3. Tissue Renewal & Repair Flashcards
- In an experiment, surgical incisions are made in a study group of laboratory rats. Observations about the wounds are
recorded over a 2-week period using various chemical mediators. Which of the following steps in the inflammatory-repair
response is most likely affected by neutralization of transforming growth factor β (TGF-β)?
□ (A) Leukocyte extravasation □ (B) Increase in vascular permeability □ (C) Production of collagen □ (D) Chemotaxis of lymphocytes □ (E) Migration of epithelial cells
1 (C) TGF-β stimulates many steps in fibrogenesis, including fibroblast chemotaxis and production of collagen by
fibroblasts, while inhibiting degradation of collagen. All of the other steps listed are unaffected by TGF-β.
- A 60-year-old woman developed chest pain that persisted for 4 hours. A radiographic imaging procedure showed an
apparent myocardial infarction involving a 3 × 4 cm area of the posterior left ventricular free wall. Laboratory findings
showed serum creatine kinase of 600 U/L. The patient received anti-arrhythmic and pressor agents to treat the decreased
cardiac output while in the hospital. Which of the following pathologic findings would most likely be seen in the left
ventricle 1 month later?
□ (A) Abscess □ (B) Complete resolution □ (C) Coagulative necrosis □ (D) Nodular regeneration □ (E) Fibrous scar
2 (E) The elevated creatine kinase level indicates that myocardial necrosis has occurred. The destruction of myocardial
fibers precludes complete resolution. The area of myocardial necrosis is gradually replaced by a fibrous scar. Liquefactive
necrosis with abscess formation is not a feature of ischemic myocardial injury. Coagulative necrosis is typical of
myocardial infarction, but after 1 month, a scar would be present. Nodular regeneration is typical of hepatocyte injury
because hepatocytes are stable cells.
- An experiment infects one group of test animals with viral hepatitis. Two months later, complete recovery of the normal
liver architecture is observed when the livers from these animals are examined microscopically. A second test group is
infected with bacterial organisms, and after the same period of time, fibrous scars from resolving abscesses are seen
microscopically in the livers. Which of the following factors best explains the different outcomes for the two test groups?
□ (A) Nature of the etiologic agent □ (B) Extent of liver cell injury □ (C) Injury to the connective tissue framework □ (D) Location of the lesion □ (E) Extent of damage to the bile ducts
3 (C) Hepatocytes are stable cells with an extensive ability to regenerate. The ability to restore normal architecture of an
organ such as the liver depends on the viability of the supporting connective tissue framework. If the connective tissue
cells are not injured, hepatocyte regeneration can restore normal liver architecture. This regeneration occurs in many cases of viral hepatitis. A liver abscess is associated with liquefactive necrosis of hepatocytes and the supporting
connective tissue. It heals by scarring. The other options listed may explain the amount of liver injury, but not the nature of
the response.
- A 23-year-old woman receiving corticosteroid therapy for an autoimmune disease has an abscess on her upper outer
right arm. She undergoes minor surgery to incise and drain the abscess, but the wound heals poorly over the next month.
Which of the following aspects of wound healing is most likely to be deficient in this patient?
□ (A) Re-epithelialization □ (B) Fibroblast growth factor elaboration □ (C) Collagen deposition □ (D) Serine proteinase production □ (E) Neutrophil infiltration
4 (C) Glucocorticoids inhibit wound healing by impairing collagen synthesis. This is a desirable side effect if the amount of
scarring is to be reduced, but it results in the delayed healing of surgical wounds. Re-epithelialization, in part driven by
epidermal growth factor, is not affected by corticosteroid therapy. Angiogenesis driven by fibroblast growth factor is not
significantly affected by corticosteroids. Serine proteinases are important in wound remodeling. Neutrophil infiltration is not
prevented by glucocorticoids.
- A cesarean section is performed on a 20-year-old woman to deliver a term infant, and the lower abdominal incision is
sutured. The sutures are removed 1 week later. Which of the following statements best describes the wound site at the
time of suture removal?
□ (A) Granulation tissue is still present
□ (B) Collagen degradation exceeds synthesis
□ (C) Wound strength is 80% of normal tissue
□ (D) Type IV collagen predominates
□ (E) No more wound strength will be gained
5 (A) At 1 week, wound healing is incomplete, and granulation tissue is still present. More collagen is synthesized in the
following weeks. Wound strength peaks at about 80% by 3 months. Type IV collagen is found in basement membranes.
- A 40-year-old man underwent laparotomy for a perforated sigmoid colon diverticulum. A wound infection complicated the
postoperative course, and surgical wound dehiscence occurred. Primary closure was no longer possible, and the wound
“granulated in.” Six weeks later, the wound is only 10% of its original size. Which of the following processes best accounts
for the observed decrease in wound size over the past 6 weeks?
□ (A) Increase in synthesis of collagen □ (B) Myofibroblast contraction □ (C) Inhibition of metalloproteinases □ (D) Resolution of subcutaneous edema □ (E) Elaboration of adhesive glycoproteins
6 (B) Wound contraction is a characteristic feature of healing by second intention that occurs in larger wounds. Collagen
synthesis helps fill the defect, but does not contract it. The inhibition of metalloproteinases leads to decreased degradation
of collagen and impaired connective tissue remodeling in wound repair. Edema diminishes over time, but this does not
result in much contraction. Adhesive glycoproteins such as fibronectin help to maintain a cellular scaffolding for growth and repair, but they do not contract.
- In an experiment involving observations on wound healing, researchers noted that intracytoplasmic cytoskeletal
elements, including actin, interact with the extracellular matrix to promote cell attachment and migration in wound healing.
Which of the following substances is most likely responsible for such interaction between the cytoskeleton and the
extracellular matrix?
□ (A) Epidermal growth factor □ (B) Fibronectin □ (C) Integrin □ (D) Platelet-derived growth factor □ (E) Type IV collagen □ (F) Vascular endothelial growth factor
7 (C) Integrins interact with the extracellular matrix proteins (e.g., fibronectin). Engagement of integrins by extracellular
matrix proteins leads to the formation of focal adhesions at which integrins link to intracellular cytoskeletal elements such
as actin. These interactions lead to intracellular signals that modulate cell growth, differentiation, and migration during
wound healing. Epidermal growth factor stimulates epithelial cell and fibroblast proliferation. Platelet-derived growth factor
(PDGF) can be produced by endothelium, macrophages, smooth muscle cells, and platelets; PDGF mediates migration
and proliferation of fibroblasts and smooth muscle cells and migration of monocytes. Type IV collagen is found in
basement membranes on which cells are anchored. Vascular endothelial growth factor promotes angiogenesis (capillary
proliferation) through endothelial cell proliferation and migration in a healing response.
- In an experiment, release of epidermal growth factor into an area of denuded skin causes mitogenic stimulation of the skin epithelial cells. Which of the following proteins is most likely to be involved in transducing the mitogenic signal from the epidermal cell membrane to the nucleus?
□ (A) G proteins □ (B) RAS proteins □ (C) Cyclin D □ (D) Cyclic AMP □ (E) Cyclin-dependent kinase
8 (B) RAS proteins transduce signals from growth factor receptors, such as epidermal growth factor, that have intrinsic
tyrosine kinase activity. G proteins perform a similar function for G protein–linked, seven-spanning receptors. Cyclic AMP
is an effector in the G protein signaling pathway. Cyclins and cyclin-dependent kinases regulate the cell cycle in the
nucleus.
- An experiment analyzes factors involved in the cell cycle during growth factor–induced cellular regeneration in a tissue
culture. Cyclin B synthesis is induced; the cyclin B binds and activates cyclin-dependent kinase 1 (CDK1). The active
kinase produced by this process is most likely to control progression in which of the following phases of the cell cycle?
□ (A) G0 to G1 □ (B) G1 to S □ (C) S to G2 □ (D) G2 to M □ (E) M to G1
9 (D) CDK1 controls an extremely important transition point, the G2 to M transition during the cell cycle, which can be regulated by CDK inhibitors. The other checkpoints are regulated by a distinct set of proteins.
- An experiment is conducted involving cellular aspects of wound healing. Components of the extracellular matrix are
analyzed to determine their sites of production and their binding patterns to other tissue components. Which of the
following molecules synthesized by fibroblasts can best bind to cellular integrins and extracellular collagen and attach epidermal basal cells to basement membrane?
□ (A) Heparin □ (B) Dermatan sulfate □ (C) Procollagen □ (D) Fibronectin □ (E) Hyaluronic acid
1 0 (D) Fibronectin is a key component of the extracellular matrix and has a structure that looks like a paper clip. Fibronectin can be synthesized by monocytes, fibroblasts, and endothelium. Heparin that is infused has an anticoagulant function. Dermatan sulfate, a glycosaminoglycan, acts to form a gel that provides resilience and lubrication. Procollagen produced by fibroblasts is formed into ropelike strands of collagen, which provide tensile strength. Hyaluronic acid binds water to form a gelatinous extracellular matrix.
- An 18-year-old man lacerated his left hand and required sutures. The sutures were removed 1 week later. Wound
healing continued, but the site became disfigured by a prominent raised, nodular scar that developed over the next 2
months. Which of the following terms best describes the process that occurred during this 2-month period?
□ (A) Organization □ (B) Dehiscence □ (C) Resolution □ (D) Keloid formation □ (E) Secondary union
1 1 (D) The healing process sometimes results in an exuberant production of collagen, giving rise to a keloid. This
tendency may run in families. Organization occurs as granulation tissue is replaced by fibrous tissue. Dehiscence occurs
when a wound pulls apart. If normal tissue architecture is restored, resolution of inflammation has occurred. Secondary
union describes the process by which large wounds fill in and contract.
- An experiment involves factors controlling wound healing. Skin ulcerations are observed, and the factors involved in the
healing process are analyzed. Which of the following factors is most likely to be effective in promoting angiogenesis?
□ (A) Platelet-derived growth factor □ (B) Epidermal growth factor □ (C) Basic fibroblast growth factor □ (D) Endostatin □ (E) Interleukin-1
12 (C) Basic fibroblast growth factor is a potent inducer of angiogenesis. It can participate in all steps of angiogenesis.
Epidermal growth factor and interleukin-1 have no angiogenic activity. Platelet-derived growth factor plays a role in
vascular remodeling. Endostatin is an inhibitor of angiogenesis.
- A 24-year-old man with acute appendicitis undergoes surgical removal of the inflamed appendix. The incision site is
sutured. A trichrome-stained section of the site is shown in the figure. How long after the surgery would this appearance
most likely be seen?
□ (A) 1 day □ (B) 2 to 3 days □ (C) 4 to 5 days □ (D) 2 weeks □ (E) 1 month
13 (E) The figure shows dense collagen with some remaining dilated blood vessels, typical of the final phase of wound
healing, which is extensive by the end of the first month. On day 1, the wound is filled only with fibrin and inflammatory
cells. Macrophages and granulation tissue are seen 2 to 3 days postoperatively. Neovascularization is most prominent by
days 4 and 5. By week 2, collagen is prominent, and fewer vessels and inflammatory cells are seen.
- A 50-year-old woman tests positive for hepatitis A antibody. The serum AST level is 275 U/L, and ALT is 310 U/L. One
month later, these enzyme levels have returned to normal. Which phase of the cell cycle best describes the hepatocytes 1
month after infection?
□ (A) G0 □ (B) G1 □ (C) S □ (D) G2 □ (E) M
14 (A) Hepatocytes are quiescent (stable) cells that can reenter the cell cycle and proliferate in response to hepatic injury,
enabling the liver to regenerate partially. Acute hepatitis results in hepatocyte necrosis, marked by elevations in AST and
ALT. After the acute process has ended, cells return to the G0 phase, and the liver becomes quiescent again.
- In an experiment, the role of low-density lipoprotein (LDL) receptors in uptake of lipids in the liver is studied. A mouse
model is created in which the LDL receptor gene is not expressed in the liver. For creating such a “knockout” mouse,
which of the following cells would be most useful?
□ (A) Adult bone marrow mesenchymal progenitor cells □ (B) Embryonic stem cells in culture □ (C) Hepatic oval cells □ (D) Hematopoietic stem cells □ (E) Regenerating hepatocytes
15 (B) Embryonic stem (ES) cells are multipotent and can give rise to all cells, including hepatocytes. Gene targeting to
produce “knockout” mice is done in cultures of ES cells, which are then injected into mouse blastocysts and implanted into
the uterus of a surrogate mother. Mesenchymal stem cells also are multipotential, but they are not useful for gene targeting. Hematopoietic stem cells can give rise to all hematopoietic cells, but not other types of cells. Hepatocytes and
oval cells within the liver can give rise only to liver cells.
