51. In the nutritional support of patients with cancer, which of the following statements is/are true?
A. Nutritional support benefits the patient's lean body mass but does not enable the tumor to grow.
B. In experimental animals, the growth of implanted tumors is directly proportional to the amount of calories and protein supplied.
C. Prospective randomized trials of nutritional support utilizing chemotherapy and radiation therapy have revealed benefits to patients receiving total parenteral nutrition.
D. Studies of nutritional support for patients with cancer about to undergo surgery revealed decreased morbidity and mortality, especially morbidity from sepsis.
Answer: B
DISCUSSION: The problem with the patient with cancer is a very vexing one. Clearly, one of the metabolic effects of cancer, cachexia, affects patients in the last quartile of their disease and makes such patients intolerant of chemotherapy, radiation therapy, and, in many cases, operative procedures. Total parenteral nutrition (TPN) has been proposed as a means of reversing cachexia and enabling patients to better tolerate surgery, chemotherapy, and radiation therapy. In experimental animals, it is clear that the provision of calories and protein, especially in excessive amounts, is associated with the more rapid growth of tumors and decreased survival, especially in the group that is overfed in the extreme. There is also evidence suggesting that overfeeding, or at least TPN, may result in increased growth (or at least change cell kinetics) in patients who are overnourished with TPN. Of the randomized prospective trials that have been carried out, no trial utilizing chemotherapy or radiation therapy has revealed a survival advantage for patients receiving TPN. Indeed, in Shamberger's study, there is a suggestion that the tumor-free interval following treatment of lymphoma may be shorter in patients receiving TPN. In patients undergoing surgery, however, especially those who are severely malnourished (as recently revealed in the VA study) or in patients with major procedures such as esophagogastrectomy (as in Muller's study), evidence suggests that TPN is beneficial. In a late follow-up in Muller's study, there was no apparent increase in recurrence, and the survival rate was the same, despite much higher mortality in the non-TPN group. This suggests that any improved survival following operation may have been offset by an increased late recurrence rate, although it is difficult to reach this conclusion. In summary, for patients with cancer TPN probably nourishes the tumor as well as the host. Nonetheless, in severely malnourished patients provision of TPN from 5 to 10 days preoperatively may increase survival and decrease morbidity. Overfeeding must be avoided. Future studies will undoubtedly reveal that there are certain nutrients that tumors require, which probably should be best avoided.
52. Glucose overload results in increased CO 2 production. Which of the following statements are true?
A. In patients with respiratory insufficiency, administration of glucose as a principal calorie source is contraindicated.
B. In patients with pulmonary infection and sepsis, calorie support should consist of 95% fat and 5% glucose.
C. In Askanazi's study, increased CO 2 production and difficulty in weaning was associated only with pronounced overfeeding.
D. CO 2 production should be measured in most patients who are supported by respirators in intensive care units and are receiving nutritional support.
Answer: C
DISCUSSION: Few papers have excited as much interest as that by Askanazi, Kinney, and co-workers, which demonstrated that glucose calories given to patients with severe respiratory impairment may result in difficulty in weaning from a respirator. Subsequent research has suggested, however, that this occurs only with severe overfeeding, when the respiratory quotient is greater than 1 and calories are excessive. If one examines the conditions under which Askanazi's patients were studied, these were a group of septic, depleted patients who were taken from almost no nutritional support to a caloric supply of 2.25 times their caloric requirement, most of the calories consisting of glucose. Suffice it to say that, in patients with impaired respiratory function, one should measure VCO2 and, when VCO2 is significantly elevated and appears to interfere with weaning, decrease the amount of glucose calories and increase the amount of fat. If one measures or estimates calorie requirements and does not overfeed, lipid can be utilized for 25% of the caloric requirement and glucose for the remainder, without much fear of excessive CO 2 production.
53. Hepatic abnormalities have been noted in adults since the beginning of hyperalimentation. Which of the following statements are true?
A. Hepatic steatosis appears to be associated with an overload of glucose.
B. Hepatic steatosis is usually associated with abnormalities in hepatic enzymes.
C. Hyperbilirubinemia is inevitably associated with hepatic steatosis.
D. Abnormalities in the portal insulin-glucagon ratio are thought to be causative of hepatic steatosis in experimental animals.
Answer: AD
DISCUSSION: The most common metabolic complication of TPN in adults is hepatic steatosis. Unlike the hepatic abnormalities in children, which may progress to cholestasis, liver damage, and in some cases death, hepatic steatosis, or fatty infiltration of the liver with triglycerides, appears to be a rather benign complication. It may be, but is not necessarily, associated with hepatic enzymatic abnormalities, which usually occur in the first week, peak at the third week, and generally disappear by the sixth week of parenteral nutrition. Abnormalities in the transaminases are most common, with alkaline phosphatase also being elevated, but there is no correlation between the degree of fatty infiltration and enzymatic abnormalities. Fatty infiltration appears to be largely vacuolization with increased storage of triglycerides. Hepatic steatosis is almost always associated with an overload of glucose. Recent studies in experimental animals have suggested that the portal insulin-glucagon ratio, which is elevated under these circumstances, may be causally related to hepatic steatosis. Insulin is the leading storage enzyme and is responsible for lipogenesis. The presence of insulin inhibits lipolysis. Glucagon, on the other hand, results in the mobilization of hepatic lipid. The liver “sees” the portal vein insulin-glucagon ratio. Excesses of insulin elicited by hypertonic dextrose increase lipid deposition in the liver, whereas glucagon, which is elicited by certain amino acids, results in the mobilization of hepatic lipid.
54. Which of the following statements about the presence of gallstones in diabetes patients is/are correct?
A. Gallstones occur with the same frequency in diabetes patients as in the healthy population.
B. The presence of gallstones, regardless of the presence of symptoms, is an indication for cholecystectomy in a diabetes patient.
C. Diabetes patients with gallstones and chronic biliary pain should be managed nonoperatively with chemical dissolution and/or lithotripsy because of severe complicating medical conditions and a high operative risk.
D. The presence of diabetes and gallstones places the patient at high risk for pancreatic cancer.
E. Diabetes patients with symptomatic gallstones should have prompt elective cholecystectomy, to avoid the complications of acute cholecystitis and gallbladder necrosis.
Answer: E
DISCUSSION: Gallstones have been found to be very prevalent in patients with type II (non–insulin-dependent) diabetes mellitus, perhaps related to the dyslipoproteinemia in such patients. Although the complications of acute cholecystitis (infection, sepsis, gangrene of the gallbladder) are more common in diabetics, a decision-analysis study has shown that prophylactic cholecystectomy cannot be justified since the risk of morbidity and/or mortality from the cholecystectomy procedure is as great as that of complications or death from acute cholecystitis. Patients who become symptomatic should be promptly prepared and should undergo elective cholecystectomy, because an emergency operation in these patients with comorbid conditions, especially coronary artery disease, has substantial added mortality associated with it. There is no causal relationship between diabetes and pancreatic cancer.
55. Intensive insulin therapy:
A. Prevents the aggressive development of atherosclerosis in diabetic patients.
B. Is not associated with unawareness of hypoglycemia.
C. Improves peripheral neuropathy.
D. Improves established retinopathy and nephropathy.
E. Is indicated in all patients with non–insulin-dependent diabetes mellitus (NIDDM).
Answer: C
DISCUSSION: Intensive insulin therapy is indicated in patients with IDDM who can actively participate in their own management and the attainment of the goals set for their blood glucose and glycosylated hemoglobin (HgA1 c) levels. Because the main complication of intensive therapy is iatrogenic hypoglycemia, this mode of treatment is not indicated for patients with NIDDM, who often have coexisting medical conditions such as coronary artery disease and who tolerate hypoglycemia poorly. There is little or no evidence that macrovascular disease is affected by intensive insulin therapy, and the added weight gain and hyperinsulinemia associated with the therapy may worsen atherosclerosis. Unawareness of hypoglycemia is directly related to a recent hypoglycemia episode, so patients treated intensively are often unaware of the problem. Intensive therapy does not improve established retinopathy or nephropathy but slows or prevents progression of these complications; however, better glucose control may improve peripheral neuropathy.
56. Which of the following statements about hypertension in diabetes patients is/are correct?
A. Hypertension worsens the macrovascular disease of diabetes patients.
B. Hypertension accelerates the progression of diabetic nephropathy.
C. Hypertension is associated with sodium retention in diabetes patients.
D. Angiotensin-converting enzyme (ACE) inhibitors should be used in all patients with chronic hyperglycemia, regardless of the presence of hypertension.
E. Diuretics, as single-drug therapy, are not indicated in the treatment of hypertension in diabetes patients.
Answer: ABCDE
DISCUSSION: All of the answers listed are correct. By damaging endothelial cells, hypertension worsens macrovascular disease in all patients but especially in diabetics. Hypertension dramatically accelerates the onset and progression of diabetic renal disease and proteinuria, and this phenomenon can be slowed or prevented by a combination of treatment modalities, including ACE inhibitors, which dilate efferent glomerular vessels and lower intraglomerular pressure. Despite sodium retention in diabetes patients, single-drug therapy with a diuretic is not indicated because the chronic state of dehydration in such patients may become worse.
57. What is the major determinant in an individual patient's risk for perioperative complications?
A. The surgical procedure.
B. The length of the surgical procedure.
C. The anesthetic technique (e.g., general, regional).
D. The length of anesthesia.
E. All of the above.
Answer: A
DISCUSSION: The planned surgical procedure is the major determining factor in assessing an individual patient's risk for perioperative complications and in deciding which anesthetic technique will be most appropriate. Good communication between the surgeon and the anesthesiologist is vital, as the surgeon knows better than anyone else the extent of the operation and the length of time it will require.
58. Which of the following are considered routine intraoperative monitors?
A. Temperature probe.
B. Electrocardiogram.
C. Capnograph.
D. Blood pressure cuff.
E. Foley catheter.
Answer: ABD
DISCUSSION: The American Society of Anesthesiologists requires that the patient's ventilation, circulation, oxygenation, and temperature be continually monitored during all anesthetics. Routine monitors are considered to be a temperature probe, electrocardiogram, pulse oximetry, and blood pressure cuff.
59. Muscle relaxants can be used for which of the following?
A. To facilitate intubation.
B. To provide optimal surgical conditions.
C. To optimize ventilator support.
D. To provide sedation.
Answer: ABC
DISCUSSION: Muscle relaxants are administered to facilitate endotracheal intubation, to provide the surgeon with optimal working conditions during anesthesia, and to optimize mechanical ventilator support in some patients. They do not produce analgesia, sedation, or amnesia. Therefore, muscle paralysis should not be performed without sedation or general anesthesia.
60. Local anesthetics:
A. Inhibit transmission of nerve impulses by increasing sodium membrane permeability and the displacement of ionized calcium.
B. Are classified as amides or esters.
C. Produce peripheral vasodilation.
D. Are weak acids.
Answer: BC
DISCUSSION: Local anesthetics act within the nerve membrane, where they inhibit transmission of nerve impulses by reducing sodium membrane permeability and the displacement of ionized calcium. All local anesthetics consist of a hydrophilic region and a hydrophobic region separated by an alkyl chain. The bond of the alkyl chain is either an ester or an amide, and these drugs are classified based on this bond. All local anesthetics except cocaine produce vasodilatation and are weak bases.
61. Absolute indications for a double-lumen endotracheal tube during thoracic surgery are:
A. Massive hemorrhage from one lung.
B. Unilateral lung infection.
C. Facilitation of surgical exposure.
D. Unilateral bronchopulmonary lavage.
E. All of the above.
Answer: ABD
DISCUSSION: The absolute indications for a double-lumen tube are for the purposes of protecting one lung from the other. These indications include ventilation with a bronchopleural fistula, massive hemorrhage from one lung, pulmonary air cyst resection, unilateral lung infection, and unilateral bronchopulmonary lavage. Relative indications include facilitation of surgical exposure, for pneumonectomy, upper lobectomy, and thoracic aneurysm repair.
62. Determinants of cerebral blood flow include:
A. Preoperative neurologic dysfunction.
B. Arterial CO 2 tension.
C. Arterial O 2 tension.
D. Systemic arterial pressure.
E. All of the above.
Answer: BCD
DISCUSSION: Determinants of cerebral blood flow include arterial CO 2 and O 2 tensions, systemic arterial pressure, and temperature. Other factors that may affect cerebral blood flow and intracranial pressure are head position, jugular venous obstruction, and positive end-expiratory pressure.
63. Discharge criteria following ambulatory surgery include:
A. Ability to eat solid food.
B. Stable vital signs.
C. Ability to ambulate.
D. Ability to have protective airway reflexes.
Answer: BCD
DISCUSSION: Discharge criteria following ambulatory surgery include the patient's being fully awake and oriented, the ability to have protective airway reflexes, stable vital signs, adequate hydration with the ability to hold down oral intake, the ability to ambulate, and adequate pain control. All patients must have a competent person with them to transport them—and ideally to stay with them on the first postoperative night.
64. Advantages of patient-controlled analgesia (PCA) include:
A. Immediate medication delivery.
B. Less contact with nursing staff.
C. Rapid onset of analgesia.
D. Patient control over pain medication.
E. All of the above.
Answer: ACD
DISCUSSION: Advantages of PCA are immediate medication delivery, rapid onset of analgesia, and patient control over pain medication. Disadvantages of PCA are less contact with nursing staff and patients' fears that they could inadvertently administer an overdose or possibly become addicted to the opioid.
65. Advantages of epidural analgesia include:
A. Earlier mobilization after surgery.
B. Earlier return of bowel function.
C. Shorter hospitalizations.
D. Decreased stress response to surgery.
E. All of the above.
Answer: E
DISCUSSION: Epidural analgesia include excellent pain relief, decreased sedation with more rapid recovery to presurgical levels of consciousness, earlier mobilization after surgery with increased ability to co-operate with respiratory therapy and physical therapy. Following vascular surgery epidural analgesia may also improve graft flow through mild sympathetic blockade. Earlier return of bowel function, decreased stress response, shorter hospitalizations, and decreased morbidity have all been associated with epidural analgesia.
66. Ketorolac:
A. Is a nonsteroidal anti-inflammatory drug (NSAID) approved for intravenous, intramuscular, and oral administration.
B. Can be used indefinitely for postoperative analgesia.
C. Can cause renal dysfunction.
D. May decrease surgical blood loss.
Answer: AC
DISCUSSION: Ketorolac tromethamine, an NSAID, is approved by the FDA for intravenous, intramuscular, and oral administration. The agent is an effective analgesic with minimal side effects; however, ketorolac, like all NSAIDs, can enhance surgical bleeding and cause renal and platelet dysfunction. Additionally, it is recommended that ketorolac should not be used for more than 5 consecutive days.
67. Factors that decrease collagen synthesis include all of the following except:
A. Protein depletion.
B. Infection.
C. Anemia.
D. Advanced age.
E. Hypoxia.
Answer: C
DISCUSSION: Collagen synthesis, an integral part of wound healing, is affected by many local and systemic factors. Protein depletion impairs fibroplasia. Hypoproteinemia leads to diminution of fibroblast proliferation, proteoglycan and collagen synthesis, angiogenesis, and wound remodeling. Although anemia was once believed to be a significant cause of wound disruption, studies have shown that, in the absence of malnutrition or hypovolemia, anemia with a hematocrit greater than 15% does not interfere with wound healing. In contrast, molecular oxygen is critical for collagen synthesis because it is one of the factors required for the hydroxylation of lysine and proline. Also, hypoxia favors wound infection. The role of age in collagen synthesis is not clear, but the incidence of wound failure and incisional hernias is greater in patients older than 60. Fibroplasia occurs at a slower rate in older animals. Perhaps more than any other factor, wound infection is associated with the risk of wound failure.
68. Wound contraction and ultimate contracture may be controlled by which of the following drugs?
A. Colchicine.
B. D-Penicillamine.
C. Thiphenamil (Trocinate).
D. Glucocorticoids.
E. Ibuprofen (Motrin).
Answer: AC
DISCUSSION: Wound contraction is carried out by highly specialized cells called myofibroblasts, which, as their name implies, have histologic characteristics of fibroblasts and smooth muscle cells. The activity of these cells, and therefore wound contraction, can be influenced by topical application of smooth muscle inhibitors such as thiphenamil. Inhibitors of microtubule formation in myofibroblasts, such as colchicine and vinblastine, also inhibit wound contraction under experimental conditions. Glucocorticoids and NSAIDs do not affect the wound contraction process.
69. Which of the following is/are true of the actions of transforming growth factor beta (TGF-b) during wound repair?
A. Increased matrix and proteoglycan synthesis.
B. Inhibition of proteases.
C. Stimulation of plasminogen inhibitor.
D. Chemotaxis for fibroblasts and macrophages.
E. Autoinduction of TGF-b.
Answer: ABDE
DISCUSSION: Through autocrine and paracrine mechanisms TGF-b stimulates the deposition of collagen and other matrix components by fibroblasts, inhibits proteases, blocks plasminogen inhibitor, enhances angiogenesis, and is chemotactic for fibroblasts, monocytes, and macrophages. TGF-b modulates the expression of cell-surface integrins in a manner that enhances cell-matrix interaction and matrix assembly. TGF-b also induces cell production by cells, thus amplifying its biologic effects. The sustained production of TGF-b at the wound site leads to tissue fibrosis.
70. In contrast to adult wound healing with scar formation, which of the following are characteristic of scarless fetal skin repair?
A. Matrix rich in hyaluronic acid.
B. Increased inflammatory response.
C. Increased production of TGF-b.
D. No collagen deposition.
E. Minimal angiogenesis.
Answer: AE
DISCUSSION: The ability of a fetus to heal without scar formation depends on its gestational age at the time of injury and the size of the wound defect. In general, linear incisions heal without scar until late in gestation, whereas excisional wounds heal with scar at an earlier gestational age. The profiles of fetal proteoglycans, collagens, and growth factors are different from those in adult wounds. The less differentiated state of fetal skin is probably an important characteristic responsible for scarless repair. There is minimal inflammation and angiogenesis in fetal wounds. Fetal wounds are characterized by high levels of hyaluronic acid and its stimulator(s) with more rapid, highly organized collagen deposition. The roles of peptide growth factors such as TGF-b and basic fibroblast growth factor are less prominent in fetal than in adult wound healing. An understanding of scarless tissue repair has possible clinical applications in the modulation of adult fibrotic diseases and abnormal scar-forming conditions.
71. Which of the following cell types are not crucial for healing a clean, incisional wound?
A. Macrophage.
B. Platelet.
C. Fibroblast.
D. Polymorphonuclear leukocyte.
E. Myofibroblast.
Answer: DE
DISCUSSION: Experimental studies have shown that healing may progress normally in the absence of polymorphonuclear leukocytes in an uninfected wound. In contrast, depletion of monocytes and macrophages causes a severe alteration in wound healing with poor débridement, delayed fibroblast proliferation, and inadequate angiogenesis. Platelets carry a cadre of biologically active substances that are important for wound repair, including peptide growth factors like platelet-derived growth factor (PDGF) and TGF-b. Fibroblasts are the principal cell for matrix synthesis and deposition. Myofibroblasts are important for wound contraction in open defects but have little if any role in clean, incisional wounds.
72. Which of the following is/are not a substrate or cofactor for prolyl hydroxylase?
A. Alpha-ketoglutarate.
B. Ascorbate.
C. Biotin.
D. Oxygen.
E. Copper.
Answer: CE
DISCUSSION: Prolyl hydroxylase is one of the rate-limiting enzymes in collagen synthesis. Substrates and cofactors such as iron, alpha-ketoglutarate, ascorbate, and oxygen are important participants in this process. If insufficient prolines are hydroxylated, then the alpha-peptide collagen chains cannot assume a stable triple helix, the collagen cannot be exported from the fibroblasts, and the incomplete, unassociated alpha chains are broken down. Thus, ascorbate deficiency (scurvy) and hypoxia have similar effects on collagen synthesis.
73. Which of the following is an adhesion glycoprotein?
A. Fibronectin.
B. Tenascin.
C. Laminin.
D. Hyaluronic acid.
E. Collagen type IV.
Answer: ABC
DISCUSSION: Cell adhesion glycoproteins such as fibronectin, vitronectin, laminin, and tenascin provide a “railroad track” to facilitate epithelial and mesenchymal cell migration over the wound matrix. Hyaluronic acid is a glycosaminoglycan, and collagen type IV is a protein that is a crucial component of basement membrane.
74. Which of the following is/are true concerning wound fibroblasts?
A. Fibroblasts synthesize and secrete collagen molecules.
B. Wound fibroblasts are derived from blood-borne precursor cells.
C. Fibroblasts migrate to a wound along fibrin strands, which are used as a scaffold.
D. Large amounts of fibrin or blood clot can act as a physical barrier to fibroblast penetration, which delays normal wound healing.
Answer: ACD
DISCUSSION: Fibroblasts appear in the wound on about the third day of healing and begin to synthesize and secrete collagen molecules. Wound fibroblasts arrive from cells surrounding the wound (e.g., the adventitia of blood vessels), change their phenotype(s), and become mobile during the process of replication. Fibroblasts migrate into a wound using the provisional fibronectin and fibrin matrix as a scaffold. Fibroblasts do not have fibrinolytic enzymes, and large amounts of fibrin and blood clot prevent fibroblasts from entering the wound.
75. Which of the following is/are true?
A. Because of its thickness, the tensile strength of a healing wound on the eyelid is much less than one on the thick skin of the back.
B. By 2 days, the experimental burst strength of skin is minimal since collagen has been formed in the wound but has not yet cross-linked.
C. Wound strength reaches a plateau by 3 weeks.
D. Wounds rarely, if ever, regain the strength of intact tissues.
Answer: BD
DISCUSSION: Tensile strength measures load per cross-section area at rupture, whereas burst strength measures load required to break a wound, regardless of dimension. Therefore, skin wounds have comparable tensile strength, regardless of thickness. Collagen appears in the wound by 3 to 4 days. Minimal wound strength on day 2 is due to fibrin polymerization and adhesion of globular proteins. Wounds rapidly gain strength for about 4 months and then continue to gain strength at a slower rate for more than a year. Wounds do not regain the strength of normal tissue.
76. Which of the following interfere with normal collagen formation or cross-linking?
A. Beta-aminopropionitrile.
B. Iron chelators.
C. Vitamin C depletion.
D. Proline analogs (e.g., cis-hydroxyproline).
E. D-Penicillamine.
Answer: ABCDE
DISCUSSION: Intramolecular and intermolecular cross-links are crucial for collagen structural stability. Formation of cross-links can be inhibited by two pharmacologic agents: beta-aminopropionitrile inhibits the enzyme lysyl oxidase, and D-penicillamine binds to collagen substrate directly to prevent collagen cross-link formation. Iron is a cofactor for prolyl hydroxylase, which is important for collagen synthesis. In high enough concentration, proline analogs prevent collagen formation with minimal effects on noncollagenase protein synthesis.
77 Which of the following statement(s) is/are true concerning the cell plasma membrane?
a. The plasma membrane is composed of amphipathic molecules
b. The hydrophobic core of the lipid bilayer of the cell membrane contains specialized transport proteins which maintain the intracellular ionic milieu different from the extracellular fluid
c. Plasma membrane proteins extend externally and bear phospholipid moieties which contribute to the cell coat
d. The membrane proteins of nerve cells are highly voltage-dependent
Answer: a, b, d
The plasma membrane defines the boundary of the cell and serves to contain and concentrate enzymes and other macromolecule constituents. The plasma membrane is composed of amphipathic molecules, mainly phospholipids and proteins that contain distinct regions that are either insoluble in water (hydrophobic) or soluble in water (hydrophilic). The plasma membrane forms a continuous barrier between the aqueous extracellular and intracellular fluids. Transport proteins in the membrane act as regulated channels or transporters to maintain the intracellular ionic milieu that is clearly different from the extracellular milieu. In some cells, membrane proteins are diversified such as in nerve cells where the ion channels are highly voltage-dependent, providing the basis for information transmission in the form of electrical impulses. Most plasma membrane proteins extend externally and bear carbohydrate moieties primarily as oligosaccharide chains that contribute to the cell coat or glycocalyx.
78 Which of the following statement(s) is/are true concerning water movement across cell membranes?
a. Water moves only actively through cell membrane transport proteins
b. For most cells of the body, the transmembrane hydrostatic pressure is 0
c. Water distribution is determined entirely by solute distribution
d. Specialized cells such as the glomerulus of the kidney actively transport water to maintain hydrostatic pressure
Answer: b, c
The energetics of water transport across cell membranes is simplified by the fact that water moves only passively due to gradients of hydrostatic pressure or water concentration. Hydrostatic pressure is an important driving force only for certain specialized cells—the capillary endothelium and the glomerulus of the kidney. For most cells of the body, the transmembrane hydrostatic pressure is 0 and water moves only in response to water concentration gradients. Because the concentration of water is determined by the amount of dissolved solute, the difference in water concentration is typically expressed as a function of the difference in solute concentration or osmotic pressure difference. Because there are no specialized, energy-converting transport mechanisms for water, water is distributed at equilibrium. Water distribution is determined entirely by solute to solute distribution.
79 The transport of proteins out of the cell is termed exocytosis. Which of the following statement(s) is/are true concerning this process?
a. Secretory vesicles fuse with the plasma membrane
b. The process can occur in either a constitutive or regulated process
c. A regulated secretion is triggered by a stimulus, most likely a hormone or a neurotransmitter
d. A decrease in cytoplasmic calcium occurs as part of the secretion process
Answer: a, b, c
Transport vesicles that bud off the Golgi network carry both material to be secreted from the cell and protein destined to become components of the plasma membrane. These vesicles can fuse with the plasma membrane in a process termed exocytosis. Vesicular transport to the cell surface can be divided into two components, constitutive and regulated secretion. Regulated secretion occurs in cells secreting digestive enzymes, hormones and other regulatory molecules, and neurotransmitters. In regulated secretion, the material to be secreted is sorted in a storage vesicle or granule; fusion with the plasma membrane in exocytosis then takes place in response to external stimulation. Regulated secretion is triggered in most cases by a hormone or neurotransmitter. The ensuing process is termed stimulus-secretion coupling. In most cases the coupling involves an increase in cytoplasmic concentration of Ca++, but may also involve generation of diacylglycerol or production of cyclic AMP which activate kinases or phosphatases.
80 Which of the following statement(s) is/are true concerning the cell function of phagocytosis?
a. Phagocytosis is a mechanistically distinct process of endocytosis performed by special cells to take up larger particles such as bacteria or erythrocytes
b. Lymphocytes are the primary blood cell involved with this process
c. The process involves a coating of the cytoplasmic surface known as clathrin
d. Phagocytosis is performed only by white blood cells and tissue macrophages
Answer: a
Phagocytosis is a specialized form of endocytosis by which large particles are internalized by specialized cells primarily macrophages and neutrophils. To be phagocytosed, particles must bind to the surface of the phagocytic cell, usually as the result of specific antibody coating the particle. The phagocytic cell then extends pseudopods which engulf the particle. This event is followed by membrane fusion and a pinching off. As opposed to endocytosis, this process does not involve the membrane protein, clathrin, but rather actin. A physiologically relevant site of phagocytosis is the thyroid gland, where thyroid follicular cells phagocytose and digest thyroglobulin from the lumen of the thyroid follicle, thereby releasing the thyroid hormones, thyroxine triiodothyronine.
81 A striking feature of living cells is a marked difference between the composition of the cytosol and the extracellular milieu. Which of the following statement(s) concerning the mechanisms of maintenance of these differences is/are true?
a. The cell membrane is able to maintain a 10,000 fold gradient between the extracellular concentration of ionized calcium and the intracellular concentration
b. The key to these differences is the fact that the plasma membrane is normally impermeable to sodium, potassium and calcium
c. The selectivity of biologic membranes is highly consistent and seldom changes
d. The selectivity of cell membranes relates only to ions and not organic compounds
Answer: a
The survival of the cell requires that cytosolic composition be maintained within narrow limits, despite the constant influx of nutrients and the simultaneous outflow of waste. A familiar example of the distribution of ions across the cell membrane is that of sodium and potassium. Cells are typically rich in potassium and contain very little sodium. Despite the fact that they are constantly bathed by fluid that is precisely the opposite composition. Even more impressive is the distribution of ionized calcium. The extracellular concentration of this ion is typically of the order of 10–3M, whereas that of cytosol is typically 10–7M, a 10,000-fold gradient. Such nonequilibrium ion distributions are even more remarkable in light of the fact that the plasma membrane is, to varying degrees, leaky to ions such as sodium, potassium and calcium. The plasma membrane is leaky to a variety of substances, but it exhibits an astonishing ability to discriminate or select one substance over another. This selectivity relates to not only ions but also for organic compounds such as glucose. Finally, the selectivity of biologic membranes can be altered drastically as a result of regulatory or signaling processes that occur within the cell.
82 Which of the following statement(s) is/are true concerning DNA?
a. DNA is contained only in the nucleus of the cell
b. DNA strands are encoded by the sequence of four bases—adenine, guanine, cytosine and uridine
c. The basic unit of information of DNA is the intron, a sequence of three bases
d. There are an infinite number of possible codons
Answer: a
The genetic blueprint of an organism is carried in the nucleus of every cell, encoded by the sequence of four bases—adenine, guanine, cytosine and thymine, which together make up two long chains bound together by hydrogen bonds to form a DNA double helix. A gene is a segment of DNA that is transcribed into a corresponding RNA molecule that either codes for a protein or forms a structural RNA molecule. Genes are commonly between 10,000 and 100,000 base pairs in length and include, in addition to the coding sequence, flanking regions and intervening sequences, termed introns. Introns are removed from the primary RNA transcript by a process called splicing. The basic unit of information is the codon, a sequence of three bases or triplet. The four nucleotide bases arranged as triplets lead to 64 possible codons. Sixty-one of these code for amino acids and three are termination signals called stop codons.
83 Which of the following statement(s) is/are true concerning cell membrane receptors?
a. The largest family of cell surface receptors are the G-protein-linked receptors
b. Activities of the G-protein involve binding and hydrolysis of ATP
c. The G protein receptor generates an intracellular messenger commonly through the use adenylate cyclase
d. Tyrosine kinase receptors are considered G-protein-linked receptors
Answer: a, c
All water-soluble regulatory molecules bind to the cell surface receptor proteins. Binding of the appropriate ligand evokes an intracellular signal which usually regulates enzyme activity, membrane transport, or in some cases gene expression. Most cell surface receptors belong to one of three functional classes—these are ion channel receptors, catalytic receptors, and G-protein-linked receptors. Ion channel receptors are multisubunit assemblies which, with each subunit, have a multiple membrane spanning segment. Together these subunits form an ion-selected pore that can be gated by a change in transmembrane electrical potential or binding of a ligand to one of the subunits. Catalytic receptors are membrane proteins that possess enzymatic activity. The best understood receptors of this class are the tyrosine kinases. The largest family of cell surface receptors are the G-protein-linked receptors. G-proteins are a family of proteins that bind and hydrolyze GTP. The final component of single transduction by G-protein-linked cell surface receptors is the effector that generates the intracellular messenger. The two best understood effectors are adenylate cyclase, which converts ATP to cAMP, and the polyphosphoinositide-specific phospholipase C.
84 Which of the following statement(s) is/are true concerning cellular ion channels?
a. Ion channels are transmembrane proteins that form pores that can conduct ions across the plasma membrane
b. Ion channels are formed by membrane-spanning peptides that are arranged so that polar moieties line a central core
c. Ion channel proteins undergo conformational changes between open states and closed states
d. Ion channels can be blocked
Answer: a, b, c, d
Ion channels are transmembrane proteins that form pores that can conduct ions across the plasma membrane. Ion channels are formed by membrane-spanning peptides that are arranged so that polar moieties line a central pore. These polar groups take the place of the water of hydration, which stabilizes an ion in an aqueous solution creating, in essence, a water-like environment into which the ion can partition and move in the presence of the appropriate driving force. Ion channels are permissive transport elements. Ions flow through a channel only through the presence of an appropriate driving force. Ion channels do not conduct all the time, rather the channel protein undergoes conformational changes between a conducting (open) state and nonconducting (closed) state. These conformational changes are collectively referred to as gating. The conduction process can also be blocked by ions or organic compounds that enter the channel, bind there, and occlude the pore.
85 Which of the following statement(s) is/are true concerning carrier proteins?
a. Carrier proteins are distinguished by three types of mechanisms: carrier-type, channel-type, and conduction-type
b. Conformational changes in the membrane protein occur between the conducting and the nonconducting states
c. A channel-type carrier protein has two states—closed and open
d. Carrier-type transport proteins are equally accessible from either side of the membrane
Answer: b, c
Most transport proteins appear to function as carriers, rather than channels. Important distinctions can be made between types of carrier proteins on the basis of transport kinetics. Two primary types can be distinctly identified based on carrier-type and channel-type mechanisms. The most important difference between the channel mechanism and the carrier mechanism is the role in the transport event played by conformational changes in the membrane protein. The channel is depicted as having two states, closed and open, so that it operates like a switch. In contrast, carrier transport is envisioned as requiring a cycle of conformational changes. The transport of one molecule of substrate requires one complete cycle of the protein. In a channel mechanism, binding sites within the open pore are equally accessible from either side of the membrane, whereas in a carrier mechanism, the binding site is available only one side of the membrane at any instant.
86 Which of the following statement(s) is/are true concerning translation of the mRNA message to protein synthesis?
a. An adaptor molecule, tRNA, recognizes specific nucleic acid bases and unites them with specific amino acids
b. Covalent attachment of tRNA to amino acids is energy dependent
c. The formation of a peptide bond between the growing peptide chain and the free amino acid occurs in the free cytoplasm
d. Complete protein synthesis takes hours
Answer: a, b
The synthesis of protein involves conversion from a four-letter nucleotide language to one of 20 chemically distinct amino acids. This process is referred to as translation. There is no mechanism for direct chemical recognition between specific nucleic acid bases and specific amino acids. Instead, an adaptor molecule, tRNA, is used. Each tRNA carries only one amino acid and must be recognized by a distinct enzyme which catalyzes the covalent attachment of the carboxyl end of the amino acid to the end of the tRNA in a process using ATP. Protein synthesis occurs by the formation of a peptide bond between the carboxyl terminal of the growing peptide chain and the free amino acid of deactivated amino acid tRNA. This event does not occur in free solution, but within ribosomes. Ribosomes are protein synthesizing machines that bring all of the necessary components together in the correct sequence and spacial orientation. Protein synthesis consumes a great deal of energy because four high-energy phosphate bonds must be split to make each peptide bond. Complete synthesis of a single protein takes 30 seconds to a few minutes, but multiple ribosomes can initiate translation and be moving down the mRNA molecules simultaneously, thus increasing the rate of protein synthesis.
87 Cell regulation can be thought of as the effector side of cell communication. Most commonly cell regulation occurs by means of extracellular chemical messengers. Which of the following statement(s) is/are true concerning these messengers?
a. Paracrine regulation involves a messenger which is produced and acts systemically
b. The extracellular signal or stimulus is received by a receptor on or in the target cell
c. Neurocrine regulation depends on a physical connection between the neuron and the target cell
d. Most hormones, local mediators, and neurotransmitters readily cross the cell plasma membrane
Answer: b, c
Depending on how the extracellular messenger arrives, cell regulation can be classified as paracrine, endocrine, or neurocrine. In paracrine regulation, a chemical messenger or mediator is produced and acts locally. In endocrine regulation, the extracellular messengers (hormones) are released into the blood and act on target cells anywhere on the body that has appropriate receptors. In neurocrine regulation, neurons secrete transmitters into highly localized regions, the synaptic cleft, so that the regulation depends on a physical connection between the neuron and the target cell as well as the presence of a specific receptor. In almost all cases of cell regulation, the extracellular signal or stimulus is restricted to being an informational molecule. This information is received by receptor on or in the target cell, which generally has an affinity for the signal molecule. Most hormones, local mediators, and neurotransmitters are water-soluble and cannot readily cross the plasma membrane.
88 Proteins that are destined to be secreted from the cells must pass through a series of organelles. These organelles include:
a. Endoplasmic reticulum
b. Golgi apparatus
c. Mitochondria
d. Lysosomes
Answer: a, b, d
Proteins targeted for the secretory pathway most commonly begin with translocation from the cytoplasm across the lipid bilayer into the lumen of the endoplasmic reticulum. It must then pass through a number of compartments including the Golgi apparatus where they are further processed and sorted and end up in a secretory vesicle or lysosome.
89 The best understood intracellular messenger is cyclic AMP (cAMP). Which of the following statement(s) concerning this intracellular messenger is/are correct?
a. Intracellular cyclic AMP is constantly degraded by a specific enzyme, cAMP phosphodiesterase
b. Most of the actions of cAMP are mediated by activation of protein kinase A
c. Intracellular levels of cAMP are relatively stable and change solely in response to activation of adenylate cyclase
d. cAMP is the only cyclic nucleotide active as an intracellular messenger
Answer: a, b
The prototypic intracellular messenger is cAMP. To function as a mediator, the concentration of cAMP must change rapidly. In resting cells, cAMP is continuously being degraded by a specific enzyme, cAMP phosphodiesterase. cAMP levels can increase 10-fold or more within seconds of receptor binding through activation of adenylate cyclase. cAMP acts as an allosteric regulator, and most, if not all, of its actions are mediated by activation of cAMP-dependent protein kinase A. cAMP is not the only cyclic nucleotide active as an intracellular messenger. Most animal cells also produce cGMP. Intracellular calcium ions also serve as second messengers in a large number of cells.
90 The activities of the cytoskeleton is dependent on which of the following types of filaments?
a. Microtubules
b. Intermediate filaments
c. Actin filaments
d. None of the above
Answer: a, b, c
The cytoskeleton is a collection of filamentous protein structures that allow cells to assume and maintain a variety of shapes, to produce directed movement of organelles within the cell, and to affect movement of the entire cell relative to other cells. These multiple activities depend upon three main types of filaments: actin filaments, intermediate filaments, and microtubules.
91 Intracellular organelles involved with protein synthesis include:
a. Mitochondria
b. Endoplasmic reticulum
c. Golgi complex
d. Lysosomes
Answer: b, c
Mitochondria are the major source of energy production in eukaryotic cells. The endoplasmic reticulum is the network of interconnected membranes forming closed vesicles, tubules, and saccules. The endoplasmic reticulum has a number of functions and is primarily involved in the synthesis of proteins and lipids. Adjacent to the rough endoplasmic reticulum and functionally involved in the sorting and package of secreted protein is the Golgi complex. Lysosomes are membrane-limited organelles containing acid hydrolytic enzymes that degrade polymers such as proteins, carbohydrates, and nucleic acids.
92 An important step in protein synthesis is transcription. Which of the following statement(s) is/are true concerning this process?
a. The first step in gene transcription involves separating the double helix of DNA by an enzyme known as DNA polymerase
b. The initial product of DNA transcription is called heterogeneous nuclear RNA which codes directly for proteins
c. After processing is complete, the mRNA is exported from the nucleus to the cytoplasm
d. Only one protein can be produced from an initial mRNA strand
Answer: c
Transcription of a gene begins at an initiation site associated with a specific DNA sequence, termed a promoter region. After binding to DNA, the RNA polymerase opens up a short region of the double helix to expose the nucleotides. Once the two strands of DNA are separated, the strand containing the promoter acts as a template to which ribonucleoside triphosphates base pair by hydrogen bonds. The initial products of transcription are known as heterogeneous nuclear RNA because of their large size variation. These primary transcripts are then processed to form mRNA. RNA splicing accounts for mature RNA being much shorter than nuclear RNA. Moreover, alternative splicing can lead to the production of different mRNA molecules and in some cases different proteins from the same gene. mRNA is exported from the nucleus only after processing is complete.
93 There are two properties of the cell necessary to maintain nonequilibrium cellular composition; the first is selectivity and the second is energy conversion. Which of the following statement(s) is/are true concerning energy converting transport?
a. The site of energy conversion and transport in the plasma membrane involves the phospholipid component
b. The Na+-K++-ATPase derives energy from hydrolysis of extracellular ATP
c. In some systems, energy inherent in the transmembrane ion gradient can be used to drive transport of a second species
d. Examples of species transported via secondary active transport include hydrogen ions, calcium, amino acids and glucose
Answer: c, d
The selectivity of the plasma membrane, although impressive, cannot account for the nonequilibrium composition of living cells. A cell can be maintained in a nonequilibrium state only by continual expenditure of energy. The maintenance of a steady-state, nonequilibrium cellular composition is possible because the plasma membrane is the site of energy converters, membrane proteins that function as biologic transport machines using energy derived from metabolic processes to perform transport work. The archetype for the biologic transport machine is the Na+-K+-ATPase, a membrane protein that hydrolyses cytosolic ATP and couples the resulting free energy to transport of Na+ and K+. A second equally important type of energy-converting transporter is one in which the energy inherent in a transmembrane ion gradient, usually that of Na+ can be used to drive the transport of a second species such as protons, calcium, amino acids, or glucose.
94 Which of the following statement(s) is/are correct concerning cell junctions?
a. The major occluding junction is the tight junction or zonula occludens
b. Tight junctions are usually located near the basal pole of the cell
c. Desmosomes are button-like points of attachment which serve to weld together adjacent cells
d. Gap junctions are a type of cell junction specialized for cell communication
Answer: a, c, d
Cell junctions are classified as occluding, anchoring, and communicating. The major occluding junction is the tight junction or zonula occludens which connects cells in epithelia and thereby allows epithelia to serve as selective permeability barriers. Tight junctions are normally located near the apical pool of the cell and form a belt that completely encircles the cell. Anchoring junctions connect the cytoskeleton of the cell to the extracellular matrix or neighboring cells. Morphologically these are adherens junctions or desmosomes. Desmosomes are button-like points of attachment with a prominent intracellular plaque that serves to weld together adjacent cells by serving as anchoring sites for intermediate filaments within the cell. The third functional type of cell junction is a gap junction which is specialized for communication. This junction mediates both electrical and chemical coupling.
95 Examples of ion channel blockers include:
a. Tetrodotoxin
b. Amiloride
c. Xylocaine
d. None of the above
Answer: a, b, c
Channel blockade is an important mechanism of action for toxins and some therapeutic agents. The deadly toxin of the puffer fish, tetrodotoxin, acts by blocking the Na+ channels that are responsible for the conduction of nerve impulse. The diuretic, amiloride, acts by blocking the Na+ channels that inhabit the apical membrane of the epithelial cells of the distal nephron. Local anesthetics such xylocaine also act by blocking ion channels.
96 Most hormone receptors are localized on the cell membrane and transduce hormone binding into altered levels of intracellular messengers. A limited number of intracellular receptors do exist. Which of the following statement(s) is/are true concerning intracellular receptors?
a. The messengers or hormones must by lipophilic
b. These intracellular receptors generally regulate protein synthesis
c. The intracellular receptors are located entirely in the nucleus of the cell
d. A heat-shock protein serves as an inhibitor protein blocking the DNA-binding domain of the steroid receptor
Answer: a, d
Although most hormone and other messenger receptors are extracellular, intracellular receptors have been identified. The hormone messengers involved for these receptors are primarily steroid and thyroid hormones and are lipophilic. By virtue of their hydrophobic nature, they are able to readily penetrate the lipid portion of the cell membrane. Receptors for these hormones exist intracellularly in the cytoplasm or in the nucleus and generally act as regulators of gene expression. These hydrophobic signaling molecules exist in plasma bound to protein, so that the concentration of this class of regulators does not fluctuate rapidly in plasma and their actions are generally slower in onset and more prolonged than those of water-soluble class. Some types of steroid receptors, particularly for glucocorticoids, are located in the cytosol in the inactive state. Once the ligand binds, the receptor undergoes a conformational change, termed activation. This allows cytoplasmic receptors to move into the nucleus and bind to DNA. Receptors already in the nucleus increase their affinity for DNA. In the case of glucocorticoid receptors and probably others of this class, the inactive receptor is associated with another protein, the heat-shock protein. They block the DNA-binding domain of the receptor. Activation involves the dissociation of the inhibitor protein.
97 Altering the amino acid profile in total parenteral nutrition solutions can be of benefit in certain conditions. Which of the following conditions are associated with a benefit by supplementation with the amino acid type listed?
a. Acute renal failure and essential amino acids
b. Hepatic failure and aromatic amino acids
c. Short gut syndrome and glutamine
d. Chronic renal failure and essential amino acids
Answer: a, c
In a number of conditions, altering the amino acid profile of the total parenteral nutrition solution can be of benefit. TPN with amino acids of high biologic value may decrease the mortality in patients with acute renal failure. These solutions, containing high quality amino acids, can improve nitrogen balance and diminish urea nitrogen. Provision of essential amino acids only allows the body to maximally utilize nitrogen for the synthesis of non-essential amino acids and thereby helps prevent rapid rises in blood urea nitrogen. There appears to be no advantages to using essential amino acids if the patient is already being dialyzed every other day and therefore a balanced standard amino acid solution is recommended. Because of liver damage and portasystemic shunting, patients with hepatic failure develop derangements in circulating levels of amino acids. The plasma aromatic/branch chain amino acid ratio is increased favoring the transport of aromatic amino acids across the blood brain barrier. These amino acids are precursors of false transmitters which contribute to lethargy and encephalopathy. Treatment of individuals with liver failure with solutions enriched in branch chain amino acids and deficient in aromatic amino acids results in improved tolerance to administration of protein and clinical improvement in encephalopathic states. Glutamine-enriched TPN partially attenuates villous atrophy and may be useful in treatment of short gut syndrome.
98 Under certain circumstances, the gut may become a source of sepsis and serve as the motor of systemic inflammatory response syndrome. Microbial translocation is the process by which microorganisms migrate across the mucosal barrier to invade the host. Which of the following mechanisms can promote bacterial translocation?
a. An increased number of gut bacteria
b. Altered intestinal mucosal permeability
c. Decreased host defense mechanisms
d. Lack of enteral feeding
Answer: a, b, c, d
99 Translocation is promoted in three general ways: 1) altered permeability of the intestinal mucosa as caused by shock, sepsis, distant injury, or cell toxins; 2) decreased host defense (secondary to glucocorticoid administration, immunosuppression, or protein depletion; and 3) an increased number of bacteria within the intestine. Because many factors that facilitate bacteria translocation occur simultaneously in surgical patients, these effects may be either additive or cumulative. In addition, many patients in Surgical Intensive Care Units do not generally receive enteral feedings and therefore current parenteral therapy results in gut atrophy which further promotes translocation.
Which of the following statement(s) is/are true concerning nutritional support of the injured patient?
a. The goal of nutritional support is maintenance of body cell mass and limitation of weight loss to less than 25% of preinjury weight
b. Under-nutrition may compromise the patient’s available defense mechanisms
c. Nutritional support is an immediate priority for the trauma patient
d. Fifty percent of non-nitrogen caloric requirements should be provided in the form of fat
Answer: b
Metabolic response to injury results in increased energy expenditure. If energy intake is less than expenditure, oxidation of body fat stores and erosion of lean body mass will occur with resultant loss of weight. When weight loss exceeds 10–15% of body weight, the complications of malnutrition interact with disease processes, with increased morbidity and mortality rates. The goal of nutritional support is maintenance of body cell mass and limitation of weight loss to less than 10% preinjury. The major impact of nutritional support in the trauma patient is to aid host defense. Under-nutrition may compromise the available host defense mechanism and may thus increase the likelihood of invasive sepsis, multiple organ system failure, and death. Resuscitation, oxygenation and arrest of hemorrhage are immediate priorities for survival. Nutritional support is an essential part of the metabolic care of the critically ill patient and should be instituted after resuscitation before significant weight loss occurs. The nutritional requirements of a trauma patient can be determined by determining basal metabolic rate with appropriate increases based on extent of injury and hospital activity. After initial determination of nitrogen requirements, caloric requirements should be distributed at a ratio of 70% as glucose and 30% as fat.
100 Which of the following statement(s) is/are true concerning body fuel reserves?
a. The largest fuel reserve in the body is skeletal muscle
b. Fat provides about 9 calories/gram
c. Free glucose and glycogen stores are a trivial fuel reserve
d. Body protein is a valuable storage form of energy
Answer: b, c
The body contains fuel reserves which it can mobilize and utilize during times of starvation or stress. By far the greatest energy component is fat, which is calorically dense since it provides about 9 calories/gram. Body protein comprises the next largest mass of utilizable energy, but amino acids yield only about 4 kcal/gram. Unlike fat reserves, body protein is not a storage form of energy but rather serves as a structural functional component of the body; loss of body protein, if severe, is associated with functional consequences. Glycogen stored in muscle and liver and free glucose have a trivial caloric value of less than 1000 kcal for a 70 kg male.
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A. Nutritional support benefits the patient's lean body mass but does not enable the tumor to grow.
B. In experimental animals, the growth of implanted tumors is directly proportional to the amount of calories and protein supplied.
C. Prospective randomized trials of nutritional support utilizing chemotherapy and radiation therapy have revealed benefits to patients receiving total parenteral nutrition.
D. Studies of nutritional support for patients with cancer about to undergo surgery revealed decreased morbidity and mortality, especially morbidity from sepsis.
Answer: B
DISCUSSION: The problem with the patient with cancer is a very vexing one. Clearly, one of the metabolic effects of cancer, cachexia, affects patients in the last quartile of their disease and makes such patients intolerant of chemotherapy, radiation therapy, and, in many cases, operative procedures. Total parenteral nutrition (TPN) has been proposed as a means of reversing cachexia and enabling patients to better tolerate surgery, chemotherapy, and radiation therapy. In experimental animals, it is clear that the provision of calories and protein, especially in excessive amounts, is associated with the more rapid growth of tumors and decreased survival, especially in the group that is overfed in the extreme. There is also evidence suggesting that overfeeding, or at least TPN, may result in increased growth (or at least change cell kinetics) in patients who are overnourished with TPN. Of the randomized prospective trials that have been carried out, no trial utilizing chemotherapy or radiation therapy has revealed a survival advantage for patients receiving TPN. Indeed, in Shamberger's study, there is a suggestion that the tumor-free interval following treatment of lymphoma may be shorter in patients receiving TPN. In patients undergoing surgery, however, especially those who are severely malnourished (as recently revealed in the VA study) or in patients with major procedures such as esophagogastrectomy (as in Muller's study), evidence suggests that TPN is beneficial. In a late follow-up in Muller's study, there was no apparent increase in recurrence, and the survival rate was the same, despite much higher mortality in the non-TPN group. This suggests that any improved survival following operation may have been offset by an increased late recurrence rate, although it is difficult to reach this conclusion. In summary, for patients with cancer TPN probably nourishes the tumor as well as the host. Nonetheless, in severely malnourished patients provision of TPN from 5 to 10 days preoperatively may increase survival and decrease morbidity. Overfeeding must be avoided. Future studies will undoubtedly reveal that there are certain nutrients that tumors require, which probably should be best avoided.
52. Glucose overload results in increased CO 2 production. Which of the following statements are true?
A. In patients with respiratory insufficiency, administration of glucose as a principal calorie source is contraindicated.
B. In patients with pulmonary infection and sepsis, calorie support should consist of 95% fat and 5% glucose.
C. In Askanazi's study, increased CO 2 production and difficulty in weaning was associated only with pronounced overfeeding.
D. CO 2 production should be measured in most patients who are supported by respirators in intensive care units and are receiving nutritional support.
Answer: C
DISCUSSION: Few papers have excited as much interest as that by Askanazi, Kinney, and co-workers, which demonstrated that glucose calories given to patients with severe respiratory impairment may result in difficulty in weaning from a respirator. Subsequent research has suggested, however, that this occurs only with severe overfeeding, when the respiratory quotient is greater than 1 and calories are excessive. If one examines the conditions under which Askanazi's patients were studied, these were a group of septic, depleted patients who were taken from almost no nutritional support to a caloric supply of 2.25 times their caloric requirement, most of the calories consisting of glucose. Suffice it to say that, in patients with impaired respiratory function, one should measure VCO2 and, when VCO2 is significantly elevated and appears to interfere with weaning, decrease the amount of glucose calories and increase the amount of fat. If one measures or estimates calorie requirements and does not overfeed, lipid can be utilized for 25% of the caloric requirement and glucose for the remainder, without much fear of excessive CO 2 production.
53. Hepatic abnormalities have been noted in adults since the beginning of hyperalimentation. Which of the following statements are true?
A. Hepatic steatosis appears to be associated with an overload of glucose.
B. Hepatic steatosis is usually associated with abnormalities in hepatic enzymes.
C. Hyperbilirubinemia is inevitably associated with hepatic steatosis.
D. Abnormalities in the portal insulin-glucagon ratio are thought to be causative of hepatic steatosis in experimental animals.
Answer: AD
DISCUSSION: The most common metabolic complication of TPN in adults is hepatic steatosis. Unlike the hepatic abnormalities in children, which may progress to cholestasis, liver damage, and in some cases death, hepatic steatosis, or fatty infiltration of the liver with triglycerides, appears to be a rather benign complication. It may be, but is not necessarily, associated with hepatic enzymatic abnormalities, which usually occur in the first week, peak at the third week, and generally disappear by the sixth week of parenteral nutrition. Abnormalities in the transaminases are most common, with alkaline phosphatase also being elevated, but there is no correlation between the degree of fatty infiltration and enzymatic abnormalities. Fatty infiltration appears to be largely vacuolization with increased storage of triglycerides. Hepatic steatosis is almost always associated with an overload of glucose. Recent studies in experimental animals have suggested that the portal insulin-glucagon ratio, which is elevated under these circumstances, may be causally related to hepatic steatosis. Insulin is the leading storage enzyme and is responsible for lipogenesis. The presence of insulin inhibits lipolysis. Glucagon, on the other hand, results in the mobilization of hepatic lipid. The liver “sees” the portal vein insulin-glucagon ratio. Excesses of insulin elicited by hypertonic dextrose increase lipid deposition in the liver, whereas glucagon, which is elicited by certain amino acids, results in the mobilization of hepatic lipid.
54. Which of the following statements about the presence of gallstones in diabetes patients is/are correct?
A. Gallstones occur with the same frequency in diabetes patients as in the healthy population.
B. The presence of gallstones, regardless of the presence of symptoms, is an indication for cholecystectomy in a diabetes patient.
C. Diabetes patients with gallstones and chronic biliary pain should be managed nonoperatively with chemical dissolution and/or lithotripsy because of severe complicating medical conditions and a high operative risk.
D. The presence of diabetes and gallstones places the patient at high risk for pancreatic cancer.
E. Diabetes patients with symptomatic gallstones should have prompt elective cholecystectomy, to avoid the complications of acute cholecystitis and gallbladder necrosis.
Answer: E
DISCUSSION: Gallstones have been found to be very prevalent in patients with type II (non–insulin-dependent) diabetes mellitus, perhaps related to the dyslipoproteinemia in such patients. Although the complications of acute cholecystitis (infection, sepsis, gangrene of the gallbladder) are more common in diabetics, a decision-analysis study has shown that prophylactic cholecystectomy cannot be justified since the risk of morbidity and/or mortality from the cholecystectomy procedure is as great as that of complications or death from acute cholecystitis. Patients who become symptomatic should be promptly prepared and should undergo elective cholecystectomy, because an emergency operation in these patients with comorbid conditions, especially coronary artery disease, has substantial added mortality associated with it. There is no causal relationship between diabetes and pancreatic cancer.
55. Intensive insulin therapy:
A. Prevents the aggressive development of atherosclerosis in diabetic patients.
B. Is not associated with unawareness of hypoglycemia.
C. Improves peripheral neuropathy.
D. Improves established retinopathy and nephropathy.
E. Is indicated in all patients with non–insulin-dependent diabetes mellitus (NIDDM).
Answer: C
DISCUSSION: Intensive insulin therapy is indicated in patients with IDDM who can actively participate in their own management and the attainment of the goals set for their blood glucose and glycosylated hemoglobin (HgA1 c) levels. Because the main complication of intensive therapy is iatrogenic hypoglycemia, this mode of treatment is not indicated for patients with NIDDM, who often have coexisting medical conditions such as coronary artery disease and who tolerate hypoglycemia poorly. There is little or no evidence that macrovascular disease is affected by intensive insulin therapy, and the added weight gain and hyperinsulinemia associated with the therapy may worsen atherosclerosis. Unawareness of hypoglycemia is directly related to a recent hypoglycemia episode, so patients treated intensively are often unaware of the problem. Intensive therapy does not improve established retinopathy or nephropathy but slows or prevents progression of these complications; however, better glucose control may improve peripheral neuropathy.
56. Which of the following statements about hypertension in diabetes patients is/are correct?
A. Hypertension worsens the macrovascular disease of diabetes patients.
B. Hypertension accelerates the progression of diabetic nephropathy.
C. Hypertension is associated with sodium retention in diabetes patients.
D. Angiotensin-converting enzyme (ACE) inhibitors should be used in all patients with chronic hyperglycemia, regardless of the presence of hypertension.
E. Diuretics, as single-drug therapy, are not indicated in the treatment of hypertension in diabetes patients.
Answer: ABCDE
DISCUSSION: All of the answers listed are correct. By damaging endothelial cells, hypertension worsens macrovascular disease in all patients but especially in diabetics. Hypertension dramatically accelerates the onset and progression of diabetic renal disease and proteinuria, and this phenomenon can be slowed or prevented by a combination of treatment modalities, including ACE inhibitors, which dilate efferent glomerular vessels and lower intraglomerular pressure. Despite sodium retention in diabetes patients, single-drug therapy with a diuretic is not indicated because the chronic state of dehydration in such patients may become worse.
57. What is the major determinant in an individual patient's risk for perioperative complications?
A. The surgical procedure.
B. The length of the surgical procedure.
C. The anesthetic technique (e.g., general, regional).
D. The length of anesthesia.
E. All of the above.
Answer: A
DISCUSSION: The planned surgical procedure is the major determining factor in assessing an individual patient's risk for perioperative complications and in deciding which anesthetic technique will be most appropriate. Good communication between the surgeon and the anesthesiologist is vital, as the surgeon knows better than anyone else the extent of the operation and the length of time it will require.
58. Which of the following are considered routine intraoperative monitors?
A. Temperature probe.
B. Electrocardiogram.
C. Capnograph.
D. Blood pressure cuff.
E. Foley catheter.
Answer: ABD
DISCUSSION: The American Society of Anesthesiologists requires that the patient's ventilation, circulation, oxygenation, and temperature be continually monitored during all anesthetics. Routine monitors are considered to be a temperature probe, electrocardiogram, pulse oximetry, and blood pressure cuff.
59. Muscle relaxants can be used for which of the following?
A. To facilitate intubation.
B. To provide optimal surgical conditions.
C. To optimize ventilator support.
D. To provide sedation.
Answer: ABC
DISCUSSION: Muscle relaxants are administered to facilitate endotracheal intubation, to provide the surgeon with optimal working conditions during anesthesia, and to optimize mechanical ventilator support in some patients. They do not produce analgesia, sedation, or amnesia. Therefore, muscle paralysis should not be performed without sedation or general anesthesia.
60. Local anesthetics:
A. Inhibit transmission of nerve impulses by increasing sodium membrane permeability and the displacement of ionized calcium.
B. Are classified as amides or esters.
C. Produce peripheral vasodilation.
D. Are weak acids.
Answer: BC
DISCUSSION: Local anesthetics act within the nerve membrane, where they inhibit transmission of nerve impulses by reducing sodium membrane permeability and the displacement of ionized calcium. All local anesthetics consist of a hydrophilic region and a hydrophobic region separated by an alkyl chain. The bond of the alkyl chain is either an ester or an amide, and these drugs are classified based on this bond. All local anesthetics except cocaine produce vasodilatation and are weak bases.
61. Absolute indications for a double-lumen endotracheal tube during thoracic surgery are:
A. Massive hemorrhage from one lung.
B. Unilateral lung infection.
C. Facilitation of surgical exposure.
D. Unilateral bronchopulmonary lavage.
E. All of the above.
Answer: ABD
DISCUSSION: The absolute indications for a double-lumen tube are for the purposes of protecting one lung from the other. These indications include ventilation with a bronchopleural fistula, massive hemorrhage from one lung, pulmonary air cyst resection, unilateral lung infection, and unilateral bronchopulmonary lavage. Relative indications include facilitation of surgical exposure, for pneumonectomy, upper lobectomy, and thoracic aneurysm repair.
62. Determinants of cerebral blood flow include:
A. Preoperative neurologic dysfunction.
B. Arterial CO 2 tension.
C. Arterial O 2 tension.
D. Systemic arterial pressure.
E. All of the above.
Answer: BCD
DISCUSSION: Determinants of cerebral blood flow include arterial CO 2 and O 2 tensions, systemic arterial pressure, and temperature. Other factors that may affect cerebral blood flow and intracranial pressure are head position, jugular venous obstruction, and positive end-expiratory pressure.
63. Discharge criteria following ambulatory surgery include:
A. Ability to eat solid food.
B. Stable vital signs.
C. Ability to ambulate.
D. Ability to have protective airway reflexes.
Answer: BCD
DISCUSSION: Discharge criteria following ambulatory surgery include the patient's being fully awake and oriented, the ability to have protective airway reflexes, stable vital signs, adequate hydration with the ability to hold down oral intake, the ability to ambulate, and adequate pain control. All patients must have a competent person with them to transport them—and ideally to stay with them on the first postoperative night.
64. Advantages of patient-controlled analgesia (PCA) include:
A. Immediate medication delivery.
B. Less contact with nursing staff.
C. Rapid onset of analgesia.
D. Patient control over pain medication.
E. All of the above.
Answer: ACD
DISCUSSION: Advantages of PCA are immediate medication delivery, rapid onset of analgesia, and patient control over pain medication. Disadvantages of PCA are less contact with nursing staff and patients' fears that they could inadvertently administer an overdose or possibly become addicted to the opioid.
65. Advantages of epidural analgesia include:
A. Earlier mobilization after surgery.
B. Earlier return of bowel function.
C. Shorter hospitalizations.
D. Decreased stress response to surgery.
E. All of the above.
Answer: E
DISCUSSION: Epidural analgesia include excellent pain relief, decreased sedation with more rapid recovery to presurgical levels of consciousness, earlier mobilization after surgery with increased ability to co-operate with respiratory therapy and physical therapy. Following vascular surgery epidural analgesia may also improve graft flow through mild sympathetic blockade. Earlier return of bowel function, decreased stress response, shorter hospitalizations, and decreased morbidity have all been associated with epidural analgesia.
66. Ketorolac:
A. Is a nonsteroidal anti-inflammatory drug (NSAID) approved for intravenous, intramuscular, and oral administration.
B. Can be used indefinitely for postoperative analgesia.
C. Can cause renal dysfunction.
D. May decrease surgical blood loss.
Answer: AC
DISCUSSION: Ketorolac tromethamine, an NSAID, is approved by the FDA for intravenous, intramuscular, and oral administration. The agent is an effective analgesic with minimal side effects; however, ketorolac, like all NSAIDs, can enhance surgical bleeding and cause renal and platelet dysfunction. Additionally, it is recommended that ketorolac should not be used for more than 5 consecutive days.
67. Factors that decrease collagen synthesis include all of the following except:
A. Protein depletion.
B. Infection.
C. Anemia.
D. Advanced age.
E. Hypoxia.
Answer: C
DISCUSSION: Collagen synthesis, an integral part of wound healing, is affected by many local and systemic factors. Protein depletion impairs fibroplasia. Hypoproteinemia leads to diminution of fibroblast proliferation, proteoglycan and collagen synthesis, angiogenesis, and wound remodeling. Although anemia was once believed to be a significant cause of wound disruption, studies have shown that, in the absence of malnutrition or hypovolemia, anemia with a hematocrit greater than 15% does not interfere with wound healing. In contrast, molecular oxygen is critical for collagen synthesis because it is one of the factors required for the hydroxylation of lysine and proline. Also, hypoxia favors wound infection. The role of age in collagen synthesis is not clear, but the incidence of wound failure and incisional hernias is greater in patients older than 60. Fibroplasia occurs at a slower rate in older animals. Perhaps more than any other factor, wound infection is associated with the risk of wound failure.
68. Wound contraction and ultimate contracture may be controlled by which of the following drugs?
A. Colchicine.
B. D-Penicillamine.
C. Thiphenamil (Trocinate).
D. Glucocorticoids.
E. Ibuprofen (Motrin).
Answer: AC
DISCUSSION: Wound contraction is carried out by highly specialized cells called myofibroblasts, which, as their name implies, have histologic characteristics of fibroblasts and smooth muscle cells. The activity of these cells, and therefore wound contraction, can be influenced by topical application of smooth muscle inhibitors such as thiphenamil. Inhibitors of microtubule formation in myofibroblasts, such as colchicine and vinblastine, also inhibit wound contraction under experimental conditions. Glucocorticoids and NSAIDs do not affect the wound contraction process.
69. Which of the following is/are true of the actions of transforming growth factor beta (TGF-b) during wound repair?
A. Increased matrix and proteoglycan synthesis.
B. Inhibition of proteases.
C. Stimulation of plasminogen inhibitor.
D. Chemotaxis for fibroblasts and macrophages.
E. Autoinduction of TGF-b.
Answer: ABDE
DISCUSSION: Through autocrine and paracrine mechanisms TGF-b stimulates the deposition of collagen and other matrix components by fibroblasts, inhibits proteases, blocks plasminogen inhibitor, enhances angiogenesis, and is chemotactic for fibroblasts, monocytes, and macrophages. TGF-b modulates the expression of cell-surface integrins in a manner that enhances cell-matrix interaction and matrix assembly. TGF-b also induces cell production by cells, thus amplifying its biologic effects. The sustained production of TGF-b at the wound site leads to tissue fibrosis.
70. In contrast to adult wound healing with scar formation, which of the following are characteristic of scarless fetal skin repair?
A. Matrix rich in hyaluronic acid.
B. Increased inflammatory response.
C. Increased production of TGF-b.
D. No collagen deposition.
E. Minimal angiogenesis.
Answer: AE
DISCUSSION: The ability of a fetus to heal without scar formation depends on its gestational age at the time of injury and the size of the wound defect. In general, linear incisions heal without scar until late in gestation, whereas excisional wounds heal with scar at an earlier gestational age. The profiles of fetal proteoglycans, collagens, and growth factors are different from those in adult wounds. The less differentiated state of fetal skin is probably an important characteristic responsible for scarless repair. There is minimal inflammation and angiogenesis in fetal wounds. Fetal wounds are characterized by high levels of hyaluronic acid and its stimulator(s) with more rapid, highly organized collagen deposition. The roles of peptide growth factors such as TGF-b and basic fibroblast growth factor are less prominent in fetal than in adult wound healing. An understanding of scarless tissue repair has possible clinical applications in the modulation of adult fibrotic diseases and abnormal scar-forming conditions.
71. Which of the following cell types are not crucial for healing a clean, incisional wound?
A. Macrophage.
B. Platelet.
C. Fibroblast.
D. Polymorphonuclear leukocyte.
E. Myofibroblast.
Answer: DE
DISCUSSION: Experimental studies have shown that healing may progress normally in the absence of polymorphonuclear leukocytes in an uninfected wound. In contrast, depletion of monocytes and macrophages causes a severe alteration in wound healing with poor débridement, delayed fibroblast proliferation, and inadequate angiogenesis. Platelets carry a cadre of biologically active substances that are important for wound repair, including peptide growth factors like platelet-derived growth factor (PDGF) and TGF-b. Fibroblasts are the principal cell for matrix synthesis and deposition. Myofibroblasts are important for wound contraction in open defects but have little if any role in clean, incisional wounds.
72. Which of the following is/are not a substrate or cofactor for prolyl hydroxylase?
A. Alpha-ketoglutarate.
B. Ascorbate.
C. Biotin.
D. Oxygen.
E. Copper.
Answer: CE
DISCUSSION: Prolyl hydroxylase is one of the rate-limiting enzymes in collagen synthesis. Substrates and cofactors such as iron, alpha-ketoglutarate, ascorbate, and oxygen are important participants in this process. If insufficient prolines are hydroxylated, then the alpha-peptide collagen chains cannot assume a stable triple helix, the collagen cannot be exported from the fibroblasts, and the incomplete, unassociated alpha chains are broken down. Thus, ascorbate deficiency (scurvy) and hypoxia have similar effects on collagen synthesis.
73. Which of the following is an adhesion glycoprotein?
A. Fibronectin.
B. Tenascin.
C. Laminin.
D. Hyaluronic acid.
E. Collagen type IV.
Answer: ABC
DISCUSSION: Cell adhesion glycoproteins such as fibronectin, vitronectin, laminin, and tenascin provide a “railroad track” to facilitate epithelial and mesenchymal cell migration over the wound matrix. Hyaluronic acid is a glycosaminoglycan, and collagen type IV is a protein that is a crucial component of basement membrane.
74. Which of the following is/are true concerning wound fibroblasts?
A. Fibroblasts synthesize and secrete collagen molecules.
B. Wound fibroblasts are derived from blood-borne precursor cells.
C. Fibroblasts migrate to a wound along fibrin strands, which are used as a scaffold.
D. Large amounts of fibrin or blood clot can act as a physical barrier to fibroblast penetration, which delays normal wound healing.
Answer: ACD
DISCUSSION: Fibroblasts appear in the wound on about the third day of healing and begin to synthesize and secrete collagen molecules. Wound fibroblasts arrive from cells surrounding the wound (e.g., the adventitia of blood vessels), change their phenotype(s), and become mobile during the process of replication. Fibroblasts migrate into a wound using the provisional fibronectin and fibrin matrix as a scaffold. Fibroblasts do not have fibrinolytic enzymes, and large amounts of fibrin and blood clot prevent fibroblasts from entering the wound.
75. Which of the following is/are true?
A. Because of its thickness, the tensile strength of a healing wound on the eyelid is much less than one on the thick skin of the back.
B. By 2 days, the experimental burst strength of skin is minimal since collagen has been formed in the wound but has not yet cross-linked.
C. Wound strength reaches a plateau by 3 weeks.
D. Wounds rarely, if ever, regain the strength of intact tissues.
Answer: BD
DISCUSSION: Tensile strength measures load per cross-section area at rupture, whereas burst strength measures load required to break a wound, regardless of dimension. Therefore, skin wounds have comparable tensile strength, regardless of thickness. Collagen appears in the wound by 3 to 4 days. Minimal wound strength on day 2 is due to fibrin polymerization and adhesion of globular proteins. Wounds rapidly gain strength for about 4 months and then continue to gain strength at a slower rate for more than a year. Wounds do not regain the strength of normal tissue.
76. Which of the following interfere with normal collagen formation or cross-linking?
A. Beta-aminopropionitrile.
B. Iron chelators.
C. Vitamin C depletion.
D. Proline analogs (e.g., cis-hydroxyproline).
E. D-Penicillamine.
Answer: ABCDE
DISCUSSION: Intramolecular and intermolecular cross-links are crucial for collagen structural stability. Formation of cross-links can be inhibited by two pharmacologic agents: beta-aminopropionitrile inhibits the enzyme lysyl oxidase, and D-penicillamine binds to collagen substrate directly to prevent collagen cross-link formation. Iron is a cofactor for prolyl hydroxylase, which is important for collagen synthesis. In high enough concentration, proline analogs prevent collagen formation with minimal effects on noncollagenase protein synthesis.
77 Which of the following statement(s) is/are true concerning the cell plasma membrane?
a. The plasma membrane is composed of amphipathic molecules
b. The hydrophobic core of the lipid bilayer of the cell membrane contains specialized transport proteins which maintain the intracellular ionic milieu different from the extracellular fluid
c. Plasma membrane proteins extend externally and bear phospholipid moieties which contribute to the cell coat
d. The membrane proteins of nerve cells are highly voltage-dependent
Answer: a, b, d
The plasma membrane defines the boundary of the cell and serves to contain and concentrate enzymes and other macromolecule constituents. The plasma membrane is composed of amphipathic molecules, mainly phospholipids and proteins that contain distinct regions that are either insoluble in water (hydrophobic) or soluble in water (hydrophilic). The plasma membrane forms a continuous barrier between the aqueous extracellular and intracellular fluids. Transport proteins in the membrane act as regulated channels or transporters to maintain the intracellular ionic milieu that is clearly different from the extracellular milieu. In some cells, membrane proteins are diversified such as in nerve cells where the ion channels are highly voltage-dependent, providing the basis for information transmission in the form of electrical impulses. Most plasma membrane proteins extend externally and bear carbohydrate moieties primarily as oligosaccharide chains that contribute to the cell coat or glycocalyx.
78 Which of the following statement(s) is/are true concerning water movement across cell membranes?
a. Water moves only actively through cell membrane transport proteins
b. For most cells of the body, the transmembrane hydrostatic pressure is 0
c. Water distribution is determined entirely by solute distribution
d. Specialized cells such as the glomerulus of the kidney actively transport water to maintain hydrostatic pressure
Answer: b, c
The energetics of water transport across cell membranes is simplified by the fact that water moves only passively due to gradients of hydrostatic pressure or water concentration. Hydrostatic pressure is an important driving force only for certain specialized cells—the capillary endothelium and the glomerulus of the kidney. For most cells of the body, the transmembrane hydrostatic pressure is 0 and water moves only in response to water concentration gradients. Because the concentration of water is determined by the amount of dissolved solute, the difference in water concentration is typically expressed as a function of the difference in solute concentration or osmotic pressure difference. Because there are no specialized, energy-converting transport mechanisms for water, water is distributed at equilibrium. Water distribution is determined entirely by solute to solute distribution.
79 The transport of proteins out of the cell is termed exocytosis. Which of the following statement(s) is/are true concerning this process?
a. Secretory vesicles fuse with the plasma membrane
b. The process can occur in either a constitutive or regulated process
c. A regulated secretion is triggered by a stimulus, most likely a hormone or a neurotransmitter
d. A decrease in cytoplasmic calcium occurs as part of the secretion process
Answer: a, b, c
Transport vesicles that bud off the Golgi network carry both material to be secreted from the cell and protein destined to become components of the plasma membrane. These vesicles can fuse with the plasma membrane in a process termed exocytosis. Vesicular transport to the cell surface can be divided into two components, constitutive and regulated secretion. Regulated secretion occurs in cells secreting digestive enzymes, hormones and other regulatory molecules, and neurotransmitters. In regulated secretion, the material to be secreted is sorted in a storage vesicle or granule; fusion with the plasma membrane in exocytosis then takes place in response to external stimulation. Regulated secretion is triggered in most cases by a hormone or neurotransmitter. The ensuing process is termed stimulus-secretion coupling. In most cases the coupling involves an increase in cytoplasmic concentration of Ca++, but may also involve generation of diacylglycerol or production of cyclic AMP which activate kinases or phosphatases.
80 Which of the following statement(s) is/are true concerning the cell function of phagocytosis?
a. Phagocytosis is a mechanistically distinct process of endocytosis performed by special cells to take up larger particles such as bacteria or erythrocytes
b. Lymphocytes are the primary blood cell involved with this process
c. The process involves a coating of the cytoplasmic surface known as clathrin
d. Phagocytosis is performed only by white blood cells and tissue macrophages
Answer: a
Phagocytosis is a specialized form of endocytosis by which large particles are internalized by specialized cells primarily macrophages and neutrophils. To be phagocytosed, particles must bind to the surface of the phagocytic cell, usually as the result of specific antibody coating the particle. The phagocytic cell then extends pseudopods which engulf the particle. This event is followed by membrane fusion and a pinching off. As opposed to endocytosis, this process does not involve the membrane protein, clathrin, but rather actin. A physiologically relevant site of phagocytosis is the thyroid gland, where thyroid follicular cells phagocytose and digest thyroglobulin from the lumen of the thyroid follicle, thereby releasing the thyroid hormones, thyroxine triiodothyronine.
81 A striking feature of living cells is a marked difference between the composition of the cytosol and the extracellular milieu. Which of the following statement(s) concerning the mechanisms of maintenance of these differences is/are true?
a. The cell membrane is able to maintain a 10,000 fold gradient between the extracellular concentration of ionized calcium and the intracellular concentration
b. The key to these differences is the fact that the plasma membrane is normally impermeable to sodium, potassium and calcium
c. The selectivity of biologic membranes is highly consistent and seldom changes
d. The selectivity of cell membranes relates only to ions and not organic compounds
Answer: a
The survival of the cell requires that cytosolic composition be maintained within narrow limits, despite the constant influx of nutrients and the simultaneous outflow of waste. A familiar example of the distribution of ions across the cell membrane is that of sodium and potassium. Cells are typically rich in potassium and contain very little sodium. Despite the fact that they are constantly bathed by fluid that is precisely the opposite composition. Even more impressive is the distribution of ionized calcium. The extracellular concentration of this ion is typically of the order of 10–3M, whereas that of cytosol is typically 10–7M, a 10,000-fold gradient. Such nonequilibrium ion distributions are even more remarkable in light of the fact that the plasma membrane is, to varying degrees, leaky to ions such as sodium, potassium and calcium. The plasma membrane is leaky to a variety of substances, but it exhibits an astonishing ability to discriminate or select one substance over another. This selectivity relates to not only ions but also for organic compounds such as glucose. Finally, the selectivity of biologic membranes can be altered drastically as a result of regulatory or signaling processes that occur within the cell.
82 Which of the following statement(s) is/are true concerning DNA?
a. DNA is contained only in the nucleus of the cell
b. DNA strands are encoded by the sequence of four bases—adenine, guanine, cytosine and uridine
c. The basic unit of information of DNA is the intron, a sequence of three bases
d. There are an infinite number of possible codons
Answer: a
The genetic blueprint of an organism is carried in the nucleus of every cell, encoded by the sequence of four bases—adenine, guanine, cytosine and thymine, which together make up two long chains bound together by hydrogen bonds to form a DNA double helix. A gene is a segment of DNA that is transcribed into a corresponding RNA molecule that either codes for a protein or forms a structural RNA molecule. Genes are commonly between 10,000 and 100,000 base pairs in length and include, in addition to the coding sequence, flanking regions and intervening sequences, termed introns. Introns are removed from the primary RNA transcript by a process called splicing. The basic unit of information is the codon, a sequence of three bases or triplet. The four nucleotide bases arranged as triplets lead to 64 possible codons. Sixty-one of these code for amino acids and three are termination signals called stop codons.
83 Which of the following statement(s) is/are true concerning cell membrane receptors?
a. The largest family of cell surface receptors are the G-protein-linked receptors
b. Activities of the G-protein involve binding and hydrolysis of ATP
c. The G protein receptor generates an intracellular messenger commonly through the use adenylate cyclase
d. Tyrosine kinase receptors are considered G-protein-linked receptors
Answer: a, c
All water-soluble regulatory molecules bind to the cell surface receptor proteins. Binding of the appropriate ligand evokes an intracellular signal which usually regulates enzyme activity, membrane transport, or in some cases gene expression. Most cell surface receptors belong to one of three functional classes—these are ion channel receptors, catalytic receptors, and G-protein-linked receptors. Ion channel receptors are multisubunit assemblies which, with each subunit, have a multiple membrane spanning segment. Together these subunits form an ion-selected pore that can be gated by a change in transmembrane electrical potential or binding of a ligand to one of the subunits. Catalytic receptors are membrane proteins that possess enzymatic activity. The best understood receptors of this class are the tyrosine kinases. The largest family of cell surface receptors are the G-protein-linked receptors. G-proteins are a family of proteins that bind and hydrolyze GTP. The final component of single transduction by G-protein-linked cell surface receptors is the effector that generates the intracellular messenger. The two best understood effectors are adenylate cyclase, which converts ATP to cAMP, and the polyphosphoinositide-specific phospholipase C.
84 Which of the following statement(s) is/are true concerning cellular ion channels?
a. Ion channels are transmembrane proteins that form pores that can conduct ions across the plasma membrane
b. Ion channels are formed by membrane-spanning peptides that are arranged so that polar moieties line a central core
c. Ion channel proteins undergo conformational changes between open states and closed states
d. Ion channels can be blocked
Answer: a, b, c, d
Ion channels are transmembrane proteins that form pores that can conduct ions across the plasma membrane. Ion channels are formed by membrane-spanning peptides that are arranged so that polar moieties line a central pore. These polar groups take the place of the water of hydration, which stabilizes an ion in an aqueous solution creating, in essence, a water-like environment into which the ion can partition and move in the presence of the appropriate driving force. Ion channels are permissive transport elements. Ions flow through a channel only through the presence of an appropriate driving force. Ion channels do not conduct all the time, rather the channel protein undergoes conformational changes between a conducting (open) state and nonconducting (closed) state. These conformational changes are collectively referred to as gating. The conduction process can also be blocked by ions or organic compounds that enter the channel, bind there, and occlude the pore.
85 Which of the following statement(s) is/are true concerning carrier proteins?
a. Carrier proteins are distinguished by three types of mechanisms: carrier-type, channel-type, and conduction-type
b. Conformational changes in the membrane protein occur between the conducting and the nonconducting states
c. A channel-type carrier protein has two states—closed and open
d. Carrier-type transport proteins are equally accessible from either side of the membrane
Answer: b, c
Most transport proteins appear to function as carriers, rather than channels. Important distinctions can be made between types of carrier proteins on the basis of transport kinetics. Two primary types can be distinctly identified based on carrier-type and channel-type mechanisms. The most important difference between the channel mechanism and the carrier mechanism is the role in the transport event played by conformational changes in the membrane protein. The channel is depicted as having two states, closed and open, so that it operates like a switch. In contrast, carrier transport is envisioned as requiring a cycle of conformational changes. The transport of one molecule of substrate requires one complete cycle of the protein. In a channel mechanism, binding sites within the open pore are equally accessible from either side of the membrane, whereas in a carrier mechanism, the binding site is available only one side of the membrane at any instant.
86 Which of the following statement(s) is/are true concerning translation of the mRNA message to protein synthesis?
a. An adaptor molecule, tRNA, recognizes specific nucleic acid bases and unites them with specific amino acids
b. Covalent attachment of tRNA to amino acids is energy dependent
c. The formation of a peptide bond between the growing peptide chain and the free amino acid occurs in the free cytoplasm
d. Complete protein synthesis takes hours
Answer: a, b
The synthesis of protein involves conversion from a four-letter nucleotide language to one of 20 chemically distinct amino acids. This process is referred to as translation. There is no mechanism for direct chemical recognition between specific nucleic acid bases and specific amino acids. Instead, an adaptor molecule, tRNA, is used. Each tRNA carries only one amino acid and must be recognized by a distinct enzyme which catalyzes the covalent attachment of the carboxyl end of the amino acid to the end of the tRNA in a process using ATP. Protein synthesis occurs by the formation of a peptide bond between the carboxyl terminal of the growing peptide chain and the free amino acid of deactivated amino acid tRNA. This event does not occur in free solution, but within ribosomes. Ribosomes are protein synthesizing machines that bring all of the necessary components together in the correct sequence and spacial orientation. Protein synthesis consumes a great deal of energy because four high-energy phosphate bonds must be split to make each peptide bond. Complete synthesis of a single protein takes 30 seconds to a few minutes, but multiple ribosomes can initiate translation and be moving down the mRNA molecules simultaneously, thus increasing the rate of protein synthesis.
87 Cell regulation can be thought of as the effector side of cell communication. Most commonly cell regulation occurs by means of extracellular chemical messengers. Which of the following statement(s) is/are true concerning these messengers?
a. Paracrine regulation involves a messenger which is produced and acts systemically
b. The extracellular signal or stimulus is received by a receptor on or in the target cell
c. Neurocrine regulation depends on a physical connection between the neuron and the target cell
d. Most hormones, local mediators, and neurotransmitters readily cross the cell plasma membrane
Answer: b, c
Depending on how the extracellular messenger arrives, cell regulation can be classified as paracrine, endocrine, or neurocrine. In paracrine regulation, a chemical messenger or mediator is produced and acts locally. In endocrine regulation, the extracellular messengers (hormones) are released into the blood and act on target cells anywhere on the body that has appropriate receptors. In neurocrine regulation, neurons secrete transmitters into highly localized regions, the synaptic cleft, so that the regulation depends on a physical connection between the neuron and the target cell as well as the presence of a specific receptor. In almost all cases of cell regulation, the extracellular signal or stimulus is restricted to being an informational molecule. This information is received by receptor on or in the target cell, which generally has an affinity for the signal molecule. Most hormones, local mediators, and neurotransmitters are water-soluble and cannot readily cross the plasma membrane.
88 Proteins that are destined to be secreted from the cells must pass through a series of organelles. These organelles include:
a. Endoplasmic reticulum
b. Golgi apparatus
c. Mitochondria
d. Lysosomes
Answer: a, b, d
Proteins targeted for the secretory pathway most commonly begin with translocation from the cytoplasm across the lipid bilayer into the lumen of the endoplasmic reticulum. It must then pass through a number of compartments including the Golgi apparatus where they are further processed and sorted and end up in a secretory vesicle or lysosome.
89 The best understood intracellular messenger is cyclic AMP (cAMP). Which of the following statement(s) concerning this intracellular messenger is/are correct?
a. Intracellular cyclic AMP is constantly degraded by a specific enzyme, cAMP phosphodiesterase
b. Most of the actions of cAMP are mediated by activation of protein kinase A
c. Intracellular levels of cAMP are relatively stable and change solely in response to activation of adenylate cyclase
d. cAMP is the only cyclic nucleotide active as an intracellular messenger
Answer: a, b
The prototypic intracellular messenger is cAMP. To function as a mediator, the concentration of cAMP must change rapidly. In resting cells, cAMP is continuously being degraded by a specific enzyme, cAMP phosphodiesterase. cAMP levels can increase 10-fold or more within seconds of receptor binding through activation of adenylate cyclase. cAMP acts as an allosteric regulator, and most, if not all, of its actions are mediated by activation of cAMP-dependent protein kinase A. cAMP is not the only cyclic nucleotide active as an intracellular messenger. Most animal cells also produce cGMP. Intracellular calcium ions also serve as second messengers in a large number of cells.
90 The activities of the cytoskeleton is dependent on which of the following types of filaments?
a. Microtubules
b. Intermediate filaments
c. Actin filaments
d. None of the above
Answer: a, b, c
The cytoskeleton is a collection of filamentous protein structures that allow cells to assume and maintain a variety of shapes, to produce directed movement of organelles within the cell, and to affect movement of the entire cell relative to other cells. These multiple activities depend upon three main types of filaments: actin filaments, intermediate filaments, and microtubules.
91 Intracellular organelles involved with protein synthesis include:
a. Mitochondria
b. Endoplasmic reticulum
c. Golgi complex
d. Lysosomes
Answer: b, c
Mitochondria are the major source of energy production in eukaryotic cells. The endoplasmic reticulum is the network of interconnected membranes forming closed vesicles, tubules, and saccules. The endoplasmic reticulum has a number of functions and is primarily involved in the synthesis of proteins and lipids. Adjacent to the rough endoplasmic reticulum and functionally involved in the sorting and package of secreted protein is the Golgi complex. Lysosomes are membrane-limited organelles containing acid hydrolytic enzymes that degrade polymers such as proteins, carbohydrates, and nucleic acids.
92 An important step in protein synthesis is transcription. Which of the following statement(s) is/are true concerning this process?
a. The first step in gene transcription involves separating the double helix of DNA by an enzyme known as DNA polymerase
b. The initial product of DNA transcription is called heterogeneous nuclear RNA which codes directly for proteins
c. After processing is complete, the mRNA is exported from the nucleus to the cytoplasm
d. Only one protein can be produced from an initial mRNA strand
Answer: c
Transcription of a gene begins at an initiation site associated with a specific DNA sequence, termed a promoter region. After binding to DNA, the RNA polymerase opens up a short region of the double helix to expose the nucleotides. Once the two strands of DNA are separated, the strand containing the promoter acts as a template to which ribonucleoside triphosphates base pair by hydrogen bonds. The initial products of transcription are known as heterogeneous nuclear RNA because of their large size variation. These primary transcripts are then processed to form mRNA. RNA splicing accounts for mature RNA being much shorter than nuclear RNA. Moreover, alternative splicing can lead to the production of different mRNA molecules and in some cases different proteins from the same gene. mRNA is exported from the nucleus only after processing is complete.
93 There are two properties of the cell necessary to maintain nonequilibrium cellular composition; the first is selectivity and the second is energy conversion. Which of the following statement(s) is/are true concerning energy converting transport?
a. The site of energy conversion and transport in the plasma membrane involves the phospholipid component
b. The Na+-K++-ATPase derives energy from hydrolysis of extracellular ATP
c. In some systems, energy inherent in the transmembrane ion gradient can be used to drive transport of a second species
d. Examples of species transported via secondary active transport include hydrogen ions, calcium, amino acids and glucose
Answer: c, d
The selectivity of the plasma membrane, although impressive, cannot account for the nonequilibrium composition of living cells. A cell can be maintained in a nonequilibrium state only by continual expenditure of energy. The maintenance of a steady-state, nonequilibrium cellular composition is possible because the plasma membrane is the site of energy converters, membrane proteins that function as biologic transport machines using energy derived from metabolic processes to perform transport work. The archetype for the biologic transport machine is the Na+-K+-ATPase, a membrane protein that hydrolyses cytosolic ATP and couples the resulting free energy to transport of Na+ and K+. A second equally important type of energy-converting transporter is one in which the energy inherent in a transmembrane ion gradient, usually that of Na+ can be used to drive the transport of a second species such as protons, calcium, amino acids, or glucose.
94 Which of the following statement(s) is/are correct concerning cell junctions?
a. The major occluding junction is the tight junction or zonula occludens
b. Tight junctions are usually located near the basal pole of the cell
c. Desmosomes are button-like points of attachment which serve to weld together adjacent cells
d. Gap junctions are a type of cell junction specialized for cell communication
Answer: a, c, d
Cell junctions are classified as occluding, anchoring, and communicating. The major occluding junction is the tight junction or zonula occludens which connects cells in epithelia and thereby allows epithelia to serve as selective permeability barriers. Tight junctions are normally located near the apical pool of the cell and form a belt that completely encircles the cell. Anchoring junctions connect the cytoskeleton of the cell to the extracellular matrix or neighboring cells. Morphologically these are adherens junctions or desmosomes. Desmosomes are button-like points of attachment with a prominent intracellular plaque that serves to weld together adjacent cells by serving as anchoring sites for intermediate filaments within the cell. The third functional type of cell junction is a gap junction which is specialized for communication. This junction mediates both electrical and chemical coupling.
95 Examples of ion channel blockers include:
a. Tetrodotoxin
b. Amiloride
c. Xylocaine
d. None of the above
Answer: a, b, c
Channel blockade is an important mechanism of action for toxins and some therapeutic agents. The deadly toxin of the puffer fish, tetrodotoxin, acts by blocking the Na+ channels that are responsible for the conduction of nerve impulse. The diuretic, amiloride, acts by blocking the Na+ channels that inhabit the apical membrane of the epithelial cells of the distal nephron. Local anesthetics such xylocaine also act by blocking ion channels.
96 Most hormone receptors are localized on the cell membrane and transduce hormone binding into altered levels of intracellular messengers. A limited number of intracellular receptors do exist. Which of the following statement(s) is/are true concerning intracellular receptors?
a. The messengers or hormones must by lipophilic
b. These intracellular receptors generally regulate protein synthesis
c. The intracellular receptors are located entirely in the nucleus of the cell
d. A heat-shock protein serves as an inhibitor protein blocking the DNA-binding domain of the steroid receptor
Answer: a, d
Although most hormone and other messenger receptors are extracellular, intracellular receptors have been identified. The hormone messengers involved for these receptors are primarily steroid and thyroid hormones and are lipophilic. By virtue of their hydrophobic nature, they are able to readily penetrate the lipid portion of the cell membrane. Receptors for these hormones exist intracellularly in the cytoplasm or in the nucleus and generally act as regulators of gene expression. These hydrophobic signaling molecules exist in plasma bound to protein, so that the concentration of this class of regulators does not fluctuate rapidly in plasma and their actions are generally slower in onset and more prolonged than those of water-soluble class. Some types of steroid receptors, particularly for glucocorticoids, are located in the cytosol in the inactive state. Once the ligand binds, the receptor undergoes a conformational change, termed activation. This allows cytoplasmic receptors to move into the nucleus and bind to DNA. Receptors already in the nucleus increase their affinity for DNA. In the case of glucocorticoid receptors and probably others of this class, the inactive receptor is associated with another protein, the heat-shock protein. They block the DNA-binding domain of the receptor. Activation involves the dissociation of the inhibitor protein.
97 Altering the amino acid profile in total parenteral nutrition solutions can be of benefit in certain conditions. Which of the following conditions are associated with a benefit by supplementation with the amino acid type listed?
a. Acute renal failure and essential amino acids
b. Hepatic failure and aromatic amino acids
c. Short gut syndrome and glutamine
d. Chronic renal failure and essential amino acids
Answer: a, c
In a number of conditions, altering the amino acid profile of the total parenteral nutrition solution can be of benefit. TPN with amino acids of high biologic value may decrease the mortality in patients with acute renal failure. These solutions, containing high quality amino acids, can improve nitrogen balance and diminish urea nitrogen. Provision of essential amino acids only allows the body to maximally utilize nitrogen for the synthesis of non-essential amino acids and thereby helps prevent rapid rises in blood urea nitrogen. There appears to be no advantages to using essential amino acids if the patient is already being dialyzed every other day and therefore a balanced standard amino acid solution is recommended. Because of liver damage and portasystemic shunting, patients with hepatic failure develop derangements in circulating levels of amino acids. The plasma aromatic/branch chain amino acid ratio is increased favoring the transport of aromatic amino acids across the blood brain barrier. These amino acids are precursors of false transmitters which contribute to lethargy and encephalopathy. Treatment of individuals with liver failure with solutions enriched in branch chain amino acids and deficient in aromatic amino acids results in improved tolerance to administration of protein and clinical improvement in encephalopathic states. Glutamine-enriched TPN partially attenuates villous atrophy and may be useful in treatment of short gut syndrome.
98 Under certain circumstances, the gut may become a source of sepsis and serve as the motor of systemic inflammatory response syndrome. Microbial translocation is the process by which microorganisms migrate across the mucosal barrier to invade the host. Which of the following mechanisms can promote bacterial translocation?
a. An increased number of gut bacteria
b. Altered intestinal mucosal permeability
c. Decreased host defense mechanisms
d. Lack of enteral feeding
Answer: a, b, c, d
99 Translocation is promoted in three general ways: 1) altered permeability of the intestinal mucosa as caused by shock, sepsis, distant injury, or cell toxins; 2) decreased host defense (secondary to glucocorticoid administration, immunosuppression, or protein depletion; and 3) an increased number of bacteria within the intestine. Because many factors that facilitate bacteria translocation occur simultaneously in surgical patients, these effects may be either additive or cumulative. In addition, many patients in Surgical Intensive Care Units do not generally receive enteral feedings and therefore current parenteral therapy results in gut atrophy which further promotes translocation.
Which of the following statement(s) is/are true concerning nutritional support of the injured patient?
a. The goal of nutritional support is maintenance of body cell mass and limitation of weight loss to less than 25% of preinjury weight
b. Under-nutrition may compromise the patient’s available defense mechanisms
c. Nutritional support is an immediate priority for the trauma patient
d. Fifty percent of non-nitrogen caloric requirements should be provided in the form of fat
Answer: b
Metabolic response to injury results in increased energy expenditure. If energy intake is less than expenditure, oxidation of body fat stores and erosion of lean body mass will occur with resultant loss of weight. When weight loss exceeds 10–15% of body weight, the complications of malnutrition interact with disease processes, with increased morbidity and mortality rates. The goal of nutritional support is maintenance of body cell mass and limitation of weight loss to less than 10% preinjury. The major impact of nutritional support in the trauma patient is to aid host defense. Under-nutrition may compromise the available host defense mechanism and may thus increase the likelihood of invasive sepsis, multiple organ system failure, and death. Resuscitation, oxygenation and arrest of hemorrhage are immediate priorities for survival. Nutritional support is an essential part of the metabolic care of the critically ill patient and should be instituted after resuscitation before significant weight loss occurs. The nutritional requirements of a trauma patient can be determined by determining basal metabolic rate with appropriate increases based on extent of injury and hospital activity. After initial determination of nitrogen requirements, caloric requirements should be distributed at a ratio of 70% as glucose and 30% as fat.
100 Which of the following statement(s) is/are true concerning body fuel reserves?
a. The largest fuel reserve in the body is skeletal muscle
b. Fat provides about 9 calories/gram
c. Free glucose and glycogen stores are a trivial fuel reserve
d. Body protein is a valuable storage form of energy
Answer: b, c
The body contains fuel reserves which it can mobilize and utilize during times of starvation or stress. By far the greatest energy component is fat, which is calorically dense since it provides about 9 calories/gram. Body protein comprises the next largest mass of utilizable energy, but amino acids yield only about 4 kcal/gram. Unlike fat reserves, body protein is not a storage form of energy but rather serves as a structural functional component of the body; loss of body protein, if severe, is associated with functional consequences. Glycogen stored in muscle and liver and free glucose have a trivial caloric value of less than 1000 kcal for a 70 kg male.
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