201 The following statement(s) is/are true concerning HIV infection.
a. Initial screening with ELISA is highly sensitive but can be associated with a false positive rate of 25%
b. Treatment with azidothymidine (AZD) appears to prolong survival when administered early in the disease
c. Predisposition to infection in HIV infection is primarily due to reduction in the number of helper T cells
d. Common infections in patients with AIDS are Pneumocystis, carinii pneumonia, CMV pneumonitis, Cryptococcus meningitis, and disseminated infection due to atypical mycobacteria
Answer: b, c, d
Acquired immunodeficiency syndrome (AIDS) is a syndrome caused by the human retrovirus (HIV-1) that infects T lymphocytes and causes severe immunosuppression. Individuals who become infected with HIV are prone to a variety of infections and different types of malignancy. A spectrum exists in which patients regress from asymptomatic infection, to development of AIDS-related complex (ARC) of diseases to AIDS itself. Common infections occurring in patients with AIDS are Pneumocystis carinii pneumonia; CMV pneumonitis; gastritis, hepatitis and meningitis due to Cryptococcus neoformans; and pneumonia and disseminated infection due to atypical mycobacteria. Predisposition to these infections is due, in part, to the lymphotrophic nature of HIV, which markedly reduces the number of helper T cells as well as the absolute number of T cells.
HIV detection typically consists of initial ELISA screening, but this test has about a 1–3% false-positive rate, thus mandating all positive tests be confirmed by the western immunoblot analysis.
Treatment of ARC and AIDS consists of aggressive antiinfective therapy once a specific infection occurs and the use of AZT. AZT has been shown to prolong survival when administered early in the course of disease and is considered routine therapy.
202 The following statement(s) is/are true concerning initial microbiologic diagnostic techniques.
a. Appropriate expeditious transport of specimens to the microbiology laboratory is essential for obtaining accurate clinical information
b. The use of potassium hydroxide in preparing a specimen slide for light microscopy will be useful in identification of anaerobic bacteria
c. Antibiotic sensitivity is determined by exposing the specific microorganism to varying amounts of antibiotic with the concentration of the antibiotic inhibiting growth referred to as the MIC (minimal inhibitory concentration)
d. Serum levels of antimicrobial agents should achieve in excess of a 4-to 8-fold increase over the MIC to be considered clinically efficacious.
Answer: a, c, d
Because most surgical infections are polymicrobial, specimens should be cultured for aerobic and anaerobic bacteria, as well as fungi. Although aerobic and aerotolerant microorganisms often do not require special transport media, a delay in specimen processing may markedly reduce the yield, and anaerobic transport media have been demonstrated to markedly increase the cultural yield of this type of organism. The initial piece of information gained concerning potential infection may come from simple staining of a specimen. Gram stain, which will identify the staining characteristics of the organisms, as well as their number should be performed on all specimens. Potassium hydroxide is useful in that it will lyse bacteria and other cellular elements within a preparation and allow observation of yeast or mycelial elements.
Initial culture results may solely indicate that microorganisms are growing and full characterization may take two to three days. Once a specific microorganism is identified, a sample is inoculated during the log phase into broth containing varying amounts of an antibiotic. After an 18-to 24-hour period, the tube or well that exhibits no visible growth is then noted, and the reciprocal of this dilution is termed the minimal inhibitory concentration (MIC). This value may be compared to either measured or known achievable serum levels for a particular antibiotic. In general, antimicrobial agents that achieve in excess of a 4-to 8-fold increase over MIC during the peak serum level have been demonstrated to be clinically efficacious.
203 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
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 antigenic cell surface. The classic pathway of complement activation usually begins with immunoglobulin G-binding which has also bound the antigen. The alternate pathway activation occurs in response to activation of direct binding of the antigen or directly through contact with fungal and bacterial cell wall compounds such as zymosan and gram-negative bacterial lipopolysaccharide (LPS endotoxin). Several complement components represent important host defenses acting to recruit or augment cellular host defenses or to directly inactivate invading microbes through lytic activity. The production of complement component fractions C3a and C5a during activation of this cascade serve primarily to markedly increase vascular permeability, and C5a functions as a PMN and macrophage chemoattractant. This process leads to the recruitment of additional humoral and cellular defenses to the specific area of infection. Excessive complement activation can produce deleterious effects in some instances. Complement activation causes enhanced PMN adhesion, margination, and release of lysosomal enzymes that can directly damage certain target tissues, such as the lung.
204 A 55-year-old renal transplant patient has been hospitalized in a Surgical Intensive Care Unit, receiving a prolonged course of antibiotics following an attack of acute cholecystitis. The following statement(s) is/are true concerning his management.
a. Due to the potential risk of Candida infection, prophylaxis with oral nystatin should be instituted early in the patient’s course
b. A Candida urinary tract infection should be treated with systemic amphotericin B
c. Changes of Candida retinitis are of little significance
d. The presence of a virulent Candida bacteremia should suggest a dosage reduction in immunosuppressive agents until the infection can be adequately controlled
Answer: a, d
Infections due to fungal pathogens have become increasingly common during the past decade, frequently occurring in patients undergoing prolonged hospitalization in the Surgical Intensive Care Unit and in immunocompromised individuals. Prophylaxis with oral antifungal agents (nystatin) is warranted, especially during periods of maximal immunosuppression in transplant patients, in patients with uncontrolled diabetes, or during some cases of prolonged antibacterial microbial therapy. In general, local, apparently noninvasive Candida infections involving the integument and mucus membranes are treated with oral decontamination and topical antifungal therapy using topical agents such as nystatin. Candida urinary tract infections can be treated with either an oral antifungal agent or with topical amphotericin B as a continuous bladder irrigation. Several studies have demonstrated that those patients with three positive sites of Candida infection, or with peritoneal or blood cultures positive for Candida exhibit higher survival rates when amphotericin B therapy is instituted earlier in the course of infection. The presence of retinal changes compatible with Candida retinitis or Candida present within the peritoneal cavity are considered indications for a limited course of amphotericin B therapy (300% to 500 mg). Patients receiving exogenous immunosuppressive agents should undergo a marked dose reduction, and some agents should be discontinued until evidence of infection is absolutely controlled or is eradicated.
205 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
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, process, and present antigen to T lymphocytes of helper lineage. These T lymphocytes, in turn, act to stimulate B lymphocytes to become mature plasmacytes (through secretion of cytokines such as interleukin 4 and 6) dedicated to the production of antibody directed against the specific antigen. An antigen may be defined as any substance that stimulates the host immune response; that is, that the host immune system recognizes is foreign. Thus, an antigen may be an invading microorganism, an inert particle, or any type of chemical compound that triggers the host immune system. Although some antigens are able to directly stimulate B lymphocytes in and of themselves to produce antibody (many polysaccharides), most antigens require coordinated efforts of the various cellular components of the immune system.
206 The following statement(s) is/are true concerning viral infections.
a. The most common post-transplantation viral infections are caused by herpes viruses and include CMV and herpes simplex virus
b. Viral infections occur at equal frequency anytime during the post-transplantation period
c. CMV infection in the post-transplant patient is most likely a pulmonary process
d. Herpes simplex virus (HSV) infection primarily presents with a mononucleosis-type syndrome with fever, lethargy, and cough
Answer: a, c,
Solid organ transplant patients are prone to develop viral infection by virtue of exogenous immunosuppression. The most common post-transplantation viral infections are those caused by herpes viruses (CMV, herpes simplex virus [HSV], Epstein-Barr virus [EBV], and Varicella-Zoster virus [VZV]). All are most common during periods of maximal host immunosuppression that occur immediately post-transplantation and during periods of allograft rejection. CMV is a common cause of fever after solid organ transplantation, and evidence of CMV infection occurs in approximately 30% of patients. The most common presentation for CMV infection is that of a febrile, leukopenic patient with a cough, diffuse interstitial infiltrates on chest x-ray, and hypoxia.
HSV infection causes primarily oral pharyngeal ulcerations in most cases, although sporadic cases of disseminated disease have been reported. EBV causes an occasional case of mononucleosis-type syndrome but has also been clearly indicated in the pathogenesis of post-transplantation lymphomas. VZV infection can present as disseminated and occasionally life-threatening infections in the nonimmune transplant patient or as painful herpes zoster in patients who have previously developed chicken pox.
207 The following statement(s) is/are true concerning necrotizing fascitis.
a. Mortality rates as high as 40% can be expected
b. The infection involves only the superficial fascia, sparing the deep muscular fascia
c. An impaired immune system is a common factor predisposing to this condition
d. The infection is usually polymicrobial
e. Necrotizing fascitis is most likely to develop in the face of impaired fascial blood supply
Answer: a, c, d, e
Necrotizing fascitis is an uncommon infection of the deep and superficial fascia that is associated with mortality as high as 40% in many series. Although many underlying disease processes predispose patients to necrotizing fascitis, three common factors are almost invariably present: 1) impairment of the immune system; 2) compromise of fascial blood supply, and 3) the presence of microorganisms that are able to proliferate within this environment. Infections of this type are usually polymicrobial in nature, with gram-positive organisms such as staphylococci and streptococci, gram-negative enteric bacteria, and gram-negative anaerobic being frequently identified. These polymicrobial cultural results are assuredly indicative of the occurrence of a synergistic process, perhaps in large part accounting for the severity of these infections. Some microorganisms possess virulence factors that, in conjunction with an underlying host predisposition, allow this disease process to occur without dependence on other bacteria. Examples of such bacteria include Clostridium, Pseudomonas, and Aeromonas. In these patients, the process is often fulminant and is frequently associated with cellulitis, myositis, fascitis, and bacteremia with attendant high mortality.
208 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
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 the host anaerobic intestinal microflora relatively undisrupted. Although a reduction and alteration of the microorganisms responsible for infectious episodes have been demonstrated in certain groups of patients, a clear-cut impact on host mortality has not been shown. Because LPS may be responsible for toxicity both directly and through host mediator systems, the availability of agents to bind against this portion of the gram-negative bacteria to reduce mortality has been intensively examined. Unfortunately, large multicenter randomized trials provide no evidence of benefit for this treatment. Similarly, since many of the systemic manifestations of gram-negative bacteremia are mediated by cytokines, the effect of an anti-TNF antibody preparation is currently in clinical trial. No proven benefits have yet been identified. Finally, the use of immunostimulants to enhance the state of activation of host defenses has been proposed. Thymopentin is a peptide that contains active thymopoetin, a thymic molecule that acts to stimulate T-lymphocyte activity. Preliminary trials indicate that this agent ameliorates host septic response after major operations and trauma but conclusive evidence that concurrent reduction of infection-related mortality occurs is not available.
209 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
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 peptidoglycan synthesis and either causing or inducing autolytic bacteriolysis. Because gram-positive and gram-negative bacteria possess different types of division plate proteins, many of these agents exhibit differential activity between these two types of microorganisms. Tetracyclines, chloramphenicol, and macrolides inhibit bacterial ribosomal activity, and thus overall protein synthesis by a variety of different mechanisms. Aminoglycosides act to inhibit protein synthesis and also presumably act on a different target site, a supposition based on the fact that aminoglycosides are bacteriolytic and the other agents are bacteriostatic. Vancomycin inhibits assembly of peptidoglycan polymers, whereas quinolones bind to DNA helicase proteins and inhibit bacterial DNA synthesis. Sulfonamides and trimethoprim act in different mechanisms to inhibit protein synthesis, therefore two agents in combination act synergistically.
210 The treatment of the following patient should include:
a. Initial empiric therapy directed against both aerobes and anaerobes
b. The addition of anti-fungal therapy in an elderly patient
c. A minimum of two weeks of antibiotic therapy is indicated
d. The addition of appropriate antibiotic therapy has made surgical therapy unnecessary in such cases
e. Either a single agent or combination therapy is appropriate if the agents selected possess activity against both aerobic and anaerobic bacteria
Answer: a, e
The primary treatment for a perforated viscus is surgical, however antimicrobial therapy is an extremely important adjunct. Empiric antibiotic therapy for secondary bacterial peritonitis and intraabdominal abscess should be directed against both aerobes and anaerobes. Administration of an agent directed against only one component of the infection or the other is inferior to combined therapy. Several studies indicate that the results of using several agents in combination is equivalent to the use of a single agent therapy as long as the agents selected possess activity against both components of the infection. The addition of antientercoccal or antifungal agents as initial therapy has not been substantiated. The most beneficial duration of antibiotic therapy must be based on the setting for the specific patient. Minimal peritoneal contamination with adequate surgical treatment may be treated with a three-to five-day course of antibiotics, whereas longer periods are indicated for immunosuppressed patients and with patients with extensive contamination.
211 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
Answer: a, b, c
The introduction of microorganisms into the normally sterile peritoneal environment invoke several potent specialized host antimicrobial defense mechanisms. Bacterial clearance, also termed translymphatic absorption, occurs through specialized structures found only on the peritoneal mesothelium on the underside of the diaphragm that act as conduits for both fluid and particulate matter. Lymphatic channels eventually form which drain into the venous circulation via the thoracic duct. Bacteria not cleared via translymphatic absorption are rapidly engulfed by resident and recruited phagocytic cells including resident macrophages on the peritoneal surface and omentum and attracted PMNs. The final primitive host defense mechanism is sequestration by which a fibrinogen-rich exudate containing plasma oposonins appears during peritoneal infection and fibrin polymerization occurs. Fibrin has the capacity to trap large numbers of bacteria and other particulate matter. Acting in conjunction with omentum and other mobile viscera, perforations are sealed and the contaminated enteric contents walled off, preventing continued soilage of the peritoneal cavity.
212 A 67-year-old male presents with an intraabdominal abscess secondary to perforated sigmoid diverticulitis. The following statement(s) is/are true concerning his intraabdominal abscess.
a. Culture will likely reveal a solitary organism
b. Both aerobic and anaerobic islets are encountered in 50% of specimens
c. The most common aerobic islet will be likely E. coli and other gram-negative enteric bacilli
d. The most common anaerobic islet will be a Bacteroides species
Answer: b, c, d
Typically an intraabdominal infection results in perforation of a hollow viscus and the ensuing contamination of a normally sterile peritoneal cavity. The normal bacterial flora found in that particular location of the alimentary tract thus determines the initial inoculum. In parallel with the overall quantity of microorganisms, (both aerobes but predominantly anaerobes) perforations of the lower small bowel and colon produce a high frequency of infections that contain anaerobic microorganisms. Certain predictable patterns of bacterial islets are found, but on average four to five islets occur in patients with established intraabdominal infection, more than half of which are anaerobes. Both aerobes and anaerobes are encountered in 80% to 90% of specimens. Commonly encountered aerobes isolated are E. coli and other gram-negative enteric bacilli such as Enterobacter, Klebsiella. Among the anaerobes, Bacteroides species (especially B. fragilis, Clostridium), and anaerobic cocci are most consistently isolated.
213 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
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 30% lethality, respectively), despite therapeutic intervention with antimicrobial agents, aggressive hemodynamic monitoring, fluid resuscitation, and metabolic support. During the past several decades, nosocomial infections due to gram-negative pathogens have increased in frequency with resultant increase in the incidence of gram-negative bacteremia to between 3 and 13 cases per 1000 hospital admissions. Factors that predispose to these infections include: 1) underlying host disease processes such as malignancy, diabetes; 2) old age and disability; 3) malnutrition; 4) previous or concurrent antimicrobial antibiotic therapy; 5) major operations; 6) respiratory or urinary manipulation or intubation; and 7) immunosuppression.
Although many different organisms cause this form of sepsis, E. coli predominates in overall frequency. Also common are isolates of Klebsiella, Enterobacter and Serratia; Pseudomonas bacteremia is less common. Some studies, however, have suggested that Pseudomonas sepsis is associated with the highest lethality. In several series, 10% to 20% of patients have had polymicrobial series, and most investigators agree that polymicrobial sepsis is more lethal than infection with a single organism.
214 Which of the following statement(s) is/are true concerning the various types of shock?
a. Traumatic shock is more commonly associated with subsequent organ injury and multiorgan failure syndrome than hemorrhagic shock
b. Cardiogenic shock can be of either an intrinsic or compressive nature
c. Hypodynamic septic shock is associated with a decreased mortality risk when compared with hyperdynamic septic shock
d. Hypoadrenal shock usually responds quickly to resuscitation
e. Neurogenic shock occurs with the absence of sympathetic activity
Answer: a, b, d, e
Classification schemes of shock based on cause have been developed for the seemingly dissimilar processes leading to circulatory collapse and the shock state. Hypovolemic shock, the most common, is the result of intravascular volume depletion through loss of red blood cell mass or plasma volume. Microvascular hypotension results from a combination of low intravascular blood volume, diminished cardiac output, and compensatory sympathetic peripheral vasoconstriction. Shock associated with trauma (traumatic shock) arises from the consequences of hypovolemia due to hemorrhage in conjunction with direct soft tissue injury and bone fracture. Hypovolemia caused by blood loss and fluid extravasation into injured tissues is compounded by activation of maladaptive inflammatory cascades initiated by the tissue injury. In contrast to pure hemorragic shock, subsequent organ injury and multiorgan failure syndrome (MOFS) occurs much more frequently following traumatic shock due to the over-expression of these immuno-inflammatory cascades. Cardiogenic shock is the result of failure of the heart as an effective pump, resulting in inadequate cardiac output, tissue perfusion and oxygen delivery. Intrinsic causes include myocardial infarction, cardiomyopathy, valvular heart disease, or rhythm disturbances. Compressive cardiogenic shock is a discrete entity that results when extrinsic compression of the heart limits diastolic filling and thus systolic ejection and cardiac output. Septic shock refers to hypotension and circulatory insufficiency developing as a consequence of infection and the systemic response to that infection. In its hyperdynamic form, septic shock is marked by diminished peripheral vascular resistance and generalized vasodilatation causing relative hypovolemia. In contrast, hypodynamic septic shock occurs in situations of inadequate resuscitation or preterminal cardiovascular decompensation, and is associated with vasoconstriction and a greatly increased mortality risk. Sympathetic denervation through spinal cord injury, spinal anesthesia, or severe head injury produces generalized arterial vasodilatation and venodilation. Shock occurs when the normal blood volume fails to fill the available intravascular space and severe relative hypovolemia exists. Despite hypotension, there is a noteworthy absence of sympathetic activity, as occurs in hypovolemia or cardiogenic shock. Profound shock can occur in surgical patients following stress due to the loss of the homeostatic corticosteroid response. Hemodynamic instability may develop after an operative procedure or coincident with an unrelated illness. The profound circulatory collapse is often refractory to vigorous resuscitation with fluids and pressor agents. The response to exogenous corticosteroids is usually dramatic and potentially life-saving.
215 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
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, lipid, protein, and oxygen metabolism occur as hypermetabolism develops. Through the Cori cycle, lactate from the periphery is shuttled back to the liver, where it is used in the production of glucose. Because pyruvate is converted to alanine in the periphery, flux of alanine also contributes to hepatic gluconeogenesis. The glycolytic oxidation of glucose to pyruvate and its subsequent glugoneogenic regeneration from lactate is an inefficient cycling of substrate. There is no net energy production, but heat is released in significant quantities. Alterations in lipid metabolism cause a progressive rise in the serum triglyceride level as a result of less efficient clearance of exogenous triglycerides coupled with increased hepatic lipogenesis. Profound alterations in protein and amino acid metabolism develop with characteristic changes in amino acid levels, nitrogen balance, and skeletal muscle mass. Initially levels of the branch chain amino acids are reduced, whereas those of the aromatic amino acids are elevated. There is an increase in the oxidative metabolism of protein to meet energy needs and a tremendous mobilization of nitrogen with net negative nitrogen balance. The branch chain amino acids are preferentially utilized in the TCA cycle to maintain an activity that otherwise would be lost from the diminished entry of carbohydrate-and fatty acid-generated acetyl coenzyme A. This results in reduced serum level of leucine, isoleucine and valine.
216 Which of the following statement(s) is/are true concerning the microvascular and cellular response to shock?
a. Osmodically induced mobilization of intracellular fluid is the initial response to restore intravascular volume
b. With larger volume hemorrhagic shock deterioration of normal cellular transmembrane potential occurs resulting in an increase in extracellular sodium and water
c. The accumulation of anaerobic metabolites override normal homeostatic vasomotor tone and contribute to the maladaptive vasodilatation
d. Abnormal intracellular calcium homeostasis may contribute to the cellular dysfunction of shock
Answer: c, d
Moderate hypovolemia results in a relatively rapid spontaneous restitution of intravascular volume through expansion of the plasma space. This plasma expansion by erythrocyte free fluid occurs within one hour as a result of alterations in pressure and osmolarity and produces an associated hemodilution. Sympathetic discharge, associated arteriolar constriction, and induced metabolic changes in osmolarity initiate the compensatory events at the microcirculatory level. The initial pressure-related phase of restitution of blood volume in shock is overlapped by a second phase involving osmotically induced mobilization of intracellular fluid. Osmotic mechanisms contributing to the restitution of blood volume after moderate hemorrhage are not adequate in hemorrhage of greater magnitude. In larger hemorrhages (over 25% blood volume), there is also deterioration of the normal cellular transmembrane potential, an increase in intracellular sodium and water, and a concomitant decrease in extracellular fluid volume. Tissue hypoxia results, anaerobic metabolites accumulate, and the cell cannot maintain the normal cell membrane potential. Accumulation of hydrogen ion, lactate, and other products of anaerobic metabolism override homeostatic vasomotor tone and contribute to a maladaptive vasodilatation, further augmenting hypotension and hypoperfusion. The uptake of fluid by the “failing” cell is a major source of food sequestration following shock. Loss of membrane function is proportional to both the extent and duration of shock or degrees of sepsis. The etiology of membrane failure is unclear but appears multifactorial. Loss of intracellular ATP energy stores during hypoperfusion or direct toxicity during sepsis may inhibit the membrane sodium-potassium pump. Cellular dysfunction also appears to be related to abnormal intracellular calcium homeostasis.
217 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
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 lung mechanics, and acute lung injury or ARDS due to sepsis. Pulmonary function may be further compromised by pathology intrinsic to the lung itself, including pulmonary contusion, aspiration, airway obstruction, pneumonia, pneumothorax, hemothorax, and atelectasis. The acute pulmonary vascular response to shock largely parallels that of the systemic vasculature. The increase in pulmonary vascular resistance, which may proportionally exceed that of the systemic circulation, transiently accompanies the systemic adrenergic response. ARDS is a syndrome of progressive lung injury that may arise as a direct consequence of shock or other disease processes. The characteristic findings of ARDS are the presence of pulmonary edema, hypoxemia, and significantly decreased lung compliance. The pulmonary edema is noncardiac in origin and occurs in the face of normal left heart pressures. The hypoxemia results from the development of intrapulmonary shunting and perfusion of under and nonventilated alveoli. The decrease in lung compliance results from the loss of surfactant and lung volume in combination with the presence of interstitial fluid and alveolar edema. Progressive histologic changes of ARDS become apparent in pulmonary capillaries, interstitium, and alveoli. Initially, interstitial edema develops with swelling of the capillary endothelial cells and the type I pneumocytes. The type I pneumocytes subsequently slough, and alveolar edema ensues. Functional surfactant is lost with a significant increase in alveoli opening pressure and decrease in alveolar surface tension. Mechanisms proposed in the pathogenesis of ARDS include injury from mediators of inflammation elaborated elsewhere, and from activated cellular blood elements.
218 Which of the following statement(s) is/are true concerning the diagnosis and management of hypovolemic shock?
a. A fall in hematocrit or hemoglobin always accompanies hemorrhagic shock
b. The treatment of shock is generic regardless of the etiology
c. Pharmacologic intervention to increase myocardial contractility in hypovolemic shock is an important part the early management
d. Complications are less frequent after treatment of hemorrhagic shock than septic or traumatic shock
Answer: d
Hypovolemic shock is readily diagnosed when there is an obvious source of volume loss and overt signs of hemodynamic instability and increased adrenergic output are present. After acute hemorrhage, hemoglobin and hematocrit values do not change until compensatory fluid shifts have occurred or exogenous fluid is administered. These values decrease once transcapillary refill, osmotic-induced shifts, or non-RBC volume resuscitation expands the blood volume. It is imperative that the distinction be made between hypovolemic and cardiogenic forms of shock, because appropriate therapy differs dramatically. Restoration of perfusion in hypovolemic shock requires reexpansion of circulating blood volume in conjunction with necessary interventions to control ongoing volume loss. Continued hemodynamic instability after fluid resuscitation implies that shock has not been reversed or that there is ongoing blood or volume loss. In severe, prolonged hypovolemia, ventricular contractile function may itself become depressed and require inotropic support to maintain ventricular performance, but in general, pharmacologic interventions directed toward increased contractility in situations of inadequate preload are ineffective, further complicate metabolic derangements, and are not indicated until adequate volume replacement has been completed. Complications are less frequent after treatment of hemorrhagic shock than in situations of septic or traumatic shock. In the later circumstances, the massive activation of inflammatory mediator response systems and consequences of their disseminated, indiscriminate cellular injury can be quite profound.
219 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
Answer: c, d
The neuroendocrine response to shock attempts to achieve restoration of effective blood volume, mobilization of metabolic substrates, and maintenance of central profusion. Both peripheral and central afferent stimuli to the central nervous system are involved in inducing this response. Hypotension, associated with a decrease in impulses from the aortic and carotid baroreceptors, disinhibits the vasomotor center. This disinhibition results in increased adrenergic output and decreased vagal activity. Sympathetic nerve endings release norepinephrine, inducing peripheral and splanchnic vasoconstriction which is responsible for greater than 80% of systemic vascular resistance and is a major contributor to maintenance of central organ perfusion and venous return. Plasma levels of both epinephrine and norepinephrine are elevated with injury, and the degree of the catecholamine elevation corresponds to the magnitude of injury. In shock the effects of endogenous epinephrine are largely metabolic. In addition to initiating autonomic nervous activity, the hypothalamus secretes releasing hormones, which induce the stress hormone release of the pituitary. As part of this response, adrenocorticotropic hormone (ACTH) secretion by the anterior pituitary is increased stimulating cortisol secretion by the adrenal cortex. In conjunction with elevated plasma levels of cortisol and epinephrine, increased pancreatic secretion of glucagon accelerates hepatic gluconeogenesis and further aggravates the glucose intolerance that follows injury and sepsis. The secretion of renin is increased in responses to adrenergic discharge and decreased perfusion of the juxtaglomerular apparatus in the kidney. Renin allows formation of angiotensin I in the liver, which is then converted to angiotensin II in the lungs. Angiotensin II is an extremely effective vasoconstrictor that further augments sympathetic-mediated vasoconstriction.
220 A 22-year-old man sustains a single stab wound to the left chest and presents to the emergency room with hypotension. Which of the following statement(s) is/are true concerning his diagnosis and management?
a. The patient likely is suffering from hypovolemic shock and should respond quickly to fluid resuscitation
b. Beck’s triad will likely be an obvious indication of compressive cardiogenic shock due to pericardial tamponade
c. Echocardiography is the most sensitive noninvasive approach for diagnosis of pericardial tamponade
d. The placement of bilateral chest tubes will likely resolve the problem
Answer: c
Shock from cardiac compression occurs when external pressure on the heart impairs ventricular filling. Because ventricular filling is a function of venous return and myocardial compliance, any process that places pressure on the heart can cause compressive cardiogenic shock. Included among these are pericardial tamponade, tension pneumothorax, mediastinal hematoma, and positive pressure from mechanical ventilation. Any patient with hypotension after a wound in proximity of the heart should be considered to have compressive cardiogenic shock until proven otherwise. The classical clinical findings of pericardial tamponade include Beck’s triad of hypotension, neck vein distention and muffled heart sounds. Pulses paradoxus may be noted (this involves a decrease rather than the normal increase of systolic blood pressure with inspiration; values 10mmHg are significant). These findings, however, may be obscured in a noisy emergency room environment by positive pressure ventilation or by associated injuries. Placement of a CVP catheter confirms the elevation of right-sided filling pressure. If a pulmonary artery catheter has been placed, findings consistent with tamponade or other forms of cardiac compression are a trend toward equalization of chamber pressures as hypotension progresses. In the patient at risk, echocardiography is an extremely sensitive and noninvasive approach to demonstrate pericardial fluid and the need for operation. Pericardial tamponade must be relieved urgently and cardiac injuries require emergent sternotomy. Chest tube placement would not be appropriate as the sole treatment in this patient.
221 A 32-year-old man suffers a spinal cord injury with a resultant paraplegia in a motorcycle accident. He presents to the emergency room with hypotension. Which of the following statement(s) is/are true concerning his diagnosis and management?
a. The low blood pressure can be assumed to be due to neurogenic shock
b. The sole cause of hypotension is the loss of sympathetic input to the venous system
c. Despite significant hypotension, secondary organ injury will be uncommon
d. There is no role for pharmacologic intervention to maintain blood pressure
Answer: c
Neurogenic shock results from interruption of sympathetic vasomotor input and develops after spinal cord injury, spinal anesthesia, and severe head injury. Under normal conditions, baseline sympathetic activity establishes a degree of arteriolar and venous constriction. Ablation of this tone results in decreased systemic vascular resistance and a dramatic increase in venous capacity, causing hypotension due to relative hypovolemia. Arteriolar dilatation not only lowers the systemic vascular resistance but also allows previously unopened vascular beds to be perfused, greatly expanding venous capacity. Removal of sympathetic inputs to innervated portions of the venous system allows further venodilatation. Restoration of an effective, albeit expanded, intravascular volume may require extremely large volumes of resuscitation fluid to restore normal cardiac filling pressures. This will restore cardiac output and reverse hypotension. However, pharmacologic intervention with vasoactive drugs may be necessary and is preferable to excessive volume resuscitation. Post-shock sequelae are infrequent. Although there is significant hypotension with neurogenic shock, there is usually little if any hypoperfusion. Thus, activation of inflammatory cascade and subsequent organ injury rarely occur.
A major pitfall in the management of neurogenic shock arises when there is coexistent hemorrhage or ongoing volume loss that is not appreciated. This is not an unusual situation because cervical spine trauma causing paraplegia or severe head injury is frequently associated with multiple injuries. Thus, in trauma the initial response to neurogenic shock is large volume resuscitation regardless of the presumed etiology. If hemodynamic instability persists after initial trauma resuscitation, one must assume that the cause is not neurogenic and search for occult blood loss or cardiogenic causes of shock.
222 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
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 protozoa have all been reported to produce a clinical picture of septic shock, but the overall response is independent of the specific type of invading organism. Septic shock develops as a consequence of the combination metabolic and circulatory derangements accompanying the systemic infection. It appears that the circulatory deficits are preceded by the metabolic abnormalities induced by infection. In fact, the circulatory changes in hyperdynamic sepsis appear to be an adaptive response to the underlying metabolic dysfunction. Cardiac output is high and systemic vascular resistance low in hyperdynamic septic shock. However, splanchnic vasoconstriction is pronounced even in the absence of systemic hypotension and even though systemic vascular resistance is reduced. Expansion of circulating blood volume can occur through either transcapillary refill or fluid resuscitation. Due to the ongoing inflammatory mediator-induced increases in capillary permeability and continued loss of intravascular volume, exogenous volume resuscitation must be provided to restore venous return and ventricular filling.
223 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
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 other inflammatory stimuli. Elevation of serum levels of TNF have been reported shortly after experimental trauma and shock, however, documentation of elevated circulating levels of TNF in human shock is less clear. Furthermore, circulating levels of TNF cannot be correlated with severity of tissue injury or shock. This variability is thought to be due to rapid clearance and uptake by membrane receptors and by soluble membrane receptors that are released from multiple cells following stress and injury. Following hypoperfusion the liver and gut appear to be the major source of TNF that is rapidly cleared but responsible for inducing hepatocyte changes following shock. The release of breakdown products and escape of bacterial and endotoxin through the damaged mucosal barrier of the gut following shock allows or induces activation of tissue-fixed macrophage (Kupffer cell) of the liver which then produces secondary inflammatory mediators contributing to the post-resuscitation clinical response and inflammatory mediator activation seen in the systemic inflammatory response syndrome.
TNF is central to inflammatory response, particularly in sepsis and following endotoxemia or bacteremia. TNF also induces secondary inflammatory responses through direct interaction with specific membrane receptors, TNF-r. Treatment with anti-TNF antibody in the experimental setting protects animals from the deleterious effects of lethal bacteremia and endotoxemia. However, recently completed clinical trials in septic patients utilizing infusion of monoclonal antibodies to the TNF molecule have shown no overall survival benefit.
224 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
Answer: d
Inflammatory mediators have recently been recognized as playing a significant role in the clinical manifestations and progression of shock and the development of subsequent complications. These mediator systems function primarily as parcrine and autocrine agents in the local environment and are not usually detectable systemically. The over-expression and systemic dissemination of these mediators produces the toxic autodestructive processes underlying multiorgan failure syndrome with attendant high mortality. The compliment cascade is activated in shock and tissue injury through both the classical and alternative pathways. Activation of either pathway results in generation of the anaphylatoxin, C3a and C5a, soluble products with potent systemic hemodynamic effects. The eicosanoids, which include the prostaglandins and leukotrienes are formed acutely from arachidonic acid released from the membrane phospholipid by phospholipase A2. Eicosanoids are not stored in any measurable level and are generated as needed from readily available arachidonic acid in response to various inflammatory phenomena. Platelets, white cells, and endothelial cells are a rich source of these compounds. Thromboxane (TXA2) is the major arachidonic acid metabolite elaborated by platelets. TXA2 induces intense vasoconstriction, platelet aggregation and degranulation, neutrophil margination in the microcirculation and bronchial constriction. PGI2, the major arachidonic acid metabolite formed by endothelial cells, serves a check against actions of TXA2. PGI2 is a vasodilator and a potent inhibitor of platelet aggregation. Platelet aggravating factor is a potent phospholipid mediator released by neutrophils, platelets, macrophages and endothelial cells in response to ischemia, tissue injury and sepsis. Its effects include decreased cardiac function, increased pulmonary vascular resistance, bronchoconstriction, peripheral vasodilatation, and increased vascular permeability.
225 Which of the following physical findings are associated with the various classes of hemorrhagic shock?
a. Mild shock (< 20% blood volume): Pallor, cool extremities, diminished capillary refill and diaphoresis
b. Moderate shock (20%–40% blood volume): All of the above plus tachycardia and hypotension
c. Severe shock (> 40% blood volume): Systemic hypotension, changes in mental status, tachycardia, oliguria
d. All of the above
Answer: a, c
PHYSICAL FINDINGS IN HEMORRHAGIC SHOCK*
Moderate
Mild (<20% (20%-40% Severe(>40%
Blood Volume) Blood Volume) Blood Volume)
Pallor Pallor Pallor
Cool extremities Cool extremities Cool extremities
Diminished capillary Diminished capillary Diminished capillary
refill refill refill
Diaphoresis Diaphoresis Diaphoresis
Collapsed Collapsed Collapsed
subcutaneous subcutaneous subcutaneous
veins veins veins
Tachycardia Tachycardia
Oliguria Oliguria
Postural Hypotension
hypotension Mental status
changes
* Alcohol or drug intoxication may alter physical findings.
226 A 68-year-old male who underwent a repair of an abdominal aortic aneurysm 5 days ago, develops tachycardia, tachypnea, hypotension with cool, pale, mottled cyanotic extremities. He is agitated and complains of shortness of breath. Which of the following statement(s) is/ are correct concerning his diagnosis and management?
a. Myocardial ischemia secondary to preexisting coronary artery disease is most likely the underlying cause of this problem
b. Invasive hemodynamic monitoring with a Swan-Gantz catheter will demonstrate a low cardiac output, a high systemic vascular resistance, and elevated cardiac filling pressures
c. The use of morphine sulphate and nitrates should be part of the initial management
d. The primary pharmacologic treatment involves the use of moderate doses of inotropic agents
e. Afterload reduction with nitroprusside is absolutely contraindicated
Answer: a, b, d
Intrinsic cardiogenic shock results from failure of the heart as an effective pump. Coronary artery disease is the most common cause of myocardial insufficiency, but contractile dysfunction may also rise as a consequence of cardiomyopathy, myocarditis, or metabolic abnormalities. Invasive hemodynamic monitoring often establishes a specific nature of shock and allows appropriate treatment to be delivered in an effective and expedient manner. Hemodynamic findings consistent with cardiogenic shock include a low cardiac output and high systemic vascular resistance, with elevated cardiac filling pressures. The initial measures in the management of cardiogenic shock include the administration of supplemental oxygen, mechanical ventilation (as needed), and appropriate treatment of dysrhythmias. Hypotension usually precludes the use of morphine sulfate and nitrates, drugs typically used in simple congestive heart failure to alleviate cardiac pain and ameliorate pulmonary vascular congestion. The use of beta-adrenergic agonists such as dopamine and dobutamine, in moderate doses, offers positive inotropic support without excessive alpha-adrenergic activity. Increasing the inotropic state of the heart shifts the entire Starling curve upward, resulting in increased cardiac output for each level of cardiac filling. Afterload reduction may prompt increases in cardiac output through decreases in resistance to flow. The use of nitroprusside or other dilators requires relative blood pressure stability and close hemodynamic monitoring. Infusion of afterload-reducing agents can be administered in conjunction with inotropic support.
227 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
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 intracellular adenine neuclotides occurs. As ATP further degrades there is an elevation in plasma and intracellular levels of hypoxanthine and xanthene which upon restoration of perfusion and reoxygenation are catalyzed by xanthine oxidase resulting in the formation of superoxide radicals. These radicals plus others such as hydrogen peroxide and hydroxyl radical are generated and lead to endothelial and parenchymal cell injury through membrane lipid peroxidation and activation of critical enzymes. These radicals have also been shown to be involved in the expression of proinflammatory phenotype endothelial cells and on macraphages and neutrophils. The proinflammatory phenotype of the endothelium includes procoagulant activity and the expression of adhesion molecules on the membrane surface, including the intercellular adhesion molecule-1 (ICAN-1) and the selectins. The subsequent adhesion of activated neutrophils to the endothelial leads to an explosive oxidative burst producing additional radicals and extensive release of proteolytic enzymes leading to injury and disruption of the endothelial lining, extensive capillary leak, and massive interstitial edema. Passive immunization of animals with monoclonal antibodies to either the neutrophil adhesive complex or the endothelial selectins dramatically lessens ischemia/reperfusion microvascular injury.
228 Which of the following statement(s) is/are true concerning the physiology of the microvascular system?
a. Filtration of capillary fluid into the interstitial and the subsequent reabsorption is influenced by Starling’s law of ultrafiltration
b. The most important variable controlling blood to a capillary bed is the length of the vessel
c. Most of the resistance to systemic blood flow occurs at the arteriolar level
d. Adrenergic vasoconstriction can arrest blood flow to an entire capillary bed
Answer: a, c, d
Exchange of material between the vascular space and the cell of various tissues via the interstitial space is essential for organ viability and occurs at the capillary level. The filtration of capillary fluid into the interstitium and its subsequent reabsorption into the post capillary venule is governed by microvascular permeability in conjunction with the balance between hydrostatic and oncotic pressures. The relation of these forces to one another (and their net effects) are illustrated by what is termed Starling’s law of ultrafiltration. In normal circumstances, a net filtration from capillary to interstitium is effected by a relatively higher capillary hydrostatic pressure, whereas net reabsorption from the interstitium back into the post capillary venule occurs as hydrostatic pressure falls and oncotic forces predominate. Although the mechanisms controlling blood flow to the capillary bed are complicated and vary among the different tissues, certain concepts are useful. Poiseuille’s law describes the relation between flow of fluid through a tube and the tube length and radius, the fluid viscosity, and the pressure gradient between ends of the tube. The radius of the tube (or vessel) is the single most important variable, because flow is proportional to the radius to the fourth power. Vasoconstrictive and vasodilatory influences directly impact local blood flow, as well as flow to other tissues through secondary effects on the systemic pressure. This secondary effect of peripheral vasoconstriction maintains the pressure gradient for central perfusion of the heart and brain. Systemic blood flow meets most of its resistance at the arteriolar level. While the individual capillary radius is significantly smaller, the vast number of capillaries offers less total resistance. The vascular smooth muscle in arterioles has both a-and b- adrenergic receptors. Alpha stimulation affects vasoconstriction where beta stimulation affects vasodilatation. The efferent sympathetic fibers innervating the precapillary resistance vessels and the venous capacitance vessels release norepinephrine on stimulation, which induces smooth muscle contraction and narrowing of the caliber of the vessels. These contractions are potent enough that blood flow to entire capillary beds can be arrested by adrenergic vasoconstriction.
229 Which of the following statement(s) is/are true concerning the effects of MOFS?
a. Pulmonary dysfunction tends to arise early and may resolve within 7 to 10 days
b. Unless the precipitating insult has prompted oliguric acute tubular necrosis, renal function tends to be maintained early in the course of MOFS
c. Although hepatic dysfunction is common with MOFS, the GI tract plays little role in this process
d. Intercurrent nosocomial infection, most commonly pulmonary, is a common complication providing a “second hit” to the patient
Answer: a, b, d
Pulmonary dysfunction typically arises early in the development of systemic inflammation and may represent mild relatively localized acute lung injury or it may be a prelude to fulminant ARDS. The lung injury, and associated dysfunction, may resolve over the initial 7 to 10 days or persist, depending on the ongoing pathologic process. Many times a “second hit” such as a nosocomial infection, which is most commonly pulmonary, is a complication which can frequently worsen the pulmonary condition. Renal function tends to be maintained early in the course unless the precipitating insult has been prompted by a sudden oliguric acute tubular necrosis. With persistent activation and inflammatory mediators, glomerular filtration falls and the development of oliguric or polyuric renal failure marks the gradual transition into MOFS. Gastrointestinal abnormalities include ileus, stress ulceration, diarrhea, and mucosal atrophy. Breakdown of the mucosal barrier allows translocation of bacteria and endotoxin. Hepatic dysfunction is marked by progressive rise in serum bilirubin levels after a latent period of several days.
230 Which of the following statement(s) is/are true concerning hypoadrenal shock?
a. In the United States, idiopathic adrenal atrophy (Addison’s disease) is the most common cause
b. Laboratory abnormalities include hyponatremia, hypochloremia, and hyperkalemia
c. Fever may be seen with hypoadrenal shock
d. ACTH stimulation test is the diagnostic test of choice to confirm hypoadrenal shock
Answer: b, c, d
Shock of a dramatic nature, poorly responsive to resuscitation, may develop as a consequence of adrenal insufficiency. In this country, adrenal insufficiency most commonly arises as a consequence of the chronic therapeutic administration of high doses exogenous corticosteroids causing adrenal suppression. Other causes include idiopathic adrenal atrophy (Addison’s disease), tuberculosis, metastatic disease, bilateral hemorrhage, and amyloidosis. The stress of illness, operation, or trauma typically requires that the adrenal glands secrete cortisol in excess of that required in the nonstressed state (approximately 3–4 fold). Insufficiency not otherwise apparent may manifest itself only after major physical stress. Findings associated with adrenal insufficiency include weakness, fatigue, anorexia, abdominal pain, nausea, vomiting, and weight loss. Surgical patients with significant adrenal insufficiency need not present with the above findings. More typical is the development of refractory shock, frequently with hyperthermia, in the course of injury or illness. Hypotension may be dramatic despite massive volume resuscitation and pressor support. Laboratory findings suggesting hypoadrenalism include hyponatremia, hypochloremia and hyperkalemia. The diagnosis of adrenal insufficiency may be confirmed or excluded by means of an ACTH stimulation test. A significant major cortisol response should be elicited by ACTH administration.
231 Which of the following statement(s) is/are correct concerning the cardiovascular response to shock?
a. Changes in cardiac contractile function shift the Frank Starling curve up and down
b. Venoconstriction from skeletal muscle is a significant contributor to the restoration of blood volume with shock
c. Arterial vasoconstriction affects all vascular beds equally
d. The total circulating blood volume is equally split between the arterial and venous system
Answer: a
Central in the general cardiovascular response to shock is the action of the heart itself. The principle determinants of cardiac function in the normal heart are the volume of blood available for the heart to pump (preload), the systolic contractile capability, and the diastolic filling of the ventricles. In hypovolemia, the two dynamic variables of cardiac function, ventricular filling and myocardial contractility remain paramount and determine the stroke volume. The product of stroke volume and heart rate in turn determines the cardiac output. Increases in ventricular end-diastolic volume, reflecting venous return, cause ventricular distention. Ventricular distention in turn produces increased volume output with each stroke, the Frank Starling mechanism. Contractile function may vary independent of volume status. Changes in the contractile function shift the Starling curve up and down, producing increases or decreases in stroke volume for any given end-diastolic volume. A fundamental requirement for cardiovascular function is adequate cardiac filling, and cardiac output cannot exceed venous return. The venous system contains nearly two-thirds of the total circulating blood volume, including 20% to 30% within the splanchnic venous system. Most of this volume resides in small veins, which comprise the bulk of venous capacitance. The venous system, especially that of the splanchnic circulation, becomes important in the physiologic compensation to hypoperfusion because it serves as a dynamic reservoir for the autoinfusion of blood volume involving both active and passive mechanisms. The splanchnic circulation makes major contributions to the maintenance of venous return, therefore, it is likely that sympathetic venoconstriction is responsible for a portion of the blood mobilized from the splanchnic venous circulation. Sympathetic mediated venoconstriction in skin and skeletal muscle is probably not as significant as a source of blood volume. Selective vasoconstriction occurs in response to alpha adrenergic receptor stimulation with increased sympathetic activity in shock. Sympathetic stimulation does not cause significant vasoconstriction of either cerebral or coronary vessels, with normal blood flow maintained in these circulations. Blood flow to the skin is sacrificed early, followed by that to the kidneys and splanchnic viscera.
232 Which of the following statement(s) is/are true concerning pharmacologic agents used in the treatment of shock?
a. The primary difference between dopamine and dobutamine is the absence of significant a adrenergic activity
b. The renal and mesenteric vasoconstrictive effects of norepinephrine complicate and sometimes restrict its use
c. The apparent paradoxical use of vasodilators, such as nitroprusside, in shock is indicated as a means to augment cardiac function
d. Isoproterenol with its potent b-adrenergic effect, is a particularly useful agent in the treatment of all forms of shock
Answer: a, b, c
Therapeutic adjustments of intravascular volume (preload) and systemic vascular resistance (afterload) form the basis of the treatment strategies for all forms of shock. Optimal volume resuscitation should precede measures to augment to contractile function of the heart. Inotropic agents are used in shock when there is inadequate cardiac output despite adequate circulating blood volume. Dopamine and dobutamine are often times first line agents in the pharmacologic treatment of shock. Dopamine, at low doses, stimulates dopaminergic receptors producing renal arteriolar vasodilatation with associated increases in renal blood flow, urine output, and sodium excretion. At moderate doses, stimulation of cardiac b-receptors produces increases in contractility and cardiac output with little effect on heart rate or blood pressure. At higher doses, peripheral vasoconstriction from increasing a activity becomes more pronounced, prompting significant increases in vascular resistance and blood pressure. Dobutamine’s predominant effect is an increasing cardiac contractility with lesser increases in heart rate. Some reduction of peripheral vascular resistance may also occur. When compared to dopamine, dobutamine produces less peripheral vasoconstriction and less chronotropic response. Norepinephrine exerts both a and b-adrenergic effects, with a effects being evident at lower infusion rates and a effects more prominent at high doses. The major use of norepinephrine in current practice is in the patient with hypotension that persists despite appropriate volume resuscitation and the use of inotropic agents. Renal and mesenteric vasoconstrictive effects of norephinepherine complicate its use, especially when support is needed for significant periods of time. Isoproterenol is a potent b-adrenergic agent. With isoproterenol, myocardial oxygen demand is increased and diastolic coronary feeling is limited by tachycardia or diminished diastolic pressure. Indications for the use of isoproterenol are fairly limited, because agents with fewer adverse effects have become available.
Vasodilators are used to augment cardiac function through optimization of ventricular filling pressures (preload) and systemic vascular resistance (afterload) both of which reduce demands on the myocardium. Decreases in afterload prompt increases in cardiac output and venodilatation contributes to decreases in pulmonary venous pressure and central venous pressure. Hypotension, however, may develop therefore patients must have careful constant monitoring of arterial pressure and repeated hemodynamic measurements with a pulmonary artery catheter.
233 Which of the following statement(s) is/are true concerning the treatment of MOFS?
a. Prevention and therapy of MOFS requires control of the infectious or inflammatory source
b. Restoration of normal clinical parameters such as blood pressure, pulse rate, and urine output ensures optimal resuscitation in most patients
c. Branch chain amino acids play and important role in the nutritional support of the patient
d. Because of the nature of gut injury, total parenteral nutrition is preferred for most patients with MOFS
Answer: a, c
The therapy of MOFS is directed towards interrupting the involving pathophysiologic process and providing an optimal physiologic environment for healing and recovery. Fundamental concerns are control of the source of infection, inflammation or instability; restoration of microcirculatory blood flow and oxygen transfer, and the institution of optimal supportive care. Both the prevention and therapy of MOFS, therefore, requires source control and restoration of adequate profusion. Resuscitation efforts are directed toward restoration of adequate microcirculatory blood flow in all organ systems. Restoration of normal clinical parameters such as blood pressure, pulse rate, urine output, and acid-base balance does not ensure optimal resuscitation. The physiologic endpoint that most closely corresponds with adequate microcirculatory flow is the level of cardiac output and the oxygen delivery at which oxygen consumption and lactate production remain independent of flow.
The importance of metabolic support in the patient with MOFS cannot be overemphasized. The malnutrition of MOFS is markedly different than that of starvation and the nutritional requirements also differ. If optimal quantities of appropriately formulated amino acid solutions are given, protein synthetic rates can approach catabolic rates and the goal of nitrogen balance can be achieved. Formulas rich in branch chain amino acids appear to be more efficient in promoting nitrogen retention and minimizing urea production. Whenever feasible, enteral feeding is preferred over TPN because evidence suggests that bacterial translocation from the gut can be limited through the use of enteral feeds. Enteral absorption and processing of nutrients appears superior to TPN and lessens overall complications.
234 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
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 inflammation and microcirculatory hypoperfusion. Endothelial injury, platelet aggregation and activation of macrophages and neutrophils occur, and the clotting, fibrinolytic, kinin, and complement cascades are activated, along with the release of potent inflammatory cytokines. The effects of shock, resuscitation, and reperfusion, and the subsequent development of MOFS appear to be critically dependent on changes in the splanchnic and pulmonary microcirculations. These vascular beds appear to be major sites of activation of subsequent inflammatory mediator production that underlies the diffuse systemic inflammatory response. Extensive activation of the liver Kupffer cell and release of inflammatory mediators coupled with the ongoing release of activated neutrophils and by-products of activated gut macrophages is responsible for the injury to the pulmonary microcirculation and secondary induction of alveolar macrophage and additional inflammatory mediator systems. Excessive and persistent macrophage activation plays an essential role in MOFS and is hypothesized to represent the penultimate step in a series of continuous immuno-inflammatory stimulatory events, including local hypoxia, exposure to bacteria and toxins, and mediator release from localized areas of inflammation. When infection is the underlying or major contributing process, the diffuse inflammatory response develops independently of the specific type of microorganism. In noninfectious cases, the response also appears independent of the specific underlying cause.
235 Invasive hemodynamic monitoring using a Swan-Gantz catheter is essential in the optimal management of patients in shock or those suffering post-shock sequelae. Which of the following physiologic characteristics are associated with the various forms of shock?
a. Hypovolemic shock: Decreased pulmonary capillary wedge pressure (PCWP), decreased cardiac output, increased systemic vascular resistance (SVR)
b. Cardiogenic shock: Increased PCWP, decreased cardiac output, decreased SVR
c. Septic shock (hypodynamic): Decreased cardiac output, increased SVR
d. Neurogenic shock: Decreased PCWP, increased cardiac output, decreased SVR
Answer: a, c
236 Which of the following statement(s) is/are true concerning the relationship between cardiac function and effective blood volume?
a. A pulmonary capillary wedge pressure of 5–10 rules out fluid overload as a cause of pulmonary edema
b. A shift to the right in the Frank-Starling curve is associated with compromised cardiac function
c. Dilutional anemia may contribute to tachycardia even though blood volume and filling pressures are normal
d. The sole purpose of a pulmonary artery catheter is to measure pulmonary artery pressure and cardiac output
Answer: b, c
Although physical findings are often adequate to establish a diagnosis and institute management of cardiac failure, direct measurement of filling pressures of the right heart (central venous pressure) or the left heart (pulmonary artery pressure) may be required. Placement of a pulmonary artery catheter allows us to measure cardiac output by thermodilution and, more importantly, to sample mixed venous blood for saturation measurements which tell us the ratio between systemic oxygen delivery and oxygen consumption. From all of these measurements we can determine if cardiac output is normal for the level of filling pressure of the left ventricle, or if contractility is decreased. In the latter case, cardiac output will be lower than predicted for a given level of filling pressure. In the Frank-Starling curve, if the patient is to the right of the normal range, then cardiac function is compromised either because of valvular disease, extrinsic pressure such as pericardial tamponade, or more commonly, a decrease in contractility. If cardiac function and anatomy are normal, then blood volume, filling pressure and cardiac function are related to the Starling curve. The intake and output of fluid and salt is autoregulated to maintain the filling pressure of the left ventricle around 10 mm Hg. Extracellular fluid expansion is usually associated with normal blood volume. Gross expansion of extracelluar space results in deleterious effects if tissue edema can and often do exist with perfectly normal blood volume. In other words, a pulmonary capillary wedge pressure of 5–10 does not rule out fluid overload as a cause of pulmonary or GI dysfunction. In critically ill patients, the fear of hypotension and effect of perfusion usually results in infusion of intravenous salt and water in quantities which exceed losses. Consequently, most patients in the Intensive Care Unit have anemia, dilutional hypoproteinemia, and a compensatory increase in cardiac output. In response to anemia, these patients are tachycardic, even though blood volume is normal, filling pressures are normal, and total body extracellular fluid is excessive.
237 Which of the following statement(s) is/are true concerning methods of nutritional support?
a. Optimal results for enteral feedings are achieved with approximately half of calories supplied as carbohydrate and half as fat
b. Diarrhea is the most common complication of enteral feeds and is due to the high osmolarity of the carbohydrate components
c. The hyperosmolar nature of parenteral fat solutions requires central venous administration
d. Approximately 25–50% of calories should be provided as fat emulsion in patients receiving total parenteral nutrition
Answer: a, b, d
Most formulas for enteral feeding range from 1.0 to 2 cal/ml and include 3 to 7% protein. Most of the calories are supplied as glucose or sucrose, so that the solutions have a very high osmolarity. Cramps or diarrhea can result when these high osmolar solutions are placed into the stomach or intestine. Diarrhea is the major complication with most tube feeding formulas. Diarrhea can be minimized by the use of starch or fat as an energy source in tube feedings. This can be supplied as part of the commercial preparation or added in the form of medium chain triglycerides or other oils. The best results are usually achieved by supplying approximately half the calories as carbohydrate and half as fat. In patients receiving total parenteral nutrition, energy source is provided as carbohydrate, fat, and amino acid solutions. Parenteral feeding with carbohydrate is limited by the sclerotic effect of hyperosmolar solutions on veins. Fat is a more efficient energy source and can be given through peripheral veins in concentrations of either 10 or 20%. Most intensivists favor supplementing standard total parenteral nutrition solution with intravenous fat to provide at least 100 grams of fat emulsion each week to preclude fatty acid deficiency. Giving up to 25 to 50% of calories each day as fat emulsion may optimize the delivery of this caloric delivery.
238 Which of the following statement(s) is/are true concerning the autoregulation necessary to maintain oxygen consumption and oxygen delivery?
a. A change in oxygen consumption is followed by a proportionate change in oxygen delivery
b. A change in oxygen delivery is followed by a change in oxygen consumption
c. Increases in oxygen delivery are due solely to an increase in cardiac output
d. The normal ratio of oxygen delivery to consumption is 2:1
Answer: a
The relationships between oxygen consumption and oxygen delivery represent one of the most interesting regulation systems in homeostasis. First of all, if one of the three components of oxygen delivery is abnormal, endogenous mechanisms regulate the other two until normal oxygen delivery has been restored. The various combinations of compensatory mechanisms supply adequate oxygen for systemic metabolism through a wide range of variations in oxygen delivery. When there is a change in oxygen consumption, there is a proportionate change in oxygen delivery, which occurs almost immediately, mediated completely by a change in cardiac output. Conversely, a primary change in oxygen delivery is not followed by any change in oxygen consumption. The normal ratio of oxygen delivery to consumption is approximately 5:1.
239 Which of the following statement(s) is/are true concerning O2 venous saturation monitoring?
a. The normal saturation of mixed venous blood is 50%
b. Mixed venous blood obtained for saturation monitoring can be obtained from any peripheral vein
c. If arterial blood is fully saturated, the saturation of mixed venous blood is 80%
d. In less than fully saturated blood, the difference between arterial and venous saturation corresponds to oxygen extraction
Answer: c, d
The relationship between oxygen delivery and oxygen consumption is reflected in the amount of oxygen in venous blood. Under normal circumstances, oxygen delivery is 1000 cc/min and oxygen consumption is 200 cc/min. The amount of oxygen extracted is 20% of that delivered, and 80% of oxygen is still present in venous blood returning to the heart. Usually arterial blood is fully saturated, and under normal circumstances, the saturation of mixed venous blood (SVO2) will be 80%. This measurement must be made in mixed venous blood since the relative extraction of organs served by the superior and inferior vena cava and coronary sinus are quite different. As long as arterial blood is fully saturated, this observation holds true regardless of the absolute level of oxygen consumption or oxygen delivery. If the arterial blood is less than fully saturated, the difference between arterial and venous saturation corresponds to the oxygen extraction, hence the oxygen delivery/oxygen consumption ratio.
240 Which of the following statement(s) is/are true concerning oxygen kinetics in a critically ill, febrile patient?
a. Oxygen consumption will likely exceed three times normal
b. The high cardiac output and pulse rate are designed to increase oxygen delivery
c. The hyperdynamic response may actually increase oxygen delivery to exceed the increase in oxygen consumption
d. The patient can maintain adequate compensation as long as the oxygen delivery/oxygen consumption rate is greater than 2:1
Answer: b, d
In critically ill patients oxygen consumption may be elevated or depressed, but slight to moderate elevations in oxygen consumption is the most common abnormality in critically ill patients. Oxygen consumption will be elevated in proportion to the amount of inflammation. A febrile patient with significant signs of septic toxicity will typically have an oxygen delivery at 1.5 to 2 times normal. It is very unusual for a critically ill patient to experience oxygen consumption greater than twice normal. This occurs only in situations of severe muscular exercise such as seizures or tetanus. During hypermetabolism, a change in oxygen consumption is followed promptly by a proportionate change in oxygen delivery. Hence, it is “normal” for a hypermetabolic patient to have a high cardiac output and pulse rate. Rarely the hyperdynamic response exceeds the increase in oxygen consumption, reflected in a ratio higher than 5:1 and venous saturation greater than 80%. Some patients cannot mount an increased oxygen delivery in response to increased oxygen consumption because of the combination of hypoxemia, anemia, and myocardial failure. If this occurs, then the oxygen delivery/oxygen consumption ratio will be less than 5:1. The patient will compensate for this by increased oxygen extraction, however, and the patient will remain stable as long as the ratio is greater than 2:1.
241 Which of the following statement(s) is/are true concerning the treatment of pulmonary interstitial edema?
a. Diuresis and blood transfusion is a valuable step
b. Salt-poor albumin leaks through the capillaries and worsens the condition
c. Mannitol is contraindicated as a diuretic in this clinical situation
d. Isoproterenol is a poor choice as an ionotropic agent
Answer: a
Treatment of pulmonary edema has two important goals, the first is to improve oxygenation if it is impaired, and the second is to minimize fibrosis and bacterial infection, which often accompany pulmonary edema caused by capillary injury. The treatment of interstitial edema is to maintain the hydrostatic pressure as low as compatible with adequate cardiac output and to raise the oncotic pressure selectively in the vascular space. These measures, combined with fluid restriction and diuresis, will decrease the amount of pulmonary edema. Since it is desirable to maintain filling pressures of the left ventricle as low as possible while maintaining a good cardiac output, inotropic drugs to improve left ventricular contractility are helpful. Isoproterenol or dopamine should be used, with serial cardiac output and filling pressure measurements. The first step in decreasing pulmonary edema is to decrease the pulmonary capillary hydrostatic pressure as low as is compatible with an adequate cardiac output. This is done by diuresis and fluid restriction. As the patient falls behind in blood volume, signs of hypovolemia may appear. Blood volume is then replenished with a fluid that stays in the vascular space. Packed red cells are ideal for this application. When the hematocrit is normal, concentrated salt-poor albumin should be used. This hyperoncotic fluid replenishes the blood volume by attracting interstitial fluid from throughout the body into the vascular space and supplements diuresis. This technique is useful even in the septic patient who may have increased capillary permeability and may loose albumin from the vascular space at a rapid rate. Even if albumin “leaks out”, the short term effects of expanding blood volume and decrease in edema will appear.
242 Which of the following statement(s) is/are true concerning the pathophysiology of gas exchange?
a. Hypoventilation in relation to perfusion can result in an oxygen saturation of less than 100%
b. Diffusion block and / mismatch can almost completely be overcome by breathing 100% oxygen
c. Transpulmonary shunting does not occur under normal circumstances
d. The normal arterial oxygen saturation should be 100%
Answer: a, b
Under normal conditions, red blood cells in the pulmonary capillaries become fully saturated and oxygen dissolves in plasma resulting in blood PO2 of 100 and O2 saturation of 100%. This equilibration may be disturbed by hypoventilation in relationship to the perfusion (/ mismatch), diffusion block caused by interstitial fibrosis, or perfusion of nonventilated alveoli. Diffusion block and / mismatch can almost be completely overcome by breathing 100% oxygen, hence hypoxemia during exposure to high alveolar PO2 is caused by total / mismatch, so-called transpulmonary shunting or venous ad mixture. Under normal circumstances, about 5% of the blood entering the left atrium has been shunted away from the pulmonary capillaries, either as the result of bronchial nutritive blood flow or through thebesian veins opening directly into the left side of the heart. This phenomenon, combined with a normal minor / mismatch associated with breathing at rest and positional changes in pulmonary blood flow, result in the fact that normal arterial PO2 is 90–100 mm Hg and the normal O2 saturation is 98%.
243 Which of the following statement(s) is/are true concerning CO2 transfer in the lung?
a. Carbon dioxide excretion is a direct function of alveolar ventilation
b. Normally end tidal CO2 should be identical to PaCO2
c. The gradient between end tidal and arterial CO2 can be an indirect measure of nonperfused alveoli
d. Positive pressure ventilation under normal airway pressures creates a significant end tidal PaCO2 gradient
Answer: a, b, c
The amount of carbon dioxide excretion is directly related to alveolar ventilation. While oxygenation is a function of matching blood flow to alveoli, carbon dioxide excretion is a direct function of ventilation or hyperventilation of alveoli with some blood flow. Normally the end tidal CO2 represents mixed alveolar gas which is at equilibrium with pulmonary capillary blood, hence with arterial blood. Therefore, the end tidal CO2 and the PaCO2 should be identical. End tidal CO2 measurement is a very useful continuous measurement of PaCO2 which can be used as a monitor when the lung is normal, as in ventilator weaning. Furthermore, the gradient between end tidal and arterial CO2, when it is large, acts as an indirect measure of nonperfused alveoli and/or compression volume. In patients who are ventilated with positive pressure ventilation, a significant end tidal PaCO2 gradient occurs only when peak airway pressures are very high (over 30 cm H2O) and the compression volume is a significant component of each exhaled breath.
244 Which of the following statement(s) is/are true concerning the assessment of protein reserve?
a. Conventional serum proteins such as albumin and globulin are early indicators of malnutrition
b. The total lymphocyte count reflects immune status and not nutrition
c. Antigen skin testing reflects patient immunity and not nutrition
d. Measurement of urea excretion in urine can be used as a measurement of protein breakdown
Answer: d
Since protein is the functional and structural chemical of the body, most nutritional assessment techniques are estimates of protein reserves. The actual nitrogen balance can be measured by measuring the amount of nitrogen excreted. This is most conveniently done by measuring the amount of urea excreted in the urine, assuming that urea constitutes 85% of the total nitrogen excretion. Knowing nitrogen excretion, the amount of protein catabolized can be estimated and compared with the amount of protein ingested by the patient. Indirect assessments of protein reserves are based on single measurements of body substances that are dependent on rapid protein synthesis for maintenance of normal levels. Conventional serum proteins such as albumin and globulin are not affected by malnutrition until it is very severe. Proteins such as prealbumen and transferrin, which turn over more rapidly, are better indicators of protein status. Lymphocytes are rapidly destroyed and protein is required for the formation of new cells. Consequently, the absolute lymphocyte count is a useful measure of the status of protein reserves. The lymphocyte count is considered by some the best single “static” measurement characterizing nutritional status. Protein is also required for synthesizing the cells and mediators involved in skin test reactivity. Although skin test reactivity is a manifestation of lymphocyte-mediated immunity, its usefulness in patient assessment is probably that of assessment of the inflammatory response than lymphocyte activity per se. Some chronically and acutely malnourished patients convert from reactive to anergic, and reactivity can be restored by nutritional repletion.
245 Useful steps to optimize systemic oxygen delivery include:
a. Maintaining mean arterial blood pressure between 50 and 90 mm Hg
b. Optimizing PEEP levels by monitoring mixed venous saturation
c. Turning the patient prone
d. Sedation or paralysis
Answer: a, b, c, d
Optimizing systemic oxygen delivery in relationship to oxygen requirement is the primary goal of management. Improving oxygenation of the blood itself by improving alveolar inflation is only one of the steps in optimizing oxygen delivery. Equally or more important are treating anemia and optimizing cardiac output. Cardiac output should be optimized to maintain delivery of four to five times consumption. In general, this means avoiding those factors which decrease cardiac output, rather than actively trying to increase cardiac output. Blood pressure should be maintained high enough to provide coronary perfusion (over 50 mm Hg mean pressure) but not so high as to limit left ventricular function (over 90 mm Hg mean arterial pressure). Alveolar collapse is treated by cleaning the airways, avoiding 100% oxygen, and moving fluid from the lung or chest, and finally by the use of positive end exploratory pressure to hold open those alveoli which have been opened by other measures. The optimal level of PEEP is that level that maintains arterial oxygenation but does not decrease venous return or cardiac output. This optimal level is best determined by monitoring mixed venous saturation. Another step in optimizing lung function is to take advantage of the gravitational effects on pulmonary blood flow by turning the patient prone or to a full lateral position to direct blood flow to areas of optimal alveolar function. This step will often result in an opening in the closed posterior alveoli which have been compressed by the weight of the fluid in the lungs. At the same time that oxygen delivery is optimized, oxygen consumption should be decreased to normal or even below normal if necessary. Treating infection, providing adequate sedation, and establishing muscular paralysis decrease oxygen consumption, and decrease the need for oxygen delivery.
246 Phases of multiorgan failure will include:
a. Generalized increased capillary permeability
b. A hypermetabolic state
c. Organ malfunction
d. All of the above
Answer: d
Clinically the multiple-organ failure patient progresses through well-defined phases. These phases include: Phase 1—a generalized increased capillary permeability resulting in edema, weight gain, and intravenous volume replacement, increased protein concentration in urine and lymph. Although the pulmonary microvasculature has been most thoroughly studied, it is apparent that the lung is simply the most obvious end organ in a generalized permeability defect. Phase 2—A hypermetabolic state, with increased oxygen consumption and a compensatory increase in oxygen delivery characterized by tachycardia and high cardiac output. This condition following systemic ischemic and reperfusion is similar to hypermetabolism following endotoxemia, localized sterile inflammation, and infusion of stress hormones, suggesting a common mechanism. Phase 3—Organ malfunction due to localized edema and cellular injury, particularly in the kidney, liver, brain, and host defense system. Hemorrhagic shock predisposes to bacterial translocation and endotoxin absorption from the intestine. Phase 4—In the absence of systemic sepsis, organs may recover to normalcy or may be irreversibly damaged, leading to a need for chronic support. If the organ failure phases lead to systemic infection or irreversible tissue damage in the lung or brain, the death of the entire organ is likely.
247 Which of the following statement(s) is/are true concerning oxygen consumption (O2)?
a. O2 is normally 100–120 cc2/m2/min
b. Resting O2 is controlled by the level of thyroid and catecholamine hormones
c. Under steady state conditions the amount of oxygen consumed exceeds the amount of oxygen taken up by the pulmonary capillaries
d. O2 is dependent on the status of pulmonary function
Answer: a, b
Oxygen consumed in the process of metabolism is expressed as the volume of oxygen per minute (O2). O2 is normally 100–120 cc2/m2/min, or 200 cc/min for a typical adult. Resting O2 is a function of metabolizing body cell mass, with fine tuning control provided by the level of thyroid and catecholamine hormones. O2 decreases under conditions of hypothermia, paralysis, and hypothyroidism. O2 increases during exercise or muscular activity, hyperthermia, profound hypothalamic injury, hyperthyroidism, catecholamines, and inflammatory mediators, particularly the interleukin cytokines. Under steady state conditions, the amount of oxygen consumed in systemic metabolism is exactly equal to the amount of oxygen taken up by the pulmonary capillaries via the airway. This is true regardless of the status of pulmonary function or dysfunction, so we measure O2 across the lung and assume that it is exactly the amount consumed in the systemic metabolism.
248 Which of the following statement(s) is/are true concerning the outcome in patients with acute renal failure?
a. Mortality for ischemic acute tubular necrosis without other organ failure is approximately 6%
b. Multiple organ failure complicated with acute renal failure is associated with mortality ranging from 50% to 90%
c. Recovery of renal function after six weeks is unlikely
d. There is no difference in survival between oliguric and nonoliguric renal failure
Answer: a, b, c
Survival of patients with acute renal failure is a function of the successful treatment of the primary disease from which the renal failure was derived. The mortality for ischemic acute tubular necrosis without organ failure has been reported at approximately 6%. By contrast, mortality of multiorgan failure complicated by acute renal failure ranges from 50% to 90%. In patients who survive the acute phase of illness, recovery of renal function after acute renal failure is dependent on the type and extent of injuries to the renal parenchyma. If renal function is not returned after six weeks, recovery is unlikely. Nonoliguric renal failure is usually limited in its extent and is almost always reversible.
249 Which of the following statement(s) is/are true concerning oxygen delivery?
a. The amount of oxygen delivered to peripheral tissues is dependent upon the oxygen content in arterial blood and cardiac output
b. Oxygen content is commonly measured in arterial blood
c. The normal arterial-venous difference is 4 cc O2/dL
d. Normal systemic oxygen delivery for a typical adult is approximately 1000 cc/min
Answer: a, c, d
The amount of oxygen that is delivered to peripheral tissues is the product of the oxygen content in arterial blood times the cardiac output. Normally, oxygen content of arterial blood is approximately
20 cc/dL, and the normal cardiac index is 5 L/min. Therefore, the normal systemic oxygen delivery is approximately 1000 cc/min. Although oxygen content is the most important measure of oxygen in the blood, PO2 and oxyhemoglobin saturation is more commonly measured in the Intensive Care Unit, hence it is necessary to convert between these measurements. The normal oxygen content of venous blood is 16 cc/dL. Hence, the normal arterial-venous difference is 4 cc O2/dL.
250 Which of the following statement(s) is/are true concerning carbon dioxide kinetics?
a. The amount of carbon dioxide produced is equivalent to the amount of oxygen consumed
b. Carbon dioxide levels in blood, present mostly as a bicarbonate ion, can quickly change
c. Normally the amount of carbon dioxide excreted through the lung is exactly equal to the amount of carbon dioxide produced in peripheral tissues
d. The amount of carbon dioxide excreted is a function of ventilation of perfused alveoli
Answer: a, c, d
The total amount of carbon dioxide produced by systemic metabolism is roughly equivalent to the amount of oxygen consumed (100–120 cc/m2/min, 200 cc/min in a typical adult). CO2 production is increased or decreased by each of the factors that causes an increase or decrease in oxygen consumption. Most of the carbon dioxide in blood is present as bicarbonate ion which cannot be changed quickly. However, the metabolically produced CO2 is mostly present as dissolved carbon dioxide, added to the blood in the peripheral tissues and excreted in the lung. In a steady state, the amount of carbon dioxide excreted through the lung is exactly equal to the amount of carbon dioxide produced in peripheral tissues. The amount of carbon dioxide excreted is a function of ventilation of perfused alveoli (i.e. the alveolar ventilation/min).
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a. Initial screening with ELISA is highly sensitive but can be associated with a false positive rate of 25%
b. Treatment with azidothymidine (AZD) appears to prolong survival when administered early in the disease
c. Predisposition to infection in HIV infection is primarily due to reduction in the number of helper T cells
d. Common infections in patients with AIDS are Pneumocystis, carinii pneumonia, CMV pneumonitis, Cryptococcus meningitis, and disseminated infection due to atypical mycobacteria
Answer: b, c, d
Acquired immunodeficiency syndrome (AIDS) is a syndrome caused by the human retrovirus (HIV-1) that infects T lymphocytes and causes severe immunosuppression. Individuals who become infected with HIV are prone to a variety of infections and different types of malignancy. A spectrum exists in which patients regress from asymptomatic infection, to development of AIDS-related complex (ARC) of diseases to AIDS itself. Common infections occurring in patients with AIDS are Pneumocystis carinii pneumonia; CMV pneumonitis; gastritis, hepatitis and meningitis due to Cryptococcus neoformans; and pneumonia and disseminated infection due to atypical mycobacteria. Predisposition to these infections is due, in part, to the lymphotrophic nature of HIV, which markedly reduces the number of helper T cells as well as the absolute number of T cells.
HIV detection typically consists of initial ELISA screening, but this test has about a 1–3% false-positive rate, thus mandating all positive tests be confirmed by the western immunoblot analysis.
Treatment of ARC and AIDS consists of aggressive antiinfective therapy once a specific infection occurs and the use of AZT. AZT has been shown to prolong survival when administered early in the course of disease and is considered routine therapy.
202 The following statement(s) is/are true concerning initial microbiologic diagnostic techniques.
a. Appropriate expeditious transport of specimens to the microbiology laboratory is essential for obtaining accurate clinical information
b. The use of potassium hydroxide in preparing a specimen slide for light microscopy will be useful in identification of anaerobic bacteria
c. Antibiotic sensitivity is determined by exposing the specific microorganism to varying amounts of antibiotic with the concentration of the antibiotic inhibiting growth referred to as the MIC (minimal inhibitory concentration)
d. Serum levels of antimicrobial agents should achieve in excess of a 4-to 8-fold increase over the MIC to be considered clinically efficacious.
Answer: a, c, d
Because most surgical infections are polymicrobial, specimens should be cultured for aerobic and anaerobic bacteria, as well as fungi. Although aerobic and aerotolerant microorganisms often do not require special transport media, a delay in specimen processing may markedly reduce the yield, and anaerobic transport media have been demonstrated to markedly increase the cultural yield of this type of organism. The initial piece of information gained concerning potential infection may come from simple staining of a specimen. Gram stain, which will identify the staining characteristics of the organisms, as well as their number should be performed on all specimens. Potassium hydroxide is useful in that it will lyse bacteria and other cellular elements within a preparation and allow observation of yeast or mycelial elements.
Initial culture results may solely indicate that microorganisms are growing and full characterization may take two to three days. Once a specific microorganism is identified, a sample is inoculated during the log phase into broth containing varying amounts of an antibiotic. After an 18-to 24-hour period, the tube or well that exhibits no visible growth is then noted, and the reciprocal of this dilution is termed the minimal inhibitory concentration (MIC). This value may be compared to either measured or known achievable serum levels for a particular antibiotic. In general, antimicrobial agents that achieve in excess of a 4-to 8-fold increase over MIC during the peak serum level have been demonstrated to be clinically efficacious.
203 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
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 antigenic cell surface. The classic pathway of complement activation usually begins with immunoglobulin G-binding which has also bound the antigen. The alternate pathway activation occurs in response to activation of direct binding of the antigen or directly through contact with fungal and bacterial cell wall compounds such as zymosan and gram-negative bacterial lipopolysaccharide (LPS endotoxin). Several complement components represent important host defenses acting to recruit or augment cellular host defenses or to directly inactivate invading microbes through lytic activity. The production of complement component fractions C3a and C5a during activation of this cascade serve primarily to markedly increase vascular permeability, and C5a functions as a PMN and macrophage chemoattractant. This process leads to the recruitment of additional humoral and cellular defenses to the specific area of infection. Excessive complement activation can produce deleterious effects in some instances. Complement activation causes enhanced PMN adhesion, margination, and release of lysosomal enzymes that can directly damage certain target tissues, such as the lung.
204 A 55-year-old renal transplant patient has been hospitalized in a Surgical Intensive Care Unit, receiving a prolonged course of antibiotics following an attack of acute cholecystitis. The following statement(s) is/are true concerning his management.
a. Due to the potential risk of Candida infection, prophylaxis with oral nystatin should be instituted early in the patient’s course
b. A Candida urinary tract infection should be treated with systemic amphotericin B
c. Changes of Candida retinitis are of little significance
d. The presence of a virulent Candida bacteremia should suggest a dosage reduction in immunosuppressive agents until the infection can be adequately controlled
Answer: a, d
Infections due to fungal pathogens have become increasingly common during the past decade, frequently occurring in patients undergoing prolonged hospitalization in the Surgical Intensive Care Unit and in immunocompromised individuals. Prophylaxis with oral antifungal agents (nystatin) is warranted, especially during periods of maximal immunosuppression in transplant patients, in patients with uncontrolled diabetes, or during some cases of prolonged antibacterial microbial therapy. In general, local, apparently noninvasive Candida infections involving the integument and mucus membranes are treated with oral decontamination and topical antifungal therapy using topical agents such as nystatin. Candida urinary tract infections can be treated with either an oral antifungal agent or with topical amphotericin B as a continuous bladder irrigation. Several studies have demonstrated that those patients with three positive sites of Candida infection, or with peritoneal or blood cultures positive for Candida exhibit higher survival rates when amphotericin B therapy is instituted earlier in the course of infection. The presence of retinal changes compatible with Candida retinitis or Candida present within the peritoneal cavity are considered indications for a limited course of amphotericin B therapy (300% to 500 mg). Patients receiving exogenous immunosuppressive agents should undergo a marked dose reduction, and some agents should be discontinued until evidence of infection is absolutely controlled or is eradicated.
205 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
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, process, and present antigen to T lymphocytes of helper lineage. These T lymphocytes, in turn, act to stimulate B lymphocytes to become mature plasmacytes (through secretion of cytokines such as interleukin 4 and 6) dedicated to the production of antibody directed against the specific antigen. An antigen may be defined as any substance that stimulates the host immune response; that is, that the host immune system recognizes is foreign. Thus, an antigen may be an invading microorganism, an inert particle, or any type of chemical compound that triggers the host immune system. Although some antigens are able to directly stimulate B lymphocytes in and of themselves to produce antibody (many polysaccharides), most antigens require coordinated efforts of the various cellular components of the immune system.
206 The following statement(s) is/are true concerning viral infections.
a. The most common post-transplantation viral infections are caused by herpes viruses and include CMV and herpes simplex virus
b. Viral infections occur at equal frequency anytime during the post-transplantation period
c. CMV infection in the post-transplant patient is most likely a pulmonary process
d. Herpes simplex virus (HSV) infection primarily presents with a mononucleosis-type syndrome with fever, lethargy, and cough
Answer: a, c,
Solid organ transplant patients are prone to develop viral infection by virtue of exogenous immunosuppression. The most common post-transplantation viral infections are those caused by herpes viruses (CMV, herpes simplex virus [HSV], Epstein-Barr virus [EBV], and Varicella-Zoster virus [VZV]). All are most common during periods of maximal host immunosuppression that occur immediately post-transplantation and during periods of allograft rejection. CMV is a common cause of fever after solid organ transplantation, and evidence of CMV infection occurs in approximately 30% of patients. The most common presentation for CMV infection is that of a febrile, leukopenic patient with a cough, diffuse interstitial infiltrates on chest x-ray, and hypoxia.
HSV infection causes primarily oral pharyngeal ulcerations in most cases, although sporadic cases of disseminated disease have been reported. EBV causes an occasional case of mononucleosis-type syndrome but has also been clearly indicated in the pathogenesis of post-transplantation lymphomas. VZV infection can present as disseminated and occasionally life-threatening infections in the nonimmune transplant patient or as painful herpes zoster in patients who have previously developed chicken pox.
207 The following statement(s) is/are true concerning necrotizing fascitis.
a. Mortality rates as high as 40% can be expected
b. The infection involves only the superficial fascia, sparing the deep muscular fascia
c. An impaired immune system is a common factor predisposing to this condition
d. The infection is usually polymicrobial
e. Necrotizing fascitis is most likely to develop in the face of impaired fascial blood supply
Answer: a, c, d, e
Necrotizing fascitis is an uncommon infection of the deep and superficial fascia that is associated with mortality as high as 40% in many series. Although many underlying disease processes predispose patients to necrotizing fascitis, three common factors are almost invariably present: 1) impairment of the immune system; 2) compromise of fascial blood supply, and 3) the presence of microorganisms that are able to proliferate within this environment. Infections of this type are usually polymicrobial in nature, with gram-positive organisms such as staphylococci and streptococci, gram-negative enteric bacteria, and gram-negative anaerobic being frequently identified. These polymicrobial cultural results are assuredly indicative of the occurrence of a synergistic process, perhaps in large part accounting for the severity of these infections. Some microorganisms possess virulence factors that, in conjunction with an underlying host predisposition, allow this disease process to occur without dependence on other bacteria. Examples of such bacteria include Clostridium, Pseudomonas, and Aeromonas. In these patients, the process is often fulminant and is frequently associated with cellulitis, myositis, fascitis, and bacteremia with attendant high mortality.
208 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
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 the host anaerobic intestinal microflora relatively undisrupted. Although a reduction and alteration of the microorganisms responsible for infectious episodes have been demonstrated in certain groups of patients, a clear-cut impact on host mortality has not been shown. Because LPS may be responsible for toxicity both directly and through host mediator systems, the availability of agents to bind against this portion of the gram-negative bacteria to reduce mortality has been intensively examined. Unfortunately, large multicenter randomized trials provide no evidence of benefit for this treatment. Similarly, since many of the systemic manifestations of gram-negative bacteremia are mediated by cytokines, the effect of an anti-TNF antibody preparation is currently in clinical trial. No proven benefits have yet been identified. Finally, the use of immunostimulants to enhance the state of activation of host defenses has been proposed. Thymopentin is a peptide that contains active thymopoetin, a thymic molecule that acts to stimulate T-lymphocyte activity. Preliminary trials indicate that this agent ameliorates host septic response after major operations and trauma but conclusive evidence that concurrent reduction of infection-related mortality occurs is not available.
209 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
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 peptidoglycan synthesis and either causing or inducing autolytic bacteriolysis. Because gram-positive and gram-negative bacteria possess different types of division plate proteins, many of these agents exhibit differential activity between these two types of microorganisms. Tetracyclines, chloramphenicol, and macrolides inhibit bacterial ribosomal activity, and thus overall protein synthesis by a variety of different mechanisms. Aminoglycosides act to inhibit protein synthesis and also presumably act on a different target site, a supposition based on the fact that aminoglycosides are bacteriolytic and the other agents are bacteriostatic. Vancomycin inhibits assembly of peptidoglycan polymers, whereas quinolones bind to DNA helicase proteins and inhibit bacterial DNA synthesis. Sulfonamides and trimethoprim act in different mechanisms to inhibit protein synthesis, therefore two agents in combination act synergistically.
210 The treatment of the following patient should include:
a. Initial empiric therapy directed against both aerobes and anaerobes
b. The addition of anti-fungal therapy in an elderly patient
c. A minimum of two weeks of antibiotic therapy is indicated
d. The addition of appropriate antibiotic therapy has made surgical therapy unnecessary in such cases
e. Either a single agent or combination therapy is appropriate if the agents selected possess activity against both aerobic and anaerobic bacteria
Answer: a, e
The primary treatment for a perforated viscus is surgical, however antimicrobial therapy is an extremely important adjunct. Empiric antibiotic therapy for secondary bacterial peritonitis and intraabdominal abscess should be directed against both aerobes and anaerobes. Administration of an agent directed against only one component of the infection or the other is inferior to combined therapy. Several studies indicate that the results of using several agents in combination is equivalent to the use of a single agent therapy as long as the agents selected possess activity against both components of the infection. The addition of antientercoccal or antifungal agents as initial therapy has not been substantiated. The most beneficial duration of antibiotic therapy must be based on the setting for the specific patient. Minimal peritoneal contamination with adequate surgical treatment may be treated with a three-to five-day course of antibiotics, whereas longer periods are indicated for immunosuppressed patients and with patients with extensive contamination.
211 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
Answer: a, b, c
The introduction of microorganisms into the normally sterile peritoneal environment invoke several potent specialized host antimicrobial defense mechanisms. Bacterial clearance, also termed translymphatic absorption, occurs through specialized structures found only on the peritoneal mesothelium on the underside of the diaphragm that act as conduits for both fluid and particulate matter. Lymphatic channels eventually form which drain into the venous circulation via the thoracic duct. Bacteria not cleared via translymphatic absorption are rapidly engulfed by resident and recruited phagocytic cells including resident macrophages on the peritoneal surface and omentum and attracted PMNs. The final primitive host defense mechanism is sequestration by which a fibrinogen-rich exudate containing plasma oposonins appears during peritoneal infection and fibrin polymerization occurs. Fibrin has the capacity to trap large numbers of bacteria and other particulate matter. Acting in conjunction with omentum and other mobile viscera, perforations are sealed and the contaminated enteric contents walled off, preventing continued soilage of the peritoneal cavity.
212 A 67-year-old male presents with an intraabdominal abscess secondary to perforated sigmoid diverticulitis. The following statement(s) is/are true concerning his intraabdominal abscess.
a. Culture will likely reveal a solitary organism
b. Both aerobic and anaerobic islets are encountered in 50% of specimens
c. The most common aerobic islet will be likely E. coli and other gram-negative enteric bacilli
d. The most common anaerobic islet will be a Bacteroides species
Answer: b, c, d
Typically an intraabdominal infection results in perforation of a hollow viscus and the ensuing contamination of a normally sterile peritoneal cavity. The normal bacterial flora found in that particular location of the alimentary tract thus determines the initial inoculum. In parallel with the overall quantity of microorganisms, (both aerobes but predominantly anaerobes) perforations of the lower small bowel and colon produce a high frequency of infections that contain anaerobic microorganisms. Certain predictable patterns of bacterial islets are found, but on average four to five islets occur in patients with established intraabdominal infection, more than half of which are anaerobes. Both aerobes and anaerobes are encountered in 80% to 90% of specimens. Commonly encountered aerobes isolated are E. coli and other gram-negative enteric bacilli such as Enterobacter, Klebsiella. Among the anaerobes, Bacteroides species (especially B. fragilis, Clostridium), and anaerobic cocci are most consistently isolated.
213 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
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 30% lethality, respectively), despite therapeutic intervention with antimicrobial agents, aggressive hemodynamic monitoring, fluid resuscitation, and metabolic support. During the past several decades, nosocomial infections due to gram-negative pathogens have increased in frequency with resultant increase in the incidence of gram-negative bacteremia to between 3 and 13 cases per 1000 hospital admissions. Factors that predispose to these infections include: 1) underlying host disease processes such as malignancy, diabetes; 2) old age and disability; 3) malnutrition; 4) previous or concurrent antimicrobial antibiotic therapy; 5) major operations; 6) respiratory or urinary manipulation or intubation; and 7) immunosuppression.
Although many different organisms cause this form of sepsis, E. coli predominates in overall frequency. Also common are isolates of Klebsiella, Enterobacter and Serratia; Pseudomonas bacteremia is less common. Some studies, however, have suggested that Pseudomonas sepsis is associated with the highest lethality. In several series, 10% to 20% of patients have had polymicrobial series, and most investigators agree that polymicrobial sepsis is more lethal than infection with a single organism.
214 Which of the following statement(s) is/are true concerning the various types of shock?
a. Traumatic shock is more commonly associated with subsequent organ injury and multiorgan failure syndrome than hemorrhagic shock
b. Cardiogenic shock can be of either an intrinsic or compressive nature
c. Hypodynamic septic shock is associated with a decreased mortality risk when compared with hyperdynamic septic shock
d. Hypoadrenal shock usually responds quickly to resuscitation
e. Neurogenic shock occurs with the absence of sympathetic activity
Answer: a, b, d, e
Classification schemes of shock based on cause have been developed for the seemingly dissimilar processes leading to circulatory collapse and the shock state. Hypovolemic shock, the most common, is the result of intravascular volume depletion through loss of red blood cell mass or plasma volume. Microvascular hypotension results from a combination of low intravascular blood volume, diminished cardiac output, and compensatory sympathetic peripheral vasoconstriction. Shock associated with trauma (traumatic shock) arises from the consequences of hypovolemia due to hemorrhage in conjunction with direct soft tissue injury and bone fracture. Hypovolemia caused by blood loss and fluid extravasation into injured tissues is compounded by activation of maladaptive inflammatory cascades initiated by the tissue injury. In contrast to pure hemorragic shock, subsequent organ injury and multiorgan failure syndrome (MOFS) occurs much more frequently following traumatic shock due to the over-expression of these immuno-inflammatory cascades. Cardiogenic shock is the result of failure of the heart as an effective pump, resulting in inadequate cardiac output, tissue perfusion and oxygen delivery. Intrinsic causes include myocardial infarction, cardiomyopathy, valvular heart disease, or rhythm disturbances. Compressive cardiogenic shock is a discrete entity that results when extrinsic compression of the heart limits diastolic filling and thus systolic ejection and cardiac output. Septic shock refers to hypotension and circulatory insufficiency developing as a consequence of infection and the systemic response to that infection. In its hyperdynamic form, septic shock is marked by diminished peripheral vascular resistance and generalized vasodilatation causing relative hypovolemia. In contrast, hypodynamic septic shock occurs in situations of inadequate resuscitation or preterminal cardiovascular decompensation, and is associated with vasoconstriction and a greatly increased mortality risk. Sympathetic denervation through spinal cord injury, spinal anesthesia, or severe head injury produces generalized arterial vasodilatation and venodilation. Shock occurs when the normal blood volume fails to fill the available intravascular space and severe relative hypovolemia exists. Despite hypotension, there is a noteworthy absence of sympathetic activity, as occurs in hypovolemia or cardiogenic shock. Profound shock can occur in surgical patients following stress due to the loss of the homeostatic corticosteroid response. Hemodynamic instability may develop after an operative procedure or coincident with an unrelated illness. The profound circulatory collapse is often refractory to vigorous resuscitation with fluids and pressor agents. The response to exogenous corticosteroids is usually dramatic and potentially life-saving.
215 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
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, lipid, protein, and oxygen metabolism occur as hypermetabolism develops. Through the Cori cycle, lactate from the periphery is shuttled back to the liver, where it is used in the production of glucose. Because pyruvate is converted to alanine in the periphery, flux of alanine also contributes to hepatic gluconeogenesis. The glycolytic oxidation of glucose to pyruvate and its subsequent glugoneogenic regeneration from lactate is an inefficient cycling of substrate. There is no net energy production, but heat is released in significant quantities. Alterations in lipid metabolism cause a progressive rise in the serum triglyceride level as a result of less efficient clearance of exogenous triglycerides coupled with increased hepatic lipogenesis. Profound alterations in protein and amino acid metabolism develop with characteristic changes in amino acid levels, nitrogen balance, and skeletal muscle mass. Initially levels of the branch chain amino acids are reduced, whereas those of the aromatic amino acids are elevated. There is an increase in the oxidative metabolism of protein to meet energy needs and a tremendous mobilization of nitrogen with net negative nitrogen balance. The branch chain amino acids are preferentially utilized in the TCA cycle to maintain an activity that otherwise would be lost from the diminished entry of carbohydrate-and fatty acid-generated acetyl coenzyme A. This results in reduced serum level of leucine, isoleucine and valine.
216 Which of the following statement(s) is/are true concerning the microvascular and cellular response to shock?
a. Osmodically induced mobilization of intracellular fluid is the initial response to restore intravascular volume
b. With larger volume hemorrhagic shock deterioration of normal cellular transmembrane potential occurs resulting in an increase in extracellular sodium and water
c. The accumulation of anaerobic metabolites override normal homeostatic vasomotor tone and contribute to the maladaptive vasodilatation
d. Abnormal intracellular calcium homeostasis may contribute to the cellular dysfunction of shock
Answer: c, d
Moderate hypovolemia results in a relatively rapid spontaneous restitution of intravascular volume through expansion of the plasma space. This plasma expansion by erythrocyte free fluid occurs within one hour as a result of alterations in pressure and osmolarity and produces an associated hemodilution. Sympathetic discharge, associated arteriolar constriction, and induced metabolic changes in osmolarity initiate the compensatory events at the microcirculatory level. The initial pressure-related phase of restitution of blood volume in shock is overlapped by a second phase involving osmotically induced mobilization of intracellular fluid. Osmotic mechanisms contributing to the restitution of blood volume after moderate hemorrhage are not adequate in hemorrhage of greater magnitude. In larger hemorrhages (over 25% blood volume), there is also deterioration of the normal cellular transmembrane potential, an increase in intracellular sodium and water, and a concomitant decrease in extracellular fluid volume. Tissue hypoxia results, anaerobic metabolites accumulate, and the cell cannot maintain the normal cell membrane potential. Accumulation of hydrogen ion, lactate, and other products of anaerobic metabolism override homeostatic vasomotor tone and contribute to a maladaptive vasodilatation, further augmenting hypotension and hypoperfusion. The uptake of fluid by the “failing” cell is a major source of food sequestration following shock. Loss of membrane function is proportional to both the extent and duration of shock or degrees of sepsis. The etiology of membrane failure is unclear but appears multifactorial. Loss of intracellular ATP energy stores during hypoperfusion or direct toxicity during sepsis may inhibit the membrane sodium-potassium pump. Cellular dysfunction also appears to be related to abnormal intracellular calcium homeostasis.
217 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
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 lung mechanics, and acute lung injury or ARDS due to sepsis. Pulmonary function may be further compromised by pathology intrinsic to the lung itself, including pulmonary contusion, aspiration, airway obstruction, pneumonia, pneumothorax, hemothorax, and atelectasis. The acute pulmonary vascular response to shock largely parallels that of the systemic vasculature. The increase in pulmonary vascular resistance, which may proportionally exceed that of the systemic circulation, transiently accompanies the systemic adrenergic response. ARDS is a syndrome of progressive lung injury that may arise as a direct consequence of shock or other disease processes. The characteristic findings of ARDS are the presence of pulmonary edema, hypoxemia, and significantly decreased lung compliance. The pulmonary edema is noncardiac in origin and occurs in the face of normal left heart pressures. The hypoxemia results from the development of intrapulmonary shunting and perfusion of under and nonventilated alveoli. The decrease in lung compliance results from the loss of surfactant and lung volume in combination with the presence of interstitial fluid and alveolar edema. Progressive histologic changes of ARDS become apparent in pulmonary capillaries, interstitium, and alveoli. Initially, interstitial edema develops with swelling of the capillary endothelial cells and the type I pneumocytes. The type I pneumocytes subsequently slough, and alveolar edema ensues. Functional surfactant is lost with a significant increase in alveoli opening pressure and decrease in alveolar surface tension. Mechanisms proposed in the pathogenesis of ARDS include injury from mediators of inflammation elaborated elsewhere, and from activated cellular blood elements.
218 Which of the following statement(s) is/are true concerning the diagnosis and management of hypovolemic shock?
a. A fall in hematocrit or hemoglobin always accompanies hemorrhagic shock
b. The treatment of shock is generic regardless of the etiology
c. Pharmacologic intervention to increase myocardial contractility in hypovolemic shock is an important part the early management
d. Complications are less frequent after treatment of hemorrhagic shock than septic or traumatic shock
Answer: d
Hypovolemic shock is readily diagnosed when there is an obvious source of volume loss and overt signs of hemodynamic instability and increased adrenergic output are present. After acute hemorrhage, hemoglobin and hematocrit values do not change until compensatory fluid shifts have occurred or exogenous fluid is administered. These values decrease once transcapillary refill, osmotic-induced shifts, or non-RBC volume resuscitation expands the blood volume. It is imperative that the distinction be made between hypovolemic and cardiogenic forms of shock, because appropriate therapy differs dramatically. Restoration of perfusion in hypovolemic shock requires reexpansion of circulating blood volume in conjunction with necessary interventions to control ongoing volume loss. Continued hemodynamic instability after fluid resuscitation implies that shock has not been reversed or that there is ongoing blood or volume loss. In severe, prolonged hypovolemia, ventricular contractile function may itself become depressed and require inotropic support to maintain ventricular performance, but in general, pharmacologic interventions directed toward increased contractility in situations of inadequate preload are ineffective, further complicate metabolic derangements, and are not indicated until adequate volume replacement has been completed. Complications are less frequent after treatment of hemorrhagic shock than in situations of septic or traumatic shock. In the later circumstances, the massive activation of inflammatory mediator response systems and consequences of their disseminated, indiscriminate cellular injury can be quite profound.
219 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
Answer: c, d
The neuroendocrine response to shock attempts to achieve restoration of effective blood volume, mobilization of metabolic substrates, and maintenance of central profusion. Both peripheral and central afferent stimuli to the central nervous system are involved in inducing this response. Hypotension, associated with a decrease in impulses from the aortic and carotid baroreceptors, disinhibits the vasomotor center. This disinhibition results in increased adrenergic output and decreased vagal activity. Sympathetic nerve endings release norepinephrine, inducing peripheral and splanchnic vasoconstriction which is responsible for greater than 80% of systemic vascular resistance and is a major contributor to maintenance of central organ perfusion and venous return. Plasma levels of both epinephrine and norepinephrine are elevated with injury, and the degree of the catecholamine elevation corresponds to the magnitude of injury. In shock the effects of endogenous epinephrine are largely metabolic. In addition to initiating autonomic nervous activity, the hypothalamus secretes releasing hormones, which induce the stress hormone release of the pituitary. As part of this response, adrenocorticotropic hormone (ACTH) secretion by the anterior pituitary is increased stimulating cortisol secretion by the adrenal cortex. In conjunction with elevated plasma levels of cortisol and epinephrine, increased pancreatic secretion of glucagon accelerates hepatic gluconeogenesis and further aggravates the glucose intolerance that follows injury and sepsis. The secretion of renin is increased in responses to adrenergic discharge and decreased perfusion of the juxtaglomerular apparatus in the kidney. Renin allows formation of angiotensin I in the liver, which is then converted to angiotensin II in the lungs. Angiotensin II is an extremely effective vasoconstrictor that further augments sympathetic-mediated vasoconstriction.
220 A 22-year-old man sustains a single stab wound to the left chest and presents to the emergency room with hypotension. Which of the following statement(s) is/are true concerning his diagnosis and management?
a. The patient likely is suffering from hypovolemic shock and should respond quickly to fluid resuscitation
b. Beck’s triad will likely be an obvious indication of compressive cardiogenic shock due to pericardial tamponade
c. Echocardiography is the most sensitive noninvasive approach for diagnosis of pericardial tamponade
d. The placement of bilateral chest tubes will likely resolve the problem
Answer: c
Shock from cardiac compression occurs when external pressure on the heart impairs ventricular filling. Because ventricular filling is a function of venous return and myocardial compliance, any process that places pressure on the heart can cause compressive cardiogenic shock. Included among these are pericardial tamponade, tension pneumothorax, mediastinal hematoma, and positive pressure from mechanical ventilation. Any patient with hypotension after a wound in proximity of the heart should be considered to have compressive cardiogenic shock until proven otherwise. The classical clinical findings of pericardial tamponade include Beck’s triad of hypotension, neck vein distention and muffled heart sounds. Pulses paradoxus may be noted (this involves a decrease rather than the normal increase of systolic blood pressure with inspiration; values 10mmHg are significant). These findings, however, may be obscured in a noisy emergency room environment by positive pressure ventilation or by associated injuries. Placement of a CVP catheter confirms the elevation of right-sided filling pressure. If a pulmonary artery catheter has been placed, findings consistent with tamponade or other forms of cardiac compression are a trend toward equalization of chamber pressures as hypotension progresses. In the patient at risk, echocardiography is an extremely sensitive and noninvasive approach to demonstrate pericardial fluid and the need for operation. Pericardial tamponade must be relieved urgently and cardiac injuries require emergent sternotomy. Chest tube placement would not be appropriate as the sole treatment in this patient.
221 A 32-year-old man suffers a spinal cord injury with a resultant paraplegia in a motorcycle accident. He presents to the emergency room with hypotension. Which of the following statement(s) is/are true concerning his diagnosis and management?
a. The low blood pressure can be assumed to be due to neurogenic shock
b. The sole cause of hypotension is the loss of sympathetic input to the venous system
c. Despite significant hypotension, secondary organ injury will be uncommon
d. There is no role for pharmacologic intervention to maintain blood pressure
Answer: c
Neurogenic shock results from interruption of sympathetic vasomotor input and develops after spinal cord injury, spinal anesthesia, and severe head injury. Under normal conditions, baseline sympathetic activity establishes a degree of arteriolar and venous constriction. Ablation of this tone results in decreased systemic vascular resistance and a dramatic increase in venous capacity, causing hypotension due to relative hypovolemia. Arteriolar dilatation not only lowers the systemic vascular resistance but also allows previously unopened vascular beds to be perfused, greatly expanding venous capacity. Removal of sympathetic inputs to innervated portions of the venous system allows further venodilatation. Restoration of an effective, albeit expanded, intravascular volume may require extremely large volumes of resuscitation fluid to restore normal cardiac filling pressures. This will restore cardiac output and reverse hypotension. However, pharmacologic intervention with vasoactive drugs may be necessary and is preferable to excessive volume resuscitation. Post-shock sequelae are infrequent. Although there is significant hypotension with neurogenic shock, there is usually little if any hypoperfusion. Thus, activation of inflammatory cascade and subsequent organ injury rarely occur.
A major pitfall in the management of neurogenic shock arises when there is coexistent hemorrhage or ongoing volume loss that is not appreciated. This is not an unusual situation because cervical spine trauma causing paraplegia or severe head injury is frequently associated with multiple injuries. Thus, in trauma the initial response to neurogenic shock is large volume resuscitation regardless of the presumed etiology. If hemodynamic instability persists after initial trauma resuscitation, one must assume that the cause is not neurogenic and search for occult blood loss or cardiogenic causes of shock.
222 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
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 protozoa have all been reported to produce a clinical picture of septic shock, but the overall response is independent of the specific type of invading organism. Septic shock develops as a consequence of the combination metabolic and circulatory derangements accompanying the systemic infection. It appears that the circulatory deficits are preceded by the metabolic abnormalities induced by infection. In fact, the circulatory changes in hyperdynamic sepsis appear to be an adaptive response to the underlying metabolic dysfunction. Cardiac output is high and systemic vascular resistance low in hyperdynamic septic shock. However, splanchnic vasoconstriction is pronounced even in the absence of systemic hypotension and even though systemic vascular resistance is reduced. Expansion of circulating blood volume can occur through either transcapillary refill or fluid resuscitation. Due to the ongoing inflammatory mediator-induced increases in capillary permeability and continued loss of intravascular volume, exogenous volume resuscitation must be provided to restore venous return and ventricular filling.
223 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
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 other inflammatory stimuli. Elevation of serum levels of TNF have been reported shortly after experimental trauma and shock, however, documentation of elevated circulating levels of TNF in human shock is less clear. Furthermore, circulating levels of TNF cannot be correlated with severity of tissue injury or shock. This variability is thought to be due to rapid clearance and uptake by membrane receptors and by soluble membrane receptors that are released from multiple cells following stress and injury. Following hypoperfusion the liver and gut appear to be the major source of TNF that is rapidly cleared but responsible for inducing hepatocyte changes following shock. The release of breakdown products and escape of bacterial and endotoxin through the damaged mucosal barrier of the gut following shock allows or induces activation of tissue-fixed macrophage (Kupffer cell) of the liver which then produces secondary inflammatory mediators contributing to the post-resuscitation clinical response and inflammatory mediator activation seen in the systemic inflammatory response syndrome.
TNF is central to inflammatory response, particularly in sepsis and following endotoxemia or bacteremia. TNF also induces secondary inflammatory responses through direct interaction with specific membrane receptors, TNF-r. Treatment with anti-TNF antibody in the experimental setting protects animals from the deleterious effects of lethal bacteremia and endotoxemia. However, recently completed clinical trials in septic patients utilizing infusion of monoclonal antibodies to the TNF molecule have shown no overall survival benefit.
224 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
Answer: d
Inflammatory mediators have recently been recognized as playing a significant role in the clinical manifestations and progression of shock and the development of subsequent complications. These mediator systems function primarily as parcrine and autocrine agents in the local environment and are not usually detectable systemically. The over-expression and systemic dissemination of these mediators produces the toxic autodestructive processes underlying multiorgan failure syndrome with attendant high mortality. The compliment cascade is activated in shock and tissue injury through both the classical and alternative pathways. Activation of either pathway results in generation of the anaphylatoxin, C3a and C5a, soluble products with potent systemic hemodynamic effects. The eicosanoids, which include the prostaglandins and leukotrienes are formed acutely from arachidonic acid released from the membrane phospholipid by phospholipase A2. Eicosanoids are not stored in any measurable level and are generated as needed from readily available arachidonic acid in response to various inflammatory phenomena. Platelets, white cells, and endothelial cells are a rich source of these compounds. Thromboxane (TXA2) is the major arachidonic acid metabolite elaborated by platelets. TXA2 induces intense vasoconstriction, platelet aggregation and degranulation, neutrophil margination in the microcirculation and bronchial constriction. PGI2, the major arachidonic acid metabolite formed by endothelial cells, serves a check against actions of TXA2. PGI2 is a vasodilator and a potent inhibitor of platelet aggregation. Platelet aggravating factor is a potent phospholipid mediator released by neutrophils, platelets, macrophages and endothelial cells in response to ischemia, tissue injury and sepsis. Its effects include decreased cardiac function, increased pulmonary vascular resistance, bronchoconstriction, peripheral vasodilatation, and increased vascular permeability.
225 Which of the following physical findings are associated with the various classes of hemorrhagic shock?
a. Mild shock (< 20% blood volume): Pallor, cool extremities, diminished capillary refill and diaphoresis
b. Moderate shock (20%–40% blood volume): All of the above plus tachycardia and hypotension
c. Severe shock (> 40% blood volume): Systemic hypotension, changes in mental status, tachycardia, oliguria
d. All of the above
Answer: a, c
PHYSICAL FINDINGS IN HEMORRHAGIC SHOCK*
Moderate
Mild (<20% (20%-40% Severe(>40%
Blood Volume) Blood Volume) Blood Volume)
Pallor Pallor Pallor
Cool extremities Cool extremities Cool extremities
Diminished capillary Diminished capillary Diminished capillary
refill refill refill
Diaphoresis Diaphoresis Diaphoresis
Collapsed Collapsed Collapsed
subcutaneous subcutaneous subcutaneous
veins veins veins
Tachycardia Tachycardia
Oliguria Oliguria
Postural Hypotension
hypotension Mental status
changes
* Alcohol or drug intoxication may alter physical findings.
226 A 68-year-old male who underwent a repair of an abdominal aortic aneurysm 5 days ago, develops tachycardia, tachypnea, hypotension with cool, pale, mottled cyanotic extremities. He is agitated and complains of shortness of breath. Which of the following statement(s) is/ are correct concerning his diagnosis and management?
a. Myocardial ischemia secondary to preexisting coronary artery disease is most likely the underlying cause of this problem
b. Invasive hemodynamic monitoring with a Swan-Gantz catheter will demonstrate a low cardiac output, a high systemic vascular resistance, and elevated cardiac filling pressures
c. The use of morphine sulphate and nitrates should be part of the initial management
d. The primary pharmacologic treatment involves the use of moderate doses of inotropic agents
e. Afterload reduction with nitroprusside is absolutely contraindicated
Answer: a, b, d
Intrinsic cardiogenic shock results from failure of the heart as an effective pump. Coronary artery disease is the most common cause of myocardial insufficiency, but contractile dysfunction may also rise as a consequence of cardiomyopathy, myocarditis, or metabolic abnormalities. Invasive hemodynamic monitoring often establishes a specific nature of shock and allows appropriate treatment to be delivered in an effective and expedient manner. Hemodynamic findings consistent with cardiogenic shock include a low cardiac output and high systemic vascular resistance, with elevated cardiac filling pressures. The initial measures in the management of cardiogenic shock include the administration of supplemental oxygen, mechanical ventilation (as needed), and appropriate treatment of dysrhythmias. Hypotension usually precludes the use of morphine sulfate and nitrates, drugs typically used in simple congestive heart failure to alleviate cardiac pain and ameliorate pulmonary vascular congestion. The use of beta-adrenergic agonists such as dopamine and dobutamine, in moderate doses, offers positive inotropic support without excessive alpha-adrenergic activity. Increasing the inotropic state of the heart shifts the entire Starling curve upward, resulting in increased cardiac output for each level of cardiac filling. Afterload reduction may prompt increases in cardiac output through decreases in resistance to flow. The use of nitroprusside or other dilators requires relative blood pressure stability and close hemodynamic monitoring. Infusion of afterload-reducing agents can be administered in conjunction with inotropic support.
227 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
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 intracellular adenine neuclotides occurs. As ATP further degrades there is an elevation in plasma and intracellular levels of hypoxanthine and xanthene which upon restoration of perfusion and reoxygenation are catalyzed by xanthine oxidase resulting in the formation of superoxide radicals. These radicals plus others such as hydrogen peroxide and hydroxyl radical are generated and lead to endothelial and parenchymal cell injury through membrane lipid peroxidation and activation of critical enzymes. These radicals have also been shown to be involved in the expression of proinflammatory phenotype endothelial cells and on macraphages and neutrophils. The proinflammatory phenotype of the endothelium includes procoagulant activity and the expression of adhesion molecules on the membrane surface, including the intercellular adhesion molecule-1 (ICAN-1) and the selectins. The subsequent adhesion of activated neutrophils to the endothelial leads to an explosive oxidative burst producing additional radicals and extensive release of proteolytic enzymes leading to injury and disruption of the endothelial lining, extensive capillary leak, and massive interstitial edema. Passive immunization of animals with monoclonal antibodies to either the neutrophil adhesive complex or the endothelial selectins dramatically lessens ischemia/reperfusion microvascular injury.
228 Which of the following statement(s) is/are true concerning the physiology of the microvascular system?
a. Filtration of capillary fluid into the interstitial and the subsequent reabsorption is influenced by Starling’s law of ultrafiltration
b. The most important variable controlling blood to a capillary bed is the length of the vessel
c. Most of the resistance to systemic blood flow occurs at the arteriolar level
d. Adrenergic vasoconstriction can arrest blood flow to an entire capillary bed
Answer: a, c, d
Exchange of material between the vascular space and the cell of various tissues via the interstitial space is essential for organ viability and occurs at the capillary level. The filtration of capillary fluid into the interstitium and its subsequent reabsorption into the post capillary venule is governed by microvascular permeability in conjunction with the balance between hydrostatic and oncotic pressures. The relation of these forces to one another (and their net effects) are illustrated by what is termed Starling’s law of ultrafiltration. In normal circumstances, a net filtration from capillary to interstitium is effected by a relatively higher capillary hydrostatic pressure, whereas net reabsorption from the interstitium back into the post capillary venule occurs as hydrostatic pressure falls and oncotic forces predominate. Although the mechanisms controlling blood flow to the capillary bed are complicated and vary among the different tissues, certain concepts are useful. Poiseuille’s law describes the relation between flow of fluid through a tube and the tube length and radius, the fluid viscosity, and the pressure gradient between ends of the tube. The radius of the tube (or vessel) is the single most important variable, because flow is proportional to the radius to the fourth power. Vasoconstrictive and vasodilatory influences directly impact local blood flow, as well as flow to other tissues through secondary effects on the systemic pressure. This secondary effect of peripheral vasoconstriction maintains the pressure gradient for central perfusion of the heart and brain. Systemic blood flow meets most of its resistance at the arteriolar level. While the individual capillary radius is significantly smaller, the vast number of capillaries offers less total resistance. The vascular smooth muscle in arterioles has both a-and b- adrenergic receptors. Alpha stimulation affects vasoconstriction where beta stimulation affects vasodilatation. The efferent sympathetic fibers innervating the precapillary resistance vessels and the venous capacitance vessels release norepinephrine on stimulation, which induces smooth muscle contraction and narrowing of the caliber of the vessels. These contractions are potent enough that blood flow to entire capillary beds can be arrested by adrenergic vasoconstriction.
229 Which of the following statement(s) is/are true concerning the effects of MOFS?
a. Pulmonary dysfunction tends to arise early and may resolve within 7 to 10 days
b. Unless the precipitating insult has prompted oliguric acute tubular necrosis, renal function tends to be maintained early in the course of MOFS
c. Although hepatic dysfunction is common with MOFS, the GI tract plays little role in this process
d. Intercurrent nosocomial infection, most commonly pulmonary, is a common complication providing a “second hit” to the patient
Answer: a, b, d
Pulmonary dysfunction typically arises early in the development of systemic inflammation and may represent mild relatively localized acute lung injury or it may be a prelude to fulminant ARDS. The lung injury, and associated dysfunction, may resolve over the initial 7 to 10 days or persist, depending on the ongoing pathologic process. Many times a “second hit” such as a nosocomial infection, which is most commonly pulmonary, is a complication which can frequently worsen the pulmonary condition. Renal function tends to be maintained early in the course unless the precipitating insult has been prompted by a sudden oliguric acute tubular necrosis. With persistent activation and inflammatory mediators, glomerular filtration falls and the development of oliguric or polyuric renal failure marks the gradual transition into MOFS. Gastrointestinal abnormalities include ileus, stress ulceration, diarrhea, and mucosal atrophy. Breakdown of the mucosal barrier allows translocation of bacteria and endotoxin. Hepatic dysfunction is marked by progressive rise in serum bilirubin levels after a latent period of several days.
230 Which of the following statement(s) is/are true concerning hypoadrenal shock?
a. In the United States, idiopathic adrenal atrophy (Addison’s disease) is the most common cause
b. Laboratory abnormalities include hyponatremia, hypochloremia, and hyperkalemia
c. Fever may be seen with hypoadrenal shock
d. ACTH stimulation test is the diagnostic test of choice to confirm hypoadrenal shock
Answer: b, c, d
Shock of a dramatic nature, poorly responsive to resuscitation, may develop as a consequence of adrenal insufficiency. In this country, adrenal insufficiency most commonly arises as a consequence of the chronic therapeutic administration of high doses exogenous corticosteroids causing adrenal suppression. Other causes include idiopathic adrenal atrophy (Addison’s disease), tuberculosis, metastatic disease, bilateral hemorrhage, and amyloidosis. The stress of illness, operation, or trauma typically requires that the adrenal glands secrete cortisol in excess of that required in the nonstressed state (approximately 3–4 fold). Insufficiency not otherwise apparent may manifest itself only after major physical stress. Findings associated with adrenal insufficiency include weakness, fatigue, anorexia, abdominal pain, nausea, vomiting, and weight loss. Surgical patients with significant adrenal insufficiency need not present with the above findings. More typical is the development of refractory shock, frequently with hyperthermia, in the course of injury or illness. Hypotension may be dramatic despite massive volume resuscitation and pressor support. Laboratory findings suggesting hypoadrenalism include hyponatremia, hypochloremia and hyperkalemia. The diagnosis of adrenal insufficiency may be confirmed or excluded by means of an ACTH stimulation test. A significant major cortisol response should be elicited by ACTH administration.
231 Which of the following statement(s) is/are correct concerning the cardiovascular response to shock?
a. Changes in cardiac contractile function shift the Frank Starling curve up and down
b. Venoconstriction from skeletal muscle is a significant contributor to the restoration of blood volume with shock
c. Arterial vasoconstriction affects all vascular beds equally
d. The total circulating blood volume is equally split between the arterial and venous system
Answer: a
Central in the general cardiovascular response to shock is the action of the heart itself. The principle determinants of cardiac function in the normal heart are the volume of blood available for the heart to pump (preload), the systolic contractile capability, and the diastolic filling of the ventricles. In hypovolemia, the two dynamic variables of cardiac function, ventricular filling and myocardial contractility remain paramount and determine the stroke volume. The product of stroke volume and heart rate in turn determines the cardiac output. Increases in ventricular end-diastolic volume, reflecting venous return, cause ventricular distention. Ventricular distention in turn produces increased volume output with each stroke, the Frank Starling mechanism. Contractile function may vary independent of volume status. Changes in the contractile function shift the Starling curve up and down, producing increases or decreases in stroke volume for any given end-diastolic volume. A fundamental requirement for cardiovascular function is adequate cardiac filling, and cardiac output cannot exceed venous return. The venous system contains nearly two-thirds of the total circulating blood volume, including 20% to 30% within the splanchnic venous system. Most of this volume resides in small veins, which comprise the bulk of venous capacitance. The venous system, especially that of the splanchnic circulation, becomes important in the physiologic compensation to hypoperfusion because it serves as a dynamic reservoir for the autoinfusion of blood volume involving both active and passive mechanisms. The splanchnic circulation makes major contributions to the maintenance of venous return, therefore, it is likely that sympathetic venoconstriction is responsible for a portion of the blood mobilized from the splanchnic venous circulation. Sympathetic mediated venoconstriction in skin and skeletal muscle is probably not as significant as a source of blood volume. Selective vasoconstriction occurs in response to alpha adrenergic receptor stimulation with increased sympathetic activity in shock. Sympathetic stimulation does not cause significant vasoconstriction of either cerebral or coronary vessels, with normal blood flow maintained in these circulations. Blood flow to the skin is sacrificed early, followed by that to the kidneys and splanchnic viscera.
232 Which of the following statement(s) is/are true concerning pharmacologic agents used in the treatment of shock?
a. The primary difference between dopamine and dobutamine is the absence of significant a adrenergic activity
b. The renal and mesenteric vasoconstrictive effects of norepinephrine complicate and sometimes restrict its use
c. The apparent paradoxical use of vasodilators, such as nitroprusside, in shock is indicated as a means to augment cardiac function
d. Isoproterenol with its potent b-adrenergic effect, is a particularly useful agent in the treatment of all forms of shock
Answer: a, b, c
Therapeutic adjustments of intravascular volume (preload) and systemic vascular resistance (afterload) form the basis of the treatment strategies for all forms of shock. Optimal volume resuscitation should precede measures to augment to contractile function of the heart. Inotropic agents are used in shock when there is inadequate cardiac output despite adequate circulating blood volume. Dopamine and dobutamine are often times first line agents in the pharmacologic treatment of shock. Dopamine, at low doses, stimulates dopaminergic receptors producing renal arteriolar vasodilatation with associated increases in renal blood flow, urine output, and sodium excretion. At moderate doses, stimulation of cardiac b-receptors produces increases in contractility and cardiac output with little effect on heart rate or blood pressure. At higher doses, peripheral vasoconstriction from increasing a activity becomes more pronounced, prompting significant increases in vascular resistance and blood pressure. Dobutamine’s predominant effect is an increasing cardiac contractility with lesser increases in heart rate. Some reduction of peripheral vascular resistance may also occur. When compared to dopamine, dobutamine produces less peripheral vasoconstriction and less chronotropic response. Norepinephrine exerts both a and b-adrenergic effects, with a effects being evident at lower infusion rates and a effects more prominent at high doses. The major use of norepinephrine in current practice is in the patient with hypotension that persists despite appropriate volume resuscitation and the use of inotropic agents. Renal and mesenteric vasoconstrictive effects of norephinepherine complicate its use, especially when support is needed for significant periods of time. Isoproterenol is a potent b-adrenergic agent. With isoproterenol, myocardial oxygen demand is increased and diastolic coronary feeling is limited by tachycardia or diminished diastolic pressure. Indications for the use of isoproterenol are fairly limited, because agents with fewer adverse effects have become available.
Vasodilators are used to augment cardiac function through optimization of ventricular filling pressures (preload) and systemic vascular resistance (afterload) both of which reduce demands on the myocardium. Decreases in afterload prompt increases in cardiac output and venodilatation contributes to decreases in pulmonary venous pressure and central venous pressure. Hypotension, however, may develop therefore patients must have careful constant monitoring of arterial pressure and repeated hemodynamic measurements with a pulmonary artery catheter.
233 Which of the following statement(s) is/are true concerning the treatment of MOFS?
a. Prevention and therapy of MOFS requires control of the infectious or inflammatory source
b. Restoration of normal clinical parameters such as blood pressure, pulse rate, and urine output ensures optimal resuscitation in most patients
c. Branch chain amino acids play and important role in the nutritional support of the patient
d. Because of the nature of gut injury, total parenteral nutrition is preferred for most patients with MOFS
Answer: a, c
The therapy of MOFS is directed towards interrupting the involving pathophysiologic process and providing an optimal physiologic environment for healing and recovery. Fundamental concerns are control of the source of infection, inflammation or instability; restoration of microcirculatory blood flow and oxygen transfer, and the institution of optimal supportive care. Both the prevention and therapy of MOFS, therefore, requires source control and restoration of adequate profusion. Resuscitation efforts are directed toward restoration of adequate microcirculatory blood flow in all organ systems. Restoration of normal clinical parameters such as blood pressure, pulse rate, urine output, and acid-base balance does not ensure optimal resuscitation. The physiologic endpoint that most closely corresponds with adequate microcirculatory flow is the level of cardiac output and the oxygen delivery at which oxygen consumption and lactate production remain independent of flow.
The importance of metabolic support in the patient with MOFS cannot be overemphasized. The malnutrition of MOFS is markedly different than that of starvation and the nutritional requirements also differ. If optimal quantities of appropriately formulated amino acid solutions are given, protein synthetic rates can approach catabolic rates and the goal of nitrogen balance can be achieved. Formulas rich in branch chain amino acids appear to be more efficient in promoting nitrogen retention and minimizing urea production. Whenever feasible, enteral feeding is preferred over TPN because evidence suggests that bacterial translocation from the gut can be limited through the use of enteral feeds. Enteral absorption and processing of nutrients appears superior to TPN and lessens overall complications.
234 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
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 inflammation and microcirculatory hypoperfusion. Endothelial injury, platelet aggregation and activation of macrophages and neutrophils occur, and the clotting, fibrinolytic, kinin, and complement cascades are activated, along with the release of potent inflammatory cytokines. The effects of shock, resuscitation, and reperfusion, and the subsequent development of MOFS appear to be critically dependent on changes in the splanchnic and pulmonary microcirculations. These vascular beds appear to be major sites of activation of subsequent inflammatory mediator production that underlies the diffuse systemic inflammatory response. Extensive activation of the liver Kupffer cell and release of inflammatory mediators coupled with the ongoing release of activated neutrophils and by-products of activated gut macrophages is responsible for the injury to the pulmonary microcirculation and secondary induction of alveolar macrophage and additional inflammatory mediator systems. Excessive and persistent macrophage activation plays an essential role in MOFS and is hypothesized to represent the penultimate step in a series of continuous immuno-inflammatory stimulatory events, including local hypoxia, exposure to bacteria and toxins, and mediator release from localized areas of inflammation. When infection is the underlying or major contributing process, the diffuse inflammatory response develops independently of the specific type of microorganism. In noninfectious cases, the response also appears independent of the specific underlying cause.
235 Invasive hemodynamic monitoring using a Swan-Gantz catheter is essential in the optimal management of patients in shock or those suffering post-shock sequelae. Which of the following physiologic characteristics are associated with the various forms of shock?
a. Hypovolemic shock: Decreased pulmonary capillary wedge pressure (PCWP), decreased cardiac output, increased systemic vascular resistance (SVR)
b. Cardiogenic shock: Increased PCWP, decreased cardiac output, decreased SVR
c. Septic shock (hypodynamic): Decreased cardiac output, increased SVR
d. Neurogenic shock: Decreased PCWP, increased cardiac output, decreased SVR
Answer: a, c
236 Which of the following statement(s) is/are true concerning the relationship between cardiac function and effective blood volume?
a. A pulmonary capillary wedge pressure of 5–10 rules out fluid overload as a cause of pulmonary edema
b. A shift to the right in the Frank-Starling curve is associated with compromised cardiac function
c. Dilutional anemia may contribute to tachycardia even though blood volume and filling pressures are normal
d. The sole purpose of a pulmonary artery catheter is to measure pulmonary artery pressure and cardiac output
Answer: b, c
Although physical findings are often adequate to establish a diagnosis and institute management of cardiac failure, direct measurement of filling pressures of the right heart (central venous pressure) or the left heart (pulmonary artery pressure) may be required. Placement of a pulmonary artery catheter allows us to measure cardiac output by thermodilution and, more importantly, to sample mixed venous blood for saturation measurements which tell us the ratio between systemic oxygen delivery and oxygen consumption. From all of these measurements we can determine if cardiac output is normal for the level of filling pressure of the left ventricle, or if contractility is decreased. In the latter case, cardiac output will be lower than predicted for a given level of filling pressure. In the Frank-Starling curve, if the patient is to the right of the normal range, then cardiac function is compromised either because of valvular disease, extrinsic pressure such as pericardial tamponade, or more commonly, a decrease in contractility. If cardiac function and anatomy are normal, then blood volume, filling pressure and cardiac function are related to the Starling curve. The intake and output of fluid and salt is autoregulated to maintain the filling pressure of the left ventricle around 10 mm Hg. Extracellular fluid expansion is usually associated with normal blood volume. Gross expansion of extracelluar space results in deleterious effects if tissue edema can and often do exist with perfectly normal blood volume. In other words, a pulmonary capillary wedge pressure of 5–10 does not rule out fluid overload as a cause of pulmonary or GI dysfunction. In critically ill patients, the fear of hypotension and effect of perfusion usually results in infusion of intravenous salt and water in quantities which exceed losses. Consequently, most patients in the Intensive Care Unit have anemia, dilutional hypoproteinemia, and a compensatory increase in cardiac output. In response to anemia, these patients are tachycardic, even though blood volume is normal, filling pressures are normal, and total body extracellular fluid is excessive.
237 Which of the following statement(s) is/are true concerning methods of nutritional support?
a. Optimal results for enteral feedings are achieved with approximately half of calories supplied as carbohydrate and half as fat
b. Diarrhea is the most common complication of enteral feeds and is due to the high osmolarity of the carbohydrate components
c. The hyperosmolar nature of parenteral fat solutions requires central venous administration
d. Approximately 25–50% of calories should be provided as fat emulsion in patients receiving total parenteral nutrition
Answer: a, b, d
Most formulas for enteral feeding range from 1.0 to 2 cal/ml and include 3 to 7% protein. Most of the calories are supplied as glucose or sucrose, so that the solutions have a very high osmolarity. Cramps or diarrhea can result when these high osmolar solutions are placed into the stomach or intestine. Diarrhea is the major complication with most tube feeding formulas. Diarrhea can be minimized by the use of starch or fat as an energy source in tube feedings. This can be supplied as part of the commercial preparation or added in the form of medium chain triglycerides or other oils. The best results are usually achieved by supplying approximately half the calories as carbohydrate and half as fat. In patients receiving total parenteral nutrition, energy source is provided as carbohydrate, fat, and amino acid solutions. Parenteral feeding with carbohydrate is limited by the sclerotic effect of hyperosmolar solutions on veins. Fat is a more efficient energy source and can be given through peripheral veins in concentrations of either 10 or 20%. Most intensivists favor supplementing standard total parenteral nutrition solution with intravenous fat to provide at least 100 grams of fat emulsion each week to preclude fatty acid deficiency. Giving up to 25 to 50% of calories each day as fat emulsion may optimize the delivery of this caloric delivery.
238 Which of the following statement(s) is/are true concerning the autoregulation necessary to maintain oxygen consumption and oxygen delivery?
a. A change in oxygen consumption is followed by a proportionate change in oxygen delivery
b. A change in oxygen delivery is followed by a change in oxygen consumption
c. Increases in oxygen delivery are due solely to an increase in cardiac output
d. The normal ratio of oxygen delivery to consumption is 2:1
Answer: a
The relationships between oxygen consumption and oxygen delivery represent one of the most interesting regulation systems in homeostasis. First of all, if one of the three components of oxygen delivery is abnormal, endogenous mechanisms regulate the other two until normal oxygen delivery has been restored. The various combinations of compensatory mechanisms supply adequate oxygen for systemic metabolism through a wide range of variations in oxygen delivery. When there is a change in oxygen consumption, there is a proportionate change in oxygen delivery, which occurs almost immediately, mediated completely by a change in cardiac output. Conversely, a primary change in oxygen delivery is not followed by any change in oxygen consumption. The normal ratio of oxygen delivery to consumption is approximately 5:1.
239 Which of the following statement(s) is/are true concerning O2 venous saturation monitoring?
a. The normal saturation of mixed venous blood is 50%
b. Mixed venous blood obtained for saturation monitoring can be obtained from any peripheral vein
c. If arterial blood is fully saturated, the saturation of mixed venous blood is 80%
d. In less than fully saturated blood, the difference between arterial and venous saturation corresponds to oxygen extraction
Answer: c, d
The relationship between oxygen delivery and oxygen consumption is reflected in the amount of oxygen in venous blood. Under normal circumstances, oxygen delivery is 1000 cc/min and oxygen consumption is 200 cc/min. The amount of oxygen extracted is 20% of that delivered, and 80% of oxygen is still present in venous blood returning to the heart. Usually arterial blood is fully saturated, and under normal circumstances, the saturation of mixed venous blood (SVO2) will be 80%. This measurement must be made in mixed venous blood since the relative extraction of organs served by the superior and inferior vena cava and coronary sinus are quite different. As long as arterial blood is fully saturated, this observation holds true regardless of the absolute level of oxygen consumption or oxygen delivery. If the arterial blood is less than fully saturated, the difference between arterial and venous saturation corresponds to the oxygen extraction, hence the oxygen delivery/oxygen consumption ratio.
240 Which of the following statement(s) is/are true concerning oxygen kinetics in a critically ill, febrile patient?
a. Oxygen consumption will likely exceed three times normal
b. The high cardiac output and pulse rate are designed to increase oxygen delivery
c. The hyperdynamic response may actually increase oxygen delivery to exceed the increase in oxygen consumption
d. The patient can maintain adequate compensation as long as the oxygen delivery/oxygen consumption rate is greater than 2:1
Answer: b, d
In critically ill patients oxygen consumption may be elevated or depressed, but slight to moderate elevations in oxygen consumption is the most common abnormality in critically ill patients. Oxygen consumption will be elevated in proportion to the amount of inflammation. A febrile patient with significant signs of septic toxicity will typically have an oxygen delivery at 1.5 to 2 times normal. It is very unusual for a critically ill patient to experience oxygen consumption greater than twice normal. This occurs only in situations of severe muscular exercise such as seizures or tetanus. During hypermetabolism, a change in oxygen consumption is followed promptly by a proportionate change in oxygen delivery. Hence, it is “normal” for a hypermetabolic patient to have a high cardiac output and pulse rate. Rarely the hyperdynamic response exceeds the increase in oxygen consumption, reflected in a ratio higher than 5:1 and venous saturation greater than 80%. Some patients cannot mount an increased oxygen delivery in response to increased oxygen consumption because of the combination of hypoxemia, anemia, and myocardial failure. If this occurs, then the oxygen delivery/oxygen consumption ratio will be less than 5:1. The patient will compensate for this by increased oxygen extraction, however, and the patient will remain stable as long as the ratio is greater than 2:1.
241 Which of the following statement(s) is/are true concerning the treatment of pulmonary interstitial edema?
a. Diuresis and blood transfusion is a valuable step
b. Salt-poor albumin leaks through the capillaries and worsens the condition
c. Mannitol is contraindicated as a diuretic in this clinical situation
d. Isoproterenol is a poor choice as an ionotropic agent
Answer: a
Treatment of pulmonary edema has two important goals, the first is to improve oxygenation if it is impaired, and the second is to minimize fibrosis and bacterial infection, which often accompany pulmonary edema caused by capillary injury. The treatment of interstitial edema is to maintain the hydrostatic pressure as low as compatible with adequate cardiac output and to raise the oncotic pressure selectively in the vascular space. These measures, combined with fluid restriction and diuresis, will decrease the amount of pulmonary edema. Since it is desirable to maintain filling pressures of the left ventricle as low as possible while maintaining a good cardiac output, inotropic drugs to improve left ventricular contractility are helpful. Isoproterenol or dopamine should be used, with serial cardiac output and filling pressure measurements. The first step in decreasing pulmonary edema is to decrease the pulmonary capillary hydrostatic pressure as low as is compatible with an adequate cardiac output. This is done by diuresis and fluid restriction. As the patient falls behind in blood volume, signs of hypovolemia may appear. Blood volume is then replenished with a fluid that stays in the vascular space. Packed red cells are ideal for this application. When the hematocrit is normal, concentrated salt-poor albumin should be used. This hyperoncotic fluid replenishes the blood volume by attracting interstitial fluid from throughout the body into the vascular space and supplements diuresis. This technique is useful even in the septic patient who may have increased capillary permeability and may loose albumin from the vascular space at a rapid rate. Even if albumin “leaks out”, the short term effects of expanding blood volume and decrease in edema will appear.
242 Which of the following statement(s) is/are true concerning the pathophysiology of gas exchange?
a. Hypoventilation in relation to perfusion can result in an oxygen saturation of less than 100%
b. Diffusion block and / mismatch can almost completely be overcome by breathing 100% oxygen
c. Transpulmonary shunting does not occur under normal circumstances
d. The normal arterial oxygen saturation should be 100%
Answer: a, b
Under normal conditions, red blood cells in the pulmonary capillaries become fully saturated and oxygen dissolves in plasma resulting in blood PO2 of 100 and O2 saturation of 100%. This equilibration may be disturbed by hypoventilation in relationship to the perfusion (/ mismatch), diffusion block caused by interstitial fibrosis, or perfusion of nonventilated alveoli. Diffusion block and / mismatch can almost be completely overcome by breathing 100% oxygen, hence hypoxemia during exposure to high alveolar PO2 is caused by total / mismatch, so-called transpulmonary shunting or venous ad mixture. Under normal circumstances, about 5% of the blood entering the left atrium has been shunted away from the pulmonary capillaries, either as the result of bronchial nutritive blood flow or through thebesian veins opening directly into the left side of the heart. This phenomenon, combined with a normal minor / mismatch associated with breathing at rest and positional changes in pulmonary blood flow, result in the fact that normal arterial PO2 is 90–100 mm Hg and the normal O2 saturation is 98%.
243 Which of the following statement(s) is/are true concerning CO2 transfer in the lung?
a. Carbon dioxide excretion is a direct function of alveolar ventilation
b. Normally end tidal CO2 should be identical to PaCO2
c. The gradient between end tidal and arterial CO2 can be an indirect measure of nonperfused alveoli
d. Positive pressure ventilation under normal airway pressures creates a significant end tidal PaCO2 gradient
Answer: a, b, c
The amount of carbon dioxide excretion is directly related to alveolar ventilation. While oxygenation is a function of matching blood flow to alveoli, carbon dioxide excretion is a direct function of ventilation or hyperventilation of alveoli with some blood flow. Normally the end tidal CO2 represents mixed alveolar gas which is at equilibrium with pulmonary capillary blood, hence with arterial blood. Therefore, the end tidal CO2 and the PaCO2 should be identical. End tidal CO2 measurement is a very useful continuous measurement of PaCO2 which can be used as a monitor when the lung is normal, as in ventilator weaning. Furthermore, the gradient between end tidal and arterial CO2, when it is large, acts as an indirect measure of nonperfused alveoli and/or compression volume. In patients who are ventilated with positive pressure ventilation, a significant end tidal PaCO2 gradient occurs only when peak airway pressures are very high (over 30 cm H2O) and the compression volume is a significant component of each exhaled breath.
244 Which of the following statement(s) is/are true concerning the assessment of protein reserve?
a. Conventional serum proteins such as albumin and globulin are early indicators of malnutrition
b. The total lymphocyte count reflects immune status and not nutrition
c. Antigen skin testing reflects patient immunity and not nutrition
d. Measurement of urea excretion in urine can be used as a measurement of protein breakdown
Answer: d
Since protein is the functional and structural chemical of the body, most nutritional assessment techniques are estimates of protein reserves. The actual nitrogen balance can be measured by measuring the amount of nitrogen excreted. This is most conveniently done by measuring the amount of urea excreted in the urine, assuming that urea constitutes 85% of the total nitrogen excretion. Knowing nitrogen excretion, the amount of protein catabolized can be estimated and compared with the amount of protein ingested by the patient. Indirect assessments of protein reserves are based on single measurements of body substances that are dependent on rapid protein synthesis for maintenance of normal levels. Conventional serum proteins such as albumin and globulin are not affected by malnutrition until it is very severe. Proteins such as prealbumen and transferrin, which turn over more rapidly, are better indicators of protein status. Lymphocytes are rapidly destroyed and protein is required for the formation of new cells. Consequently, the absolute lymphocyte count is a useful measure of the status of protein reserves. The lymphocyte count is considered by some the best single “static” measurement characterizing nutritional status. Protein is also required for synthesizing the cells and mediators involved in skin test reactivity. Although skin test reactivity is a manifestation of lymphocyte-mediated immunity, its usefulness in patient assessment is probably that of assessment of the inflammatory response than lymphocyte activity per se. Some chronically and acutely malnourished patients convert from reactive to anergic, and reactivity can be restored by nutritional repletion.
245 Useful steps to optimize systemic oxygen delivery include:
a. Maintaining mean arterial blood pressure between 50 and 90 mm Hg
b. Optimizing PEEP levels by monitoring mixed venous saturation
c. Turning the patient prone
d. Sedation or paralysis
Answer: a, b, c, d
Optimizing systemic oxygen delivery in relationship to oxygen requirement is the primary goal of management. Improving oxygenation of the blood itself by improving alveolar inflation is only one of the steps in optimizing oxygen delivery. Equally or more important are treating anemia and optimizing cardiac output. Cardiac output should be optimized to maintain delivery of four to five times consumption. In general, this means avoiding those factors which decrease cardiac output, rather than actively trying to increase cardiac output. Blood pressure should be maintained high enough to provide coronary perfusion (over 50 mm Hg mean pressure) but not so high as to limit left ventricular function (over 90 mm Hg mean arterial pressure). Alveolar collapse is treated by cleaning the airways, avoiding 100% oxygen, and moving fluid from the lung or chest, and finally by the use of positive end exploratory pressure to hold open those alveoli which have been opened by other measures. The optimal level of PEEP is that level that maintains arterial oxygenation but does not decrease venous return or cardiac output. This optimal level is best determined by monitoring mixed venous saturation. Another step in optimizing lung function is to take advantage of the gravitational effects on pulmonary blood flow by turning the patient prone or to a full lateral position to direct blood flow to areas of optimal alveolar function. This step will often result in an opening in the closed posterior alveoli which have been compressed by the weight of the fluid in the lungs. At the same time that oxygen delivery is optimized, oxygen consumption should be decreased to normal or even below normal if necessary. Treating infection, providing adequate sedation, and establishing muscular paralysis decrease oxygen consumption, and decrease the need for oxygen delivery.
246 Phases of multiorgan failure will include:
a. Generalized increased capillary permeability
b. A hypermetabolic state
c. Organ malfunction
d. All of the above
Answer: d
Clinically the multiple-organ failure patient progresses through well-defined phases. These phases include: Phase 1—a generalized increased capillary permeability resulting in edema, weight gain, and intravenous volume replacement, increased protein concentration in urine and lymph. Although the pulmonary microvasculature has been most thoroughly studied, it is apparent that the lung is simply the most obvious end organ in a generalized permeability defect. Phase 2—A hypermetabolic state, with increased oxygen consumption and a compensatory increase in oxygen delivery characterized by tachycardia and high cardiac output. This condition following systemic ischemic and reperfusion is similar to hypermetabolism following endotoxemia, localized sterile inflammation, and infusion of stress hormones, suggesting a common mechanism. Phase 3—Organ malfunction due to localized edema and cellular injury, particularly in the kidney, liver, brain, and host defense system. Hemorrhagic shock predisposes to bacterial translocation and endotoxin absorption from the intestine. Phase 4—In the absence of systemic sepsis, organs may recover to normalcy or may be irreversibly damaged, leading to a need for chronic support. If the organ failure phases lead to systemic infection or irreversible tissue damage in the lung or brain, the death of the entire organ is likely.
247 Which of the following statement(s) is/are true concerning oxygen consumption (O2)?
a. O2 is normally 100–120 cc2/m2/min
b. Resting O2 is controlled by the level of thyroid and catecholamine hormones
c. Under steady state conditions the amount of oxygen consumed exceeds the amount of oxygen taken up by the pulmonary capillaries
d. O2 is dependent on the status of pulmonary function
Answer: a, b
Oxygen consumed in the process of metabolism is expressed as the volume of oxygen per minute (O2). O2 is normally 100–120 cc2/m2/min, or 200 cc/min for a typical adult. Resting O2 is a function of metabolizing body cell mass, with fine tuning control provided by the level of thyroid and catecholamine hormones. O2 decreases under conditions of hypothermia, paralysis, and hypothyroidism. O2 increases during exercise or muscular activity, hyperthermia, profound hypothalamic injury, hyperthyroidism, catecholamines, and inflammatory mediators, particularly the interleukin cytokines. Under steady state conditions, the amount of oxygen consumed in systemic metabolism is exactly equal to the amount of oxygen taken up by the pulmonary capillaries via the airway. This is true regardless of the status of pulmonary function or dysfunction, so we measure O2 across the lung and assume that it is exactly the amount consumed in the systemic metabolism.
248 Which of the following statement(s) is/are true concerning the outcome in patients with acute renal failure?
a. Mortality for ischemic acute tubular necrosis without other organ failure is approximately 6%
b. Multiple organ failure complicated with acute renal failure is associated with mortality ranging from 50% to 90%
c. Recovery of renal function after six weeks is unlikely
d. There is no difference in survival between oliguric and nonoliguric renal failure
Answer: a, b, c
Survival of patients with acute renal failure is a function of the successful treatment of the primary disease from which the renal failure was derived. The mortality for ischemic acute tubular necrosis without organ failure has been reported at approximately 6%. By contrast, mortality of multiorgan failure complicated by acute renal failure ranges from 50% to 90%. In patients who survive the acute phase of illness, recovery of renal function after acute renal failure is dependent on the type and extent of injuries to the renal parenchyma. If renal function is not returned after six weeks, recovery is unlikely. Nonoliguric renal failure is usually limited in its extent and is almost always reversible.
249 Which of the following statement(s) is/are true concerning oxygen delivery?
a. The amount of oxygen delivered to peripheral tissues is dependent upon the oxygen content in arterial blood and cardiac output
b. Oxygen content is commonly measured in arterial blood
c. The normal arterial-venous difference is 4 cc O2/dL
d. Normal systemic oxygen delivery for a typical adult is approximately 1000 cc/min
Answer: a, c, d
The amount of oxygen that is delivered to peripheral tissues is the product of the oxygen content in arterial blood times the cardiac output. Normally, oxygen content of arterial blood is approximately
20 cc/dL, and the normal cardiac index is 5 L/min. Therefore, the normal systemic oxygen delivery is approximately 1000 cc/min. Although oxygen content is the most important measure of oxygen in the blood, PO2 and oxyhemoglobin saturation is more commonly measured in the Intensive Care Unit, hence it is necessary to convert between these measurements. The normal oxygen content of venous blood is 16 cc/dL. Hence, the normal arterial-venous difference is 4 cc O2/dL.
250 Which of the following statement(s) is/are true concerning carbon dioxide kinetics?
a. The amount of carbon dioxide produced is equivalent to the amount of oxygen consumed
b. Carbon dioxide levels in blood, present mostly as a bicarbonate ion, can quickly change
c. Normally the amount of carbon dioxide excreted through the lung is exactly equal to the amount of carbon dioxide produced in peripheral tissues
d. The amount of carbon dioxide excreted is a function of ventilation of perfused alveoli
Answer: a, c, d
The total amount of carbon dioxide produced by systemic metabolism is roughly equivalent to the amount of oxygen consumed (100–120 cc/m2/min, 200 cc/min in a typical adult). CO2 production is increased or decreased by each of the factors that causes an increase or decrease in oxygen consumption. Most of the carbon dioxide in blood is present as bicarbonate ion which cannot be changed quickly. However, the metabolically produced CO2 is mostly present as dissolved carbon dioxide, added to the blood in the peripheral tissues and excreted in the lung. In a steady state, the amount of carbon dioxide excreted through the lung is exactly equal to the amount of carbon dioxide produced in peripheral tissues. The amount of carbon dioxide excreted is a function of ventilation of perfused alveoli (i.e. the alveolar ventilation/min).
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