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.
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.
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