Rubin's Chapter 3

Question 1

74 yo F presents w/ acute chest pain and SOB. Cardiac cath shows occlusion of LAD. Labs and ECG show acute MI. Which pathological finding is likely in the affected heart muscle 4 weeks later?

Answer 1

Collagen-rich scar tissue. CHF pathological findings include microscopic signs of coagulative necrosis, approx 24 hrs after onset of vascular occlusion. PMN and leukocytes predominate in first 2-5 days. Capillary-rich granulation tissue is seen at the end of week 1 and ultimately, the necrotic myocardium is replaced by collagen-rich scar tissue, weeks to months later.

Question 2

4 yo M falls on rusty nail and punctures skin. Would is clean and covered with sterile gauze. What’s the initial event in the healing process?

Answer 2

Formation of a fibrin clot. The initial phase of repair, which usually starts with hemorrhage, involves forming a fibrin clot that fills the gap created by the wound. Acute inflammatory cells might follow. Thrombus (clot) or scab, forms later as a barrier to infection on top of the wound. The thrombus later undergoes proteolysis and regenerating epithelium comes in.

Question 3

82 yo M dies 4 yrs after getting CHF. He had multiple MI’s over the past 10 yrs. A trichrome stain of heart muslce at autopsy shows which type of collagen in mature scar tissue?

Answer 3

Type I. A mature scar is composed primarily of type I collagen, which increases wound strength. Early matrix of granulation tissue contains proteoglycans, glycoproteins and type III collagen.

Question 4

25 yo F sustains a deep, open laceration of her right forearm in a motorcycle accident. The wound is cleaned and sutured. Which cell type mediates contraction of the wound to facilitate healing?

Answer 4

Myofibroblasts = cells responsible for wound contraction as well as the deforming pathological process of wound contracture.

Question 5

Over 3 months, a wound heals w/ formation of a linear scar. Which nutritional factor is required for proper collagen assembly in scar tissue?

Answer 5

Vitamin C. Also called ascorbic acid, Vit C is a powerful biologic reducing agent that is necessary for hydroxylation of proline residues in collagen. Most of the clinical features of Vit C deficiency (scurvy) are caused by abnormal collagen that lacks tensile strength – poor wound healing and bursting open of old wounds - dehiscence.

Question 6

70 yo W w/ diabetes develops an ulcer on her right leg, which is covered in granulation tissue. What are the principle cellular components of the bed of this wound?

Answer 6

Fibroblasts and endothelial cells. Granulation tissue has 2 major components: cells and proliferating capillaries. The cells are: fibroblasts, myofibroblasts and macrophages. Capillaries arise from adjacent blood vessels by division of endothelial cells - angiogenesis. Once repair has been achieved, the capillaries are obliterate and reabsored – resulting in avascular, pale scar.

Question 7

What protein helps stimulate healing and angiogenesis in an ulcerous wound?

Answer 7

Metalloproteinase. Matrix metalloproteinases (MMPs) are crucial components in wound healing because they enable cells to migrate by degrading matrix proteins. Members of this protein family include: collagenase, stromelysin and gelatinase.

Question 8

68 yo man presents for repair of an abdominal aortic aneurysm. Severe complicated atherosclerosis is noted at surgery, prompting concern for embolism of atheromatuous material to the kidneys and other organs. If the patient were to develop a renal cortical infarct due to surgery, what would be the most likely outcome?

Answer 8

Scar formation. A large infarct of the kidney will heal by fibrosis (scar formation).

Question 9

40 yo F presents w/ painless lesion on her right earlobe, 4 months after ear piercing. What is the pathogenesis of this lesion?

Answer 9

Mutation arrest of collagen assembly. Keloid is an exuberent scar that tends to progress beyond the site of initial injury and recurs after excision. More frequent in dark skinned people. Characterized by changes in the ratio of type III to type I collagen, suggesting a mutation arrest in the healing process.

Question 10

58 yo F undergoes lumpectomy for breast cancer. 1 month after surgery she notices a firm 0.3 cm nodule along one edge of the surgical incision. Biopsy: chronic inflammatory cells, multinucleate giant cells and extensive fibrosis. The multinucleated cells in this nodule most likely formed in response to what pathological stimuli?

Answer 10

Foreign material. Granulomatous inflammation is a subtype of chronic inflammation that develops when acute inflammatory cells are unable to digest the injurous agent. Fusion of macrophages within the lesion result in formation of multinucleate giant cells.

Question 11

57 yo M, ho of alcoholism presents w/ yellow discoloration of skin and sclera. Labs: elevated serum levels of liver enzymes - AST and ALT. A trichrome stain of liver biopsy shows a pattern of regeneration and fibrosis. A similar pattern would be expected in what condition?

Answer 11

Chronic viral hepatitis. This patient has alcoholic liver disease/cirrhosis –> chronic liver injury. Chronic liver injury is associated w/ development of broad collagenous scars within the hepatic parenchyma. This is termed cirrhosis. Hepatocytes form regenerative nodules that lack central veins and expand to obstruct blood vessels and bile flow.

Question 12

10 yo M trips at scrapes his palms. The wounds are cleaned and covered w/ sterile gauze. What term characterizes the healing of these superficial abrasions?

Answer 12

Regeneration. Superficial abrasions of the skin heal by a process of regeneration. It is mediated by stem cells.

Question 13

Which cellular process helps restore normal epithelial structure and function after a minor scrape?

Answer 13

Contact inhibition of epithelial growth and motility. Maturation of the epidermis requires an intact layer of basal cells that are in direct contact w/ each other. If this contact is disrupted, basal epithelial cells at the wound margin become activated and eventually reestablish contact with basal cells through extensive cell migration and mitosis. When the epithelial contact is reestablished, the growth regulation can continue.

Question 14

34 yo F has a benign nevus removed from her back under local anesthesia. What family of cell adhesion molecules is the principle component of the provisional matrix that forms during early wound healing?

Answer 14

Fibronectins. – adhesive glycoproteins that are widely distributed in the stromal connective tissue and deposited at the site of tissue injury. During the initial phase of healing, fibronectin in the extravasated plasma is cross-linked to fibrin, collage, and other extracellular matrix components by transglutaminases.

Question 15

Which family of glycoproteins plays the most important role in regulating the migration and differentiation of leukocytes and connective tissue cells during wound healing?

Answer 15

Integrins. The movement of leukocytes is powered by membrane extensions called lamellipodia. Integrins are cell surface glycoproteins that transmit mechanical and chemical signals, thereby regulating cellular survival, proliferation, differentiation and migration. `

Question 16

29 yo F, laceration to arm. What is the most important factor in determining whether this wound will heal by primary or secondary intention?

Answer 16

Apposition of edges. Healing by primary intention occurs in wounds with closely apposed edges and minimal tissue loss. Such a wound requires only minimal cell proliferation and neovascularization to heal.

Question 17

Activated fibroblasts, myofibroblasts, and capillary sprouts are most abundant in a laceration wound at which time after injury?

Answer 17

3-5 days.
Neutrophils accumulate 12-24 hours after injury.
Activated fibroblasts, myofibroblasts, and capillary sprouts are abundant in healing wounds 3-5 days later.
Mature scar tissue starts forming 2 weeks after injury.

Question 18

A 9 yo M received a deep laceration over his right eye. The wound is cleaned and sutured. What describes the principle function of macrophages that are present in the wound 24-48 hours after the injury?

Answer 18

Phagocytosis. Macrophages arrive at the site of injury shortly after neutrophils, but they persist in the wound for several days longer. Macrophages remove debris and orchestrate the formation of granulation tissue by releasing cytokines and chemoattractants.

Question 19

Which collagen is deposited first during wound healing?

Answer 19

Type III. Concurrent w/ fibrinolysis, a temporary matrix of glycoproteins, proteoglycans and type III collagen is formed. Type I comes later, adding tensile force to the wound.

Question 20

16 yo M suffers a concussion during an ice hockey game and is rushed to the ER. CT: cerebral contusion in left frontal lobe. Boy is comatose for 3 days but eventually regains consciousness. Which cell is the principle mediator of scar formation in the patient’s CNS?

Answer 20

Glial cells. Damage to the brain or spinal cord is followed by growth of capillaries and gliosis – proliferation of astrocytes and microglia. Gliosis in the CNS is the equivalent of scar formation elsewhere.

Question 21

30 yo firefighter suffers extensive 3rd degree burns on arms and hands. He’s at high risk for which complication of wound healing?

Answer 21

Contracture. A mechanical reduction in the size of a wound depends on the presence of myofibrils and sustained cell contraction. An exaggeration of this is called contracture and can cause severe deformity. Contracture is likely after burns.

Question 22

23 yo M suffers from a crush injury of his food which becomes secondarily infected. He undergoes a below-the-knee amputation. 6 mo later the patient complains of chronic pain at the amputation site and a firm nodule is found. A biopsy of the nodule shows haphazard growth of nerves. What is the diagnosis?

Answer 22

Neuroma. Neurons in the PNS can regenerate their axons and under ideal circumstances, interruption in the continuity of a peripheral nerve results in complete functional recovery. However, if the cut ends are not in perfect alignment or are prevented from healing, a traumatic neuroma results.

Question 23

34 yo M presents w/ a 5 day ho painful sore on hand. Physical: 05 cm abscess that drains a thick, purulent material. Diapedesis of leukocytes into and around this infected wound occurs at which anatomical location?

Answer 23

Postcapillary venules. One of the earliest responses following tissue injury occurs within the capillary and postcapillary venule, where the major components of the inflammatory response are found: plasma, platelets, erythrocytes and leukocytes. Leukocytes are recruited from the post-capillary venules.

Question 24

35 yo F w/ ho chronic gastritis presents to ED w/ acute abdominal pain. Physical: hepatomegaly, ascites, mild juandice. The patient develops acute renal failure and dies. Autopsy: thrombosis of hepatic veins (Budd-Chiari syndrome). During autopsy, a lesion is identified in the distal stomach and examined by light microscopy…what is this finding?

Answer 24

Ulcer. A peptic ulcer is identified in the distal stomach. Histologic examination shows
focal destruction of the mucosa and full-thickness replace-
ment of the muscularis with collagen-rich connective tissue. Gastric ulcers are usually single and less than 2 cm in diameter. Ulcers on the lesser curvature are commonly associated with chronic gastritis.