and promotional effects on fibroblast growth b. TNFa stimulates fibroblast collagen synthesis c. IL-1 and TNFa have opposite effects on the healing of bone d. In human clinical trials, EGF (epithelial growth factor) has been demonstrated to accelerate epidermal regeneration in cutaneous wounds

Description : Which of the following statements regarding fibroblasts and their function in wound healing are true? a. IL-1 has both inhibitory and promotional effects on fibroblast growth b. TNFa ... EGF (epithelial growth factor) has been demonstrated to accelerate epidermal regeneration in cutaneous wounds

Last Answer : Answer: a, d IL-1 appears to be important in the process of normal wound repair. IL-1 has been shown to stimulate skin fibroblast and keratinocyte growth, as well as ... that recombinant EGF enhances keratinocyte migration. EGF is also a potent chemoattractant for granulation tissue fibroblasts

Which of the following statement(s) is/are true concerning ischemia reperfusion injury? a. During ischemia, ATP degradation results in increased plasma and intracellular levels of hypoxanthine and xanthene b. Oxygen free radicals such as the superoxide radical are involved in the expression of the proinflammatory phenotype of endothelial cells, macrophages and neutrophils c. The intracellular adhesion molecule-1 (ICAN-1) contributes to injury and disruption of the endothelial lining, with extensive capillary leak and resultant interstitial edema d. Animal models have demonstrated that passive immunization with antibodies to neutrophil adhesive complex lessen the ischemic/reperfusion microvascular injury

Description : Which of the following statement(s) is/are true concerning ischemia reperfusion injury? a. During ischemia, ATP degradation results in increased plasma and intracellular levels of ... immunization with antibodies to neutrophil adhesive complex lessen the ischemic/reperfusion microvascular injury

Last Answer : Answer: a, b, c, d During the ischemia and hypoperfusion phase, degradation of ATP stores essential to maintain cell integrity and significant loss of diffusible ... either the neutrophil adhesive complex or the endothelial selectins dramatically lessens ischemia/reperfusion microvascular injury

Which of the following statement(s) is/are true concerning the role of antibiotics in wound care? a. Systemic antibiotics are indicated for all open wounds b. Bacterial resistance can occur with systemic but not topical antibiotics c. An indication for systemic antibiotic administration is a granulation tissue bacterial count in excess of greater than 105 organisms/gram of tissue on quantitative analysis d. Silver sulfadiazine is useful only for the management of burns

Description : Which of the following statement(s) is/are true concerning the role of antibiotics in wound care? a. Systemic antibiotics are indicated for all open wounds b. Bacterial resistance can occur with ... of tissue on quantitative analysis d. Silver sulfadiazine is useful only for the management of burns

Last Answer : Answer: c The role of antibiotics in wound care is controversial. All open wounds are colonized with bacteria. Only when surrounding tissue is invaded (cellulitis) are systemic antibiotics clearly ... of relevant drug-resistant plasmids in bacteria, and its low cost make it a good choice

Under certain circumstances, the gut may become a source of sepsis and serve as the motor of systemic inflammatory response syndrome. Microbial translocation is the process by which microorganisms migrate across the mucosal barrier to invade the host. Which of the following mechanisms can promote bacterial translocation? a. An increased number of gut bacteria b. Altered intestinal mucosal permeability c. Decreased host defense mechanisms d. Lack of enteral feeding

Description : Under certain circumstances, the gut may become a source of sepsis and serve as the motor of systemic inflammatory response syndrome. Microbial translocation is the process by which microorganisms ... intestinal mucosal permeability c. Decreased host defense mechanisms d. Lack of enteral feeding

Last Answer : Answer: a, b, c, d 99 Translocation is promoted in three general ways: 1) altered permeability of the intestinal mucosa as caused by shock, sepsis, distant injury, or cell toxins; 2) ... trauma patient d. Fifty percent of non-nitrogen caloric requirements should be provided in the form of fat

The following statement(s) is/are true concerning host defense mechanisms to intraabdominal infection. a. Bacterial clearance can occur via translymphatic absorption b. Phagocytic activity and bacterial killing can occur via resident phagocytic cells and an influx of PMNs c. A fibrinogen-rich inflammatory exudate is released into the peritoneal cavity, trapping large numbers of bacteria and other particulate matter d. Perforations of a bowel may be walled off but are seldom sealed by the omentum and other mobile viscera

Description : The following statement(s) is/are true concerning host defense mechanisms to intraabdominal infection. a. Bacterial clearance can occur via translymphatic absorption b. Phagocytic activity and bacterial killing can ... may be walled off but are seldom sealed by the omentum and other mobile viscera

Last Answer : Answer: a, b, c The introduction of microorganisms into the normally sterile peritoneal environment invoke several potent specialized host antimicrobial defense mechanisms. Bacterial clearance, ... the contaminated enteric contents walled off, preventing continued soilage of the peritoneal cavity

Answer: b Metabolic response to injury results in increased energy expenditure. If energy intake is less than expenditure, oxidation of body fat stores and erosion of lean body mass will occur with resultant loss of weight. When weight loss exceeds 10–15% of body weight, the complications of malnutrition interact with disease processes, with increased morbidity and mortality rates. The goal of nutritional support is maintenance of body cell mass and limitation of weight loss to less than 10% preinjury. The major impact of nutritional support in the trauma patient is to aid host defense. Under-nutrition may compromise the available host defense mechanism and may thus increase the likelihood of invasive sepsis, multiple organ system failure, and death. Resuscitation, oxygenation and arrest

Description : Answer: b Metabolic response to injury results in increased energy expenditure. If energy intake is less than expenditure, oxidation of body fat stores and erosion of lean body mass will occur ... requirements, caloric requirements should be distributed at a ratio of 70% as glucose and 30% as fat

Last Answer : Which of the following statement(s) is/are true concerning body fuel reserves? a. The largest fuel reserve in the body is skeletal muscle b. Fat provides about 9 calories/gram c. Free glucose and glycogen stores are a trivial fuel reserve d. Body protein is a valuable storage form of energy

Sepsis causes a marked metabolic response. Which of the following statement(s) is/are true concerning the metabolic response to sepsis? a. Oxygen consumption is increased in the face of infection b. In a patient with a maximal metabolic rate secondary to trauma, the presence of infection will increase the rate further c. Metabolic rate increases at a rate of approximately 10% for each increase of 1°C in central temperature d. The extent of increase in oxygen consumption relates to the severity of the infection

Description : Sepsis causes a marked metabolic response. Which of the following statement(s) is/are true concerning the metabolic response to sepsis? a. Oxygen consumption is increased in the face of infection ... d. The extent of increase in oxygen consumption relates to the severity of the infection

Last Answer : Answer: a, c, d Oxygen consumption is usually elevated in the infected patient. The extent of this increase is related to the severity of the infection, with peak elevations reaching 50% ... suggest that the metabolic rate increases 10% to 13% for each elevation of 1°C in central temperature

The first line of host defense is the barrier presented to the external environment. Which of the following statement(s) is/are true concerning host barriers? a. Sebaceous glands secrete chemical compounds that maintain a relatively high pH, providing effective bacterial stasis b. Within the respiratory tract, ciliary function serves to extrude microorganisms trapped within the mucus secretion layer c. The low pH within the stomach markedly decreases bacterial content of the upper gastrointestinal tract d. Gut peristalsis serves to prevent microbial adherence and invasion

Description : The first line of host defense is the barrier presented to the external environment. Which of the following statement(s) is/are true concerning host barriers? a. Sebaceous glands secrete ... of the upper gastrointestinal tract d. Gut peristalsis serves to prevent microbial adherence and invasion

Last Answer : Answer: b, c, d The skin, mucus membranes, and epithelial layers of various organs of the body constitute effective physical barriers against microbial invasion. In certain portions of the ... very low pH within the stomach and gut peristalsis both serve to prevent microbial adherence and invasion

Which of the following statement(s) is/are true concerning the cell function of phagocytosis? a. Phagocytosis is a mechanistically distinct process of endocytosis performed by special cells to take up larger particles such as bacteria or erythrocytes b. Lymphocytes are the primary blood cell involved with this process c. The process involves a coating of the cytoplasmic surface known as clathrin d. Phagocytosis is performed only by white blood cells and tissue macrophages

Description : Which of the following statement(s) is/are true concerning the cell function of phagocytosis? a. Phagocytosis is a mechanistically distinct process of endocytosis performed by special cells to take ... known as clathrin d. Phagocytosis is performed only by white blood cells and tissue macrophages

Last Answer : Answer: a Phagocytosis is a specialized form of endocytosis by which large particles are internalized by specialized cells primarily macrophages and neutrophils. To be phagocytosed, particles ... the lumen of the thyroid follicle, thereby releasing the thyroid hormones, thyroxine triiodothyronine

Which of the following statement(s) is/are true concerning the multiorgan failure syndrome (MOFS)? a. Changes in the splanchnic and pulmonary microcirculation are critical to the development of MOFS b. Tissue fixed microphages, including the liver Kupffer cell, have little role in the development of MOFS c. MOFS represents systemic consequences of loss of homeostatic control of local inflammation and microcirculatory hypoperfusion d. The nature of MOFS is highly dependent upon the etiology of the underlying problem

Description : Which of the following statement(s) is/are true concerning the multiorgan failure syndrome (MOFS)? a. Changes in the splanchnic and pulmonary microcirculation are critical to the development of MOFS ... d. The nature of MOFS is highly dependent upon the etiology of the underlying problem

Last Answer : Answer: a, c The nature of multiorgan failure syndrome (MOFS) is that of a diffuse cellular injury, developing systemically as a consequence of losing homeostatic control of local ... of microorganism. In noninfectious cases, the response also appears independent of the specific underlying cause

Which of the following statement(s) is/are true concerning wound contraction? a. Wound contraction accounts for similar rates of reduction of wound size regardless of their location b. The fibroblast, at the cellular level, is the primary force driving wound contraction c. Excessive wound contraction, when occurring over a joint, may lead to disability d. Actin microfillaments are found in fibroblasts and may play a role in wound contracture

Description : Which of the following statement(s) is/are true concerning wound contraction? a. Wound contraction accounts for similar rates of reduction of wound size regardless of their location b. The fibroblast ... d. Actin microfillaments are found in fibroblasts and may play a role in wound contracture

Last Answer : Answer: b, c, d Wound contraction is an important event which contrasts healing open wounds and closed incisions. When open wounds contract, the surrounding skin is pulled over the open wound ... number in contracting wounds and are felt to play an active role in the process of wound contraction

Which of the following statement(s) is/are correct concerning the immunoinflammatory response to shock? a. The anaphylactoxins, C3a and C5a, are products of activation of only the classical pathway of the compliment cascade b. Eicosanoids, such as prostaglandins are stored in platelets and endothelial cells and released in response to inflammatory stimuli c. Thromboxane and PGI2 have similar effects d. Platelet-activating factor can be released by both circulating and fixed tissue cells

Description : Which of the following statement(s) is/are correct concerning the immunoinflammatory response to shock? a. The anaphylactoxins, C3a and C5a, are products of activation of only the classical pathway ... effects d. Platelet-activating factor can be released by both circulating and fixed tissue cells

Last Answer : Answer: d Inflammatory mediators have recently been recognized as playing a significant role in the clinical manifestations and progression of shock and the development ... increased pulmonary vascular resistance, bronchoconstriction, peripheral vasodilatation, and increased vascular permeability

Which of the following statement(s) is/are true concerning heparin-associated thrombocytopenia? a. Heparin-associated thrombocytopenia occurs only in the face of over anticoagulation with heparin b. Severe thrombocytopenia (platelet count less than 100,000) is seen in less than 10% of patients treated with heparin c. Heparin-associated thrombocytopenia is due to the aggregation of platelets and may result in thrombosis or embolic episodes d. Heparin-associated thrombocytopenia may be seen within hours of initiation of heparin therapy

Description : Which of the following statement(s) is/are true concerning heparin-associated thrombocytopenia? a. Heparin-associated thrombocytopenia occurs only in the face of over anticoagulation with heparin b. ... d. Heparin-associated thrombocytopenia may be seen within hours of initiation of heparin therapy

Last Answer : Answer: b, c Heparin-associated thrombocytopenia occurs in 0.6% to 30% of patients who receive heparin, although severe thrombocytopenia (platelet counts less than 100,000) is seen in ... as coating on pulmonary artery catheters or low rate infusion into arterial catheters may cause this syndrome

A 17-year-old patient involved in an automobile accident is paralyzed with multiple peripheral extremity injuries. Nutritional support is instituted with a transnasal feeding catheter. Which of the following statement(s) is/are true concerning the patient’s management? a. Feeding into the stomach results in stimulation of the biliary/pancreatic axis which is probably trophic for small bowel b. Gastric secretions will dilute the feedings increasing the risk of diarrhea c. The major risk in this patient is tracheobronchial aspiration d. Placement of the feeding catheter through the pylorus into the first portion of the duodenum reduces the risk of regurgitation and aspiration

Description : A 17-year-old patient involved in an automobile accident is paralyzed with multiple peripheral extremity injuries. Nutritional support is instituted with a transnasal feeding catheter. Which of the ... pylorus into the first portion of the duodenum reduces the risk of regurgitation and aspiration

Last Answer : Answer: a, c, d The use of transnasal feeding catheters for intragastric feeding or for duodenal intubation are popular adjuncts for providing nutritional support by the enteral route. The ... the fourth portion of the duodenum reduces the risk of regurgitation and aspiration of feeding formulas

The transport of proteins out of the cell is termed exocytosis. Which of the following statement(s) is/are true concerning this process? a. Secretory vesicles fuse with the plasma membrane b. The process can occur in either a constitutive or regulated process c. A regulated secretion is triggered by a stimulus, most likely a hormone or a neurotransmitter d. A decrease in cytoplasmic calcium occurs as part of the secretion process

Description : The transport of proteins out of the cell is termed exocytosis. Which of the following statement(s) is/are true concerning this process? a. Secretory vesicles fuse with the plasma membrane b. ... or a neurotransmitter d. A decrease in cytoplasmic calcium occurs as part of the secretion process

Last Answer : Answer: a, b, c Transport vesicles that bud off the Golgi network carry both material to be secreted from the cell and protein destined to become components of the plasma ... but may also involve generation of diacylglycerol or production of cyclic AMP which activate kinases or phosphatases

Which of the following statements about the role of the gut in shock and sepsis are true? A. Selective decontamination of the digestive tract with the use of oral antibiotics has been shown to reduce nosocomial pneumonias and to improve mortality rates. B. Enteral nutrition, as compared with parenteral nutrition, preserves the villus architecture of the gut. C. Gut dysfunction may be an effect of shock, but it may also contribute to the development of MODS by the mechanism of bacterial translocation. D. As compared with parenteral nutrition, enteral nutrition is associated with a reduction in septic morbidity.

Description : Which of the following statements about the role of the gut in shock and sepsis are true? A. Selective decontamination of the digestive tract with the use of oral antibiotics has been ... As compared with parenteral nutrition, enteral nutrition is associated with a reduction in septic morbidity.

Last Answer : Answer: BCD DISCUSSION: The gut has a vital role in the pathophysiology of shock. The splanchnic circulation is very vulnerable to the circulatory redistribution that occurs in shock, thus, gut ... , enteral feeding is more cost effective and is associated with a lower rate of septic morbidity

Which of the following statement(s) is/are true concerning excessive scarring processes? a. Keloids occur randomly regardless of gender or race b. Hypertrophic scars and keloid are histologically different c. Keloids tend to develop early and hypertrophic scars late after the surgical injury d. Simple reexcision and closure of a hypertrophic scar can be useful in certain situations such as a wound closed by secondary intention

Description : Which of the following statement(s) is/are true concerning excessive scarring processes? a. Keloids occur randomly regardless of gender or race b. Hypertrophic scars and keloid are histologically different ... scar can be useful in certain situations such as a wound closed by secondary intention

Last Answer : Answer: d True keloids are uncommon and occur predominantly in dark skinned people with a genetic predisposition for keloid formation. In most cases, the gene appears to be ... subside. Hypertrophic scars usually develop within the first month after wounding and often subside gradually

Antibacterial agents can be classified with regard to their structure, mechanism of action, and activity pattern against various types of bacterial pathogens. Which of the following statement(s) is/are true concerning antimicrobial classes? a. Penicillins and cephalosporins share the compound structure of a b-lactam ring which binds to bacterial division plate proteins b. Tetracyclines and macrolides such as erythromycin inhibit bacterial ribosomal activity and therefore protein synthesis c. Aminoglycosides act in a similar fashion to tetracyclines and therefore are both bacteriostatic d. Sulfonamides and trimethoprim act synergistically to inhibit purine synthesis

Description : Antibacterial agents can be classified with regard to their structure, mechanism of action, and activity pattern against various types of bacterial pathogens. Which of the following ... are both bacteriostatic d. Sulfonamides and trimethoprim act synergistically to inhibit purine synthesis

Last Answer : Answer: a, b, d Penicillins, cephalosporins, and monobactams possess a b-lactam ring of some type and act to bind bacterial division plate proteins, thus inhibiting cell wall ... act in different mechanisms to inhibit protein synthesis, therefore two agents in combination act synergistically

Which of the following statements concerning monitoring techniques in the intensive care unit are true? A. Pulmonary artery and pulmonary capillary wedge pressure readings should be made at end inspiration, to minimize ventilatory artifacts. B. Continuous SvO 2 monitoring based on the technique of reflectance spectrophotometry has been shown to be accurate and reliable. C. Direct measurement of gastric intramucosal pH can be provided by gastrointestinal tonometry. D. Hyperlactatemia may be seen in a number of clinical conditions not associated with tissue hypoxia, including liver disease and hypermetabolic states.

Description : Which of the following statements concerning monitoring techniques in the intensive care unit are true? A. Pulmonary artery and pulmonary capillary wedge pressure readings should be made ... clinical conditions not associated with tissue hypoxia, including liver disease and hypermetabolic states.

Last Answer : Answer: BD DISCUSSION: Many different monitoring techniques may be used to assess the adequacy of therapy for shock. The pulmonary artery catheter can provide important hemodynamic and oxygen ... also be seen with liver disease, toxin ingestion, and hypermetabolic states not associated with shock