A. Lysine.

B. Tyrosine.

C. Alanine.

D. Glutamine.

E. Arginine.

Answer: CD

DISCUSSION: Alanine is released from skeletal muscle and extracted by the liver, where it is converted to new glucose. Glutamine is also released from muscle and participates in renal acid-base homeostasis and serves as fuel for rapidly growing cells such as enterocytes, stimulated macrophages, and fibroblasts. Together, these two amino acids account for approximately two thirds of the nitrogen released from skeletal muscle.

A. Lean body mass increases.

B. Total body water increases.

C. Adipose tissue decreases.

D. Body weight decreases.

Answer: A

DISCUSSION: Lean body mass represents the body compartment that contains protein. Because critical illness stimulates proteolysis and increased excretion of body nitrogen, this compartment is consistently reduced, not increased. The change in body composition is associated with a loss of body weight, an increase in total body water, and a decrease in body fat.

A. Central nervous system.

B. Skeletal muscle.

C. Bone.

D. Kidney.

E. Tissue in the healing wound.

Answer: ADE

DISCUSSION: Glucose is produced in increased amounts to satisfy the fuel requirements of the healing wound. In addition, nerve tissue and the renal medulla also utilize this substrate. Skeletal muscle primarily utilizes fatty acids, and bone utilizes mineral substrate.

A. Local cell proliferation within the wound.

B. The central nervous system to initiate fever.

C. The production of “acute-phase proteins.”

D. Hypoferremia.

E. Septic shock.

Answer:ABCD

DISCUSSION: Although cytokines exert primarily autocrine and paracrine effects, they may also cause systemic effects.

A. Hypermetabolism.

B. Fever.

C. Tachypnea.

D. Hyperphagia.

E. Negative nitrogen balance.

Answer: D

DISCUSSION: The characteristic metabolic response to injury includes hypermetabolism, fever, accelerated gluconeogenesis, and increased proteolysis (creating a negative nitrogen balance). Food intake is generally impossible because of abdominal injury or ileus. With time, food intake increases, but the patient generally experiences anorexia, not hyperphagia.

A. Hypotension.

B. Hypoperfusion of tissues.

C. Hypoxemia.

D. All of the above.

Answer: B

DISCUSSION: Shock, no matter what the cause, is a syndrome associated with tissue hypoperfusion. Tissue hypoperfusion leads to tissue hypoxia, which may or may not be due to hypoxemia. Hypotension is a late sign of shock and, therefore, is not a good clinical indicator of the presence of tissue hypoperfusion.

A. Continuous cardiac output monitoring may unmask events not detected by intermittent cardiac output measurements.

B. Continuous cardiac output monitoring by the thermodilution method requires continuous infusion of fluid injectate at a constant rate and temperature.

C. The major advantage of the Fick method over the thermodilution method of calculating cardiac output is that it is noninvasive, requiring only the determination of oxygen consumption by respiratory gas analysis.

D. The technique of thoracic electrical bioimpedance utilizes sensors to determine stroke volume by detecting changes in resistance to a small, applied alternating current.

Answer: AD

DISCUSSION: Various techniques are available to measure cardiac output continuously. The advantages of continuous cardiac output monitoring, as compared with intermittent methods, are (1) previously undetected events may be unmasked; (2) more prompt recognition of adverse events may be achieved; and (3) earlier therapeutic intervention may be possible. Continuous cardiac output monitoring using the thermodilution method appears to be as accurate as the “standard” intermittent bolus method, but it does not require fluid injectates. In this method, a modified pulmonary artery catheter incorporating a thermal filament heats blood in the right ventricle at pulsed intervals, and a distal thermistor detects the temperature change, which can be related mathematically to cardiac output. The Fick method combines respiratory gas analysis with oximetery to determine oxygen consumption (V(overdot)O 2) and to estimate mixed venous and arterial oxygen content differences, respectively. Cardiac output (CO) is then determined from the formula: CO = V(overdot)O 2/ {C(a-v)O 2 × 10} @ V(overdot)O 2/ {SaO 2 - SvO 2) × (Hb) × (1.39) × 10}. Thoracic electrical bioimpedance is a technique by which the resistance to a small-amplitude alternating current (i.e., the impedance) is measured using various electrodes. The impedance change induced by each cardiac ejection is a function of the stroke volume, which then can be used to calculate the cardiac output.

A. Cytokines act directly on target cells and may potentiate the actions of one another.

B. Interleukin 1 (IL-1) is a major proinflammatory mediator with multiple effects, including regulation of skeletal muscle proteolysis in patients with sepsis or significant injury.

C. Platelet-activating factor (PAF) is a major cytokine that results in platelet aggregation, bronchoconstriction, and increased vascular permeability.

D. Tumor necrosis factor alpha (TNF-a), despite its short plasma half-life, appears to be a principal mediator in the evolution of sepsis and the multiple organ dysfunction syndrome because of its multiple actions and the secondary cascades that it stimulates.

Answer: C

DISCUSSION: Cytokines are soluble peptide molecules that are synthesized and secreted by a number of cell types in response to injury, inflammation, and infection. Cytokines, which include the interleukins, tumor necrosis factor, colony-stimulating factors, and the interferons, comprise only one category of inflammatory mediators involved in the host response. Endotoxin, complement fragments, eicosanoids, kinins, nitric oxide, oxidants, and PAF are noncytokine mediators that also have important roles in the systemic inflammatory response. IL-1 and TNF-a, like other cytokines, have multiple effects on target cells and potentiate the actions of other mediators to produce an amplified inflammatory response. TNF-a is thought to play a central role in the stress response, particularly in response to endotoxemia.

A. Adrenocortical insufficiency may manifest itself as severe shock refractory to volume and pressor therapy.

B. The presence of hyperglycemia and hypotension may suggest the diagnosis of shock due to adrenocortical insufficiency.

C. Hydrocortisone does not interfere with the serum cortisol assay and should be given to hemodynamically unstable patients suspected of having hypoadrenal shock.

D. The rapid adrenocorticotropic hormone (ACTH) stimulation test should be performed to help establish the diagnosis of acute adrenocortical insufficiency.

Answer: AD

DISCUSSION: Shock due to acute adrenocortical insufficiency is relatively uncommon but must be considered when shock refractory to volume replacement and pressor therapy is present. Hypoglycemia may be present. Patients with high metabolic stress may exhibit adrenal insufficiency only under conditions of severe stress; thus, a history of adrenal insufficiency or steroid dependency need not be elicited. When adrenocortical insufficiency is suspected, the rapid ACTH (cosyntropin) stimulation test should be performed. Serum cortisol levels should be drawn before intravenous administration of 250 mg. of cosyntropin, and 30 and 60 minutes afterward. A peak cortisol level of less than 20 mg./100 ml. suggests abnormal adrenal function. In a hemodynamically unstable patient therapy should be instituted before the test results become available. Dexamethasone does not interfere with the cortisol assay, and it is the corticosteroid of choice while the ACTH stimulation test is being performed.

A. There is a decrease in systemic vascular resistance and an increase in venous capacitance.

B. Tachycardia or bradycardia may be observed, along with hypotension.

C. The use of an alpha agonist such as phenylephrine is the mainstay of treatment.

D. Severe head injury, spinal cord injury, and high spinal anesthesia may all cause neurogenic shock.

Answer: C

DISCUSSION: Neurogenic shock occurs when severe head injury, spinal cord injury, or pharmacologic sympathetic blockade leads to sympathetic denervation and loss of vasomotor tone. Both arteriolar and venous vessels dilate, causing reduced systemic vascular resistance and a great increase in venous capacitance. The patient's extremities appear warm and dry, in contrast to those of a patient in cardiogenic or hypovolemic shock. Tachycardia is frequently observed, though the classic description of neurogenic shock includes bradycardia and hypotension. Volume administration to fill the expanded intravascular compartment is the mainstay of treatment. The use of alpha-adrenergic agonist is infrequently necessary to treat neurogenic shock.

A. Prostaglandins and thromboxanes are synthesized via the cyclo-oxygenase pathway.

B. The vasoconstricting, platelet-aggregating, and bronchoconstricting effects of thromboxane A 2 are balanced by the actions of prostacyclin, which produces the opposite effects.

C. Leukotriene synthesis is inhibited by the action of nonsteroidal anti-inflammatory drugs (NSAIDs).

D. The principal prostaglandins have a short circulation half-life and exert most of their effects locally.

Answer: ABD

DISCUSSION: The eicosanoids are a group of compounds arising from the metabolism of arachidonic acid. The prostaglandins and thromboxanes are synthesized via the cyclo-oxygenase pathway; thus, their synthesis is blocked by NSAIDs. Leukotrienes, on the other hand, are synthesized via the lipoxygenase pathway. Prostacyclin, produced largely by vascular endothelium, inhibits platelet aggregation and causes vasodilatation as well as bronchodilatation. Its effects are balanced by those of thromboxane A 2, which is produced by platelets and also local actions, including platelet aggregation, vasoconstriction, and bronchoconstriction. The leukotrienes also have pulmonary and hemodynamic effects and may be involved in the physiologic responses associated with anaphylactic and septic shock.

A. Below the critical oxygen delivery (D(overdot)O 2crit), one would expect to see a decrease in the lactate-pyruvate ratio.

B. D(overdot)O 2crit may be increased in patients with sepsis.

C. A desirable goal in the treatment of shock is to achieve delivery-independent oxygen consumption.

D. The oxygen extraction ratio remains constant as long as oxygen delivery remains above D(overdot)O 2crit.

Answer: BC

DISCUSSION: Oxygen consumption is said to be delivery dependent below a critical point, D(overdot)O 2crit, at which anaerobic metabolism supervenes. Above this point, oxygen consumption is relatively independent of oxygen delivery because the body's cells can compensate for falls in oxygen delivery by extracting more oxygen. In the delivery-dependent region, if cellular hypoxia is present, the lactate-pyruvate ratio rises, owing to the switch to anaerobic metabolism. Generally, it is desirable to achieve delivery-independent oxygen consumption, to avoid ongoing tissue hypoxia. There is considerable debate, however, about the nature of the oxygen consumption–oxygen delivery relationship in cases of established sepsis or multiple organ dysfunction syndrome. In such cases, D(overdot)O 2crit may be increased, although the therapeutic benefit of trying to achieve “supranormal” oxygen delivery has not been firmly established.

A. Dobutamine.

B. Sodium nitroprusside.

C. Pneumatic antishock garment.

D. Intra-aortic balloon pump.

Answer: C

DISCUSSION: Cardiogenic shock occurs when the heart fails to generate adequate cardiac output to maintain tissue perfusion. Intrinsic causes such as myocardial dysfunction secondary to coronary artery disease, or extrinsic causes such as pulmonary embolism, tension pneumothorax, and pericardial tamponade, may produce cardiogenic shock. Principles of treatment of cardiogenic shock are aimed at optimizing preload, cardiac contractility, and afterload. Preload is usually adequate or high in cardiogenic shock. Dobutamine is a useful inotropic agent, particularly when filling pressures are high, because of its mild vasodilatory effect, as well as its effect to enhance cardiac contractility. Afterload-reducing agents, such as sodium nitroprusside, may be beneficial in cardiogenic shock in the setting of elevated filling pressures, low cardiac output, and elevated systemic vascular resistance. Cardiac output may improve with use of afterload-reducing agents by decreasing myocardial wall tension and optimizing the myocardial oxygen supply-demand ratio. The intra-aortic balloon pump (IABP), by providing diastolic augmentation, reducing left ventricular afterload, and reducing myocardial oxygen consumption, is sometimes useful in the treatment of cardiogenic shock. The IABP is especially useful in low–cardiac output postcardiotomy patients, in patients awaiting revascularization, and in patients with acute myocardial infarction complicated by mitral insufficiency or ventricular septal defect. The pneumatic antishock garment (PASG), which causes an increase in systemic vascular resistance, is contraindicated in cardiogenic shock.

A. Pulmonary artery and pulmonary capillary wedge pressure readings should be made at end inspiration, to minimize ventilatory artifacts.

B. Continuous SvO 2 monitoring based on the technique of reflectance spectrophotometry has been shown to be accurate and reliable.

C. Direct measurement of gastric intramucosal pH can be provided by gastrointestinal tonometry.

D. Hyperlactatemia may be seen in a number of clinical conditions not associated with tissue hypoxia, including liver disease and hypermetabolic states.

Answer: BD

DISCUSSION: Many different monitoring techniques may be used to assess the adequacy of therapy for shock. The pulmonary artery catheter can provide important hemodynamic and oxygen transport data that are very useful in directing therapy aimed at optimizing cardiac function and oxygen delivery. Pulmonary artery and pulmonary capillary wedge pressure readings should be made at end-expiration to minimize ventilatory artifacts. Continuous SvO 2 monitoring, an accurate, reliable method that combines pulmonary artery catheterization with the technique of reflectance spectrophotometry, may provide early warning signs of hemodynamic compromise or inadequate oxygen delivery. Gastrointestinal tonometry provides information that allows one to infer the adequacy of splanchnic tissue perfusion. In this technique, intramucosal pH is calculated using the Henderson-Hasselbalch equation and measurements of gut intraluminal PCO 2 and arterial bicarbonate concentration. Serum lactate concentration may be monitored in shock to detect metabolic acidosis associated with anaerobic metabolism; however, mild to moderate hyperlactatemia may also be seen with liver disease, toxin ingestion, and hypermetabolic states not associated with shock.

A. Administration of one liter of Ringer's lactate solution.

B. Subxiphoid pericardiotomy.

C. Needle decompression of the left chest in the second intercostal space.

D. Emergency thoracotomy to cross-clamp the aorta.

Answer: AC

DISCUSSION: The finding of distended neck veins in conjunction with hypotension should suggest tension pneumothorax or pericardial tamponade. Absent ipsilateral breath sounds and a trachea deviated to the contralateral side may provide additional evidence for a tension pneumothorax, the immediate treatment of which is needle decompression of the chest in the second or third intercostal space in the midclavicular line. Pericardial tamponade may initially respond to volume administration by enhancing preload. Pericardiocentesis may need to be performed emergently if hemodynamic instability persists after an initial fluid bolus when signs of compressive cardiogenic shock are present. Subxiphoid pericardiotomy should be performed only in the operating room by experienced persons who are trained to deal with penetrating cardiac injuries. There is no role for aortic cross-clamping in this scenario of cardiogenic shock.

A. The “two-hit” model proposes that secondary MODS may be produced when even a relatively minor second insult reactivates, in a more amplified form, the systemic inflammatory response that was primed by an initial insult to the host.

B. The systemic inflammatory response syndrome (SIRS), shock due to sepsis or SIRS, and MODS may be regarded as a continuum of illness severity.

C. Prolonged stimulation or activation of Kupffer cells in the liver is thought to be a critical factor in the sustained, uncontrolled release of inflammatory mediators.

D. The incidence of MODS in intensive care units has decreased owing to increased awareness, prevention, and treatment of the syndrome.

Answer: ABC

DISCUSSION: MODS is part of a clinical continuum that begins with the systemic inflammatory response syndrome, which is the host's stress response to any major insult such as injury or infection. MODS may develop as a result of the initial insult, but more commonly, it develops following a second or subsequent insult to the host. The two-hit theory holds that the systemic inflammatory response is amplified following the second hit, such as nosocomial pneumonia, leading to exaggerated, persistent release of inflammatory mediators that contribute to the pathogenesis of MODS. The liver appears to be a pivotal organ in the progression and outcome of MODS, partly because of the activation and prolonged stimulation of the Kupffer cells, which comprise the majority of the body's macrophage population. Macrophages are known to play a critical role in the elaboration of numerous inflammatory mediators. Despite advances in critical care and in the understanding of the pathogenesis of MODS, the incidence of MODS continues to increase without a significant improvement in outcome.

A. Following hemorrhagic shock, there is an initial interstitial fluid volume contraction.

B. Dopamine, or a similar inotropic agent, should be given immediately for resuscitation from hemorrhagic shock, to increase cardiac output and improve oxygen delivery to hypoperfused tissues.

C. The use of colloid solutions or hypertonic saline solutions is contraindicated for treatment of hemorrhagic shock.

D. In hemorrhagic shock, a narrowed pulse pressure is commonly seen before a fall in systolic blood pressure.

Answer: BC

DISCUSSION: Hemorrhagic shock is associated with a contraction of the interstitial fluid compartment because of precapillary vasoconstriction and reabsorption of interstitial fluid into the vascular compartment along hydrostatic pressure gradients. Systolic hypotension may not be evident in hemorrhagic shock until at least 30% or more of blood volume is exsanguinated. A decrease in the pulse pressure (the difference between systolic and diastolic pressures) may be observed with losses of 15% to 30% of blood volume. Treatment of hemorrhagic shock includes intravascular fluid administration and definitive control of the source of the hemorrhage. Inotropic agents should not be started before volume resuscitation but may be added to improve oxygen delivery to hypoxic tissues if volume administration alone does not produce resuscitative goals. Colloid or hypertonic saline solutions are not contraindicated in the treatment of hemorrhagic shock; however, definitive evidence that such solutions are better than standard crystalloid solutions is lacking.

A. A circulating myocardial depressant factor may account for the cardiac dysfunction sometimes seen with shock due to sepsis or SIRS.

B. A cardiac index (CI) of 6 liters per minute per square meter of body surface, a pulmonary capillary wedge pressure of 15 mm. Hg, and a systemic vascular resistance index (SVRI) of 800 dynes-sec/(cm 5-m 2) is a hemodynamic profile consistent with septic shock.

C. An increase in SvO 2 in septic patients may be explained by the finding of anatomic arteriovenous shunts.

D. Results of human trials employing antimediator therapy, such as antiendotoxin antibodies, IL-1 receptor antagonist, and tumor necrosis factor (TNF) antibodies, have confirmed animal studies that demonstrate a significant improvement in survival with the use of such agents.

Answer: AB

DISCUSSION: Shock due to sepsis or SIRS frequently manifests as a hyperdynamic cardiovascular response, consisting of an elevated CI and a decreased SVR or SVRI. Occasionally, myocardial depression may be seen, characterized by increased ventricular volumes and decreased ejection fractions. A circulating myocardial depressant factor, possibly TNF, may be responsible for the cardiac dysfunction in such instances. The cause of the increased SvO 2 frequently observed in septic patients is unclear, but it may be secondary to bioenergetic failure, metabolic downregulation, or microcirculatory maldistribution leading to physiologic shunting. True anatomic arteriovenous shunting has not been demonstrated in humans in septic shock. Treatment of septic shock consists of appropriate antibiotic use and supportive therapy. Experimental antimediator therapies have not been encouraging thus far in human clinical trials, despite the promising results from many animal studies.

A. In addition to their pathophysiologic roles in inflammation, injury, and infection, oxidants also have physiologic roles.

B. Oxidants may be generated from activated neutrophils and during reperfusion following a period of ischemia.

C. The deleterious effects of oxidants include lipid peroxidation and cell membrane damage, oxidative damage to DNA, and inhibition of adenosine triphosphate (ATP) synthesis.

D. The mechanism of ischemia-reperfusion injury involved the catalytic production of superoxide anion (O 2•) by the enzyme xanthine oxidase.

Answer: ABCD

DISCUSSION: Oxidants are reactive oxygen metabolites that have both physiologic and pathophysiologic roles. As potent oxidizing agents, oxidants are involved in cytochrome P 450–mediated oxidations, for example. In pathophysiologic processes associated with inflammation, injury, and infection, oxidants may be generated by activated neutrophils and in ischemia-reperfusion injury. During ischemia, the enzyme xanthine oxidase accumulates. When oxygen availability increases during reperfusion, O 2• is formed in a reaction catalyzed by xanthine oxidase. Further oxidant formation ensues, causing the production of H 2O 2 and the extremely reactive hydroxyl ion (OH•). Oxidants may cause direct cell damage by the mechanisms of lipid peroxidation and cell membrane disruption, inhibition of ATP synthesis, reduction of cellular nicotinamide adenine dinucleotide (NAD), and oxidative damage to DNA and amino acids. In addition, oxidants may have a chemotactic role, leading to leukocyte infiltration and activation, causing further tissue damage by the release of cytotoxic proteases.

A. Selective decontamination of the digestive tract with the use of oral antibiotics has been shown to reduce nosocomial pneumonias and to improve mortality rates.

B. Enteral nutrition, as compared with parenteral nutrition, preserves the villus architecture of the gut.

C. Gut dysfunction may be an effect of shock, but it may also contribute to the development of MODS by the mechanism of bacterial translocation.

D. As compared with parenteral nutrition, enteral nutrition is associated with a reduction in septic morbidity.

Answer: BCD

DISCUSSION: The gut has a vital role in the pathophysiology of shock. The splanchnic circulation is very vulnerable to the circulatory redistribution that occurs in shock, thus, gut ischemia may occur early in the various shock syndromes. Gut injury, as a result of ischemia or reperfusion injury, leads to disruption in the intestinal mucosal barrier and increased gut permeability. Translocation of enteric flora or bacterial toxins across the gut wall may then occur, resulting in amplification of the systemic inflammatory response and the development of multiple organ dysfunction. Gut dysfunction, therefore, may perpetuate the inflammatory process. Various methods have been tried to modulate the deleterious effects of gut dysfunction. Selective decontamination of the digestive tract by oral antibiotics has been shown to reduce the incidence of nosocomial pneumonias, but no improvement in mortality has been demonstrated thus far with this controversial technique. Early enteral nutrition probably has the biggest impact on the preservation of gut architecture and function. When compared to parenteral nutrition, enteral feeding is more cost effective and is associated with a lower rate of septic morbidity.

A. There are no primary alterations in cardiovascular signs.

B. Signs of increased intracranial pressure may be masked by the hyponatremia.

C. Oliguric renal failure is an unlikely complication.

D. Rapid correction of the hyponatremia may prevent central pontine injury.

E. This patient is best treated by restriction of water intake.

Answer: A

DISCUSSION: Acute symptomatic hyponatremia is characterized by central nervous system signs of increased intracranial pressure. Changes in blood pressure and pulse are secondary to increased intracranial pressure. In the absence of hypovolemia, asymptomatic patients may be treated by restriction of water intake; however, in such patients, hyponatremia should be partially corrected by parenteral sodium administration. Rapid correction, particularly to hypernatremia, may lead to central pontine myelinolysis. Oliguric renal failure may rapidly develop in severe hyponatremia.

A. Females and obese persons have an increased percentage of body water.

B. Increased muscle mass is associated with decreased total body water.

C. Newborn infants have the greatest proportion of total body water.

D. Total body water decreases steadily with age.

E. Any person's percentage of body water is subject to wide physiologic variation.

Answer: CD

DISCUSSION: Since fat contains little water, lean persons with a proportionately greater muscle mass have a greater than expected volume of total body water. Likewise, the female body habitus and obesity contribute to decreased total body water percentage. The highest proportion of total body water is found in newborn infants, and total body water decreases steadily and significantly with age. The actual figure for a healthy person is remarkably constant.

A. The total extracellular fluid volume represents 40% of the body weight.

B. The plasma volume constitutes one fourth of the total extracellular fluid volume.

C. Potassium is the principal cation in extracellular fluid.

D. The protein content of the plasma produces a lower concentration of cations than in the interstitial fluid.

E. The interstitial fluid equilibrates slowly with the other body compartments.

Answer: B

DISCUSSION: The total extracellular fluid volume represents 20% of body weight. The plasma volume is approximately 5% of body weight. Sodium is the principal cation. The Gibbs-Donan equilibrium equation explains the higher total concentration of cations in plasma. Except for joint fluid and cerebrospinal fluid, the majority of the interstitial fluid exists as a rapidly equilibrating component.

A. The sodium concentration must be corrected by 5 mEq. per 100 mg. per 100 ml. elevation in blood glucose.

B. With normal renal function, this patient is likely to be volume overloaded.

C. Proper fluid therapy would be unlikely to include potassium administration.

D. Insulin administration will increase the potassium content of cells.

E. Early in treatment adequate urine output is a reliable measure of adequate volume resuscitation.

Answer: D

DISCUSSION: Each 100-mg. per 100 ml. elevation in blood glucose causes a fall in serum sodium concentration of approximately 2 mEq. per liter. Excess serum glucose acts as an osmotic diuretic, producing increased urine flow, which can lead to volume depletion. Insulin therapy and the correction of the patient's associated acidosis produce movement of potassium ions into the intracellular compartment.

A. Compensation occurs by a shift of chloride out of the red blood cells.

B. Renal compensation occurs rapidly.

C. Retention of bicarbonate and increased ammonia formation are normal compensatory mechanisms.

D. Narcotic administration is an unusual cause of respiratory acidosis.

E. The ratio of bicarbonate to carbonic acid is less than 20:1.

Answer: CE

DISCUSSION: Renal compensation for acute hypoventilation is relatively slow. Depression of the respiratory center by morphine can lead to respiratory acidosis. Renal retention of bicarbonate, ammonia formation, and shift of chloride into red cells combine to increase the ratio of bicarbonate to carbonic acid to 20:1.

A. Hypoperfusion from the shock state rarely produces an elevated anion gap.

B. Retention of sulfuric and phosphoric acids may lead to this form of acidosis.

C. Copious diarrhea does not produce this condition.

D. Rapid volume expansion may produce this form of acidosis.

E. Use of lactated Ringer's solution is inappropriate in the treatment of lactic acidosis.

Answer: BC

DISCUSSION: An elevated anion gap may be produced by lactic acidosis from shock or by retention of inorganic acids from uremia. Lactated Ringer's solution rapidly corrects the lactic acidosis from hypovolemia, as lactate is converted to bicarbonate with hepatic reperfusion. Bicarbonate loss from diarrhea and “dilutional acidosis” are non–anion gap types of metabolic acidosis.

A. Gastric losses are best replaced with a balanced salt solution.

B. Potassium supplementation is unnecessary in replacement of gastric secretions.

C. Bicarbonate wasting is an unusual complication of a high-volume pancreatic fistula.

D. Balanced salt solution is a reasonable replacement fluid for a small bowel fistula.

E. A patient with persistent vomiting usually requires hyperchloremic replacement fluids.

Answer: DE

DISCUSSION: Gastric secretions are relatively high in chloride and potassium. Other than an isolated pancreatic fistula, gastrointestinal tract losses below the pylorus are best replaced by a balanced salt solution. Although potassium concentrations are low, copious losses require potassium supplementation to prevent hypokalemia.

A. The symptoms of hypercalcemia may mimic some symptoms of hyperglycemia.

B. Metastatic breast cancer is an unusual cause of hypercalcemia.

C. Calcitonin is a satisfactory long-term therapy for hypercalcemia.

D. Severely hypercalcemic patients exhibit the signs of extracellular fluid volume deficit.

E. Urinary calcium excretion may be increased by vigorous volume repletion.

Answer: ADE

DISCUSSION: Markedly elevated serum calcium levels produce polydipsia, polyuria, and thirst. Vigorous volume repletion and saline diuresis correct the extracellular fluid volume deficit and promote the urinary excretion of calcium. Metastatic breast cancer is the most common cause of hypercalcemia, from bony metastasis. The calcitonin effect on calcium is diminished with repeat administrations.

A. The products of catabolism may be excreted by as little as 300 ml. of urine per day.

B. The lungs represent the primary source of insensible water loss.

C. The normal daily insensible water loss is 600 to 900 ml.

D. Excessive cell catabolism causes significant loss of total body water.

E. In normal humans, urine represents the greatest source of daily water loss.

Answer: CE

DISCUSSION: The skin is the primary source of insensible water loss. Including losses from the lungs, this averages 600 to 900 ml. per day. Catabolism liberates “water of solution.” In normal humans, urine represents the greatest source of water loss. The patient deprived of external access to water must still excrete a minimum of 500 to 800 ml. of urine per day to expel the products of catabolism.

A. Age over 70 years.

B. Chronic malnutrition.

C. Controlled diabetes mellitus.

D. Long-term steroid use.

E. Infection at a remote body site.

Answer: C

DISCUSSION: Controlled diabetes mellitus has been shown repeatedly not to be associated with increased likelihood of incisional infection provided one avoids operations on body parts that may be ischemic or neuropathic. Uncontrolled diabetes mellitus, such as ketoacidosis, is associated with a dramatic increase in surgical infection. The other parameters noted—age over 70, chronic malnutrition, regular steroid use, and an infection at a remote body site—are well-recognized adverse predictive factors and are identified in tables within the chapter.

A. Myocardial infarct 4 months previously.

B. Clinical evidence of congestive heart failure in a patient with 8.5 gm. per dl. hemoglobin.

C. Premature atrial or ventricular contractions on electrocardiogram.

D. A harsh aortic systolic murmur.

E. Age over 70 years.

Answer: B

DISCUSSION: Clinical evidence of congestive heart failure in a patient with 8.5 gm. per dl. hemoglobin concentration is a misleading sign. Evidence of congestive failure is ordinarily a major risk factor, but in this particular patient the anemia lends itself to correction by preoperative transfusion with packed red blood cells, and often it is found that congestive failure and the associated increased risks disappear when the hemoglobin concentration is returned to the 12 gm. per dl. or higher ratio. All other factors are overt signs of increased likelihood of a postoperative cardiac event, the most ominous being a myocardial infarction 4 months preoperatively or the presence of a harsh aortic systolic murmur suggesting the presence of aortic stenosis. Age over 70 years and the presence of premature atrial or ventricular contractions on the electrocardiogram are less strong determinants of a postoperative cardiac complication.

A. Transabdominal hysterectomy in an obese woman that requires 3 hours of anesthesia time.

B. Right middle lobectomy for bronchogenic cancer in a 65-year-old smoker.

C. Vagotomy and pyloroplasty for chronic duodenal ulcer disease in a 50-year-old who had chest film findings of old, healed tuberculosis.

D. Right hemicolectomy in an obese 60-year-old smoker.

E. Modified radical mastectomy in a 58-year-old woman who is obese.

Answer: BDCAE

DISCUSSION: If one considers the constellation of risk factors for pulmonary complications that is provided in tabular form in the accompanying chapter, one should readily recognize B, right middle lobectomy for bronchogenic cancer in a 65-year-old smoker, as the highest risk of a clinical situation for the likelihood of serious pulmonary complications. The next in rank may be properly debated between answer D and answer C. D, right hemicolectomy, is judged to have somewhat greater likelihood of complications since the patient is older, smokes, and is obese, although the procedure may be done through a transverse or lower abdominal incision. C, vagotomy and pyloroplasty, is viewed as being somewhat less serious since it is an upper abdominal operation on an elective basis in a 50-year-old whose only abnormalities include old, healed tuberculosis on a chest film. A very low risk of pulmonary complication should follow a transabdominal hysterectomy done through a lower abdominal incision in a woman whose only risk factors are obesity and a 3-hour anesthesia time. The lowest risk probably resides with the younger patient undergoing modified radical mastectomy, whose only risk factor is obesity. This is particularly true since this operation is conducted on the surface of the body, is associated with relatively little postoperative pain, and provides free and unrestricted respiratory function.

A. Carcinoembryonic antigen (CEA).

B. Blood urea nitrogen (BUN).

C. Electrocardiogram (ECG).

D. Hemoglobin concentration (Hgb).

E. Serum creatinine (Cr).

F. Arterial blood oxygen tension (PaO 2) on room air.

G. Serum sodium concentration (Na+).

Answer: CDFEBAG

DISCUSSION: The most important test by far is the electrocardiogram, with its capacity to indicate signs of occult heart disease. The second most important evaluation is the hemoglobin concentration, which in this patient may show an anemia related to chronic alimentary tract blood loss that would require correction prior to safe induction of a general anesthetic. Arterial blood gases vary from individual to individual depending primarily on smoking habits and age. Accordingly, each older person should have a resting baseline determination prior to operation. Serum creatinine may show evidence of occult renal disease and is substantially more useful than blood urea nitrogen, which is more vulnerable to transient volume changes. Carcinoembryonic antigen is important to know in many patients with cancer with respect to postoperative follow-up since in some cases it may be an early herald of recurrent disease. However, it has little to do with the patient's preoperative assessment in terms of risk and preparation for an elective operation. The presence of liver metastases, for example, can be discovered with significant accuracy by palpation at the time of operation, and an elevated carcinoembryonic antigen in no set of circumstances would lead one to withhold colon resection with its relief of potential obstruction and bleeding. Finally, serum sodium concentration in a 65-year-old woman who is admitted electively for resection of the colon is always normal and would be of least value among these tests.

A. Whole blood is the most commonly used red cell preparation for transfusion in the United States.

B. Whole blood is effective in the replacement of acute blood loss.

C. Most blood banks in the United States have large supplies of whole blood available.

D. The use of whole blood produces higher rates of disease transmission than the use of individual component therapies.

Answer: B

DISCUSSION: Whole blood is effective as a replacement fluid for acute blood loss because it provides both volume and oxygen-carrying capacity (red blood cells). It is rarely used in the United States nowadays, and most blood banks do not provide whole blood transfusions. It is significantly more efficient to separate donated blood into its components. In this manner, the red blood cell mass can be used to provide oxygen-carrying capacity, the plasma can be used for factor replacement, and the platelets and white cells can be used for patients deficient in these components. The use of whole blood to replace acute blood loss is associated with lower disease transmission rates than the use of packed red blood cells, fresh frozen plasma, and platelets, each from a different donor.

A. Solutions containing citrate prevent coagulation by binding calcium.

B. The shelf life of packed red blood cells preserved with CPDA-1 is approximately 35 days at 1º to 6º C.

C. There are normal numbers of platelets in packed red blood cells stored at 1º to 6º C for more than 2 days.

D. The storage lesion affecting refrigerated packed red blood cells includes development of acidosis, hyperkalemia, and decreased intracellular 2,3DPG (diphosphoglycerate).

Answer: ABD

DISCUSSION: After blood has been collected from a donor, it is anticoagulated with a solution containing citrate, which acts by binding calcium. Blood is then separated into its components. Packed red blood cells stored at 1º to 6º C using CPDA-1 preservative have a shelf life of 35 days. There are essentially no functional platelets in refrigerated blood stored at 1º to 6º C after approximately 48 hours in storage. Refrigerated packed red blood cells undergo progressive changes termed a storage lesion. Such changes include acidosis, hyperkalemia, and decreased levels of 2,3-DPG, which are reversed after transfusion or produce effects other than those predicted based on the content of the unit of blood.

A. Rapid, acute blood loss with unstable vital signs but no available hematocrit or hemoglobin determination.

B. Symptomatic anemia: orthostatic hypotension, severe tachycardia (greater than 120 beats per minute), evidence of myocardial ischemia, including angina.

C. To increase wound healing.

D. A hematocrit of 26% in an otherwise stable, asymptomatic patient.

Answer: AB

DISCUSSION: Currently accepted guidelines for the transfusion of packed red blood cells include acute ongoing blood loss, as might occur in an injured patient, and the development of symptomatic anemia with manifestations of decreased tissue perfusion related to decreased oxygen-carrying capacity of the blood. This includes situations in which the patient is unable to compensate for a decreased oxygen-carrying capacity by the usual mechanisms, such as increased cardiac output. Such patients develop myocardial dysfunction if an excessive demand is placed on the heart. The patient should be transfused with packed red blood cells, which afford added oxygen-carrying capacity. This decreases the workload on the myocardium while providing the necessary oxygen-delivery capability. The use of packed red blood cells to improve wound healing or to improve the patient's sense of well-being is highly questionable. No data support such a practice. In general, the use of a transfusion trigger such as a hematocrit of 30% or hemoglobin of 10 gm. per dl. constitutes a questionable indication for transfusion. If a patient is asymptomatic and stable and has no risk of myocardial ischemia, packed red blood cell transfusion should not be given based solely or predominantly on a numerical value such as a hematocrit of 28%.

A. Volume replacement.

B. As a nutritional supplement.

C. Specific coagulation factor deficiency with an abnormal prothrombin time (PT) and/or an abnormal activated partial thromboplastin time (APTT).

D. For the correction of abnormal PT secondary to warfarin therapy, vitamin K deficiency, or liver disease.

Answer: CD

DISCUSSION: The use of FFP as a volume expander is not indicated. There are currently several preparations (both crystalloid and colloid) that are equally effective and do not carry the infectious and other risks associated with the use of FFP. The use of FFP as a “nutritional” supplement is to be condemned. Patients with specific deficiencies of coagulation factors generally benefit greatly from the infusion of FFP. In cases of specific factor deficiency, other preparations may be more appropriate, but FFP is generally immediately available and is effective in most patients. Patients receiving warfarin therapy, those who have vitamin K deficiency, and those with liver dysfunction have abnormalities of the vitamin K–dependent factors II, VII, IX, and X, as well as protein C and protein S.

A. Packed red blood cells and crystalloid solution should be infused to restore oxygen-carrying capacity and intravascular volume.

B. Two units of FFP should be given with every 5 units of packed red blood cells in most cases.

C. A “six pack” of platelets should be administered with every 10 units of packed red blood cells in most cases.

D. One to two ampules of sodium bicarbonate should be administered with every 5 units of packed red blood cells to avoid acidosis.

E. One ampule of calcium chloride should be administered with every 5 units of packed red blood cells to avoid hypocalcemia.

Answer: A

DISCUSSION: Patients who are suffering from acute blood loss require crystalloid resuscitation as the initial maneuver to restore intravascular volume and re-establish vital signs. If 2 to 3 liters of crystalloid solution is inadequate to restore intravascular volume status, packed red blood cells should be infused as soon as possible. There is no role for “prophylactic infusion” of FFP, platelets, bicarbonate, or calcium to patients receiving massive blood transfusion. If specific indications exist patients should receive these supplemental components. In particular, patients who have abnormal coagulation tests and have ongoing bleeding should receive FFP. Patients who have depressed platelet counts along with clinical evidence of oozing (microvascular bleeding) benefit from platelet infusion. Sodium bicarbonate is not necessary, since most patients who receive blood transfusion ultimately develop alkalosis from the citrate contained in stored red blood cells. The use of calcium chloride is usually unnecessary unless the patient has depressed liver function, ongoing prolonged shock associated with hypothermia, or, rarely, when the infusion of blood proceeds at a rate exceeding 1 to 2 units every 5 minutes.

A. Adherence of platelets to exposed subendothelial glycoproteins and collagen with subsequent aggregation of platelets and formation of a hemostatic plug.

B. Interaction of tissue factor with factor VII circulating in the plasma.

C. The production of thrombin via the coagulation cascade with conversion of fibrinogen to fibrin.

D. Cross-linking of fibrin by factor XIII.

Answer: ABCD

DISCUSSION: Hemostasis requires the interaction of platelets with the exposed subendothelial structures at the site of injury followed by aggregation of more platelets in that area. Interactions between endothelial cell and subendothelial tissue factor with factor VII activate the coagulation cascade. The end product is large amounts of thrombin that catalyze the conversion of fibrinogen into fibrin. Fibrin thus formed is cross-linked by factor XIII to form a stable clot that incorporates the platelet plug and fibrin thrombus into a stable clot.

A. Acquired bleeding disorders are more common than congenital defects.

B. Deficiencies of vitamin K decrease production of factors II, VII, IX, and X, protein C, and protein S.

C. Hypothermia below 32ºC rarely causes a bleeding disorder.

D. Von Willebrand's disease is a very uncommon congenital bleeding disorder.

Answer: AB

DISCUSSION: Acquired bleeding disorders are significantly more common than congenital bleeding defects. Vitamin K deficiency may be related to malnutrition or competitive inhibition of the production of the vitamin K–dependent factors II, VII, IX, X, protein C, and protein S by warfarin (Coumadin). Hypothermia causes significant platelet dysfunction with a significant bleeding disorder in many patients. It is among the least recognized causes of altered coagulation in surgical patients. Von Willebrand's disease is a relatively common disorder of bleeding and is generally undetectable by routine screening methods.

A. History and physical examination.

B. Complete blood count (CBC), including platelet count.

C. Prothrombin time (PT) and activated partial thromboplastin time (APTT).

D. Studies of platelet aggregation with adenosine diphosphate (ADP) and epinephrine.

Answer: A

DISCUSSION: The evaluation of most patients scheduled for elective surgery who do not have a history of significant bleeding disorders is somewhat controversial. An adequate history and physical examination screen out most patients with bleeding problems. For patients who are scheduled to undergo a major surgical procedure, it is advisable to obtain a CBC and platelet count, as well as a PT and APTT level. This detects a large number of bleeding disorders but does not rule out all possible causes of perioperative bleeding. Studies of platelet aggregation are indicated only for patients who are suspected of having qualitative defects of platelet function (e.g., von Willebrand's disease).

A. The transmission rates for human immunodeficiency virus (HIV) have been decreasing progressively since the early 1980s.

B. The transmission rates of hepatitis have been decreasing steadily since the 1980s.

C. Cytomegalovirus (CMV) is the infectious agent most commonly transmitted in blood.

D. Severely immunocompromised patients (such as patients undergoing transplantation) should receive specially screened blood products.

Answer: ABCD

DISCUSSION: The incidence of both HIV and hepatitis transmitted via blood transfusions has been steadily decreasing since the 1980s. This is related to improved methods for detection and increased awareness of surrogate markers of disease. The currently available techniques for the detection of HIV are highly effective, provided the donor is not in the “window” before the formation of specific antibody. The surrogate markers for hepatitis C, as well as the specific assays for the organism, are now sufficiently refined to allow the detection of a large percentage of hepatitis C infection in donated blood. Screening for hepatitis B surface antigen has effectively eliminated the transmission of hepatitis B through blood products in most cases. CMV is the most commonly transmitted infectious agent in blood. Since a large percentage of the population carry the virus, routine screening is not performed for this organism; however, severely compromised patients such as those undergoing transplantation should receive CMV-negative blood products.

A. An allergic reaction.

B. An anaphylactoid reaction.

C. A clerical error.

D. An acute bacterial infection transmitted in blood.

Answer: C

DISCUSSION: The most common cause of fatalities related to transfusion reactions result from ABO-incompatible transfusion related to clerical error. Most such reactions occur if a type O person receives type A red cells owing to a clerical error that occurs either at the time the blood sample was drawn, during processing in the laboratory, or at the time a unit is administered. The importance of extremely careful labeling, transfer, and handling of specimens and of cross-matched blood products cannot be overemphasized. Allergic and other reactions are common but rarely fatal. The transmission of bacterial organisms (e.g., Staphylococcus aureus) has been reported especially with platelet concentrates maintained at or near room temperature. Fortunately, such reactions are rare.

A. The intrinsic pathway of coagulation is the predominant pathway in vivo for hemostasis and coagulation.

B. The intrinsic pathway beginning with the activation of factor XII is the predominant in vivo mechanism for activation of the coagulation cascade.

C. Deficiencies of factor VIII and IX cause highly significant coagulation abnormalities.

D. Deficiencies of factor XII cause severe clinical bleeding syndromes.

Answer: AC

DISCUSSION: Although it was previously held that two somewhat distinct pathways existed for the activation of the coagulation cascade, it is now recognized that the predominant mechanism for coagulation in vivo is the “extrinsic pathway.” Tissue factor is exposed in the subendothelial tissues when endothelial cell injury occurs. Tissue factor then tightly binds factor VII circulating in the plasma and activates the coagulation cascade. Factor VIII and factor IX deficiency cause the clinical syndromes of hemophilia A and hemophilia B, respectively. Both of these disorders involve very severe clinical bleeding disorders, whereas deficiencies of factor XII do not generally cause clinically significant bleeding. This further emphasizes the secondary role that the “intrinsic pathway” plays in coagulation.

45. A major problem in nutritional support is identifying patients at risk. Recent studies suggest that these patients can be identified. Which of the following findings identify the patient at risk?

A. Weight loss of greater than 10% over 2 to 4 months.

B. Serum albumin of less than 3 gm. per 100 ml. in the hydrated state.

C. Malnutrition as identified by global assessment.

D. Serum transferrin of less than 220 mg. per 100 ml.

E. Functional impairment by history.

Answer: ABCDE

DISCUSSION: All of these are at least partially correct. It is not clear whether weight loss of 10% or 15% is the required threshold, but it certainly is close. Serum albumin of less than 3 gm per 100 ml. remains the most constant identifier of patients at risk in the literature and has been so for years. Global assessment in the hands of an experienced investigator is quite efficacious at identifying persons at risk. Serum transferrin is certainly a confirmatory identifier of patients with malnutrition—and may be even a primary one. Graham Hill and his co-workers have pioneered the concept of global assessment using functional parameters, and in the hands of an experienced observer is quite a reasonable way of approaching and identifying patients at risk.

46. Essential fatty acid deficiency may complicate total parenteral nutrition (TPN). Which of the following statements are true?

A. Essential fatty acid deficiency may be prevented by the administration of 1% to 2% of total calories as fat emulsion.

B. Fat-free parenteral nutrition results in the appearance of plasma abnormalities, indicating essential fatty acid deficiency, within 7 to 10 days of initiation.

C. An abnormal plasma eicosatrienoic-arachidonic acid ratio is always associated with essential fatty acid deficiency.

D. Following initiation of fat-free parenteral nutrition, dry, scaly skin associated with a maculopapular rash indicates essential fatty acid deficiency.

Answer: BD

DISCUSSION: Biochemical evidence of essential fatty acid deficiency may occur as early as 7 to 10 days following initiation of fat-free parenteral nutrition. The decrease in arachidonic acid in plasma and the appearance of the abnormal eicosatrienoic acid may yield the earliest indication of prostaglandin deficiency; it is not absolute. Decreased intraocular pressure, another early indication of prostaglandin deficiency, may appear as soon as 7 days following initiation of fat-free parenteral nutrition. While my current practice is to give at least 500 ml. of 10% lipid emulsion daily to provide 20% to 25% of total calories to support hepatic protein synthesis, as little as 4% to 6% of total daily calories as fat prevents essential fatty acid deficiency. Practically, this may be undertaken by the administration of 500 ml. of 10% lipid three times weekly. The appearance of eicosatrienoic acid and a decrease in arachidonic acid, and a change in ratio, is not essential to the diagnosis of essential fatty acid deficiency, but this plasma abnormality is often present.

47. It is stated that enteral nutrition is safer than parenteral nutrition. Which of the following may be complications of enteral nutrition?

A. Hyperosmolar, nonketotic coma.

B. Vomiting and aspiration.

C. Pneumatosis cystoides intestinalis.

D. Perforation and peritonitis.

Answer: ABCD

DISCUSSION: It is not necessarily true that enteral nutrition is safer than parenteral nutrition, and it may in fact be associated with a higher risk of death than parenteral nutrition. Specifically, a well-run parenteral nutrition service should not be associated with significant mortality, except for the occasional death due to undetected yeast infection. On the other hand, enteral nutrition, especially if not carried out safely, can result in significant mortality. The most common of the severe complications of enteral nutrition result from the gastrostomy, or tube feedings into the stomach. Sudden changes in gastric motility, such as those associated with sepsis, may result in aspiration. Nasoenteric or nasoduodenal tubes help prevent this complication, as does shutting off enteral feedings between the hours of 11 P.M. and 7 A.M. It is also essential to keep the patient's head elevated 30 degrees. Also necessary is the use of extreme care when initiating enteral nutrition. If hypertonic material is given into the stomach, one can increase osmolality followed by an increase in volume. If, however, the material is given into the small bowel, volume must be increased first and then tonicity, with the expectation that osmolality greater than 400 or 500 mOsm per liter may never be achieved without provoking severe diarrhea. If care is not taken with the initiation of enteral nutrition, massive diarrhea may result, including fluid loss, the absorption of enormous amounts of carbohydrate into the circulation with inadequate fluid to support it, and the development of hyperosmolar, nonketotic coma. Alternatively, severe unremitting diarrhea may result in necrosis of the intestinal wall, the appearance of pneumatosis cystoides intestinalis, and, finally, perforation and death. All of these complications may be prevented by judicious use of enteral nutrition with the same care one uses for parenteral nutrition.

48. It has been suggested that enterocyte-specific fuels be utilized for all patients receiving parenteral nutrition. Theoretically, the benefits of such fuels include:

A. Glutamine increases gut mucosal protein content and wall thickness.

B. Butyrate increases jejunal mucosal protein content and wall thickness.

C. The short-chain fatty acids—butyrate, propionate, and acetate—are useful in supporting ileal mucosal protein content and thickness.

D. The use of glutamine-enriched solutions for parenteral nutrition for patients with chemotherapy toxicity or radiation enteritis is without hazards.

Answer: NONE IS ENTIRELY TRUE

DISCUSSION: The use of enterocyte-specific fuels is part of a new and potentially exciting phase of “nutritional pharmacology” in parenteral nutrition; however, exciting as the research may be, the use of such fuels is by no means acceptable for indiscriminate use at present. Though some studies have shown that the provision of glutamine in amounts up to 2% in standard parenteral nutrition solutions increases both jejunal and ileal mucosal protein content, cell wall thickness, and DNA content, this has not been the case in all studies, and this reported effect seems very dependent on experimental design. In many of the studies that have shown such an effect, 2% glutamine has been used to replace virtually all nonessential amino acids, probably initiating a deficiency state. The beneficial effects seen with glutamine are far less impressive than those seen with epidermal growth factor, for example, and disappear entirely when a different experimental design is used in which 2% glutamine is added to an adequate amino acid formulation in which glutamine does not replace nonessential amino acids but is added to them. Nonetheless, the use of enterocyte-specific fuels, specifically glutamine, is potentially exciting and should be carefully investigated. More striking are the results that follow massive bowel resection, radiation enteritis, and chemotherapy toxicity. Glutamine may help the small bowel regenerate more quickly, enabling more rapid use of the small bowel for nutrition. It should be pointed out, however, that glutamine is a fuel utilized by many tumors and, thus, one runs the risk of stimulating the growth of the tumor with excessive glutamine. The short-chain fatty acids, produced from bacterial fermentation of soluble pectin, may be useful in both the maintenance of colonocyte-specific nutrition and, in the case of butyrate, ileal enterocyte nutrition.

49. Essential amino acids have been advocated as standard therapy for renal failure. Which of the following statements are true?

A. Increased survival from acute renal failure has been reported with both essential and nonessential amino acid therapy of patients in renal failure.

B. Essential amino acids retard the rise of blood urea nitrogen (BUN) secondary to decreased urea appearance.

C. Essential amino acids and hypertonic dextrose are a convenient form of therapy for hyperkalemia.

D. Essential amino acids decrease BUN and creatinine to the same degree as solutions containing excessive nonessential amino acids.

Answer: BC

DISCUSSION: Essential amino acids and hypertonic dextrose, as opposed to hypertonic dextrose alone, was reported by Abel and co-workers to be associated with a decreased mortality rate in mostly surgical patients with acute tubular necrosis. The most significant improvement in mortality, as compared with the control group receiving hypertonic dextrose, was among patients who required dialysis (i.e., the more severely affected patients). Another group responding favorably to treatment includes patients with nonoliguric renal failure whose need for dialysis is not clearly established. The effect of essential amino acids in preventing a rise in BUN, as well as its beneficial effect in preventing hyperkalemia, may obviate dialysis in such patients. With increasing amounts of nonessential amino acids, BUN increases, and thus, dialysis is required. Prospective randomized studies comparing the use of essential versus nonessential amino acids in patients with acute renal failure have not been carried out in sufficient numbers to yield answers to this question.

50. A modified amino acid solution with increased equimolar branched-chain amino acids and decreased aromatic amino acids has been proposed for patients with hepatic insufficiency. Which of the following statements is/are true?

A. This formulation is proposed for the use of patients with fulminant hepatitis.

B. Nitrogen balance is achieved in such patients with amounts of 40 gm. of amino acids per 24 hours.

C. The use of 80 to 100 gm. of such solutions is associated with hepatic encephalopathy.

D. In some studies of surgical patients, improvements in mortality have been reported.

Answer: D

DISCUSSION: The use of modified amino acid solutions is based on the false neurotransmitter hypothesis of the cause of hepatic coma. According to this hypothesis, the imbalance between aromatic and branched-chain amino acids in the plasma results in abnormally high levels of the toxic aromatic amino acids in the brain, thus provoking hepatic encephalopathy. The use of modified amino acid mixtures, with glucose as the calorie base, has been associated in a number of studies with improvement in encephalopathy. Meta-analysis has concluded that the use of such solutions is indicated as therapy for hepatic encephalopathy but has been proposed only for hepatic encephalopathy complicating acute exacerbation of chronic liver disease. Although there are a few anecdotal reports of beneficial effects on hepatic encephalopathy of acute fulminant hepatitis, the use of such a solution has not been advocated, but such a modified solution is tolerated better than standard amino acid mixtures in patients requiring TPN. In some studies, particularly in complicated surgical cases, the use of a high–branched-chain, low–aromatic amino acid solution has been associated with lower mortality. These statements are true only for studies in which the modified solutions are given with hypertonic glucose as a calorie base. Studies in which lipid was the principal calorie source have not revealed such improvements in mortality. In recent studies, giving an aromatic amino acid–deficient, branched-chain amino acid–enriched solution to patients about to undergo resection of the liver has proved particularly efficacious in a group of patients with cirrhosis, decreasing morbidity and showing a trend toward decreased mortality.

51. In the nutritional support of patients with cancer, which of the following statements is/are true?

A. Nutritional support benefits the patient's lean body mass but does not enable the tumor to grow.

B. In experimental animals, the growth of implanted tumors is directly proportional to the amount of calories and protein supplied.

C. Prospective randomized trials of nutritional support utilizing chemotherapy and radiation therapy have revealed benefits to patients receiving total parenteral nutrition.

D. Studies of nutritional support for patients with cancer about to undergo surgery revealed decreased morbidity and mortality, especially morbidity from sepsis.

Answer: B

DISCUSSION: The problem with the patient with cancer is a very vexing one. Clearly, one of the metabolic effects of cancer, cachexia, affects patients in the last quartile of their disease and makes such patients intolerant of chemotherapy, radiation therapy, and, in many cases, operative procedures. Total parenteral nutrition (TPN) has been proposed as a means of reversing cachexia and enabling patients to better tolerate surgery, chemotherapy, and radiation therapy. In experimental animals, it is clear that the provision of calories and protein, especially in excessive amounts, is associated with the more rapid growth of tumors and decreased survival, especially in the group that is overfed in the extreme. There is also evidence suggesting that overfeeding, or at least TPN, may result in increased growth (or at least change cell kinetics) in patients who are overnourished with TPN. Of the randomized prospective trials that have been carried out, no trial utilizing chemotherapy or radiation therapy has revealed a survival advantage for patients receiving TPN. Indeed, in Shamberger's study, there is a suggestion that the tumor-free interval following treatment of lymphoma may be shorter in patients receiving TPN. In patients undergoing surgery, however, especially those who are severely malnourished (as recently revealed in the VA study) or in patients with major procedures such as esophagogastrectomy (as in Muller's study), evidence suggests that TPN is beneficial. In a late follow-up in Muller's study, there was no apparent increase in recurrence, and the survival rate was the same, despite much higher mortality in the non-TPN group. This suggests that any improved survival following operation may have been offset by an increased late recurrence rate, although it is difficult to reach this conclusion. In summary, for patients with cancer TPN probably nourishes the tumor as well as the host. Nonetheless, in severely malnourished patients provision of TPN from 5 to 10 days preoperatively may increase survival and decrease morbidity. Overfeeding must be avoided. Future studies will undoubtedly reveal that there are certain nutrients that tumors require, which probably should be best avoided.

52. Glucose overload results in increased CO 2 production. Which of the following statements are true?

A. In patients with respiratory insufficiency, administration of glucose as a principal calorie source is contraindicated.

B. In patients with pulmonary infection and sepsis, calorie support should consist of 95% fat and 5% glucose.

C. In Askanazi's study, increased CO 2 production and difficulty in weaning was associated only with pronounced overfeeding.

D. CO 2 production should be measured in most patients who are supported by respirators in intensive care units and are receiving nutritional support.

Answer: C

DISCUSSION: Few papers have excited as much interest as that by Askanazi, Kinney, and co-workers, which demonstrated that glucose calories given to patients with severe respiratory impairment may result in difficulty in weaning from a respirator. Subsequent research has suggested, however, that this occurs only with severe overfeeding, when the respiratory quotient is greater than 1 and calories are excessive. If one examines the conditions under which Askanazi's patients were studied, these were a group of septic, depleted patients who were taken from almost no nutritional support to a caloric supply of 2.25 times their caloric requirement, most of the calories consisting of glucose. Suffice it to say that, in patients with impaired respiratory function, one should measure VCO2 and, when VCO2 is significantly elevated and appears to interfere with weaning, decrease the amount of glucose calories and increase the amount of fat. If one measures or estimates calorie requirements and does not overfeed, lipid can be utilized for 25% of the caloric requirement and glucose for the remainder, without much fear of excessive CO 2 production.

53. Hepatic abnormalities have been noted in adults since the beginning of hyperalimentation. Which of the following statements are true?

A. Hepatic steatosis appears to be associated with an overload of glucose.

B. Hepatic steatosis is usually associated with abnormalities in hepatic enzymes.

C. Hyperbilirubinemia is inevitably associated with hepatic steatosis.

D. Abnormalities in the portal insulin-glucagon ratio are thought to be causative of hepatic steatosis in experimental animals.

Answer: AD

DISCUSSION: The most common metabolic complication of TPN in adults is hepatic steatosis. Unlike the hepatic abnormalities in children, which may progress to cholestasis, liver damage, and in some cases death, hepatic steatosis, or fatty infiltration of the liver with triglycerides, appears to be a rather benign complication. It may be, but is not necessarily, associated with hepatic enzymatic abnormalities, which usually occur in the first week, peak at the third week, and generally disappear by the sixth week of parenteral nutrition. Abnormalities in the transaminases are most common, with alkaline phosphatase also being elevated, but there is no correlation between the degree of fatty infiltration and enzymatic abnormalities. Fatty infiltration appears to be largely vacuolization with increased storage of triglycerides. Hepatic steatosis is almost always associated with an overload of glucose. Recent studies in experimental animals have suggested that the portal insulin-glucagon ratio, which is elevated under these circumstances, may be causally related to hepatic steatosis. Insulin is the leading storage enzyme and is responsible for lipogenesis. The presence of insulin inhibits lipolysis. Glucagon, on the other hand, results in the mobilization of hepatic lipid. The liver “sees” the portal vein insulin-glucagon ratio. Excesses of insulin elicited by hypertonic dextrose increase lipid deposition in the liver, whereas glucagon, which is elicited by certain amino acids, results in the mobilization of hepatic lipid.

54. Which of the following statements about the presence of gallstones in diabetes patients is/are correct?

A. Gallstones occur with the same frequency in diabetes patients as in the healthy population.

B. The presence of gallstones, regardless of the presence of symptoms, is an indication for cholecystectomy in a diabetes patient.

C. Diabetes patients with gallstones and chronic biliary pain should be managed nonoperatively with chemical dissolution and/or lithotripsy because of severe complicating medical conditions and a high operative risk.

D. The presence of diabetes and gallstones places the patient at high risk for pancreatic cancer.

E. Diabetes patients with symptomatic gallstones should have prompt elective cholecystectomy, to avoid the complications of acute cholecystitis and gallbladder necrosis.

Answer: E

DISCUSSION: Gallstones have been found to be very prevalent in patients with type II (non–insulin-dependent) diabetes mellitus, perhaps related to the dyslipoproteinemia in such patients. Although the complications of acute cholecystitis (infection, sepsis, gangrene of the gallbladder) are more common in diabetics, a decision-analysis study has shown that prophylactic cholecystectomy cannot be justified since the risk of morbidity and/or mortality from the cholecystectomy procedure is as great as that of complications or death from acute cholecystitis. Patients who become symptomatic should be promptly prepared and should undergo elective cholecystectomy, because an emergency operation in these patients with comorbid conditions, especially coronary artery disease, has substantial added mortality associated with it. There is no causal relationship between diabetes and pancreatic cancer.

55. Intensive insulin therapy:

A. Prevents the aggressive development of atherosclerosis in diabetic patients.

B. Is not associated with unawareness of hypoglycemia.

C. Improves peripheral neuropathy.

D. Improves established retinopathy and nephropathy.

E. Is indicated in all patients with non–insulin-dependent diabetes mellitus (NIDDM).

Answer: C

DISCUSSION: Intensive insulin therapy is indicated in patients with IDDM who can actively participate in their own management and the attainment of the goals set for their blood glucose and glycosylated hemoglobin (HgA1 c) levels. Because the main complication of intensive therapy is iatrogenic hypoglycemia, this mode of treatment is not indicated for patients with NIDDM, who often have coexisting medical conditions such as coronary artery disease and who tolerate hypoglycemia poorly. There is little or no evidence that macrovascular disease is affected by intensive insulin therapy, and the added weight gain and hyperinsulinemia associated with the therapy may worsen atherosclerosis. Unawareness of hypoglycemia is directly related to a recent hypoglycemia episode, so patients treated intensively are often unaware of the problem. Intensive therapy does not improve established retinopathy or nephropathy but slows or prevents progression of these complications; however, better glucose control may improve peripheral neuropathy.

56. Which of the following statements about hypertension in diabetes patients is/are correct?

A. Hypertension worsens the macrovascular disease of diabetes patients.

B. Hypertension accelerates the progression of diabetic nephropathy.

C. Hypertension is associated with sodium retention in diabetes patients.

D. Angiotensin-converting enzyme (ACE) inhibitors should be used in all patients with chronic hyperglycemia, regardless of the presence of hypertension.

E. Diuretics, as single-drug therapy, are not indicated in the treatment of hypertension in diabetes patients.

Answer: ABCDE

DISCUSSION: All of the answers listed are correct. By damaging endothelial cells, hypertension worsens macrovascular disease in all patients but especially in diabetics. Hypertension dramatically accelerates the onset and progression of diabetic renal disease and proteinuria, and this phenomenon can be slowed or prevented by a combination of treatment modalities, including ACE inhibitors, which dilate efferent glomerular vessels and lower intraglomerular pressure. Despite sodium retention in diabetes patients, single-drug therapy with a diuretic is not indicated because the chronic state of dehydration in such patients may become worse.

57. What is the major determinant in an individual patient's risk for perioperative complications?

A. The surgical procedure.

B. The length of the surgical procedure.

C. The anesthetic technique (e.g., general, regional).

D. The length of anesthesia.

E. All of the above.

Answer: A

DISCUSSION: The planned surgical procedure is the major determining factor in assessing an individual patient's risk for perioperative complications and in deciding which anesthetic technique will be most appropriate. Good communication between the surgeon and the anesthesiologist is vital, as the surgeon knows better than anyone else the extent of the operation and the length of time it will require.

58. Which of the following are considered routine intraoperative monitors?

A. Temperature probe.

B. Electrocardiogram.

C. Capnograph.

D. Blood pressure cuff.

E. Foley catheter.

Answer: ABD

DISCUSSION: The American Society of Anesthesiologists requires that the patient's ventilation, circulation, oxygenation, and temperature be continually monitored during all anesthetics. Routine monitors are considered to be a temperature probe, electrocardiogram, pulse oximetry, and blood pressure cuff.

59. Muscle relaxants can be used for which of the following?

A. To facilitate intubation.

B. To provide optimal surgical conditions.

C. To optimize ventilator support.

D. To provide sedation.

Answer: ABC

DISCUSSION: Muscle relaxants are administered to facilitate endotracheal intubation, to provide the surgeon with optimal working conditions during anesthesia, and to optimize mechanical ventilator support in some patients. They do not produce analgesia, sedation, or amnesia. Therefore, muscle paralysis should not be performed without sedation or general anesthesia.

60. Local anesthetics:

A. Inhibit transmission of nerve impulses by increasing sodium membrane permeability and the displacement of ionized calcium.

B. Are classified as amides or esters.

C. Produce peripheral vasodilation.

D. Are weak acids.

Answer: BC

DISCUSSION: Local anesthetics act within the nerve membrane, where they inhibit transmission of nerve impulses by reducing sodium membrane permeability and the displacement of ionized calcium. All local anesthetics consist of a hydrophilic region and a hydrophobic region separated by an alkyl chain. The bond of the alkyl chain is either an ester or an amide, and these drugs are classified based on this bond. All local anesthetics except cocaine produce vasodilatation and are weak bases.

61. Absolute indications for a double-lumen endotracheal tube during thoracic surgery are:

A. Massive hemorrhage from one lung.

B. Unilateral lung infection.

C. Facilitation of surgical exposure.

D. Unilateral bronchopulmonary lavage.

E. All of the above.

Answer: ABD

DISCUSSION: The absolute indications for a double-lumen tube are for the purposes of protecting one lung from the other. These indications include ventilation with a bronchopleural fistula, massive hemorrhage from one lung, pulmonary air cyst resection, unilateral lung infection, and unilateral bronchopulmonary lavage. Relative indications include facilitation of surgical exposure, for pneumonectomy, upper lobectomy, and thoracic aneurysm repair.

62. Determinants of cerebral blood flow include:

A. Preoperative neurologic dysfunction.

B. Arterial CO 2 tension.

C. Arterial O 2 tension.

D. Systemic arterial pressure.

E. All of the above.

Answer: BCD

DISCUSSION: Determinants of cerebral blood flow include arterial CO 2 and O 2 tensions, systemic arterial pressure, and temperature. Other factors that may affect cerebral blood flow and intracranial pressure are head position, jugular venous obstruction, and positive end-expiratory pressure.

63. Discharge criteria following ambulatory surgery include:

A. Ability to eat solid food.

B. Stable vital signs.

C. Ability to ambulate.

D. Ability to have protective airway reflexes.

Answer: BCD

DISCUSSION: Discharge criteria following ambulatory surgery include the patient's being fully awake and oriented, the ability to have protective airway reflexes, stable vital signs, adequate hydration with the ability to hold down oral intake, the ability to ambulate, and adequate pain control. All patients must have a competent person with them to transport them—and ideally to stay with them on the first postoperative night.

64. Advantages of patient-controlled analgesia (PCA) include:

A. Immediate medication delivery.

B. Less contact with nursing staff.

C. Rapid onset of analgesia.

D. Patient control over pain medication.

E. All of the above.

Answer: ACD

DISCUSSION: Advantages of PCA are immediate medication delivery, rapid onset of analgesia, and patient control over pain medication. Disadvantages of PCA are less contact with nursing staff and patients' fears that they could inadvertently administer an overdose or possibly become addicted to the opioid.

65. Advantages of epidural analgesia include:

A. Earlier mobilization after surgery.

B. Earlier return of bowel function.

C. Shorter hospitalizations.

D. Decreased stress response to surgery.

E. All of the above.

Answer: E

DISCUSSION: Epidural analgesia include excellent pain relief, decreased sedation with more rapid recovery to presurgical levels of consciousness, earlier mobilization after surgery with increased ability to co-operate with respiratory therapy and physical therapy. Following vascular surgery epidural analgesia may also improve graft flow through mild sympathetic blockade. Earlier return of bowel function, decreased stress response, shorter hospitalizations, and decreased morbidity have all been associated with epidural analgesia.

66. Ketorolac:

A. Is a nonsteroidal anti-inflammatory drug (NSAID) approved for intravenous, intramuscular, and oral administration.

B. Can be used indefinitely for postoperative analgesia.

C. Can cause renal dysfunction.

D. May decrease surgical blood loss.

Answer: AC

DISCUSSION: Ketorolac tromethamine, an NSAID, is approved by the FDA for intravenous, intramuscular, and oral administration. The agent is an effective analgesic with minimal side effects; however, ketorolac, like all NSAIDs, can enhance surgical bleeding and cause renal and platelet dysfunction. Additionally, it is recommended that ketorolac should not be used for more than 5 consecutive days.

67. Factors that decrease collagen synthesis include all of the following except:

A. Protein depletion.

B. Infection.

C. Anemia.

D. Advanced age.

E. Hypoxia.

Answer: C

DISCUSSION: Collagen synthesis, an integral part of wound healing, is affected by many local and systemic factors. Protein depletion impairs fibroplasia. Hypoproteinemia leads to diminution of fibroblast proliferation, proteoglycan and collagen synthesis, angiogenesis, and wound remodeling. Although anemia was once believed to be a significant cause of wound disruption, studies have shown that, in the absence of malnutrition or hypovolemia, anemia with a hematocrit greater than 15% does not interfere with wound healing. In contrast, molecular oxygen is critical for collagen synthesis because it is one of the factors required for the hydroxylation of lysine and proline. Also, hypoxia favors wound infection. The role of age in collagen synthesis is not clear, but the incidence of wound failure and incisional hernias is greater in patients older than 60. Fibroplasia occurs at a slower rate in older animals. Perhaps more than any other factor, wound infection is associated with the risk of wound failure.

68. Wound contraction and ultimate contracture may be controlled by which of the following drugs?

A. Colchicine.

B. D-Penicillamine.

C. Thiphenamil (Trocinate).

D. Glucocorticoids.

E. Ibuprofen (Motrin).

Answer: AC

DISCUSSION: Wound contraction is carried out by highly specialized cells called myofibroblasts, which, as their name implies, have histologic characteristics of fibroblasts and smooth muscle cells. The activity of these cells, and therefore wound contraction, can be influenced by topical application of smooth muscle inhibitors such as thiphenamil. Inhibitors of microtubule formation in myofibroblasts, such as colchicine and vinblastine, also inhibit wound contraction under experimental conditions. Glucocorticoids and NSAIDs do not affect the wound contraction process.

69. Which of the following is/are true of the actions of transforming growth factor beta (TGF-b) during wound repair?

A. Increased matrix and proteoglycan synthesis.

B. Inhibition of proteases.

C. Stimulation of plasminogen inhibitor.

D. Chemotaxis for fibroblasts and macrophages.

E. Autoinduction of TGF-b.

Answer: ABDE

DISCUSSION: Through autocrine and paracrine mechanisms TGF-b stimulates the deposition of collagen and other matrix components by fibroblasts, inhibits proteases, blocks plasminogen inhibitor, enhances angiogenesis, and is chemotactic for fibroblasts, monocytes, and macrophages. TGF-b modulates the expression of cell-surface integrins in a manner that enhances cell-matrix interaction and matrix assembly. TGF-b also induces cell production by cells, thus amplifying its biologic effects. The sustained production of TGF-b at the wound site leads to tissue fibrosis.

70. In contrast to adult wound healing with scar formation, which of the following are characteristic of scarless fetal skin repair?

A. Matrix rich in hyaluronic acid.

B. Increased inflammatory response.

C. Increased production of TGF-b.

D. No collagen deposition.

E. Minimal angiogenesis.

Answer: AE

DISCUSSION: The ability of a fetus to heal without scar formation depends on its gestational age at the time of injury and the size of the wound defect. In general, linear incisions heal without scar until late in gestation, whereas excisional wounds heal with scar at an earlier gestational age. The profiles of fetal proteoglycans, collagens, and growth factors are different from those in adult wounds. The less differentiated state of fetal skin is probably an important characteristic responsible for scarless repair. There is minimal inflammation and angiogenesis in fetal wounds. Fetal wounds are characterized by high levels of hyaluronic acid and its stimulator(s) with more rapid, highly organized collagen deposition. The roles of peptide growth factors such as TGF-b and basic fibroblast growth factor are less prominent in fetal than in adult wound healing. An understanding of scarless tissue repair has possible clinical applications in the modulation of adult fibrotic diseases and abnormal scar-forming conditions.

71. Which of the following cell types are not crucial for healing a clean, incisional wound?

A. Macrophage.

B. Platelet.

C. Fibroblast.

D. Polymorphonuclear leukocyte.

E. Myofibroblast.

Answer: DE

DISCUSSION: Experimental studies have shown that healing may progress normally in the absence of polymorphonuclear leukocytes in an uninfected wound. In contrast, depletion of monocytes and macrophages causes a severe alteration in wound healing with poor débridement, delayed fibroblast proliferation, and inadequate angiogenesis. Platelets carry a cadre of biologically active substances that are important for wound repair, including peptide growth factors like platelet-derived growth factor (PDGF) and TGF-b. Fibroblasts are the principal cell for matrix synthesis and deposition. Myofibroblasts are important for wound contraction in open defects but have little if any role in clean, incisional wounds.

72. Which of the following is/are not a substrate or cofactor for prolyl hydroxylase?

A. Alpha-ketoglutarate.

B. Ascorbate.

C. Biotin.

D. Oxygen.

E. Copper.

Answer: CE

DISCUSSION: Prolyl hydroxylase is one of the rate-limiting enzymes in collagen synthesis. Substrates and cofactors such as iron, alpha-ketoglutarate, ascorbate, and oxygen are important participants in this process. If insufficient prolines are hydroxylated, then the alpha-peptide collagen chains cannot assume a stable triple helix, the collagen cannot be exported from the fibroblasts, and the incomplete, unassociated alpha chains are broken down. Thus, ascorbate deficiency (scurvy) and hypoxia have similar effects on collagen synthesis.

73. Which of the following is an adhesion glycoprotein?

A. Fibronectin.

B. Tenascin.

C. Laminin.

D. Hyaluronic acid.

E. Collagen type IV.

Answer: ABC

DISCUSSION: Cell adhesion glycoproteins such as fibronectin, vitronectin, laminin, and tenascin provide a “railroad track” to facilitate epithelial and mesenchymal cell migration over the wound matrix. Hyaluronic acid is a glycosaminoglycan, and collagen type IV is a protein that is a crucial component of basement membrane.

74. Which of the following is/are true concerning wound fibroblasts?

A. Fibroblasts synthesize and secrete collagen molecules.

B. Wound fibroblasts are derived from blood-borne precursor cells.

C. Fibroblasts migrate to a wound along fibrin strands, which are used as a scaffold.

D. Large amounts of fibrin or blood clot can act as a physical barrier to fibroblast penetration, which delays normal wound healing.

Answer: ACD

DISCUSSION: Fibroblasts appear in the wound on about the third day of healing and begin to synthesize and secrete collagen molecules. Wound fibroblasts arrive from cells surrounding the wound (e.g., the adventitia of blood vessels), change their phenotype(s), and become mobile during the process of replication. Fibroblasts migrate into a wound using the provisional fibronectin and fibrin matrix as a scaffold. Fibroblasts do not have fibrinolytic enzymes, and large amounts of fibrin and blood clot prevent fibroblasts from entering the wound.

75. Which of the following is/are true?

A. Because of its thickness, the tensile strength of a healing wound on the eyelid is much less than one on the thick skin of the back.

B. By 2 days, the experimental burst strength of skin is minimal since collagen has been formed in the wound but has not yet cross-linked.

C. Wound strength reaches a plateau by 3 weeks.

D. Wounds rarely, if ever, regain the strength of intact tissues.

Answer: BD

DISCUSSION: Tensile strength measures load per cross-section area at rupture, whereas burst strength measures load required to break a wound, regardless of dimension. Therefore, skin wounds have comparable tensile strength, regardless of thickness. Collagen appears in the wound by 3 to 4 days. Minimal wound strength on day 2 is due to fibrin polymerization and adhesion of globular proteins. Wounds rapidly gain strength for about 4 months and then continue to gain strength at a slower rate for more than a year. Wounds do not regain the strength of normal tissue.

76. Which of the following interfere with normal collagen formation or cross-linking?

A. Beta-aminopropionitrile.

B. Iron chelators.

C. Vitamin C depletion.

D. Proline analogs (e.g., cis-hydroxyproline).

E. D-Penicillamine.

Answer: ABCDE

DISCUSSION: Intramolecular and intermolecular cross-links are crucial for collagen structural stability. Formation of cross-links can be inhibited by two pharmacologic agents: beta-aminopropionitrile inhibits the enzyme lysyl oxidase, and D-penicillamine binds to collagen substrate directly to prevent collagen cross-link formation. Iron is a cofactor for prolyl hydroxylase, which is important for collagen synthesis. In high enough concentration, proline analogs prevent collagen formation with minimal effects on noncollagenase protein synthesis.

Which of the following statement(s) is/are true concerning the cell plasma membrane?

Answer: a, b, d

The plasma membrane defines the boundary of the cell and serves to contain and concentrate enzymes and other macromolecule constituents. The plasma membrane is composed of amphipathic molecules, mainly phospholipids and proteins that contain distinct regions that are either insoluble in water (hydrophobic) or soluble in water (hydrophilic). The plasma membrane forms a continuous barrier between the aqueous extracellular and intracellular fluids. Transport proteins in the membrane act as regulated channels or transporters to maintain the intracellular ionic milieu that is clearly different from the extracellular milieu. In some cells, membrane proteins are diversified such as in nerve cells where the ion channels are highly voltage-dependent, providing the basis for information transmission in the form of electrical impulses. Most plasma membrane proteins extend externally and bear carbohydrate moieties primarily as oligosaccharide chains that contribute to the cell coat or glycocalyx.

Which of the following statement(s) is/are true concerning water movement across cell membranes?

Answer: b, c

The energetics of water transport across cell membranes is simplified by the fact that water moves only passively due to gradients of hydrostatic pressure or water concentration. Hydrostatic pressure is an important driving force only for certain specialized cells—the capillary endothelium and the glomerulus of the kidney. For most cells of the body, the transmembrane hydrostatic pressure is 0 and water moves only in response to water concentration gradients. Because the concentration of water is determined by the amount of dissolved solute, the difference in water concentration is typically expressed as a function of the difference in solute concentration or osmotic pressure difference. Because there are no specialized, energy-converting transport mechanisms for water, water is distributed at equilibrium. Water distribution is determined entirely by solute to solute distribution.

The transport of proteins out of the cell is termed exocytosis. Which of the following statement(s) is/are true concerning this process?

Answer: a, b, c

Transport vesicles that bud off the Golgi network carry both material to be secreted from the cell and protein destined to become components of the plasma membrane. These vesicles can fuse with the plasma membrane in a process termed exocytosis. Vesicular transport to the cell surface can be divided into two components, constitutive and regulated secretion. Regulated secretion occurs in cells secreting digestive enzymes, hormones and other regulatory molecules, and neurotransmitters. In regulated secretion, the material to be secreted is sorted in a storage vesicle or granule; fusion with the plasma membrane in exocytosis then takes place in response to external stimulation. Regulated secretion is triggered in most cases by a hormone or neurotransmitter. The ensuing process is termed stimulus-secretion coupling. In most cases the coupling involves an increase in cytoplasmic concentration of Ca++, but may also involve generation of diacylglycerol or production of cyclic AMP which activate kinases or phosphatases.

Which of the following statement(s) is/are true concerning the cell function of phagocytosis?

Answer: a

Phagocytosis is a specialized form of endocytosis by which large particles are internalized by specialized cells primarily macrophages and neutrophils. To be phagocytosed, particles must bind to the surface of the phagocytic cell, usually as the result of specific antibody coating the particle. The phagocytic cell then extends pseudopods which engulf the particle. This event is followed by membrane fusion and a pinching off. As opposed to endocytosis, this process does not involve the membrane protein, clathrin, but rather actin. A physiologically relevant site of phagocytosis is the thyroid gland, where thyroid follicular cells phagocytose and digest thyroglobulin from the lumen of the thyroid follicle, thereby releasing the thyroid hormones, thyroxine triiodothyronine.

A striking feature of living cells is a marked difference between the composition of the cytosol and the extracellular milieu. Which of the following statement(s) concerning the mechanisms of maintenance of these differences is/are true?

Answer: a

The survival of the cell requires that cytosolic composition be maintained within narrow limits, despite the constant influx of nutrients and the simultaneous outflow of waste. A familiar example of the distribution of ions across the cell membrane is that of sodium and potassium. Cells are typically rich in potassium and contain very little sodium. Despite the fact that they are constantly bathed by fluid that is precisely the opposite composition. Even more impressive is the distribution of ionized calcium. The extracellular concentration of this ion is typically of the order of 10–3M, whereas that of cytosol is typically 10–7M, a 10,000-fold gradient. Such nonequilibrium ion distributions are even more remarkable in light of the fact that the plasma membrane is, to varying degrees, leaky to ions such as sodium, potassium and calcium. The plasma membrane is leaky to a variety of substances, but it exhibits an astonishing ability to discriminate or select one substance over another. This selectivity relates to not only ions but also for organic compounds such as glucose. Finally, the selectivity of biologic membranes can be altered drastically as a result of regulatory or signaling processes that occur within the cell.

Which of the following statement(s) is/are true concerning DNA?

Answer: a

The genetic blueprint of an organism is carried in the nucleus of every cell, encoded by the sequence of four bases—adenine, guanine, cytosine and thymine, which together make up two long chains bound together by hydrogen bonds to form a DNA double helix. A gene is a segment of DNA that is transcribed into a corresponding RNA molecule that either codes for a protein or forms a structural RNA molecule. Genes are commonly between 10,000 and 100,000 base pairs in length and include, in addition to the coding sequence, flanking regions and intervening sequences, termed introns. Introns are removed from the primary RNA transcript by a process called splicing. The basic unit of information is the codon, a sequence of three bases or triplet. The four nucleotide bases arranged as triplets lead to 64 possible codons. Sixty-one of these code for amino acids and three are termination signals called stop codons.

Which of the following statement(s) is/are true concerning cell membrane receptors?

Answer: a, c

All water-soluble regulatory molecules bind to the cell surface receptor proteins. Binding of the appropriate ligand evokes an intracellular signal which usually regulates enzyme activity, membrane transport, or in some cases gene expression. Most cell surface receptors belong to one of three functional classes—these are ion channel receptors, catalytic receptors, and G-protein-linked receptors. Ion channel receptors are multisubunit assemblies which, with each subunit, have a multiple membrane spanning segment. Together these subunits form an ion-selected pore that can be gated by a change in transmembrane electrical potential or binding of a ligand to one of the subunits. Catalytic receptors are membrane proteins that possess enzymatic activity. The best understood receptors of this class are the tyrosine kinases. The largest family of cell surface receptors are the G-protein-linked receptors. G-proteins are a family of proteins that bind and hydrolyze GTP. The final component of single transduction by G-protein-linked cell surface receptors is the effector that generates the intracellular messenger. The two best understood effectors are adenylate cyclase, which converts ATP to cAMP, and the polyphosphoinositide-specific phospholipase C.

Which of the following statement(s) is/are true concerning cellular ion channels?

Answer: a, b, c, d

Ion channels are transmembrane proteins that form pores that can conduct ions across the plasma membrane. Ion channels are formed by membrane-spanning peptides that are arranged so that polar moieties line a central pore. These polar groups take the place of the water of hydration, which stabilizes an ion in an aqueous solution creating, in essence, a water-like environment into which the ion can partition and move in the presence of the appropriate driving force. Ion channels are permissive transport elements. Ions flow through a channel only through the presence of an appropriate driving force. Ion channels do not conduct all the time, rather the channel protein undergoes conformational changes between a conducting (open) state and nonconducting (closed) state. These conformational changes are collectively referred to as gating. The conduction process can also be blocked by ions or organic compounds that enter the channel, bind there, and occlude the pore.

Which of the following statement(s) is/are true concerning carrier proteins?

Answer: b, c

Most transport proteins appear to function as carriers, rather than channels. Important distinctions can be made between types of carrier proteins on the basis of transport kinetics. Two primary types can be distinctly identified based on carrier-type and channel-type mechanisms. The most important difference between the channel mechanism and the carrier mechanism is the role in the transport event played by conformational changes in the membrane protein. The channel is depicted as having two states, closed and open, so that it operates like a switch. In contrast, carrier transport is envisioned as requiring a cycle of conformational changes. The transport of one molecule of substrate requires one complete cycle of the protein. In a channel mechanism, binding sites within the open pore are equally accessible from either side of the membrane, whereas in a carrier mechanism, the binding site is available only one side of the membrane at any instant.

Which of the following statement(s) is/are true concerning translation of the mRNA message to protein synthesis?