MedCosmos Surgery

Surgery Lecture Notes, Books, MCQ and Good Articles

Friday, September 5, 2008

General Surgery MCQ

1. Skeletal muscle breakdown produces predominantly liberation of
which two amino acids?
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.

2. In “catabolic” surgical patients, which of the following changes in

body composition do not occur?
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.
3. The hormonal alterations that follow operation and injury favor
accelerated gluconeogenesis. This new glucose is consumed by which
of the following tissues?
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.

4. Cytokines are endogenous signals that stimulate:

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.

5. The characteristic changes that follow a major operation or

moderate to severe injury do not include the following:
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.

6. Shock can best be defined as:

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.

7. Which of the following statements about continuous cardiac output

monitoring are true?
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.

8. Which of the following statements regarding cytokines is incorrect?

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

9. True statements concerning hypoadrenal shock include which of

the following?
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.

10. All of the following are true about neurogenic shock except:
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.

11. True statements regarding eicosanoids include which of the

following?
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.

12. Which of the following statements about delivery-dependent

oxygen consumption are true?
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.

13. All of the following may be useful in the treatment of cardiogenic

shock except:
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.

14. Which of the following statements concerning monitoring

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

15. An 18-year-old man shot once in the left chest has a blood
pressure of 80/50 mm. Hg, a heart rate of 130 beats per minute, and
distended neck veins. Immediate treatment might include:
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.

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

17. All of the following statements about hemorrhagic shock are true
except:
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.

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

19. Which of the following statements are true of oxidants?

A. In addition to their pathophysiologic roles in inflammation, injury,
and infection, oxidants also have physiologic roles.
B. Oxidants may be generated from activated neutrophils and during
reperfusion following a period of ischemia.
C. The deleterious effects of oxidants include lipid peroxidation and
cell membrane damage, oxidative damage to DNA, and inhibition of
adenosine triphosphate (ATP) synthesis.
D. The mechanism of ischemia-reperfusion injury involved the
catalytic production of superoxide anion (O 2•) by the enzyme
xanthine oxidase.
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.
20. Which of the following statements about the role of the gut in
shock and sepsis are true?
A. Selective decontamination of the digestive tract with the use of oral
antibiotics has been shown to reduce nosocomial pneumonias and to
improve mortality rates.
B. Enteral nutrition, as compared with parenteral nutrition, preserves
the villus architecture of the gut.
C. Gut dysfunction may be an effect of shock, but it may also
contribute to the development of MODS by the mechanism of
bacterial translocation.
D. As compared with parenteral nutrition, enteral nutrition is
associated with a reduction in septic morbidity.
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.

21. Which of the following statements about head injury and

concomitant hyponatremia are true?
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.

22. Which of the following statements about total body water

composition are correct?
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.

23. Which of the following statements about extracellular fluid are

true?
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.

24. Which of the following statements are true of a patient with

hyperglycemia and hyponatremia?
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.

25. Which of the following statements about respiratory acidosis are

true?
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.

26. Which of the following statements are true of elevated–anion gap

metabolic acidosis?
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.

27. Which of the following is true of loss of gastrointestinal secretions?

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.

28. Which of the following statements regarding hypercalcemia are

true?
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.

29. Which of the following statements about normal salt and water
balance are true?
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.

30. Which of the following is/are not associated with increased

likelihood of infection after major elective surgery?
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.
31. Which of the following are not determinants of a postoperative
cardiac complication?
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.

32. Rank the clinical scenarios in order of greatest likelihood of

serious postoperative pulmonary complications.
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.

33. Rank the following laboratory tests and procedures in terms of

their relative value to a 65-year-old woman who is to undergo elective
resection of a sigmoid cancer.
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.

34. Which of the following statements regarding whole blood

transfusion is/are correct?
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.

35. Which of the following statements about the preparation and

storage of blood components is/are true?
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 1‫ ؛‬to 6‫ ؛‬C.
C. There are normal numbers of platelets in packed red blood cells
stored at 1‫ ؛‬to 6‫ ؛‬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 1‫ ؛‬to 6‫ ؛‬C using CPDA-1 preservative have a
shelf life of 35 days. There are essentially no functional platelets in
refrigerated blood stored at 1‫ ؛‬to 6‫ ؛‬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.

36. Which of the following is/are acceptable reasons for the

transfusion of red blood cells based on currently available data?
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%.

37. The transfusion of fresh frozen plasma (FFP) is indicated for which
of the following reasons?
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.

38. In patients receiving massive blood transfusion for acute blood

loss, which of the following is/are correct?
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.

39. Hemostasis and the cessation of bleeding require which of the

following processes?
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.

40. Which of the statements listed below about bleeding disorders

is/are correct?
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 32‫؛‬C 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.

41. The evaluation of a patient scheduled for elective surgery should

always include the following as tests of hemostasis and coagulation:
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).

42. Which of the following statements regarding the transmission of

infectious agents through blood transfusions is/are true?
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.

43. The most common cause of fatal transfusion reactions is:

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.

44. Which of the following statements about the coagulation cascade

is/are true?
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.

77 Which of the following statement(s) is/are true concerning the cell

plasma membrane?
a. The plasma membrane is composed of amphipathic molecules
b. The hydrophobic core of the lipid bilayer of the cell membrane
contains specialized transport proteins which maintain the
intracellular ionic milieu different from the extracellular fluid
c. Plasma membrane proteins extend externally and bear
phospholipid moieties which contribute to the cell coat
d. The membrane proteins of nerve cells are highly voltage-dependent
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.

78 Which of the following statement(s) is/are true concerning water

movement across cell membranes?
a. Water moves only actively through cell membrane transport
proteins
b. For most cells of the body, the transmembrane hydrostatic
pressure is 0
c. Water distribution is determined entirely by solute distribution
d. Specialized cells such as the glomerulus of the kidney actively
transport water to maintain hydrostatic pressure
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.

79 The transport of proteins out of the cell is termed exocytosis.

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

80 Which of the following statement(s) is/are true concerning the cell

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

81 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?
a. The cell membrane is able to maintain a 10,000 fold gradient
between the extracellular concentration of ionized calcium and the
intracellular concentration
b. The key to these differences is the fact that the plasma membrane
is normally impermeable to sodium, potassium and calcium
c. The selectivity of biologic membranes is highly consistent and
seldom changes
d. The selectivity of cell membranes relates only to ions and not
organic compounds

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.

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

a. DNA is contained only in the nucleus of the cell
b. DNA strands are encoded by the sequence of four bases—adenine,
guanine, cytosine and uridine
c. The basic unit of information of DNA is the intron, a sequence of
three bases
d. There are an infinite number of possible codons
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.

83 Which of the following statement(s) is/are true concerning cell

membrane receptors?
a. The largest family of cell surface receptors are the G-protein-linked
receptors
b. Activities of the G-protein involve binding and hydrolysis of ATP
c. The G protein receptor generates an intracellular messenger
commonly through the use adenylate cyclase
d. Tyrosine kinase receptors are considered G-protein-linked
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.

84 Which of the following statement(s) is/are true concerning cellular

ion channels?
a. Ion channels are transmembrane proteins that form pores that can
conduct ions across the plasma membrane
b. Ion channels are formed by membrane-spanning peptides that are
arranged so that polar moieties line a central core
c. Ion channel proteins undergo conformational changes between
open states and closed states
d. Ion channels can be blocked
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.

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

proteins?
a. Carrier proteins are distinguished by three types of mechanisms:
carrier-type, channel-type, and conduction-type
b. Conformational changes in the membrane protein occur between
the conducting and the nonconducting states
c. A channel-type carrier protein has two states—closed and open
d. Carrier-type transport proteins are equally accessible from either
side of the membrane
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.

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

translation of the mRNA message to protein synthesis?
a. An adaptor molecule, tRNA, recognizes specific nucleic acid bases
and unites them with specific amino acids
b. Covalent attachment of tRNA to amino acids is energy dependent
c. The formation of a peptide bond between the growing peptide
chain and the free amino acid occurs in the free cytoplasm
d. Complete protein synthesis takes hours
Answer: a, b

The synthesis of protein involves conversion from a four-letter

nucleotide language to one of 20 chemically distinct amino acids. This
process is referred to as translation. There is no mechanism for direct
chemical recognition between specific nucleic acid bases and specific
amino acids. Instead, an adaptor molecule, tRNA, is used. Each tRNA
carries only one amino acid and must be recognized by a distinct
enzyme which catalyzes the covalent attachment of the carboxyl end
of the amino acid to the end of the tRNA in a process using ATP.
Protein synthesis occurs by the formation of a peptide bond between
the carboxyl terminal of the growing peptide chain and the free amino
acid of deactivated amino acid tRNA. This event does not occur in free
solution, but within ribosomes. Ribosomes are protein synthesizing
machines that bring all of the necessary components together in the
correct sequence and spacial orientation. Protein synthesis consumes
a great deal of energy because four high-energy phosphate bonds
must be split to make each peptide bond. Complete synthesis of a
single protein takes 30 seconds to a few minutes, but multiple
ribosomes can initiate translation and be moving down the mRNA
molecules simultaneously, thus increasing the rate of protein
synthesis.

87 Cell regulation can be thought of as the effector side of cell

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

Depending on how the extracellular messenger arrives, cell regulation

can be classified as paracrine, endocrine, or neurocrine. In paracrine
regulation, a chemical messenger or mediator is produced and acts
locally. In endocrine regulation, the extracellular messengers
(hormones) are released into the blood and act on target cells
anywhere on the body that has appropriate receptors. In neurocrine
regulation, neurons secrete transmitters into highly localized regions,
the synaptic cleft, so that the regulation depends on a physical
connection between the neuron and the target cell as well as the
presence of a specific receptor. In almost all cases of cell regulation,
the extracellular signal or stimulus is restricted to being an
informational molecule. This information is received by receptor on or
in the target cell, which generally has an affinity for the signal
molecule. Most hormones, local mediators, and neurotransmitters are
water-soluble and cannot readily cross the plasma membrane.

88 Proteins that are destined to be secreted from the cells must pass
through a series of organelles. These organelles include:
a. Endoplasmic reticulum
b. Golgi apparatus
c. Mitochondria
d. Lysosomes
Answer: a, b, d
Proteins targeted for the secretory pathway most commonly begin
with translocation from the cytoplasm across the lipid bilayer into the
lumen of the endoplasmic reticulum. It must then pass through a
number of compartments including the Golgi apparatus where they
are further processed and sorted and end up in a secretory vesicle or
lysosome.

89 The best understood intracellular messenger is cyclic AMP (cAMP).

Which of the following statement(s) concerning this intracellular
messenger is/are correct?
a. Intracellular cyclic AMP is constantly degraded by a specific enzyme,
cAMP phosphodiesterase
b. Most of the actions of cAMP are mediated by activation of protein
kinase A
c. Intracellular levels of cAMP are relatively stable and change solely in
response to activation of adenylate cyclase
d. cAMP is the only cyclic nucleotide active as an intracellular
messenger
Answer: a, b

The prototypic intracellular messenger is cAMP. To function as a

mediator, the concentration of cAMP must change rapidly. In resting
cells, cAMP is continuously being degraded by a specific enzyme,
cAMP phosphodiesterase. cAMP levels can increase 10-fold or more
within seconds of receptor binding through activation of adenylate
cyclase. cAMP acts as an allosteric regulator, and most, if not all, of its
actions are mediated by activation of cAMP-dependent protein kinase
A. cAMP is not the only cyclic nucleotide active as an intracellular
messenger. Most animal cells also produce cGMP. Intracellular
calcium ions also serve as second messengers in a large number of
cells.

90 The activities of the cytoskeleton is dependent on which of the

following types of filaments?
a. Microtubules
b. Intermediate filaments
c. Actin filaments
d. None of the above
Answer: a, b, c

The cytoskeleton is a collection of filamentous protein structures that

allow cells to assume and maintain a variety of shapes, to produce
directed movement of organelles within the cell, and to affect
movement of the entire cell relative to other cells. These multiple
activities depend upon three main types of filaments: actin filaments,
intermediate filaments, and microtubules.
91 Intracellular organelles involved with protein synthesis include:
a. Mitochondria
b. Endoplasmic reticulum
c. Golgi complex
d. Lysosomes
Answer: b, c

Mitochondria are the major source of energy production in eukaryotic

cells. The endoplasmic reticulum is the network of interconnected
membranes forming closed vesicles, tubules, and saccules. The
endoplasmic reticulum has a number of functions and is primarily
involved in the synthesis of proteins and lipids. Adjacent to the rough
endoplasmic reticulum and functionally involved in the sorting and
package of secreted protein is the Golgi complex. Lysosomes are
membrane-limited organelles containing acid hydrolytic enzymes that
degrade polymers such as proteins, carbohydrates, and nucleic acids.

92 An important step in protein synthesis is transcription. Which of

the following statement(s) is/are true concerning this process?
a. The first step in gene transcription involves separating the double
helix of DNA by an enzyme known as DNA polymerase
b. The initial product of DNA transcription is called heterogeneous
nuclear RNA which codes directly for proteins
c. After processing is complete, the mRNA is exported from the
nucleus to the cytoplasm
d. Only one protein can be produced from an initial mRNA strand
Answer: c

Transcription of a gene begins at an initiation site associated with a

specific DNA sequence, termed a promoter region. After binding to
DNA, the RNA polymerase opens up a short region of the double helix
to expose the nucleotides. Once the two strands of DNA are
separated, the strand containing the promoter acts as a template to
which ribonucleoside triphosphates base pair by hydrogen bonds. The
initial products of transcription are known as heterogeneous nuclear
RNA because of their large size variation. These primary transcripts
are then processed to form mRNA. RNA splicing accounts for mature
RNA being much shorter than nuclear RNA. Moreover, alternative
splicing can lead to the production of different mRNA molecules and
in some cases different proteins from the same gene. mRNA is
exported from the nucleus only after processing is complete.

93 There are two properties of the cell necessary to maintain

nonequilibrium cellular composition; the first is selectivity and the
second is energy conversion. Which of the following statement(s)
is/are true concerning energy converting transport?
a. The site of energy conversion and transport in the plasma
membrane involves the phospholipid component
b. The Na+-K++-ATPase derives energy from hydrolysis of extracellular
ATP
c. In some systems, energy inherent in the transmembrane ion
gradient can be used to drive transport of a second species
d. Examples of species transported via secondary active transport
include hydrogen ions, calcium, amino acids and glucose
Answer: c, d

The selectivity of the plasma membrane, although impressive, cannot

account for the nonequilibrium composition of living cells. A cell can
be maintained in a nonequilibrium state only by continual
expenditure of energy. The maintenance of a steady-state,
nonequilibrium cellular composition is possible because the plasma
membrane is the site of energy converters, membrane proteins that
function as biologic transport machines using energy derived from
metabolic processes to perform transport work. The archetype for the
biologic transport machine is the Na+-K+-ATPase, a membrane
protein that hydrolyses cytosolic ATP and couples the resulting free
energy to transport of Na+ and K+. A second equally important type of
energy-converting transporter is one in which the energy inherent in a
transmembrane ion gradient, usually that of Na+ can be used to drive
the transport of a second species such as protons, calcium, amino
acids, or glucose.

94 Which of the following statement(s) is/are correct concerning cell

junctions?
a. The major occluding junction is the tight junction or zonula
occludens
b. Tight junctions are usually located near the basal pole of the cell
c. Desmosomes are button-like points of attachment which serve to
weld together adjacent cells
d. Gap junctions are a type of cell junction specialized for cell
communication
Answer: a, c, d

Cell junctions are classified as occluding, anchoring, and

communicating. The major occluding junction is the tight junction or
zonula occludens which connects cells in epithelia and thereby allows
epithelia to serve as selective permeability barriers. Tight junctions
are normally located near the apical pool of the cell and form a belt
that completely encircles the cell. Anchoring junctions connect the
cytoskeleton of the cell to the extracellular matrix or neighboring cells.
Morphologically these are adherens junctions or desmosomes.
Desmosomes are button-like points of attachment with a prominent
intracellular plaque that serves to weld together adjacent cells by
serving as anchoring sites for intermediate filaments within the cell.
The third functional type of cell junction is a gap junction which is
specialized for communication. This junction mediates both electrical
and chemical coupling.

95 Examples of ion channel blockers include:

a. Tetrodotoxin
b. Amiloride
c. Xylocaine
d. None of the above
Answer: a, b, c

Channel blockade is an important mechanism of action for toxins and

some therapeutic agents. The deadly toxin of the puffer fish,
tetrodotoxin, acts by blocking the Na+ channels that are responsible
for the conduction of nerve impulse. The diuretic, amiloride, acts by
blocking the Na+ channels that inhabit the apical membrane of the
epithelial cells of the distal nephron. Local anesthetics such xylocaine
also act by blocking ion channels.

96 Most hormone receptors are localized on the cell membrane and

transduce hormone binding into altered levels of intracellular
messengers. A limited number of intracellular receptors do exist.
Which of the following statement(s) is/are true concerning
intracellular receptors?
a. The messengers or hormones must by lipophilic
b. These intracellular receptors generally regulate protein synthesis
c. The intracellular receptors are located entirely in the nucleus of the
cell
d. A heat-shock protein serves as an inhibitor protein blocking the
DNA-binding domain of the steroid receptor
Answer: a, d

Although most hormone and other messenger receptors are

extracellular, intracellular receptors have been identified. The
hormone messengers involved for these receptors are primarily
steroid and thyroid hormones and are lipophilic. By virtue of their
hydrophobic nature, they are able to readily penetrate the lipid
portion of the cell membrane. Receptors for these hormones exist
intracellularly in the cytoplasm or in the nucleus and generally act as
regulators of gene expression. These hydrophobic signaling molecules
exist in plasma bound to protein, so that the concentration of this
class of regulators does not fluctuate rapidly in plasma and their
actions are generally slower in onset and more prolonged than those
of water-soluble class. Some types of steroid receptors, particularly
for glucocorticoids, are located in the cytosol in the inactive state.
Once the ligand binds, the receptor undergoes a conformational
change, termed activation. This allows cytoplasmic receptors to move
into the nucleus and bind to DNA. Receptors already in the nucleus
increase their affinity for DNA. In the case of glucocorticoid receptors
and probably others of this class, the inactive receptor is associated
with another protein, the heat-shock protein. They block the
DNA-binding domain of the receptor. Activation involves the
dissociation of the inhibitor protein.

97 Altering the amino acid profile in total parenteral nutrition

solutions can be of benefit in certain conditions. Which of the
following conditions are associated with a benefit by supplementation
with the amino acid type listed?
a. Acute renal failure and essential amino acids
b. Hepatic failure and aromatic amino acids
c. Short gut syndrome and glutamine
d. Chronic renal failure and essential amino acids
Answer: a, c

In a number of conditions, altering the amino acid profile of the total

parenteral nutrition solution can be of benefit. TPN with amino acids
of high biologic value may decrease the mortality in patients with
acute renal failure. These solutions, containing high quality amino
acids, can improve nitrogen balance and diminish urea nitrogen.
Provision of essential amino acids only allows the body to maximally
utilize nitrogen for the synthesis of non-essential amino acids and
thereby helps prevent rapid rises in blood urea nitrogen. There
appears to be no advantages to using essential amino acids if the
patient is already being dialyzed every other day and therefore a
balanced standard amino acid solution is recommended. Because of
liver damage and portasystemic shunting, patients with hepatic failure
develop derangements in circulating levels of amino acids. The
plasma aromatic/branch chain amino acid ratio is increased favoring
the transport of aromatic amino acids across the blood brain barrier.
These amino acids are precursors of false transmitters which
contribute to lethargy and encephalopathy. Treatment of individuals
with liver failure with solutions enriched in branch chain amino acids
and deficient in aromatic amino acids results in improved tolerance to
administration of protein and clinical improvement in
encephalopathic states. Glutamine-enriched TPN partially attenuates
villous atrophy and may be useful in treatment of short gut syndrome.

98 Under certain circumstances, the gut may become a source of

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

Answer: a, b, c, d

99 Translocation is promoted in three general ways: 1) altered

permeability of the intestinal mucosa as caused by shock, sepsis,
distant injury, or cell toxins; 2) decreased host defense (secondary to
glucocorticoid administration, immunosuppression, or protein
depletion; and 3) an increased number of bacteria within the
intestine. Because many factors that facilitate bacteria translocation
occur simultaneously in surgical patients, these effects may be either
additive or cumulative. In addition, many patients in Surgical Intensive
Care Units do not generally receive enteral feedings and therefore
current parenteral therapy results in gut atrophy which further
promotes translocation.
Which of the following statement(s) is/are true concerning nutritional
support of the injured patient?
a. The goal of nutritional support is maintenance of body cell mass
and limitation of weight loss to less than 25% of preinjury weight
b. Under-nutrition may compromise the patient’s available defense
mechanisms
c. Nutritional support is an immediate priority for the trauma patient
d. Fifty percent of non-nitrogen caloric requirements should be
provided in the form of fat
Answer: b

Metabolic response to injury results in increased energy expenditure.

If energy intake is less than expenditure, oxidation of body fat stores
and erosion of lean body mass will occur with resultant loss of weight.
When weight loss exceeds 10–15% of body weight, the complications
of malnutrition interact with disease processes, with increased
morbidity and mortality rates. The goal of nutritional support is
maintenance of body cell mass and limitation of weight loss to less
than 10% preinjury. The major impact of nutritional support in the
trauma patient is to aid host defense. Under-nutrition may
compromise the available host defense mechanism and may thus
increase the likelihood of invasive sepsis, multiple organ system
failure, and death. Resuscitation, oxygenation and arrest of
hemorrhage are immediate priorities for survival. Nutritional support
is an essential part of the metabolic care of the critically ill patient and
should be instituted after resuscitation before significant weight loss
occurs. The nutritional requirements of a trauma patient can be
determined by determining basal metabolic rate with appropriate
increases based on extent of injury and hospital activity. After initial
determination of nitrogen requirements, caloric requirements should
be distributed at a ratio of 70% as glucose and 30% as fat.

100 Which of the following statement(s) is/are true concerning body

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

The body contains fuel reserves which it can mobilize and utilize
during times of starvation or stress. By far the greatest energy
component is fat, which is calorically dense since it provides about 9
calories/gram. Body protein comprises the next largest mass of
utilizable energy, but amino acids yield only about 4 kcal/gram. Unlike
fat reserves, body protein is not a storage form of energy but rather
serves as a structural functional component of the body; loss of body
protein, if severe, is associated with functional consequences.
Glycogen stored in muscle and liver and free glucose have a trivial
caloric value of less than 1000 kcal for a 70 kg male.
101 Which of the following statement(s) is/are true concerning the
indications and administration of nutritional support to cancer
patients?
a. Preoperative nutritional support should be provided to all patients
with cancer
b. To be effective, preoperative nutrition must be given for at least
two weeks preoperatively
c. Parenteral nutrition is the preferred route of feeding for all cancer
patients
d. Standard total parenteral nutrition solutions maintain integrity of
the small bowel
e. None of the above
Answer: e

The role of nutritional support in the cancer patient remains an

important component of overall therapy. Preoperative nutritional
support should be given only to those patients who do not require an
emergency operation and who have severe weight loss (> 15% of
pre-illness body weight) and a serum albumen < 2.9 mg%.
Preoperative nutrition (enteral or parenteral) should not be given for
longer than 7 to 10 days. Enteral nutrition is always the preferred
route of feeding cancer patients if the GI tract is functional. There are
several benefits of using the bowel lumen for nutrient delivery. The
trophic effects of enteral feeding on small bowel mucosa have been
well described. The integrity of the mucosal lining is maintained and it
may provide an effective barrier to intraluminal enteric organisms
which might otherwise translocate into the systemic circulation.
Atrophic changes may be seen in the intestinal epithelium after
several days of bowel rest; this atrophy is not reversed by currently
available total parenteral nutrition solutions.

102 Which of the following hormones can be expected to be released

as part of the stress response?
a. Antidiuretic hormone (ADH)
b. Aldosterone
c. Insulin
d. Epinephrine
nswer: a, b, d

Several important responses occur in response to stress. The body

immediately attempts to compensate for a reduction in circulating
blood volume in order to maintain adequate organ perfusion. Afferent
nerve signals are also initiated which stimulate the release of both
antidiuretic hormone (ADH) and aldosterone. The pain and fear
associated with the stress response lead to excessive production to
catecholamines which also increase metabolic rate, stimulate lipolysis,
hepatic glycolysis, and gluconeogenesis. Glucagon, which has a potent
glycogenolytic and gluconeogenic effect in the liver, is also released.
This hormone has the exact opposite effect of insulin, which promotes
glucose storage and uptake by the cells.

103 Cytokines which play an important role in the metabolic response

to injury include:
a. Tumor necrosis factor—a (TNF)
b. Interleukin-1 (IL-1)
c. Interleukin-6 (IL-6)
d. Interferon-g
Answer: a, b, c, d

TNF or cachetin is considered the primary mediator of the systemic

effects of endotoxin, producing anorexia, fever, tachypnea, and
tachycardia at low doses and hypotension, organ failure, and death at
higher doses. TNF is produced primarily by macrophages, but
lymphocytes, Kupffer cells, and a number of other cell types have
been identified as sources of TNF. IL-1, like TNF, has a variety of
pro-inflammatory activities. IL-6 is now recognized as a primary
mediator of altered hepatic protein synthesis known as acute-phase
protein synthetic response. Glucocorticoid hormones augment the
cytokine effects on acute phase protein synthesis. Interferons are a
family of proteins which are readily identified for their ability to inhibit
viral replication in infected sells. IFN-g has the ability to upregulate the
number of TNF receptors on various cell types.
104 A 16-year-old boy suffers a mid-gut volvulus with massive loss of
small intestine. Which of the following statement(s) is/are true
concerning his nutritional requirements and management?
a. If at least 18 inches of residual small intestine survives, the patient
may tolerate some form of enteral nutrition
b. A nutritional regimen consisting of supplemental glutamine, growth
hormone, and a modified high carbohydrate, low fat diet may be
beneficial in this patient
c. The regimen described above may decrease the cost of care
d. TPN needs will increase after discontinuation of growth hormone
Answer: a, b, c

Prior to the availability of TPN, most patients developing short bowel

syndrome from either surgery or catastrophic event died. In selected
patients, however, with residual small intestine (at least 18 inches),
post-resectional hyperplasia may develop with time such that they
can tolerate enteral feeds. Recent studies have demonstrated the
requirement for TPN could be decreased or even eliminated in
patients with short-gut syndrome by providing a nutritional regimen
consisting of supplemental glutamine, growth hormone, and a
modified high carbohydrate, low fat diet. There was a marked
improvement in absorption of nutrients with this combination of
therapy and a decrease in stool output. In addition, TPN requirements
were reduced by 50% as were costs associated with the care of these
individuals. Discontinuation of the growth hormone did not increase
TPN needs in patients once they had undergone successful gut
rehabilitation.

105 A number of changes in trace mineral metabolism are noted

during sepsis. Which of the following change(s) may be observed in a
septic or trauma patient?
a. Plasma iron levels are noted to decrease
b. Plasma copper levels are noted to decrease
c. Plasma serum zinc levels may decrease
d. Administration of iron is appropriate
Answer: a, c

Changes in the balance of magnesium, inorganic phosphate, zinc, and

potassium generally follow alterations in nitrogen balance. Although
the iron-binding capacity of transferrin is usually unchanged in early
infection, iron disappears from the plasma, especially during severe
pyogenic infection; similar alterations are observed in serum zinc
levels. The administration of iron to the infected host, especially early
into the disease, is contraindicated, however, because increased
serum iron concentrations may impair resistance. Unlike iron and
zinc, copper levels generally rise, and the increased plasma
concentrations can be ascribed almost entirely to the levels of the
ceruloplasmin produced by the liver.

106 A 17-year-old patient involved in an automobile accident is

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

The use of transnasal feeding catheters for intragastric feeding or for

duodenal intubation are popular adjuncts for providing nutritional
support by the enteral route. The stomach is easily accessed by
passage of a soft flexible feeding tube. Intragastric feeding provides
several advantages for the patient. The stomach has the capacity and
reservoir for bolus feedings. Feeding into the stomach results in
stimulation of the biliary/pancreatic axis which is probably trophic for
the small bowel. Gastric secretions will have a dilutional effect on the
osmolarity of the feedings, reducing the risk of diarrhea. The major
risk of intragastric feeding is the regurgitation of gastric contents
resulting in aspiration into the tracheobronchial tree. This risk is
highest in patients who have an altered sensorium or who are
paralyzed. The placement of the feeding tube through the pylorus into
the fourth portion of the duodenum reduces the risk of regurgitation
and aspiration of feeding formulas.

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

A number of studies have examined the effects of TPN on intestinal

function and immunity. Although most of these studies have been
done in animal models, TPN has consistently been shown to have
some detrimental effects. In rats, TPN results in significant disruption
of the intestinal microflora and bacterial translocation of the gut to
the mesenteric lymph nodes. In addition, when stresses such as a
burn injury, chemotherapy, or radiation are introduced into these
models, animals on TPN have a much higher mortality. The body of
literature suggests that TPN under certain circumstances may
predispose patients to an increase in gut-derived infectious
complications. In a study in human volunteers, individuals receiving
TPN had an accentuated systemic response to endotoxin challenge
compared to enterally fed volunteers. This study is consistent with
impairment of gut barrier function during parenteral feedings which
may promote the release of bacteria and/or cytokines leading to
pronounced systemic responses and possibly multiple organ failure.

108 Total body mass is composed of an aqueous component and a

nonaqueous component. The nonaqueous component is made up of
which of the following?

a. Liver
b. Tendons
c. Skeletal muscle
d. Extracellular fluid
e. Adipose tissue
Answer: b, e

The nonaqueous portion of total body mass is made up of bones,

tendons, and mineral mass as well as adipose tissue. The aqueous
component contains the body cell mass which is made up of skeletal
muscle, intraabdominal and intrathoracic organs, skin, and circulating
blood cells. Also contributing to the aqueous portion is the interstitial
fluid and intravascular volume.

109 Fatty acids are a major energy source for the body. Which of the
following statement(s) is/are true concerning the use of fatty acids as
an energy source?
a. Fatty acids are stored in adipocytes as triglycerides
b. Hormone-sensitive lipase is present only in adipose tissue
c. Fatty acids are released into the circulation traveling freely in
plasma
d. Approximately 25% of total nonprotein caloric needs supplied via
total parenteral nutrition should be in the form of fat
Answer: a, b, d

In most tissues, fatty acids are readily oxidized for energy. They are
especially important energy sources for the heart, liver and skeletal
muscle. In adipose tissue, fatty acids may be re-esterified with glycerol
and stored as triglycerides in adipocytes. Stored fat is mobilized
during starvation and stress. Hormone-sensitive lipase, present only
in adipose tissue, catalyzes the breakdown of stored triglycerides into
glycerol and fatty acids. The fatty acids that are produced are released
in the circulation. The major lipids in plasma do not circulate in a free
form, thus free fatty acids must be bound to albumin. During stress,
the activity of hormone-sensitive lipase is increased which leads to
mobilization of fat stores. However, fat remains an important fuel
source for critically ill patients and as a rule the amount of fat
administered to patients receiving total parenteral nutrition should
comprise about 5–30% of total nonprotein caloric needs.

110 Which of the following metabolic effects may be observed in

patients with sepsis?
a. Increased gluconeogenesis
b. Accelerated proteolysis
c. Increased lipolysis
d. Impaired gut metabolism of glutamine
Answer: a, b, c, d

A number of metabolic responses to sepsis have been defined.

Glucose production is increased in infected patients which appears to
be additive to the augmented gluconeogenesis that occurs following
injury. Accelerated proteolysis, increased nitrogen excretion and
prolonged negative nitrogen balance also occur following infection
with a response pattern similar to that described with injury. Severe
infection is often associated with a hypercatabolic state that initiates
marked changes in interorgan glutamine metabolism. This process
results in accelerated muscle proteolysis and net skeletal muscle
glutamine release. The bulk of glutamine is taken up by the liver at the
expense of the gut. It appears that sepsis can impair gut metabolism
of glutamine. Fat is a major fuel oxidized in infected patients, and
increased metabolism of lipids from peripheral fat stores is especially
prominent during a period of inadequate nutritional support.

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

protein/amino acid metabolism in man?
a. The major source of amino acids is breakdown of circulating
proteins
b. The recommended daily allowance for protein may triple in critically
ill patients
c. Urinary nitrogen losses will approach 0 in the face of protein
starvation
d. Negative nitrogen balance refers to a decrease in nitrogen taken
into the body versus the amount of nitrogen lost
Answer: b, d
About 15% of the total body weight is made up of proteins, about half
of which are intracellular and half extracellular. In man and other
animals, dietary protein is the source of most amino acids. Intestinal
absorption is the only physiological pathway by which the body
obtains exogenous amino acids. Digestion of ingested protein
provides free amino acids that are absorbed by the small intestine
and transported to the liver where they can be incorporated into new
proteins or other biosynthetic products. Excess amino acids are
degraded and their carbon skeleton is oxidized to produce energy or
it is incorporated into glycogen or into free fatty acids. In addition to
the metabolism of dietary amino acids, the existing proteins in the cell
are continuously recycled, such that total protein turnover in the body
is about 300 g/day. Vertebrates cannot reutilize nitrogen with 100%
efficiency; therefore, obligatory nitrogen losses occur, mainly in the
urine. Urinary nitrogen losses will diminish when individuals are fed a
protein-free diet, but will never become 0 because of the body’s
inability to completely reutilize nitrogen. In stressed patients, this
ability to adapt to starvation is compromised such that proteolysis of
body proteins continues at a substantial rate. This increases the
amount of obligatory nitrogen losses which are accentuated by the
catabolic disease states. This results in a negative nitrogen balance in
which the amount of nitrogen taken in by the patient is exceeded by
the amount of nitrogen lost in the urine, stool, skin, wounds, and
fistula drainage.

112 Which of the following statement(s) concerning intravenous

nutritional support is/are true?
a. Concentrations of glucose no higher than 5% should be used to
avoid peripheral vein sclerosis
b. A major disadvantage of the peripheral technique is limited caloric
delivery
c. If total parenteral nutrition is required, access to the superior vena
cava via the external jugular vein is the most suitable site
d. Venous thrombosis is an uncommon complication for long-term
central vein catheterization
Answer: b

Although peripheral access can be used for intravenous nutrition, the

major disadvantage of this technique is limited caloric delivery to
meet catabolic demands within tolerated fluid limits. Infusion of
glucose (up to 10%), amino acid solutions, and fat emulsions can be
administered peripherally but these solutions must be nearly isotonic
to avoid peripheral vein sclerosis. The preferred method of access for
total parenteral nutrition is into the superior vena cava by cutaneous
cannulation of the subclavian vein. Alternative sites include the
internal and external jugular vein but the catheter exiting from the
neck region makes it more difficult to secure and maintain a sterile
dressing. Complications from long-term central venous
catheterization include venous thrombosis and venous catheter-
related infection. Thrombosis of central vessels is a complication
which is often overlooked. The clinical suspicion of subclavian vein
thrombosis is only about 3%, whereas studies that use phlebography
or radionucleotide venography indicate the incidence is as high as
35%.

113 Sepsis causes a marked metabolic response. Which of the

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

Oxygen consumption is usually elevated in the infected patient. The

extent of this increase is related to the severity of the infection, with
peak elevations reaching 50% to 60% above normal. If the patient’s
metabolic rate is already elevated to a maximal extent because of
severe injury, no further increase will be observed. In patients with
only a slightly accelerated rate of oxygen consumption, the presence
of infection will cause a rise in metabolic rate added to the preexisting
state. A portion of the increase in metabolism may be ascribed to
increase in reaction rate associated with fever. Calculations suggest
that the metabolic rate increases 10% to 13% for each elevation of 1°C
in central temperature.

114 Interleukin-6 is recognized as the cytokine primarily responsible

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

IL-6 is now recognized at the cytokine primarily responsible for the

alteration in hepatic synthesis recognized as the acute phase
response. Glucocorticoid hormones augment this response. The
primary metabolic component of the acute phase response is a
qualitative alteration in hepatic protein synthesis with resulting
alteration in plasma protein composition. Characteristically, proteins
which act as serum transport in binding molecules, (albumin,
transferrin) are reduced in quantity and acute phase proteins
(fibrinogen, C-reactive proteins) are increased. Acute phase proteins
are elaborated for the purpose of reducing the systemic effects of
tissue damage. Many act as anti-proteases, opsonins, or coagulation
and wound healing factors that generally inhibit the tissue destruction
that is associated with the local initiation of inflammation.

115 A 59-year-old trauma patient has suffered multiple septic

complications including severe pneumonia, intraabdominal abscess,
and major wound infection. He has now developed signs of
multisystem organ failure. Which of the following statement(s) is/are
true concerning necessary changes to be made in his nutritional
management?
a. Carbohydrate load should be reduced in the face of respiratory
failure
b. In patients with renal failure, protein intake should be diminished
c. During hemodialysis protein intake should be limited to the same
extent
d. In patients with hepatic failure, carbohydrate load should be
increased
Answer: a, b

The most severe complication of sepsis is multiple system organ

dysfunction syndrome, which may result in death. The development
of organ failure requires changes in the nutritional requirements and
creates special feeding problems. A problem associated with systemic
infection is oxygenation and elimination of carbon dioxide. Most of
the enteral and parenteral formulas used to provide nutritional
support for critically ill patients contain large amounts of
carbohydrate, which generate large amounts of carbon dioxide
following oxygenation. Such a large CO2 load may worsen pulmonary
function or may delay weaning from the respirator. If this factor
becomes a problem, the carbohydrate load should be reduced to 50%
of metabolic requirements and fat emulsion administered to provide
additional calories. When renal failure becomes progressive, the use
of hemodialysis minimizes the effect of uremia superimposed on the
metabolism of sepsis. Metabolic studies in patients with acute and
chronic renal failure have limited the intake of nonessential amino
acids, in an attempt to lower urea production. Proteins of high
biologic value, but in much smaller quantities than usually given, are
administered along with adequate calories, usually in the form of
glucose. When enteral feedings are not feasible, a central venous
infusion of an essential amino acid solution and hypertonic dextrose
provides calories and a small quantity of nitrogen to reduce protein
catabolism while simultaneously controlling the rise in BUN. During
dialysis, protein intake is liberalized, but the BUN should still be
maintained below 100 mg/dl. Hepatic dysfunction is a common
manifestation of septicemia. The carbohydrate load is usually reduced
to consist of no more than 5% of metabolic requirements, and the
additional calories should be provided as fat emulsion. If
encephalopathy develops, protein load should also be reduced0.

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

role of glutamine in total parenteral nutrition?
a. Glutamine is an essential amino acid
b. Glutamine appears to be of primary benefit in critical illness
c. Glutamine is included in most standard TPN solutions
d. Glutamine is the primary energy source for intestinal mucosal cells
of the small bowel and colon
Answer: b

Glutamine is the most studied gut-specific nutrient. Glutamine has

been classified as a nonessential or nutritionally dispensable amino
acid since glutamine can be synthesized in adequate quantities from
other amino acids and precursors. Glutamine is not included in most
nutritional formulas and has been eliminated from TPN solutions
because of its relative instability and short half life compared to other
amino acids. With few exceptions, glutamine is present in oral enteral
diets but only at relatively low levels characteristic of the
concentration in most animal and plant stores (about 7% of total
amino acids). Several recent studies, however, have demonstrated
that glutamine may be an essential amino acid during critical illness,
particularly as it relates to supporting the metabolic requirements of
the intestinal mucosa. These studies demonstrate that dietary
glutamine is not required during states of health but appears to be
beneficial when glutamine depletion is severe and/or when intestinal
mucosa is damaged by insults such as chemotherapy or radiation
therapy. The addition of glutamine to enteral diet reduces the
incidence of gut translocation but these improvements are dependent
upon the amount of supplemental glutamine and the type of insult
studied. Glutamine-enriched TPN partially attenuates villous atrophy
that develops during parenteral nutrition. The use of intravenous
glutamine in patients appears to be safe and effective in its ability to
maintain muscle glutamine stores and improve nitrogen balance. In
contrast to glutamine, short chain fatty acids are primary energy
source for colonocytes.

117 Which of the following are determinants of the host response to

surgical stress?
a. Gender
b. Age
c. Nutritional status
d. Body composition
Answer: a, b, c, d

The pattern of physiologic changes elicited in response to surgical

stress results from the specific interaction of an individual patient with
a stressful stimulus. Several factors specific to the patient may
determine the nature of the host response to stress. Body
composition is a major determinant of the metabolic responses
observed during surgical illness. Post-traumatic nitrogen excretion is
directly related to the size of the body protein mass. A strong
relationship between protein depletion and postoperative
complications has been demonstrated in nonseptic,
nonimmunocompromised patients undergoing elective major
gastrointestinal surgery. Protein-depleted patients have significantly
lower preoperative respiratory muscle strength and vital capacity,
increased incidence of postoperative pneumonia, and longer
postoperative hospital stay. Impaired wound healing and respiratory,
hepatic, and muscle function in protein-depleted patients awaiting
surgery has also been reported. Many of the changes in the metabolic
responses to surgical illnesses that occur with aging can be attributed
to alterations in body composition and to long-standing patterns of
physical activity. Fat mass tends to increase with age and muscle mass
tends to decrease. Loss of strength that accompanies immobility,
starvation and acute surgical illness may have marked functional
consequences. Furthermore, the prevalence of cardiovascular and
pulmonary diseases increase with age. Thus, the delivery of oxygen to
tissues may be impaired in the elderly. Finally, observed differences in
metabolic responses of men and women generally reflect differences
in body composition. Lean body mass is lower in women than in men;
and this difference is thought to account for the net loss of nitrogen
after major elective abdominal surgery generally being lower in
women than in men.

118 In contrast to a patient undergoing an elective operation, which of

the following statement(s) is/are true concerning a patient who has
suffered a multiple trauma?
a. Basal metabolic rates are similar
b. The patient is highly sensitive to insulin
c. Utilization of the amino acids, glutamine and alanine, is similar to
their composition in skeletal muscle
d. Fat and protein stores are rapidly depleted
Answer: b, d
The degree of hypermetabolism is generally related to the severity of
injury. Patients with long-bone fractures have a 15–25% increase in
metabolic rate, whereas metabolic rates in patients with multiple
injuries increases by 50%. These metabolic rates in trauma patients
are contrasted with those in postoperative patients, who rarely
increase their BMR by more than 10–15% following operation. Studies
have shown that uninjured volunteers are able to dispose of
exogenous glucose load much more readily than injured patients.
Other studies have demonstrated a failure to suppress hepatic
glucose production in trauma patients during glucose loading or
insulin infusion. Thus, profound insulin resistance occurs in injured
patients. Skeletal muscle is the major source of nitrogen that is lost in
the urine following extensive injury. Although it is recognized that
amino acids are released by muscle in increased quantities following
injuries, it has only been recently appreciated that the composition of
amino acid reflux does not reflect the composition of muscle protein.
The release is skewed towards glutamine and alanine, each of which
comprise about one-third of the total amino acids released by skeletal
muscle. To support hypermetabolism, stored triglyceride is mobilized
at an accelerated rate. Although mobilization and use of free fatty
acids are accelerated in injured subjects, if unfed, severely injured
patients rapidly deplete their fat and protein stores.

119 A 47-year-old patient undergoing a complicated laparotomy for

bowel obstruction develops a postoperative enterocutaneous fistula.
Which of the following statement(s) is/are true concerning parenteral
nutritional support in the postoperative period?
a. Oral intake can result in severe dehydration, electrolyte
abnormalities, and perifistula skin injury
b. Total parenteral nutrition increases the spontaneous closure rate of
intestinal fistula
c. Total parenteral nutrition decreases mortality rate in patients with
intestinal fistulas
d. The use of TPN better prepares the patient for surgery if surgical
intervention proves necessary
Answer: a, b, d

Patients with gastrointestinal-cutaneous fistulas represent the

classical indication for TPN. In such patients, oral intake of food
almost invariably results in increased fistula output with associated
metabolic disturbances, dehydration, skin breakdown, and death.
Several comprehensive reviews have concluded that TPN clearly
impacts on the treatment course of the disease in patients with GI
fistulas. The following conclusions can be drawn from studies
evaluating the use of TPN in patients with enterocutaneous fistula.
First, TPN increases spontaneous closure rate of enterocutaneous
fistulas but does not markedly decrease the mortality rate in patients
with fistulas. Second, if spontaneous closure of the fistula does not
occur, patients are better prepared for operative intervention because
of the nutritional support they have received. Finally, certain fistulas
are associated with a lower rate of spontaneous closure than others
and should be treated more aggressively surgically after a defined
period of nutritional support (unless closure occurs).

120 Appropriate guidelines for the use of TPN in cancer patients

include:
a. Long-term TPN in patients with rapid progressive tumor growth
unresponsive to other therapy
b. Mildly malnourished patients undergoing surgery for a curable
cancer
c. Preoperatively administered TPN prior to surgery or other therapy
in patients with severe malnutrition
d. Patients in whom treatment toxicity precludes the use of enteral
nutrition
Answer: c, d

As a general rule, the most important factor to consider when making

decisions about the use of TPN in patients with cancer is the response
of the tumor to antineoplastic therapy. Appropriate guidelines would
include the following: Short-term TPN is indicated in severely
malnourished patients or in those in whom gastrointestinal or other
toxicities preclude adequate enteral intake for seven days or a longer
period. TPN is not indicated in well nourished or mildly malnourished
patients undergoing therapy or surgery who would be expected to be
able to resume adequate nutrition in approximately seven days.
Long-term TPN is indicated in patients in whom treatment associated
toxicities preclude the use of enteral nutrition and represent the
primary impediment to the restoration of performance status. These
patients should be expected to be responding to anti-tumor therapy.
Long-term TPN is not indicated with rapidly progressive tumor growth
which is unresponsive to such therapy.

121 Which of the following statements(s) is/are true concerning

human energy requirement?
a. In normal subjects, less than 5% of basal energy requirement is
spent on cardiac output and the work of breathing
b. Mechanical ventilation can decrease the energy expenditure for
normal respiration
c. For a 70 kg male, average resting energy consumption is almost
1500 kcal/day
d. Similar increases in energy expenditures are associated with
elective surgery and trauma or thermal injury
Answer: a, c
Basal energy requirements are measured with the subject at rest
when no external work is being done; the energy is used mainly for
transport and synthetic work within cells. A surprisingly small
percentage (< 5%) of this energy is spent on cardiac output and the
work of breathing in normal subjects. In contrast, the work of
breathing in individuals with chronic obstructive lung disease or in
patients on a ventilator may account for 15–20% of caloric
expenditure. The average resting post-absorptive 70 kg male
consumes about 1500 kcal/day. Energy needs increase as severity of
illness increases. The expenditure of kcal is only minimally increased
after elective surgery. The largest increase in energy expenditure
occurs in patients with severe multiple trauma or major thermal
injury. The average-sized adult who sustains a major burn rarely may
require more than 3500 kcal/day for maintenance.

122 Which of the following complications of TPN are appropriately

managed with the listed treatment?
a. Air embolism—place patient in reverse Trendelenburg and the left
lateral decubitus position and aspirate venous air
b. Hyperchloremic metabolic acidosis—give sodium and potassium as
acetate salts
c. Carbon dioxide retention—decrease glucose calories and replace
with fat
d. Line sepsis—intravenous antibiotics
Answer: b, c

A number of complications of TPN can occur which can be divided

into three types: mechanical, metabolic, and infectious.

123 A 55-year-old male undergoes a total abdominal colectomy.

Which of the following statement(s) is/are true concerning the
hormonal response to the surgical procedure?
a. Adrenocorticotropic hormone (ACTH) is secreted from the anterior
pituitary gland
b. ACTH stimulation results in elevation of serum cortisol levels for up
to a week after the operation
c. An increased secretion of aldosterone and ADH may contribute to
postoperative fluid retention
d. An increase in serum insulin and a fall in glucagon accelerate
hepatic glucose production and maintain gluconeogenesis
Answer: a, c

One of the earliest consequence of a surgical procedure is the rise in

levels of circulating cortisol that occur in response to a sudden
outpouring of ACTH from the anterior pituitary. The rise in ACTH
stimulates the adrenal cortex to elaborate cortisol which remains
elevated for 24–48 hours after operation. The neuroendocrine
responses to operation also modify the various mechanisms that
regulate salt and water excretion. Alterations in serum osmolarity and
tonicity of body fluids secondary to anesthesia and operative stress,
stimulate the secretion of aldosterone and ADH. Thus, the ability to
excrete a water load after elective surgical procedures is restricted,
and weight gain secondary to salt and water retention is usual
following an operation. Alterations occur in response to the endocrine
pancreas following elective operation. Insulin elaboration is
diminished and glucagon concentrations rise. The rise in glucagon and
the corresponding fall in insulin are important signals to accelerate
hepatic glucose production, and, with other hormones (epinephrine
and glucocorticoids), gluconeogenesis is maintained.

124 A number of prospective clinical trials have addressed the role of

total parenteral nutrition in the cancer patient. The results have been
somewhat conflicting. Which of the following statement(s) have been
proven correct by prospective trials?
a. Preoperative TPN is beneficial in surgical patients with severe
preoperative nutrition
b. Postoperative TPN is of value following pancreatic resection
c. Routine use of perioperative (including prior to the procedure) TPN
is of benefit in patients undergoing hepatectomy for hepatoma
d. TPN is of no benefit in patients undergoing bone marrow transplant
Answer: a, c

Numerous clinical trials have failed to yield a consensus with regard to

the efficacy of TPN in cancer patients. In 1991, a multicenter VA
cooperative trial demonstrated that preoperative TPN is of benefit in
surgical patients (many of whom had cancer) with severe preoperative
malnutrition. Another study examined the use of routine
postoperative TPN following major pancreatic resection. Patients
randomized to receive TPN starting on postoperative day 1 were
noted to have an increased incidence of intra-abdominal abscesses as
well as a tendency towards increased incidence in peritonitis and
bowel obstruction. These investigators concluded that routine use of
postoperative TPN was not indicated and may, in fact, be harmful
following pancreatic resection. In another study, however,
perioperative (starting 7 days prior to the planned procedure) TPN for
patients undergoing hepatectomy for hepatocellular carcinoma
demonstrated that this regimen statistically reduced infectious
complications compared to patients who did not receive TPN. This
was one of the few studies that demonstrated that routine TPN
(without the requirement of severe preoperative malnutrition) was of
benefit. The use of TPN in patients receiving bone marrow
transplantation has also been shown to be a valuable component of
overall care.
125 Which of the following statements concerning perioperative
nutrition is true concerning the above-described patient?
a. Since the patient’s weight had been stable with no preoperative
nutritional deficit, 5% dextrose intravenous solutions are adequate for
the initial postoperative source of nutrition
b. Preoperative immunologic status should be determined including
total peripheral lymphocyte count and delayed hypersensitivity
reaction to determine skin-test response to common antigens
c. Routine postoperative fluid administration with intravenous 5%
glucose solutions can provide the calories to meet basal energy
requirements
d. A jejunal feeding catheter should be placed at the time of surgery
for postoperative enteral feeding
Answer: a

Most patients undergoing elective operations are adequately

nourished. Unless the patient has suffered significant preoperative
malnutrition, characterized by weight loss greater than 10–15%, or
has major intraoperative or postoperative complications, solutions
containing 5% dextrose may be administered for five to seven days
before initiation of enteral nutrition, with no detrimental effect on
outcome. The usual postoperative surgical patient is given
intravenous glucose at 125 cc/hour receives about 500 kcal/day, far
less than the actual number of kcal needed to meet energy
requirements. The increased cost of feedings and potential
complications associated with intravenous nutrition cannot be
justified. Although the use of jejunal feedings in the postoperative
period may be useful in some patients, especially those undergoing
extensive gastrointestinal surgery, this technique would not appear
indicated in the patient described above.

126 The neurohormonal arm of the stress response is well defined.

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

Cytokines, which are produced at the site of injury by endothelial cells

and by diverse immune cells throughout the body, also occupy a
pivotal position in the stress response. Cytokines differ from classic
endocrine hormones in that they are produced by a variety of cell
types and in that they have the capacity to exert their tissue effects
locally via direct cell-to-cell communications in a paracrine and/or
autocrine fashion. Cytokines can stimulate the production of other
cytokines, leading to important cascades which both amplify and
diversify the effects of the proximal cytokine. Occasionally, when in
excess, cytokines act as hormones and “spill over” into the systemic
circulation and become detectable in the bloodstream.

127 Which of the following tissues contain significant collagen useful

for placing sutures to allow the prolonged tension necessary to
maintain tissue approximation?
a. Dermis
b. Intestinal submucosa
c. Muscular fascia
d. Blood vessel wall
Answer: a, b, c, d

It takes at least three weeks for collagen to undergo sufficient

remodeling and cross linking to attain moderate strength. Since most
skin sutures are removed at one to two weeks, the wound has only a
small fraction of its eventual strength and may therefore disrupt with
even modest stress. Therefore, deep sutures are placed in collagen
containing structures to maintain the prolonged tension necessary.
Dermis, intestinal submucosa, muscular fascia, tendon, ligament,
Scarpa’s fascia, and blood vessel wall represent a partial list of tissues
with high collagen content.

128 Products of platelet degranulation include:

a. Tumor necrosis factor
b. Interleukin-1
c. Transforming growth factor b
d. Platelet-derived growth factor
Answer: c, d

The initial response to injury and disruption of a blood vessel is

bleeding. The hemostatic response to this is clot formation to stop
hemorrhage. Platelet plug formation initiates the hemostatic process
along with clotting factors activated by collagen and the basement
membrane proteins exposed by the injury. Platelets then degranulate,
releasing the contents of their alpha granules and dense granules,
most notably platelet derived growth factor and transforming growth
factor b. These substances initiate chemotaxis and proliferation of
inflammatory cells, beginning the inflammatory response that will
ultimately heal the wound. Tumor necrosis factor and interleukin-1
also stimulate fibroblast proliferation, however are produced by
macrophages.
129 A patient with gross fecal contamination and peritonitis from a
ruptured sigmoid diverticulum has his midline wound left open to
heal by secondary intention. Which of the following statement(s)
describes this healing process?
a. Wounds healing in this fashion have an altered sequence of healing
compared to a primarily closed wound
b. A bed of granulation tissue forms over exposed subcutaneous
tissue
c. Epithelialization is enhanced in the face of bacterial colonization
d. The ability of a wound to form granulation tissue is dependent on
the blood supply of the tissue
Answer: b, d

Open wounds, whether they be ulcers or open surgical incisions

closing by secondary intention, heal with the same sequence of
inflammation, matrix deposition, epithelialization, and scar
maturation as in all wounds. The major difference is in the healing
incisional wound, the healing process progresses in an orderly
temporal sequence. In an open wound, the healing events are
spatially separated. In the healing wound, a bed of granulation tissue
forms over the exposed subcutaneous tissue. Granulation tissue is
composed of new capillaries, proliferating fibroblasts, an immature
matrix of collagen, proteoglycans, substrate adhesion molecules, and
acute and chronic inflammatory cells. Granulation tissue is the
cobblestone pink surface of the healthy new tissue in an open wound.
The ability of an open wound to form granulation tissue is governed
by the blood supply to the tissue and the relative absence of
devitalized tissue and bacteria. Epithelialization is therefore enhanced
by limiting bacterial growth which presumably interferes via bacterial
and phagocytic cell products such as proteases, collagenases,
elastases, and other enzymes.

130 Which of the following factors can be associated with impaired

wound healing?
a. Chemotherapy
b. Chronic steroid use
c. Peripheral vascular disease
d. Radiation therapy
e. Diabetes mellitus
Answer: a, b, c, d, e

Bone marrow suppression, a common consequence of

chemotherapy, is detrimental to wound healing. Quantitative and
qualitative lymphocyte and monocyte deficiency impairs cellular
proliferation in the inflammatory phase of wound healing. Any
chemotherapeutic agent that suppresses the bone marrow will impair
healing. Glucocorticoids inhibit wound healing based on their
anti-inflammatory and immunosuppressive effects. The
anti-inflammatory effect of steroids is, in part, the result of inhibiting
arachidonic acid metabolism by impairing macrophage migration, and
by altering neutrophil function. Glucocorticoids also inhibit the
synthesis of procollagen by fibroblasts, thus delaying wound
contraction. Radiation injury leads to arteriolar fibrosis and impaired
oxygen delivery. In addition, there is progressive obliteration of blood
vessels in the radiated area over time. Radiation also causes
intranuclear and cytoplasmic damage to fibroblasts, and this appears
to limit their proliferative potential. Diabetes mellitus is often
associated with decreased healing of open wounds and increased
susceptibility of infection. Many factors contribute to poor healing in
diabetic patients and most of them reflect local wound ischemia.
However, healing is not impaired in a normally perfused area in a
well-controlled diabetic. Peripheral arterial occlusive disease
secondary to atherosclerosis can be a primary cause of impaired
healing, and may be also a cofactor with other conditions.

131 Which of the following cells or blood elements play a role in the
initial phases of wound healing?
a. Polymorphonuclear leukocytes (PMNs)
b. Platelets
c. Monocytes
d. Lymphocytes
Answer: a, b, c, d

Shortly after the initial injury, the wound is full of debris which is
cleared over the next several days by recruited and activated
phagocytic cells. PMNs begin to arrive immediately, reaching large
numbers within 24 hours. The PMNs are followed by macrophages
which appear in wounds in significant numbers within two to three
days. Macrophages are mononuclear phagocytic cells derived from
circulating monocytes or resident tissue macrophages. They complete
the process of removing all material not necessary for the ensuing
steps of wound healing. Lymphocytes also appear in wounds in small
numbers during the inflammatory response. The role of lymphocytes
in the wound healing process remains to be clarified, but they are
thought to be more related to the chronic inflammatory processes
than the initial response to wounding. Platelets are anuclear discoid
blood elements derived from bone marrow megakarocytes which play
a role in the initial hemostatic process as well as releasing
chemotactic factors and factors leading to fibroblast proliferation.

132 Which of the following surgical techniques lead to improved

wound healing?
a. Atraumatic handling of tissue
b. Approximation of underlying fatty tissue to obliterate dead space
c. Protecting the wound from water for at least one week
d. Meticulous hemostasis
Answer: a, d

There are numerous practical implications for the care of wounds and
surgical incisions. Meticulous hemostasis reduces the inflammation of
phagocytosis necessary to clear the wound of blood. Atraumatic
handling of tissue decreases the load of necrotic or nonviable cells at
the wound margin. Deep sutures are best placed only into collagen
laden structures that will hold tension, i.e., fascia and dermis. These
tissues have a tensile strength to hold sutures under tension. Fat does
not contain collagen and will not hold tension. Therefore, fatty tissue
should not be sutured as a separate layer. Given that epithelialization
of an incision is normally complete within 24–48 hours, there is no
reason to protect the incision from water beyond this time period.
Allowing the patient to wash or shower one or two days after surgery
actually serves useful purpose in debriding the wound.

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

clinical management of an open wound?
a. A wet-to-dry dressing is the most optimal form of wound
management
b. A moist occlusive dressing promotes epithelialization and reduces
pain
c. The protein rich plasma exudate covering the open wound
facilitates healing
d. Irrigation of the wound disrupts epithelialization therefore
inhibiting the healing process
Answer: b

Epithelialization is more rapid under moist conditions than dry

conditions. Without dressings, a superficial wound, or one with
minimal devitalized tissue forms a scab or crust, meaning that the
blood and serum will coagulate, dry, and form a protective moisture
barrier over the open wound. If a wound is kept moist with an
occlusive dressing, then epithelial migration is optimized. In addition,
the pain of an open wound is dramatically reduced under an occlusive
dressing. The traditional wet-to-dry dressing if truly left to dry, simply
produces desiccation and necrosis of the surface layer of the wound
which delays epithelialization. Although wet-to-dry dressings can be
effective for debridement of wound exudate, they are generally less
desirable than a moist healing environment combined with effective
cleaning of the wound (i.e. water irrigation). Any open wound will leak
plasma. With more inflammation, the plasma capillary permeability is
further increased. This exudate of serum proteins and inflammatory
cells serves as a rich culture medium. This, in turn, will continue to
cycle bacterial proliferation and lead to further exudate formation.
The net result of this cycle is delayed or absent wound healing. In
addition, the edema that results from capillary dysfunction, increases
the distance for diffusion from oxygen and nutrient sources to their
metabolic targets.

134 Which of the following statement(s) is/are correct concerning the

management of an open wound?
a. Frequent surgical debridement is usually necessary
b. Water irrigation can effectively debride most wounds
c. Hydrogen peroxide is particularly useful in the management of
open wounds
d. A number of the newer dressing products have clearly been shown
to promote wound healing compared to simple moist occlusive
dressing
Answer: b

Although there are numerous dressing products commercially

available at present, no treatment has been demonstrated to improve
healing beyond that of standard treatment which adheres to basic
principles. In the absence of large amounts of necrotic tissue, wound
debridement does not need to be accomplished surgically. Simple
water irrigation either with whirlpool or by water from a hand held
shower spray can generate enough power to effectively debride most
wounds. Frequent moist dressing changes can accomplish this as well,
and in some cases, occlusive absorptive dressings can generate
enough tissue proteases to effectively degrade proteins which the
absorptive dressings remove. Deeper portions of a wound may
accumulate exudate and bacteria. In such cases, water irrigation may
be particularly useful. Commonly used agents such as hydrogen
peroxide actually may be harmful to normal tissue and are weak
oxidants and do a poor job of debriding. Enzymatic debriding agents
can be effective when used properly. Most of the newer dressing
products have been designed to be more absorptive and achieve
moist healing without infection from excess exudate. However, it
must be emphasized that as long as moist healing is achieved, there
has been no evidence that one product is better than another.

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

proliferative phase of wound healing?
a. The macrophage is the predominant cell type
b. The pink or purple-red appearance of a wound is due to ingrowth
and proliferation of endothelial cells
c. Collagen, the dominant structural molecule of the wound matrix,
contains two unique amino acids, hydroxyproline and hydroxylysine
d. The predominant collagen type in a scar is type 3
Answer: b, c
The proliferative phase of wound healing begins with the formation of
a provisional matrix of fibrin and fibronectin as part of the initial clot
formation. Initially, the provisional matrix is populated by
macrophages; however, by day three fibroblasts appear in the
fibronectin-fibrin framework and initiate collagen synthesis.
Fibroblasts proliferate in response to growth factors become the
dominant cell type during this phase. Growth factors produced by
macrophages simultaneously induce angiogenesis which results in the
ingrowth and proliferation of endothelial cells, forming new
capillaries. This neovascularity is visible through the epithelium and
gives the wound a pink or purple-red appearance.
Collagen is the dominant structural molecule in the wound matrix and
in the final scar. Collagen is synthesized into an organized cable-like
network in a multi-step process with both intra- and intercellular
components. The collagen molecule has quantities of two unique
amino acids, hydroxyproline and hydroxylysine. The hydroxylization
processes which form these amino acids require ascorbic acid
(vitamin C) and is necessary for the subsequent stabilization and cross
linkage of collagen. The principal collagen type scar is type 1, with
lesser amounts of type 3 collagen also present.

136 Which of the following statement(s) is/are true about the role of
macrophages in the wound healing process?
a. Macrophages are the dominant cell type during the inflammatory
phase of wound healing
b. Macrophages are not essential for wound healing
c. The macrophage role in wound healing is limited to phagocytosis
d. Macrophages are a source of a number of humoral factors
essential for wound healing
Answer: a, d

Within three or four days after injury, macrophages become the

dominant cell type in the inflammatory phase of wound healing. The
role of macrophages is not limited only to phagocytosis. In addition,
macrophages are the source of more than 30 different growth factors
and cytokines. These growth factors induce fibroblast proliferation,
endothelial cell proliferation (angiogenesis), extracellular matrix
production, and recruit and activate additional macrophages. The
result is the induction of a wound healing amplification cycle as
growth factors recruit macrophages and elicit additional growth factor
release. Experimental studies in which antibodies, which either
destroy PMNs or block certain aspects of their function, have shown
that wounds heal normally, but that healing is significantly impaired
without functional macrophages. These studies confirm the dominant
role of the macrophage and the inflammatory phase of wound
healing.
137 Which of the following statement(s) is/are true concerning the
role of antibiotics in wound care?
a. Systemic antibiotics are indicated for all open wounds
b. Bacterial resistance can occur with systemic but not topical
antibiotics
c. An indication for systemic antibiotic administration is a granulation
tissue bacterial count in excess of greater than 105 organisms/gram
of tissue on quantitative analysis
d. Silver sulfadiazine is useful only for the management of burns
Answer: c

The role of antibiotics in wound care is controversial. All open wounds

are colonized with bacteria. Only when surrounding tissue is invaded
(cellulitis) are systemic antibiotics clearly indicated. Antibiotics may
also be useful in other situations such as when granulation tissue has
a high bacterial count (> 105 organisms/gram tissue), or in the case of
reduced resistance to bacteria such as in a diabetic foot ulcer. The
routine use of systemic antibiotics for chronic wounds should be
avoided to reduce the development of resistant bacterial strains
within the wound. Topical ointments are frequently used and can be
useful. The topical vehicle may help keep the wound moist and the
bacterial count in the wound may be lowered as the result. However,
as with most antibiotics, resistant organisms quickly emerge. Silver
sulfadiazine, frequently used for burn care, is also useful for chronic
wounds. Its broad spectrum of activity, lack of relevant drug-resistant
plasmids in bacteria, and its low cost make it a good choice.

138 Which of the following statement(s) is/are true concerning wound

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

Wound contraction is an important event which contrasts healing

open wounds and closed incisions. When open wounds contract, the
surrounding skin is pulled over the open wound to reduce its size.
This can occur much faster than epithelialization. As opposed to other
animals, human skin does not have a significant degree of mobility in
most sites and specifically on the lower leg, the skin is tightly adherent
and less elastic. Therefore, although contraction may account for 90%
of reduction of wound size on the perineum, it accounts for, at most,
30–40% of healing of a lower leg ulcer. All healing wounds generate a
strong contractile force. When this force is exerted across a joint, it
may result in scar contracture which may limit the functional range of
motion. At the cellular level, the force which drives wound contraction
comes from fibroblasts. Fibroblasts, like muscle cells, contain actin
microfilaments. When these filaments increase in number, the cells
take a morphologic appearance of myofibroblasts. Myofibroblasts are
seen in an increased number in contracting wounds and are felt to
play an active role in the process of wound contraction.

139 There are a multitude of various dressings available. Which of the

following statement(s) is/are true concerning options for surgical
dressings?
a. Hydrocolloids, such as karaya compounds, offer the primary
advantage of increased absorptive ability
b. Films, such as Op-site, provide a water impermeable environment
to achieve a dry wound
c. Impregnates are fine gauze impregnated with a variety of
substances such as antibiotics or moisturizing agents that adhere
tightly to the wound and do not require a secondary dressing
d. Absorptive powders and paste are highly useful in debriding
necrotic and fibrous material from wounds and absorbing wound
serum
Answer: a, d

Although the simplest dressing of gauze and tape combined with the
use of antibacterial ointment can achieve moist wound healing in
most patients. A multitude of other products are available. These can
be classified into films, foams, hydrocolloids, hydrogels, and
absorptive powders. Films are semipermeable to water, generally
made of polyurethane, and are nonabsorptive. They are useful to
achieve a moist wound healing environment over a minimally
exudative wound such as split thickness skin graft donor sites. The
hydrocolloids deserve special mention because they have achieved
widespread use. These agents contain hydrophilic materials such as
karaya or carboxymethyl cellulose with an adhesive material and are
covered by a semipermeable polyurethane film. The material adheres
to the skin surrounding the wound, is highly absorptive, and achieves
a moist healing environment. Impregnants are generally fine mesh
gauze impregnated with either moisturizing, antibacterial, or
bactericidal compounds. They are generally not adherent and require
a secondary dressing. They do promote reepithelialization and have a
antiinfective effect when combined with antibacterial or bactericidal
agents. A variety of absorptive powders and pastes are available
which consist of starch copolymers or colloidal hydrophilic particles.
These agents have high absorbency for tissue wound fluid and
debride necrotic and fibrous material from the wound.

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

remodeling phase of wound healing?
a. Total collagen content increases steadily through this phase
b. The normal adult ratio of collagen is approximately 4:1 of type I to
type III collagen.
c. Eventually a scar will achieve the strength of unwounded skin
d. The proteoglycans are responsible for the ground substance of the
extracellular matrix
Answer: b, d

The transition from the proliferative phase to the remodeling phase of

wound healing is defined by reaching collagen equilibrium. Collagen
accumulation within the wound becomes maximal by two to three
weeks after wounding. Although supramaximal rates of synthesis and
degradation continue throughout remodeling, there is no further
change in total collagen content. During the initial phase of wound
healing, there is a relative abundance of type III collagen in the
wound. With remodeling, the normal adult ratio of 4:1 (type I to type
III) collagen is restored. The other important component of the
extracellular matrix is the ground substance or proteoglycans. These
substances are composed of a protein background with long
hydrophilic carbohydrate side chains. The hydrophilic nature of these
molecules accounts for much of the water content of scar.
Scars never achieve the degree of order advanced by collagen in
normal skin or tendons, but they do increase in strength for six
months or more, eventually reaching 70% of the strength of
unwounded skin.

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

pharmacologic agents used to accelerate wound healing?
a. A number of these agents are now currently approved for use in
this country
b. PDGF (platelet-derived growth factor) promotes fibroblast
proliferation, chemotaxis, and collagenase synthesis
c. PDGF has been demonstrated in a number of clinical trials to
promote healing in chronic wounds
d. Growth hormone functions by promoting fibroblast proliferation
and collagen synthesis
Answer: b, c

Currently there are no approved clinical agents that accelerate normal

healing. Although a number of clinical trials are in progress, no agents
are currently approved. PDGF (platelet-derived growth factor)
accelerates wound healing by promoting fibroblast proliferation and
chemotaxis and collagenase synthesis. Clinical trials have
demonstrated that PDGF has accelerated healing in patients with
chronic wounds such as pressure sores and diabetic ulcers. Growth
hormone has been successfully used in some situations to reverse the
catabolic effect of severe injuries. Wound healing is fundamentally an
anabolic event, and in the setting of a severe burn, growth hormone
administration significantly accelerates donor site healing,
presumably due to its effects in minimizing catabolism.

142 Which of the following statement(s) describe the effects of aging

on wound healing?
a. A finer, more cosmetic scar might be expected
b. In vitro studies demonstrate decreased proliferative potential of
fibroblasts and epithelial cells
c. Skin sutures should be left in for a longer period of time
d. Wound infection occurs more frequently in elderly patients due to
diminished ability to fight infection
Answer: a, b, c

There are important age-dependent aspects of wound healing. The

elderly heal more slowly and with less scarring. There is a gradual
attenuation of the inflammatory response with age, and decreased
wound healing is one of the consequences. In vitro studies have
documented an age-dependent decrease in proliferative potential of
fibroblasts and epithelial cells. Clinically this will account for the
formation of finer scars and improved cosmetic appearance in the
elderly. Sutures should be left in place longer to allow for the slow
regain of tensile strength in the aged. This can also be done without
concern for formation of suture marks as slower epithelialization
occurs along the sutures. There is no evidence to suggest that wound
infections occur more commonly in elderly patients.

143 Reconstitution of the epithelial barrier (epithelialization) begins

within hours of the initial injury. Which of the following statement(s)
is/are true concerning the process of epithelialization?
a. Bacteria, protein exudate, and necrotic tissue all will compromise
this process
b. Epithelial cells exhibit contact proliferation
c. Epithelialization occurs only from the margins of the wound
d. Visible scarring can occur only when the injury extends deeper than
the superficial dermis
Answer: a, d

The initial step of epithelialization involves epithelial cells from the

basal layer of the wound edge flattening and migrating across the
wound, completing wound coverage within 24–48 hours in a co-opted
surgical wound. Epithelial cells exhibit contact inhibition. That is, they
will continue to migrate across an appropriate bed until a single
continuous layer is formed. Epithelial cell migration occurs by a
process in which the epithelial cells send out pseudopods, attaching
to the underlying extracellular matrix by integrin receptors. Bacteria,
large amounts of protein exudate from leaky capillaries, and necrotic
tissue all compromise this process delaying epithelialization. In the
case of open wounds, epithelialization results from migration of
epithelial cells from remaining dermal appendages, sweat glands, and
hair follicles, if the dermis is not completely destroyed. In a full
thickness injury, the entire dermis is destroyed or removed.
Epithelialization therefore occurs only at the margins of a wound, at a
dermal rate of 1–2 mm/day.
Visible scarring occurs only when the injury extends deeper than the
superficial dermis. Superficial abrasions and burns usually heal
without scar, while deeper abrasions and burns may scar significantly.
Whenever the dermis is incised, a scar will form.

144 Scar formation is part of the normal healing process following

injury. Which of the following tissues has the ability to heal without
scar formation?
a. Liver
b. Skin
c. Bone
d. Muscle
Answer: c

Every tissue in the body undergoes reparative processes after injury.

Bone has the unique ability to heal without scar and liver has the
potential to regenerate parenchyma, the only organ that has
maintained that ability in the adult human. Although liver does
regenerate, it often heals with scar (cirrhosis) as well. With these
exceptions, all other mature human tissues heal with scar.

145 Which of the following factors have been demonstrated to

promote wound healing in normal individuals?
a. Vitamin A supplementation
b. Vitamin C supplementation
c. Vitamin E application to the wound
d. Zinc supplementation
e. None of the above
Answer: e

Several important systemic factors or conditions influence wound

healing. Interestingly, there are no known systemic conditions that
lead to enhanced or more rapid wound healing. Overall nutrition as
well as adequate vitamins play an important role in wound healing.
Vitamin A is involved in the stimulation of fibroplasia, collagen cross-
linking, and epithelialization. Although there is no conclusive evidence
in humans, vitamin A may be useful clinically for steroid-dependent
patients who have problematic wounds or who are undergoing
extensive surgical procedures. Vitamin C is a necessary cofactor in
hydroxylization of lysine and proline in collagen synthesis and cross-
linkage. The utility of vitamin C supplementation in patients who
otherwise take in a normal diet has not been established. Vitamin E is
applied to wounds and incisions empirically by many patients. The
evidence to support this practice is entirely anecdotal. In fact, large
doses of vitamin E have been found to inhibit wound healing. Zinc and
copper are also important cofactors for many enzyme systems that
are important to wound healing. Deficiency states are seen with
parenteral nutrition but are rare and readily recognized and treated
with supplements. Overall, vitamin and mineral deficiency states are
extremely rare in the absence of parenteral nutrition or other
extreme dietary restrictions. There is no evidence to support the
concept that supranormal provision of these factors enhance wound
healing in normal patients.

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

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

True keloids are uncommon and occur predominantly in dark skinned

people with a genetic predisposition for keloid formation. In most
cases, the gene appears to be transmitted as an autosomal dominant
pattern. The primary difference between a keloid and a hypertrophic
scar is that a keloid extends beyond the boundary of the original
tissue injury. It behaves as a tumor and extends into or invades the
normal surrounding tissue creating a scar that is larger than the
original wound. Histologically, keloids and hypertrophic scars are
similar. Both contain an overabundance of collagen. Although the
absolute number of fibroblasts is not increased, the production of
collagen continually out paces the activity of collagenase, resulting in a
scar of ever increasing dimensions. Hypertrophic scars respect the
boundaries of the original injury and do not extend into normal
unwounded tissue. There is less of a genetic predisposition, but
hypertrophic scars also occur more frequently in Orientals and the
Black population. They are often seen on the upper torso and across
flexor surfaces. Some improvement in a keloid can be obtained with
excision followed by intra-lesional steroid injection. However, the
resulting scar is unpredictable and potentially worse. Reexcision and
closure should, however, be considered for hypertrophic scars, if the
condition of closure can be improved. This is especially pertinent for
wounds that originally healed by secondary intention or that are
complicated by infection. Keloids typically develop several months
after the injury and rarely, if ever, subside. Hypertrophic scars usually
develop within the first month after wounding and often subside
gradually.

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

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

After wounding, there is transient vasoconstriction mediated by

catecholamines, thromboxane, and prostaglandin F2 (PGF2a). This
period of vasoconstriction lasts for only five to ten minutes. Once a
clot has been formed and active bleeding has stopped, vasodilatation
occurs in an around the wound. Vasodilatation increases local blood
flow to the wounded area, supplying the cells and substrate necessary
for further wound repair. The vascular endothelial cells also deform,
increasing vascular permeability. The vasodilatation and increased
endothelial permeability is mediated by histamine, PGE2, and
prostacyclin as well as growth factor VEGF (vascular endothelial cell
growth factor). These vasodilatory substances are released by injured
endothelial cells and mast cells and enhance the egress of cells and
substrate into the wound and tissue.

148 Which of the following statement(s) concerning laboratory studies

used in monitoring a patient with intravenous heparinization is/are
correct?
a. The platelet count should be followed because of the risk of
heparin-associated thrombocytopenia
b. The prothrombin time should be observed if prolonged treatment
is necessary
c. The activated partial thromboplastin time (aPTT) should be
maintained at approximately 1.5 times normal
d. The serum creatinine should be measured daily to allow
adjustments in dose based on renal function
Answer: a, c

In monitoring the effect of heparin, an activated partial

thromboplastin time (aPTT) of 1.5 control or a thrombin clotting time
(TCT) of 2 times control reflects adequate anticoagulation. The
prothrombin time remains normal. Heparin-associated
thrombocytopenia from an immune mechanism is a potential
complication of the use of this anticoagulant. Therefore any patient
undergoing heparin therapy should have a platelet count determined
every other day after the fourth day of therapy or earlier if he or she is
known to have been exposed to heparin in the past. Heparin is not
excreted through the kidneys or the liver but is cleared through the
reticuloendothelial system. Therefore the dose of heparin need not be
adjusted in cases of liver or renal dysfunction.

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

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

Heparin-associated thrombocytopenia occurs in 0.6% to 30% of

patients who receive heparin, although severe thrombocytopenia
(platelet counts less than 100,000) is seen in fewer than 10% of
patients treated with heparin. It is caused by a plasma factor, most
likely a heparin-dependent platelet antibody, that causes aggregation
of platelets when exposed to heparin. Activation of platelets in this
setting results in thrombocytopenia, thrombosis and embolic
episodes, which can lead to death. Both bovine and porcine heparin
have been associated with this syndrome, which usually begins 5 to
15 days after initiating heparin therapy. Even trivial exposure with
heparin such as coating on pulmonary artery catheters or low rate
infusion into arterial catheters may cause this syndrome.

150 Antithrombin III deficiency is a commonly observed

hypercoaguable state. Which of the following statement(s) is/are true
concerning this condition?
a. A patient with this deficiency usually presents with thrombosis
while on heparin or exhibits an inability to become adequately
anticoagulated with heparin
b. This deficiency may be either congenital or acquired
c. Thrombotic episodes are related to predisposing events such as
operations, childbirth, and infections
d. Treatment involves acutely the administration of fresh frozen
plasma followed by long-term treatment with Coumadin
Answer: a, b, c, d

Antithrombin III deficiency accounts for about 2% of venous

thrombotic event. This deficiency has been described in patients with
pulmonary embolism, mesenteric venous thrombosis, lower extremity
venous thrombosis, arterial thrombosis, and dialysis fistula failure.
Antithrombin III is a serine protease inhibitor of thrombin and factors
Xa, IXa and XIa. Because one of the main actions of heparin is to
potentiate the anticoagulant effects of antithrombin III, a patient with
this deficiency usually presents with thrombosis while on heparin or
exhibits the inability to become adequately anticoagulated with
heparin. This deficiency may be either congenital (1n2000–5000
births) or acquired. Acquired defects occur with inadequate
production, as in liver disease, malignancy, nephrotic syndrome,
disseminated intervascular coagulation, malnutrition, or increased
protein catabolism. Thrombotic episodes are related to predisposing
events such as operations, childbirth, and infections. Once the
diagnosis of antithrombin III deficiency is established, fresh frozen
plasma should be administered followed by long-term treatment with
Coumadin.

151 Mini-dose heparin has been shown to be useful in the prophylaxis

of postoperative venous thrombosis. Mechanism(s) by which low-dose
heparin is/are thought to protect against venous thrombosis include:
a. Enhancement of antithrombin III activity
b. A decrease in thrombin availability
c. Inhibition of platelet aggregation and subsequent platelet release
action
d. A mild prolongation of activated partial thromboplastin time
Answer: a, b, c

Low-dose heparin is thought to protect against venous thrombosis

through three different mechanisms. First, antithrombin III activity
with its inhibition of activated Factor X is enhanced by only trace
amounts of heparin; second, there is a decrease in thrombin
availability that prevents its activation and thus its fibrin-stabilizing
effect; and third, small doses of heparin may inhibit the second wave
of platelet aggregation and subsequent platelet release reaction. The
standard doses of heparin administered (5000 units bid) does not
affect aPTT.

152 Tests of coagulation are used to monitor anticoagulation

treatment and detect intrinsic abnormalities in coagulation. Which of
the following statement(s) is/are true concerning coagulation tests?
a. Prothrombin time (PT) measures both the intrinsic and extrinsic
clotting pathways and fibrinogen
b. Activated partial thromboplastin time (aPTT) can be used to
monitor both oral anticoagulation with Warfarin and intravenous
anticoagulation with heparin
c. Thrombin clotting time (TCT) is a measurement of the time it takes
for exogenously administered thrombin to turn plasma fibrinogen
into fibrin clot
d. Whole blood activated clotting time (ACT) is a measurement of the
ability of whole blood to clot and is used to monitor heparin levels
intraoperatively during cardiovascular and peripheral vascular
operations
Answer: a, c, d

Coagulation tests include prothrombin time (PT), which measures the

intrinsic and extrinsic pathways of fibrinogen production and is the
most common method for measuring a level of oral anticoagulant
therapy. The activated partial thromboplastin time (aPTT) identifies
the abnormalities of the contact and intrinsic phases of coagulation.
Values of aPTT have variably been shown to correlate with heparin
dosages and serum heparin levels and are therefore most commonly
used in monitoring heparin therapy. It is of no value in long-term
management of patients on oral Warfarin therapy. Thrombin clotting
time (TCT) is the measure of the time it takes for exogenously
administered thrombin to turn plasma fibrinogen into fibrin clot. It is
extremely sensitive to levels of heparin and is an excellent measure of
measuring the level of heparin-induced anticoagulation. The beauty of
the TCT is that it is not specific for any disease condition; thus it may
be used to differentiate factor deficiencies from the presence of
heparin, or to separate lupus anticoagulant from abnormalities in
fibrinogen levels. The whole blood activated clotting time (ACT) is a
measurement of the ability of whole blood to clot, and as such, is an
available technique for monitoring heparin levels intraoperatively. The
ACT responds in a linear fashion to increasing heparin dosage and
correlates well with the observed clinical anticoagulation. Adequate
anticoagulation for extracorporeal circulation is defined as an ACT of
480 seconds or more while for peripheral vascular applications, values
of 250 seconds or greater are considered appropriate.

153 Thrombolytic therapy has become a useful adjunct in the

management of peripheral arterial occlusion. In this setting, direct
intraarterial administration rather than intravenous has been
advocated to decrease the risk of systemic bleeding. Which of the
following true statement(s) concerning the use of thrombolytic agents
for arterial occlusion is/are true?
a. A standard technique involves infusing high-dose urokinase, 4000
units per minute for 1–2 hours, directly into the clot by a catheter
embedded in the thrombus
b. If progress is made, further fibrinolytic therapy is given at 1000 to
2000 units per minute until clot lysis has occurred
c. The usual infusion time by the above-stated technique is usually in
excess of 24 hours
d. Successful clot lysis occurs more frequently in arterial graft
occlusions than native arterial occlusions
e. The use of intraoperative thrombolytic therapy may be indicated for
situations where complete clot evacuation cannot be accomplished
surgically
Answer: a, b, e

The most popular method for intraarterial thrombolytic therapy for

arterial occlusion involves passing a guidewire through the thrombus
with arteriographic guidance and then infusing high-dose urokinase,
4000 units per minute for 1–2 hours, directly into the clot. If progress
is made, further fibrinolytic therapy is given at 1000 to 2000 units per
minute for a 6–12 hour period or until clot lysis has occurred. Using
this technique, mean infusion time in a recent study was found to be
18 hours and the incidence of bleeding complications was significantly
lessened. Selective intraarterial infusion of urokinase was associated
with complete clot resolution in 77% of native arterial occlusions
versus only 41% with arterial graft occlusion. After thrombolytic
therapy has reopened an occluded vessel or graft, radiologic or
surgical correction of the lesion responsible for the thrombosis in the
first place must be addressed for any hope of long-term success. The
use of intraoperative thrombolytic therapy is advocated in those
situations where complete clot resolution cannot be accomplished
(such as following balloon embolectomy for acute arterial occlusion)
or when distal vasculative is occluded and precludes appropriate
inflow patency.

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

hemophilia A?
a. Hemophilia A is inherited as a sex-linked recessive deficiency of
factor VIII
b. A positive family history for bleeding disorders present in all
patients
c. Laboratory tests reveal a prolongation of aPTT, prothrombin time
(PT), thrombin clotting time and platelet aggregation
d. Spontaneous bleeding is unusual with factor VIII levels greater than
10% of normal
Answer: a, d

Hemophilia A is inherited as a sex-linked recessive deficiency of factor

VIII although 0% of cases are secondary to spontaneous mutation. The
incidence of this abnormality is approximately 1/10,000 births.
Laboratory screening tests usually reveal a prolongation of an aPTT
but normal prothrombin time (PT), thrombin clotting time (TCT) and
platelet aggregation testing. The minimum level of VIII required for
hemostasis is 30% for minor bleeding, whereas spontaneous bleeding
is unusual with factor levels greater than 5 to 10% of normal. In
severe genetic deficiency states however, factor levels as low as 1%
have been noted and patients are at risk for spontaneous bleeding.

155 Fibrinolytic therapy is based on activation of plasminogen, the

inactive proteolytic enzyme of plasma that binds to fibrin during the
formation of thrombosis. Activation of plasminogen to plasmin results
in selective thrombolysis at the fibrin clot surface. Which of the
following statement(s) is/are true concerning agents used in
thrombolytic therapy?
a. Streptokinase is a bacterial protein which is antigenic in humans,
resulting in allergic reactions in up to l5% of cases
b. Tissue plasminogen activator acts directly on plasmin without an
intermediate drug–plasmin complex
c. The half-life of urokinase, streptokinase, and TPA all exceed 30
minutes
d. Streptokinase is significantly cheaper than urokinase or TPA
Answer: a, b, d

Streptokinase is a bacterial protein produced by group C b-hemolytic

streptococci. It is therefore antigenic in humans and can be associated
with allergic reaction in between 2 and 18% of cases. In addition an
unusual serum sickness has been reported with streptokinase.
Neither urokinase or TPA which is now manufactured with
recombinant DNA technology are either associated with allergic side
effects or antigenicity. Streptokinase acts through a streptokinase-
plasmin complex, whereas urokinase and TPA act directly on plasmin
without intermediate drug plasmin complex. The level of the lytic
state is greatest with streptokinase, intermediate with urokinase, and
least with TPA with the half-lives ranging all less than 1/2 hour in
duration. Although the relative efficacy of the three agents has been
compared in a number of studies, there appears to be no significant
benefit of one agent over the other. Streptokinase however, is
markedly less expensive than either urokinase or TPA.

156 Von Willebrand’s disease is a common, congenital bleeding

disorder. Which of the following statement(s) is/are true concerning
Von Willebrand’s disease?
a. As in hemophilia, it is much more common in men
b. A history of spontaneous bleeding is common
c. Screening laboratory tests will include a prolonged aPTT with a
normal prothrombin time
d. Pre-treatment for elective surgery require administration of
cryoprecipitate to achieve levels of 23–50% of normal
Answer: c, d
Von Willebrand’s factor is an adhesive protein that mediates platelet
adhesion to collagen. In addition, it protects and prevents the rapid
removal of factor VIII from blood. The classical deficiency state, Von
Willebrand’s disease, is caused by reduction of factor VIII activity
(although not as great as Hemophilia A) and the Von Willebrand
factor. Clinical manifestations include epistaxis, gingival bleeding,
menorrhagia, rare joint or muscle bleeding, and subcutaneous
bleeding. Spontaneous bleeding is not as common as in classic
Hemophilia A. The syndrome is transmitted as both autosomal
dominant (heterozygous) and autosomal recessive disease
(homozygous) traits. Therefore there is no sex predilection. Screening
laboratory tests include a prolonged aPTT with a normal prothrombin
time. In addition, because of the importance of this factor in platelet
adhesion, patients display a prolonged bleeding time and have
decreased level of factor VIII activity, decreased immunoreactive levels
of Von Willebrand’s antigen, and abnormal platelet aggregation
responses to ristocetin. The most reliable source of Von Willebrand’s
factor is cryoprecipitate.

157 External pneumatic compression has been advocated for the

prevention of deep venous thrombosis during operative procedures.
Which of the following statement(s) concerning the use of external
pneumatic compression devices is/are true?
a. Intermittent pneumatic compression is as effective as low-dose
heparin in prevention of venous thrombosis
b. These devices function by compressing the lower extremities
therefore augmenting venous return
c. Pneumatic compression devices may also exhibit their
antithrombotic effect through stimulating local and systemic
fibrinolysis
d. The length of time that intermittent pneumatic compression should
be used includes through the operation and for at least several days
in the postoperative period
Answer: b, c, d

In many well-controlled studies of venous prophylaxis, intermittent

pneumatic compression has been found to be as effective as low-dose
heparin therapy. In addition to augmentation of venous return with
these devices, local and systemic fibrinolysis appears to be stimulated.
Fibrinolytic activities are usually reduced for a 7–10 day period after
an operation. Studies have demonstrated that the pneumatic-
compression devices may exhibit their antithrombotic effect through
prevention of this fibrinolytic shutdown even when applied to the
upper extremity. The length of time that intermittent pneumatic
compression should be used has not been adequately determined
but most data suggest that devices should be used through the
operation and for at least five days in the face or prolonged
immobilization.

158 The standard management oral anticoagulant therapy for chronic

treatment of venous thromboembolism is with the drug warfarin.
Which of the following statement(s) is/are true concerning the
administration of warfarin?
a. An important complication of warfarin therapy is skin necrosis in
patients with protein C deficiency
b. Warfarin interferes with vitamin K dependent clotting factors II, VII,
IX, X
c. For effective anticoagulation the prothrombin time (PT) should be
kept at 2 control
d. It is recommended that warfarin be continued for at least one year
after initial episode of deep venous thrombosis
Answer: a, b

Warfarin interferes with the vitamin K dependent clotting factors II,

VII, IX and X, protein C, and protein S. An important complication of
warfarin is skin necrosis with patients both with and without protein C
deficiency. This syndrome usually involves full thickness skin slough
over fatty areas such as the breasts and buttocks. Warfarin therapy
should be monitored using the one stage prothrombin time (PT). The
PT should be kept at 1.3 to 1.4 control for effective anticoagulation. At
higher levels, there is a five-fold increase in the frequency of bleeding
complications. Two major complications of Warfarin therapy include
recurrent thrombosis and bleeding. It is recommended that Warfarin
be continued four months after an initial episode of deep venous
thrombosis. Between ten weeks and four to six months after deep
vein thrombosis, there is a recurrent thrombosis rate of 8.3 episodes
per 1000 patient months. Between four months and three years,
recurrences fall to four episodes per 1000 patient-months. At four
months, the risks of bleeding complications matches and exceeds the
benefit from anticoagulant therapy and thus is the basis for
discontinuing warfarin administration at this time.

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

management of a patient with hemophilia A undergoing an elective
surgical operation?
a. Concentrates of factor VIII should be given several days prior to
elective surgery
b. The half-life of factor VIII concentrates is less than 24 hours
c. A dose of 40–50 IU/kg of factor VIII concentrate should be given
prior to the planned surgical procedure
d. Factor VIII concentration administration should be given for the first
24 hours after surgery but may then be stopped if no abnormal
bleeding has been observed
e. A new recombinant preparation of factor VIII offers the advantage
of being virus-free
Answer: b, c, e

Although the half-life of factor VIII is 2.9 days in normal individuals,

the half-life of factor VIII concentrates is 9 to l8 hours. Levels of 80% to
100% of normal should be obtained for surgical bleeding or
life-threatening hemorrhage. A dose of 40 to 50 IU/kg of factor VIII
should be given with half of this dose then administered every twelve
hours. After surgery, transfusion of factor VIII concentrates should be
continued for at least ten days. Unfortunately, past use of
concentrates of factor VIII obtained from donors has led to a high
incidence of HIV infection in the hemophilia population. A new
recombinant preparation of factor VIII offers the advantage of being
virus-free.

160 Transfusions of blood products can be associated with a number

of complications including immediate and delayed hemolytic
reactions; nonhemolytic reactions; infectious disease transmission;
and complications of massive transfusions. Which of the following
statements are true concerning complications of blood transfusions?
a. Immediate hemolytic transfusion reactions are caused by major
ABO blood group incompatibility
b. Nonhemolytic transfusion reactions are usually due to RH
incompatibility and are therefore more common in women of
childbearing age
c. The most common complication of massive blood transfusion is
dilutional thrombocytopenia
d. Routine impaired calcium supplementation is necessary during
most massive transfusion episodes
Answer: a, c

Immediate hemolytic reactions are usually caused by blood group

ABO incompatibility although they may be caused by antigens of
other blood group systems on the transfused red blood cells. The
clinical manifestations revolve around the antigen on the red blood
cell stroma and the antibody in the patient’s serum, and include
production of bradykinin, compliment activation, release of vasoactive
agents from platelets, and initiation of systemic clotting. Chills and
fevers, chest pain and lumbar pain, tachycardia and hypotension in
the conscious patient, and often diffuse bleeding in the anesthetized,
unconscious patient constitute this syndrome. Although reaction
occurs immediately, death related to the syndrome is uncommon,
unless associated with a transfusion of more than 100 ml of blood.
Death usually occurs from acute renal failure or hemorrhage due to
DIC. Nonhemolytic reactions occur with the frequency of 1 to 2% of all
transfusions and consist primarily of chills and fevers during the
transfusion or in the first 2 to 3 hours after the transfusion is
complete. Mechanism of these reactions includes the presence of
antibodies to white blood cell antigens in the transfused blood,
especially in the multitransfused or multiparous patient. Massive
transfusion complications relate to the rate and volume of blood
transfused. The most common complication is dilutional
thrombocytopenia. Factor deficiency of the labile factors V and VIII
rarely is of sufficient magnitude to result in problems with
hemostasis. For hypocalcemia to occur with massive transfusion,
citrated blood must be administered, one unit every five minutes.
Routine empiric calcium supplementation is unnecessary during most
massive transfusion episodes. Conversely, hypothermia is clearly a
problem, especially when associated with massive transfusion during
complex intraoperative procedures such as thoracoabdominal
aneurysm resection.

161 A 67-year-old male with advanced cholangiocarcinoma develops

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

Disseminated intravascular coagulation (DIC) is the primary form of

acute thrombosis. Causes of this syndrome include abruptio placenta,
gram-positive and gram-negative sepsis, endotoxemia, malignant
tumors, pelvic operations, certain snake bites, hematologic
malignancies, and hepatic failure. Blood coagulation is activated by
the release of tissue factor into the circulation, which activates factor
VII of the extrinsic pathway to VIIa, leading to massive thrombin
production and fibrin generation. This in turn activates the fibrinolytic
system, leading to bleeding in the later stages of the syndrome due to
consumption of coagulation factors, depletion of fibrinogen, and
unchecked plasma activities. Laboratory values in DIC usually include
a decline in the platelet count and fibrinogen level, along with an
elevation of fibrin split products.

162 Which of the following substances, not normally present in the

circulation, trigger the initiating events in the hemostatic process?
a. Thrombin
b. Platelet factor 3
c. Tissue factor
d. Collagen
Answer: c, d

The initiating agents for hemostasis involve two substances that are
not normally present in the circulation—collagen and tissue factor.
Tissue factor is released from injured cells, beginning the activation of
the extrinsic pathway of coagulation, while disruption of the
protective endothelial barrier of blood vessels exposes the underlying
collagen to the activation of platelets. In the bloodstream, tissue
factor complexes with factor VII which then activates factor X to factor
Xa. At the same time, activated platelets change from their discoid
shape with their procoagulant phospholipid (termed platelet factor 3)
buried on the inner side of the surface membrane to a spreading
shape to allow for the externalization of platelet factor 3 activity.
Activated factor X, activated factor V, ionized calcium and factor II
(prothrombin) then assemble on the platelet phospholipid surface to
form the so-called prothrombinase complex which catalyzes the
formation of thrombin.

163 Bleeding complications are frequently associated with fibrinolytic

therapy. Which of the following statement(s) concerning complications
of fibrinolytic therapy is/are true?
a. Careful monitoring of prothrombin time and aPTT time are
necessary to avoid bleeding complications
b. A level of serum fibrinogen less than 100 mg/dl is associated with
an increased risk of bleeding
c. Recent (less than 10 days) major surgery is a contraindication to
systemic but not regional fibrinolytic therapy
d. A patient with a cerebrovascular event occurring less than two
months ago can be treated with fibrinolytic therapy if head CT scan is
normal
Answer: b

Fibrinolytic therapy induces a hemostatic defect through a

combination of factors. Hypofibrinogenemia and fibrin degradation
products inhibit fibrin polymerization and, in combination with a
decrease in the clotting factors V and VIII, prolong the ability of blood
to clot. However, coagulation tests in general do not correlate well
with bleeding complications. A level of fibrinogen less than 100 mg/dl
is associated with an increased risk of bleeding. Absolute
contraindications to thrombolytic therapy include active internal
bleeding, recent (less than 2 months) cerebral vascular accident, and
documented left heart thrombosis. Recent (less than 10 days) major
surgery, obstetric delivery, organ biopsy, or major trauma is
considered a major relative contraindication to either regional or
systemic thrombolytic therapy.

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

results of a National Institute of Health Consensus Conference on
venous thrombosis and low-dose heparin prophylaxis?
a. The odds of developing deep venous thrombosis with low-dose
heparin prophylaxis decreases by 67%
b. The risk of pulmonary embolism is decreased by almost 50%
c. There is no increase in mortality from other causes found in
patients treated with low-dose heparin
d. There was no difference in the incidence of bleeding complications
Answer: a, b, c

In a metaanalysis of 70 randomized trials in 16,000 patients

comparing low-dose heparin prophylaxis with standard therapy, the
odds of developing deep venous thrombosis with low-dose heparin
prophylaxis decreased 67%, whereas for pulmonary embolism (both
fatal and non-fatal), the odds decreased by 47%. For fatal pulmonary
embolism, the odds reduction was even greater (64%). No increase in
mortality from other causes was found in those patients treated with
low-dose heparin. Bleeding complications were more frequent in the
heparin-treated patients, with no difference between 5000 units twice
daily and 5000 units three times daily. Similarly, the effectiveness of
prophylaxis was not influenced by either two or three times daily
dosage.

165 Laboratory monitoring of coagulation and anticoagulation

includes testing of platelet function. Which of the following
statements is/are true concerning tests of platelet function?
a. A platelet count of 50,000/µL or more usually ensures hemostasis
b. Bleeding time assays assessibility of platelets to perform
hemostatic plugs and is determined from a sample of blood drawn in
an EDTA coated test tube
c. Aspirin therapy can be associated with a bleeding time in the range
of 8–15 minutes
d. Tests of platelet aggregation should be part of the standard
preoperative evaluation of patients using aspirin
Answer: a, c

Tests of platelet function include peripheral platelet counts, bleeding

times, and platelet aggregation. Usually, a platelet count of 50,000/mL
or more ensures adequate hemostasis, whereas counts less than
10,000/mL are dangerous and may lead to spontaneous bleeding.
Bleeding time performed by observing the clotting of blood induced
with a small needle stick, assesses the ability of platelets to perform
hemostatic plugs and are usually shorter than eight minutes. A
bleeding time between 8 and 15 minutes most often reflects a low
plasma level of Von Willebrand’s Factor or the use of antiplatelet
drugs. A bleeding time greater than 15 minutes is clearly prolonged
and indicates severe platelet functional impairment. Platelet
aggregation studies involve the use of a number of different agonists.
Although a relatively straightforward technique, platelet aggregation
is not available in most laboratories, probably because of the
observer-dependent nature of the test.

166 As thrombin generation proceeds, the body has natural

anticoagulant systems opposing further thrombus formation. Natural
anticoagulants include:
a. Tissue plasminogen activator (TPA)
b. Antithrombin III
c. Activated protein C
d. Heparin cofactor II
Answer: b, c, d

Just as thrombin generation is the key to coagulation, antithrombin III

is the most central anticoagulant proteins. This glycoprotein binds to
thrombin, preventing its removal of fibrinoprotein A and B from
fibrinogen, prevents the activation of factor V and VIII and the
activation and aggregation of platelets. The second line of defense is
the activated protein C, which inactivates factors Va and VIIIa. This
inactivation reduces the ability of the prothrombinase complex to
accelerate the rate of thrombin formation. A third natural
anticoagulant is heparin cofactor II. Its concentration in plasma is
estimated to be some four-fold lower than antithrombin III, and its
action is primarily implicated in the regulation of thrombin formation
in extravascular tissues. Tissue plasminogen activator (TPA) is a
natural catalyst for the activation of plasminogen to plasmin, the main
fibrinolytic enzyme in the body. Therefore, TPA is part of the
fibrinolytic system rather than a natural anticoagulant.

167 Infectious disease transmission during blood transfusions is of

clinical significance to surgeons and of major importance to patients
contemplating surgery potentially associated with the need for blood
administration. Which of the following statement(s) is/are true
concerning the transmission of infectious disease during blood
transfusions?
a. Post-transfusion hepatitis is usually due to hepatitis B
b. Hepatitis and HIV transmission is greatest with the administration
of pooled plasma products such as serum albumin
c. The most important cause of post-transfusion disease in
immunosuppressed patients is CMV infection
d. The risk of HIV transmission in blood transfusions is significantly
less than the risk of hepatitis transmission
Answer: c, d

The most common infectious diseases transmitted during blood

transfusions include viral hepatitis, CMV, and HIV infection.
Post-transfusion hepatitis in 90% of cases consists of non-A, non-B
hepatitis known as hepatitis C. All blood products except for immune
serum globulin and albumin can carry and transmit this form of
hepatitis. Because heat treatment eliminates the risk of viral
transmission, products from pooled plasma that are heat treated such
as albumin are not at risk for HIV or hepatitis transmission. CMV
transmission exists in three forms—primary, reinfection, and
reactivation. Primary exposure results in an IgM response to the virus.
Reactivation is most commonly related to pregnancy, transplantation,
and immunosuppression, and is the most important cause of
post-transfusion disease accompanying immunosuppression of
patients. Although the risk of the public concern for transmission of
HIV disease associated with blood transfusions has significantly
outweighed other infectious disease transmission, the risks of HIV
transmission is markedly less than that of hepatitis.

168 There are a number of hypercoaguable states which can be

associated with arterial or venous thrombosis and embolic
phenomenon. These include:
a. Heparin-associated thrombocytopenia
b. Antithrombin III deficiency
c. Von Willebrand disease
d. Vitamin C deficiency
Answer: a, b

A number of hypercoaguable states are present. These include

heparin-associated thrombocytopenia in which a heparin-dependent
platelet antibody causes aggregation of platelets when the patient is
exposed to heparin. Activation of platelets in this setting results in
thrombocytopenia, thrombosis, and embolic episodes. Antithrombin
III deficiency accounts for about 2% of venous thrombotic events and
has been described in pulmonary embolism, mesenteric venous
thrombosis, lower extremity venous thrombosis, arterial thrombosis,
and dialysis fistula failure. Von Willebrand’s disease is a hereditary
complex coagulation factor deficiency which is manifested by a
reduction of factor VIII activity, and the Von Willebrand factor which is
an adhesive protein that mediates platelet adhesion to collagen.
Severe vitamin C deficiency results in a disorder in soft tissue
increasing vascular permeability and fragility resulting in the potential
for bleeding disorders.

169 Cytokines with clearly defined actions in acute inflammation and

early tissue injury include which of the following?
a. Cysteine-X-Cysteine (C-X-C) chemokines
b. Tumor Necrosis Factor (TNFa)
c. Transforming Growth Factor-b (TGF-b)
d. Interleukin-6 (IL-6)
e. Platelet Derived Growth Factor (PDGF)
Answer: a, b, c, d, e

Polypeptide mediators, such as TNFa and IL-1, are considered “early

response” cytokines and are actively involved in the initiation of the
cascade of events which precipitate acute inflammation. In addition to
being important triggers for the induction of other cytokines
important inflammatory network, TNFa and IL-1 appear to be key
mediators in promoting the adherence of inflammatory cells to the
endothelium. IL-1 is a complex, multifunctional molecule that shares
many overlapping biological properties with TNFa. In addition, both
IL-1 and TNFa potentiate the effects of one another. The most
important function of IL-6 appears to be the regulation of the hepatic
acute phase response. Following injury, a number of physiologic
changes develop within several hours. IL-6 is one of the primary
stimuli for the production of acute phase proteins from the liver.
Endotoxin, IL-1, TNFa and PDGF are capable of causing significant
induction of IL-6 synthesis.
Over the last decade, at least 12 different C-X-C chemokines have
been identified. These include IL-8, one of the most potent mediators
of chemotaxis known. TNFa and IL-1 are key molecules for the
induction of IL-8, which in turn is important for the induction of
neutrophil recruitment and activation.
Similar properties are apparent for other members of this chemokine
family.
Platelet activation and degranulation occur during coagulation
following injury, leading to the deposition of a number of cytokines
into the provisional matrix. These cytokines include transforming
growth factor-a, (TGFa), transforming growth factor b (TGF-b), platelet-
derived growth factor (PDGF), and neutrophil activating peptide-2
(NAP-2). These cytokines are either important growth factors or
chemotaxis for leukocytes, endothelial cells, fibroblasts, and
keratinocytes which are key components in the process of tissue
repair. Thus, coagulation and platelet activation provide the initial
foundation for subsequent cellular recruitment.

170 Which of the following statements regarding transforming growth

factor b (TGF-b) are true?
a. TGF-b expression is autoregulated
b. TGF-b enhances collagen synthesis
c. TGF-b inhibits extracellular matrix production
d. TGF-b may inhibit or promote cellular proliferation
Answer: a, b, d

TGF-b appears to be one of the key cytokines in control of tissue

repair. TGF-b is strongly chemotactic for neutrophils, T cells,
monocytes, and fibroblasts. TGF-b activates inflammatory cells to
elaborate fibroblast growth factor, TNFa, IL-1 and increase their
synthesis of extracellular matrix proteins. TGF-b also induces both the
infiltrating cells and resident cells to produce more TGF-b. This
auto-induction amplifies its biological effects at the site of injury and
may play an important role in the development of chronic fibrosis in a
variety of pathologic states. TGF-b enhances collagen synthesis as
well. Lastly, TGF-b may function as a mitogen or growth inhibitor for a
wide variety of cell types, including selected cell types of mesenchymal
origin. Whether TGF-b stimulates or inhibits proliferation depends on
the presence of other growth factors, the concentration of TGF-b, and
the cell density. Thus, at low doses, TGF-b stimulates the proliferation
of densely plated human marrow fibroblasts, but is inhibitory at high
concentrations.

171 Leukocyte activation and adhesion to vascular endothelial cells is

a critical step in the inflammatory process. This process is regulated
by which of the following molecules?
a. The selectins
b. The b5 integrins
c. The immunoglobulin supergene family
d. Nitric oxide
e. IL-8
Answer: a, c, d, e

The temporal events that initiate and propagate neutrophil

recruitment and inflammation include endothelial cell activation and
expression of endothelial-derived neutrophil adhesion molecules,
neutrophil-endothelial cell adherence, and neutrophil
transendothelial migration via established neutrophil chemotactic
gradients. There are three major families of adhesion molecules
which are expressed on the surface of leukocytes and endothelial cells
and are important for leukocyte-endothelial cell interactions. These
include the immunoglobin supergene family (ICAM-1, VCAM-1, and
PECAM-1), the selectins (E-selectin, P-selectin and L-selectin), and the
integrins. The leukocyte b2 integrin adhesion molecule family consists
of three members with heterodimeric glycoproteins displayed as a
variable alpha and a constant beta chain. Nitric oxide regulates the
adhesion process both by direct influence on leukocyte binding as
well as by regulation of regional blood flow. IL-8 is one of the most
potent mediators of chemotaxis in the C-X-C chemokine family. It
serves an important role in neutrophil recruitment and activation, and
the continued propagation of the inflammatory response.

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

Tumor cachexia appears to be mediated by TNFa. Lipopolysaccharide

(LPS), as well as other cytokines, activate a variety of inflammatory
cells, most importantly macrophages, to produce TNFa. Both the
chronic administration of TNFa to rats and implantation of tumors
secreting TNFa in mice induce a syndrome of cachexia. In vitro, higher
TNFa concentrations alter glucose metabolism in cultured myotubules
by increasing glucose uptake and glycogen breakdown. It has also
been demonstrated that purified TNFa suppresses lipoprotein lipase
activity and stimulates lipolysis in cultured adipocytes. Further, TNFa
not only inhibits the differentiation process of preadipocytes, but
partially reverses differentiated adipocytes to a preadipocyte
morphology and pattern of gene expression. All of these metabolic
effects at least partially explain the chronic syndromes of anorexia,
weight loss, and cachexia that are associated with both chronic
infection and malignancy.

173 Which of the following statements regarding fibroblasts and their

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

IL-1 appears to be important in the process of normal wound repair.

IL-1 has been shown to stimulate skin fibroblast and keratinocyte
growth, as well as fibroblast collagen synthesis and keratinocyte
chemotaxis. IL-1 also promotes increased transcription of the matrix
degradative enzymes collagenase and stromelysin. These are
important and potent tissue degrading proteinases. Other studies
have demonstrated that IL-1 inhibits fibroblast growth and matrix
synthesis, and stimulates collagenase production. These actions are at
least partly due to the ability of IL-1 to upregulate prostaglandin E2
production which results in the down regulation of matrix synthesis.
IL-1 has both promoting and inhibiting effects on fibroblast collagen
synthesis, therefore, the overall activity in this area is somewhat
unclear in comparison to other well-defined fibroblast growth-
promoting cytokines. TNFa inhibits fibroblast collagen synthesis,
however it also has potent mitogenic effects. The mitogenic response
correlates well with an increased stimulation of tyrosine
phosphorylation. Both IL-1 and TNFa have similar effects upon bone.
Both stimulate cartilage resorption, the release of proteoglycans from
cartilage by limited proteolytic degradation, and both inhibit
proteoglycan synthesis. Recent studies have also demonstrated that
TNFa inhibits fracture healing in experimental animals. This is due to
the inhibition of cartilage formation and new bone synthesis, and the
inhibition of mesenchymal cell differentiation into chondroblasts. The
family of epithelial growth factor (EGF)-like molecules induce
mitogenesis and play a role in wound healing. In human clinical trials,
EGF has been demonstrated to accelerate epidermal regeneration in
cutaneous wounds. In vitro data show that recombinant EGF
enhances keratinocyte migration. EGF is also a potent
chemoattractant for granulation tissue fibroblasts.

174 Neutrophil chemotaxis is a fundamental aspect of inflammatory

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

There is a large collection of peptide, polypeptide and lipid mediators

which have chemotactic properties. Although TNF a, IL-1 and LPS were
initially reported to have direct neutrophil chemotactic activity, recent
studies have demonstrated that these molecules are not directly
chemotactic for neutrophils. This finding suggests that cytokine
networks may be operative in vivo and depend on the initial
expression of early response cytokines. This initial interaction is
followed by the generation of more distal inflammatory mediators
that directly influence neutrophil chemotaxis and activation. There is a
particularly important group of novel chemotactic cytokines which
share significant homology with the presence of four conserved
cysteine amino acid residues. These cytokines in their monomeric
forms are all less than 10 kD, are characteristically basic heparin-
binding proteins, have specific neutrophil chemotactic activity and
display four highly conserved cysteine amino acid residues, with the
first two cysteines separated by one non-conserved amino acid
residue. Because of their chemotactic properties and the presence of
C-X-C cysteine motif, these have been designated the C-X-C
chemokine family. Twelve different chemokines have been identified
in the last decade. These include IL-8, epithelial neutrophil activating
protein (ENA-78), and others. Among the other endogenous
chemoattractants are several complement-derived peptides. Perhaps,
the most potent of these is the short-lived C5a peptide.

175 Which of the following statements regarding angiogenesis are

true?
a. Angiogenesis is a seminal biologic event with clinical relevance
limited to its effect upon tumor growth
b. C-X-C chemokines regulate angiogenesis
c. PF-4 has angiogenic properties
d. Sites of atherosclerosis demonstrate chronic angiogenic activity
Answer: b, d

An important component of tissue repair and wound healing is the

process of angiogenesis. This normal, physiologic process is a local,
transient event which is regulated strictly. A biological imbalance in
the production of angiogenic and angiostatic factors contributes to
the pathogenesis of several angiogenesis-dependent disorders. These
include both malignant and nonmalignant disorders such as
rheumatoid arthritis, scleroderma, psoriasis, atherosclerosis, and
idiopathic pulmonary fibrosis. Persistent neovascularization in these
benign disorders is a prerequisite for the perpetuation of
fibroproliferation. IL-8 and potentially other C-X-C chemokines are
involved with the angiogenesis process. IL-8 is a potent angiogenic
factor. In contrast, another member of the C-X-C chemokine family,
PF-4 has angiostatic properties. This suggests that the C-X-C
chemokines may function as either angiostatic or angiogenic factors,
and the biologic balance that is maintained between these factors
may govern overall angiogenic potential in a variety of physiological
and pathophysiological states.

176 Which of the following statements regarding IL-1 are correct?

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

IL-1 and TNFa share many biologic properties. In addition, each

potentiates the effects of the other one when given concurrently.
Overall, IL-1 alone probably has weaker effects than TNFa with respect
to the induction of shock; its role is likely to be important with respect
to its marked potentiating abilities as it relates to TNFa. IL-1
expression is regulated by a host of factors including IL-2, granulocyte
macrophage colony stimulating factor (GM-CSF), transforming growth
factor b (TGF-b), TNFa, all of the interferons, and IL-1 itself. Other
endogenous stimuli for IL-1 production include antigen-antibody
complex, the Fc region of IgG, and C5a; other nonspecific exogenous
stimuli include silica particles and UV irradiation.
One of the key proinflammatory features of IL-1-induced
inflammation is the stimulation of arachadonic acid metabolism. IL-1
stimulates the release of pituitary stress hormones and increases the
synthesis of collagenases, resulting in the destruction of cartilage,
bone and other collagen-rich structures. IL-1 stimulates prostaglandin
production.
One of the most important properties of IL-1 involves its interaction
with the vascular endothelium. This includes the adherence of
neutrophils, basophils, eosinophils, monocytes, and lymphocytes to
the vascular endothelium via interaction between adhesion molecules
on leukocytes and adhesion-receptor complex on the endothelial
cells. By inducing the expression of ICAM-1, E-selectin, and VCAM-1 on
endothelial cells, IL-1 provides a key step in the extravasation of
leukocytes to sites of local inflammation and injury.

177 Which of the following statements regarding TNFa are true?

a. TNFa has a marked procoagulant effect
b. Passive immunization of patients with neutralizing antibodies to
TNFa improves survival from multi-organ system failure
c. TNFa upregulates E-selectin expression
d. The most potent known stimulus for TNFa production and release
is IL-1
Answer: a, c

TNFa has a marked procoagulant effect on endothelial cells,

precipitating intravascular thrombosis. TNFa causes endothelial cells
to release procoagulant activity (tissue factor), platelet activating
factor, and von Willebrand factor, all of which favor thrombosis. TNFa
also down regulates the expression of thrombomodulin, which has
the potential to block the assembly of protein C and protein S
complexes, further decreasing the anticoagulant properties of the
endothelial cell surfaces.
Administration of recombinant TNFa to experimental animals
produces a clinical syndrome similar to that seen in septic shock and
multi-organ system failure in humans. Passive immunization of
animals with neutralizing antibodies against TNFa, prior to the
infusion of TNFa or endotoxin, has been shown to prevent the
development of this syndrome. No such evidence exists in human
patients.
TNFa upregulates a variety of leukocytic adhesion molecules including
ICAM-1, PECAM-1, VCAM-1, E-selectin and P-selectin. A variety of
exogenous and endogenous factors (including IL-1) are capable of
inducing cells to produce TNFa, however the most potent stimulus for
TNFa production and release is endotoxin.

178 Which of the following belong to the family of C-X-C chemokines?

a. IL-8
b. IL-10
c. Growth Related Oncogene-a
d. Leukotreine B4
e. b Thromboglobulin
Answer: a, c, e

A particularly important group of novel chemotactic cytokines has

been elucidated over the last decade. Twelve are known and are listed
below.
C-X-C Chemokines
Connective Tissue Activating Protein III
b-Thromboglobulin
Growth Related Oncogene-a
Growth Related Oncogene-b
Related Oncogene-g
Interleukin-8
Epithelial Neutrophil Activating Protein
Granulocyte Chemotactic Protein-2
Platelet Factor-4
g-Interferon-inducible Protein
Monokine-induced by g-Interferon
Each has unique biologic functions. There appear to be important in
vivo cytokine networks involving these molecules which regulate
chemotaxis, and other fundamental aspects of inflammation.

179 Which of the following statements regarding the complement

system are true?
a. Complement activation yields products which are directly cytotoxic
as well as products which act indirectly via activated leukocytes
b. Complement products referred to as anaphylatoxins include C1,
C3a, C4a, and C5a
c. The principal role of C5a is in bacterial opsonization
d. The alternative and classical pathways converge proximal to
generating the membrane attack complex (C5b-9)
Answer: a, d

The complement system is composed of two different but linked

sequences, the classic and alternative pathways. The pathways involve
serum proteins that act to amplify the inflammatory-immune
response as well as to directly mediate tissue injury. Complement
activation by either pathway has been associated with a cascade of
events, some of which are mediated directly at a physiologic level by
complement products and some of which occur indirectly via
activated leukocytes. The direct physiologic effects mediated by C3a
and C5a, and to a lesser extent C4a, include increased vascular
permeability and contraction of smooth muscle. These are key
elements of anaphylaxis. C1 is not an anaphylatoxin as it is the initial
complement component which binds to antigen-antibody complex to
initiate classical pathway activation. C5a acts principally to alter the
behavioral characteristics of leukocytes. Effects include enhanced
adherence, enhanced chemotactic activity, release of proteinases, and
production of toxic metabolites of oxygen. C3, on the other hand,
plays a key role in bacterial opsonization, resulting in enhanced
phagocytosis of invading microorganisms. The alternative and
classical complement pathways converge at the C5 level proximal to
generating the membrane attack complex (C5b-9) (Figure 6-3).

180 Which of the following statements regarding neutrophils are true?

a. The neutrophil undergoes final maturation after release into the
circulation
b. Patients with chronic granulomatous disease have a defective
neutrophil H-oxidase system
c. Neutrophil killing of bacteria is achieved by oxidants, proteinases
and cationic proteins
d. The normal human neutrophil circulates in the blood for 7–10 days
Answer: b, c

The neutrophil is a migratory phagocytic cell that defends the host

against bacteria and eliminates necrotic tissue. The neutrophil
matures in the bone marrow and is released into the circulation as a
fully differentiated cell. It is loaded with granules containing a variety
of proteinases, hydrolases, antimicrobial agents and cationic proteins.
The cell phagocytoses material and the granules fuse with the
phagocytic vacuoles to degrade the foreign material. When the cells
are challenged with a large amount of material, the granule contents
may be released into the extracellular space where damage to
surrounding tissue occurs. The neutrophil normally circulates in the
human bloodstream for 7 to 10 hours. Thereafter, neutrophils are
thought to exist for 1 to 2 days in the tissues before being cleared
from the system. Granule constituents are formed during
differentiation and replenishment of spent granules does not occur
once the cells are in the circulation. Hence, the neutrophil is a fully
differentiated end-cell poised to respond rapidly to stimuli, but it is
rapidly spent in the process. Neutrophils have a NADPH-oxidase
enzyme system on the plasma membrane which can be activated to
produce toxic oxygen species including the superoxide anion (02–).
Patients with chronic granulomatous disease (CGD) have a defective
NADPH-oxidase system in their neutrophils, and are thus unable to
generate 02–. Although neutrophils from patients with CGD are able
to phagocytose bacteria, they are unable to kill the intracellular
microbes and chronic, unresolved infections result.

181 Which of the following statements regarding the alternative

complement pathway are true?
a. C1, C4 and C2 are involved
b. NH3 apparently activates complement via this pathway
c. Factors B and D are involved
d. Endotoxin activates complement via the alternative pathway
Answer: b, c, d

The alternative pathway differs from the classic pathway in that the
first steps involving C1, C4 and C2 are bypassed. (See Figure 6-3
previously reproduced.) This pathway can be directly activated by
agents other than antigen–antibody complex (e.g., complex
polysaccharides like endotoxin and zymosan). Other serum protein
factors (e.g., factors B and D) are involved in the activation sequence.
Ammonia can attack the thiol-ester, producing amidated C3 and
activate the alternative pathway. This leads to membrane attack
complex formation (C5b-9) and activation of a number of phagocytic
cell functions including toxic oxidant production. This phenomenon
may have relevance to several in vivo disease states. In animal models
of renal failure, elevated levels of renal vein NH3 have been correlated
with impaired renal function and the presence of complement
components at the sites of renal injury.

182 Platelet activating factor is:

a. Generated by the action of phospholipase A2 on membrane
phospholipids
b. Antiinflammatory in most of its actions
c. Synthesized by endothelial and other cells
d. Exerts a variety of biologic effects which are platelet-independent
Answer: a, c, d

Like the eicosanoids, platelet-activating factor (PAF) is not stored in

cells but is rapidly produced during inflammation. PAF exerts a variety
of biologic effects that are platelet-independent. The synthesis of PAF
is initiated by the activation of phospholipase A2. Activation of
phospholipase A2 releases arachidonic acid in addition to lyso-PAF.
Hence, PAF synthesis and eicosanoid production are coordinately
regulated. PAF is synthesized on activation of a variety of
inflammatory cells including platelets, neutrophils, basophils, mast
cells, mononuclear phagocytes, eosinophils and vascular
endothelium. PAF is a stimulatory agonist for many inflammatory
cells, as well as for smooth muscle cells, vascular endothelium and
others. PAF enhances the ability of neutrophils to respond to
challenge with N-formylpeptides and LTB4. There is considerable
overlap and redundancy in the effects produced by PAF and
eicosanoids.

183 Platelets have a wide array of functions in inflammation. Which of

the following are among these?
a. Synthesis and release of vasoactive eicosanoids
b. Release of chemotactic factors
c. Adherence to and coating of bacterial and tumor cells
d. Increase of vascular permeability
e. Phagocytosis of bacteria
Answer: a, b, c, d

Platelets are anucleated cells derived from megakaryocytes in the

bone marrow. Their central role in hemostasis is well known. Platelets
possess a wide array of functions in inflammation, including the
following:
Synthesis and release of vasoactive eicosanoids
Release of chemotactic factors
Interaction with other inflammatory cells
Interaction with endothelial cells
Adherence to and coating of bacterial and tumor cells
Platelets are not capable of phagocytosis.
Few of the factors released or the functions carried by platelets during
inflammation are unique to this cell type. Other inflammatory cells
often have the same or similar capabilities. Indeed, some platelet
functions may reflect vestigial functions inherited from a primitive
precursor inflammatory cell. Platelets serve primarily as an amplifier
or modulator of the inflammatory response.

184 Eicosanoids mediate inflammation in a variety of ways. Of the

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

The eicosanoids are derived from arachidonic acid (eicosatetraenoic

acid) and consist of prostaglandins, thromboxanes, leukotrienes and
lipoxins. The eicosanoids are not stored in cells but are rapidly
synthesized by cells in response to a variety of stimuli. They have
potent effects on vascular and bronchial smooth muscle including
vasodilatation, vasoconstriction, bronchodilation and
bronchoconstriction. In addition, they directly regulate vascular
permeability. LTB4 is a potent, neutrophil chemoattractant whereas
lipoxin A4 inhibits other chemoattractants. It appears that eicosanoids
are important regulators of the endogenous inflammatory response.
The rapid destruction of eicosanoids in the circulation limits their role
primarily to that of mediators of local inflammatory changes. The local
effects can be substantial. In general, the eicosanoids are rapidly
metabolized or are so chemically unstable that they primarily exert
their effects near the site of synthesis. Arachidonic acid does not exist
in cells but is esterified to membrane phospholipids. Thus, the first
step in the production of eicosanoids is phospholipase action, which
liberates arachidonic acid. (Figure 6-6)

185 Which of the following statements are true?

a. Eosinophils are the major, if not sole, source of histamine in the
blood
b. Basophils are effector cells in allergic reactions by virtue of IgE
receptors
c. Mast cells are the major source of tissue histamine except in the
stomach and central nervous system
d. Mononuclear phagocytes release a variety of proinflammatory
cytokines and growth factors
Answer: b, c, d

Eosinophils constitute 1% to 3% of the leukocyte population of the

bloodstream. They also reside in tissues and they exhibit phagocytic
capabilities. They are less effective as bactericidal cells than
neutrophils, but play a major role in defense against parasites.
Eosinophils are primary effectors in allergic reactions by virtue of IgE
receptors (which are not found on neutrophils).
Basophils are fully differentiated cells released into the circulation
from bone marrow. Basophils are the major, if not sole, source of
histamine in the blood. Histamine is a vasoactive amine and the major
mediator of the IgE-mediated immediate hypersensitivity response.
Histamine release from basophils is induced by complement products
as well as by IgE receptors.
Mast cells are formed from bone marrow precursors that differentiate
and proliferate in connective tissue. Mast cell granules contain
histamine and proteoglycans. They represent the major source of
histamine in most tissues except the stomach and central nervous
system.
The monocyte–macrophage system consists of phagocytic cells
scattered throughout the body. During acute inflammation,
monocytes respond to chemoattractants released and are recruited
to the site of inflammation. Mononuclear phagocytes respond to
inflammatory stimuli by releasing M-CSF, GM-CSF, IL-1, and TNF, in
addition to a variety of growth factors. These factors increase the
production of mononuclear phagocytes and several of these factors
enhance the ability of effector cells to respond to chemotactic stimuli
released at the site of injury. Thus, the mononuclear phagocytes are
important in initiating and augmenting the cycle of events that result
in recruitment and activation of inflammatory cells at sites of
inflammation.

186 Cellular injury from oxidants may be manifest by which of the

following?
a. Cell membrane lipid peroxidation
b. DNA strand breaks
c. Cytoskeletal disassembly
d. ATP depletion
Answer: a, b, c, d

Free oxygen radicals are chemical species that are intermediates in

the normal process of cellular respiration. Oxidants that are free
radicals have been implicated as initiators of reactions which lead to a
variety of cellular injuries. Oxidants are derived from several sources,
notably phagocytes. Among the effects of oxygen free radicals are
membrane lipid peroxidation, DNA strand breaks, cytoskeletal
disassembly and inhibition of glucose metabolism leading to
decreased cellular ATP concentrations. (Figure 6-16)

187 Which of the following acute-phase protein levels are increased in

human plasma following acute inflammation?
a. C-reactive protein
b. Serum amyloid
c. a -Proteinase inhibitor
d. Fibrinogen
e. Albumin
Answer: a, b, c, d

The acute-phase response is a series of homeostatic responses of the

organism to tissue injury in infection and inflammation. After an
inflammatory stimulus occurs, a number of events occur within hours.
These reflect altered set-points for various physiologic parameters
including thermoregulation (fever), nitrogen balance (negative), and
levels of various plasma proteins (increased or decreased). The
erythrocyte sedimentation rate, which increases with inflammatory
states, is an example of this phenomenon. The increased
sedimentation rate is due to increased levels of fibrinogen and some
of the other acute-phase reactants in plasma. Some proteins show a
large increase (about 1000-fold), some a 4-to 5-fold increase, and
others about a 50% increase over resting nonstressed levels.
Note that albumin is an acute-phase reactant. Levels of albumin drop
after an inflammatory stimulus, usually 30% to 50% of the level before
injury. The reason for the decrease in production is poorly
understood.

188 Which of the following statements regarding endothelial cells in

acute inflammation are true?
a. Endothelial cells are characterized by phenotypic homogeneity
b. Specific patterns of receptor expression regulate leukocyte
adherence
c. Endothelial cell nitric oxide generation regulates regional blood flow
and leukocyte adhesion
d. Endothelial cells may be capable of phagocytosis
Answer: b, c, d

Endothelial cells are increasingly recognized to be phenotypically

heterogeneous. Specific receptor molecules are expressed at various
sites where they help to direct lymphocytes and other leukocytes to
their appropriate target organ. In the high endothelial venues, these
receptor molecules are known as vascular addressing. Endothelial
cells play a major role in regulating vascular tone. This is the result of
angiotensin-converting enzyme on the cell surface as well as the
production of both endothelia (a potent vasoconstrictor) and nitric
oxide (a potent vasodilator). Both play important physiologic roles in
determining the distribution of blood flow. In addition, recent
evidence suggests that NO may have direct effects upon the
expression of a variety of leukocyte adhesion molecules. Under
unusual circumstances, endothelial cells can exhibit macrophage-like
properties in that they can act as antigen-presenting cells and also
phagocytose particles. They may also be a significant source of
oxidants in inflammatory reactions after ischemic injury. Endothelial
cells are not passive participants in inflammatory processes; rather,
they possess the ability to direct and focus many aspects of an
inflammatory event.

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

The skin, mucus membranes, and epithelial layers of various organs

of the body constitute effective physical barriers against microbial
invasion. In certain portions of the body, these barriers have
developed ancillary adaptations to increase the effectiveness of the
barrier functions. Skin structures such as sebaceous glands secrete
chemical compounds that serve to maintain a relatively low pH,
providing effective bacterial stasis. Mucus secretion by specialized
glands within the bronchi and gut provide a mucus layer that
represents a physical and chemical barrier to microbial invasion.
Within the respiratory tract, ciliary function serves to extrude
microorganisms trapped within this mucus layer. In the alimentary
track, the very low pH within the stomach and gut peristalsis both
serve to prevent microbial adherence and invasion.

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

antibody response to an invading antigen?
a. All antibodies are composed of one type of heavy and one type of
light protein chain
b. The carboxyl terminus of the heavy chain is the antigen binding site
c. Antibody of the immunoglobulin G class is the initial antibody
produced in response to an antigenic stimulus
d. Immunoglobulins A, D, and E play an active role in the circulating
humoral response
Answer: a

Humoral defenses consist of antibody (immunoglobulin; Ig) and

complement. All Ig classes (IgM, IgG, IgA, IgE, IgD) and IgG subclasses
are composed of one type (M, G, A, E, D) of heavy and one type (K and
g ) of light protein chains that consist of several domains both
structurally and functionally. Each Ig molecule contains one or more
units that consist of two heavy and two light chains linked by disulfide
bonds. The amino terminus of both heavy and light chains contain
several hypervariable regions that fold in three dimensions to
produce the antigen-binding site. The carboxyl terminus of the heavy
chains contain regions that activate complement and bind Fc
receptors, by which direct adherence to polymorphonuclear
leukocytes and macrophages take place after antigen binding occurs.
Initially, antibody of the IgM class is produced in response to an
antigenic stimulus. A second exposure to the same antigen, or a cross-
reactive antigen, leads to the so-called second set response, in which
antibody of the IgG class with two binding sites is produced more
rapidly and in larger quantity compared to the initial IgM primary
response. Immunoglobulin of the IgA class is secreted by
gut-associated lymphoid tissue and is combined with secretory
components of protein to form a dimer termed secretory IgA. This
antibody acts at a variety of epithelial sites to prevent microbial
adherence and invasion. IgD and IgE exist in smaller amounts in the
circulation and do not appear to play a major role as host defense
components.

191 Increasing evidence has implicated gram-negative bacterial

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

The LPS molecule exerts diverse effects on the mammalian host.

Immunologic responses to LPS include nonspecific polyclonal B-cell
proliferation, macrophage activation and cytokine secretion, tolerance
to subsequent LPS or bacterial challenge, and production of antibody
directed against various portions of the LPS molecule after repeated
challenge. Physiologic responses similar to those seen during
gram-negative bacterial sepsis occur during LPS administration alone
and include hypotension, hypoxemia, acidosis, bacterial translocation
across the gut, complement and coagulation cascade activation, white
blood cell and platelet margination, and death. Indirect effects result
from LPS-triggering of host macrophages. Activated macrophages
secrete a wide array of cytokines that include TNF-a, IL-1a, and IL-1b,
IL-6 and interferon-a (IFNa). Excessive secretion of cytokines produce
substantial systemic effects in the mammalian host. TNFa and IL-1b
appear to be the primary mediators within the local host milieu,
exerting deleterious effects on the host only after large amounts are
secreted and reach the systemic circulation.

192 Which of the following statement(s) concerning the gut microflora

is/are correct?
a. Gut microflora evolves constantly throughout development
b. The gut microflora can contribute to the physical and chemical
barriers at the mucus membrane level
c. Most of the microorganisms found in the oropharynx eventually
pass into the intestine
d. In the colon, anaerobic organisms outnumber aerobic organisms in
a ratio in excess of 100:1
Answer: b, d

The composition of the gut microflora is established in neonates after

ingestion of microbes that are acquired during contamination from
the birth canal and during initial feeding, and remain relatively
constant thereafter. Although this flora acts to promote development
of the immune system, the specific interactions that produce this
effect have not been fully elucidated. The microflora also contributes
to physical and chemical barriers at the mucus membrane level, in
that many autochthonous microbes possess adhesion proteins by
which they can bind to certain areas of the mucosal cell or to specific
types of bacteria, occupying potential binding sites for pathogenic
organisms and producing a substantial physical mucobacterial layer.
The oropharynx contains a number of aerobic and anaerobic
microorganisms, however, these microbial inhabitants do not usually
pass into the intestine, because the stomach itself represents a
significant barrier to invading microorganisms by virtue of its low pH,
which kills most microbes. The upper small intestine contains few
organisms, mainly gram-positive aerobes and lactobacilli. Conversely,
the lower small intestine contains a large number of aerobes and
anaerobic forms, especially in patients in whom the ileocecal valve
allows free backwash of cecal contents into the terminal ileum. Within
the colon, a wide diversity and a large number of facultative and strict
anaerobic isolates are present. Only a small number of aerobes are
present, these microbes being outnumbered 100–300 to 1 by
anaerobes.

193 The use of antibiotics can be based on either the clinical course of
a patient without the benefit of well-defined microbiologic data
(empiric therapy), or targeted at specific identified pathogens once
sensitivity reports are available (directed therapy). The following
statement(s) is/are true concerning these therapies.
a. The issue of toxic side effects of antibiotics is only important in
dealing with emperic therapy
b. Single agent therapy is generally inferior to specific multi-drug
therapy (aminoglycoside plus an antianaerobic agent) for the
treatment of secondary bacterial peritonitis due to appendicitis,
diverticulitis, penetrating gastrointestinal injury, or anastomotic leak
c. With the empiric use of antibiotics, a diligent search for the septic
source should be undertaken and continued until identified
d. In clinical situations in which polymicrobial infection is identified,
specifically-directed treatment for the predominant organism is
satisfactory
Answer: c
The use of empiric therapy without the benefit of well-defined
microbiologic data is appropriate when there is sufficient clinical
evidence to support the diagnosis such that it would be imprudent to
withhold antimicrobial therapy. In this setting, however, a diligent
search for the septic focus source should be undertaken and
continued (cultures, radiographic procedures, etc.), and initial limits
should be placed in the course of empiric therapy with continued
reevaluation based on the clinical course of the patient. The choice of
antibiotic agents should be based on the clinical situation and known
activity patterns within the given institution. Single broad-spectrum
agents, although suffering slightly from a lack of individual pathogen
specificity, are useful in this setting in that they provide a broad
coverage against several groups of pathogens and may avoid some of
the toxic effects with specific combined modality regimens. Similarly,
for directed therapy, single-agent therapy has been demonstrated to
be equivalent to combined therapy and should be chosen in an
attempt to select agents with appropriate sensitivities which retain
suitable clinical efficacy but exhibit minimal toxicity. After review of
cultural reports, many patients have demonstrated polymicrobial
infection. Because experimental clinical evidence supports the
concept of aerobic-anaerobic synergy, therapy should be directed
against all potential components of the infection if the body site is
such that these microorganisms may be present.

194 The following statement(s) is/are true concerning newer detection

methods of systemic infection.
a. Enzyme-linked immunosorbent assay (ELISA) is a rapid
immunologic assay used for both antigen and antibody detection
b. Southern, northern, and western immunoblot techniques are used
to detect DNA, RNA, or proteins, respectively
c. Polymerase chain reaction (PCR) is a sensitive assay used to detect
small amounts of microbial DNA, thus detecting infection at its early
stages
d. Infectious agents currently detected using advanced molecular
techniques include cytomegalovirus (CMV) and human
immunodeficiency virus (HIV)
Answer: a, b, c, d

Although the classic detection of infection based on clinical signs of

infection and bacterial culture remain the most common clinical tools,
increasing reliance has been placed on assays that do not employ
cultural data. Specifically, the antibody and cytokine host responses
are being intensely examined and extremely sensitive amplified
assays that rely on antigen, antibody or microbial DNA detection are
employed in the clinical setting. Enzyme-linked immunosorbent assay
(ELISA) is a rapid, antigen-based, immunologic assay that can be used
for both antigen and antibody detection, for determination of
antibody titer, as well as for screening for monoclonal antibody
production. Transblot techniques are being used increasingly in the
clinical setting. These include southern, northern, and western
immunotransblot techniques used to detect DNA, RNA, or proteins,
respectively. The polymerase chain reaction (PCR) is being used in
some centers as a sensitive assay to detect small amounts of
microbial DNA. This technique involves extraction of the DNA from the
test sample with in vitro amplification through repeated nucleic acid
denaturing and polymerization so that the gene copy number
increases exponentially. This marked amplification of the gene copy
number results in extremely sensitive tests which can detect infection
at its early stages.
Clinically, these detection methods are being used to detect a wide
variety of infectious agents including CMV and HIV. Furthermore,
preliminary investigations into possible detection of fungal pathogens
are underway.

195 Cytokines are low-molecular-weight polypeptides exerting a wide

variety of biologic effects at both local and systemic levels. Which of
the following statement(s) is/are true concerning the production and
actions of cytokines?
a. Cytokines are produced solely by macrophages
b. Cytokines act only on other cells within the same local environment
c. Cytokines may have both protective and deleterious effects on the
host
d. Each specific cytokine is produced by a single cell type
Answer: c

Macrophages, endothelial cells, lymphocytes, and other cells secrete a

large number of different compounds, termed cytokines, that are
most probably evolved for the purpose of local intercellular and
intracellular signaling. Cytokines frequently are secreted after initial
lymphocyte or macrophage activation, and may act on the secreting
cell itself (autocrine activation) or on other cells within the same local
environment (paracrine activation) to cause increased secretion of the
same cytokine or other cytokines, respectively. Some cytokines are
produced by several cell types, and most produce a wide array of
effects. The duality of the effects of the cytokine component of host
defenses, exerting both salutatory and deleterious effects on the host,
has become increasingly evident.

196 The following statement(s) is/are true concerning cellular defense

mechanisms.
a. Macrophages function solely as antigen processing cells in the
initial reaction to exposure to an antigen
b. Macrophages may become activated and secrete cytokines
c. Macrophages serve as phagocytic cells in the tissues but not within
the bloodstream
d. Polymorphonucleocytes (PMNS) are normally present in only small
numbers within the tissue and enter an area of infection through
diapedesis
Answer: b, d

A wide variety of cell types serve to provide host defense at several

levels. Macrophages act as the initial antigen processing cell that
serves to present antigen to help T cells, thus initiating the immune
response. Macrophages, however, are pluripotent cells that, in the
process of engulfing and processing antigen, may become activated.
Activated macrophages secrete a variety of cytokines. Macrophages
also act as phagocytic cells in the tissues and within the bloodstream,
and because of their resident nature in many tissues, also represent
the first line of host defenses in many areas of the body, even before
activation. PMNS are present within the bloodstream, but only in
small numbers within the tissue, and enter an area of infection
through diapedesis after chemotactic stimuli are excluded by
macrophages, bacterial breakdown products, and complement
activation.

197 A diabetic develops a severe perineal infection with skin necrosis,

subcutaneous crepitance, and drainage of a thin, watery, grayish and
foul-smelling fluid. Management should consist of:
a. Gram stain of the fluid, which will likely demonstrate multiple
bacteria including predominantly gram-positive rods
b. A CT scan is indicated in a stable patient to define the extent of the
disease
c. Broad spectrum antibiotics followed with prompt extensive
debridement is indicated
d. A safe guideline is to resect infected necrotic tissue so that a several
centimeter margin of grossly normal, healthy tissue can be achieved
e. A colostomy is of little benefit in this situation
Answer: a, b, c, d

The presence of severe perineal infection (referred to as Fournier

gangrene when this process involves the perineum and scrotum in
males) is associated with a continued high mortality despite
aggressive and appropriate therapy. The clinical description provided
would suggest an underlying soft tissue necrosis. In a stable patient
radiologic studies including a CT scan to define the extent of the
disease and the presence of pelvic infection is indicated. Gram stain
will likely show evidence of polymicrobial organisms but the presence
of Clostridia marked by gram-positive rods would suggest
involvement with this organism. Prompt, aggressive and extensive
debridement to remove all devitalized and affected tissue and the
addition of broad spectrum antibiotics, fluid resuscitation,
hemodynamic monitoring, and nutritional support would appear to
afford the patient the best chance of survival. The clearest guidelines
to determine the limits of resection involve removal of clearly
infected, necrotic tissue so that margins several centimeters into
grossly normal, healthy tissue are achieved. Because the entire
perineal region and buttocks are frequently involved in these patients,
performance of a fecal stream diversion by means of a colostomy
often provides improved wound care and patient management,
although it is not invariably a positive outcome.

198 The use of prophylactic antibiotics has become commonplace.

Which of the following statement(s) is/are true concerning the
prophylactic use of antibiotics?
a. The appropriate use of prophylactic antibiotics must include the
initiation of the agent prior to the surgical procedure
b. Continuing the antibiotic into the postoperative period has led to
improved results in antibiotic prophylaxis
c. The prophylactic administration of broad-spectrum agents (third-
generation cephalosporins) has been shown to be particularly
advantageous
d. The topical use of antimicrobial agents is of no advantage in the
prophylactic setting
Answer: a

Intravenous administration of an antibiotic is clearly indicated for

patients undergoing clean contaminated operations. These antibiotics
should be administered prior to surgery to obtain adequate tissue
levels at the time of potential contamination. However, there has
been no added benefit demonstrated for the postoperative use of
antibiotics with regard to prophylaxis. The choice of antibiotic is a
complex issue which remains unresolved largely because both
superficial and deep wound infections can occur as a result of either
or both skin (superficial wound) flora (e.g., Staphylococcus aureus)
and body site (deep wound) infection. For this reason, the
administration of agents which possess activity directed against these
expected agents is reasonable. Although administration of a first-
generation cephalosporin is acceptable, second-generation
cephalosporins or extended-spectrum penicillins with gram-positive
and gram-negative activity and biliary tract excretion may be more
suitable for patients undergoing gastrointestinal or biliary tract
procedures. Similarly, the use of agents with additional anaerobic
activity for patients undergoing gastrointestinal procedures involving
the small bowel or colon should be considered. The administration of
broad-spectrum agents such as third-generation cephalosporins for
prophylaxis does not seem to provide additional benefit in
comparison to the above-mentioned type antibiotics and may foster
the development of resistant organisms within a given institution or
superinfection within a given patient. There is evidence that in some
cases the topical use of antimicrobial agents is equivalent to the
administration of intravenous antimicrobial agent antibiotics.

199 If a necrotizing soft tissue infection is considered, therapy

mandates:
a. Empiric administration of antibiotics active against gram-positive,
gram-negative, and anaerobic bacteria
b. Due to usually resistant species, penicillin is not indicated
c. Immediate operative intervention and aggressive resection of all
involved tissues is mandatory
d. The use of hyperbaric oxygen has been demonstrated to be clearly
advantageous
Answer: a, c

Identification of a necrotizing, soft tissue infection mandates

immediate operative intervention with aggressive resection of all
involved tissues and empiric administration of antibiotics active
against gram-positive, gram-negative, and anaerobic bacteria. In most
cases, this involves the use of several antimicrobial antibiotics in
combination. Because of concern in all cases for the presence of
Clostridia infection, high doses of aqueous penicillin G are
administered. Gram-positive organisms are treated with vancomycin
or a semisynthetic penicillin and gram-negative organisms are treated
with an aminoglycoside or a monobactam. Anaerobic coverage is
typically achieved by use of metronidazole of clindamycin. The use of
hyperbaric oxygen therapy is controversial and unfortunately due to
the rarity of the disease, prospective randomized data is not available
so that the literature remains without controlled trials demonstrating
any additional benefits derived from hyperbaric oxygen therapy.

200 Wounds are classified according to the likelihood of bacterial

contamination. Which of the following statement(s) is/are true
concerning wound classifications?
a. A clean-contaminated wound would be that associated with an
elective colon resection with adequate mechanical and antibiotic
bowel preparation
b. A contaminated wound would include a resection of obstructed
bowel with gross spillage of intestinal contents
c. In a clean wound, no viscus is entered
d. Antibiotic prophylaxis should be administered for all clean-
contaminated and contaminated wounds and selectively in patients
involving a clean wound
Answer: a, b, c, d

Wounds are classified under three classes according to the likelihood

of bacterial contamination: 1) clean (no viscus is entered; e.g.,
herniorrhaphy); 2) clean-contaminated (minimal contamination; e.g.,
elective colon resection with adequate mechanical and antibiotic
bowel preparation, and 3) contaminated (heavily contaminated
surgery; e.g., resection of unprepared, obstructed bowel with gross
spillage of intestinal contents or stool, drainage of abscesses,
debridement of traumatic neglected wounds). Antibiotic prophylaxis
generally should be administered for class 2 and 3 types of wounds,
but patients undergoing clean surgery do not always require
antimicrobial antibiotic prophylaxis. An exception to this tenet
involves cases in which a prosthetic material may be used (artificial
joint, heart valve, tissue patch).

201 The following statement(s) is/are true concerning HIV infection.

a. Initial screening with ELISA is highly sensitive but can be associated
with a false positive rate of 25%
b. Treatment with azidothymidine (AZD) appears to prolong survival
when administered early in the disease
c. Predisposition to infection in HIV infection is primarily due to
reduction in the number of helper T cells
d. Common infections in patients with AIDS are Pneumocystis, carinii
pneumonia, CMV pneumonitis, Cryptococcus meningitis, and
disseminated infection due to atypical mycobacteria
Answer: b, c, d

Acquired immunodeficiency syndrome (AIDS) is a syndrome caused by

the human retrovirus (HIV-1) that infects T lymphocytes and causes
severe immunosuppression. Individuals who become infected with
HIV are prone to a variety of infections and different types of
malignancy. A spectrum exists in which patients regress from
asymptomatic infection, to development of AIDS-related complex
(ARC) of diseases to AIDS itself. Common infections occurring in
patients with AIDS are Pneumocystis carinii pneumonia; CMV
pneumonitis; gastritis, hepatitis and meningitis due to Cryptococcus
neoformans; and pneumonia and disseminated infection due to
atypical mycobacteria. Predisposition to these infections is due, in
part, to the lymphotrophic nature of HIV, which markedly reduces the
number of helper T cells as well as the absolute number of T cells.
HIV detection typically consists of initial ELISA screening, but this test
has about a 1–3% false-positive rate, thus mandating all positive tests
be confirmed by the western immunoblot analysis.
Treatment of ARC and AIDS consists of aggressive antiinfective
therapy once a specific infection occurs and the use of AZT. AZT has
been shown to prolong survival when administered early in the
course of disease and is considered routine therapy.

202 The following statement(s) is/are true concerning initial

microbiologic diagnostic techniques.
a. Appropriate expeditious transport of specimens to the
microbiology laboratory is essential for obtaining accurate clinical
information
b. The use of potassium hydroxide in preparing a specimen slide for
light microscopy will be useful in identification of anaerobic bacteria
c. Antibiotic sensitivity is determined by exposing the specific
microorganism to varying amounts of antibiotic with the
concentration of the antibiotic inhibiting growth referred to as the MIC
(minimal inhibitory concentration)
d. Serum levels of antimicrobial agents should achieve in excess of a
4-to 8-fold increase over the MIC to be considered clinically
efficacious.
Answer: a, c, d

Because most surgical infections are polymicrobial, specimens should

be cultured for aerobic and anaerobic bacteria, as well as fungi.
Although aerobic and aerotolerant microorganisms often do not
require special transport media, a delay in specimen processing may
markedly reduce the yield, and anaerobic transport media have been
demonstrated to markedly increase the cultural yield of this type of
organism. The initial piece of information gained concerning potential
infection may come from simple staining of a specimen. Gram stain,
which will identify the staining characteristics of the organisms, as well
as their number should be performed on all specimens. Potassium
hydroxide is useful in that it will lyse bacteria and other cellular
elements within a preparation and allow observation of yeast or
mycelial elements.
Initial culture results may solely indicate that microorganisms are
growing and full characterization may take two to three days. Once a
specific microorganism is identified, a sample is inoculated during the
log phase into broth containing varying amounts of an antibiotic. After
an 18-to 24-hour period, the tube or well that exhibits no visible
growth is then noted, and the reciprocal of this dilution is termed the
minimal inhibitory concentration (MIC). This value may be compared
to either measured or known achievable serum levels for a particular
antibiotic. In general, antimicrobial agents that achieve in excess of a
4-to 8-fold increase over MIC during the peak serum level have been
demonstrated to be clinically efficacious.

203 The complement system consists of a series of serum proteins

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

Complement activation can occur through either classic or alternate

(properdin) pathways, both of which eventuate in deposition of
terminal complement pathway components on the antigenic cell
surface. The classic pathway of complement activation usually begins
with immunoglobulin G-binding which has also bound the antigen.
The alternate pathway activation occurs in response to activation of
direct binding of the antigen or directly through contact with fungal
and bacterial cell wall compounds such as zymosan and
gram-negative bacterial lipopolysaccharide (LPS endotoxin). Several
complement components represent important host defenses acting
to recruit or augment cellular host defenses or to directly inactivate
invading microbes through lytic activity. The production of
complement component fractions C3a and C5a during activation of
this cascade serve primarily to markedly increase vascular
permeability, and C5a functions as a PMN and macrophage
chemoattractant. This process leads to the recruitment of additional
humoral and cellular defenses to the specific area of infection.
Excessive complement activation can produce deleterious effects in
some instances. Complement activation causes enhanced PMN
adhesion, margination, and release of lysosomal enzymes that can
directly damage certain target tissues, such as the lung.

204 A 55-year-old renal transplant patient has been hospitalized in a

Surgical Intensive Care Unit, receiving a prolonged course of
antibiotics following an attack of acute cholecystitis. The following
statement(s) is/are true concerning his management.
a. Due to the potential risk of Candida infection, prophylaxis with oral
nystatin should be instituted early in the patient’s course
b. A Candida urinary tract infection should be treated with systemic
amphotericin B
c. Changes of Candida retinitis are of little significance
d. The presence of a virulent Candida bacteremia should suggest a
dosage reduction in immunosuppressive agents until the infection can
be adequately controlled
Answer: a, d

Infections due to fungal pathogens have become increasingly

common during the past decade, frequently occurring in patients
undergoing prolonged hospitalization in the Surgical Intensive Care
Unit and in immunocompromised individuals. Prophylaxis with oral
antifungal agents (nystatin) is warranted, especially during periods of
maximal immunosuppression in transplant patients, in patients with
uncontrolled diabetes, or during some cases of prolonged
antibacterial microbial therapy. In general, local, apparently
noninvasive Candida infections involving the integument and mucus
membranes are treated with oral decontamination and topical
antifungal therapy using topical agents such as nystatin. Candida
urinary tract infections can be treated with either an oral antifungal
agent or with topical amphotericin B as a continuous bladder
irrigation. Several studies have demonstrated that those patients with
three positive sites of Candida infection, or with peritoneal or blood
cultures positive for Candida exhibit higher survival rates when
amphotericin B therapy is instituted earlier in the course of infection.
The presence of retinal changes compatible with Candida retinitis or
Candida present within the peritoneal cavity are considered
indications for a limited course of amphotericin B therapy (300% to
500 mg). Patients receiving exogenous immunosuppressive agents
should undergo a marked dose reduction, and some agents should be
discontinued until evidence of infection is absolutely controlled or is
eradicated.

205 The initiation of a humoral immune response involves a complex

interaction of the antigen, cells and intercellular messengers. Which of
the following statement(s) concerning the initiation of the humoral
immune response is/are correct?
a. Helper T lymphocytes stimulate B lymphocytes through secretion of
cytokines such as interleukin 4 and 6
b. A number of cells can aid in presenting the antigen to the helper T
cell including B lymphocytes and macrophages
c. All antigens require coordinated efforts of the various cellular
components of the immune system
d. An antigen must be a living microorganism
Answer: a, b
Stimulation of the immune system occurs after a variety of antigen-
presenting cells (B lymphocytes, macrophages, dendritic cells, and
Langerhans cells) act to engulf, process, and present antigen to T
lymphocytes of helper lineage. These T lymphocytes, in turn, act to
stimulate B lymphocytes to become mature plasmacytes (through
secretion of cytokines such as interleukin 4 and 6) dedicated to the
production of antibody directed against the specific antigen. An
antigen may be defined as any substance that stimulates the host
immune response; that is, that the host immune system recognizes is
foreign. Thus, an antigen may be an invading microorganism, an inert
particle, or any type of chemical compound that triggers the host
immune system. Although some antigens are able to directly
stimulate B lymphocytes in and of themselves to produce antibody
(many polysaccharides), most antigens require coordinated efforts of
the various cellular components of the immune system.

206 The following statement(s) is/are true concerning viral infections.

a. The most common post-transplantation viral infections are caused
by herpes viruses and include CMV and herpes simplex virus
b. Viral infections occur at equal frequency anytime during the
post-transplantation period
c. CMV infection in the post-transplant patient is most likely a
pulmonary process
d. Herpes simplex virus (HSV) infection primarily presents with a
mononucleosis-type syndrome with fever, lethargy, and cough
Answer: a, c,

Solid organ transplant patients are prone to develop viral infection by

virtue of exogenous immunosuppression. The most common
post-transplantation viral infections are those caused by herpes
viruses (CMV, herpes simplex virus [HSV], Epstein-Barr virus [EBV], and
Varicella-Zoster virus [VZV]). All are most common during periods of
maximal host immunosuppression that occur immediately
post-transplantation and during periods of allograft rejection. CMV is
a common cause of fever after solid organ transplantation, and
evidence of CMV infection occurs in approximately 30% of patients.
The most common presentation for CMV infection is that of a febrile,
leukopenic patient with a cough, diffuse interstitial infiltrates on chest
x-ray, and hypoxia.
HSV infection causes primarily oral pharyngeal ulcerations in most
cases, although sporadic cases of disseminated disease have been
reported. EBV causes an occasional case of mononucleosis-type
syndrome but has also been clearly indicated in the pathogenesis of
post-transplantation lymphomas. VZV infection can present as
disseminated and occasionally life-threatening infections in the
nonimmune transplant patient or as painful herpes zoster in patients
who have previously developed chicken pox.

207 The following statement(s) is/are true concerning necrotizing

fascitis.
a. Mortality rates as high as 40% can be expected
b. The infection involves only the superficial fascia, sparing the deep
muscular fascia
c. An impaired immune system is a common factor predisposing to
this condition
d. The infection is usually polymicrobial
e. Necrotizing fascitis is most likely to develop in the face of impaired
fascial blood supply
Answer: a, c, d, e

Necrotizing fascitis is an uncommon infection of the deep and

superficial fascia that is associated with mortality as high as 40% in
many series. Although many underlying disease processes predispose
patients to necrotizing fascitis, three common factors are almost
invariably present: 1) impairment of the immune system; 2)
compromise of fascial blood supply, and 3) the presence of
microorganisms that are able to proliferate within this environment.
Infections of this type are usually polymicrobial in nature, with
gram-positive organisms such as staphylococci and streptococci,
gram-negative enteric bacteria, and gram-negative anaerobic being
frequently identified. These polymicrobial cultural results are
assuredly indicative of the occurrence of a synergistic process,
perhaps in large part accounting for the severity of these infections.
Some microorganisms possess virulence factors that, in conjunction
with an underlying host predisposition, allow this disease process to
occur without dependence on other bacteria. Examples of such
bacteria include Clostridium, Pseudomonas, and Aeromonas. In these
patients, the process is often fulminant and is frequently associated
with cellulitis, myositis, fascitis, and bacteremia with attendant high
mortality.

208 New treatment modalities designed to modulate host defense

mechanisms that have been demonstrated conclusively to be of
benefit include:
a. Gut decontamination
b. Anti-LPS antibody
c. Anti-TNF antibody
d. Thymopentin
e. None of the above
Answer: e
Selective gut decontamination involves the use of orally administered
antibiotics that achieve a high intraluminal level directed against
gram-negative aerobes and yeast, leaving the host anaerobic
intestinal microflora relatively undisrupted. Although a reduction and
alteration of the microorganisms responsible for infectious episodes
have been demonstrated in certain groups of patients, a clear-cut
impact on host mortality has not been shown. Because LPS may be
responsible for toxicity both directly and through host mediator
systems, the availability of agents to bind against this portion of the
gram-negative bacteria to reduce mortality has been intensively
examined. Unfortunately, large multicenter randomized trials provide
no evidence of benefit for this treatment. Similarly, since many of the
systemic manifestations of gram-negative bacteremia are mediated
by cytokines, the effect of an anti-TNF antibody preparation is
currently in clinical trial. No proven benefits have yet been identified.
Finally, the use of immunostimulants to enhance the state of
activation of host defenses has been proposed. Thymopentin is a
peptide that contains active thymopoetin, a thymic molecule that acts
to stimulate T-lymphocyte activity. Preliminary trials indicate that this
agent ameliorates host septic response after major operations and
trauma but conclusive evidence that concurrent reduction of
infection-related mortality occurs is not available.

209 Antibacterial agents can be classified with regard to their

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

Penicillins, cephalosporins, and monobactams possess a b-lactam ring

of some type and act to bind bacterial division plate proteins, thus
inhibiting cell wall peptidoglycan synthesis and either causing or
inducing autolytic bacteriolysis. Because gram-positive and
gram-negative bacteria possess different types of division plate
proteins, many of these agents exhibit differential activity between
these two types of microorganisms. Tetracyclines, chloramphenicol,
and macrolides inhibit bacterial ribosomal activity, and thus overall
protein synthesis by a variety of different mechanisms.
Aminoglycosides act to inhibit protein synthesis and also presumably
act on a different target site, a supposition based on the fact that
aminoglycosides are bacteriolytic and the other agents are
bacteriostatic. Vancomycin inhibits assembly of peptidoglycan
polymers, whereas quinolones bind to DNA helicase proteins and
inhibit bacterial DNA synthesis. Sulfonamides and trimethoprim act in
different mechanisms to inhibit protein synthesis, therefore two
agents in combination act synergistically.

210 The treatment of the following patient should include:

a. Initial empiric therapy directed against both aerobes and anaerobes
b. The addition of anti-fungal therapy in an elderly patient
c. A minimum of two weeks of antibiotic therapy is indicated
d. The addition of appropriate antibiotic therapy has made surgical
therapy unnecessary in such cases
e. Either a single agent or combination therapy is appropriate if the
agents selected possess activity against both aerobic and anaerobic
bacteria
Answer: a, e

The primary treatment for a perforated viscus is surgical, however

antimicrobial therapy is an extremely important adjunct. Empiric
antibiotic therapy for secondary bacterial peritonitis and
intraabdominal abscess should be directed against both aerobes and
anaerobes. Administration of an agent directed against only one
component of the infection or the other is inferior to combined
therapy. Several studies indicate that the results of using several
agents in combination is equivalent to the use of a single agent
therapy as long as the agents selected possess activity against both
components of the infection. The addition of antientercoccal or
antifungal agents as initial therapy has not been substantiated. The
most beneficial duration of antibiotic therapy must be based on the
setting for the specific patient. Minimal peritoneal contamination with
adequate surgical treatment may be treated with a three-to five-day
course of antibiotics, whereas longer periods are indicated for
immunosuppressed patients and with patients with extensive
contamination.

211 The following statement(s) is/are true concerning host defense

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

The introduction of microorganisms into the normally sterile

peritoneal environment invoke several potent specialized host
antimicrobial defense mechanisms. Bacterial clearance, also termed
translymphatic absorption, occurs through specialized structures
found only on the peritoneal mesothelium on the underside of the
diaphragm that act as conduits for both fluid and particulate matter.
Lymphatic channels eventually form which drain into the venous
circulation via the thoracic duct. Bacteria not cleared via
translymphatic absorption are rapidly engulfed by resident and
recruited phagocytic cells including resident macrophages on the
peritoneal surface and omentum and attracted PMNs. The final
primitive host defense mechanism is sequestration by which a
fibrinogen-rich exudate containing plasma oposonins appears during
peritoneal infection and fibrin polymerization occurs. Fibrin has the
capacity to trap large numbers of bacteria and other particulate
matter. Acting in conjunction with omentum and other mobile viscera,
perforations are sealed and the contaminated enteric contents walled
off, preventing continued soilage of the peritoneal cavity.

212 A 67-year-old male presents with an intraabdominal abscess

secondary to perforated sigmoid diverticulitis. The following
statement(s) is/are true concerning his intraabdominal abscess.
a. Culture will likely reveal a solitary organism
b. Both aerobic and anaerobic islets are encountered in 50% of
specimens
c. The most common aerobic islet will be likely E. coli and other
gram-negative enteric bacilli
d. The most common anaerobic islet will be a Bacteroides species
Answer: b, c, d

Typically an intraabdominal infection results in perforation of a hollow

viscus and the ensuing contamination of a normally sterile peritoneal
cavity. The normal bacterial flora found in that particular location of
the alimentary tract thus determines the initial inoculum. In parallel
with the overall quantity of microorganisms, (both aerobes but
predominantly anaerobes) perforations of the lower small bowel and
colon produce a high frequency of infections that contain anaerobic
microorganisms. Certain predictable patterns of bacterial islets are
found, but on average four to five islets occur in patients with
established intraabdominal infection, more than half of which are
anaerobes. Both aerobes and anaerobes are encountered in 80% to
90% of specimens. Commonly encountered aerobes isolated are E.
coli and other gram-negative enteric bacilli such as Enterobacter,
Klebsiella. Among the anaerobes, Bacteroides species (especially B.
fragilis, Clostridium), and anaerobic cocci are most consistently
isolated.

213 The following statement(s) is/are true concerning gram-negative

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

Gram-negative bacterial sepsis is a serious disease process that

produces substantial morbidity and mortality in both normal and
immunocompromised patients (10% to 20% and 30% lethality,
respectively), despite therapeutic intervention with antimicrobial
agents, aggressive hemodynamic monitoring, fluid resuscitation, and
metabolic support. During the past several decades, nosocomial
infections due to gram-negative pathogens have increased in
frequency with resultant increase in the incidence of gram-negative
bacteremia to between 3 and 13 cases per 1000 hospital admissions.
Factors that predispose to these infections include: 1) underlying host
disease processes such as malignancy, diabetes; 2) old age and
disability; 3) malnutrition; 4) previous or concurrent antimicrobial
antibiotic therapy; 5) major operations; 6) respiratory or urinary
manipulation or intubation; and 7) immunosuppression.
Although many different organisms cause this form of sepsis, E. coli
predominates in overall frequency. Also common are isolates of
Klebsiella, Enterobacter and Serratia; Pseudomonas bacteremia is less
common. Some studies, however, have suggested that Pseudomonas
sepsis is associated with the highest lethality. In several series, 10% to
20% of patients have had polymicrobial series, and most investigators
agree that polymicrobial sepsis is more lethal than infection with a
single organism.

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

various types of shock?
a. Traumatic shock is more commonly associated with subsequent
organ injury and multiorgan failure syndrome than hemorrhagic
shock
b. Cardiogenic shock can be of either an intrinsic or compressive
nature
c. Hypodynamic septic shock is associated with a decreased mortality
risk when compared with hyperdynamic septic shock
d. Hypoadrenal shock usually responds quickly to resuscitation
e. Neurogenic shock occurs with the absence of sympathetic activity
Answer: a, b, d, e

Classification schemes of shock based on cause have been developed

for the seemingly dissimilar processes leading to circulatory collapse
and the shock state. Hypovolemic shock, the most common, is the
result of intravascular volume depletion through loss of red blood cell
mass or plasma volume. Microvascular hypotension results from a
combination of low intravascular blood volume, diminished cardiac
output, and compensatory sympathetic peripheral vasoconstriction.
Shock associated with trauma (traumatic shock) arises from the
consequences of hypovolemia due to hemorrhage in conjunction with
direct soft tissue injury and bone fracture. Hypovolemia caused by
blood loss and fluid extravasation into injured tissues is compounded
by activation of maladaptive inflammatory cascades initiated by the
tissue injury. In contrast to pure hemorragic shock, subsequent organ
injury and multiorgan failure syndrome (MOFS) occurs much more
frequently following traumatic shock due to the over-expression of
these immuno-inflammatory cascades. Cardiogenic shock is the result
of failure of the heart as an effective pump, resulting in inadequate
cardiac output, tissue perfusion and oxygen delivery. Intrinsic causes
include myocardial infarction, cardiomyopathy, valvular heart disease,
or rhythm disturbances. Compressive cardiogenic shock is a discrete
entity that results when extrinsic compression of the heart limits
diastolic filling and thus systolic ejection and cardiac output. Septic
shock refers to hypotension and circulatory insufficiency developing
as a consequence of infection and the systemic response to that
infection. In its hyperdynamic form, septic shock is marked by
diminished peripheral vascular resistance and generalized
vasodilatation causing relative hypovolemia. In contrast, hypodynamic
septic shock occurs in situations of inadequate resuscitation or
preterminal cardiovascular decompensation, and is associated with
vasoconstriction and a greatly increased mortality risk. Sympathetic
denervation through spinal cord injury, spinal anesthesia, or severe
head injury produces generalized arterial vasodilatation and
venodilation. Shock occurs when the normal blood volume fails to fill
the available intravascular space and severe relative hypovolemia
exists. Despite hypotension, there is a noteworthy absence of
sympathetic activity, as occurs in hypovolemia or cardiogenic shock.
Profound shock can occur in surgical patients following stress due to
the loss of the homeostatic corticosteroid response. Hemodynamic
instability may develop after an operative procedure or coincident
with an unrelated illness. The profound circulatory collapse is often
refractory to vigorous resuscitation with fluids and pressor agents.
The response to exogenous corticosteroids is usually dramatic and
potentially life-saving.

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

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

A broad spectrum of metabolic abnormalities become apparent in

sepsis and the systemic inflammatory response syndrome following
shock. Disruption of the normal cycles of carbohydrate, lipid, protein,
and oxygen metabolism occur as hypermetabolism develops. Through
the Cori cycle, lactate from the periphery is shuttled back to the liver,
where it is used in the production of glucose. Because pyruvate is
converted to alanine in the periphery, flux of alanine also contributes
to hepatic gluconeogenesis. The glycolytic oxidation of glucose to
pyruvate and its subsequent glugoneogenic regeneration from lactate
is an inefficient cycling of substrate. There is no net energy
production, but heat is released in significant quantities. Alterations in
lipid metabolism cause a progressive rise in the serum triglyceride
level as a result of less efficient clearance of exogenous triglycerides
coupled with increased hepatic lipogenesis. Profound alterations in
protein and amino acid metabolism develop with characteristic
changes in amino acid levels, nitrogen balance, and skeletal muscle
mass. Initially levels of the branch chain amino acids are reduced,
whereas those of the aromatic amino acids are elevated. There is an
increase in the oxidative metabolism of protein to meet energy needs
and a tremendous mobilization of nitrogen with net negative nitrogen
balance. The branch chain amino acids are preferentially utilized in
the TCA cycle to maintain an activity that otherwise would be lost from
the diminished entry of carbohydrate-and fatty acid-generated acetyl
coenzyme A. This results in reduced serum level of leucine, isoleucine
and valine.
216 Which of the following statement(s) is/are true concerning the
microvascular and cellular response to shock?
a. Osmodically induced mobilization of intracellular fluid is the initial
response to restore intravascular volume
b. With larger volume hemorrhagic shock deterioration of normal
cellular transmembrane potential occurs resulting in an increase in
extracellular sodium and water
c. The accumulation of anaerobic metabolites override normal
homeostatic vasomotor tone and contribute to the maladaptive
vasodilatation
d. Abnormal intracellular calcium homeostasis may contribute to the
cellular dysfunction of shock
Answer: c, d

Moderate hypovolemia results in a relatively rapid spontaneous

restitution of intravascular volume through expansion of the plasma
space. This plasma expansion by erythrocyte free fluid occurs within
one hour as a result of alterations in pressure and osmolarity and
produces an associated hemodilution. Sympathetic discharge,
associated arteriolar constriction, and induced metabolic changes in
osmolarity initiate the compensatory events at the microcirculatory
level. The initial pressure-related phase of restitution of blood volume
in shock is overlapped by a second phase involving osmotically
induced mobilization of intracellular fluid. Osmotic mechanisms
contributing to the restitution of blood volume after moderate
hemorrhage are not adequate in hemorrhage of greater magnitude.
In larger hemorrhages (over 25% blood volume), there is also
deterioration of the normal cellular transmembrane potential, an
increase in intracellular sodium and water, and a concomitant
decrease in extracellular fluid volume. Tissue hypoxia results,
anaerobic metabolites accumulate, and the cell cannot maintain the
normal cell membrane potential. Accumulation of hydrogen ion,
lactate, and other products of anaerobic metabolism override
homeostatic vasomotor tone and contribute to a maladaptive
vasodilatation, further augmenting hypotension and hypoperfusion.
The uptake of fluid by the “failing” cell is a major source of food
sequestration following shock. Loss of membrane function is
proportional to both the extent and duration of shock or degrees of
sepsis. The etiology of membrane failure is unclear but appears
multifactorial. Loss of intracellular ATP energy stores during
hypoperfusion or direct toxicity during sepsis may inhibit the
membrane sodium-potassium pump. Cellular dysfunction also
appears to be related to abnormal intracellular calcium homeostasis.
217 Which of the following statement(s) is/are true concerning the
pulmonary response to shock?
a. The acute pulmonary vascular response to shock differs markedly
from that of systemic vasculature
b. The pulmonary edema of ARDS occurs in the face of elevated left
heart pressures
c. The initial physiologic changes of ARDS involve the capillary
endothelial cells and the type I pneumocyte
d. Mechanisms proposed in the pathogenesis of ARDS include injury
from mediators of inflammation elsewhere and from activated cellular
elements
e. A decrease in lung compliance may result from the loss of type I
pneumocytes
Answer: c, d, e

Contributing pathophysiologic processes to the pulmonary

manifestations of shock include the pulmonary component of the
cardiovascular response, disruption of the normal lung mechanics,
and acute lung injury or ARDS due to sepsis. Pulmonary function may
be further compromised by pathology intrinsic to the lung itself,
including pulmonary contusion, aspiration, airway obstruction,
pneumonia, pneumothorax, hemothorax, and atelectasis. The acute
pulmonary vascular response to shock largely parallels that of the
systemic vasculature. The increase in pulmonary vascular resistance,
which may proportionally exceed that of the systemic circulation,
transiently accompanies the systemic adrenergic response. ARDS is a
syndrome of progressive lung injury that may arise as a direct
consequence of shock or other disease processes. The characteristic
findings of ARDS are the presence of pulmonary edema, hypoxemia,
and significantly decreased lung compliance. The pulmonary edema is
noncardiac in origin and occurs in the face of normal left heart
pressures. The hypoxemia results from the development of
intrapulmonary shunting and perfusion of under and nonventilated
alveoli. The decrease in lung compliance results from the loss of
surfactant and lung volume in combination with the presence of
interstitial fluid and alveolar edema. Progressive histologic changes of
ARDS become apparent in pulmonary capillaries, interstitium, and
alveoli. Initially, interstitial edema develops with swelling of the
capillary endothelial cells and the type I pneumocytes. The type I
pneumocytes subsequently slough, and alveolar edema ensues.
Functional surfactant is lost with a significant increase in alveoli
opening pressure and decrease in alveolar surface tension.
Mechanisms proposed in the pathogenesis of ARDS include injury
from mediators of inflammation elaborated elsewhere, and from
activated cellular blood elements.
218 Which of the following statement(s) is/are true concerning the
diagnosis and management of hypovolemic shock?
a. A fall in hematocrit or hemoglobin always accompanies
hemorrhagic shock
b. The treatment of shock is generic regardless of the etiology
c. Pharmacologic intervention to increase myocardial contractility in
hypovolemic shock is an important part the early management
d. Complications are less frequent after treatment of hemorrhagic
shock than septic or traumatic shock
Answer: d

Hypovolemic shock is readily diagnosed when there is an obvious

source of volume loss and overt signs of hemodynamic instability and
increased adrenergic output are present. After acute hemorrhage,
hemoglobin and hematocrit values do not change until compensatory
fluid shifts have occurred or exogenous fluid is administered. These
values decrease once transcapillary refill, osmotic-induced shifts, or
non-RBC volume resuscitation expands the blood volume. It is
imperative that the distinction be made between hypovolemic and
cardiogenic forms of shock, because appropriate therapy differs
dramatically. Restoration of perfusion in hypovolemic shock requires
reexpansion of circulating blood volume in conjunction with necessary
interventions to control ongoing volume loss. Continued
hemodynamic instability after fluid resuscitation implies that shock
has not been reversed or that there is ongoing blood or volume loss.
In severe, prolonged hypovolemia, ventricular contractile function
may itself become depressed and require inotropic support to
maintain ventricular performance, but in general, pharmacologic
interventions directed toward increased contractility in situations of
inadequate preload are ineffective, further complicate metabolic
derangements, and are not indicated until adequate volume
replacement has been completed. Complications are less frequent
after treatment of hemorrhagic shock than in situations of septic or
traumatic shock. In the later circumstances, the massive activation of
inflammatory mediator response systems and consequences of their
disseminated, indiscriminate cellular injury can be quite profound.

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

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

The neuroendocrine response to shock attempts to achieve

restoration of effective blood volume, mobilization of metabolic
substrates, and maintenance of central profusion. Both peripheral
and central afferent stimuli to the central nervous system are involved
in inducing this response. Hypotension, associated with a decrease in
impulses from the aortic and carotid baroreceptors, disinhibits the
vasomotor center. This disinhibition results in increased adrenergic
output and decreased vagal activity. Sympathetic nerve endings
release norepinephrine, inducing peripheral and splanchnic
vasoconstriction which is responsible for greater than 80% of systemic
vascular resistance and is a major contributor to maintenance of
central organ perfusion and venous return. Plasma levels of both
epinephrine and norepinephrine are elevated with injury, and the
degree of the catecholamine elevation corresponds to the magnitude
of injury. In shock the effects of endogenous epinephrine are largely
metabolic. In addition to initiating autonomic nervous activity, the
hypothalamus secretes releasing hormones, which induce the stress
hormone release of the pituitary. As part of this response,
adrenocorticotropic hormone (ACTH) secretion by the anterior
pituitary is increased stimulating cortisol secretion by the adrenal
cortex. In conjunction with elevated plasma levels of cortisol and
epinephrine, increased pancreatic secretion of glucagon accelerates
hepatic gluconeogenesis and further aggravates the glucose
intolerance that follows injury and sepsis. The secretion of renin is
increased in responses to adrenergic discharge and decreased
perfusion of the juxtaglomerular apparatus in the kidney. Renin
allows formation of angiotensin I in the liver, which is then converted
to angiotensin II in the lungs. Angiotensin II is an extremely effective
vasoconstrictor that further augments sympathetic-mediated
vasoconstriction.

220 A 22-year-old man sustains a single stab wound to the left chest
and presents to the emergency room with hypotension. Which of the
following statement(s) is/are true concerning his diagnosis and
management?
a. The patient likely is suffering from hypovolemic shock and should
respond quickly to fluid resuscitation
b. Beck’s triad will likely be an obvious indication of compressive
cardiogenic shock due to pericardial tamponade
c. Echocardiography is the most sensitive noninvasive approach for
diagnosis of pericardial tamponade
d. The placement of bilateral chest tubes will likely resolve the
problem
Answer: c
Shock from cardiac compression occurs when external pressure on
the heart impairs ventricular filling. Because ventricular filling is a
function of venous return and myocardial compliance, any process
that places pressure on the heart can cause compressive cardiogenic
shock. Included among these are pericardial tamponade, tension
pneumothorax, mediastinal hematoma, and positive pressure from
mechanical ventilation. Any patient with hypotension after a wound in
proximity of the heart should be considered to have compressive
cardiogenic shock until proven otherwise. The classical clinical findings
of pericardial tamponade include Beck’s triad of hypotension, neck
vein distention and muffled heart sounds. Pulses paradoxus may be
noted (this involves a decrease rather than the normal increase of
systolic blood pressure with inspiration; values 10mmHg are
significant). These findings, however, may be obscured in a noisy
emergency room environment by positive pressure ventilation or by
associated injuries. Placement of a CVP catheter confirms the
elevation of right-sided filling pressure. If a pulmonary artery catheter
has been placed, findings consistent with tamponade or other forms
of cardiac compression are a trend toward equalization of chamber
pressures as hypotension progresses. In the patient at risk,
echocardiography is an extremely sensitive and noninvasive approach
to demonstrate pericardial fluid and the need for operation.
Pericardial tamponade must be relieved urgently and cardiac injuries
require emergent sternotomy. Chest tube placement would not be
appropriate as the sole treatment in this patient.

221 A 32-year-old man suffers a spinal cord injury with a resultant

paraplegia in a motorcycle accident. He presents to the emergency
room with hypotension. Which of the following statement(s) is/are
true concerning his diagnosis and management?
a. The low blood pressure can be assumed to be due to neurogenic
shock
b. The sole cause of hypotension is the loss of sympathetic input to
the venous system
c. Despite significant hypotension, secondary organ injury will be
uncommon
d. There is no role for pharmacologic intervention to maintain blood
pressure
Answer: c

Neurogenic shock results from interruption of sympathetic vasomotor

input and develops after spinal cord injury, spinal anesthesia, and
severe head injury. Under normal conditions, baseline sympathetic
activity establishes a degree of arteriolar and venous constriction.
Ablation of this tone results in decreased systemic vascular resistance
and a dramatic increase in venous capacity, causing hypotension due
to relative hypovolemia. Arteriolar dilatation not only lowers the
systemic vascular resistance but also allows previously unopened
vascular beds to be perfused, greatly expanding venous capacity.
Removal of sympathetic inputs to innervated portions of the venous
system allows further venodilatation. Restoration of an effective,
albeit expanded, intravascular volume may require extremely large
volumes of resuscitation fluid to restore normal cardiac filling
pressures. This will restore cardiac output and reverse hypotension.
However, pharmacologic intervention with vasoactive drugs may be
necessary and is preferable to excessive volume resuscitation.
Post-shock sequelae are infrequent. Although there is significant
hypotension with neurogenic shock, there is usually little if any
hypoperfusion. Thus, activation of inflammatory cascade and
subsequent organ injury rarely occur.
A major pitfall in the management of neurogenic shock arises when
there is coexistent hemorrhage or ongoing volume loss that is not
appreciated. This is not an unusual situation because cervical spine
trauma causing paraplegia or severe head injury is frequently
associated with multiple injuries. Thus, in trauma the initial response
to neurogenic shock is large volume resuscitation regardless of the
presumed etiology. If hemodynamic instability persists after initial
trauma resuscitation, one must assume that the cause is not
neurogenic and search for occult blood loss or cardiogenic causes of
shock.

222 Which of the following statement(s) is/are true concerning septic

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

The clinical findings in sepsis and septic shock represent the host
response to infection. Gram-positive and gram-negative bacteria,
viruses, fungi, rickettsiae, and protozoa have all been reported to
produce a clinical picture of septic shock, but the overall response is
independent of the specific type of invading organism. Septic shock
develops as a consequence of the combination metabolic and
circulatory derangements accompanying the systemic infection. It
appears that the circulatory deficits are preceded by the metabolic
abnormalities induced by infection. In fact, the circulatory changes in
hyperdynamic sepsis appear to be an adaptive response to the
underlying metabolic dysfunction. Cardiac output is high and systemic
vascular resistance low in hyperdynamic septic shock. However,
splanchnic vasoconstriction is pronounced even in the absence of
systemic hypotension and even though systemic vascular resistance is
reduced. Expansion of circulating blood volume can occur through
either transcapillary refill or fluid resuscitation. Due to the ongoing
inflammatory mediator-induced increases in capillary permeability
and continued loss of intravascular volume, exogenous volume
resuscitation must be provided to restore venous return and
ventricular filling.

223 Which of the following statement(s) is/are true concerning tumor

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

Tumor necrosis factor (TNF), a protein product of activated

macrophages, is secreted in response to contact with endotoxin or
lipopolysaccharide, antibody complexes, or other inflammatory
stimuli. Elevation of serum levels of TNF have been reported shortly
after experimental trauma and shock, however, documentation of
elevated circulating levels of TNF in human shock is less clear.
Furthermore, circulating levels of TNF cannot be correlated with
severity of tissue injury or shock. This variability is thought to be due
to rapid clearance and uptake by membrane receptors and by soluble
membrane receptors that are released from multiple cells following
stress and injury. Following hypoperfusion the liver and gut appear to
be the major source of TNF that is rapidly cleared but responsible for
inducing hepatocyte changes following shock. The release of
breakdown products and escape of bacterial and endotoxin through
the damaged mucosal barrier of the gut following shock allows or
induces activation of tissue-fixed macrophage (Kupffer cell) of the liver
which then produces secondary inflammatory mediators contributing
to the post-resuscitation clinical response and inflammatory mediator
activation seen in the systemic inflammatory response syndrome.
TNF is central to inflammatory response, particularly in sepsis and
following endotoxemia or bacteremia. TNF also induces secondary
inflammatory responses through direct interaction with specific
membrane receptors, TNF-r. Treatment with anti-TNF antibody in the
experimental setting protects animals from the deleterious effects of
lethal bacteremia and endotoxemia. However, recently completed
clinical trials in septic patients utilizing infusion of monoclonal
antibodies to the TNF molecule have shown no overall survival
benefit.

224 Which of the following statement(s) is/are correct concerning the

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

Inflammatory mediators have recently been recognized as playing a

significant role in the clinical manifestations and progression of shock
and the development of subsequent complications. These mediator
systems function primarily as parcrine and autocrine agents in the
local environment and are not usually detectable systemically. The
over-expression and systemic dissemination of these mediators
produces the toxic autodestructive processes underlying multiorgan
failure syndrome with attendant high mortality. The compliment
cascade is activated in shock and tissue injury through both the
classical and alternative pathways. Activation of either pathway results
in generation of the anaphylatoxin, C3a and C5a, soluble products
with potent systemic hemodynamic effects. The eicosanoids, which
include the prostaglandins and leukotrienes are formed acutely from
arachidonic acid released from the membrane phospholipid by
phospholipase A2. Eicosanoids are not stored in any measurable level
and are generated as needed from readily available arachidonic acid
in response to various inflammatory phenomena. Platelets, white
cells, and endothelial cells are a rich source of these compounds.
Thromboxane (TXA2) is the major arachidonic acid metabolite
elaborated by platelets. TXA2 induces intense vasoconstriction,
platelet aggregation and degranulation, neutrophil margination in the
microcirculation and bronchial constriction. PGI2, the major
arachidonic acid metabolite formed by endothelial cells, serves a
check against actions of TXA2. PGI2 is a vasodilator and a potent
inhibitor of platelet aggregation. Platelet aggravating factor is a potent
phospholipid mediator released by neutrophils, platelets,
macrophages and endothelial cells in response to ischemia, tissue
injury and sepsis. Its effects include decreased cardiac function,
increased pulmonary vascular resistance, bronchoconstriction,
peripheral vasodilatation, and increased vascular permeability.

225 Which of the following physical findings are associated with the
various classes of hemorrhagic shock?
a. Mild shock (< 20% blood volume): Pallor, cool extremities,
diminished capillary refill and diaphoresis
b. Moderate shock (20%–40% blood volume): All of the above plus
tachycardia and hypotension
c. Severe shock (> 40% blood volume): Systemic hypotension, changes
in mental status, tachycardia, oliguria
d. All of the above
Answer: a, c
PHYSICAL FINDINGS IN HEMORRHAGIC SHOCK*

Moderate
Mild (<20% (20%-40% Severe(>40%
Blood Volume) Blood Volume) Blood Volume)
Pallor Pallor Pallor
Cool extremities Cool extremities Cool extremities
Diminished capillary Diminished capillary Diminished capillary
refill refill refill
Diaphoresis Diaphoresis Diaphoresis
Collapsed Collapsed Collapsed
subcutaneous subcutaneous subcutaneous
veins veins veins
Tachycardia Tachycardia
Oliguria Oliguria
Postural Hypotension
hypotension Mental status
changes

* Alcohol or drug intoxication may alter physical findings.

226 A 68-year-old male who underwent a repair of an abdominal

aortic aneurysm 5 days ago, develops tachycardia, tachypnea,
hypotension with cool, pale, mottled cyanotic extremities. He is
agitated and complains of shortness of breath. Which of the following
statement(s) is/ are correct concerning his diagnosis and
management?
a. Myocardial ischemia secondary to preexisting coronary artery
disease is most likely the underlying cause of this problem
b. Invasive hemodynamic monitoring with a Swan-Gantz catheter will
demonstrate a low cardiac output, a high systemic vascular resistance,
and elevated cardiac filling pressures
c. The use of morphine sulphate and nitrates should be part of the
initial management
d. The primary pharmacologic treatment involves the use of moderate
doses of inotropic agents
e. Afterload reduction with nitroprusside is absolutely contraindicated
Answer: a, b, d

Intrinsic cardiogenic shock results from failure of the heart as an

effective pump. Coronary artery disease is the most common cause of
myocardial insufficiency, but contractile dysfunction may also rise as a
consequence of cardiomyopathy, myocarditis, or metabolic
abnormalities. Invasive hemodynamic monitoring often establishes a
specific nature of shock and allows appropriate treatment to be
delivered in an effective and expedient manner. Hemodynamic
findings consistent with cardiogenic shock include a low cardiac
output and high systemic vascular resistance, with elevated cardiac
filling pressures. The initial measures in the management of
cardiogenic shock include the administration of supplemental oxygen,
mechanical ventilation (as needed), and appropriate treatment of
dysrhythmias. Hypotension usually precludes the use of morphine
sulfate and nitrates, drugs typically used in simple congestive heart
failure to alleviate cardiac pain and ameliorate pulmonary vascular
congestion. The use of beta-adrenergic agonists such as dopamine
and dobutamine, in moderate doses, offers positive inotropic support
without excessive alpha-adrenergic activity. Increasing the inotropic
state of the heart shifts the entire Starling curve upward, resulting in
increased cardiac output for each level of cardiac filling. Afterload
reduction may prompt increases in cardiac output through decreases
in resistance to flow. The use of nitroprusside or other dilators
requires relative blood pressure stability and close hemodynamic
monitoring. Infusion of afterload-reducing agents can be
administered in conjunction with inotropic support.

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

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

During the ischemia and hypoperfusion phase, degradation of ATP

stores essential to maintain cell integrity and significant loss of
diffusible intracellular adenine neuclotides occurs. As ATP further
degrades there is an elevation in plasma and intracellular levels of
hypoxanthine and xanthene which upon restoration of perfusion and
reoxygenation are catalyzed by xanthine oxidase resulting in the
formation of superoxide radicals. These radicals plus others such as
hydrogen peroxide and hydroxyl radical are generated and lead to
endothelial and parenchymal cell injury through membrane lipid
peroxidation and activation of critical enzymes. These radicals have
also been shown to be involved in the expression of proinflammatory
phenotype endothelial cells and on macraphages and neutrophils.
The proinflammatory phenotype of the endothelium includes
procoagulant activity and the expression of adhesion molecules on
the membrane surface, including the intercellular adhesion
molecule-1 (ICAN-1) and the selectins. The subsequent adhesion of
activated neutrophils to the endothelial leads to an explosive
oxidative burst producing additional radicals and extensive release of
proteolytic enzymes leading to injury and disruption of the endothelial
lining, extensive capillary leak, and massive interstitial edema. Passive
immunization of animals with monoclonal antibodies to either the
neutrophil adhesive complex or the endothelial selectins dramatically
lessens ischemia/reperfusion microvascular injury.

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

physiology of the microvascular system?
a. Filtration of capillary fluid into the interstitial and the subsequent
reabsorption is influenced by Starling’s law of ultrafiltration
b. The most important variable controlling blood to a capillary bed is
the length of the vessel
c. Most of the resistance to systemic blood flow occurs at the
arteriolar level
d. Adrenergic vasoconstriction can arrest blood flow to an entire
capillary bed
Answer: a, c, d

Exchange of material between the vascular space and the cell of

various tissues via the interstitial space is essential for organ viability
and occurs at the capillary level. The filtration of capillary fluid into the
interstitium and its subsequent reabsorption into the post capillary
venule is governed by microvascular permeability in conjunction with
the balance between hydrostatic and oncotic pressures. The relation
of these forces to one another (and their net effects) are illustrated by
what is termed Starling’s law of ultrafiltration. In normal
circumstances, a net filtration from capillary to interstitium is effected
by a relatively higher capillary hydrostatic pressure, whereas net
reabsorption from the interstitium back into the post capillary venule
occurs as hydrostatic pressure falls and oncotic forces predominate.
Although the mechanisms controlling blood flow to the capillary bed
are complicated and vary among the different tissues, certain
concepts are useful. Poiseuille’s law describes the relation between
flow of fluid through a tube and the tube length and radius, the fluid
viscosity, and the pressure gradient between ends of the tube. The
radius of the tube (or vessel) is the single most important variable,
because flow is proportional to the radius to the fourth power.
Vasoconstrictive and vasodilatory influences directly impact local
blood flow, as well as flow to other tissues through secondary effects
on the systemic pressure. This secondary effect of peripheral
vasoconstriction maintains the pressure gradient for central perfusion
of the heart and brain. Systemic blood flow meets most of its
resistance at the arteriolar level. While the individual capillary radius is
significantly smaller, the vast number of capillaries offers less total
resistance. The vascular smooth muscle in arterioles has both a-and
b- adrenergic receptors. Alpha stimulation affects vasoconstriction
where beta stimulation affects vasodilatation. The efferent
sympathetic fibers innervating the precapillary resistance vessels and
the venous capacitance vessels release norepinephrine on
stimulation, which induces smooth muscle contraction and narrowing
of the caliber of the vessels. These contractions are potent enough
that blood flow to entire capillary beds can be arrested by adrenergic
vasoconstriction.

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

effects of MOFS?
a. Pulmonary dysfunction tends to arise early and may resolve within
7 to 10 days
b. Unless the precipitating insult has prompted oliguric acute tubular
necrosis, renal function tends to be maintained early in the course of
MOFS
c. Although hepatic dysfunction is common with MOFS, the GI tract
plays little role in this process
d. Intercurrent nosocomial infection, most commonly pulmonary, is a
common complication providing a “second hit” to the patient
Answer: a, b, d

Pulmonary dysfunction typically arises early in the development of

systemic inflammation and may represent mild relatively localized
acute lung injury or it may be a prelude to fulminant ARDS. The lung
injury, and associated dysfunction, may resolve over the initial 7 to 10
days or persist, depending on the ongoing pathologic process. Many
times a “second hit” such as a nosocomial infection, which is most
commonly pulmonary, is a complication which can frequently worsen
the pulmonary condition. Renal function tends to be maintained early
in the course unless the precipitating insult has been prompted by a
sudden oliguric acute tubular necrosis. With persistent activation and
inflammatory mediators, glomerular filtration falls and the
development of oliguric or polyuric renal failure marks the gradual
transition into MOFS. Gastrointestinal abnormalities include ileus,
stress ulceration, diarrhea, and mucosal atrophy. Breakdown of the
mucosal barrier allows translocation of bacteria and endotoxin.
Hepatic dysfunction is marked by progressive rise in serum bilirubin
levels after a latent period of several days.

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

hypoadrenal shock?
a. In the United States, idiopathic adrenal atrophy (Addison’s disease)
is the most common cause
b. Laboratory abnormalities include hyponatremia, hypochloremia,
and hyperkalemia
c. Fever may be seen with hypoadrenal shock
d. ACTH stimulation test is the diagnostic test of choice to confirm
hypoadrenal shock
Answer: b, c, d

Shock of a dramatic nature, poorly responsive to resuscitation, may

develop as a consequence of adrenal insufficiency. In this country,
adrenal insufficiency most commonly arises as a consequence of the
chronic therapeutic administration of high doses exogenous
corticosteroids causing adrenal suppression. Other causes include
idiopathic adrenal atrophy (Addison’s disease), tuberculosis,
metastatic disease, bilateral hemorrhage, and amyloidosis. The stress
of illness, operation, or trauma typically requires that the adrenal
glands secrete cortisol in excess of that required in the nonstressed
state (approximately 3–4 fold). Insufficiency not otherwise apparent
may manifest itself only after major physical stress. Findings
associated with adrenal insufficiency include weakness, fatigue,
anorexia, abdominal pain, nausea, vomiting, and weight loss. Surgical
patients with significant adrenal insufficiency need not present with
the above findings. More typical is the development of refractory
shock, frequently with hyperthermia, in the course of injury or illness.
Hypotension may be dramatic despite massive volume resuscitation
and pressor support. Laboratory findings suggesting hypoadrenalism
include hyponatremia, hypochloremia and hyperkalemia. The
diagnosis of adrenal insufficiency may be confirmed or excluded by
means of an ACTH stimulation test. A significant major cortisol
response should be elicited by ACTH administration.

231 Which of the following statement(s) is/are correct concerning the

cardiovascular response to shock?
a. Changes in cardiac contractile function shift the Frank Starling curve
up and down
b. Venoconstriction from skeletal muscle is a significant contributor to
the restoration of blood volume with shock
c. Arterial vasoconstriction affects all vascular beds equally
d. The total circulating blood volume is equally split between the
arterial and venous system
Answer: a

Central in the general cardiovascular response to shock is the action

of the heart itself. The principle determinants of cardiac function in
the normal heart are the volume of blood available for the heart to
pump (preload), the systolic contractile capability, and the diastolic
filling of the ventricles. In hypovolemia, the two dynamic variables of
cardiac function, ventricular filling and myocardial contractility remain
paramount and determine the stroke volume. The product of stroke
volume and heart rate in turn determines the cardiac output.
Increases in ventricular end-diastolic volume, reflecting venous return,
cause ventricular distention. Ventricular distention in turn produces
increased volume output with each stroke, the Frank Starling
mechanism. Contractile function may vary independent of volume
status. Changes in the contractile function shift the Starling curve up
and down, producing increases or decreases in stroke volume for any
given end-diastolic volume. A fundamental requirement for
cardiovascular function is adequate cardiac filling, and cardiac output
cannot exceed venous return. The venous system contains nearly
two-thirds of the total circulating blood volume, including 20% to 30%
within the splanchnic venous system. Most of this volume resides in
small veins, which comprise the bulk of venous capacitance. The
venous system, especially that of the splanchnic circulation, becomes
important in the physiologic compensation to hypoperfusion because
it serves as a dynamic reservoir for the autoinfusion of blood volume
involving both active and passive mechanisms. The splanchnic
circulation makes major contributions to the maintenance of venous
return, therefore, it is likely that sympathetic venoconstriction is
responsible for a portion of the blood mobilized from the splanchnic
venous circulation. Sympathetic mediated venoconstriction in skin
and skeletal muscle is probably not as significant as a source of blood
volume. Selective vasoconstriction occurs in response to alpha
adrenergic receptor stimulation with increased sympathetic activity in
shock. Sympathetic stimulation does not cause significant
vasoconstriction of either cerebral or coronary vessels, with normal
blood flow maintained in these circulations. Blood flow to the skin is
sacrificed early, followed by that to the kidneys and splanchnic
viscera.

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

pharmacologic agents used in the treatment of shock?
a. The primary difference between dopamine and dobutamine is the
absence of significant a adrenergic activity
b. The renal and mesenteric vasoconstrictive effects of
norepinephrine complicate and sometimes restrict its use
c. The apparent paradoxical use of vasodilators, such as nitroprusside,
in shock is indicated as a means to augment cardiac function
d. Isoproterenol with its potent b-adrenergic effect, is a particularly
useful agent in the treatment of all forms of shock
Answer: a, b, c

Therapeutic adjustments of intravascular volume (preload) and

systemic vascular resistance (afterload) form the basis of the
treatment strategies for all forms of shock. Optimal volume
resuscitation should precede measures to augment to contractile
function of the heart. Inotropic agents are used in shock when there is
inadequate cardiac output despite adequate circulating blood volume.
Dopamine and dobutamine are often times first line agents in the
pharmacologic treatment of shock. Dopamine, at low doses,
stimulates dopaminergic receptors producing renal arteriolar
vasodilatation with associated increases in renal blood flow, urine
output, and sodium excretion. At moderate doses, stimulation of
cardiac b-receptors produces increases in contractility and cardiac
output with little effect on heart rate or blood pressure. At higher
doses, peripheral vasoconstriction from increasing a activity becomes
more pronounced, prompting significant increases in vascular
resistance and blood pressure. Dobutamine’s predominant effect is
an increasing cardiac contractility with lesser increases in heart rate.
Some reduction of peripheral vascular resistance may also occur.
When compared to dopamine, dobutamine produces less peripheral
vasoconstriction and less chronotropic response. Norepinephrine
exerts both a and b-adrenergic effects, with a effects being evident at
lower infusion rates and a effects more prominent at high doses. The
major use of norepinephrine in current practice is in the patient with
hypotension that persists despite appropriate volume resuscitation
and the use of inotropic agents. Renal and mesenteric
vasoconstrictive effects of norephinepherine complicate its use,
especially when support is needed for significant periods of time.
Isoproterenol is a potent b-adrenergic agent. With isoproterenol,
myocardial oxygen demand is increased and diastolic coronary feeling
is limited by tachycardia or diminished diastolic pressure. Indications
for the use of isoproterenol are fairly limited, because agents with
fewer adverse effects have become available.
Vasodilators are used to augment cardiac function through
optimization of ventricular filling pressures (preload) and systemic
vascular resistance (afterload) both of which reduce demands on the
myocardium. Decreases in afterload prompt increases in cardiac
output and venodilatation contributes to decreases in pulmonary
venous pressure and central venous pressure. Hypotension, however,
may develop therefore patients must have careful constant
monitoring of arterial pressure and repeated hemodynamic
measurements with a pulmonary artery catheter.

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

treatment of MOFS?
a. Prevention and therapy of MOFS requires control of the infectious
or inflammatory source
b. Restoration of normal clinical parameters such as blood pressure,
pulse rate, and urine output ensures optimal resuscitation in most
patients
c. Branch chain amino acids play and important role in the nutritional
support of the patient
d. Because of the nature of gut injury, total parenteral nutrition is
preferred for most patients with MOFS
Answer: a, c

The therapy of MOFS is directed towards interrupting the involving

pathophysiologic process and providing an optimal physiologic
environment for healing and recovery. Fundamental concerns are
control of the source of infection, inflammation or instability;
restoration of microcirculatory blood flow and oxygen transfer, and
the institution of optimal supportive care. Both the prevention and
therapy of MOFS, therefore, requires source control and restoration
of adequate profusion. Resuscitation efforts are directed toward
restoration of adequate microcirculatory blood flow in all organ
systems. Restoration of normal clinical parameters such as blood
pressure, pulse rate, urine output, and acid-base balance does not
ensure optimal resuscitation. The physiologic endpoint that most
closely corresponds with adequate microcirculatory flow is the level of
cardiac output and the oxygen delivery at which oxygen consumption
and lactate production remain independent of flow.
The importance of metabolic support in the patient with MOFS cannot
be overemphasized. The malnutrition of MOFS is markedly different
than that of starvation and the nutritional requirements also differ. If
optimal quantities of appropriately formulated amino acid solutions
are given, protein synthetic rates can approach catabolic rates and the
goal of nitrogen balance can be achieved. Formulas rich in branch
chain amino acids appear to be more efficient in promoting nitrogen
retention and minimizing urea production. Whenever feasible, enteral
feeding is preferred over TPN because evidence suggests that
bacterial translocation from the gut can be limited through the use of
enteral feeds. Enteral absorption and processing of nutrients appears
superior to TPN and lessens overall complications.

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

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

The nature of multiorgan failure syndrome (MOFS) is that of a diffuse

cellular injury, developing systemically as a consequence of losing
homeostatic control of local inflammation and microcirculatory
hypoperfusion. Endothelial injury, platelet aggregation and activation
of macrophages and neutrophils occur, and the clotting, fibrinolytic,
kinin, and complement cascades are activated, along with the release
of potent inflammatory cytokines. The effects of shock, resuscitation,
and reperfusion, and the subsequent development of MOFS appear to
be critically dependent on changes in the splanchnic and pulmonary
microcirculations. These vascular beds appear to be major sites of
activation of subsequent inflammatory mediator production that
underlies the diffuse systemic inflammatory response. Extensive
activation of the liver Kupffer cell and release of inflammatory
mediators coupled with the ongoing release of activated neutrophils
and by-products of activated gut macrophages is responsible for the
injury to the pulmonary microcirculation and secondary induction of
alveolar macrophage and additional inflammatory mediator systems.
Excessive and persistent macrophage activation plays an essential
role in MOFS and is hypothesized to represent the penultimate step in
a series of continuous immuno-inflammatory stimulatory events,
including local hypoxia, exposure to bacteria and toxins, and mediator
release from localized areas of inflammation. When infection is the
underlying or major contributing process, the diffuse inflammatory
response develops independently of the specific type of
microorganism. In noninfectious cases, the response also appears
independent of the specific underlying cause.
235 Invasive hemodynamic monitoring using a Swan-Gantz catheter is
essential in the optimal management of patients in shock or those
suffering post-shock sequelae. Which of the following physiologic
characteristics are associated with the various forms of shock?
a. Hypovolemic shock: Decreased pulmonary capillary wedge pressure
(PCWP), decreased cardiac output, increased systemic vascular
resistance (SVR)
b. Cardiogenic shock: Increased PCWP, decreased cardiac output,
decreased SVR
c. Septic shock (hypodynamic): Decreased cardiac output, increased
SVR
d. Neurogenic shock: Decreased PCWP, increased cardiac output,
decreased SVR
Answer: a, c

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

relationship between cardiac function and effective blood volume?

a. A pulmonary capillary wedge pressure of 5–10 rules out fluid

overload as a cause of pulmonary edema
b. A shift to the right in the Frank-Starling curve is associated with
compromised cardiac function
c. Dilutional anemia may contribute to tachycardia even though blood
volume and filling pressures are normal
d. The sole purpose of a pulmonary artery catheter is to measure
pulmonary artery pressure and cardiac output
Answer: b, c

Although physical findings are often adequate to establish a diagnosis

and institute management of cardiac failure, direct measurement of
filling pressures of the right heart (central venous pressure) or the left
heart (pulmonary artery pressure) may be required. Placement of a
pulmonary artery catheter allows us to measure cardiac output by
thermodilution and, more importantly, to sample mixed venous blood
for saturation measurements which tell us the ratio between systemic
oxygen delivery and oxygen consumption. From all of these
measurements we can determine if cardiac output is normal for the
level of filling pressure of the left ventricle, or if contractility is
decreased. In the latter case, cardiac output will be lower than
predicted for a given level of filling pressure. In the Frank-Starling
curve, if the patient is to the right of the normal range, then cardiac
function is compromised either because of valvular disease, extrinsic
pressure such as pericardial tamponade, or more commonly, a
decrease in contractility. If cardiac function and anatomy are normal,
then blood volume, filling pressure and cardiac function are related to
the Starling curve. The intake and output of fluid and salt is
autoregulated to maintain the filling pressure of the left ventricle
around 10 mm Hg. Extracellular fluid expansion is usually associated
with normal blood volume. Gross expansion of extracelluar space
results in deleterious effects if tissue edema can and often do exist
with perfectly normal blood volume. In other words, a pulmonary
capillary wedge pressure of 5–10 does not rule out fluid overload as a
cause of pulmonary or GI dysfunction. In critically ill patients, the fear
of hypotension and effect of perfusion usually results in infusion of
intravenous salt and water in quantities which exceed losses.
Consequently, most patients in the Intensive Care Unit have anemia,
dilutional hypoproteinemia, and a compensatory increase in cardiac
output. In response to anemia, these patients are tachycardic, even
though blood volume is normal, filling pressures are normal, and total
body extracellular fluid is excessive.

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

methods of nutritional support?

a. Optimal results for enteral feedings are achieved with

approximately half of calories supplied as carbohydrate and half as fat
b. Diarrhea is the most common complication of enteral feeds and is
due to the high osmolarity of the carbohydrate components
c. The hyperosmolar nature of parenteral fat solutions requires
central venous administration
d. Approximately 25–50% of calories should be provided as fat
emulsion in patients receiving total parenteral nutrition
Answer: a, b, d

Most formulas for enteral feeding range from 1.0 to 2 cal/ml and
include 3 to 7% protein. Most of the calories are supplied as glucose
or sucrose, so that the solutions have a very high osmolarity. Cramps
or diarrhea can result when these high osmolar solutions are placed
into the stomach or intestine. Diarrhea is the major complication with
most tube feeding formulas. Diarrhea can be minimized by the use of
starch or fat as an energy source in tube feedings. This can be
supplied as part of the commercial preparation or added in the form
of medium chain triglycerides or other oils. The best results are
usually achieved by supplying approximately half the calories as
carbohydrate and half as fat. In patients receiving total parenteral
nutrition, energy source is provided as carbohydrate, fat, and amino
acid solutions. Parenteral feeding with carbohydrate is limited by the
sclerotic effect of hyperosmolar solutions on veins. Fat is a more
efficient energy source and can be given through peripheral veins in
concentrations of either 10 or 20%. Most intensivists favor
supplementing standard total parenteral nutrition solution with
intravenous fat to provide at least 100 grams of fat emulsion each
week to preclude fatty acid deficiency. Giving up to 25 to 50% of
calories each day as fat emulsion may optimize the delivery of this
caloric delivery.

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

autoregulation necessary to maintain oxygen consumption and
oxygen delivery?

a. A change in oxygen consumption is followed by a proportionate

change in oxygen delivery
b. A change in oxygen delivery is followed by a change in oxygen
consumption
c. Increases in oxygen delivery are due solely to an increase in cardiac
output
d. The normal ratio of oxygen delivery to consumption is 2:1
Answer: a

The relationships between oxygen consumption and oxygen delivery

represent one of the most interesting regulation systems in
homeostasis. First of all, if one of the three components of oxygen
delivery is abnormal, endogenous mechanisms regulate the other two
until normal oxygen delivery has been restored. The various
combinations of compensatory mechanisms supply adequate oxygen
for systemic metabolism through a wide range of variations in oxygen
delivery. When there is a change in oxygen consumption, there is a
proportionate change in oxygen delivery, which occurs almost
immediately, mediated completely by a change in cardiac output.
Conversely, a primary change in oxygen delivery is not followed by
any change in oxygen consumption. The normal ratio of oxygen
delivery to consumption is approximately 5:1.

239 Which of the following statement(s) is/are true concerning O2

venous saturation monitoring?

a. The normal saturation of mixed venous blood is 50%

b. Mixed venous blood obtained for saturation monitoring can be
obtained from any peripheral vein
c. If arterial blood is fully saturated, the saturation of mixed venous
blood is 80%
d. In less than fully saturated blood, the difference between arterial
and venous saturation corresponds to oxygen extraction
Answer: c, d

The relationship between oxygen delivery and oxygen consumption is

reflected in the amount of oxygen in venous blood. Under normal
circumstances, oxygen delivery is 1000 cc/min and oxygen
consumption is 200 cc/min. The amount of oxygen extracted is 20% of
that delivered, and 80% of oxygen is still present in venous blood
returning to the heart. Usually arterial blood is fully saturated, and
under normal circumstances, the saturation of mixed venous blood
(SVO2) will be 80%. This measurement must be made in mixed venous
blood since the relative extraction of organs served by the superior
and inferior vena cava and coronary sinus are quite different. As long
as arterial blood is fully saturated, this observation holds true
regardless of the absolute level of oxygen consumption or oxygen
delivery. If the arterial blood is less than fully saturated, the difference
between arterial and venous saturation corresponds to the oxygen
extraction, hence the oxygen delivery/oxygen consumption ratio.

240 Which of the following statement(s) is/are true concerning oxygen

kinetics in a critically ill, febrile patient?

a. Oxygen consumption will likely exceed three times normal

b. The high cardiac output and pulse rate are designed to increase
oxygen delivery
c. The hyperdynamic response may actually increase oxygen delivery
to exceed the increase in oxygen consumption
d. The patient can maintain adequate compensation as long as the
oxygen delivery/oxygen consumption rate is greater than 2:1
Answer: b, d

In critically ill patients oxygen consumption may be elevated or

depressed, but slight to moderate elevations in oxygen consumption
is the most common abnormality in critically ill patients. Oxygen
consumption will be elevated in proportion to the amount of
inflammation. A febrile patient with significant signs of septic toxicity
will typically have an oxygen delivery at 1.5 to 2 times normal. It is very
unusual for a critically ill patient to experience oxygen consumption
greater than twice normal. This occurs only in situations of severe
muscular exercise such as seizures or tetanus. During
hypermetabolism, a change in oxygen consumption is followed
promptly by a proportionate change in oxygen delivery. Hence, it is
“normal” for a hypermetabolic patient to have a high cardiac output
and pulse rate. Rarely the hyperdynamic response exceeds the
increase in oxygen consumption, reflected in a ratio higher than 5:1
and venous saturation greater than 80%. Some patients cannot
mount an increased oxygen delivery in response to increased oxygen
consumption because of the combination of hypoxemia, anemia, and
myocardial failure. If this occurs, then the oxygen delivery/oxygen
consumption ratio will be less than 5:1. The patient will compensate
for this by increased oxygen extraction, however, and the patient will
remain stable as long as the ratio is greater than 2:1.

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

treatment of pulmonary interstitial edema?

a. Diuresis and blood transfusion is a valuable step

b. Salt-poor albumin leaks through the capillaries and worsens the
condition
c. Mannitol is contraindicated as a diuretic in this clinical situation
d. Isoproterenol is a poor choice as an ionotropic agent
Answer: a

Treatment of pulmonary edema has two important goals, the first is

to improve oxygenation if it is impaired, and the second is to minimize
fibrosis and bacterial infection, which often accompany pulmonary
edema caused by capillary injury. The treatment of interstitial edema
is to maintain the hydrostatic pressure as low as compatible with
adequate cardiac output and to raise the oncotic pressure selectively
in the vascular space. These measures, combined with fluid restriction
and diuresis, will decrease the amount of pulmonary edema. Since it
is desirable to maintain filling pressures of the left ventricle as low as
possible while maintaining a good cardiac output, inotropic drugs to
improve left ventricular contractility are helpful. Isoproterenol or
dopamine should be used, with serial cardiac output and filling
pressure measurements. The first step in decreasing pulmonary
edema is to decrease the pulmonary capillary hydrostatic pressure as
low as is compatible with an adequate cardiac output. This is done by
diuresis and fluid restriction. As the patient falls behind in blood
volume, signs of hypovolemia may appear. Blood volume is then
replenished with a fluid that stays in the vascular space. Packed red
cells are ideal for this application. When the hematocrit is normal,
concentrated salt-poor albumin should be used. This hyperoncotic
fluid replenishes the blood volume by attracting interstitial fluid from
throughout the body into the vascular space and supplements
diuresis. This technique is useful even in the septic patient who may
have increased capillary permeability and may loose albumin from the
vascular space at a rapid rate. Even if albumin “leaks out”, the short
term effects of expanding blood volume and decrease in edema will
appear.

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

pathophysiology of gas exchange?

a. Hypoventilation in relation to perfusion can result in an oxygen

saturation of less than 100%
b. Diffusion block and / mismatch can almost completely be overcome
by breathing 100% oxygen
c. Transpulmonary shunting does not occur under normal
circumstances
d. The normal arterial oxygen saturation should be 100%
Answer: a, b

Under normal conditions, red blood cells in the pulmonary capillaries

become fully saturated and oxygen dissolves in plasma resulting in
blood PO2 of 100 and O2 saturation of 100%. This equilibration may
be disturbed by hypoventilation in relationship to the perfusion (/
mismatch), diffusion block caused by interstitial fibrosis, or perfusion
of nonventilated alveoli. Diffusion block and / mismatch can almost be
completely overcome by breathing 100% oxygen, hence hypoxemia
during exposure to high alveolar PO2 is caused by total / mismatch,
so-called transpulmonary shunting or venous ad mixture. Under
normal circumstances, about 5% of the blood entering the left atrium
has been shunted away from the pulmonary capillaries, either as the
result of bronchial nutritive blood flow or through thebesian veins
opening directly into the left side of the heart. This phenomenon,
combined with a normal minor / mismatch associated with breathing
at rest and positional changes in pulmonary blood flow, result in the
fact that normal arterial PO2 is 90–100 mm Hg and the normal O2
saturation is 98%.

243 Which of the following statement(s) is/are true concerning CO2

transfer in the lung?

a. Carbon dioxide excretion is a direct function of alveolar ventilation

b. Normally end tidal CO2 should be identical to PaCO2
c. The gradient between end tidal and arterial CO2 can be an indirect
measure of nonperfused alveoli
d. Positive pressure ventilation under normal airway pressures
creates a significant end tidal PaCO2 gradient
Answer: a, b, c

The amount of carbon dioxide excretion is directly related to alveolar

ventilation. While oxygenation is a function of matching blood flow to
alveoli, carbon dioxide excretion is a direct function of ventilation or
hyperventilation of alveoli with some blood flow. Normally the end
tidal CO2 represents mixed alveolar gas which is at equilibrium with
pulmonary capillary blood, hence with arterial blood. Therefore, the
end tidal CO2 and the PaCO2 should be identical. End tidal CO2
measurement is a very useful continuous measurement of PaCO2
which can be used as a monitor when the lung is normal, as in
ventilator weaning. Furthermore, the gradient between end tidal and
arterial CO2, when it is large, acts as an indirect measure of
nonperfused alveoli and/or compression volume. In patients who are
ventilated with positive pressure ventilation, a significant end tidal
PaCO2 gradient occurs only when peak airway pressures are very high
(over 30 cm H2O) and the compression volume is a significant
component of each exhaled breath.

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

assessment of protein reserve?

a. Conventional serum proteins such as albumin and globulin are

early indicators of malnutrition
b. The total lymphocyte count reflects immune status and not
nutrition
c. Antigen skin testing reflects patient immunity and not nutrition
d. Measurement of urea excretion in urine can be used as a
measurement of protein breakdown
Answer: d

Since protein is the functional and structural chemical of the body,

most nutritional assessment techniques are estimates of protein
reserves. The actual nitrogen balance can be measured by measuring
the amount of nitrogen excreted. This is most conveniently done by
measuring the amount of urea excreted in the urine, assuming that
urea constitutes 85% of the total nitrogen excretion. Knowing nitrogen
excretion, the amount of protein catabolized can be estimated and
compared with the amount of protein ingested by the patient. Indirect
assessments of protein reserves are based on single measurements
of body substances that are dependent on rapid protein synthesis for
maintenance of normal levels. Conventional serum proteins such as
albumin and globulin are not affected by malnutrition until it is very
severe. Proteins such as prealbumen and transferrin, which turn over
more rapidly, are better indicators of protein status. Lymphocytes are
rapidly destroyed and protein is required for the formation of new
cells. Consequently, the absolute lymphocyte count is a useful
measure of the status of protein reserves. The lymphocyte count is
considered by some the best single “static” measurement
characterizing nutritional status. Protein is also required for
synthesizing the cells and mediators involved in skin test reactivity.
Although skin test reactivity is a manifestation of lymphocyte-
mediated immunity, its usefulness in patient assessment is probably
that of assessment of the inflammatory response than lymphocyte
activity per se. Some chronically and acutely malnourished patients
convert from reactive to anergic, and reactivity can be restored by
nutritional repletion.
245 Useful steps to optimize systemic oxygen delivery include:

a. Maintaining mean arterial blood pressure between 50 and 90 mm

Hg
b. Optimizing PEEP levels by monitoring mixed venous saturation
c. Turning the patient prone
d. Sedation or paralysis
Answer: a, b, c, d

Optimizing systemic oxygen delivery in relationship to oxygen

requirement is the primary goal of management. Improving
oxygenation of the blood itself by improving alveolar inflation is only
one of the steps in optimizing oxygen delivery. Equally or more
important are treating anemia and optimizing cardiac output. Cardiac
output should be optimized to maintain delivery of four to five times
consumption. In general, this means avoiding those factors which
decrease cardiac output, rather than actively trying to increase cardiac
output. Blood pressure should be maintained high enough to provide
coronary perfusion (over 50 mm Hg mean pressure) but not so high
as to limit left ventricular function (over 90 mm Hg mean arterial
pressure). Alveolar collapse is treated by cleaning the airways,
avoiding 100% oxygen, and moving fluid from the lung or chest, and
finally by the use of positive end exploratory pressure to hold open
those alveoli which have been opened by other measures. The
optimal level of PEEP is that level that maintains arterial oxygenation
but does not decrease venous return or cardiac output. This optimal
level is best determined by monitoring mixed venous saturation.
Another step in optimizing lung function is to take advantage of the
gravitational effects on pulmonary blood flow by turning the patient
prone or to a full lateral position to direct blood flow to areas of
optimal alveolar function. This step will often result in an opening in
the closed posterior alveoli which have been compressed by the
weight of the fluid in the lungs. At the same time that oxygen delivery
is optimized, oxygen consumption should be decreased to normal or
even below normal if necessary. Treating infection, providing
adequate sedation, and establishing muscular paralysis decrease
oxygen consumption, and decrease the need for oxygen delivery.

246 Phases of multiorgan failure will include:

a. Generalized increased capillary permeability

b. A hypermetabolic state
c. Organ malfunction
d. All of the above
Answer: d

Clinically the multiple-organ failure patient progresses through

well-defined phases. These phases include: Phase 1—a generalized
increased capillary permeability resulting in edema, weight gain, and
intravenous volume replacement, increased protein concentration in
urine and lymph. Although the pulmonary microvasculature has been
most thoroughly studied, it is apparent that the lung is simply the
most obvious end organ in a generalized permeability defect. Phase
2—A hypermetabolic state, with increased oxygen consumption and a
compensatory increase in oxygen delivery characterized by
tachycardia and high cardiac output. This condition following systemic
ischemic and reperfusion is similar to hypermetabolism following
endotoxemia, localized sterile inflammation, and infusion of stress
hormones, suggesting a common mechanism. Phase 3—Organ
malfunction due to localized edema and cellular injury, particularly in
the kidney, liver, brain, and host defense system. Hemorrhagic shock
predisposes to bacterial translocation and endotoxin absorption from
the intestine. Phase 4—In the absence of systemic sepsis, organs may
recover to normalcy or may be irreversibly damaged, leading to a
need for chronic support. If the organ failure phases lead to systemic
infection or irreversible tissue damage in the lung or brain, the death
of the entire organ is likely.

247 Which of the following statement(s) is/are true concerning oxygen

consumption (O2)?

a. O2 is normally 100–120 cc2/m2/min

b. Resting O2 is controlled by the level of thyroid and catecholamine
hormones
c. Under steady state conditions the amount of oxygen consumed
exceeds the amount of oxygen taken up by the pulmonary capillaries
d. O2 is dependent on the status of pulmonary function
Answer: a, b

Oxygen consumed in the process of metabolism is expressed as the

volume of oxygen per minute (O2). O2 is normally 100–120
cc2/m2/min, or 200 cc/min for a typical adult. Resting O2 is a function
of metabolizing body cell mass, with fine tuning control provided by
the level of thyroid and catecholamine hormones. O2 decreases
under conditions of hypothermia, paralysis, and hypothyroidism. O2
increases during exercise or muscular activity, hyperthermia,
profound hypothalamic injury, hyperthyroidism, catecholamines, and
inflammatory mediators, particularly the interleukin cytokines. Under
steady state conditions, the amount of oxygen consumed in systemic
metabolism is exactly equal to the amount of oxygen taken up by the
pulmonary capillaries via the airway. This is true regardless of the
status of pulmonary function or dysfunction, so we measure O2
across the lung and assume that it is exactly the amount consumed in
the systemic metabolism.

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

outcome in patients with acute renal failure?

a. Mortality for ischemic acute tubular necrosis without other organ

failure is approximately 6%
b. Multiple organ failure complicated with acute renal failure is
associated with mortality ranging from 50% to 90%
c. Recovery of renal function after six weeks is unlikely
d. There is no difference in survival between oliguric and nonoliguric
renal failure
Answer: a, b, c

Survival of patients with acute renal failure is a function of the

successful treatment of the primary disease from which the renal
failure was derived. The mortality for ischemic acute tubular necrosis
without organ failure has been reported at approximately 6%. By
contrast, mortality of multiorgan failure complicated by acute renal
failure ranges from 50% to 90%. In patients who survive the acute
phase of illness, recovery of renal function after acute renal failure is
dependent on the type and extent of injuries to the renal
parenchyma. If renal function is not returned after six weeks, recovery
is unlikely. Nonoliguric renal failure is usually limited in its extent and
is almost always reversible.

249 Which of the following statement(s) is/are true concerning oxygen

delivery?

a. The amount of oxygen delivered to peripheral tissues is dependent

upon the oxygen content in arterial blood and cardiac output
b. Oxygen content is commonly measured in arterial blood
c. The normal arterial-venous difference is 4 cc O2/dL
d. Normal systemic oxygen delivery for a typical adult is
approximately 1000 cc/min
Answer: a, c, d

The amount of oxygen that is delivered to peripheral tissues is the

product of the oxygen content in arterial blood times the cardiac
output. Normally, oxygen content of arterial blood is approximately
20 cc/dL, and the normal cardiac index is 5 L/min. Therefore, the
normal systemic oxygen delivery is approximately 1000 cc/min.
Although oxygen content is the most important measure of oxygen in
the blood, PO2 and oxyhemoglobin saturation is more commonly
measured in the Intensive Care Unit, hence it is necessary to convert
between these measurements. The normal oxygen content of venous
blood is 16 cc/dL. Hence, the normal arterial-venous difference is 4 cc
O2/dL.

250 Which of the following statement(s) is/are true concerning carbon

dioxide kinetics?

a. The amount of carbon dioxide produced is equivalent to the

amount of oxygen consumed
b. Carbon dioxide levels in blood, present mostly as a bicarbonate ion,
can quickly change
c. Normally the amount of carbon dioxide excreted through the lung
is exactly equal to the amount of carbon dioxide produced in
peripheral tissues
d. The amount of carbon dioxide excreted is a function of ventilation
of perfused alveoli
Answer: a, c, d

The total amount of carbon dioxide produced by systemic metabolism

is roughly equivalent to the amount of oxygen consumed (100–120
cc/m2/min, 200 cc/min in a typical adult). CO2 production is increased
or decreased by each of the factors that causes an increase or
decrease in oxygen consumption. Most of the carbon dioxide in blood
is present as bicarbonate ion which cannot be changed quickly.
However, the metabolically produced CO2 is mostly present as
dissolved carbon dioxide, added to the blood in the peripheral tissues
and excreted in the lung. In a steady state, the amount of carbon
dioxide excreted through the lung is exactly equal to the amount of
carbon dioxide produced in peripheral tissues. The amount of carbon
dioxide excreted is a function of ventilation of perfused alveoli (i.e. the
alveolar ventilation/min).

251 Which of the following result in a decrease in functional residual

capacity?

a. Shallow breathing
b. Partial airway occlusion
c. Absorption atelectasis
d. Hemothorax
Answer: a, b, c, d

A decrease in functional residual capacity is caused by incomplete

alveolar inflation related to 1) shallow breathing; 2) partial or
complete airway occlusion, which may be generalized (as in
bronchospasm) or localized (as in gastric aspiration); 3) absorption
atelectasis, which occurs when oxygen is substituted for nitrogen in
the inspired gas; or 4) conditions in which air or fluid is occupying a
potential alveolar space in the chest such as pneumothorax,
hemothorax, or pulmonary edema.

252 Which of the following statement(s) meet the criteria for organ
failure?

a. Bilirubin greater than 5 mg/dl

b. Creatinine greater than 3 mg/dl
c. Alveoloarterial O2 gradient greater than 300 mm Hg
d. Glasgow Coma score less than 10
Answer: a, b, c, d

Multiple organ failure is defined by dysfunction of two or more of the

six vital organ systems: cardiovascular, respiratory, nervous system,
renal, liver, and host defenses.

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

pulmonary edema?

a. Pulmonary edema effectively narrows bronchi and increases

pulmonary vascular resistance
b. Ventilation and perfusion are decreased equally
c. Positive pressure ventilation improves gas exchange by decreasing
lung edema
d. The condition is frequently caused by decreased plasma protein
levels
Answer: a

The causes of pulmonary edema are: 1) increased hydrostatic

pressure; 2) increased capillary permeability and 3) decreased plasma
oncotic pressure. The latter, however, is rarely a problem unless the
concentration of plasma protein is very low. When fluid begins to
collect in the lung interstitium, it migrates to the loose areolar portion
of the lung microanatomy that surround the small bronchioles and
pulmonary arteries. The edema in these areas has the effect of
narrowing bronchi and increasing resistance in the pulmonary
vasculature. This will decrease both ventilation and perfusion in the
edematous area, but ventilation is often affected more than blood
flow, resulting in a decreased / ratio, with all of its attendant effects on
gas exchange. Ventilator treatment of pulmonary edema which
increases airway pressure tends to hold the alveoli open, spreading
out the space available for water accumulation and overcomes the
effect of small bronchial occlusion. Positive pressure ventilation does
not, therefore, affect the amount of edema in the lung, only its
manifestations.

254 Which of the following statement(s) is/are true concerning various

causes of acute renal failure?

a. Acute tubular necrosis is the most common pathologic finding of

acute renal failure
b. Drug-induced renal failure is compounded in situations of
hypovolemia
c. Myoglobin-induced renal failure can be prevented using diuretics
and alkalization of urine
d. The incidence of radiographic contrast dye-induced renal failure
occurs independent of preexisting conditions
Myoglobin is a direct nephrotoxin
Answer: a, b, c

Acute tubular necrosis results from ischemia to the renal parenchyma

and is the most common pathologic finding of acute renal failure. In
conditions of diminishing renal blood flow, perfusion to the kidneys is
first maintained by vasomotor responses which dilate the afferent
arteriole and constrict the efferent arteriole. As continued
hypotension occurs, the renin-angiotensin system is activated and
vasoconstriction of the afferent arteriole occurs which exacerbates
corticohypoperfusion. Pigment nephropathy is a common cause of
acute renal failure occurring after trauma, burns, operations, or
hemodynamic catastrophe. With ischemia or blunt injury to large
muscles, myoglobin is released into the circulation. In the kidney, it is
filtered from blood and reabsorbed by the tubule. Although
myoglobin is not a direct nephrotoxin, in the presence of aciduria,
myoglobin is converted to ferrihemate, which is toxic to renal cells.
Prevention of myoglobin-induced renal failure may include the use of
diuretics and alkalinization of urine. Drug-induced acute renal failure
is responsible for approximately 5% of all cases of acute renal failure.
Through normal reabsorption and secretion, the kidney is exposed to
high concentrations of drugs and solutes, which may be toxic. This
problem is compounded by hypovolemia, which causes increased
reabsorption of water and solutes and exposes the lumen to even
higher concentrations of toxins. The incidence of radiographic
contrast dye induced nephropathy is approximately 1 to 10% and may
be predicted according to a number of risk factors which include
contrast load, age, preexisting renal insufficiency, and diabetes. The
incidence in patients with normal renal function is significantly lower
at 1% to 2%.
255 The patient requires renal replacement therapy. Which of the
following statement(s) is/are true concerning the differences between
hemodialysis and continuous arteriovenous hemodialysis (CAVHD)?

a. Anticoagulation is not required for CAVHD

b. Hemodynamic instability will be a particular problem with both
techniques
c. Both techniques will decrease serum urea ni+62trogen levels
d. CAVHD will likely result in better removal of excessive volume
Answer: c, d

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

continuous arteriovenous hemofiltration (CAVH)?

a. The technique runs continuously

b. It is not associated with the hemodynamic instability
c. Systemic heparin anticoagulation is necessary
d. Fluid balance and correcting electrolyte abnormalities takes several
days
Answer: a, b

Continuous arteriovenous hemofiltration (CAVH) is an extracorporial

filtration technique that removes extracellular fluid across a synthetic
membrane via hydrostatic pressure gradient created between the
indwelling arterial and venous catheters. Arteriovenous access is
accomplished by percutaneous cannulation of femoral artery and vein
with a low incidence of complications. Although full systemic
anticoagulation is not necessary for CAVH, heparinization of the
extracorporial circuit is required. CAVH is run continuously for as
many days as renal replacement is required. Experience with CAVH
has demonstrated very little or no hemodynamic instability with
treatment of critically ill renal failure patients. The stable nature of this
therapy is attributed to a slow and continuous fluid and solute
removal and to the fact that the membrane does not induce
compliment activation when in contact with blood. Fluid balance and
serum electrolyte concentrations can be titrated to any level in a
matter of hours by manipulating the composition and rate of
replacement solution. Solute clearance with CAVH is limited by the
ultrafiltration and replacement fluid exchange rate. In patients with
high urea generation rates, solute removal with CAVH may be
inadequate and variations of the technique may be used to enhance
clearance.

257 A 64-year-old diabetic patient develops acute renal failure

following an aortic aneurysm repair. Which of the following
statement(s) is/are true concerning his diagnosis and management?

a. Resting energy expenditure will likely be less than would be

expected for a patient with normal renal function
b. Maintenance of positive energy balance reduces protein catabolism
and makes the management of renal failure easier
c. Expected metabolic abnormalities include hyperkalemia,
hypercalcemia, and metabolic alkalosis
d. A nonoliguric renal failure is usually associated with a better
outcome
Answer: b, d

In patients with nonoliguric renal failure, treatment may differ little

from that required for identical patients with normal renal function.
Management of fluids, solutes, and nutrition is usually unaffected by
nonoliguric renal failure, although BUN may be elevated. The extent
of renal dysfunction is limited and almost always reversible. The use
of renal replacement therapies is rarely necessary. Acute renal failure
can result in severe derangements in electrolyte and acid-based
physiology. Of all electrolyte abnormalities that might occur,
hyperkalemia is the most serious. Other electrolyte abnormalities
such as hyponatremia, hyperphosphatemia, hypocalcemia, and
metabolic acidosis are common and must be monitored carefully.
The metabolic requirements of a patient with acute renal failure are
those of a critically ill hospitalized patient. The actual measurements
of resting energy expenditure has shown that caloric requirements for
multiorgan failure patients with renal failure are often 50% above
normal, healthy individuals. Although acute renal failure may require
fluid restriction, providing adequate nutrition is an important aspect
of their treatment. Positive energy balance may make management of
uremia and hyperkalemia less difficult. By providing adequate
calories, endogenous protein catabolism with resultant generation of
urea and release of potassium can be avoided. Maintenance of
positive energy balance with glucose and lipids should reduce protein
catabolism, urea generation, and hyperkalemia.

258 Which of the following statement(s) is/are true concerning various

energy sources?

a. Carbohydrate is the most efficient source of energy

b. Endogenous fat is the major source of energy during starvation
c. The respiratory quotient of carbohydrate is greater than either fat
or protein
d. Ketones can be used as a source of energy during starvation
Answer: b, c, d
The major sources of energy are carbohydrates and fats.
Carbohydrates are a major source of energy during normal,
non-starving existence. The brain, the red cells, and some other
organs are obligate glucose users. The brain and red cells can develop
the capacity to use ketones as an energy source, a process known as
starvation adaptation. Fat is the most efficient source of energy. Fat
produces 9 calories of energy per gram of substrate metabolized
while carbohydrate produces only 4 calories. The respiratory quotient
represents the number of molecules of carbon dioxide for each
molecule of oxygen consumed. For carbohydrates it is 1.0, whereas
for fat, this respiratory quotient is 0.7. Endogenous fat is the major
source of energy during starvation. The glycogen storage is basically
depleted after a day of fasting and fat becomes a major energy source
with protein breakdown supplying glucose through the process of
gluconeogenesis.

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

treatment of multisystem organ failure?

a. Forced diuresis with negative fluid balance may improve survival

and acute respiratory failure
b. The titration of ionotropic drugs based on desired blood pressure
optimizes the results.
c. Nutritional support should be withheld for several days until the
patient’s condition stabilizes
d. Continuous arteriovenous hemofiltration is preferred to
intermittent hemodialysis for most critically ill patients
e. Hepatic failure should be treated specifically with pharmacologic
manipulation
Answer: a, d

The important principles in the management of multiple organ failure

are to avoid further episodes of local or systemic ischemia and to
keep the brain viable by pharmacologic or mechanical support of the
failing organs until organ recovery occurs. Respiratory failure is
treated by mechanical assistance for lung inflation and ventilation and
by decreasing lung edema as much as possible. Airway intubation is
usually required. There is now good evidence that forced diuresis and
negative fluid balance is associated with improved survival and acute
respiratory failure. Cardiac failure is treated with inotropic drugs.
Although ionotropic drugs are usually titrated to achieve a desired
arterial blood pressure, it is more sensible to titrate ionotropes to
achieve a normal oxygen delivery/oxygen consumption ratio.
Pulmonary artery pressure and mixed venous saturation monitoring
are essential for intelligent management of the patient with severe
respiratory or cardiac failure. Adequate nutrition is also important for
recovery from organ failure. Renal failure is treated by mechanical
substitution of renal function. Although hemodialysis and peritoneal
dialysis can serve this purpose, each has a significant drawback in the
critically ill, multiple organ failure patient. Continuous arteriovenous
hemofiltration (CAVH) and continuous arteriovenous hemodialysis
(CAVHD) are the methods of choice for renal replacement therapy.
Hepatic failure often occurs as part of the multiple organ failure
syndrome but unfortunately there is no specific treatment.

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

pulmonary mechanics?

a. The standard compliance or volume pressure curve is measured

during lung inflation
b. The decreased compliance in acute respiratory failure occurs
because the lung is smaller not stiffer
c. In acute respiratory failure, higher pressures are required to
achieve the same level of inflation
d. Areas of normal lungs are more vulnerable to overdistention which
may lead to progressive lung dysfunction
Answer: b, c, d

The standard compliance or volume pressure curve is drawn by

measuring volume and pressure at stages of lung deflation after total
inflation. The decreased compliance in acute respiratory distress
syndrome occurs because the lung is smaller, not stiffer. In acute
respiratory failure, the cause of decreased compliance is almost
always associated with a decrease in functional residual capacity
(FRC). The decreased FRC represents lost alveoli which are either
collapsed or filled with fluid but still perfused with blood. Because the
lung is smaller, the compliance curve has shifted to the right and
much higher pressures are required to achieve the same level of
inflation. Lung damage can be caused by high airway pressure, so that
overdistension is not merely inefficient but actually detrimental. Since
the most normal areas of lung have the best compliance, they are
most vulnerable to overdistension, contributing to the steady
progression of lung dysfunction in patients ventilated at high peak
pressure.

261 Which of the following statement(s) is/are true concerning the use
of a ventilator in the treatment of respiratory failure?

a. The assist-control mode is appropriate in the paralyzed patient

b. Peak inspiratory pressure should be optimized at a level in excess
of 40 cm H2O
c. A patient receiving excessive carbohydrate as a nutritional support
may have an elevated minute ventilation and may tire with
spontaneous breathing
d. In general, weaning requires an adequate inspiratory force, vital
capacity, and a minute ventilation less than 10 L/min
Answer: c, d

Most intensivists favor setting the ventilator on the assist-control

mode at a low sensitivity. In this fashion, the patient breathes at a rate
that regulates the PaCO2 to normal, but each breath is mechanically
assisted, providing maximal inflation. The volume of each breath is set
by limiting the maximal pressure or maximal volume of each breath.
Whichever method is used, the peak inspiratory pressure should not
generally exceed 40 cm H2O. If the patient is comatose or paralyzed,
the assist mode cannot be used and the rate is set in addition to the
volume.
Adequate weaning indices are: inspiratory force greater than 20 cm
H2O, vital capacity twice the tidal volume, adequate gas exchange at
assisted ventilation at FiO2 of 0.3 and 5 cm H2O of PEEP, and minute
ventilation less than 10 L/min. If the patient is hypermetabolic or is
receiving excessive carbohydrate as nutritional support, the minute
ventilation will be elevated, even during assisted mechanical
ventilation. If this is the case, the patient will tire rapidly on
spontaneous breathing.

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

estimation and measurement of energy requirements in the critically
ill patient?

a. One can only estimate energy expenditure with actual

measurement not technically possible
b. The amount of oxygen absorbed through the lungs is equal to the
amount of oxygen consumed by metabolic processes
c. Metabolic rate, normalized to body surface area, may
underestimate metabolism in a fat person
d. To convert cc’s of oxygen per minute to calories per day, a
conversion factor of 10 kcal of energy per liter of oxygen should be
used
Answer: b, c

The actual metabolic rate of any patient can be estimated from the
predicted basal rate according to the clinical situation. The amount of
energy is most conveniently expressed in calories/day. The metabolic
rate is normalized to body surface area; however, the actively
metabolizing tissue is the lean body cell mass. Consequently,
reporting “per square meter” underestimates metabolism in a fat
person and overestimates in a very lean person. Although most of
studies on nutrition in critical illness have been based on estimated
energy expenditure, actual measurement is much more accurate and
has become an important aspect of critical care management. The
most commonly used method of measurement is indirect calorimetry.
In this method, the amount of oxygen absorbed across the lungs into
the pulmonary blood is measured over a given period of time.
Assuming the patient is at a metabolic steady state during this time,
the amount of oxygen absorbed across the lungs is equal to the
amount of oxygen consumed in the metabolic process. The metabolic
rate, measured in cubic centimeters of oxygen/minute, can be
converted to calories/hour or /day if the oxygenated substrates are
known. For practical purposes, a conversion factor of 5 kcal of
energy/liter of oxygen consumed is a reasonable approximation.

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

response to a decrease in functional residual capacity percent (FRC)?

a. Supplying supplemental oxygen will always improve the situation

b. Respiratory alkalosis may occur
c. Decreasing compliance is a common occurrence
d. Respiratory rate and depth of breathing generally decrease
Answer: b, c

Pulmonary arterial spasm in response to local hypoxia autoregulates

pulmonary blood flow and maintains adequate gas exchange during
alveolar collapse—up to a point. However, when the loss in ventilation
exceeds the decrease in perfusion, a ventilation-perfusion mismatch
occurs, which results in incomplete oxygenation of blood perfusing
that area of the lung. The resultant hypoxemia stimulates an
increased rate and depth of breathing which may serve to reexpand
the person’s inflated area of lung. If it does not, hypoxemia will
continue but increased ventilation in other areas of the lung will result
in excess CO2 excretion, hypocapnea and respiratory alkalosis. The
blood gas picture, hypoxemia with respiratory alklalosis, is the most
common abnormality of gas exchange in surgical patients and it is a
hallmark of ventilation-perfusion imbalance. Oxygenation of blood in
the poorly ventilated area of lung can be improved by increasing
concentration of oxygen in the inspired gas. The use of supplemental
oxygen, however, treats the symptom rather than the basic cause and
may actually make the problem worse by adding to absorption
atelectasis, depriving the poorly ventilated area of nitrogen to hold
alveoli open. This may result in total alveolar collapse. In this
circumstance, blood perfusing the nonventilated area will mix with
blood from other areas of the lung, resulting in hypoxemia that does
not improve significantly in response of administration of oxygen.
Aside from the effects on gas exchange, loss of alveolar space results
in changes in the volume-pressure relationships in the lung. A
decrease in functional residual capacity always results in a shift in the
volume-pressure relationship toward a condition of decreasing
compliance.

264 Which of the following statement(s) is/are correct concerning the

body fluid compartments?

a. Both the extracellular and intracellular components of total body

water can be directly measured
b. The intravascular space accounts for the majority of extracellular
fluid
c. All water in the interstitial space is freely exchangeable
d. Transcellular fluid, separated from other compartments by both
endothelial and epithelial barriers, constitute about 4% of total body
water
Answer: d

Total body water (TBW) is distributed within the intracellular and

extracellular compartments. Intracellular fluid cannot be measured
directly but is calculated as the difference between TBW and the
measured extracellular water. Extracellular fluid can be measured
directly. The extracellular fluid compartment can be further simplified
into the intravascular and interstitial spaces. Intravascular space,
which accounts for 20% of the extracellular fluid, contains the plasma
volume which is approximately 8% of TBW or 5% of body weight. The
interstitial space extends from the blood vessels to the cells
themselves and includes the complex ground substance making up
the acellular matrix of tissue. Although the water within the space is
thought to be freely exchangeable, this water exists in two phases.
The free phase contains water that is generally freely exchangeable
and in a constant state of flux. The bound or gel phase is composed of
water that is closely associated with glycosaminoglycans,
mucopolysaccharides, and other matrix components. This water is
much less freely exchangeable. An additional extracellular fluid
compartment, the transcellular compartment, consists of water that is
poorly exchangeable under normal circumstances. This fluid is
separated from other compartments by both endothelial and
epithelial barriers and includes cerebrospinal fluid, synovial fluid,
water within cartilage and bone, fluids of the eye, and the lubricating
fluids of the serous membranes. Together, these fluids constitute
about 4% of TBW.

265 Which of the following statements(s) is/are true concerning

metabolic alkalosis?

a. Either increased extracellular bicarbonate concentration or

inhibited renal excretion of bicarbonate can cause metabolic alkalosis
b. In metabolic alkalosis secondary to prolonged gastric outlet
obstruction, the urine pH is usually acidic
c. Hypokalemia can lead to metabolic alkalosis
d. The respiration compensatory mechanisms for metabolic alkalosis
are quite ineffective
Answer: b, c, d

Sustained metabolic alkalosis occurs only if extracellular bicarbonate

concentration is increased and renal excretion of excess bicarbonate
is inhibited. Alone, neither is sufficient to result in metabolic alkalosis.
Extracellular bicarbonate concentration is increased by numerous
mechanisms. Loss of HCl is the leading cause of metabolic alkalosis in
surgical patients. External loss of gastric acid results in net gain in
bicarbonate, which causes metabolic alkalosis. Although the kidney
can excrete excess bicarbonate, this must be accompanied by
excretion of sodium. Renal excretion of sodium is limited in the face
of volume depletion, which also occurs with external losses of gastric
secretion. As volume depletion progresses, sodium is conserved in
exchange for hydrogen. Thus, in metabolic alkalosis secondary to
prolonged gastric outlet obstruction, the urine, although initially
alkalotic, becomes paradoxically acidotic in prolonged or uncorrected
cases. Hypokalemia and cellular exchange of potassium for hydrogen
can also lead to metabolic alkalosis. Hypokalemia results in enhanced
proximal tubular bicarbonate reabsorption and distal tubular acid
secretion. The major compensatory mechanism in metabolic alkalosis
is respiratory, since the presence of metabolic alkalosis implies renal
dysfunction in either generating or failing to excrete increased
amounts of bicarbonate. Hypoventilation is limited by the
development of hypoxemia, which stimulates ventilation. Among the
four major types of acid-base disorders, this compensatory
mechanism is the least effective.

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

respiratory acidosis?

a. Respiratory acidosis is associated with chronic pulmonary disease

far more commonly than is hypoxemia
b. The initial buffering effect occurs at the cellular level
c. Renal compensation occurs within 24 hours
d. Correction of hypoxemia in patients with chronic lung disease may
worsen respiratory acidosis
Answer: b, d
Respiratory acidosis, the decrease in extracellular pH from a primary
increase in PCO2, is due to inadequate ventilation. Although
pulmonary disease commonly causes hypoxemia, respiratory acidosis
is far less common, since defusion of O2 is more readily impaired
than diffusion of CO2. Increased PCO2 results in increased H2CO3
which disassociates into H+ and HCO3–. Cellular exchange of Na+ and
K+ for H+ allows the reaction to continue in this direction with
increased extracellular bicarbonate. This tissue buffering is
accomplished within minutes. Persistently elevated PCO2 also
stimulates increased renal acid excretion. Full renal compensation
occurs over 3 to 5 days. The treatment of chronic compensated
respiratory acidosis may be complicated by accompanying
hypoxemia. In chronic hypercapnia, the chemical chemoreceptors
may be insensitive and the accompanying hypoxemia may supply the
main respiratory drive through the stimulation of peripheral
chemoreceptors. In such patients, complete correction of hypoxemia
may further depress respiration and worsen the respiratory acidosis.

267 Which of the following(s) is/are true concerning the control of the
volume of body water?

a. Osmoreceptors and baroreceptors work equally to control fluid

balance during normal conditions
b. The cardiac atrium regulates volume only by means of its
sympathetic and parasympathetic connections
c. The kidney is the primary effector organ in controlling water
balance
d. The conversion of angiotensin I to angiotensin II is dependent on
the amount of the enzyme, renin, available
e. Nitric oxide plays a number of important roles in regulation of renal
hemodynamics
Answer: c, d, e

Changes in volume are detected both by osmoreceptors, which detect

changes in plasma osmolality and baroreceptors, which are sensitive
to changes in pressure. The osmoreceptors are responsible for
day-to-day fine-tuning of volume whereas the baroreceptors
contribute relatively little to the control of fluid balance under normal
conditions. Changes in effective circulating volume are sensed by the
volume receptors of the intrathoracic capacitance vessels and atria,
the pressure receptors of the aortic arch and carotid arteries, the
intrarenal baroreceptors, and, to a lesser extent, by the hepatic and
cerebrospinal volume receptors. These baroreceptors control volume
by means of sympathetic and parasympathetic connections. The atria
also appear to serve as endocrine organs capable of directing
responses to volume changes with the elaboration of the hormone,
atrial natriuretic peptide. The major hormonal mediator of
baroreceptor modulation of volume control is the renin-angiotensin
system. The end result of this complex system of receptors or
messengers is a change in sodium and water balance mediated by the
kidneys. It is through changes in sodium and water reabsorption that
volume and pressure ultimately normalize. Renin is a proteolytic
enzyme that is released in response to changes in arterial pressure,
changes in delivery of sodium to the macula densa of the distal
convoluted renal tubule, increases in beta adrenergic activity and
increases in cellular cAMP. Renin cleaves angiotensin I from circulating
angiotensinogen. Angiotensinogen is abundant, so this reaction is
enzyme dependent rather than substrate dependent. Angiotensin I is
further cleaved to angiotensin II which acts with locally and
systemically to increase vascular tone. Angiotensin II affects sodium
reabsorption by decreasing renal plasma flow and the glomerular
filtration coefficient. Finally, angiotensin II increases sodium
reabsorption by direct tubular action as well as by stimulation of
aldosterone release from the adrenal cortex.
The importance of nitric oxide and its many biologic functions has
recently been recognized. Nitric oxide participates in the regulation of
renal hemodynamics and renal handling of water and electrolytes.

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

maintenance intravenous fluid therapy?

a. The total daily water requirement for a 70-kg man is about 2500
mL/day
b. Normal maintenance IV therapy requires administration of sodium,
potassium, calcium, phosphate, and magnesium
c. Fluid volume calculations for elderly patients generally are
decreased compared to their younger counterparts
d. A child requires a lesser amount of maintenance fluid per kilogram
than a larger individual
Answer: a, c

Maintenance fluid replacement is aimed at replacing fluids normally

lost during the course of a day. Calculation of maintenance fluid
replacement does not include replacement of preexisting deficits or
ongoing additional losses. Formulas exist for calculating maintenance
fluid requirements which adjust for differences in body weight and for
changes in TBW content. A smaller (or younger) individual who has a
high percentage of TBW in relation to body weight requires a greater
amount of maintenance fluid per kilogram than a larger individual.
The total daily water requirement for a 70-kg man is about 2500
mL/day. Because hypervolemia is poorly tolerated in older individuals
and in patients with cardiac disease, the volume calculated is
generally diminished in this age group. Normal maintenance therapy
requires administration of sodium and potassium. Replacement of
calcium, phosphate or magnesium are generally not necessary in
patients requiring short-term therapy. In critically ill patients,
however, critical deficits in these electrolytes may occur and must be
replaced.

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

abnormalities in calcium concentration?

a. Parathyroid hormone affects calcium homeostasis only at the

exchange of calcium between bone and extracellular fluid
b. About 45% of total plasma calcium is in the ionized state and is
responsible for most physiologic actions
c. Changes in plasma protein levels or pH can alter the proportion of
calcium in the ionized state
d. Intravenous normal saline administration is the first step in
treatment of hypercalcemia
e. Classic signs of hypocalcemia include hyperactive deep tendon
refluxes, Cvostek’s sign and Trousseau’s sign
Answer: b, c, d, e

Calcium is a divalent cation found in abundance in the human body.

About 99% of total body calcium is located in bone in the form of
hydroxyapatite crystals. Calcium homeostasis depends on the
exchange of calcium between bone and extracellular fluid, renal
excretion, and intestinal absorption. These three processes are
controlled to a great extent by parathyroid hormone. In extracellular
fluid, calcium exists in three forms: ionized calcium, non-ionized
calcium, and protein-bound calcium. Ionized calcium, which comprises
about 45% of total calcium is responsible for most physiologic actions
of calcium in the body, and its level is tightly controlled by a regulatory
mechanisms. Some nonionized calcium is complexed with
non-protein anions, including phosphate and citrate, and does not
easily disassociate. These molecular forms make up only about 15% of
total calcium present in plasma. About 40% of extracellular
nonionized calcium is bound to proteins, with most being bound to
albumin. Changes in either plasma protein levels or pH can alter the
proportion of calcium in the ionized state. The most common cause of
hypercalcemia is primary hyperparathyroidism. Hypercalcemia can
also occur secondary to malignant disease, caused either by a
metastasis to bone or by autonomous tumor secretion of
hormone-like substances that alter calcium homeostasis.
Neuromuscular effects may be the earliest manifestations and include
muscle fatigue, weakness, personality disorders, psychosis, confusion,
and coma. Elevation of total serum calcium concentrations to greater
than 14mg/dL requires prompt treatment to prevent any serious and
potentially lethal complications. Immediate measures are directed
toward maximizing renal excretion of calcium. Vigorous hydration
with 0.9% saline solution to prompt diuresis should be the initial step
in treatment. The addition of potassium to the resuscitation fluid as
well as the use of furosemide can also be used for treatment.
Serum calcium levels below 8 mg/dL may be associated with
symptoms and signs that are primary manifestations of
neuromuscular abnormalities. These include muscle cramps, perioral
tingling, parastesias, laryngeal stridor, tetany, seizures and psychotic
behavior. Classic signs of hypocalcemia include hyperactive, deep
tendon reflexes, Cvostek’s sign, and Trousseau’s sign. Symptomatic
hypocalcemia is best treated with intravenous infusion of calcium in
the form of calcium gluconate or calcium chloride.

270 Which of the following statement(s) is/are true concerning total

body water?

a. Total body water in men represents a higher percent body weight

than in women
b. In infants, water comprises up to 80% of body weight
c. Total body water content decreases with increasing age
d. Total body water is equally distributed within the intra-and
extracellular compartments
Answer: a, b, c

The total volume of water within the body is termed total body water.
The relationship between total body water (TBW) and body weight is
relatively consistent for any given individual and depends on the
amount of fat within the body. Because fat contains little water, TBW
as a percentage of body weight decreases with increasing body fat.
The estimated TBW in men is 60% of body weight, whereas in women,
who typically have more adipose tissue, the average TBW is 50% of
body weight. The percentage of body weight accounted for by water
also varies with age. In infants, water comprises about 80% of body
weight. Throughout adult life, a gradual decrease occurs in TBW
content because of the amount of fat within the body usually
increases with age. In obese patients, estimates of TBW should be
decreased by 10% to 20% whereas in lean patients, estimates should
be increased by about 10%.
TBW is distributed within the intra and extracellular compartments.
Intracellular fluid makes up about 2/3 of the TBW, or 40% of body
weight.

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

clinical presentation and treatment of severe metabolic alkalosis?

a. In most cases clinical signs are obvious

b. Correction of potassium and volume depletion corrects most cases
of metabolic alkalosis
c. Acetazolamide can enhance renal excretion of bicarbonate
d. Acid replacement should be provided at a molar equivalent basis
for excess serum bicarbonate
Answer: b, c

Clinical signs of metabolic alkalosis may not be prominent, since the

condition usually develops relatively slowly. Correction of the
underlying cause is the mainstay of treatment in this disorder. In
general, correction of potassium and volume depletion corrects the
metabolic alkalosis. In patients without intravascular volume deficits,
renal excretion of bicarbonate can be enhanced by administration of
the carbonic acid anhydrase inhibitor acetazolamide. If renal excretion
of bicarbonate cannot be increased because of underlying renal
insufficiency or if the metabolic alkalosis is severe, acid may be
administered to directly titrate the excess extracellular bicarbonate.
Acids that can be used include ammonium chloride, arginine
hydrochloride, or dilute hydrochloric acid. Partial correction of
alkalosis is the initial goal. A general guide is that 2.2 mEq/kg
decreases serum bicarbonate by about 5 mEq/L.

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

abnormalities in serum sodium?

a. The most common cause of hyponatremia is a deficit in total body

sodium
b. Hyponatremia can occur in situations of excessive solute
c. Most surgical patients with hyponatremia are best treated by free
water restriction
d. Central nervous system effects are the predominant symptom of
hypernatremia
e. Hypernatremia should be rapidly corrected with free water
administration
Answer: b, c, d

The most common cause of hyponatremia is an excess of free water

rather than a deficit of total body sodium. Hyponatremia is frequently
seen in the postoperative or post-trauma patients because increased
ADH secretion acts on the collecting tubules of the kidney to increase
free water reabsorption. Although hyponatremia most often results
from excess free water, it can occur in the presence of excess solute.
In this situation, TBW content is either normal or diminished but the
plasma osmolality is increased. An example of this hyperosmolar-
hyponatremic state is untreated hyperglycemia. Excess solute may
also be due to exogenous administration or ingestion of mannitol,
ethanol, methanol, or ethylene glycol. Most surgical patients with
hyponatremia are euvolemic or hypervolemic. Such patients, if
asymptomatic, are best treated by free water restriction, since free
water overload is the cause of the condition. Hypernatremia is a less
common problem in surgical patients than hyponatremia and is
usually the result of excess free water loss associated with
hypovolemia. Hypernatremia may also be secondary to increased
total body content of sodium, which is usually related to exogenous
administration of sodium. The symptoms of hypernatremia are
related to the hyperosmolar state. CNS effects predominate because
of cellular dehydration as water passes into the extracellular space.
Once hypernatremia becomes symptomatic, it is associated with
significant morbidity and mortality. Prompt treatment of
hypernatremia is essential. Rapid correction, however, of
hypernatremia is associated with significant risk of cerebral edema
and herniation. Because chronic hypernatremia is relatively well
tolerated, there are few advantages to rapidly correcting the free
water deficit. Moderate degrees of hypernatremia are tolerated well,
and symptoms rarely develop unless serum sodium levels exceed 160
mEq/liter. The development of symptoms also depends on the
rapidity at which hypernatremia develops.

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

abnormalities in serum potassium?

a. Hyperkalemia can occur in the otherwise normal surgical patient

due to excessive intravenous potassium administration
b. The primary EKG change associated with severe hyperkalemia is
peaked T-waves
c. Temporary treatment of hyperkalemia includes administration of
calcium, sodium bicarbonate, or glucose and insulin
d. Alterations in membrane potentials reflected in cardiac and skeletal
muscle are common results of both hypo-and hyperkalemia
e. A reduction in serum potassium of 1mEq/liter requires replacement
of 40mEq of potassium
Answer: c, d

Potassium is the major intracellular cation and is a major determinant

of intracellular osmolality. Because of the large differences between
intracellular and extracellular potassium concentrations, a
transmembrane potential is generated. Alterations in potassium
concentration gradient (both hyper- and hypokalemia) have profound
effects on transmembrane potential and consequently on cellular
function. This is especially true for cardiac, skeletal, and smooth
muscle. Extracellular potassium concentration is primarily determined
by renal excretion. About 90% of ingested potassium is secreted by
the urine. Hyperkalemia therefore rarely develops from excessive
potassium intake in the absence of renal insufficiency, since the
capacity for renal potassium excretion is large. In the surgical patient,
diminished renal function is perhaps the most common problem
leading to hyperkalemia. Both chronic and acute renal failure result in
the deficit in potassium excretion. Hyperkalemia can also be
associated with cellular disruption, such as with crush injuries or lysed
erythrocytes in large hematomas or after massive blood transfusion.
The clinical manifestations of hyperkalemia are primarily related to
membrane depolarization. The most life-threatening manifestations
are related to the cardiac effects of membrane depolarization. Mild
hyperkalemia results in peaked T-waves on the EKG and may cause
parethesia and weakness. More severe forms of hyperkalemia cause
flattened P-waves, prolongation of the QRS complex, and deep
S-waves on EKG. Ventricular fibrillation and cardiac arrest may follow.
Severe hyperkalemia with EKG abnormalities requires urgent
treatment. Rapid infusion of 10% to 20% calcium gluconate may
reduce the effects of hyperkalemia on membrane potentials.
Administration of sodium bicarbonate is another temporary measure.
The increase in serum sodium antagonizes the effects of
hyperkalemia on the membrane potential, whereas the increase in
extracellular pH shifts potassium into the cells. Movement of
potassium into the intracellular compartment can also be achieved by
giving insulin and glucose.
Hypokalemia is usually caused by total body potassium depletion
secondary to the decreased potassium intake, increased extra-renal
potassium losses, or increased renal potassium losses. Decreased
serum potassium levels may also be secondary to redistribution of
potassium into the intracellular space. Symptoms of hypokalemia, like
those of hyperkalemia, are manifested by disturbances in membrane
potentials. As potassium levels fall below 2.5mEq/L, muscle weakness
is common. The primary treatment of hypokalemia is potassium
replacement. The route and rate of potassium replacement depends
on the presence and severity of symptoms. A reduction in serum
potassium of 1mEq/L represents a total body potassium deficiency of
100 to 200 mEq.

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

derangement of metabolic acidosis?

a. A major source of acid production of the body is sulfuric acid

b. Excessive loss of bicarbonate can occur with intestinal or pancreatic
fistulas
c. Ketoacidosis can occur in conditions of either hyper-or
hypoglycemia
d. Lactic acidosis is present when serum lactate concentration is > 2
mEq/L
e. Lactic acidosis can be associated with ethanol toxicity
Answer: a, b, c, e

Most clinically significant metabolic acidosis is related to the net loss

of bicarbonate, which occurs when consumption due to either loss or
titration is greater than bicarbonate generation. Under normal
circumstances of ingestion of the average amount of protein in an
American diet, about 70 mEq acid is generated daily. The major
source of acid production is sulfuric acid from the metabolism of
sulphur-containing amino acids. Increased protein intake and tissue
catabolism resulting in greater metabolism of sulphur containing
amino acids may lead to a generation of increased amounts of sulfuric
acid. This excess acid utilizes excess bicarbonate for neutralization.
Diarrhea, intestinal or pancreatic fistulas, and burns can cause
metabolic acidosis secondary to loss of bicarbonate. The two most
common types of organic acidosis are ketoacidosis and lactic acidosis.
The abnormality primarily responsible for ketoacidosis is deficiency of
insulin whether primary, as in diabetic ketoacidosis, or secondary to
hypoglycemia. Under normal conditions a small amount of ketoacids
is produced. During prolonged starvation, production of ketoacids
increase to modest levels, providing an important source of energy to
nonhepatic tissues, particularly the brain. In ketoacidosis, the ketoacid
production is excessive because of insulin deficiency. In diabetic
acidosis, insulin deficiency also contributes to hyperglycemia by
decreasing the metabolism of glucose by extrahepatic tissue and
increasing hepatic production of glucose.
Lactic acidosis can be divided into type A, caused by tissue hypoxia,
and type B, caused by other mechanisms. Hypoxia, the most common
cause of lactic acidosis, impairs the mitochondrial oxidation of NADH
to NAD that is necessary for glycolysis. Normal serum lactate
concentration is below 2 mEq/L. Lactate acidosis is secondary to
hypoxemia, usually due to an increased production of lactate as well
as decreased use, and serum lactate concentrations greater than 6
mEq/L. The most common cause of type B lactate acidosis is ethanol
intoxication.

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

osmotic activity of body fluids?

a. Urea contributes to the osmolality of a solution but not its tonicity

b. The osmolality of the body remains fairly constant at approximately
289 mOsm/kg H2O
c. The two primary regulators of water balance are antidiuretic
hormone and aldosterone
d. Serum sodium is the most valuable laboratory indicator of
abnormal total body water content
Answer: a, b, d

Body fluids are aqueous solutions composed primarily of water and

contained in different compartments of the body. The movement of
water from these compartments depends on a number of physical
properties, the most important of which is osmosis. According to the
principles of osmosis, if two solutions are separated by
semipermeable membrane, water moves across the membrane to
equalize the concentration of the osmotically active particles. The
osmotic activity across a semipermeable membrane is determined by
the concentration of solutes on each side of the membrane. The body
is capable of fine regulation of solute and water concentrations, so
that osmolality remains fairly constant at an average of 289 mOsm/kg
H2O. In response to small changes in cell volume, osmoreceptors in
the paraventricular and supraoptic nuclei of the hypothalamus send
signals to the neuronal centers that control the two primary
regulators of water balance, thirst and antidiuretic hormone
secretion. Changes in TBW are reflected by changes in extracellular
solute concentration. Because sodium is the primary extracellular
cation and potassium is the predominant intracellular cation, the
serum sodium approximates the sum of the exchangeable total body
sodium and exchangeable total body potassium divided by the TBW.
Because total body solute content remains relatively stable over time,
changes in TBW content result in inversely proportional changes in
serum sodium. Thus, abnormalities in serum sodium are the
indication of abnormal TBW content. In contrast to impermeable
solutes that are excluded from the intracellular space, such as
sodium, permeable solutes such as urea can freely cross the cell
membranes. Although urea contributes to the osmolality of a solution,
it has no effect on tonicity because it distributes equally across
membranes, and as such does not contribute to the osmols that
affects cell volume.

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

compensatory mechanisms and treatment of metabolic acidosis?

a. Maximal renal compensation for metabolic acidosis occurs before

full respiratory compensation can occur
b. All patients with lactic acidosis should receive prompt treatment
with bicarbonate
c. Potassium replacement is essential even in the face of normal or
high serum potassium when treating diabetic ketoacidosis
d. Sodium bicarbonate administration should begin simultaneous
with volume resuscitation in patients with hypoxia secondary to shock
Answer: c

The kidney is extremely sensitive to changes in serum bicarbonate

concentration and responds by increasing net acid excretion primarily
by increasing ammonia excretion. Maximal renal compensation
requires 2 to 4 days. Delay in achieving maximal renal response to an
increased acid load causes blood pH to decline, which stimulates
hyperventilation. Although effective in promptly raising blood pH,
ventilatory compensation is only partial, and full respiration
compensation requires 12 to 24 hours. The major principal of
treatment for mild to moderate acute metabolic acidosis is correction
of the underlying cause. In surgical and trauma patients, metabolic
acidosis is often the result of hypoxia secondary to inadequate tissue
perfusion and subsequent lactic acidosis. Volume and/or blood
resuscitation alone may be enough to correct the acidosis. Attempts
to correct acidosis with exogenous bicarbonate before correction of
inadequate tissue perfusion are usually unsuccessful. The use of
bicarbonate for the treatment of lactic acidosis is controversial at
best. In several studies the use of bicarbonate in patients with lactic
acidosis does not improve clinical parameters or outcome. The
correction of both acidosis and hypoglycemia of diabetic ketoacidosis
is best achieved by the administration of insulin. Volume resuscitation
is also required. Potassium replacement is essential, even in the face
of normal or high serum potassium, and as hypokalemia develops as
acidosis in hyperglycemia are corrected.

277 Which of the following statement(s) is/are true concern renal

tubular acidosis?

a. Renal tubular acidosis is primarily caused by reduction in ammonia

excretion
b. The renal tubular defect in renal tubular acidosis can either be at
the distal or proximal renal tubule
c. In distal renal tubular acidosis associated with hyperkalemia, the
defect involves increased tubular permeability with backleak of
secreted sodium and potassium into the tubular cell
d. Uremic acidosis occurs independently of protein intake
Answer: a, b

The impaired ability of the kidney to excrete acid and hence generate
bicarbonate may be secondary to a decrease in the number of
functioning nephrons and is termed uremic acidosis or renal tubular
acidosis. Renal tubular acidosis, which can occur both in acute and
chronic renal failure, is primarily caused by reduction in ammonia
excretion secondary to a reduction in the number of functioning
proximal tubular cells. In addition, decreased proximal tubular
bicarbonate reabsorption contributes to the development of acidosis.
Although the onset of uremic acidosis is related to declining renal
function, its appearance may be influenced by diet-dependent protein
and organic anion ingestion. Renal tubular acidosis may be classified
as distal or proximal, depending on the primary site of the renal
tubular defect leading to acidosis. In renal tubular acidosis with
hyperkalemia, the mechanism is decreased luminal negativity
secondary to impaired sodium reabsorption. In distal renal tubular
acidosis with hypokalemia, mechanisms including increased tubular
permeability with backleak of secreted H+ into the tubular cell and
reduced H+ pump activity are proposed mechanisms.

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

postoperative fluid management in a surgical patient?

a. Standard formulas are available that essentially can direct the

therapy for all patients
b. Isotonic solutions containing potassium should be used throughout
the entire postoperative period
c. Urine output should be maintained at a level greater than 0.5
ml/kg/h
d. A urine specific gravity of greater than 1.012 may indicate that the
patient is dehydrated
Answer: c, d

Fluid therapy during the postoperative period should be tailored to

each patient and depends on the adequacy of patient’s volume status
at the completion of the operative procedure, as well as ongoing fluid
losses. Maintenance fluid should be supplemented by replacement of
the additional fluids needed to replace the ongoing third space loss as
well as losses from various tubes and drains. In general, isotonic
solution should be used for volume resuscitation during the early
postoperative period. It is best not to give potassium supplements
during this period unless they are specifically required as indicated by
serum electrolyte measurements. Monitoring fluid status during the
postoperative period is best accomplished by careful monitoring of
vital signs, urine output, and central venous pressure, if necessary.
Urine output is maintained at a level greater than 0.5 mL/kg/h. A urine
specific gravity of greater than 1.010 to 1.012 indicates that urine is
being concentrated and the patient may not be receiving adequate
hydration.

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

parenternal electrolyte solutions?

a. Lactated Ringer’s solution contains physiologic concentrations of all

important electrolytes
b. Glucose is added to hypotonic saline solutions to increase their
tonicity
c. About 1/2 of all exogenously administered albumin ends up in the
extravascular space
d. Normal saline solution provides excessive sodium and chloride
which may lead to body sodium overload
Answer: b, c, d

A number of electrolytes solutions are available for parenteral

administration. Lactated Ringer’s solution is a physiologic solution
containing many of the electrolytes found in plasma. The
disadvantage of this solution is the relatively low sodium content (130
mEq/L) as compared to plasma. Hyponatremia can occur with
extended use of lactated Ringer’s solution. Isotonic saline (0.9% or
normal saline) contains 154 mEq of both sodium and chloride. The
excess of both sodium and chloride can lead to electrolyte and
acid-base disturbances. Infusion of large volumes of 0.9% saline can
lead to total body sodium overload and hyperchloremia. The
less-concentrated saline solutions are hypo-osmotic and have excess
free water. In addition, 0.2% saline solution is hypotonic with respect
to plasma and can result in red blood cell lysis if rapidly infused. For
this reason, 5% dextrose is added to these solutions to increase the
tonicity. Plasma expanders are commonly used in surgical patients.
Plasma protein solutions such as 5% and 25% albumin act initially by
increasing plasma oncotic pressures. Abnormalities in microvascular
permeability such as those found in the pulmonary circulation in adult
respiratory distress syndrome, in regional circulatory bed burns or
infections, and in the systemic circulation in sepsis, may result in
extravasation of these proteins into the interstitial space. About half
of all exogenously administered albumin eventually ends up in the
extravascular space. The half life of exogenously administered
albumin is about 11 days.

280 An 11-year-old boy has experienced severe diarrhea for 10 days.

He presents with decreased skin tungor, sunken eyes, orthostatic
hypotension, and tachycardia. Which of the following statement(s)
may be true concerning his diagnosis and treatment?

a. His hematocrit will likely be elevated

b. His BUN may be elevated out of proportion to serum creatinine
c. His serum sodium will be elevated
d. Fluid resuscitation should begin with D5/.2 normal saline because
of the expected high serum sodium associated with excessive fluid
loss
Answer: a, b

Chronic volume deficits may be manifested by decreased skin turgor,

weight loss, sunken eyes, hypothermia, oliguria, orthostatic
hypotension and tachycardia. Serum BUN and creatinine may be
elevated, with a high BUN/creatinine ratio. The hematocrit may be
elevated as well. Plasma sodium is not an indicator of intravascular
volume, and if the loses have been isotonic, plasma sodium
concentration remains normal. Fluid resuscitation for hypovolemia is
initiated with an isotonic solution such as lactated Ringer’s solution.
Urine flow in critically ill patients is monitored with an indwelling Foley
catheter, with the goal of a urine output 0.5mL/kg/h desirable.

281 Clinical manifestations of acute metabolic acidosis include:

a. Decreased cardiac contractility

b. Decreased catecholamine secretion
c. Peripheral arteriolar dilitation
d. Shift of the oxygen-hemoglobin disassociation curve to the left
Answer: a, b, c

The major cardiovascular effects of acute metabolic acidosis are

peripheral arteriolar dilitation, decreased cardiac contractility, and
central venous constriction. These may lead to cardiovascular collapse
and pulmonary edema. Catecholamine secretion is stimulated by
metabolic acidosis and in mild cases, heart rate may be increased. In
addition to these cardiovascular effects, metabolic acidosis may also
affect oxygen delivery by shifting the oxygen-hemoglobin
disassociation curve to the right.

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

respiratory alkalosis?

a. Exposure to high altitudes can result in respiratory alkalosis

b. Renal compensation for respiratory alkalosis is obtained by
increasing excretion of bicarbonate
c. Symptoms of respiratory alkalosis may mimic those of
hypocalcemia
d. The treatment of acute respiratory alkalosis may involve a brown
paper bag
Answer: a, c, d

A primary decrease in PCO2 resulting in an increase extracellular pH is

referred to as respiratory alkalosis. Hyperventilation and the ensuing
fall in PCO2 may be secondary to hypoxia, reflux simulation from
decreased pulmonary compliance, drugs, mechanical ventilation, and
other causes. The two most common causes of hypoxia resulting in
respiratory alkalosis are pulmonary disease and exposure to high
altitudes. Renal compensation for respiratory alkalosis is not achieved
by increasing excretion of bicarbonate but by decreasing net acid
excretion, primarily through the reduction in ammonia excretion and
increases in organic anion excretion. Chronic respiratory alkalosis is
generally asymptomatic. Acute respiratory alkalosis may cause
sensations of breathlessness, dizziness, and nervousness and can
result in circumoral and extremity parathesias, altered levels of
consciousness, and tetany. These signs are related to decreased
cerebral blood flow secondary to decreased PCO2 and decreased
ionized calcium concentration secondary to increased blood pH. In
acute symptomatic respiratory alkalosis rebreathing, by breathing in
and out of a paper bag, can temporarily relieve the symptoms.

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

alterations in serum magnesium?

a. Renal failure is the primary cause of hypermagnesemia

b. Hypomagnesemia may occur during prolonged periods of
intravenous fluid replacement
c. Symptoms of hypomagnesemia may mimic symptoms of
hypocalcemia
d. Intravenous administration of magnesium sulfate is usually the
most efficient method of correction of magnesium deficiency
Answer: a, b, c, d

Renal failure is the primary cause of hypermagnesemia. Because of

the kidneys ability to excrete large magnesium loads,
hypermagnesemia rarely occurs if renal function remains normal.
Because the kidneys are able to conserve magnesium well in states of
magnesium depletion, hypomagnesemia rarely occurs from poor
intake alone. The combination of low intake and increased
gastrointestinal loss may lead to hypomagnesemia. Prolonged periods
of intravenous fluid replacement without magnesium replacement
and the chronic use of loop diuretics or other medications such as
cyclosporine or aminoglycosides can also result in hypomagnesemia.
Deficiencies of magnesium may present signs and symptoms similar
to hypocalcemia. Hypomagnesemia may be treated by the oral
administration of magnesium however large doses frequently leads to
diarrhea. Correction of major deficits is therefore best managed by
intravenous administration of magnesium sulfate at a dose of 50 to
100 mEq/d.
284 Muscle relaxants are a class of anesthetic agents used to prevent
movement and facilitate surgical exposure. Which of the following
statement(s) is/are true concerning the use of muscle relaxants in
surgical procedures.

a. Succinylcholine produces rapid obvious muscle fasciculations

b. Pancuronium can be reversed by increasing the acetylcholine
concentration using an anticholinesterase inhibitor (neostigmine)
c. Prolonged periods of muscle relaxation in patients requiring
prolonged ventilation should be used in conjunction with analgesics
and amnesic agents
d. The best clinical test for complete reversal of neuromuscular
blockade is the ability of the patient to produce a large negative
inspiratory force
Answer: a, b, c

Neuromuscular blocking agents can be classified as depolarizing or

nondepolarizing inhibitors of the neurotransmitter, acetylcholine at
the neuromuscular junction. The only noncompetitive inhibitor
employed clinically is succinylcholine. This drug rapidly binds to the
neuromuscular junction and produces depolarization, clinically
obvious as fine muscle fasciculations occurring approximately 60
seconds after injection. All other clinically useful muscle relaxants are
termed competitive inhibitors and do cause depolarization when they
attach to the neuromuscular junction. Since these agents compete
with acetylcholine, the block produced is in direct proportion to the
concentration of the agent relative to the concentration of
acetylcholine. If the concentration ratio is low enough, competitive
relaxants can be “reversed” if the concentration of acetylcholine is
artificially elevated. Increase of acetylcholine concentration can be
achieved by giving a drug which blocks metabolism of
anticholinesterase (neostigmine).
Nondepolarizing relaxants are frequently used in critically ill patients
who are difficult to manage otherwise during prolonged periods of
mechanical ventilation. It is imperative that these drugs be given in
conjunction with analgesics and amnesic agents, since neuromuscular
blocking agents have no analgesic or amnestic properties and only
prevent motion of voluntary muscles. Patients may therefore be
totally aware and in pain and unable to communicate. All muscles of
the body do not have equal sensitivity in muscle relaxants. The
diaphragm is both resistant to neuromuscular blockade while the
neck and pharyngeal muscles that support the airway are most
sensitive. It is possible for an intubated patient to spontaneously
ventilate and even to produce a large negative inspiratory force and
yet have complete airway obstruction when extubated due to effects
of residual muscle relaxants on upper airway muscles. The definitive
clinical test for complete reversal of neuromuscular blockade is the
ability of the patient to sustain a head lift from the bed for five
seconds.

285 Local anesthetics are essential agents used in current surgical

practice. Which of the following statement(s) is/are true concerning
the use of local anesthetic agents.

a. Complications due to excessive plasma concentration can result

only from inadvertent intravascular injection of the agent
b. Bupivacaine is noted for a slow onset but long duration
c. The addition of epinephrine to a local anesthetic agent will both
lower the toxicity and increase the duration of local anesthesia
d. Hypotension observed when a local anesthetic is administered in
the form of a spinal epidural block, is the result of myocardial
depression
Answer: b, c

Local anesthetics constitute a class of drugs which produce temporary

blockage of nerve conduction by binding to neuronal sodium
channels. Adverse consequences associated with the use of local
anesthetics fall into three categories: acute central nervous system
toxicity due to excessive plasma concentration, hemodynamic and
respiratory consequences due to excessive conduction block of the
sympathetic or motor nerves, and allergic reactions. Whenever a local
anesthetic has been injected, there may be inadvertent intravascular
injection or an overdose of the drug due to rapid uptake from the
tissues. All may produce seizures. Complications can be minimized by
aspirating prior to injection to avoid intravascular injection and
limiting the doses to the safe range. When local anesthetics are
administered for a spinal or epidural block, there will be a progressive
blockade of the sympathetic nervous system which will produce
systemic vasodilatation. If the block travels along the thoracolumbar
region, a sympathetic blockade will result in profound systemic
vasodilatation and bradycardia with resultant hypotension.
Local anesthetics are divided into two groups: esters and amides.
Most commonly used agents, the amides, include lidocaine and
bupivacaine. Lidocaine is noted for a fast onset of action but a short
duration whereas bupivacaine has a slower onset with the duration
lasting for four to 12 hours. The addition of epinephrine (100 µg) will
lower the toxicity and increase the duration of the local anesthetic.

286 A 65-year-old gentleman with a history of coronary artery disease

and a recent myocardial infarction requires an elective colon resection
for a nonobstructing neoplasm. Which of the following statement(s)
is/are true concerning the risks of general anesthetic in this patient?

a. The age of the previous infarct has no effect on the perioperative

reinfarction risk
b. The incidence of reinfarction appears to stabilize after six months
c. Invasive hemodynamic monitoring has no effect on perioperative
reinfarction rates
d. Reinfarction has minimal effect on mortality
e. Perioperative infarction most frequently occurs after the first 72
hours from surgery
Answer: b, d

The history of myocardial infarction is an important risk factor for

general anesthesia. Large retrospective studies have found that the
incidence of reinfarction is related to the time elapsed since the
previous myocardial infarction. The incidence of reinfarction appears
to stabilize at approximately 1% after six months, with the highest
rate of reinfarction occurring in the first three months after the
infarct. Mortality from reinfarction, for patients undergoing
non-cardiac surgery, has been reported to be between 20–50% and
usually occurs within the first 48 hours after surgery. Invasive
hemodynamic monitoring with pulmonary artery catheters and
aggressive pharmacologic intervention has been demonstrated to
reduce reinfarction rates.

287 General anesthesia is not without risks. Which of the following

statement(s) is/are true concerning the risk associated with general
anesthesia.

a. Current estimates for mortality due to anesthesia alone are

1:10,000
b. Human error accounts for between 50 and 75% of anesthetic-
related deaths
c. Most anesthetic-related deaths are associated with overdose of
analgesic agents
d. The most common problems associated with adverse anesthetic
outcomes are related to the airway
Answer: b, d

Anesthetic agents effectively obtund or completely block nearly all

physiologic protective mechanisms, therefore, there is an associated
risk even without a surgical procedure. Fortunately, with the advent of
newer agents and monitoring techniques, it is estimated the mortality
due to anesthesia alone has decreased from approximately 1:10,000
in the 1950s to as low as 1:100,000 or less for healthy patients today.
It has been estimated that between 50–75% of anesthetic-related
deaths are due to human error and are preventable. The most
common problems associated with adverse outcomes are related to
the airway: inadequate ventilation, unrecognized esophageal
intubation, unrecognized extubation, and unrecognized disconnection
from the ventilator.

288 Over the last decade, the routine use of both invasive and
noninvasive monitoring devices has been instituted for the
administration of most anesthetics. The following statement(s) is/are
true concerning monitoring of the surgical patient.

a. A pulse oximeter reading will reflect changes in PaO2 only below 80

mm Hg
b. Monitoring of end tidal CO2 will reflect changes in ventilation but
not cardiac output
c. Intermittent, noninvasive systemic blood pressure monitoring using
an oscillometric blood pressure cuff has essentially replaced clinical
measurement by auscultation
d. Pulmonary arterial catheter monitoring is generally reserved for
critically ill patients with significant left ventricular dysfunction
Answer: a, c, d

Pulse oximetry continuously, noninvasively and inexpensively

provides arterial hemoglobin saturation and peripheral pulse
determination. It must be remembered, however, that a pulse
oximeter measures oxygen saturation and not arterial oxygen tension
(PaO2). The PaO2 must drop below 80 mm Hg before any significant
change in oxygen saturation will occur. End tidal CO2 monitoring
reflects metabolism (the production of CO2), circulation (blood flow to
the lungs), and ventilation (respiratory rate in an intact ventilatory
circuit). It can be used as a surveillance monitor for both the
respiratory circuit and the cardiovascular system. Any acute decrease
in cardiac output will decrease output to the lung and increase
alveolar dead space, causing an acute drop in end tidal CO2.
Hemodynamic stability can be monitored in a variety of methods, the
most basic of which is systemic arterial blood pressure measure.
Intermittent, noninvasive measure of systemic blood pressure with an
oscillometric blood pressure cuff has become the standard in the
operating room with an accuracy equal to that of clinical
measurement by auscultation. When tighter control is required in
patients with significant hypertension, serious heart disease, or in
patients who may suffer acute blood loss, invasive arterial monitoring
is employed. In patients with left ventricular dysfunction who are
undergoing extended surgical procedures with significant fluid shifts
and potential blood loss, central venous pressure monitoring is
frequently used, with pulmonary arterial catheter monitoring reserved
for more critically ill patients and for those with significant left
ventricular dysfunction.

289 Correct statement(s) concerning complications occurring in the

post-anesthetic care unit include which of the following?

a. The use of nitrous oxide has been well documented to increase the
incidence of postoperative nausea
b. Perioperative myocardial ischemia is usually easily diagnosed in the
early postoperative period
c. Hypothermia results in a deleterious effect on drug metabolism
therefore delaying recovery from anesthesia
d. The serotonin antagonist, odansetron, holds promise as the
superior antiemetic agent in the perioperative period
Answer: c, d

Twenty-four percent of patients experience a post-anesthetic care unit

complication. Nausea, vomiting and airway support comprise 70% of
these complications. The need to maintain airway support is by far the
most common respiratory complication. Hypothermia has a
deleterious effect on altering drug metabolism and delaying recovery.
Nausea and vomiting are rarely unifactorial and cause considerable
discomfort to the patient. There is little evidence to favor one
anesthetic or anesthetic technique over another. Nitrous oxide does
not appear to increase incidence of nausea in well documented
studies. The new serotonin antagonist, odansetron, has been shown
in several studies to be superior to other agents as a perioperative
antiemetic agent.
Perioperative myocardial ischemia is an extremely important
complication but difficult to recognize. Diagnosis is complicated by the
fact that only 10—30% of patients suffering documented myocardial
infarction will have pain and that postoperative EKG changes are often
nonspecific. One must therefore look for secondary indications of
on-going ischemia such as hypotension, arrhythmias, elevated filling
pressures, or postoperative oliguria.

290 Patient-controlled analgesia ( PCA) is a commonly used technique

for postoperative analgesia. The following statement(s) is/are true for
the use of PCA.

a. Satisfactory pain relief is provided by the administration of higher

narcotic doses
b. The technique is not applicable in the semiconscious or
uncooperative patient
c. PCA is as safe as conventional intramuscular administration of pain
medication
d. Excessive administration of narcotic medication can be limited by a
lockout duration which controls administration of the narcotic
Answer: b, c, d

The technique of patient-controlled analgesia is based on

investigations that small intravenous bolus doses of narcotic on
demand can provide patients with improved pain relief at the same or
less total narcotic dose. The system requires some degree of
sophistication and a conscious patient who has been instructed in the
technique. Numerous studies have demonstrated that PCA is as safe
as conventional IM medication. The patient can be restricted from
receiving excessive agents via setting a lockout interval duration of
several minutes during which time a dose of narcotic cannot be
successfully administered. In addition, limits to the total hourly dose
can be set.

291 Narcotics are commonly used in the administration of general

anesthesia. Which of the following statement(s) is/are true concerning
this class of agents.

a. Narcotics have both profound analgesic and amnestic properties

b. Narcotics can cause hypotension by direct myocardial depressive
effects
c. Naloxone should be used routinely for the reversal of narcotic
analgesia
d. Acutely injured hypovolemic patients are at significant risk for
decreased blood pressure with the use of narcotic analgesics
e. Propofol is a new intravenous short-acting narcotic used frequently
in the outpatient setting
Answer: d

Narcotics and synthetic analogues belong in the class of drugs called

opioids. Narcotics produce profound analgesia and respiratory
depression. They have no amnesic properties, no myocardial
depressive effects, and no muscle relaxant properties. Narcotics may
produce significant hemodynamic effects indirectly through the
release of histamine and/or blunting of the patient’s sympathetic
vascular tone due to analgesic properties. Acutely injured patients
may be hypovolemic and in pain, with high sympathetic tone and
peripheral resistance. Therefore, such patients can experience a
dramatic drop in systemic blood pressure with minimal doses of
opioids. All opioids can be reversed with naloxone. Naloxone reversal,
however, can be dangerous because the agent acutely reverses not
only the analgesic effects of the opioid but also analgesics effects of
native opioids. Naloxone treatment has been associated with acute
pulmonary edema and myocardial ischemia and should not be used
electively to reverse the effects of narcotic. Propofol is a lipid-soluble
substitute isopropyl phenol non-narcotic agent that produces rapid
induction of anesthesia followed by awakening in four to eight
minutes.

292 Anesthetic techniques used in the management of patients with

significant pulmonary disease include:

a. Intubation at a deep level of anesthesia

b. Choice of an anesthetic agent which produces bronchodilatation
c. The use of epidural analgesia for postoperative pain control
d. Perioperative use of intermittent positive pressure breathing
Answer: a, b, c

Patients with significant pulmonary diseases require special

anesthetic techniques. Obstructive pulmonary disease can either be
chronic (COPD) or acute (asthma). In either case, the reversible
component of obstruction should be reversed prior to elective
surgery. In patients with reactive airway disease, the endotracheal
tube may induce severe bronchospasm. Even in patients who are well
treated preoperatively, reactive bronchospasm may complicate
anesthetic induction and emergence from anesthesia. The principal
method used to prevent or diminish this “foreign body” induced
bronchospasm is intubation of the patient at a deep level of
anesthesia when reflexes are blunted. The classic way of managing a
patient with severe asthma is to induce with an agent that produces
bronchodilatation and to ventilate the patient with an inhalation agent
until deeply anesthetized prior to laryngoscopy and intubation. The
patient should be extubated while spontaneously ventilating, but with
the inhalation agent still in effect, bringing the patient to
consciousness while ventilating by mask.
Because of the potential adverse effects of systemic narcotics on
respiratory drive, the use of epidural narcotics and local anesthetics
for postoperative pain control has become very popular. These
techniques allow the patient to be extubated earlier, and patients with
intrathoracic and upper abdominal surgery, help restore pulmonary
function toward preoperative values. Preoperative use of intermittent
positive pressure breathing has not been demonstrated to decrease
the incidence of postoperative pulmonary complications.

293 Which of the factors listed below will adversely affect the risk of
perioperative cardiac complications and reinfarction in the patient
described above?

a. Greater than five premature ventricular beats per minute on EKG

rhythm strip
b. The anesthetic technique used
c. Withdrawal of medical therapy with beta blockers and topical
nitrates
d. Length of surgical procedure less than three hours
e. Known three vessel coronary artery disease
Answer: a, c, e

The incidence of reinfarction is increased in patients undergoing

intrathoracic or intra-abdominal procedures lasting longer than three
hours. The site of surgery or anesthetic technique have not been
shown to change the incidence of reinfarction if the procedure is less
than three hours in duration. Patients with known three-vessel or left
main coronary artery disease are at increased risk, while those who
have undergone prior coronary artery bypass grafting are of
substantially decreased risk of reinfarction. Prophylactic therapy with
beta blockers, calcium channel agents, and nitrates has not been
proven beneficial; however, withdrawal of these agents has been
associated with perioperative ischemia, myocardial infarction, and
death. CHF is the single most important factor predicting
postoperative cardiac morbidity. Rhythm disturbances, particularly
frequent premature ventricular beats, more than five beats/minute,
are also independently associated with an increased risk of
perioperative cardiac complications.

MedCosmos at 6:08 PM

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