Systemic Response to Injury

Question 1

Cytokines involved in the initial proinflammatory response include all of the following except:

A. Interleukin-6

B. Interleukin-10

C. Tumor necrosis factor-α

D. Interleukin-1

E. Interleukin-8

Answer 1

B

The complement cascade is the earliest humoral system activated in response to injury.

C3a and C5a, the biologically active anaphylatoxins, induce the release of proinflammatory cytokines.

Tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) are the key mediators of this cascade.

IL-6 induces T and B cells, and IL-8 recruits and activates inflammatory cells at the site of injury.

IL-10, in contrast, is one of the key mediators of the anti-inflammatory response and acts to inhibit the aforementioned cytokines.

Question 2

Which of the following is true regarding the role of TNF-α release in the inflammatory response?

A. It can be effectively blocked by anti–TNF-α antibodies to halt systemic inflammatory response syndrome (SIRS).

B. It does not have any beneficial effects in the early phases of the inflammatory response.

C. It is primarily from leukocytes.

D. It promotes polymorphonuclear (PMN) cell adherence and further cytokine release.

E. It is always deleterious.

Answer 2

D

TNF-α is a vital component of the early inflammatory response, especially locally, at the site of injury. It is released when the biologically active anaphylatoxins C3a and C5a are stimulated by the humoral system. Infusion of low doses of TNF-α in rats simulates the septic response, resulting in fever, hypotension, fatigue, and anorexia.

TNF-α promotes adherence of PMN cells to endothelium, production of prostaglandins by fibroblasts, and activation of neutrophils and stimulates the release of multiple other cytokines from lymphocytes.

TNF-α becomes deleterious when the proinflammatory stimuli are unchecked, leading to cellular damage and multiorgan system failure. TNF-α is released by macrophages and natural killer cells, but not leukocytes.

Trials involving anti–TNF-α antibodies (NORASEPT, INTERSEPT) have not shown statistically significant improvement in patient outcomes.

Question 3

A 56-year-old female is admitted to the intensive care unit (ICU) with a diffuse axonal injury after a motor vehicle crash. The nursing staff notices coffee ground material coming from her orogastric tube. What is the best intervention to prevent this complication?

A. Enteral feeding

B. Oral sucralfate

C. Oral proton pump inhibitor (PPI)

D. Intravenous (IV) H2 blocker

E. IV PPI drip

Answer 3

D

Stress-related gastritis can cause clinically significant bleeding in up to 5%–10% of ICU patients; therefore stress ulcer prophylaxis is now routinely administered in the ICU.

Ulcers and bleeding are thought to be secondary to mucosal damage caused by low-flow states and subclinical hypoperfusion to the gastric mucosa. Patients with the following criteria should receive stress ulcer prophylaxis:

• coagulopathy defined as platelets 50,000 cells per m (microliter); INR > 1.5; or PTT > two times the normal reference range
• mechanical ventilation > 48h
• history of gastrointestinal ulcer or bleed
• traumatic brain/spinal cord injury or burn
• two or more of the following minor criteria:
  
  • Sepsis
  • ICU admission
  • Occult gastrointestinal bleed > 6 days
  • Glucocorticoids > 250 mg

Clinical data suggest that if enteral access is possible, the best agent is an oral PPI. If enteral access is not feasible, an IV PPI or H2 antagonist is an alternative. IV PPIs are costly, so most centers favor an IV H2 antagonist.

Sucralfate has been studied and is effective in protecting against stress gastritis, but a disadvantage is its interference with the absorption of other medications such as antibiotics, warfarin, and phenytoin.

Previously, it was thought that the use of H2 blockers was associated with nosocomial pneumonia because of gastric bacterial colonization and subsequent aspiration. However, more recent trials have not demonstrated any difference between other protective agents and H2 receptor antagonists in the rate of ventilator-associated pneumonia.

Antacids have not shown efficacy in preventing stress related mucosal lesions in the ICU patients and are not considered as appropriate prophylactic agents.

Question 4

A 64-year-old male with severe pancreatitis is transferred to the ICU from an outside hospital. A report is given to the nurse that the patient has received “large-volume resuscitation.” Upon reaching the ICU, he is afebrile, tachycardic to 127, and has a BP of 120/60 mmHg. His abdomen is tense and full; he has a Foley in place but no urine in the bag. You suspect abdominal compartment syndrome (ACS). What is the mechanism of his
oliguria?

A. Extrinsic compression of abdominal organs on the kidneys, leading to reduced GFR

B. Elevated renal venous pressure, leading to reduced GFR

C. Decreased arterial flow to the kidney, leading to reduced glomerular filtration rate (GFR)

D. Extrinsic compression of the ureters, causing an obstructive oliguric renal failure

E. Compression of the bladder, causing an obstructive oliguric renal failure

Answer 4

B

Intraabdominal hypertension can be defined as intraabdominal pressure greater than or equal to 20cm H2O. ACS occurs in the setting of intraabdominal hypertension and evidence of abdominal hypoperfusion.

ACS reduces the GFR secondary to elevated renal venous pressure and causes oliguria. Other physiologic derangements that can be seen are elevation of the diaphragms impeding oxygenation and ventilation raising the central intrathoracic, venous, and intracranial pressures.

All of these issues can be treated with decompressive laparotomy. Decompressive laparotomy should be employed as a treatment for ACS when there is evidence of end-organ dysfunction.

Question 5

For ACS, which of the following parameters would necessitate a decompressive laparotomy for treatment?

A. Peak airway pressures of 30 mmHg

B. Systemic vascular resistance of 1400 dyn/s/cm5

C. Pulmonary capillary wedge pressure of 18 mmHg

D. Urine output of 0 ml

E. Requirements of Fraction of inspired oxygen (FiO)2 of 80% with positive end-expiratory pressure (PEEP) of 12

Answer 5

D

Decompressive laparotomy should be performed only when there is evidence of end-organ dysfunction. Of all the answer choices provided, only decreased urine output indicates end-organ dysfunction.

The rest of the parameters may be seen in ACS but do not indicate organ damage secondary to ACS; however, laparotomy would improve all of the parameters above.

Question 6

A patient is brought to the emergency department after being found unresponsive. Electroencephalography (EEG) indicates status epilepticus. A potential secondary clinical consequence is:

A. Meningitis

B. Hypothermia

C. Myoglobinuria

D. Cerebrovascular accident

E. Hypoglycemia

Answer 6

C

Status epilepticus is an entity that should be considered in any patient with recurrent or persistent seizure activity, or in those who do not wake up after seizure activity.

One of the potential systemic complications is rhabdomyolysis, which would result in myoglobinuria, elevated serum creatinine kinase, and pigmented granular urinary casts.

The other options are potential primary causes of seizure activity.

Rhabdomyolysis is a direct result of muscle injury and can be caused by prolonged seizure activity; major trauma; drug overdose; vascular embolism; extremity compartment syndrome; malignant hyperthermia; neuroleptic malignant syndrome; myositis; severe exertion; alcoholism; and medications such as statins, macrolide antibiotics, and cyclosporine.

Question 7

Euthyroid sick syndrome is diagnosed in a patient in the surgical ICU. All of the following are part of this clinical phenomenon except:

A. The patient behaves as though clinically hypothyroid

B. Normal or decreased total serum thyroxine (T4) level

C. Increased serum reversed triiodothyronine (rT3) level

D. Decreased thyroid stimulating hormone (TSH) level

E. Decreased total serum T3 level

Answer 7

A

The hallmark of this diagnosis is that the patient behaves neither clinically hypothyroid nor hyperthyroid. The other choices are the expected laboratory findings in patients with this syndrome.

Referred to alternatively as euthyroid sick syndrome, low T3 syndrome, low T4 syndrome, and nonthyroidal illness, considerable debate exists regarding whether this syndrome represents a pathologic process or an adaptive response to systemic illness that allows the body to lower its tissue energy requirements. In light of this controversy, no consensus has been reached on how to treat this entity or whether any treatment at all is necessary.

Because the interpretation of thyroid function tests in critically ill patients is complex, these tests should not be done in an ICU setting unless a thyroid disorder is strongly suspected.

Question 8

Acute respiratory distress syndrome (ARDS) develops in an acutely injured patient. If an alveolar biopsy specimen were taken within the first 24 h, the histologic examination would demonstrate:

A. Influx of protein-rich fluid and leukocytes

B. Preservation of type II pneumocytes

C. Bacterial colonization

D. Alveolar hemorrhage

E. High levels of collagen and fibronectin

Answer 8

A

ARDS involves three distinct phases.

The early, exudative phase is characterized by disruption of the alveolar epithelium with an influx of protein-rich fluid and leukocytes. Type II pneumocytes are damaged, and therefore surfactant production is halted.

The second fibroproliferative phase includes the arrival of mesenchymal cells that produce collagen and fibronectin.

The third, or resolution, phase involves gradual remodeling and clearance of edema.

Question 9

An obese patient with a body mass index (BMI) of 50 underwent a laparoscopic gastric bypass. Because of a technical difficulty in the case, the procedure lasted for 8 h. The patient was doing well postoperatively until 4 h, when the nurse noted a change in the urine color from yellow to dark brown. She also reported that the patient’s urine output decreased and his creatinine increased from 1.0 to 1.5. Which test would confirm the cause of these findings?

A. Renal ultrasound

B. Haptoglobin

C. Serum creatinine kinase

D. Complete blood count

E. Urine electrolytes

Answer 9

C

Rhabdomyolysis can occur postoperatively in obese patients whose back and buttock muscles were compressed against the operating table for a prolonged time.

Preventive measures include the use of larger tables to better distribute body weight, effective padding at all pressure points, intraoperative changing of patient position, and limitation of operative times.

Physicians should have a high index of suspicion for rhabdomyolysis in this patient population so that early recognition and treatment can prevent the potentially devastating consequence of acute renal failure (ARF) in this already high-risk group.

Creatinine kinase should be measured in any patient complaining of muscle pain or in whom dark urine, oliguria, or rising plasma creatinine develops.

Question 10

The primary algorithm for Rhabdomyolysis includes all of the following except:

A. Loop diuretics

B. Mannitol

C. Aggressive intravenous fluid resuscitation

D. Sodium bicarbonate

E. Serial basic metabolic panels

Answer 10

A

The goal of the treatment algorithm for rhabdomyolysis is to prevent ARF.

The cause of rhabdomyolysis-induced ARF is multifactorial and includes hypovolemia, ischemia, direct tubule toxicity caused by the heme pigment in myoglobin, and intratubular obstruction by casts.

Treatment of rhabdomyolysis is to induce prompt polyuria with sufficient intravenous fluid resuscitation to produce 1.5 to 2 mL/kg/h of urine.

Concurrently, urine alkalinization with a goal urine pH greater than 6.5 should be instituted with sodium bicarbonate to prevent precipitation of casts and obstruction of nephrons.

Mannitol may also act as a free radical scavenger in addition to a diuretic, although this is somewhat controversial.

Loop diuretics can be used as an alternative if brisk urine output cannot be achieved with the aforementioned measures, but they have the disadvantage of acidifying the urine.

Question 11

An 82-year-old female with multiple prior abdominal surgeries presents with a small bowel obstruction. She undergoes an exploratory laparotomy with an extensive lysis of adhesions for 7h. She receives 2L of crystalloid during the case and has 200cc of urine output. Her creatinine increases by 0.6 mg/dL the next day. All of the following are appropriate treatments except:

A. Rule out causes of outflow obstruction

B. Recheck hemoglobin

C. Calculate fractional excretion of sodium (FeNa)

D. Give a bolus of fluid

E. Start vasopressors for a mean arterial pressure (MAP) goal of 65 mmHg

Answer 11

E

The most common cause of postoperative acute kidney injury (AKI) is renal hypoperfusion secondary to hypovolemia.

Nephrogenic injury in patients with hypovolemia occurs when the renal arteries constrict in response to increased levels of epinephrine, angiotensin II, and vasopressin and the nephrons receive inadequate delivery of oxygen.

The goal of the treatment is to quickly reverse shock and restore renal blood flow. The primary treatment is always intravenous fluid resuscitation.

Active bleeding and obstruction should be ruled out. FeNa should be calculated to confirm your cause.

Vasopressors should be avoided whenever possible because the resultant vasoconstriction may exacerbate the ischemic insult to the kidneys.

Question 12

A 52-year-old diabetic male presents to the emergency department with chest pain, diaphoresis, and an elevated troponin. He is taken to the cardiac catheterization lab. Which of the following is true of contrast-induced AKI (CIAKI)?

A. It is the most common form of iatrogenic AKI in hospitalized patients.

B. CIAKI is characterized by oliguria.

C. Evidence of CIAKI occurs within 6 to 24 h of contrast administration.

D. The creatinine returns to normal within 1 month of insult for most patients.

E. The 1-year mortality associated with CIAKI is <5%.

Answer 12

A

CIAKI is the most common cause of iatrogenic AKI in hospitalized patients.

It generally presents as a non-oliguric injury, with an increase in creatinine seen 48 to 72h after the dye load was administered. Patients’ creatinine returns to baseline within 7 to 10 days. The 1-year associated mortality is 30%.

Question 13

Which of the following interventions reduces the likelihood of CIAKI?

A. N-acetylcysteine administration before giving the dye load

B. A one-time dose of prednisone 40mg before administration of dye load

C. 0.9% normal saline for 12h before and after giving the dye load

D. 0.45% normal saline for 12h before and after giving the dye load

E. 1L bolus of 0.9 normal saline at the time of giving the dye load

Answer 13

C

The pathogenesis of CIAKI is primarily an ischemic form of injury caused by the vasoconstrictive properties of contrast media.

In addition, contrast media can potentially have direct toxic effects on endothelial cells and renal tubules. Patients with diminished renal vasodilatory capacity (i.e., diabetic nephropathy) have an increased risk of CIAKI.

Hydration is the only intervention proven to prevent CIAKI, with oral hydration more efficient than PO. Randomized controlled trials have found a small superiority in treatment, with 0.9% over 0.45% saline.

There have also been multiple smaller studies demonstrating that 12h of rehydration before and after dye load is more beneficial than a single bolus before the contrast load.

N-acetylcysteine has been used for the prevention of CIAKI, with mixed results in the literature. However, due to the low cost and low side-effect profile, some authors still advocate its use.

Question 14

A 47-year-old male with Crohn’s colitis maintained on 40mg prednisone daily for the past year presents for elective colectomy. The procedure was uncomplicated, and he was adequately resuscitated. In the postanesthesia care unit (PACU) the patient is noted to be febrile and hypotensive with MAPs in the 50s. What is your next step in management?

A. IV dobutamine

B. Hydrocortisone

C. 1 unit of packed red blood cells

D. Antibiotics

E. Epinephrine

Answer 14

B

The patient in the above scenario has been exposed to prolonged steroids and, as a result, has relative adrenal insufficiency.

These patients may experience shock when they do not receive glucocorticoid replacement during times of relative corticoid and mineralocorticoid deficiencies.

Signs and symptoms of acute insufficiency include fever, nausea, vomiting, refractory hypotension, and lethargy.

Intravenous volume replacement with isotonic fluids and immediate IV steroid treatment with hydrocortisone are essential.

Question 15

You are called by a PACU nurse for a patient who just underwent an elective splenectomy for idiopathic thrombotic purpura. The patient is afebrile, tachycardic, and hypotensive. What is your next step in management?

A. Check hemoglobin

B. IV fluid resuscitation

C. Electrocardiogram

D. Antibiotics

E. Start vasopressors

Answer 15

A

Anytime a patient in the immediate postoperative period becomes unstable, evaluation for bleeding is critical.

Hemoglobin should be checked, and if necessary, the patient should be returned to the operating room.

The other steps may ultimately be required; however, bleeding must be ruled out first.

Question 16

Which of the following metabolic changes occur during times of physiologic stress?

A. Increase in growth hormone (GH) release

B. Increase in TSH

C. Increased levels of T4 and T3

D. Initial insulin increase and then suppression

E. Increase in cortisol excretion

Answer 16

E

There are many metabolic changes in times of stress. Cortisol is a major effector of metabolism and is the main hormone increased in the stress response. Cortisol inhibits growth hormone (GH) release, decreasing GH levels.

Insulin-like growth factor levels are decreased in these times as well.

Injury decreases TSH and conversion of T4 into T3, resulting in decreased levels of both T4 and T3.

There are two patterns of insulin release, initial suppression followed by elevated release but increased peripheral resistance, leading to hyperglycemia.

Question 17

Which of the following patients most likely has sepsis and should have prompt evaluation for transfer to an ICU?

A. A 27-year-old female after lithotripsy for nephrolithiasis who is afebrile with a heart rate (HR) of 102, BP 90/40 mmHg, altered mental status, and white blood cell (WBC) count of 9

B. A 72-year-old male with pancreatitis and a temperature of 102 degrees Farenheit, HR 110 beats/min, BP 110/60 mmHg, and WBC count of 14 cells per mcl

C. A 53-year-old female at postoperative day 0 from a colon resection who is tachycardic to 120 s and requires intubation in the PACU

D. An 84-year-old nursing home resident with a urine culture positive for Proteus spp.

E. An 18-year-old male who presented with a gangrenous appendicitis, is now at postoperative day 0 from a laparoscopic appendectomy, and is febrile to 103 and tachycardic to 130 s with BP of 140/70

Answer 17

A

In 2016, the consensus guidelines on the definitions of sepsis and septic shock were revised for the first time since 2001. The aim of the consensus committee was to change the definitions to reflect the change in understanding of the pathophysiology and natural history of sepsis.

The committee defined sepsis as a life-threatening organ dysfunction caused by dysregulated host responses to infection. The prior definition of sepsis included two or more SIRS criteria plus a possible source of infection.

SIRS may reflect a host response that is merely adaptive; therefore the old definition did not adequately identify all patients who may benefit from intensive therapies.

Through examination of large data sets, the quick sepsis-related organ failure assessment (qSOFA) was developed to help promptly identify patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital.

Criteria for the qSOFA are altered mental status, respiratory rate > 22/min, or systolic BP < 100 mmHg.

Patients who screen positive warrant a higher level of care and intervention.

Of the patients listed above, only patient A meets the criterion for qSOFA. While several of the others may meet criteria based on the former definition of sepsis, their conditions may be physiologic responses to injury and not suggestive of impending life-threatening injury and therefore do not need intensive monitoring.

Question 18

Which of the following is the best parameter for monitoring septic shock?

A. Central venous pressure (CVP)

B. Vasopressor requirement

C. Urine output

D. Serum lactate

E. Mental status changes

Answer 18

D

Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

Patients with septic shock can be identified with a clinical construct of sepsis with persistent hypotension requiring vasopressors to maintain a MAP >65mmHg and a serum lactate level >2mmol/L despite adequate volume resuscitation.

With these criteria, hospital mortality is in excess of 40%. Serum lactate is a good indicator of global perfusion.

By definition, patients with sepsis suffer global hypoperfusion. CVP is often unreliable and can be affected by patient positioning, catheter positioning, and other physiologic derangements.

Vasopressor requirements are often needed in septic shock to help improve perfusion but cannot be used as a direct measure of perfusion.

Oliguria and altered mental status are signs of end-organ damage.

Question 19

All of the following are negative outcomes that have been directly associated with perioperative hypothermia except:

A. Coagulopathy

B. Wound infections

C. Nosocomial pneumonia

D. Myocardial ischemia

E. Delayed wound healing

Answer 19

C

Preservation of normothermia in surgical patients is important and is one of the goals of the Surgical Care Improvement Project (SCIP).

Hypothermia results in peripheral vasoconstriction, which leads to decreased subcutaneous oxygen tension and antibiotic delivery. Both neutrophil activity and leukocyte chemotaxis are impaired. All of these sequelae give rise to an increased incidence of wound infections.

Globally reduced enzyme function leads to coagulopathy.

Collagen cross-linking and therefore wound healing is affected by hypothermia.

An increased risk for myocardial ischemia in patients with known coronary artery disease has been associated with hypothermic states.

There has not been a direct correlation between the development of nosocomial pneumonia and hypothermia.

The SCIP measures aim to achieve a target temperature of 36.0°C in perioperative patients using active warming methods.

Question 20

An obese 21-year-old male suffers multiple fractures and a liver injury; 21 days later, he develops acute dyspnea, diaphoresis, and desaturates to 86% at room air. A computed tomography (CT) of the chest is positive for pulmonary embolus. All of the following are risk factors for venous thromboembolic events except:

A. Severity of injury

B. BMI

C. Smoking

D. Pelvic fractures

E. Hypertriglyceridemia

Answer 20

E

Venous thromboembolic disease (VTE), which can manifest as deep venous thrombus (DVT) or pulmonary embolism (PE), is common and can have serious or fatal consequences.

Risk factors for VTE frequently encountered by surgeons include increased severity of injury, increased BMI, history of smoking, intraabdominal cancers, pelvic fractures or surgery, lithotomy positioning, and operative times longer than 2h.

Hypertriglyceridemia and hypercholesterolemia have been examined as risk factors for VTE, but no statistically significant association has been established.

Question 21

Which of the following patients should receive prolonged prophylaxis (28 days) for VTE?

A. Female with a newly diagnosed DVT in her right popliteal vein

B. Male with chronic pulmonary embolus who undergoes a laparoscopic cholecystectomy

C. Female with gastric cancer who undergoes a total gastrectomy

D. Female with uterine fibroids undergoing total abdominal hysterectomy

E. Female with breast cancer undergoing bilateral mastectomy

Answer 21

C

Continued prophylaxis after surgery should be based on the assessment of risk of VTE.

In patients with abdominal cancer, VTE is an important cause of death. About 29% of patients with abdominal cancer will develop a complication of VTE during their disease course.

Continuing chemical prophylaxis for 28 days postoperatively decreases the incidence of thromboembolic events and has a risk reduction of >50% in mortality, which persists for greater than 3 months.

Patients A and B both require therapeutic treatment and not prophylaxis.

Question 22

Which of the following is a contraindication to enteral feeding?

A. Ileus

B. Small bowel anastomosis

C. Hemodynamic instability requiring vasopressors

D. Pancreatitis

E. Pneumonia

Answer 22

C

Enteral feeding should be initiated early in the course of critical illness or injury.

The intestine plays a role in digestion and absorption of nutrients and acts as a barrier to enteric flora, preventing host invasion by microorganisms or their toxins. This intestinal barrier can be impaired during critical illness, making patients susceptible to bacterial translocation.

Enteral feeding is protective against microvilli atrophy and impairment of the intestinal barrier. Patients can and should be fed in all of the scenarios above with the exception of hemodynamic instability.

In times of global hypoperfusion there is a risk of intestinal ischemia caused by enteral feedings.

Patients with pancreatitis may receive enteral feedings; however, postpyloric feedings are preferred.

Question 23

A patient with a previous history of ischemic bowel requiring extensive bowel resection, now with only 100cm of bowel remaining and dependent on total parenteral nutrition (TPN), presents to your office complaining of hair loss, rash on the extremities, and dry skin. Which nutrient deficiency is this patient most likely suffering from?

A. Copper

B. Selenium

C. Vitamin D

D. Essential fatty acids

E. Zinc

Answer 23

D

Short gut as a result of small bowel loss and or dysfunction of the remaining bowel is characterized by malabsorption of nutrients, diarrhea, and weight loss.

Essential fatty acids are not part of TPN formulas, and deficiency causes dermatitis, diarrhea, alopecia, patchy red areas on the skin, brittle nails, easy bruising, bleeding tendencies, and delayed wound healing.

Question 24

Strategies that have been suggested to decrease the risk for postoperative pulmonary complications include all of the following except:

A. Routine nasogastric tube decompression

B. Lung expansion maneuvers

C. Preoperative smoking cessation

D. Postoperative epidural anesthesia

E. Use of intraoperative short-acting neuromuscular blocking agents

Answer 24

A

Postoperative pulmonary complications include atelectasis, pneumonia, prolonged mechanical ventilation, bronchospasm, and exacerbation of the underlying lung disease.

Aggressive pulmonary toilet, smoking cessation, epidural analgesia, and minimal neuromuscular blockade have been shown to be effective means of reducing postoperative respiratory complications.

In contrast, because systemic reviews have found that routine use of nasogastric decompression increases pulmonary complications, nasogastric tubes should be used postoperatively only when specifically indicated for the operative procedure.

An early postoperative fever is most likely due to atelectasis causing a respiratory shunt secondary to alveolar collapse. This results in varying degrees of hypoxemia. Persistent collapse leaves alveoli prone to bacterial colonization. Aggressive pulmonary toilet with incentive spirometry, forced coughing, and frequent turning is the best prevention.

Question 25

A patient with resolving ARDS requires a tracheostomy. The family wants to know the benefit of early tracheostomy compared with prolonged intubation. Which of the following is correct?

A. There is no difference in overall mortality between patients receiving prolonged endotracheal (ET) intubation and those receiving tracheostomy.

B. There is increased sedation and pain requirement with a surgically placed tracheostomy.

C. There is an increased risk of pneumonia with ET intubation.

D. There is a decrease in the time required for mechanical ventilation with tracheostomy.

E. ICU stays are the same for both ET intubation and tracheostomy.

Answer 25

A

There is no mortality difference between patients receiving prolonged endotracheal intubation and those receiving a tracheostomy.

Patients with a tracheostomy do have shorter stays in the ICU and decreased sedation and pain requirements.

There are equivocal rates of pneumonia and days requiring mechanical ventilation in both tracheostomy and ET intubation.

Question 26

C-reactive protein (CRP)

A. Is secreted in a circadian rhythm with higher levels in the morning

B. Increases after eating a large meal

C. Does not increase in response to stress in patients with liver failure

D. Is less sensitive than erythrocyte sedimentation rate as a marker of inflammation

Answer 26

C

The acute phase proteins are nonspecific biochemical markers produced by hepatocytes in response to tissue injury, infection, or inflammation.

Interleukin (IL)-6 is a potent inducer of acute phase proteins that can include proteinase inhibitors, coagulation and complement proteins, and transport proteins.

Clinically, only C-reactive protein (CRP) has been consistently used as a marker of injury response due to its dynamic reflection of inflammation.

Importantly, CRP levels do not show diurnal variations and are not affected by feeding. Only pre-existing liver failure will impair CRP production.

Therefore, it has become a useful biomarker of inflammation as well as response to treatment. Its accuracy surpasses that of the erythrocyte sedimentation rate.

(See Schwartz 10thed., p.17.)

Question 27

Which of the following is true regarding the inflammatory response following traumatic injury?

A. There is an acute proinflammatory response caused by stimulation of the adaptive immune system.

B. There is an anti-inflammatory response that leads to a return to homeostasis accompanied suppression of the innate immune system.

C. The degree of inflammation is proportional to injury severity.

D. Systemic inflammation following trauma is related to the immune response to microbes.

Answer 27

C

The degree of the systemic inflammatory response following trauma is proportional to injury severity and is an independent predictor of subsequent organ dysfunction and resultant mortality. Recent work has provided insight into the mechanisms by which immune activation in this setting is triggered.

The clinical features of the injury-mediated systemic inflammatory response, characterized by increased body temperature, heart rate, respirations, and white blood cell count, are similar to those observed with infection.

While significant efforts have been devoted to establishing a microbial etiology or this response, it is now widely accepted that systemic inflammation following trauma is sterile.

(See Schwartz 10th ed., p.14.)

Question 28

High-mobility group protein B1 (HMGB1)

A. Is associated with the best-characterized damage-associated molecular pattern (DAMP), detectable in the circulation within 30 minutes of trauma

B. Is a protein secreted by immune-competent cells stimulated by pathogen-associated molecular patterns (PAMPs) or inflammatory cytokines

C. Is also secreted by endothelial cells, platelets, and also as a part of cell death

D. All of the above

Answer 28

D

The best-characterized DAMP in the context of the injury- associated inflammatory response is high-mobility group protein B1 (HMGB1), which is rapidly released into the circulation within 30 minutes following trauma.

Subsequent studies have proven, however, that HMGB1 is actively secreted from immune-competent cells stimulated by PAMPs (eg, endotoxin) or by inflammatory cytokines (eg, tumor necrosis factor and interleukin-1).

Stressed nonimmune cells, such as endothelial cells, and platelet also actively secrete HMGB1.

Finally, passive release of HMGB1 can occur following cell death, whether it is programmed or uncontrolled (necrosis).

The diverse proinflammatory biological responses that result from HMGB1 signaling include:

(1) the release of cytokines and chemokines from macrophage/monocytes and dendritic cells;
(2) neutrophil activation and chemotaxis;
(3) alterations in epithelial barrier function, including increased permeability; and
(4) increased procoagulant activity on platelet surfaces; among others.

(See Schwartz 10th ed., p.15.)

Question 29

The most abundant amino acid in the human body is

A. Carnitine

B. Arginine

C. Glutamine

D. Methionine

Answer 29

D

Glutamine is the most abundant amino acid in the human body, comprising nearly two-thirds of the free intracellular amino acid pool.

(See Schwartz 10th ed., p. 53.)

Question 30

What is the role of mitochondrial DAMPs in the injury-mediated inflammatory response?

A. Mitochondrial DNA induces production of HMGB1.

B. Mitochondrial DNA and peptides from damaged mitochondria activate the macrophage inflammasome.

C. Mitochondrial DNA and peptides modulate the anti-inflammatory response that suppresses the adaptive immune system.

D. Mitochondrial DNA is directly toxic to the liver and lung in high amounts.

Answer 30

B

Mitochondrial proteins and/or DNA can act as DAMPs by triggering an inflammatory response to necrosis and cellular stress.

Specifically, the release of mitochondrial DNA (mtDNA) and formyl peptides from damaged or dysfunctional mitochondria has been implicated in activation of the macrophage inflammasome, a cytosolic signaling complex that responds to cellular stress.

With stress or tissue injury, mtDNA and peptides are released from damaged mitochondria where they can contribute to a sterile inflammatory response.

From an evolutionary perspective, given that eukaryotic mitochondria derive from bacterial origin, it would make sense that they retain bacterial features capable of eliciting a strong response that is typically associated with a pathogen trigger.

(See Schwartz 10th ed., p. 16.)

Question 31

Which is FALSE regarding the hypothalamic-pituitary- adrenal (HPA) axis and injury-associated stress?

A. The HPA is initiated by the hypothalamus producing corticotropin-releasing hormone (CRH) in response to inflammatory cytokines.

B. CRH acts on the anterior pituitary to stimulate adrenocorticotropin hormone (ACTH) secretion.

C. CRH simulates the zona fasciculata of the adrenal gland to synthesize and secrete glucocorticoids.

D. Insufficient cortisol in response to critical illness can lead to tachycardia, hypotension, weakness, hypoglycemia, hyponatremia, and hyperkalemia

Answer 31

C

The HPA is initiated by the hypothalamus producing corticotropin-releasing hormone (CRH) in response to inflammatory cytokines. CRH acts on the anterior pituitary to stimulate the secretion of adrenocorticotropin hormone (ACTH) into the systemic circulation. ACTH acts on the zona fasciculata of the adrenal glands to synthesize and secrete glucocorticoids.

Cortisol is the major glucocorticoid in humans and is essential for survival during significant physiologic stress. The resulting increase in cortisol levels following trauma has several important anti-inflammatory actions.

Adrenal insufficiency represents a clinical syndrome highlighted largely by inadequate amounts of circulating cortisol and aldosterone. Classically, adrenal insufficiency is described in patients with atrophic adrenal glands caused by exogenous steroid administration who undergo a stressor such as surgery. These patients subsequently manifest signs and symptoms such as tachycardia, hypotension, weakness, nausea, vomiting, and fever.

(See Schwartz 10th ed., p. 20.)

Question 32

Nutritional formulas used to treat pulmonary failure typically increase the fat intake of a patient’s total caloric intake to

A. 50%

B. 20%

C. 80%

D. 10%

Answer 32

A

In pulmonary failure formulas, fat content is usually increased to 50% of the total calories, with a corresponding reduction in carbohydrate content.

The goal is to reduce carbon dioxide production and alleviate ventilation burden or ailing lungs.

Question 33

A 27-year-old male presents with perforated appendicitis. He is in severe discomfort and shows signs of activating his sympathoadrenal axis. All of the following activate the sympathoadrenal and hypothalamic–pituitary axes during stress or injury except:

A. Pain

B. Hypovolemia

C. Acidosis

D. Hypercapnia

E. Acetylcholine

Answer 33

ANSWER: E

COMMENTS: In response to stress or injury, neural afferent signals converge on the brain to activate the sympathetic nervous system and hypothalamic stimulation.

Catecholamines are released from the sympathetic nervous system and result in increases in blood pressure, heart rate, cardiac output, and minute ventilation.

Hypothalamic release of corticotropin-releasing hormone leads to release of corticotropin from the pituitary gland, which in turn induces the adrenal cortex to synthesize and release cortisol.

These responses are designed to compensate for lost circulatory volume, maintain organ perfusion, and provide the energy substrates needed for organ function.

Pain is a potent activator of these pathways.

Hypovolemia simulates baroreceptors in the aorta and carotid bodies, which stimulates these pathways. Chemoreceptors in the carotid bodies and aorta are activated by hypoxemia, acidosis, and hypercapnia.

These receptors also trigger the hypothalamic- pituitary-adrenal axis.

Cytokines can likewise affect these pathways, though in a less direct manner since they do not have direct neural input into these axes.

Acetylcholine has antiinflammatory effects and is not a part of the afferent response to injury.

Question 34

The patient above exhibits signs of a systemic inflammatory response. All of the following are a part of the systemic inflammatory response syndrome (SIRS) except:

A. Temperature of 36°C or lower

B. Pulse rate lower than 56 beats/min

C. Respiratory rate of 20 breaths/min or higher

D. White blood cell count of 12,000/μL or greater

E. 10% or greater band forms on complete blood count (CBC) with differential

Answer 34

ANSWER: B

The clinical spectrum of SIRS includes two or more of the following criteria:

• Temperature of 38°C or higher or 36°C or lower
• Pulse rate of 90 beats/min or greater
• Respiratory rate of 20 breaths/min or greater or a Paco2 of 32mmHg or lower
• White blood cell count of 12,000/μL or greater or 4000/μL or lower or 10% or more band forms on the CBC with differential

SIRS is a sterile response. Sepsis includes an identifiable source of infection in addition to SIRS.

Question 35

A patient with pheochromocytoma shows signs of an amino acid deficiency, with coarse hair, dry skin and nails, and constipation. Which of the amino acids is critical to the synthesis of catecholamines?

A. Tyrosine

B. Phenylalanine

C. Glutamate

D. Aspartic acid

E. Methionine

Answer 35

ANSWER: A

COMMENTS: Tyrosine from the diet or from conversion of phenylalanine is the prime substrate for the synthesis of catecholamines.

Tyrosine is hydroxylated to form dihydroxyphenylalanine (dopa), which undergoes decarboxylation to form dopamine.

Dopamine is then hydroxylated to form norepinephrine.

Norepinephrine is subsequently methylated in the adrenal medulla to form epinephrine.

In patients with pheochromocytoma, tyrosine can be used up and the patient can become tyrosine deficient, exhibiting the symptoms above.

Question 36

The patient above undergoes an open adrenalectomy and has an early postoperative fever, indicating inflammation due to cytokine release. All of the following are secreted as a part of the endocrine response to stress except:

A. Corticotropin

B. Antidiuretic hormone (ADH)

C. Growth hormone

D. Thyroid hormone

E. None of the above

Answer 36

ANSWER: E

COMMENTS: Trauma induces the release of hormones, which directly affect the metabolism of carbohydrates, fats, and proteins.

Corticotropin is released from the pituitary gland and stimulates the release of cortisol, which stimulates hepatic gluconeogenesis and increases the release of amino acids from skeletal muscles.

Release of ADH from the posterior pituitary gland in response to a decreased effective circulating plasma volume leads to increased peripheral vasoconstriction, increased water reabsorption, increased hepatic gluconeogenesis, and glycogenolysis.

Growth hormone is released from the anterior pituitary and increases amino acid uptake and hepatic protein synthesis. Thyroid hormone release increases after injury in response to the release of thyroid-stimulating hormone (TSH) from the anterior pituitary.

It induces glycolysis and gluconeogenesis and increases the metabolic rate and heat production.

Question 37

A patient presents with an aldosteronoma and clinical Which of the following is true of the system?

A. It is activated by an increase in the renal tubular sodium concentration.

B. Angiotensinogen is found in the renal medulla.

C. Angiotensin-converting enzyme in the liver converts angiotensin I to angiotensin II.

D. Angiotensin II stimulates the release of aldosterone.

E. Angiotensin II decreases splanchnic vasoconstriction.

Answer 37

ANSWER: D

COMMENTS: The renin–angiotensin system is activated by decreases in renal arterial blood flow and renal tubular sodium concentration, as well as increased β-adrenergic stimulation.

Renin is secreted from the juxtaglomerular cells of the renal afferent arteriole. It converts angiotensinogen in the liver to angiotensin I.

Angiotensin-converting enzyme produced by the lung converts angiotensin I to angiotensin II.

Angiotensin II simulates the release of aldosterone, increases peripheral and splanchnic vasoconstriction, and decreases the renal excretion of salt and water.

Question 38

A 35-year-old woman presents to you after running her first marathon with complaints of muscle aches. Which of the following is not an action of cortisol in this metabolically stressed patient?

A. It stimulates release of insulin by the pancreas.

B. It induces insulin resistance in muscles and adipose tissue.

C. It stimulates release of lactate from skeletal muscle.

D. It induces release of glycerol from adipose tissue.

E. It leads to immunosuppression.

Answer 38

ANSWER: A

COMMENTS: Cortisol is the major glucocorticoid released during physiologic stress.

After injury, cortisol levels are elevated in proportion to the degree of stress to the patient.

Metabolically, cortisol potentiates the actions of glucagon and epinephrine, which is manifested as hyperglycemia.

It also stimulates enzymatic activities favoring hepatic gluconeogenesis.

In skeletal muscle, cortisol induces protein degradation and release of lactate; lactate serves as a substrate for hepatic gluconeogenesis.

It also potentiates the release of free fatty acids, triglycerides, and glycerol from adipose tissue to provide additional energy sources.

In a stressed patient, cortisol induces insulin resistance in muscles and adipose tissue. All these actions are directed at increasing blood glucose levels in the stressed system.

Answer A is therefore incorrect because insulin causes a decrease in blood glucose levels.

Additionally, glucocorticoids cause depressed cell-mediated immune responses (decreased killer T-cell and natural killer cell function, as well as T-cell generation) and delayed hypersensitivity responses.

Question 39

The patient above is found to have marked rhabdomyolysis. Which of the following are effects of epinephrine in response to injury in this patient?

A. It enhances the adherence of leukocytes to vascular endothelial membranes.

B. It stimulates the release of aldosterone.

C. It inhibits the secretion of thyroid hormones.

D. It increases glucagon secretion.

E. It decreases lipolysis in adipose tissue.

Answer 39

ANSWER: D

COMMENTS: The catecholamines norepinephrine and epinephrine are increased up to fourfold in plasma immediately after injury.

In the liver, epinephrine promotes glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis.

It decreases insulin release and increases glucagon secretion. Epinephrine increases lipolysis in adipose tissue and induces insulin resistance in skeletal muscle.

The overall effect of these actions is stress-induced hyperglycemia.

Catecholamines also increase the secretion of thyroid and parathyroid hormones as a part of the stress response.

Epinephrine induces leukocyte demargination from vascular endothelial membranes, which is manifested as leukocytosis.

Question 40

Which of the following substances has been shown to be useful as a measurable marker of the response to injury?

A. Tumor necrosis factor-α (TNF-α)

B. Interleukin-2 (IL-2)

C. IL-6

D. IL-10

E. C-reactive protein (CRP)

Answer 40

ANSWER: E

COMMENTS: Cytokines released as a part of the stress response have a myriad of effects that both drive and inhibit the inflammatory process.

TNF-α is among the earliest detectable cytokines after injury. It is secreted by macrophages, Kupffer cells, neutrophils, natural killer cells, T lymphocytes, mast cells, and endothelial cells, among others. It has a half-life of less than 20 min. TNF-α induces significant shock and catabolism.

IL-2 is secreted by T lymphocytes and has a half-life of less than 10 min. It promotes lymphocyte proliferation, immunoglobulin production, and gut barrier integrity. It also regulates lymphocyte apoptosis.

IL-6 is released by macrophages, B lymphocytes, neutrophils, basophils, mast cells, and endothelial cells.

It has a long half-life and prolongs the survival of activated neutrophils.

It is a potent inducer of acute-phase proteins in the liver. IL-10 is secreted by B and T lymphocytes, macro- phages, basophils, and mast cells.

It is an antiinflammatory cytokine and has been shown to reduce mortality in animal models of sepsis and acute respiratory distress syndrome (ARDS).

CRP is useful as a marker of the response to injury because it reflects the degree of inflammation fairly accurately. CRP levels are not subject to diurnal variations and do not change with feeding. Consequently, it is used as a biomarker of inflammation and response to treatment.

Question 41

After a gunshot wound to the lower extremity requiring operative exploration and repair of the popliteal artery, a patient has pain, pallor, and coldness of his leg. You suspect reperfusion injury causing compartment syndrome. Which of
the following is true regarding reactive oxygen metabolites?

A. Reactive oxygen metabolites are synthesized and stored within leukocytes before being released in response to injury.

B. Reactive oxygen metabolites cause injury by oxidation of unsaturated fatty acids within cell membranes.

C. Cells secreting reactive oxygen metabolites are immune to damage after the release of these metabolites.

D. In ischemic tissue, the mechanisms for the production of reactive oxygen metabolites are downregulated.

E. Reactive oxygen metabolites are quenched by inhibitory cytokines.

Answer 41

ANSWER: B

COMMENTS: Reactive oxygen metabolites are short-lived, highly reactive molecules that cause tissue injury by oxidation of fatty acids within cell membranes.

They are produced during anaerobic glucose oxidation, with the resulting production of superoxide anion from the reduction of oxygen.

Superoxide anion is further metabolized to hydrogen peroxide and hydroxyl radicals. Cells are not immune to injury from the reactive oxygen metabolites that they release, but they are usually protected from damage by oxygen scavengers such as glutathione and catalases, not inhibitory cytokines.

In ischemic tissues, the mechanisms for the production of oxygen metabolites are actually activated, but because of the lack of oxygen supply, the production of reactive oxygen metabolites is kept to a minimum.

Once blood flow is restored, oxygen is redelivered, thereby allowing large quantities of reactive oxygen metabolites to be produced, which in turn leads to reperfusion injury. This is the inciting insult in compartment syndrome after the repair of vessels.

Question 42

A patient presents with an acute gastrointestinal bleed and receives multiple transfusions of packed red blood cells. The following day, hypoxemia and bilateral infiltrates are observed on his chest x-ray. Which of the following statements about eicosanoids is true?

A. Their synthesis is dependent on the enzymatic activation of phospholipase A2.

B. They originate from lymphocytes around the site of injury.

C. They are stored within inflammatory cells and released on tissue injury.

D. The production of leukotrienes is dependent on the enzymatic activation of cyclooxygenase.

E. The production of prostaglandins is dependent on the enzymatic activation of lipoxygenase.

Answer 42

ANSWER: A

COMMENTS: Eicosanoids are a class of mediators that includes prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids, and lipoxins.

They are secreted by all nucleated cells except for lymphocytes.

Phospholipids are converted by phospholipase A2 into arachidonic acid. Arachidonic acid is then metabolized by cyclooxygenase to yield cyclic endoperoxides and eventually prostaglandins and thromboxanes.

Alternatively, arachidonic acid is metabolized by lipoxygenase to yield hydroperoxyeicosatetraenoic acid and, eventually, hydroxyeicosatetraenoic acid and leukotrienes.

Eicosanoids are not stored within cells but are synthesized and released in response to hypoxia or direct tissue injury.

Other substances such as endotoxin, norepinephrine, vasopressin, angiotensin II, bradykinin, serotonin, acetylcholine, cytokines, and histamine can also induce the production and release of eicosanoids.

Eicosanoids have a variety of deleterious effects, including acute lung injury, pancreatitis, and renal failure. They are extremely potent in promoting capillary leakage, leukocyte adherence, neutrophil activation, bronchoconstriction, and vasoconstriction.

Question 43

In the patient above, you suspect transfusion-induced acute lung injury and intubate. The next day he has severe diffuse edema. Which of the following is true regarding the kallikrein–kinin system?

A. Bradykinins are potent vasoconstrictors produced in ischemic tissues.

B. Bradykinins are stored in macrophages and released in response to tissue injury.

C. Bradykinin release and elevation are proportional to the magnitude of injury.

D. Bradykinin antagonists have been shown to improve survival in septic trauma patients.

E. Bradykinin release is actually decreased in sepsis.

Answer 43

ANSWER: C

COMMENTS: Bradykinins are vasodilators produced by kininogen degradation by the protease kallikrein.

Kallikrein circulates in blood and tissues in an inactive form until it is activated by Hageman factor, trypsin, plasmin, factor XI, kaolin, and collagen.

Bradykinins increase capillary permeability, which leads to tissue edema. They also increase renal vasodilation, thereby leading to a reduction in renal perfusion pressure, which in turn activates the renin–angiotensin system and culminates in retention of sodium and water.

Bradykinins are released during hypoxia and ischemia and after hemorrhage, sepsis, and endotoxemia.

Elevations in bradykinins are proportional to the magnitude of the injury present. Studies in which bradykinin antagonists have been used to reduce the effects of sepsis show no improvement in survival.

Question 44

Which of the following is true with regard to the complement cascade in the setting of injury, as in acute lung injury in the patient above?

A. Complement deactivates granulocyte activation.

B. Complement induces the release of TNF-α and IL-1.

C. Complement induces the relaxation of endothelial smooth muscle.

D. The complement components C3b and C5b are strong anaphylatoxins.

E. The complement cascade is inhibited by hemorrhage.

Answer 44

ANSWER: B

COMMENTS: Ischemia and endothelial injuries lead to the activation of complement, a series of plasma proteins involved in the inflammatory response.

Complement is activated with the release of biologically active anaphylatoxins C3a and C5a during hemorrhage.

These components cause granulocyte activation and aggregation, increased vascular permeability, smooth muscle contraction, and release of histamine and arachidonic acid metabolites. They also promote the release of TNF-α and IL-1, both major cytokines in the inflammatory response.

Although the activation of complement can lead to the destruction and lysis of invading organisms, overactivation may result in tissue destruction and damage, as seen in ARDS.

Question 45

A patient presents to the emergency room after a pitchfork puncture wound the day before, concerned about infection. Which of the following is true with regard to the inflammatory response?

A. Clot at the site of injury is the primary chemoattractant for neutrophils and monocytes.

B. Migration of neutrophils to the site of injury is inhibited by the release of serotonin.

C. Mast cells appear at the site of injury after migrating to the injury via chemoattractants such as cytokines.

D. Surgical or traumatic injury is associated with upregula- tion of cell-mediated immunity via type 1 helper T (TH1) cells and downregulation of antibody-mediated immunity via type 2 helper T (TH2) cells.

E. Eosinophils involved in the inflammatory response are inactivated by the complement anaphylatoxins C3a and C5a.

Answer 45

ANSWER: A

COMMENTS: Formation of clot at the site of injury serves as the primary chemoattractant for Band monocytes during the inflammatory response of the body to injury.

Migration of neutrophils along with platelets through the vascular endothelium occurs within hours of injury and is facilitated by serotonin, platelet-activating factor, and prostaglandin E2.

Mast cells are preexistent in tissues and are therefore the first to be involved in the inflammatory response.

They release histamine, cytokines, eicosanoids, proteases, and TNF-α, which results in local vasodi- lation, capillary leakage, and recruitment of other inflammatory cells to the area.

In severe injuries, there is a reduction in cell- mediated immunity and TH1 cytokine production and a shift toward antibody-mediated immunity through the action of TH2 cells. A TH1 response is favored in lesser injuries, with intact cell-mediated opsonizing capability and antibody immunity against microbial infections and with the activation of monocytes, B lymphocytes, and cytotoxic T lymphocytes.

A shift to the TH2 response is associated with more severe injuries and includes activation of eosinophils, mast cells, and B-lymphocyte antibody production.

Eosinophils involved in the inflammatory response are activated by IL-3, granulocyte–macrophage colony-stimulating factor (GM-CSF), IL-5, platelet-activating factor, and the complement anaphylatoxins C3a and C5a.

Question 46

In acute wounds as in the patient above, the initial recruit- ment of neutrophils to endothelial surfaces is mediated primarily by:

A. Immunoglobulins

B. Integrins

C. Selectins

D. All of the above

E. None of the above

Answer 46

ANSWER: C

COMMENTS: In endothelial injury, the initial recruitment of inflammatory leukocytes, specifically neutrophils, to the endothelial surfaces is mediated by adhesion molecules known as selectins, which are found on cell surfaces.

Neutrophil rolling in the first 20 min after injury is mediated by P-selectin, which is stored within endothelial cells.

After 20 min, P-selectin is degraded and L-selectin becomes the primary mediator of leukocyte rolling.

Firm adhesion and transmigration of neutrophils through the endothelium and into the site of injury are mediated by integrins and the immunoglobulin family of adhesion molecules, including intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and platelet–endothelial cell adhesion molecule (PECAM).

Question 47

Which of the following regarding macrophages/ monocytes is true?

A. Macrophages and monocytes become hyperresponsive to
continued injury/insult after trauma.

B. Functional impairment in macrophage/monocyte capability may persist for a week and is overcome with the development and growth of newer, more immature monocytes.

C. Macrophages present peptides in association with major histocompatibility complex (MHC) class II molecules to prime CD8+ cytotoxic T lymphocytes.

D. Human leukocyte antigen (HLA)/MHC II expression on monocytes increases after a major injury.

E. Macrophages present peptides in association with MHC class I molecules to prime CD4+ helper T lymphocytes.

Answer 47

ANSWER: B

COMMENTS: After the initial short-lived hyperactivation involving the release of TNF and IL-1, macrophages and monocytes actually become hyporesponsive.

Deactivation of these cells results in a type of immunologic paralysis. With stress, these cells release prostaglandin E2, which has immunosuppressive effects. It inhibits T-cell mitogenesis, along with IL-1 and TNF-α production.

This functional impairment in the patient’s innate cellular immunity lasts for up to 7 days, until newly recruited monocytes are produced to bolster the immune response.

Additional mediators such as transforming growth factor-β (TGF-β), IL-10, and IL-4 are also secreted after stress or trauma and inhibit the capability of macrophages and monocytes to present antigen to T cells, thereby contributing to impairment in antigen-specific immunity as well.

The overall decrease in the adaptive immune response has been found to be associated with decreased resistance to infection.

The functional impairment in macrophage/monocyte capability may persist for up to 7 days and is overcome with the development and growth of newer, more immature monocytes, which may lack the abilities of their predecessor monocytes.

HLA-DR/MHC II expression on monocytes decreases after a major injury, with prolonged depression being associated with an increased infection rate.

Macrophages present peptides in association with MHC class I molecules to prime CD8+ cytotoxic T lymphocytes and peptides in association with MHC class II to prime CD4+ helper T lymphocytes.

Question 48

A patient with a history of alcohol abuse presents with profound hepatic failure after a Tylenol overdose. She is hypotensive, and you suspect delayed degradation of nitric oxide (NO) from her failing liver. Which of the following is true regarding NO?

A. NO is inhibited by acetylcholine stimulation.

B. NO is expressed constitutively.

C. NO can induce platelet adhesion and thus lead to microthrombosis.

D. NO has a half-life of 5 min.

E. NO is formed from the oxidation of l-alanine.

Answer 48

ANSWER: B

COMMENTS: NO is derived from the endothelial surfaces in response to acetylcholine stimulation, hypoxia, endotoxins, and cellular injury.

It is expressed constitutively at low levels and helps maintain normal vascular smooth muscle relaxation.

It reduces platelet adhesion and aggregation, thus making thrombosis of small vessels less likely.

It is diffusible, with a half-life measured in seconds. NO is formed from the oxidation of l-arginine via the enzyme NO synthase.

In liver failure, NO is not broken down efficiently, leading to hypotension.

Question 49

A patient presents with complaints of weight loss and is found to have colon cancer. Which of the following regarding TNF-α is true?

A. It is predominantly a local mediator that induces the classic inflammatory febrile response to injury by stimulating local prostaglandin activity in the anterior hypothalamus.

B. It is effective in promoting the maturation/recruitment of functional leukocytes needed for a normal cytokine response and delays apoptosis of macrophages and neutrophils, which may contribute to organ injury.

C. It has both a proinflammatory and antiinflammatory roles; is a mediator of the hepatic acute-phase response to injury; induces neutrophil activation but also delays disposal of neutrophils; and can attenuate TNF-α and IL-1 activity, thereby curbing the inflammatory response.

D. It is an inducer of muscle catabolism and cachexia during stress by shunting available amino acids to the hepatic circulation as fuel substrates; it also activates coagulation and promotes the expression/release of adhesion mol- ecules, prostaglandin E2, platelet-activating factor, glucocorticoids, and eicosanoids.

E. It promotes T-cell proliferation, production of immuno- globulins, and gut barrier integrity.

Answer 49

ANSWER: D

COMMENTS: Cytokines are the most potent mediators of the inflammatory response.

On a local level, they promote wound healing and proliferation of microorganisms. In excess levels, as sometimes occurs during the response to injury, they may induce hemodynamic instability, which can lead to organ failure or death.

There is considerable overlap regarding the effects of cytokines with regard to promoting or attenuating the inflammatory response.

Choice A describes IL-1. 
Choice B describes GM-CSF. 
Choice C describes IL-6. 
Choice D describes TNF-α. 
Choice E describes IL-2. 

TNF-α is thought to be responsible for the cachexia observed in cancer patients.

Question 50

Which of the following is considered an antiinflammatory cytokine?

A. IL-1

B. IL-4

C. IL-6

D. IL-8

E. Interferon-γ (IFN-γ)

Answer 50

ANSWER: B

COMMENTS: The alterations in the hemodynamic, metabolic, and immune responses evident in stressed patients are orchestrated by endogenous polypeptides known as cytokines.

They are produced by immune cells in direct response to injury, with levels correlating with the degree of tissue damage. Despite considerable overlap in bioactivity among cytokines, they are commonly classified by their predominant effect as proinflammatory or antiinflammatory.

Those commonly considered proinflammatory include IL-1, IL-6, IL-8, and IFN-γ.

Those usually considered antiinflammatory include IL-4, IL-10, IL-13, and TGF-β.

Question 51

Which of the following is true with regard to TNF-α and
IL-1?

A. Levels of soluble molecules that antagonize the effects of TNF-α and IL-1 have been shown to be predictive of organ failure.

B. Secretion of TNF-α and IL-1 is conducive to a hypoco- agulable state during an acute injury.

C. Secretion of TNF-α and IL-1 in response to injury leads to the downregulation of the synthesis of NO and subsequent vasoconstriction.

D. TNF-α and IL-1 have a long half-life, which makes them effective markers for determining the magnitude and severity of the inflammatory response.

E. TNF-α and IL-1 have no natural antagonists; rather, their systemic effects diminish because of natural cytokine degradation.

Answer 51

ANSWER: A

COMMENTS: TNF-α and IL-1 are overproduced in patients after posttraumatic inflammation. They induce increased synthesis of NO; activation of the cyclooxygenase and lipoxygenase pathways, which leads to the formation of thromboxanes and prostaglandins; and production of platelet-activating factor, intra- cellular adhesion molecules, and selectins, which is conducive to hypercoagulability.

TNF-α and IL-1 have a short half-life, thus making them unreliable predictors of the severity of injury in the clinical setting.

Soluble molecules that antagonize their effects are more stable and have been found to be predictive of lethal outcome and end-organ failure.

IL-1 receptor antagonist (IL-1Ra) binds to the IL-1 receptor and blocks IL-1 activity. Soluble TNF receptors I and II (sTNF-RI and sTNF-RII) bind biologically active TNF and antagonize its effects.

Question 52

All of the following with regard to IL-6 are true except:

A. IL-6 is a sensitive marker for the degree of tissue injury.

B. IL-6 induces the synthesis of CRP.

C. IL-6 secretion is inhibited by TNF-α and IL-1.

D. IL-6 levels peak early after injury.

E. IL-6 has antiinflammatory effects.

Answer 52

ANSWER: C

COMMENTS: IL-6 is a very sensitive marker for the degree of tissue injury. It is secreted by monocytes, macrophages, neutrophils, T and B cells, endothelial cells, smooth muscle cells, and fibroblasts.

IL-6 expression is induced by bradykinin, TGF-β, platelet-derived growth factor, TNF-α, and IL-1, among others.

IL-6 levels peak early after injury, with levels found to be predictive of risk for and mortality from organ failure after trauma.

IL-6 induces the synthesis of acute-phase proteins such as fibrinogen, complement factors, α1-antitrypsin, and CRP. CRP itself is a marker for states with increased inflammation and, in addition, is predictive of adverse outcomes following a secondary surgery.

IL-6 also has some antiinflammatory effects, including inhibition of proteases and reduction of TNF-α and IL-1 synthesis; furthermore, it can cause the release of immunosuppressive glucocorticoids.

Question 53

All of the following with regard to IL-8 are true except:

A. IL-8 levels after injury have been shown to correlate with the onset of multiorgan failure.

B. IL-8 exerts important inhibitory effects on polymorpho- nuclear cells.

C. IL-8 is associated with ARDS.

D. Local hypoxia induces the production of IL-8 from macrophages.

E. IL-8 does not produce the hemodynamic instability characteristic of TNF-α and IL-1.

Answer 53

ANSWER: B

COMMENTS: Like IL-6, IL-8 levels peak within the first 24 h of injury.

Prolonged elevation of IL-8 is predictive of the onset of multiorgan failure and even mortality.

IL-8 is secreted by monocytes, macrophages, neutrophils, and endothelial cells. It is a potent chemoattractant for polymorphonuclear cells, particularly in the lung, where it is thought to have a role in initiating ARDS.

Local hypoxia is thought to play a role in stimulating IL-8 production by pulmonary macrophages.

Circulating polymorphonuclear cells migrate in response to IL-8 production, thereby leading to massive infiltration into the lungs, which in turn can progress to full-blown ARDS.

Interestingly, IL-8 does not produce the hemodynamic instability characteristic of TNF-α and IL-1.

Question 54

Which of the following with regard to IL-10 is true?

A. IL-10 is a strong proinflammatory cytokine.

B. IL-10 is secreted primarily by platelets in response to injury.

C. IL-10 inhibits some proinflammatory cytokines such as IL-1.

D. IL-10 has a short half-life and is therefore not a useful marker for assessing the severity of injury.

E. IL-10 secretion is inhibited by the stress of surgical
procedures.

Answer 54

ANSWER: C

COMMENTS: IL-10 originates from T cells and monocytes. It has strong antiinflammatory properties and is capable of inhibiting the synthesis of proinflammatory cytokines such as IL-1 and TNF- α.

It also induces a reduction in class II MHC molecules on monocytes, thereby leading to the downregulation of the immune response.

IL-10 levels in trauma patients have been shown to reflect the severity of injury and are predictive of patients in whom sepsis or multiorgan dysfunction syndrome will develop.

Release of IL-10 is increased in direct proportion to tissue damage, thus suggesting that more invasive surgical procedures augment the release of IL-10.

Question 55

A patient in your intensive care unit (ICU) has hyperglycemia at 250 mg/dL 17 h after coronary artery bypass grafting. All of the following regarding insulin therapy are true except:

A. Hyperglycemia increases the morbidity of critically ill patients in the surgical ICU setting without significantly affecting mortality rates.

B. Maintaining blood glucose levels of 80 to 110 mg/dL is beneficial in surgical ICU patients.

C. Hyperglycemia impairs macrophage ability.

D. Insulin has antiinflammatory effects.

E. Hyperglycemia promotes coagulation.

Answer 55

ANSWER: A

COMMENTS: Prospective, randomized data from Van den Berge and colleagues have shown that hyperglycemia increases mortality rates in critically ill surgical ICU patients.

Hyperglycemia promotes oxidative stress, coagulation, and phagocyte dysfunction.

Advanced glycation end products resulting from hyperglycemia are themselves proinflammatory.

Insulin has anabolic, antiinflammatory, and antiapoptotic effects.

For all these reasons, insulin therapy for tight blood glucose control has been shown to improve outcomes in ICU patients.

However, maintaining very strict glucose control (80 to 110 mg/dL) has been shown to worsen outcomes and increase mortality, and a higher threshold is recommended.

Question 56

A patient remains intubated and is without enteral feeding for 3 days. Which of the following is the main energy source during critical illness/injury?

A. Skeletal muscle

B. Liver

C. Adipose tissue

D. Kidney

E. Gut

Answer 56

ANSWER: C

COMMENTS: Lipids are nonprotein, noncarbohydrate fuel sources that minimize protein breakdown in injured patients. In response to catecholamines released during stress, triglyceride lipase induces fat mobilization/lipolysis from adipose stores.

Glycerol is released and provides a substrate for hepatic gluconeogenesis.

Fatty acids are released and processed into ketone bodies by the liver to provide an additional fuel source.

Free fatty acids can also serve as a direct source of energy for such tissues as cardiac, kidney, liver, and muscle cells.

Question 57

When attempting to wean from the ventilator on postoperative day 6, you notice the above patient has persistent hypercapnea and suspect overfeeding. Which of the follow- ing is correct with respect to the respiratory quotient (RQ)?

A. RQ = 1: greater oxidation of protein for fuel

B. RQ > 1: overfeeding/greater carbohydrate oxidation

C. RQ = 0.7: greater oxidation of carbohydrate for fuel

D. RQ = 0.85: greater oxidation of fatty acid for fuel

E. RQ < 1: excess breakdown of proteins for fuel

Answer 57

ANSWER: B

COMMENTS: The RQ is a unitless number used for the calculation of basal metabolic rate when estimated from carbon dioxide production.

It is calculated from the ratio of CO2 produced and O2 consumed.

The RQ in patients who are in metabolic balance usually ranges from 1.0 (the value expected for pure carbohydrate oxidation) to 0.7 (the value expected for pure fat oxidation).

A mixed diet of fat and carbohydrate results in an average value between these numbers.

The RQ may rise above 1.0 in an organism oxidizing carbohydrate to produce fat, as in overfeeding.

In summary,
RQ = 1: greater oxidation of carbohydrate for fuel
RQ > 1: overfeeding/greater carbohydrate oxidation
RQ = 0.7: greater oxidation of fatty acid for fuel
RQ = 0.85: oxidation of equal amounts of fatty acids and glucose