Hemodynamic Disorders [Robbins and Cotran Review of Pathology (4E) CH4/Rubins Illustrated Pathology Review (2E) CH7] Question bank

B The most important and the most common cause of venous thrombosis is vascular stasis, which often occurs with immobilization. Calcium is a cofactor in the coagula- tion pathway, but an increase in calcium has minimal effect on the coagulation process. Aspirin inhibits platelet function and limits thrombosis. Nitric oxide is a vasodilator and an inhibitor of platelet aggregation. Turbulent blood flow may promote thrombosis, but this risk factor is more common in fast-flowing arterial circulation.

23 A 55-year-old woman following major abdominal sur- gery has had discomfort and swelling of her left leg for the past week. On physical examination, the leg is slightly diffi- cult to move, and on palpation there is tenderness. A Doppler sonogram shows thrombosis of deep left leg veins. Which of the following mechanisms is most likely to contribute to her condition? A Hypercalcemia B Immobilization C Ingestion of aspirin D Nitric oxide release E Turbulent blood flow

(C) Hypovolemic shock Hypovolemic shock may be caused by hemorrhage, fluid loss from severe burns, diarrhea, excessive urine formation, perspiration, or trauma. In the case of burns or trauma, direct damage to the micro- circulation increases vascular permeability. Persons with third-degree burns weep large amounts of plasma. The other choices are unlikely causes of death in an acute burn victim. Dx: Hyperthermia, hypovolemic shock

A 50-year-old fire fighter emerges from a burning house with third-degree burns over 70% of his body. The patient expires 24 hours later. Which of the following was the most likely cause of death? (A) Congestive heart failure (B) Disseminated intravascular coagulation (C) Hypovolemic shock (D) Pulmonary saddle embolism (E) Toxic shock syndrome

(B) Dehydration Increased hematocrit in this patient reflects hemoconcentration caused by dehydration, secondary to diarrhea. This hematologic condition, termed relative polycythemia, is characterized by decreased plasma volume with a normal red cell mass. When patients suffer from burns, vomiting, excessive sweating, or diarrhea, they not only lose fluid but also suffer electrolyte disturbances. Systemic blood pressure falls with continuous dehydration, and declining perfusion eventually leads to death. Diabetes insipidus (choice C) may cause dehydration but is an unlikely choice because the patient has a history of diarrhea. None of the other choices cause relative polycythemia. Dx: Dehydration, relative polycythemia

A 1-year-old girl is brought to the emergency room by her parents who report she has had a fever and diarrhea for 3 days. Her tem- perature is 38°C (101°F). The CBC shows a normal WBC count and increased hematocrit (48 g/dL). Which of the following is the most likely cause of increased hematocrit in this patient? (A) Acute phase response (B) Dehydration (C) Diabetes insipidus (D) Malabsorption (E) Septic shock

A) Decrease in production of thrombin He has hemophilia A. Factor VIII, tissue factor (III), and factor V act as cofactors or reaction accelerators in the clot- ting cascade leading to thrombin production. Factor VIII acts as a reaction accelerator for the conversion of factor X and factor Xa. The platelet surface provides phospholipid for assembly of coagulation factors. Platelet aggregation is promoted by thromboxane A2 and ADP. Thromboxane A2 is released when platelets are activated during the process of platelet adhesion. Fibrin polymerization is promoted by factor XIII. Antithrom- bin III inhibits thrombin to prolong the prothrombin time.

A 12-year-old boy has a 10-year history of multiple soft tissue hemorrhages and acute upper airway obstruction from hematoma formation in the neck. On physical examination, he has decreased range of motion of the large joints, particularly the knees and ankles. He has no petechiae or purpura of the skin. Laboratory studies show normal prothrombin time, el- evated partial thromboplastin time (PTT), and normal platelet count, but markedly decreased factor VIII activity. Which of the following mechanisms best describes the development of his disease? A Decrease in production of thrombin B Decrease in membrane phospholipid C Failure of platelet aggregation D Failure of fibrin polymerization E Inability to neutralize antithrombin III F Inability of platelets to release thromboxane A2

C) Prostacyclin Endothelial injury releases glycoprotein tissue factor (factor III) that drives the coagulation process and activates platelets. Adjacent intact endothelium generates prostacyclin (PGI2) via arachidonic acid metabolism to inhibit clot propagation beyond where it is needed. PGI2 and nitric oxide are powerful vasodilators and inhibitors of plate- let aggregation. This limits thrombus formation just to the area of injury. Glycoprotein IIb/IIIa, which induces shape change; phospholipid, which binds fibrinogen and calcium; and platelet-activating factor are procoagulants that drive thrombosis and platelet activation. Tissue-type plasminogen activator promotes fibrinolytic activity after a thrombus has formed. Thrombomodulin binds to thrombin to form an anti- coagulant that activates protein C, which then cleaves activated factor V and factor VIII. Thromboxane is generated via arachidonic acid metabolism in platelets to promote platelet activation and vasoconstriction.

A 15-year-old girl incurs a cut to the sole of her foot after stepping on a piece of broken glass. On examination, a superficial 0.5-cm laceration ceases to bleed within 5 minutes after application of local pressure. Which of the following substances is released by endothelium and is most likely to counteract platelet aggregation near this site of injury? A Glycoprotein IIb/IIIa B Platelet-activating factor C Prostacyclin D Tissue-type plasminogen activator E Thrombomodulin F Thromboxane

(C) Decreased intravascular oncotic pressure The pressure differential between the intravascular and the interstitial compartments is largely determined by the concentration of plasma proteins, especially albumin. Any condition that lowers plasma albumin levels, whether from albuminuria in nephrotic syndrome or reduced albumin synthesis in chronic liver disease, tends to promote generalized edema. Dx: Minimal change nephrotic syndrome

A 19-year-old woman complains of swelling of her eyelids, abdomen, and ankles. At bedtime, there are depressions in her legs at the location of the elastic in her socks. A chest X-ray shows bilateral pleural effusions. Urine protein electrophoresis demonstrates 4+ proteinuria. A percutaneous needle biopsy of the kidney establishes the diagnosis of minimal change nephrotic syndrome. Soft tissue edema in this patient is most likely caused by which of the following mechanisms of disease? (A) Active hyperemia (B) Chronic passive congestion (C) Decreased intravascular oncotic pressure (D) Hyperalbuminemia (E) Increased capillary permeability

D) Pulmonary diffuse alveolar damage The patient is quickly going into shock after trauma. So-called shock lung, with diffuse alveolar damage, is common in this situation. Infarction of the liver is uncommon because of this organ's dual blood supply. Basal ganglia hemorrhages are more typical of hypertension, not hypotension with shock. Gangrene requires much longer to develop and is not a common complication of shock. Passive congestion is less likely because of the diminished blood volumes and tissue perfusion that occur in shock.

A 20-year-old man develops palpitations within 1 hour after a gunshot wound to the abdomen. On examination his heart rate is 112/minute and blood pressure 80/30 mm Hg. His skin is cool and clammy to the touch. Which of the fol- lowing organ-specific changes is most likely to occur within 2 days after this injury? A Acute hepatic infarction B Cerebral basal ganglia hemorrhage C Gangrenous necrosis of the lower legs D Pulmonary diffuse alveolar damage E Renal passive congestion

(D) Hypovolemic shock Hypovolemic shock is secondary to a pronounced decrease in blood or plasma volume, caused by the loss of fluid from the vascular compartment. Hemorrhage, fluid loss from severe burns, diarrhea, excessive urine formation, perspiration, and trauma are major mechanisms of fluid loss that can lead to hypovolemic shock. Cardiogenic shock (choice B) is caused by myocardial pump failure. Septic shock (choice E) is improbable in this setting. Dx: Hypovolemic shock

A 20-year-old man is brought to the emergency room after rupturing his spleen in a motorcycle accident. His blood pres- sure on admission is 80/60 mm Hg. Analysis of arterial blood gasses demonstrates metabolic acidosis. This patient is most likely suffering from which of the following conditions? (A) Acute pancreatitis (B) Cardiogenic shock (C) Hypersplenism (D) Hypovolemic shock (E) Septic shock

(E) Tumor necrosis factor-α Tumor necrosis factor-a (TNF-a). Septicemia with Gram-negative organisms is the most common cause of septic shock. The invading bacteria are responsible for the release of endotoxin, a lipopolysaccharide (LPS). On entry into the circulation, LPS binds to the surface of monocytes/ macrophages. The CD14 recognition complex mediates signaling through activation of nuclear transcription factor- kappa B (NF-κB) and upregulates the expression of TNF-α. In septic shock, this protein is released in great excess, resulting in effects that are often lethal. None of the other mediators cause severe injury to vascular endothelium in patients with septic shock. Dx: Meningitis, septic shock

A 20-year-old woman presents to the emergency room complaining of having had a severe headache for 4 hours. Physical examination reveals numerous small red spots on the extremities and a stiff neck. Her temperature is 38.7°C (103°F). Lumbar puncture returns purulent fluid, with segmented neutrophils and Gram-negative organisms resembling meningococci. A few hours later, the patient goes into shock and becomes comatose. Severe endothelial injury in this patient is primarily mediated by which of the following proteins? (A) α-Fetoprotein (B) IgG (C) Interferon-γ (D) Transforming growth factor-β (E) Tumor necrosis factor-α

(C) Infarction Hypotension caused by postpartum bleeding can, in rare cases, lead to infarction of the pituitary. The pituitary is particularly susceptible at this time because its enlargement during pregnancy renders it vulnerable to a reduction in blood flow. None of the other choices causeclinical features of pan-hypopituitarism. Dx: Sheehan syndrome, pituitary infarction

A 21-year-old pregnant woman experiences abruptio placentae at 37 weeks of gestation and develops severe vaginal bleeding that is difficult to control. Five months later, the patient presents with profound lethargy, pallor, muscle weakness, failure of lactation, and amenorrhea. Which of the following best explains the pathogenesis of pituitary insufficiency in this patient? (A) Abscess (B) Embolism (C) Infarction (D) Passivehyperemia (E) Thrombosis

B) Factor V mutation Recurrent thrombotic episodes at such a young age strongly suggest an inherited coagulopathy. The factor V (Leiden) mutation affects 2% to 15% of the population, and more than half of all individuals with a history of recurrent deep venous thrombosis have such a defect. Inherited deficiencies of the anticoagulant proteins antithrombin III and protein C can cause hypercoagulable states, but these are much less common than factor V mutation. Hyperhomocysteinemia is a less common cause of inherited risk of thrombosis than is factor V mutation. It also is a risk factor for atherosclerosis that predisposes to arterial thrombosis. Although some cancers elaborate factors that promote thrombosis, this patient is unlikely to have cancer at such a young age; a 10-year history of thrombosis is unlikely to occur in a patient with cancer. Oral contraceptive usage contributes to risk for thrombosis, but mainly in older women, particularly past age 40 years. Smoking promotes atherosclerosis with arterial thrombosis.

A 21-year-old woman has had multiple episodes of deep venous thrombosis during the past 10 years and one episode of pulmonary thromboembolism during the past year. Laboratory tests show that her prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and platelet function studies all are normal. Which of the following risk factors is the most common cause for such a coagulopathy? A Antithrombin III deficiency B Factor V mutation C Hyperhomocysteinemia D Mutation in protein C E Occult malignancy F Oral contraceptive use G Smoking cigarettes

(C) Fat embolism Fat emboli originate from adipose tissue in the medulla of fractured long bones. Fat carried by venous blood reaches the lungs, filters through the pulmonary circulation, enters arterial blood, and is disseminated throughout the body. The occlusion of cerebral capillaries is accompanied by petechial hemorrhages in the brain and is the most important complication of fat embolism. Acute myocardial infarction (choice A) would be unlikely in a 22-year-old patient. Deep venous thrombosis (choice B) and septic shock (choice E) would be unlikely within this time frame. Paradoxical embolism (choice D) refers to emboli that arise in the venous circulation and bypass the lungs by traveling through an incompletely closed foramen ovale, subsequently entering the arterial circulation. Dx: Fat embolism

A 22-year-old construction worker falls 30 ft and fractures several bones, including his femoral shafts. Six hours later, the patient develops shortness of breath and cyanosis. Which of the following hemodynamic disorders best explains the pathogenesis of shock in this patient? (A) Acute myocardial infarction (B) Deep venous thrombosis (C) Fat embolism (D) Paradoxical embolism (E) Septic shock

(A) Anoxic injury The pathogenesis of RDS of the newborn is intimately linked to a deficiency of surfactant. This material lowers the surface tension of the alveoli at low lung volumes and thereby prevents collapse (atelectasis) of the alveoli during expiration. Atelectasis secondary to surfactant deficiency results in perfused but not ventilated alveoli, a situation that leads to hypoxia and acidosis. Intraventricular cerebral hemorrhage is a major complication of RDS. The periventricular germinal matrix in the newborn brain is particularly vulnerable to hemorrhage because the dilated, thin-walled veins in this area rupture easily (see photograph). The pathogenesis of this complication is believed to reflect anoxic injury to the periventricular capillaries, venous sludging and thrombosis, and impaired vascular autoregulation. Despite advances in neonatal intensive care, the overall mortality of RDS is about 15%, and one third of infants born before 30 weeks of gestational age die of this disorder. Although the other choices are associated with bleeding, they are unlikely causes of periventricular hemorrhage in a baby with RDS. Dx: Respiratory distress syndrome of the neonate

A 22-year-old woman delivers a baby at 29 weeks of gestation. Shortly after birth, the neonate becomes short of breath. The neonate is placed on a ventilator, but dies of respiratory insufficiency. The brain at autopsy is shown. Which of the following mechanisms of disease best explains this complication of respiratory distress syndrome (RDS) of the neonate? (A) Anoxic injury (B) Birth trauma (C) Chronic passive congestion (D) Hemolytic anemia (E) Hypertension

B) Amniotic fluid Amniotic fluid embolism rarely occurs in pregnancy, but it has a high mortality rate. The fluid reaches torn uterine veins through ruptured fetal membranes. Aggregates of platelets represent localized thrombosis, an unlikely event in the lungs. Fat globules are seen in fat embolism, usually after severe trauma. Gas bubbles in vessels from air embolism can be a rare event in some obstetric procedures, but it is an unlikely event in natural deliveries. Peripheral pulmonary thromboemboli are most likely to produce chronic pulmonary hypertension and develop over weeks to months.

A 22-year-old woman with an uncomplicated pregnancy develops sudden dyspnea with cyanosis and hypotension intrapartum during routine vaginal delivery of a term infant. She has a generalized seizure and becomes comatose. Her condition does not improve over the next 2 days. Which of the fol- lowing findings is most likely to be present in her peripheral pulmonary arteries? A Aggregates of platelets B Amniotic fluid C Fat globules D Gas bubbles E Thromboemboli

(A) Hemarthrosis Hemarthrosis refers to bleeding into the joint cavity. It is associated with joint swelling and is a crippling complication of hemophilia. Repeated bleeding may cause deformities and may limit the mobility of the joints. Hematemesis (choice B) is vomiting blood. Hematocephalus (choice C) is an intracranial infusion of blood. Hematochezia (choice D) is passage of blood caused by lower gastrointestinal hemorrhage. Hemoptysis (choice E) is coughing up blood. Dx: Hemophilia, hemarthrosis

A 23-year-old man with hemophilia is recently wheelchair bound. Which of the following best accounts for this development? (A) Hemarthrosis (B) Hematemesis (C) Hematocephalus (D) Hematochezia (E) Hemoptysis

(E) Passive hyperemia Passive hyperemia (chronic passive congestion) may be confined to a limb or an organ as a result of localized obstruction to venous drainage. Examples include deep venous thrombosis of the leg veins, with resulting edema of the lower extremity, and thrombosis of the hepatic veins (Budd-Chiari syndrome, this patient) with secondary chronic passive congestion of the liver. Active hype- remia (choice A) is an augmented supply of blood to an organ, usually as a physiologic response to an increased functional demand. The most striking active hyperemia occurs in asso- ciation with inflammation. Arterial embolism (choice B) typi- cally causes infarction. Hematoma (choice C) and hemorrhage (choice D) represent extravascular accumulation of blood. Dx: Budd-Chiari syndrome

A 23-year-old woman complains of a recent onset of yellowing of her skin and increasing abdominal girth. Physical examination reveals jaundice and ascites. Ultrasound examination of her abdomen demonstrates thrombosis of the hepatic veins. A liver biopsy discloses severe sinusoidal dilation within the centrilobular regions. This pathologic finding is caused by which of the following hemodynamic disorders? (A) Active hyperemia (B) Arterial embolism (C) Hematoma (D) Hemorrhage (E) Passive hyperemia

B) Fat embolism The mechanism for fat embolism is unknown, in particular, why onset of symptoms is delayed 1 to 3 days after the initial injury (or up to 1 week for cerebral symptoms). The cumulative effect of many small fat globules filling peripheral pulmonary arteries is the same as one large pulmonary thromboembolus. Cardiac tamponade and hemothorax would be immediate complications after traumatic injury, not delayed events. Pulmonary edema severe enough to cause dyspnea would be unlikely to occur in hos- pitalized patients because fluid status is closely monitored. Pulmonary infarction may cause dyspnea, but pulmonary thromboembolus from deep venous thrombosis is typically a complication of a longer hospitalization.

A 32-year-old man is involved in a vehicular accident and sustains fractures of the right femur and tibia and the left humerus. The fractures are stabilized surgically. He is in stable condition for 2 days, but then suddenly becomes severely dyspneic. Which of the following complications from his injuries is the most likely cause of his sudden respiratory difficulty? A Cardiac tamponade B Fat embolism C Pulmonary edema D Pulmonary infarction E Right hemothorax

A) Antiphospholipid antibody These findings are characteristic of a hypercoagulable state. The patient has antibodies that react with cardiolipin, a phospholipid antigen used for the serologic diagnosis of syphilis. These so-called antiphospholipid antibodies are directed against phospholipid-protein complexes such as β2-glycoprotein I and thrombin and are sometimes called lupus anticoagulant because they are present in some patients with systemic lupus erythematosus (SLE) or other autoimmune states. Patients with antiphospholipid syndrome have recurrent arterial and venous thrombosis and repeated miscarriages. In vitro, these antibodies inhibit coagulation by interfering with the assembly of phospholipid complexes, and a "mixing study" with normal serum will not correct the PTT (which primarily measures factors II, V, VIII, IX, X, XI, and XII and fibrinogen in the "intrinsic pathway" of in vitro coagulation). In vivo, the antibodies induce a hypercoagulable state by unknown mechanisms. Disseminated intravascular coagulation is an acute consumptive coagulopathy characterized by elevated PT and PTT, and decreased platelet count. The PT and PTT are normal in patients with factor V (Leiden) mutation. Hypercholesterolemia promotes atherosclerosis over many years, and the risk of arterial thrombosis increases. Von Willebrand disease affects platelet adhesion and leads to a bleeding tendency, not to thrombosis.

A 23-year-old woman has had altered consciousness and slurred speech for the past 24 hours. A head CT scan shows a right temporal hemorrhagic infarction. Cerebral angiography shows a distal right middle cerebral arterial occlusion. Within the past 3 years, she has had an episode of pulmonary embo- lism. A pregnancy 18 months ago ended in miscarriage. Labo- ratory studies show a false-positive serologic test for syphilis, normal prothrombin time (PT), elevated partial thromboplas- tin time (PTT), and normal platelet count. Which of the follow- ing is the most likely cause of these findings? A Antiphospholipid antibody B Disseminated intravascular coagulation C Factor V mutation D Hypercholesterolemia E Von Willebrand disease

(A) Amniotic fluid embolism Amniotic fluid embolism refers to the entry of amniotic fluid containing fetal cells and debris into the maternal circulation through open uterine and cervical veins. It is a rare maternal complication of childbirth, but when it occurs, it is often catastrophic. This disorder usually occurs at the end of labor when the pulmonary emboli are composed of the epithelial constituents (squamae) contained in the amniotic fluid. None of the other choices show these pathologic findings. Dx: Amniotic fluid embolism

A 25-year-old woman delivers a healthy baby at 39 weeks of gestation. Six hours later, the mother develops severe shortness of breath and appears cyanotic. Despite resuscitation, she dies 2 hours later. A section of lung at autopsy is shown in the image. These pathologic findings are associated with which of the following mechanisms of disease? (A) Amniotic fluid embolism (B) Cardiogenic shock (C) Maternal-fetal histoincompatibility (D) Metastatic squamous cell carcinoma (E) Pulmonary thromboembolism

B) Platelet adhesion Von Willebrand factor (vWF) acts like a "glue" between platelets and the exposed extracellular matrix of the vessel wall after vascular injury. None of the other steps listed depends upon vWF. Because the patient's prothrombin time (PT) is normal, a lack of prothrombin or the presence of an inhibitor is unlikely. Because vWF stabilizes factor VIII, a deficiency of vWF may prolong the partial thromboplastin time (PTT).

A 26-year-old woman has a history of frequent nose- bleeds and increased menstrual blood flow. On physical examination, petechiae and purpura are present on the skin of her extremities. Laboratory studies show normal partial thromboplastin time (PTT), prothrombin time (PT), and platelet count, but decreased von Willebrand factor activity. This patient most likely has a derangement in which of the following steps in hemostasis? A Fibrin polymerization B Platelet adhesion C Platelet aggregation D Prothrombin generation E Prothrombin inhibition F Vasoconstriction

D) Liver The liver has a dual blood supply, with a hepatic arterial circulation and a portal venous circulation. Infarction of the liver caused by occlusion of hepatic artery is uncommon. Cerebral infarction typically produces liquefactive necrosis. Infarcts of most solid parenchymal organs such as the kidney, heart, and spleen exhibit coagulative necrosis, and emboli from the left heart often go to these organs.

A 28-year-old woman with a 15-year history of recur- rent thrombosis from a prothrombin gene mutation develops septicemia after a urinary tract infection with Pseudomonas aeruginosa. She develops multiple infarcts and organ failure over the next 2 weeks. Which of the following organs is most likely to be spared from the effects of ischemic injury in this woman? A Brain B Heart C Kidney D Liver E Spleen

D) Lactate dehydrogenase In the nonprogressive phase of shock, neurohumoral mechanisms include catecholamine release, activation of the renin-angiotensin axis, antidiuretic hormone (ADH) release, and generalized sympathetic stimulation with tachycardia, peripheral vasoconstriction, and renal conservation of fluid to support tissue perfusion. As shock progresses, there is hypo- tension with diminished tissue perfusion, anaerobic glycolysis, and lactic acidosis. An irreversible stage of shock is marked by tissue injury, hypoxia, marked metabolic acidosis, activation of coagulation pathways with consumption of coagulation factors, multiple organ failure, and leakage of lysosomal and cytosolic enzymes, such as lactate dehydrogenase (LDH).

A 30-year-old man is cutting wood alone in the forest and incurs a deep cut to his leg from his chain saw. He loses a large amount of blood. He is not found until the next day. A marked increase in which of the following blood analytes is most likely to indicate that he has reached an irreversible stage of shock? A Antidiuretic hormone B Bicarbonate C Catecholamines D Lactate dehydrogenase E Prothrombin

C) Nitrogen gas bubbles These findings are characteristic of decompression sickness (the bends), a form of air embolism. At high pressures, such as occur during a deep scuba dive, nitrogen is dissolved in blood and tissues in large amounts. Ascending too quickly does not allow for slow release of the gas, and formation of small gas bubbles causes symptoms from occlusion of small arteries and arterioles. Fat globules in pulmonary arteries are a feature of fat embolism, which usually follows trauma. Fibrin thrombi may form with widespread activation of coagulation, as with DIC. Platelet thrombi may form with microangiopathic hemolytic anemia, such as thrombotic thrombocytopenic purpura. Atherosclerosis typically occurs in elastic arteries, not arterioles.

A 31-year-old man is on a scuba diving trip and descends to a depth of 50 m in the Blue Hole off the coast of Belize. After 30 minutes, he has a malfunction in his equipment and quickly returns to the boat on the surface. He develops difficulty breathing within 5 minutes, with dyspnea and substernal chest pain, followed by a severe headache and vertigo. An hour later, he develops severe, painful myalgias and arthralgias. These symptoms abate within 24 hours. Which of the following occluding his arterioles is the most likely cause of his findings? A Fat globules B Fibrin clots C Nitrogen gas bubbles D Platelet thrombi E Ruptured atheromatous plaque

(D) Melena Melena (black stool) is a symptom of upper gastrointestinal bleeding. Blood from ruptured esophageal varices or a peptic ulcer is partially digested by hydrochloric acid. Hemoglobin is transformed into a black pigment (hematin), which imparts a typical "coffee-grounds" color to the stool. Hematemesis (choice A) is vomiting of blood. Hematobilia (choice B) is bleeding into the biliary passages, as a complication of trauma or neoplasia. Hematochezia (choice C) is passage of bloody stools caused by lower gas- trointestinal hemorrhage. Steatorrhea (choice E) is passage of fatty stools caused by pancreatic disease and malabsorption. Dx: Peptic ulcer disease

A 33-year-old woman presents with black stools. Laboratory studies demonstrate a hypochromic, microcytic anemia. Upper GI endoscopy reveals a duodenal ulcer. Which of the following best describes the stools in this patient with peptic ulcer disease? (A) Hematemesis (B) Hematobilia (C) Hematochezia (D) Melena (E) Steatorrhea

D) Lymphatic obstruction Spread of the cancer to the dermal lymphatics produces a peau d'orange appearance of the breast. Because the breast has an extensive venous drainage, cancer or other focal mass lesions are unlikely to cause significant congestion and edema of the breast. Chronic inflammation is rare in breast tissue and is not associated with cancer. Passive congestion does not involve the breast. Ischemia is rare in the breast because of the abundant arterial supply.

A 37-year-old woman has noticed a lump in her left breast over the past 2 months. On physical examination, the skin overlying the left breast is thickened, reddish orange, and pitted. Mammography shows a 3-cm underlying density. A fine-needle aspirate of the density is performed and on microscopic examination shows carcinoma. Which of the following mechanisms best explains the gross appearance of the skin of her left breast? A Chronic inflammation B Chronic passive congestion C Ischemic necrosis D Lymphatic obstruction E Venous thrombosis

(D) Petechia Petechiae are pinpoint hemorrhages, usually in the skin or conjunctiva. This lesion represents the rupture of a capillary or arteriole and occurs in conjunction with vasculitis and coagulopathy. Petechiae may also be produced by microemboli from infected heart valves (bacterial endocarditis). Hyperemia (choice C) refers to increased blood in a tissue or organ. Erythema (choice B) is inflammatory redness of the skin. Ecchymosis (choice A) is a larger superficial hemorrhage in the skin. Purpura (choice E) is a diffuse superficial hemorrhage in the skin up to 1 cm in diameter. Dx: Endocarditis, petechia

A 40-year-old man with a history of bacterial endocarditis notices numerous pinpoint hemorrhages around the orbit of his eyes (shown in the image; see arrows). What is the appropriate term used to describe this form of superficial hemorrhage? (A) Ecchymosis (B) Erythema (C) Hyperemia (D) Petechia (E) Purpura

(A) Ecchymosis Ecchymosis is a larger superficial hemorrhage in the skin. Following hemorrhage, the initially purple discoloration of the skin turns green and then yellow before resolving. This sequence of events reflects the progressive oxidation of bilirubin released from the hemoglobin of degraded erythrocytes. A "black eye" is a good example of an ecchymosis. Petechiae (choice D) are pinpoint hemorrhages, usually in the skin or conjunctiva. Purpura (choice E) is a diffuse superficial hemorrhage in the skin up to 1 cm in diameter. Dx: Ecchymosis

A 42-year-old woman undergoes a face lift. Two days later, she presents for follow-up care with confluent bluish hemorrhages in the skin around her eyes ("black eyes"). Which of the following best describes this pattern of superficial skin hemorrhage? (A) Ecchymosis (B) Hematocephalus (C) Maculopapular rash (D) Petechiae (E) Purpura

B) Ischemic infarct The figure shows a pale ischemic infarction of the renal cortex extending nearly to the renal capsule, a typical finding when a medium-sized arterial thromboembolus lodges in a peripheral renal artery branch. The infarct is wedge-shaped, typical for many parenchymal organs, because there is minimal collateral circulation. An abscess is a form of liquefactive necrosis from a localized collection of neutrophils in association with infection, and though it could be yellowish, it is likely to be round. Liquefactive necrosis from arterial occlusion and infarction occurs in the brain. Multiorgan failure occurs with shock, and whole organs are affected by ischemia. Venous thrombosis tends to produce hemorrhagic lesions.

A 44-year-old man with dilated cardiomyopathy and heart failure develops left atrial mural thrombosis. He develops the complication shown in the figure, manifested by hematuria. Which of the following is the best term for this complication? A Abscess B Ischemic infarct C Liquefactive necrosis D Multiorgan failure E Venous thrombosis

C) Increased hydrostatic pressure The hydrostatic pressure exerted from standing upright leads to edema in dependent parts of the body. In a healthy patient, normal renal function would be sufficient to clear free water ingested orally. Hypoalbuminemia leads to more generalized edema, although the effect is more pro- nounced in dependent areas. Lymphatic obstruction from infection or tumor can lead to lymphedema, but this is a chronic process. Secondary aldosteronism results from con- gestive heart failure and renal hypoperfusion, but this is a generalized process.

A 45-year-old woman who works while standing for long periods notices at the end of her 8-hour shift that her lower legs and feet are swollen, although there was no swelling at the beginning of the day. There is no pain or erythema associated with this swelling. She is otherwise healthy and takes no medications; laboratory testing reveals normal liver and renal function. Which of the following mechanisms best explains this phenomenon? A Excessive free water intake B Hypoalbuminemia C Increased hydrostatic pressure D Lymphatic obstruction E Secondary aldosteronism

(A) Ascites A protruding belly and fluid accumulation in patients with cirrhosis represents ascites (i.e., accumulation of serous fluid in the abdominal cavity). It is primarily a consequence of portal hypertension and hypoalbuminemia. None of the other choices describe serous fluid accumulation in the abdomen. Dx: Cirrhosis, portal hypertension

A 50-year-old alcoholic is rushed to the hospital with bleeding esophageal varices and expires. At autopsy, the patient's protruding abdomen is found to contain a large volume of serous fluid. What is the appropriate term used to describe this fluid? (A) Ascites (B) Exudate (C) Hemorrhage (D) Hydrothorax (E) Lymphedema

B) Alveolar transudate Acute left ventricular failure after a myocardial infarction causes venous congestion in the pulmonary capillary bed and increased hydrostatic pressure, which leads to pulmonary edema by transudation in the alveolar space. Neutrophils and fibrin would be found in cases of acute inflammation of the lung (i.e., pneumonia). Fibrosis and hemosiderin-filled macrophages (heart failure cells) would be found in long-standing, not acute, left ventricular failure. Purulent exudate in the pleural space (empyema) or draining from bronchi results from bacterial infection, not heart failure. No pleural effusions are present in this radiograph. Fluid collections are likely to be transudates (few cells and minimal protein) in noninflammatory conditions.

A 50-year-old man suffers an infarction of the anterior left ventricular wall. He receives therapy with anti-arrhythmic and pressor agents. He is in stable condition until he develops severe breathlessness 3 days later. An echocardiogram shows a markedly decreased ejection fraction. Representative chest radiographic findings are shown in the figure above. Which of the following microscopic changes is most likely to be present in his lungs? A Alveolar neutrophilic exudate B Alveolar transudate C Alveolar wall fibrosis D Pleural fibrosis E Pleural space neutrophilic exudate F Pleural space transudate

(A) Chylothorax Obstruction of lymphatic flow may occur in a number of clinical settings, but is most common because of surgical removal of lymph nodes or tumor obstruction. For example, the lymphatic system may be obstructed after axillary lymph node dissection for breast cancer. Prolonged lymphatic obstruction in the patient's shoulder causes edema, progressive dilation of lymphatic vessels (lymphangiectasia), and overgrowth of fibrous tissue. Lymphangiosarcoma has also been described. Chylothorax (choice A) represents an accumulation of lymphedema in the pleural space. Exudates (choices D and E) are associated with acute inflammation. Dx: Lymphedema, breast cancer

A 50-year-old woman appears at your office. She was subjected to radical mastectomy and axillary node dissection for breast cancer a year ago. She now notices that her arm becomes swollen by the end of the day. What is the appropriate name for this fluid accumulation? (A) Chylothorax (B) Hydrothorax (C) Lymphedema (D) Purulent exudate (E) Fibrinous exudate

(A) Arterial embolism Cardiac myxoma is the most common primary tumor of the heart. One third of patients with a left atrial or left ventricular myxoma die from tumor embolization to the brain. Less likely causes of stroke in this patient with a cardiac myxoma include atherosclerosis (choice B) and hypertensive hemorrhage (choice D). Dx: Cardiac myxoma

A 50-year-old woman presents with fatigue and shortness of breath. Physical examination shows evidence of pulmonary edema, enlargement of the left atrium, and calcification of the mitral valve. A CT scan demonstrates a large obstructing mass in the left atrium. Before open heart surgery can be performed to remove the tumor, the patient suffers a stroke and expires. Which of the following hemodynamic disorders best explains the pathogenesis of stroke in this patient? (A) Arterial embolism (B) Atherosclerosis (C) Cardiogenic shock (D) Hypertensive hemorrhage (E) Septic shock

(E) Stasis Venous thrombosis is caused by the same factors that predispose to arterial thrombosis, namely endothelial injury, stasis, and a hypercoagulable state. Although all of the choices are risk factors for deep venous thrombosis, the most likely choice, given the patients' immobilization, is stasis. Most venous thromboses occur in the deep veins of the legs. Dx: Deep venous thrombosis

A 53-year-old man is hospitalized after injuring his neck in an automobile accident. He is placed in cervical traction. One week later, the patient develops painful swelling and erythema of his left calf. Doppler imaging discloses deep venous thrombosis. Which of the following is the most likely cause for the development of thrombosis in this patient? (A) Age (B) Endothelialdamage (C) Hypercoagulability (D) Infection (E) Stasis

D) Pulmonary infarction The figure shows a dark red hemorrhagic infarction extending to the pleura, a typical finding when a medium-sized thromboembolus lodges in a peripheral pulmonary artery branch. The infarct is hemorrhagic because the bronchial arterial circulation in the lung (derived from the systemic arterial circulation and separate from the pulmonary arterial circulation) continues to supply a small amount of blood to the interstitium in the affected area of infarction. Persons with underlying heart or lung disease are at greater risk for pulmonary infarction. Passive congestion, whether acute or chronic, is a diffuse process, as is edema, which does not impart a red color. Pulmonary venous thrombosis is rare.

A 53-year-old man with congestive heart failure develops pulmonary Streptococcus pneumoniae infection after a bout of influenza. After recuperating for 2 weeks, he notes pleuritic chest pain. The pain is caused by the development of the lesion shown in the figure. Which of the following events has most likely occurred in this man? A Acute pulmonary congestion B Chronic pulmonary congestion C Pulmonary edema D Pulmonary infarction E Pulmonary venous thrombosis

D) Lymphedema The surgery disrupted lymphatic return, resulting in functional lymphatic obstruction and lymphedema of the arm. The lymphatic channels are important in scavenging fluid and protein that have leaked into the extravascular tissues from the intravascular compartment. Although the amount of fluid that is drained through the lymphatics is not great, it can build up gradually. Cellulitis is caused by an infection of the skin and subcutaneous tissue, and displays erythema, warmth, and tenderness. Congestive heart failure can lead to peripheral edema, which is most marked in dependent areas such as the lower extremities and over the sacrum (in bedridden patients). Decreased plasma oncotic pressure from hypoalbuminemia, or sodium and water retention with heart or renal failure, leads to more generalized edema. Phlebothrombosis leads to swelling with pain and tenderness, but it is uncommon in the upper extremities.

A 56-year-old woman diagnosed with cancer in her left breast underwent a mastectomy with axillary lymph node dissection. Postoperatively, she develops marked swelling of the left arm that has persisted for 6 months. Now on physical examination, her temperature is 36.9° C. Her left arm is not tender or erythematous, and it is not painful with movement or to touch, but it is enlarged with a doughy consistency. Which of the following is the most likely mechanism for these findings? A Cellulitis B Congestive heart failure C Decreased plasma oncotic pressure D Lymphedema E Sodium and water retention F Phlebothrombosis

F Vitamin K deficiency His elevated prothrombin time that corrects with normal plasma points to coagulation factor deficiency, and factors II, VII, IX, and X are synthesized in the liver and affect this "extrinsic" in vitro coagulation pathway. They are vitamin K dependent and therefore may also be affected by warfarin therapy or by parenchymal liver disease. Antiphospholipid syndrome has an inhibitory effect upon in vitro coagulation tests and does not correct with addition of normal plasma. The factor V Leiden mutation leads to difficulty inactivating factor V by the action of protein C, thus causing thrombosis, not bleeding. Hemophilia A results from loss of factor VIII function and affects just the partial thromboplastin time (PTT). Scurvy from vitamin C deficiency affects vascular integrity, not coagulation factors. Gram-negative sepsis releases lipopolysaccharide that activates coagulation on a wide scale, consuming coagulation factors and platelets, so both the prothrombin time (PT) and PTT are elevated while the platelet count is decreased, typical for disseminated intravascular coagulopathy.

A 58-year-old man has had episodes of prolonged epistaxis in the past 6 months. On examination he has occult blood detected in his stool. Coagulation studies show that his prothrombin time is elevated, but his partial thromboplastin time (PTT), platelet count, and platelet function are all normal. When his plasma is mixed with an equal amount of normal plasma, the prothrombin time corrects to normal. Which of the following underlying diseases is most likely to be associated with these findings? A Antiphospholipid syndrome B Factor V Leiden mutation C Hemophilia A D Scurvy E Sepsis with Escherichia coli F Vitamin K deficiency

C) Congestive heart failure The figure shows a so-called nutmeg liver caused by chronic passive congestion from congestive heart failure. The elevated enzyme levels suggest that the process is so severe that hepatic centrilobular necrosis has also occurred. The physical findings suggest right-sided heart failure that can occur with pulmonary emphysema and pulmonary arterial hypertension. Biliary tract obstruction would produce bile stasis (cholestasis) with icterus. Hepatic congestion is not directly related to renal failure, and hepatorenal syndrome has no characteristic gross appearance. A portal vein thrombus would diminish blood flow to the liver, but it would not be likely to cause necrosis because of that organ's dual blood supply. The regular pattern of red lobular discoloration seen in the figure is unlikely to occur in hemorrhage from thrombocytopenia, characterized by petechiae and ecchymoses.

A 58-year-old man with pulmonary emphysema has a 10-year history of congestive heart failure. On physical examination, he has lower leg swelling with grade 2 pitting edema to the knees and prominent jugular venous distention to the level of the mandible. His serum levels of AST and ALT are increased. The representative gross appearance of his liver is shown in the figure. Which of the following underlying conditions is most likely to be present in this man? A Chronic renal failure B Common bile duct obstruction C Congestive heart failure D Portal vein thrombosis E Thrombocytopenia

(C) Increased intravascular hydrostatic pressure This patient with alcoholic cirrhosis has portal hypertension (increased hydrostatic pressure) and bleeding esophageal varices. Massive hematemesis is a frequent cause of death in patients with esophageal varices. Decreased intravascular oncotic pressure (choice A) contributes to the development of ascites in patients with cirrhosis but not to the development of esophageal varices. Dx: Esophageal varices, hematemesis

A 58-year-old woman is brought to the emergency department 4 hours after vomiting blood and experiencing bloody stools. The patient was diagnosed with alcoholic cirrhosis 2 years ago. Endoscopy reveals large esophageal varices, one of which is actively bleeding. Which of the following best explains the pathogenesis of dilated esophageal veins in this patient? (A) Decreased intravascular oncotic pressure (B) Increased capillary permeability (C) Increased intravascular hydrostatic pressure (D) Vasoconstriction of arterioles (E) Vasodilatation of capillaries

B Aggregation of platelets Aspirin blocks the cyclooxygenase pathway of arachidonic acid metabolism and generation of eicosanoids in platelets, including thromboxane A2, to block vasoconstriction and inhibit platelet aggregation. Platelet adhesion to extracellular matrix is mediated by interactions with von Willebrand factor. Tissue factor (factor III), produced by injured endothelium as well as subendothelial smooth muscle and fibroblasts, is released with tissue injury and is not platelet dependent. Endothelial cells produce von Willebrand factor independent of platelet action. Antithrombin III has anticoagulant properties because it inactivates several coagulation factors, but its function is not affected by aspirin.

A 59-year-old woman with a history of diabetes mellitus had a myocardial infarction 3 months ago. Her BMI is 35. She is now taking a low dose of aspirin to reduce the risk for recur- rent arterial thrombosis. On which of the following steps in hemostasis does aspirin have its greatest effect? A Adhesion of platelets to collagen B Aggregation of platelets C Production of tissue factor D Synthesis of von Willebrand factor E Synthesis of antithrombin III

F) Organization with occlusion The figure shows an organizing thrombus in a small artery. Such a peripheral arterial occlusion was insufficient to produce infarction, as evidenced by the lack of enzyme elevation. Thrombi become organized over time if they are not dis- solved by fibrinolytic activity. After a thrombus has formed, it may become organized with ingrowth of capillaries, fibroblast proliferation, and macrophage infiltration, which eventually clears part or most of the clot; there can be formation of one or more new lumens (recanalization). Air emboli are uncommon and usually the result of trauma. Air emboli on the arterial side can cause ischemia through occlusion even when very small, whereas on the venous side, more than 100 mL of air trapped in the heart may reduce cardiac output. When gases that became dissolved in tissues at high pressure bubble out at decompression with lower pressure in blood and tissues, then air emboli form. Cholesterol emboli can break off from atheromas in arteries and proceed distally to occlude small arteries; however, because these emboli are usually quite small, they are seldom clinically significant. Chronic passive congestion refers to capillary, sinusoidal, or venous stasis of blood within an organ such as the lungs or liver. Fat emboli are globules of lipid that are most likely to form after traumatic injury, typically to long bones. Mural thrombi are thrombi that form on the surfaces of the heart or large arteries.

A 59-year-old woman with hyperlipidemia has had anginal pain for the past 24 hours. Laboratory findings show no increase in serum troponin I or creatine kinase-MB. She is in stable condition 2 weeks later and has no chest pain, but a small artery in the epicardium has undergone the changes seen in the figure. Which of the following terms best describes this finding in this epicardial artery? A Air embolus B Cholesterol embolization C Chronic passive congestion D Fat embolism syndrome E Mural thrombosis F Organization with occlusion G Phlebothrombosis

(C) Deep venous thrombosis One of the most tragic calamities complicating hospitalization is the sudden death of a patient who appeared to be on the way to recovery. The cause of this catastrophe is often massive pulmonary embolism. A large pulmonary embolus may lodge at the bifurcation of the main pulmonary artery (saddle embolus), obstructing blood flow to both lungs. With acute obstruction of more than half of the pulmonary arterial tree, the patient experiences severe hypotension and may die within minutes. The other choices are causes of arterial embolism. Dx: Pulmonary thromboembolism

A 60-year-old man who is recovering from surgery to correct an abdominal aneurysm suddenly develops acute chest pain and dies. A thromboembolus at the bifurcation of the left and right pulmonary arteries is noted at autopsy (shown in the image). Which of the following is the most likely cause of this patient's pulmonary embolus? (A) Bacterial endocarditis (B) Complicated atherosclerotic plaque (C) Deep venous thrombosis (D) Paradoxical embolization (E) Right ventricular mural thrombus

(E) Vascular congestion and hemosiderin-laden macrophages Vascular congestion and hemosiderin-laden macrophages. Left ventricular failure leads to chronic passive congestion of the lungs. Blood leaks from the congested pulmonary capillaries into the alveoli. Alveolar macrophages degrade RBCs and accumulate hemosiderin. These hemosiderin-laden macrophages are called heart failure cells. Diffuse alveolar damage with hyaline membranes (choice A) is a feature of adult respiratory distress syndrome. Purulent exudate (choice B) is observed in bacterial pneumonia. Lymphocytic interstitial pneumonitis (choice C) is characteristic of viral pneumonitis. Plexiform lesions (choice D) are typically seen in patients with pulmonary hypertension. Dx: Congestive heart failure, pulmonary edema

A 60-year-old man with a history of multiple myocardial infarcts is hospitalized for shortness of breath. Physical examination reveals marked jugular distension, hepatomegaly, ascites, and pitting edema. A chest X-ray reveals cardiomegaly. The patient subsequently dies of cardiorespiratory failure. Examination of the lungs at autopsy would most likely dis- close which of the following pathologic changes? (A) Diffuse alveolar damage with hyaline membranes (B) Intra-alveolar purulent exudate (C) Lymphocytic interstitial pneumonitis (D) Pulmonary arteriopathy with plexiform lesions (E) Vascular congestion and hemosiderin-laden macrophages

B) Damage to endothelium Atherosclerotic damage to vascular endothelium is the most common cause of arterial thrombosis; this damage accumulates almost imperceptibly over many years. Diabetes mellitus types I and II accelerate atherosclerosis. Inhibitors to coagulation, such as antiphospholipid antibodies, typically prolong the partial thromboplastin time (PTT), the prothrombin time (PT), or both. Decreased levels of antithrombin III and mutation in the factor V gene are inherited causes of hypercoagulability; they are far less common than atherosclerosis of coronary vessels. Decreased production of tissue plasminogen activator from intact endothelial cells may occur in anoxia of the endothelial cells in veins with sluggish circulation. Stasis of blood flow is important in thrombosis within the low-pressure venous circulation.

A 60-year-old woman with a history of diabetes mellitus has had left-sided chest pain radiating to the arm for the past 5 hours. Serial measurements of serum creatine kinase-MB levels show an elevated level 24 hours after the onset of pain. Par- tial thromboplastin time (PTT) and prothrombin time (PT) are normal. Coronary angiography shows occlusion of the left anterior descending artery. Which of the following mechanisms is the most likely cause of thrombosis in this patient? A Antibody inhibitor to coagulation B Damage to endothelium C Decreased antithrombin III level D Decreased tissue plasminogen activator E Mutation in factor V gene F Stasis of blood flow

(C) Hemorrhage Pericardial fluid may accumulate rapidly, particularly with hemorrhage caused by a ruptured myocardial infarct, dissecting aortic aneurysm (seen in this patient), or trauma. In these circumstances, the pressure in the pericardial cavity exceeds the filling pressure of the heart, a condition termed cardiac tamponade. The term "electromechanical dissociation" refers to a heart rhythm that should produce a pulse, but does not. The most common cause of this condition is hypovolemia. The resulting precipitous decline in cardiac output is often fatal. The pathogenesis of dissecting aortic aneurysm in most instances can be traced to a weakening of the aortic media (cystic medial necrosis). Most patients have a history of hypertension. Disseminated intravascular coagulation (choice A) refers to widespread ischemic changes secondary to microvascular thrombi. Passive hyperemia (choice D) refers to the engorgement of an organ with venous blood. Dx: Dissecting aortic aneurysm

A 62-year-old man with a history of hypertension is rushed to the emergency room with severe "tearing pain" of the anterior chest. His blood pressure is 80/50 mm Hg. Physical examination shows pallor, diaphoresis, and a murmur of aortic regurgitation. Laboratory studies and ECG show no evidence of acute myocardial infarction. Four hours later, the patient goes into cardiac arrest. An ECG reveals electromechanical dissociation. Which of the following best explains the pathogenesis of cardiac tamponade in this patient? (A) Disseminated intravascular coagulation (B) Embolism (C) Hemorrhage (D) Passivehyperemia (E) Thrombosis

(D) Myocardial infarction Myocardial infarction is the most common cause of mural thrombi in the left ventricle. These mural thrombi are a common source of arterial thromboemboli. Such emboli may occlude cerebral arteries and cause cerebral infarcts, known clinically as strokes. Atrial fibrillation (choice A) predisposes to the formation of mural thrombi in that location. Dx: Mural thrombus

A 63-year-old man suffers a massive stroke and expires. At autopsy, the pathologist finds a laminated thrombus adherent to the wall of the left ventricle (shown in the image). Which of the following is the most likely cause of this autopsy finding? (A) Atrial fibrillation (B) Bacterial endocarditis (C) Marantic endocarditis (D) Myocardial infarction (E) Viral myocarditis

A) Blood culture positive for Citrobacter Progressive septic shock with poor tissue perfusion is evidenced by the high lactate level. Vasodilation is a feature of septic shock, typically as a result of gram-negative endotoxemia. Decreased hematocrit suggests hypovolemic shock from blood loss. Elevated creatine kinase suggests an acute myocardial infarction, which produces cardiogenic shock. Increased blood urea nitrogen concentration is a feature of renal failure, not the cause of renal failure. Reduction in Po2 suggests a problem with lung ventilation or perfusion.

A 63-year-old woman has had a fever and felt faint for the past 2 days. On physical examination, her temperature is 38.4° C, pulse is 101/min, respirations are 17/min, and blood pressure is 85/40 mm Hg. She has marked peripheral vasodilation. The serum lactic acid level is 6.8 mg/dL. Which of the following laboratory findings is most likely related to the cause of her clinical condition? A Blood culture positive for Citrobacter B Decreased hematocrit C Elevated serum creatine kinase D Increased blood urea nitrogen E Reduced PO2 on blood gas measurement

E Phlebothrombosis Venous stasis favors the development of phlebothrombosis (venous thrombosis), particularly in the leg and pelvic veins. This is a common complication in hospitalized patients who are bedridden. The obstruction may produce local pain and swelling, or it may be asymptomatic. Such deep thrombi in large veins create a risk for pulmonary thromboembolism. Phlebothrombosis occurs when stasis in large veins promotes thrombosis formation, typically in leg and pelvic veins; because there is often clinically apparent swelling, warmth, and pain, the term thrombophlebitis is often employed regardless of whether true vascular inflammation is present. The figure shows alternating pink platelet-fibrin and RBC layers (lines of Zahn) at the left. After a thrombus has formed, it may become organized with ingrowth of capillaries, fibroblast proliferation, and macrophage infiltration that eventually clears part or most of the clot, forming one or more new lumens (recanalization) as shown at the right of the figure. Atherosclerosis occurs in arteries, not veins. Chronic passive congestion refers to capillary, sinusoidal, or venous stasis of blood within an organ such as the lungs or liver. Vasculitis typically involves the vascular wall with inflammatory cell infiltrates. Mural thrombi are thrombi that form on the surfaces of the heart or large arteries. A vegetation is a localized thrombus formation on cardiac endothelium, typically a valve.

A 65-year-old woman sustained fractures of the right femur, pelvis, and left humerus in a motor vehicle collision. The fractures were stabilized, and the patient's recovery was uneventful. During a physical examination 3 weeks later, while still in the hospital, she has swelling and warmth in the left leg, and there is local pain and tenderness in the left thigh. Which of the following processes, as shown in the figure, is most likely occurring in her left femoral vein? A Atherosclerosis B Chronic passive congestion C Inflammation D Mural thrombosis E Phlebothrombosis F Vegetation

D) Tissue plasminogen activator Tissue plasminogen activator (t-PA) is a thrombolytic agent that promotes generation of plasmin, which cleaves fibrin to dissolve clots. Aspirin prevents formation of new thrombi by inhibiting platelet aggregation and works best as preventive therapy. Heparin prevents thrombosis by activating antithrombin III. Nitric oxide is a vasodilator. Vitamin K is required for synthesis of clotting factors II, VII, IX, and X and facilitates the ability to form clots.

A 66-year-old woman has the sudden onset of chest pain that radiates to her neck and left arm. On examination 30 minutes later, she is diaphoretic and hypotensive. Her serum troponin I level is elevated. Which of the following drugs is most likely to be administered emergently as thrombolytic therapy for this woman? A Acetylsalicylic acid (aspirin) B Low-molecular-weight heparin C Nitric oxide D Tissue plasminogen activator E Vitamin K

(B) Arterial thromboembolism Embolism of an artery of the leg leads to sudden pain, absence of pulses, and a cold limb. In some cases, the limb must be amputated. None of the other choices would cause this clinical presentation. Ruptured aortic aneurysm (choice E) presents with pain, shock, and a pulsatile mass in the abdomen. Dx: Arterial thromboembolism

A 67-year-old man presents with sudden left leg pain, absence of pulses, and a cold limb. His past medical history is significant for coronary artery disease and a small aortic aneurysm. Which of the following is most likely responsible for development of a cold limb in this patient? (A) Acute myocardial infarction (B) Arterial thromboembolism (C) Cardiogenic shock (D) Deep venous thrombosis (E) Ruptured aortic aneurysm

(A) Cardiogenic shock Cardiogenic shock is caused by myocardial pump failure. This condition usually arises as a result of a large myocardial infarction, but myocarditis may also be responsible. Conditions that prevent left or right heart filling reduce cardiac output, resulting in obstructive shock. Such conditions include pulmonary embolism, cardiac tamponade, and (rarely) atrial myxoma. The other choices do not reflect a loss of cardiac output secondary to the loss of myocardial tissue owing to ischemia. Dx: Acute myocardial infarction

A 68-year-old man develops sudden, severe substernal chest pain. Laboratory studies and ECG confirm an acute myocardial infarct. Despite vigorous therapy, the patient cannot maintain his blood pressure and expires 24 hours later. A cross section of the left ventricle is examined at autopsy (shown in the image). The arrows point to a soft, yellow area of necrosis. Which of the following was the most likely cause of death? (A) Cardiogenic shock (B) Hypovolemic shock (C) Neurogenic shock (D) Septic shock (E) Pulmonary edema

(B) Chronic passive congestion A generalized increase in venous pressure, typically from chronic heart failure, results in an increase in the volume of blood in many organs (e.g., liver, spleen, and kidneys). The liver is particularly vulnerable to chronic passive congestion because the hepatic veins empty into the vena cava immediately inferior to the heart. Budd-Chiari syndrome (thrombosis of the hepatic vein; choice E) may cause hepatomegaly, but it is not a complication of congestive heart failure. Dx: Congestive heart failure, nutmeg liver

A 68-year-old man with ischemic heart disease and a history of smoking complains of increasing shortness of breath. On physical examination, the patient has swollen legs, an enlarged liver, and fluid in the pleural spaces (bubbly rales are heard on oscultation). Which of the following hemodynamic disorders explains the pathogenesis of hepatomegaly in this patient? (A) Arterial thromboembolism (B) Chronic passive congestion (C) Deep venous thrombosis (D) Multiple hepatic infarcts (E) Thrombosis of the hepatic vein

(C) Heart The heart is the most common source of arterial thromboemboli, which usually arise from mural thrombi or diseased valves. These emboli tend to lodge at points where the vessel lumen narrows abruptly (e.g., at bifurcations or in the area of an atherosclerotic plaque). The viability of the tissue supplied by the vessel depends on the availability of collateral circulation and on the fate of the embolus itself. Paradoxical emboli from the right side of the circulation are exceedingly rare. Dx: Cerebral embolism, stroke

A 69-year-old man is brought to the emergency room complaining of visual difficulty and weakness. On physical examination, the patient is aphasic with a right-sided hemiplegia. Retinal hemorrhages are seen bilaterally. You suspect that a thromboembolus coursed to the left middle cerebral artery and smaller emboli traveled to the retinal arteries. Which of the following anatomic sites is the most likely source for these emboli in this patient? (A) Adrenals (B) Deep leg veins (C) Heart (D) Liver (E) Lungs

(E) Thromboembolism This patient with mild congestive heart failure developed pulmonary embolism. Small pulmonary emboli rarely cause infarctions because of the dual blood supply to the lungs and because oxygen can diffuse from the alveoli into lung tissue. Symptoms depend upon the extent of blockage of the pulmonary arterial tree, whether there is already cardiopulmonary disease, and whether pulmonary infarction occurs. The other choices do not induce these pleural signs and symptoms. Dx: Pulmonary thromboembolism

A 69-year-old retired man is brought to the emergency department because of the sudden onset of left-sided chest pain, which is exacerbated upon inspiration. Physical examination reveals dyspnea and hemoptysis. His temperature is 38°C (101°F), pulse 110 per minute, respirations 35 per minute, and blood pressure 158/100 mm Hg. A lateral chest wall friction rub is present on auscultation. The left leg is markedly edematous with a positive Homans' sign. A chest X-ray reveals a left pleural effusion. What is the most likely cause of this patient's pulmonary condition? (A) Congestive heart failure (B) Corpulmonale (C) Mitral stenosis (D) Subacute endocarditis (E) Thromboembolism

F) Increased salt retention This child has nephrotic syndrome with loss of albu- min into the urine and hypoalbuminemia that decreases plasma oncotic pressure, leading to movement of intravascular water into the extravascular compartment to produce edema. In response, hypovolemia with renal hypoperfusion induces increased production of renin, angiotensin, and aldosterone, which all promote sodium and water retention, further exacerbating his edema. Thiazide diuretics increase renal excretion of sodium. Hypovolemia would increase antidiuretic hormone output. Though corticosteroids are used to treat nephrotic syndrome caused by minimal change disease, the effect is probably to diminish abnormal T-cell function that is driving the glomerular damage. Cortisol leads to sodium retention, but not in response to hypovolemia.

A 7-year-old boy has had increasing lethargy for a week. On physical examination, he has periorbital edema and pit- ting edema at the ankles, but is normotensive and afebrile. Laboratory studies show marked albuminuria. He is given a thiazide diuretic and his urine output increases and his edema resolves. Which of the following changes most likely potenti- ated his edema? A Decreased aldosterone B Decreased renin C Increased albumin D Increased cortisol E Decreased antidiuretic hormone F Increased salt retention

D) Leg vein thrombosis The figure shows a large pulmonary thromboembolus. The most common risk factor is immobilization leading to venous stasis with phlebothrombosis, often called thrombophlebitis, since the lower extremities may be swollen and tender, but there is minimal inflammation. These thrombi form in the large deep leg or pelvic veins, not in the pulmonary arteries. Coagulopathies from acquired or inherited disorders, such as those from lupus anticoagulant (antiphospholipid antibodies) or factor V (Leiden) mutation, are possible causes of thrombosis, but they usually manifest at a younger age. These causes also are far less common risks for pulmonary thromboembolism than venous stasis. Local inflammation from pneumonia may result in thrombosis of small vessels in affected peripheral areas of lung. Pulmonary atherosclerosis occurs with long-standing pulmonary hypertension, not the factors driving systemic arterial atherosclerosis.

A 70-year-old man was hospitalized 3 weeks ago for a cerebral infarction. He is now is ambulating for the first time. Within minutes of returning to his hospital room, he has sudden onset of dyspnea with diaphoresis. He cannot be resuscitated. The gross appearance of the hilum of the left lung at autopsy is shown in the figure. Which of the following risk factors most likely contributed to this finding? A Antiphospholipid antibody B Bronchopneumonia C Factor V mutation D Leg vein thrombosis E Pulmonary arterial atherosclerosis

B) Gangrene of the foot The figure shows a mural thrombus at the right, filling an atherosclerotic aortic aneurysm below the renal arteries. Diabetes mellitus accelerates and worsens atherosclerosis, including peripheral muscular arteries. One possible complication of mural thrombosis is embolization, which occurs when a small piece of the clot breaks off. The embolus is carried distally and may occlude the popliteal artery, which is an end artery for the lower leg. A venous thrombus, not arterial, produces leg swelling from edema. Because the thrombus is in the arterial circulation, an embolus would not travel to the lungs. The thrombus is below the renal arteries. Although platelets contribute to the formation of thrombi, the platelet count does not decrease appreciably with formation of a localized thrombus, and a generalized process such as disseminated intravascular coagulation is needed to consume enough platelets to cause thrombocytopenia.

A 71-year-old man with a history of diabetes mellitus died of an acute myocardial infarction. At autopsy, the aorta, opened longitudinally and with the superior aspect of the kidneys below the forceps, appeared as shown in the figure. Which of the following complications associated with this aortic disease would most likely have been present during his life? A Edema of the left leg B Gangrene of the foot C Pulmonary thromboembolism D Renal infarction E Thrombocytopenia

(A) Abdominal aorta In patients with severe aortic atherosclerosis, embolization of atheromatous debris into the renal arteries and vascular tree may cause acute renal failure. Cholesterol clefts are observed in the photomicrograph shown. None of the other choices are sources of renal atheroemboli. Dx: Renal infarct, arterial embolism

A 72-year-old man is dead on arrival after collapsing at home. Renal cortical infarcts are noted at autopsy. A section through the arcuate artery is shown. Which of the following is the most likely source of the atheroembolus occluding this artery? (A) Abdominal aorta (B) Common carotid artery (C) Inferior vena cava (D) Left ventricle (E) Mesenteric artery

(E) Pulmonary edema Patients in left-sided congestive heart failure complain of shortness of breath (dyspnea) on exertion and when recumbent (orthopnea). They may be awakened from sleep by sudden episodes of shortness of breath (paroxysmal nocturnal dyspnea). Physical examination usually reveals distended jugular veins. Persons with right-sided failure have pitting edema of the lower extremities and an enlarged and tender liver. Patients in congestive heart failure with pulmonary edema have crackling breath sounds (rales) caused by the expansion of fluid-filled alveoli. Cardiac tamponade (choice B) occurs when the pressure in the pericardial cavity rises to exceed the filling pressure of the heart. Orthopnea is not a feature of the other choices. Dx: Congestive heart failure

A 72-year-old woman complains of shortness of breath on exertion. She states that she also becomes short of breath at night unless she uses three pillows (orthopnea). Physical examination reveals mild obesity, bilateral pitting leg edema, an enlarged liver and spleen, and fine crackling sounds on inspiration (rales). A chest X-ray shows cardiomegaly. What is the most likely cause of orthopnea in this patient? (A) Asthma (B) Cardiac tamponade (C) Emphysema (D) Hypovolemic shock (E) Pulmonary edema

E) Pulmonary thromboembolism He has deep venous thrombosis as a consequence of venous stasis from immobilization. The large, deep thrombi in leg veins can embolize to the lungs, leading to death. Disseminated intravascular coagulation is not a common complication in patients with thrombosis of the extremities or in patients recuperating from an injury. Fat embolism can occur with fractures, but pulmonary problems typically appear 1 to 3 days after the traumatic event. Gangrene typically occurs from arterial, not venous, occlusion in the leg. Vessels with thrombi typically stay intact; if a hematoma had developed as a consequence of the trauma from the fall, it would be organizing and decreasing in size after 2 weeks.

A 75-year-old man is hospitalized after falling and fracturing his left femoral trochanter. Two weeks later, the left leg is swollen, particularly below the knee. He experiences pain on movement of the leg; on palpation, there is swelling and tenderness. Which of the following complications is most likely to occur in this man? A Disseminated intravascular coagulation B Fat embolism syndrome C Gangrenous necrosis of the foot D Hematoma of the thigh E Pulmonary thromboembolism

(C) Hemorrhage from bronchial arteries The gross and microscopic appearance of an infarct depends on its location and age. Pale infarcts are typically seen in the heart, kidneys, and spleen. Red infarcts may result from either arterial or venous occlusion. They are distinguished from pale infarcts by bleeding into the necrotic area from adjacent arteries and veins. Red infarcts occur principally in organs with a dual blood supply, such as the lung, or those with extensive collateral circulation, such as the small intestine and brain. In the heart, a red infarct occurs when the infarcted area is reperfused, as may occur following spontaneous or therapeutically induced lysis of the occluding thrombus. Grossly, red infarcts are sharply circumscribed, firm, and dark red to purple. Over a period of several days, acute inflammatory cells infiltrate the necrotic area from the viable border. The cellular debris is phagocytosed and digested by polymorphonuclear leukocytes and later by macrophages. Granulation tissue eventually forms, to be replaced ultimately by a scar. None of the other choices would cause hemorrhage into an infarct. Dx: Pulmonary infarction, pulmonary thromboembolism

A 76-year-old woman is brought to the emergency department because of the sudden onset of two episodes of hemoptysis and left-sided chest pain, which is exacerbated upon inspiration. Her temperature is 38°C (101°F), pulse 110 per minute, respirations 35 per minute, and blood pressure 158/100 mm Hg. The patient is admitted, but suffers a massive stroke and expires 48 hours later. Autopsy reveals a pulmonary infarct in upper segments of the lower lobe (shown in the image). Which of the following best explains the color of this patient's pulmonary infarct? (A) Accumulation of hemosiderin-laden macrophages (B) Development of bronchopneumonia (C) Hemorrhage from bronchial arteries (D) Organization of a pulmonary thromboembolus (E) Passive congestion of bronchopulmonary segments

F) Vegetation A thrombotic mass that forms on a cardiac valve (or, less commonly, on the cardiac mural endocardium) is known as a vegetation. Such vegetations may produce thromboemboli. Vegetations on the right-sided heart valves may embolize to the lungs; vegetations on the left embolize systemically to organs such as the brain, spleen, and kidney. A so-called paradoxical embolus occurs when a right-sided cardiac thrombus crosses a patent foramen ovale and enters the systemic arterial circulation. Patients with malignant neoplasms may have a hypercoagulable state (Trousseau syndrome) that favors the development of arterial and venous thromboses. Atherosclerosis occurs within arteries, not the chambers of the heart. Endocardial metastases are quite rare. Chronic passive congestion refers to capillary, sinusoidal, or venous stasis of blood within an organ such as the lungs or liver. Mural thrombi are thrombi that form on the surfaces of the heart or large arteries. The term typically is reserved for large thrombi in a cardiac chamber or dilated aorta or large aortic branch; it is not used to describe thrombotic lesions on cardiac valves. A myxoma is a primary neoplasm of the heart that usually arises on an atrial surface; it is not associated with malignancies elsewhere. Phlebothrombosis occurs when stasis in large veins promotes thrombosis formation.

A 77-year-old woman has a brief fainting episode. She was diagnosed 1 year ago with pancreatic adenocarcinoma. On auscultation of her chest, a heart murmur is heard. Echocardiography shows a 1-cm nodular lesion on the superior aspect of an intact anterior mitral valve leaflet. A blood culture is negative. Which of the following terms best describes this mitral valve lesion? A Atheroma B Chronic passive congestion C Mural thrombus D Myxoma E Phlebothrombosis F Vegetation

(B) Congestive heart failure Chronic failure of the left ventricle constitutes an impediment to the exit of blood from the lungs and leads to chronic passive congestion of the lungs. The pressure in the alveolar capillaries increases, and the vessels become engorged with blood. Microhemorrhages release erythrocytes into the alveolar spaces, where they are degraded by alveolar macrophages. The released iron, in the form of hemosiderin, remains in the macrophages, which are then labeled "heart failure cells." None of the other choices are consistent with chronic microhemorrhages in the lung. Dx: Congestive heart failure

A 78-year-old woman dies in her sleep. A Prussian blue stain of the lungs at autopsy is shown in the image. Which of the following is the most likely cause of these histopathologic findings? (A) Acute myocardial infarction (B) Congestive heart failure (C) Diffuse alveolar damage (D) Hereditary hemochromatosis (E) Pulmonary infarction

(B) Infarct Volvulus is an example of intestinal obstruction in which a segment of gut twists on its mesentery, thereby kinking the bowel and usually interrupting the blood supply. Ischemia leads to infarction and intestinal gangrene (this case). Volvulus is virtually always a consequence of an underlying congenital abnormality. Defective intestinal rotation in fetal life leads to abnormal positions of the small intestine and colon, anomalous attachments, and bands. The clinical importance of such rotational anomalies lies in their propensity to cause catastrophic volvulus of the small and large intestine and incarceration of the bowel in an internal hernia. Malrotation of the bowel permits undue mobility of the bowel loops and predisposes to midgut volvulus. When the cecum or right colon is invested with a mesentery rather than being retroperitoneal, the result may be cecal volvulus. An unusually long sigmoid colon, which occurs sometimes in patients with idiopathic constipation, permits the development of sigmoid volvulus. Meconium ileus in babies with cystic fibrosis may be complicated by volvulus and intestinal atresia. Ecchymosis (choice A), petechia (choice C), and purpura (choice D) represent hemorrhages of various sizes in the skin. Dx: Volvulus, ischemic colitis

A 9-month-old infant is brought to the emergency room with a 3-hour history of intense abdominal pain and bloody diarrhea. Physical examination reveals a tender abdomen without ascites. The child dies 24 hours later, and torsion (volvulus) of the small bowel is discovered at autopsy. The small bowel appears dilated and hemorrhagic (shown in the image). Which of the following best describes these pathologic findings? (A) Ecchymosis (B) Infarct (C) Petechia (D) Purpura (E) Ulcer

(E) Septic shock Septic shock results from a systemic inflammatory response syndrome that leads to multiple organ dysfunction and hypotension. Clinical features include two or more signs of systemic inflammation (e.g., fever, tachycardia, tachypnea, leukocytosis, or leukopenia) in the setting of a known cause of inflammation. These processes often progress to multiple organ dysfunction syndrome in critically ill patients. Septicemia with Gram-negative organisms is the most common cause of septic shock. Anaphylactic shock (choice A) occurs as a consequence of a systemic type I hypersensitivity reaction. Neurogenic shock (choice D) can follow acute injury to the brain or spinal cord, which impairs the neural control of vasomotor tone, leading to generalized vasodilation. Cardiogenic shock (choice B) is a feature of advanced heart failure. Hypovolemic shock (choice C) occurs following blood loss.

A 92-year-old woman is brought unconscious to the emergency room from a nursing home. Her blood pressure is 70/30 mm Hg. She is febrile (38°C/100.5°F) and tachypneic. Laboratory studies demonstrate a WBC count of 22,000/μL with 92% neutrophils. Urinalysis reveals numerous Gram-negative organisms. Which of the following most likely accounts for this patient's signs and symptoms? (A) Anaphylactic shock (B) Cardiogenic shock (C) Hypovolemic shock (D) Neurogenic shock (E) Septic shock

C) Increased hydrostatic pressure She has congestive heart failure, with bilateral diffuse pulmonary infiltrates due to edema. The left side of her heart has failed, which increases hydrostatic pressure in the pulmonary vasculature. The higher pressure forces fluid to leak into the alveoli, and it is then coughed up. Note the enlarged heart with prominent border of the left atrium in the figure. This fluid is a transudate because there is little protein or cells present. The kidneys can generally compensate for decreased salt intake, but in modern society we suffer from too much dietary salt, not too little. Edema from hypoalbuminemia is not limited to the lungs, and it is more likely to appear in areas of loose connective tissue, such as the periorbital region. She is afebrile, so the pulmonary infiltrates are unlikely to represent pneumonia that could locally produce edema in regions of inflammation. Pulmonary venous obstruction is typical for pulmonary thromboembolism that may lead to right-sided heart failure and peripheral edema if chronic.

A 94-year-old woman has dyspnea and an increasing cough with frothy sputum production for the past month. She is afebrile. A chest radiograph shows the findings in the figure. Which of the following is the most likely mechanism for development of her pulmonary infiltrates? A Decreased sodium intake B Hypoalbuminemia C Increased hydrostatic pressure D Inflammation E Pulmonary venous obstruction

E) Vasoconstriction The initial response to arteriolar injury is vasoconstriction, since there is smooth muscle in the vessel wall. But this is transient, and the coagulation mechanism must be initiated to maintain hemostasis. Fibrin polymerization is part of secondary hemostasis after the vascular injury is initially closed. Neutrophils are not essential to hemostasis. Platelet aggregation occurs with release of factors such as ADP, but this takes several minutes. Protein C is involved in anticoagulation to counteract clotting.

A superficial puncture wound from a needlestick injury leads to a small amount of bleeding in a healthy person. Sec- onds after this injury occurs, the bleeding stops. Which of the following mechanisms is most likely to stop small arteriolar blood loss from this injury? A Fibrin polymerization B Neutrophil chemotaxis C Platelet aggregation D Protein C activation E Vasoconstriction

(C) Increased intravascular hydrostatic pressure In patients with congestive heart failure, venous engorgement of the lung leads to accumulation of a transudate in the alveoli. Chronic left ventricle failure impedes blood flow out of the lungs and leads to passive pulmonary congestion. As a result, pressure in the alveolar capillaries increase (increased hydrostatic pressure) and these vessels become engorged with blood. Increased pressure forces fluid from the blood into the alveolar spaces, resulting in pulmonary edema, which interferes with gas exchange. The photomicrograph shows pink staining fluid in the alveoli. None of the other choices cause pulmonary edema in patients with congestive heart failure. Dx: Pulmonary edema, congestive heart failure

An 80-year-old woman with a history of hypertension is rushed to the emergency room complaining of chest pain of 1-hour duration. Physical examination discloses bilateral pit- ting leg edema, hepatosplenomegaly, and rales at the bases of both lungs. The patient is apprehensive and sweating. The patient loses consciousness and dies of a cardiac arrhythmia. Microscopic examination of the lungs at autopsy is shown. Which of the following hemodynamic processes best explains this pathologic finding? (A) Decreased capillary permeability (B) Decreased intravascular oncotic pressure (C) Increased intravascular hydrostatic pressure (D) Increased intravascular oncotic pressure (E) Vasoconstriction of precapillary arterioles

B Lipopolysaccharide The patient has septic shock from infection with gram-negative organisms that have lipopolysaccharide, which binds along with other microbe-derived sub- stances containing pathogen-associated molecular patterns (PAMPs) to cells via Toll-like receptors (TLRs). Binding initiates release of various cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) that produce fever. Macrophages are stimulated to destroy the organisms. Nitric oxide is released, promoting vasodilation and circulatory collapse. Complement C3b generated by bacteria via the alternative pathway acts as an opsonin. Platelet- activating factor mediates many features of acute inflammation and in large quantities can cause vasoconstriction and bronchoconstriction. Toxic shock syndrome toxin-1 is a superantigen released by staphylococcal organisms that is a potent activator of T lymphocytes, inducing cytokine release with septic shock.

An 80-year-old woman with dysuria for 1 week now has a fever. On examination, her temperature is 37.9° C, pulse 103/min, and blood pressure 80/40 mm Hg. She has right flank pain. A urinalysis shows numerous WBCs. Her plasma lactate is increased. Urine culture and blood culture grow Escherichia coli. Which of the following is most likely to con- tribute to her cardiovascular collapse by triggering Toll-like cell receptors? A Complement C3b B Lipopolysaccharide C Nitric oxide D Platelet-activating factor E Toxic shock syndrome toxin-1

C) Hematoma He has a subdural hematoma from this traumatic injury causing tearing of cerebral veins. A hematoma is a collection of blood in a potential space or within tissue. Congestion occurs when there is vascular dilation with pooling of venous blood within an organ. Ecchymoses are blotchy areas of hemorrhage beneath skin, serosal surfaces, or mucous membrane surfaces from a contusion (bruise), which he likely has on the back of his head. Petechiae are 1- to 2-mm pinpoint areas of hemorrhage. Purpura denotes blotchy hemorrhage on skin, serosal surfaces, or mucous membrane surfaces larger than 3 mm; areas from 1 to 2 cm in size are called ecchymoses.

An 85-year-old man falls in the bathtub and strikes the back of his head. Over the next 24 hours, he becomes increasingly somnolent. A head CT scan shows an accumulation of fluid beneath the dura, compressing the left cerebral hemisphere. Which of the following terms best describes this collection of fluid? A Congestion B Ecchymosis C Hematoma D Petechiae E Purpura

(B) Hypotensive shock Myocardial infarcts are described as transmural (through the entire wall) or subendocardial. A transmural infarct results from complete occlusion of a major extramural coronary artery. Subendocardial infarction reflects prolonged ischemia caused by partially occluding lesions of the coronary arteries when the requirement for oxygen exceeds the supply. Such a situation prevails in disorders such as shock, anoxia, or severe tachycardia. Thrombotic occlusion (choices D and E) is more likely to cause transmural myocardial infarcts. Dx: Myocardial infarction

An autopsy of a 70-year-old woman reveals a subendocardial, circumferential infarct of the left ventricle. This type of infarct is most commonly associated with which of the following? (A) Deep venous thrombosis (B) Hypotensive shock (C) Pericardial tamponade (D) Thrombotic occlusion of the right coronary artery (E) Thrombotic occlusion of the circumflex artery

D) Petechiae Note the small punctate 1- to 2-mm petechial hemorrhages on the epicardial surface shown in the figure. Such hemorrhages most often result from reduced numbers of platelets or reduced platelet function. It is platelets that plug small vascular defects. Congestion occurs when there is vascular dilation with pooling of blood within an organ. A hematoma is a collection of blood in a potential space or within tissue. Purpura denotes blotchy hemorrhage on skin, serosal surfaces, or mucous membrane surfaces larger than 3 mm; areas from 1 to 2 cm in size are called ecchymoses.

An autopsy study is performed to correlate patterns of hemorrhage with underlying causes. Patients with the gross appearance of hemorrhage shown in the figure had minimal blood volume loss, but an appearance similar to this in many other organs. Which of the following terms best describes this pattern? A Congestion B Ecchymosis C Hematoma D Petechiae E Purpura

(C) Organization Once formed, arterial thrombi may undergo (1) lysis, (2) propagation, (3) organization, (4) canalization, or (5) embolization. Organization refers to the invasion of connective tissue elements, which causes a thrombus to become firm and appear grayish white. Canalization (choice A) is the process by which new lumina lined by endothelial cells form within an organized thrombus. Propagation (choice D) implies an increase in size. Dx: Mural thrombus

Histologic examination of the heart in the patient described in the previous question (63-year-old man with myocardial infarction) shows extensive growth of fibroblasts and deposition of collagen in the mural thrombus. Which of the following terms describes this outcome of thrombosis? (A) Canalization (B) Hyalinization (C) Organization (D) Propagation (E) Regeneration

(B) Disseminated intravascular coagulation The clinical presentation of amniotic fluid embolism can be dramatic, with the sudden onset of cyanosis and shock, followed by coma and death. If the mother survives the acute episode, she may die of DIC. Should she overcome this complication, she is at risk of developing acute respiratory dis- tress syndrome. DIC is a thrombotic microangiopathy. Fibrin thrombi form in small blood vessels because of uncontrollable coagulopathy, which consumes fibrin and other coagulation factors. Once coagulation factors are depleted, uncontrollable hemorrhage ensues. None of the other choices are complications of amniotic fluid embolism. Dx: Amniotic fluid embolism

If the patient described in the previous question (amniotic fluid embolism) had survived the acute episode of cyanosis and shock, she would have been at risk for developing which of the following life-threatening complications? (A) Bacterialendocarditis (B) Disseminated intravascular coagulation (C) Fatembolism (D) Neurogenicshock (E) Septicshock

A) Adenosine diphosphate ADP is released from the platelet-dense granules and is a potent stimulator of platelet aggregation. ADP also stimulates further release of ADP from other platelets. Many other substances involved in hemostasis, such as fibrinogen, fibronectin, and factors V and VIII, are stored in the α granules of platelets. Thromboxane A2, another powerful aggregator of platelets, is synthesized by the cyclooxygenase pathway. Fibronectin forms part of the extracellular matrix between cells that "glues" them together. Plasminogen is activated to promote thrombolysis. Platelet aggregation requires active platelet metabolism; platelet stimulation by agonists such as ADP, thrombin, collagen, or epinephrine; the presence of calcium or magnesium ions and specific plasma proteins such as fibrinogen or von Willebrand factor (vWF); and a plate- let receptor, the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. Platelet stimulation results in the generation of intracellular second messengers that transmit the stimulus back to the platelet surface, exposing protein-binding sites on GPIIb/ IIIa. Fibrinogen then binds to GPIIb/IIIa and cross-links adjacent platelets to produce platelet aggregates; vWF binds to drive shape change and granule release. The patients in this experiment could have Glanzmann thrombasthenia, in which platelets are deficient or defective in the GPIIb/IIIa complex, do not bind fibrinogen, and cannot form aggregates, although the platelets can be stimulated by ADP, can undergo shape change, and are of normal size.

In an experiment, platelet function is analyzed. A sub- stance is obtained from the dense body granules of normal pooled platelets from healthy blood donors. When this sub- stance is added to platelets obtained from patients with a bleeding disorder, no platelet aggregation occurs. Adding the substance to platelets from a normal control group induces platelet aggregation. Which of the following substances is most likely to produce these effects? A Adenosine diphosphate B Antithrombin III C Fibronectin D Fibrinogen E Plasminogen F Thromboxane A2

E) Thrombomodulin Thrombomodulin is present on intact endothelium and binds thrombin, which then inhibits coagulation by activating protein C. Normally, thrombin activates factors V, VIII, and IX, and also stabilizes the secondary hemostatic plug by activating factor XIII, which cross-links fibrin. Thrombin helps activate platelets. Calcium is a cofactor that assists clotting in the coagulation cascade (ethylene-diaminetetraacetic acid [EDTA] in some blood collection tubes binds calcium to prevent clotting). Fibrin protein forms a meshwork that is essential to thrombus formation. Platelet factor 4 is released from the α granules of platelets and promotes platelet aggregation during the coagulation process. Prothrombin is converted to thrombin in the coagulation cascade. Tumor necrosis factor (TNF) is not significantly involved in coagulation.

In an experiment, thrombus formation is studied in areas of vascular damage. The propagation of a thrombus in an area of vascular injury to adjacent normal arteries is prevented. Which of the following substances diminishes thrombus propagation by activating protein C? A Calcium B Fibrin C Platelet factor 4 D Prothrombin E Thrombomodulin F Tumor necrosis factor (TNF)

(E) Intravenous drug use Embolism is the pas- sage through the venous or arterial circulations of any material capable of lodging in a blood vessel and, thereby, obstructing its lumen. Intravenous drug abusers who use talc as a carrier for illicit drugs may introduce it into the lung via the blood- stream (i.e., venous embolism). None of the other choices exhibit bi-refringence under polarized light. Dx: Pulmonary embolism, talc embolism

The body of a 28-year-old homeless man is brought to the coroner's office. Histologic examination of the lungs under polarized light is shown. Which of the following is the most likely cause of the bi-refringence observed in this pulmonary lesion? (A) Alcoholism (B) Aspiration of mineral oil (C) Bacterial pneumonia (D) Cocaine abuse (E) Intravenous drug use

(E) Sinusoids dilated with blood In patients with chronic passive congestion of the liver, the central veins of the hepatic lobule become dilated. The increased venous pressure leads to dilation of the sinusoids and pressure atrophy of the centrilobular hepatocytes. Grossly, the cut surface of the chronically congested liver exhibits dark foci of centrilobular congestion surrounded by paler zones of unaffected peripheral portions of the lobules. The result resembles a cross section of a nutmeg and is appropriately called nutmeg liver. Longstanding passive congestion leads to bridging fibrosis; however, only in the most extreme cases is the fibrosis sufficiently severe to justify the label cardiac cirrhosis (choice D). None of the other choices are associated with congestive heart failure. Dx: Congestive heart failure, nutmeg liver

The patient described in Question 13 suffers a massive heart attack and expires. Microscopic examination of the liver at autopsy would most likely reveal which of the following his-topathologic changes? (A) Diffuse hydropic degeneration (B) Large iron deposits within hepatocytes (C) Massive hepatic necrosis (D) Regenerating hepatic nodules surrounded by fibrous bands (E) Sinusoids dilated with blood