Hemodynamic disorders (part 1)

the partial thromboplastin time (PTT) assay screens the function of the proteins in the intrinsic pathway (factors 1, and 2)

1: 2, 5, 8, 9, 10, 11, 12 2: fibrinogen

genetic deficiency of GpIb results in a bleeding disorder called 1

1: Bernard-Soulier syndrome

inherited deficiency of GpIIb-IIIa results in a bleeding disorder called 1

1: Glanzmann thrombasthenia

white infarcts occur with 1 in solid organs with end-arterial circulations (e.g., heart, spleen, and kidney), and where tissue density limits the seepage of blood from adjoining patent vascular beds

1: arterial occlusions

thrombi can develop anywhere in the cardiovascular system 1 thrombi typically arise at sites of endothelial injury or turbulence 2 thrombi characteristically occur at sites of stasis

1: arterial or cardiac thrombi 2: venous thrombi (phlebothrombosis)

pulmonary emboli originate from 1

1: deep venous thromboses

endothelial injury leading to platelet activation almost inevitably underlies thrombus formation in the 1 and the 2, where the high rates of blood flow impede clot formation

1: heart 2: arterial circulation

the cellular and tissue effects of shock are essentially those of 1 and are caused by a combination of 2 and 3

1: hypoxic injury 2: hypoperfusion 3: microvascular thrombosis

stages of shock: - an 1 stage during which reflex compensatory mechanisms are activated and vital organ perfusion is maintained - a 2 stage characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic derangement, including acidosis - an 3 stage in which cellular and tissue injury is so severe that even if the hemodynamic defects are corrected, survival is not possible

1: initial nonprogressive stage 2: progressive stage 3: irreversible stage

most systemic emboli (80%) arise from 1; 2/3 of these are associated with 2 and another 25% with 3

1: intracardiac mural thrombi 2: left ventricular infarcts 3: dilated left atria (e.g., secondary to mitral valve disease)

in most tissues, the main histologic finding associated with infarcts is 1

1: ischemic coagulative necrosis

the primary consequence of systemic embolization is 1 of downstream tissues, whereas embolization in the pulmonary circulation leads to 2

1: ischemic necrosis (infarction) 2: hypoxia hypotension, and right-sided heart failure

pulmonary edema is a common clinical problem. It is seen most frequently in the setting of 1, but also may occur in 2

1: left ventricular failure 2: renal failure acute respiratory distress syndrome, and inflammatory and infectious disorders of the lung

subcutaneous edema is most pronounced in the 1 with standing and the 2 with recumbency

1: legs 2: sacrum

thrombi can have grossly (and microscopically) apparent laminations called 1

1: lines of Zahn

edema resulting from renal dysfunction or nephrotic syndrome often manifests first in 1

1: loose connective tissues (e.g., the eyelids, causing periorbital edema)

pulmonary emboli derive primarily from 1

1: lower-extremity deep vein thrombi

septic shock is triggered by 1 and is associated with severe 2

1: microbial infections 2: systemic inflammatory response syndrome (SIRS)

thrombi on heart valves are called 1

1: vegetations

red infarcts occur:

(1) as a result of venous occlusions (2) in loose tissues (3) in tissues with dual circulations (4) in previously congested tissues (5) when flow is reestablished after infarction has occurred

what are the primary abnormalities that lead to intravascular thrombosis?

(1) endothelial injury (2) stasis or turbulent blood flow, and (3) hypercoagulability of the blood (the so-called "Virchow triad")

define congestion:

- an increase in blood volume within a tissue - a passive process resulting from impaired outflow of venous blood from a tissue

define hyperemia:

- an increase in blood volume within a tissue - is an active process resulting from arteriolar dilation and increased blood inflow

name 4 types of hemorrhage:

- hematoma (accumulate within a tissue) - petechiae (1-2 mm) - purpura (3-5 mm) - ecchymoses (1-2 cm)

describe the general sequence of events leading to hemostasis at a site of vascular injury:

1) arteriolar vasoconstriction 2) primary hemostasis: the formation of the platelet plug 3) secondary hemostasis: deposition of fibrin 4) clot stabilization and resorption

systemic emboli derive primarily from 1

1: cardiac mural or valvular thrombi, aortic aneurysms, or atherosclerotic plaques

the prothrombin time (PT) assay assesses the function of the proteins in the extrinsic pathway (factors 1, and 2)

1: 2 (prothrombin), 5, 7, 10 2: fibrinogen

A 28-year-old woman is evaluated for possible thrombophilia since she has had two episodes of deep vein thrombosis, as well as two pregnancies that terminated in spontaneous abortion. The activated partial thromboplastin time is prolonged, and she has a positive VDRL screening test for syphilis. This combination of findings is most suggestive of (A) antiphospholipid antibody syndrome. (B) disseminated intravascular coagulation. (C) factor V Leiden. (D) methylene tetrahydrofolate reductase mutation. (E) prothrombin 20210A transition.

a

A 40-year-old woman presents with a "skin rash." Questioning reveals easy bruising on minimal trauma, menorrhagia, and frequent bouts of epistaxis. She is not taking any medications, and there is no history of toxic exposures. Physical examination reveals multiple petechial hemorrhages, most prominently on the dependent portions of the lower extremities. Splenomegaly is not detected. Laboratory studies reveal marked thrombocytopenia, and a bone marrow aspiration reveals increased numbers of megakaryocytes. Which of the following is the most likely mechanism of this disorder? (A) Antibody-mediated platelet destruction (B) DIC, with consumption of platelets and coagulation factors (C) Intravascular spontaneous lysis of platelets due to increased osmotic fragility (D) Myeloid stem cell suppression in the bone marrow, with inability to produce platelets (E) Physical destruction of platelets while negotiating through partially blocked microvasculature

a

A 60-year-old chronic alcoholic with known alcoholic cirrhosis presents with upper gastrointestinal hemorrhage. Despite prolonged tamponade, bleeding is persistent. A coagulation defect related to the liver disease is suspected. Which of the following abnormalities is most consistent with this possibility? (A) Deficiency of all clotting factors except for vWF (B) Deficiency of factors II, VII, IX, and X (C) Deficiency of factors II, V, VII, and X (D) Deficiency of factors IX, X, XI, and XII (E) Deficiency of vWF

a

During a laboratory exercise on coagulation testing, a 23-year-old medical student is found to have a prolonged bleeding time. She has had a long history of "easy bleeding," with frequent bleeding of the gums, epistaxis, cutaneous bleeding, and menorrhagia. Further testing revealed a deficiency of von Willebrand factor. Which of the following thrombogenic processes involving platelets is most directly impaired? (A) Adhesion (B) Conformational change with activation of phospholipid surface (C) Formation of fibrinogen bridges (D) Release reaction (E) Stabilization of platelet plug

a

define embolus:

an embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction

define infarction:

an infarct is an area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue

name 3 variables that influence infarct development:

anatomy of the vascular supply rate of occlusion tissue vulnerability to hypoxia

define atherosclerosis:

atherosclerosis is a major cause of arterial thromboses because it is associated with the loss of endothelial integrity and with abnormal blood flow

A 36-year-old man dies during cardiac surgery. He had a history of long-standing rheumatic heart disease with mitral stenosis. At autopsy, the pathologist reports findings consistent with mitral stenosis and noted the presence of "heart failure cells." This finding results from (A) activation of the coagulation cascade. (B) chronic passive congestion of the lungs. (C) hypoxic myocardial injury. (D) myocardial hyperemia.

b

name 4 functions of thrombin:

conversion of fibrinogen into crosslinked fibrin platelet activation proinflammatory effects anti-coagulant effects

A 35-year-old woman presents with fever, fatigue, mucocutaneous bleeding, and changing neurologic signs. Laboratory examination reveals thrombocytopenia, anemia, and reticulocytosis, as well as increased concentrations of creatinine and urea nitrogen. Examination of a peripheral blood smear reveals many fragmented circulating red cells (helmet cells and schistocytes). The most likely diagnosis is (A) Bernard-Soulier disease. (B) DIC. (C) ITP. (D) TTP. (E) von Willebrand disease.

d

A 60-year-old man with unstable angina (a form of acute coronary syndrome) is treated with an intravenously administered glycoprotein IIb-IIIa inhibitor. The mechanism of action of this agent is the ability to (A) dilate coronary arteries. (B) inhibit atherogenesis. (C) inhibit platelet adhesion. (D) inhibit platelet aggregation. (E) lyse thrombi.

d

A 7-year-old boy presents with palpable purpura on the buttocks and legs, fever, abdominal pain and vomiting, arthritis in his knees and ankles, melena, and hematuria. His mother states that he had an upper respiratory illness approximately 1 week ago, but has otherwise been well. Blood tests reveal mild renal insufficiency. The most likely cause of the bleeding into the skin observed in this patient is (A) coagulation factor deficiency. (B) qualitative platelet dysfunction. (C) quantitative platelet dysfunction. (D) vasculitis. (E) vitamin deficiency.

d

define disseminated intravascular coagulation (DIC):

disseminated intravascular coagulation (DIC) is widespread thrombosis within the microcirculation that may be of sudden or insidious onset

A 14-year-old girl presents with prolonged bleeding from wounds and minor trauma and severe menorrhagia. Family history reveals that her father also has prolonged bleeding from wounds and minor trauma, as does her brother. Which of the following is the most likely mechanism of this patient's disorder? (A) Absence of platelet glycoprotein IIb-IIIa (B) Antiplatelet antibodies reacting with platelet surface glycoproteins (C) Deficiency of factor VIII (D) Deficiency of factor IX (E) Deficiency of vWF

e

A 26-year-old woman dies after a short illness beginning in the late stages of labor. At autopsy, blood vessels in the lungs contained fetal debris (e.g., squamous cells, vernix, mucin), as did other vessels of multiple organs. Review of the clinical history reveals that she had become acutely ill with dyspnea, hypotension, and seizures, and a chest radiograph had demonstrated evidence of pulmonary edema. This was all followed by prolonged hemorrhage from the vagina and generalized bleeding from multiple other sites. The changes that were found within multiple blood vessels most likely are (A) bone marrow emboli. (B) fat emboli. (C) gas emboli. (D) septic emboli. (E) widespread thrombosis.

e

A 56-year-old man is surgically treated by a four-vessel coronary artery bypass graft procedure and placed on prophylactic daily aspirin therapy. Aspirin has been shown to prevent recurrent myocardial infarction through its ability to inhibit the synthesis of (A) adenosine diphosphate (ADP). (B) leukotriene B4 (LTB4). (C) nitric oxide (NO). (D) prostaglandin I2 (PGI2). (E) thromboxane A2 (TxA2).

e

An 86-year-old man with a history of recurrent urinary tract infection presents with fever, tachypnea, tachycardia, mental obtundation, and reduced blood pressure. Which of the following forms of shock is most likely? (A) Anaphylactic shock (B) Cardiogenic shock (C) Hypovolemic shock (D) Neurogenic shock (E) Septic shock

e

Two days following a cholecystectomy, a 32-year-old hospitalized woman has sudden onset of dyspnea, pleural pain, and cough productive of frothy, blood-tinged sputum. Ventilation-perfusion scintigraphy indicates a perfusion defect. If it were possible to examine a portion of the affected lung, which of the following would most likely have been found? (A) Air embolism (B) Anemic (white or pale) infarct (C) Disseminated intravascular coagulation (DIC) (D) Generalized thrombosis (E) Hemorrhagic (red) infarct

e

define edema:

edema is an accumulation of interstitial fluid within tissues. The fluid may be protein poor (transudate) or protein rich (exudate)

platelets contain proteins involved in coagulation. Name 3 of them:

fibrinogen coagulation factor 5 vWF

platelets contain proteins involved in wound healing. Name 4 of them:

fibronectin platelet factor 4 (a heparin-binding chemokine) platelet-derived growth factor (PDGF) transforming growth factor-β

define hemorrhage:

hemorrhage, defined as the extravasation of blood from vessels, is most often the result of damage to blood vessels or defective clot formation

define hemostasis:

hemostasis is a process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, which serves to prevent or limit the extent of bleeding

define hypercoagulability:

hypercoagulability refers to an abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors

name 4 symptoms of hypovolemic and cardiogenic shock:

hypotension weak rapid pulse tachypnea cool, clammy, cyanotic skin

name 5 causes of edema:

increased hydrostatic pressure: - impaired venous return - arteriolar dilation reduced plasma osmotic pressure (hypoproteinemia) lymphatic obstruction sodium retention inflammation

name 5 factors believed to play major roles in the pathophysiology of septic shock:

inflammatory and counterinflammatory responses endothelial activation and injury induction of a procoagulant state metabolic abnormalities organ dysfunction

thromboembolism lies at the heart of 3 major causes of morbidity and death in developed countries. Name them:

myocardial infarction pulmonary embolism (PE) cerebrovascular accident (stroke)

name the 3 effects of endothelium:

platelet inhibitory effects anticoagulant effects fibrinolytic effects

define platelets:

platelets play a critical role in hemostasis by forming the primary plug that initially seals vascular defects and by providing a surface that binds and concentrates activated coagulation factors

describe the fate of a thrombus:

propagation embolization dissolution organization and recanalization

name 3 platelet inhibitory factors of endothelium:

prostacyclin (PGI2) nitric oxide (NO) adenosine diphosphatase

name 4 types of infarcts:

red infarcts white infarcts septic infarcts bland infarcts

define shock:

shock is a state in which diminished cardiac output or reduced effective circulating blood volume impairs tissue perfusion and leads to cellular hypoxia

name 1 symptom of septic shock:

skin may be warm and flushed owing to peripheral vasodilation

name 1 fibrinolytic factor of endothelium:

t-PA

define coagulation cascade:

the coagulation cascade is a series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot

define mural thrombus:

thrombi occurring in heart chambers or in the aortic lumen

name 4 anticoagulant factors of endothelium:

thrombomodulin endothelial protein C receptor heparin-like molecules tissue factor pathway inhibitor (TFPI)

A 50-year-old man has been in the medical intensive care unit for septic shock for the past few days. He has now developed rectal bleeding, epistaxis, and gingival bleeding. DIC is suspected. Which of the following sets of results for a panel of screening tests is most consistent with this diagnosis? (A) Normal bleeding time, PT, APTT, thrombin time, and platelet count (B) Prolonged bleeding time, PT, APTT, and thrombin time; reduced platelet count (C) Prolonged PT and APTT; normal bleeding time, platelet count, and thrombin time (D) Prolonged PT and APTT; reduced plate- let count; normal bleeding time and thrombin time (E) Prolonged bleeding time, PT, and APTT; normal platelet count and thrombin time

b

A 55-year-old woman with chronic pancreatitis undergoes coagulation screening tests before surgery. The PT and APTT are found to be prolonged. Given the following choices, which of the following is the most likely reason for the abnormal coagulation test results? (A) Congenital inherited bleeding disorder (B) Fat malabsorption and vitamin K deficiency (C) Glutamate deficiency due to impaired digestion of dietary protein (D) Nutritional vitamin C deficiency (E) Post-pancreatitic carcinoma of the pancreas

b

A 56-year-old physician who has had a recent episode of unstable angina is advised by his cardiologist to take one "baby aspirin" a day because of the antithrombotic effect of aspirin. What is the mechanism by which aspirin acts as an antithrombotic agent? (A) Acetylation and activation of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) (B) Acetylation and inhibition of both COX-1 and COX-2 (C) Selective inhibition of COX-1 (D) Selective inhibition of COX-2

b

A 70-year-old man seeks medical attention because of shortness of breath on minimal exertion. A posteroanterior chest radiograph reveals blunting of the right costophrenic sulcus interpreted as a right-sided pleural effusion. The aspirated fluid is straw colored and clear. The protein concentration is low, and the specific gravity is 1.011. Microscopic examination reveals an occasional mesothelial cell. Which of the following is the most likely cause of the effusion? (A) Decreased oncotic pressure (B) Left ventricular heart failure (C) Mesothelioma (D) Pneumonia (E) Tuberculosis

b

A bedridden elderly patient experiences the sudden onset of pleuritic pain and hemoptysis. The underlying lesion that led to this complication was most likely located in which of the following sites? (A) Hepatic veins (B) Lower extremity veins (C) Pelvic veins (D) Portal vein (E) Pulmonary veins

b

Fluid is aspirated from the grossly distended abdomen of a 47-year-old chronic alcoholic man. The fluid is straw colored and clear and is found to have a protein content (largely albumin) of 2.5 g/dL. Which of the following is a major contributor to the fluid accumulation in this patient? (A) Blockage of lymphatics (B) Decreased oncotic pressure (C) Decreased sodium retention (D) Increased capillary permeability (E) Inflammatory exudation

b

A 23-year-old man undergoes surgery for fractures of the pelvis and left femur resulting from a high-speed motor vehicle accident. The following day he develops dyspnea, speech difficulties, and a petechial skin rash. Which of the following types of embolism is the likely cause of these findings? (A) Air (B) Amniotic fluid (C) Fat (D) Paradoxical (E) Thrombotic

c

A 25-year-old man has a lifelong hemorrhagic diathesis. The PT and bleeding time are normal, but the APTT is prolonged. The most likely cause of the bleeding disorder is (A) a platelet functional disorder. (B) factor VII deficiency. (C) factor VIII deficiency. (D) factor IX deficiency. (E) von Willebrand disease.

c

A 4-year-old boy presents with recurrent joint pain involving the knees and hips. He had always bruised easily, and recently the parents had seen blood in his urine. A presumptive diagnosis of classic hemophilia (hemophilia A) is made, and coagulation blood tests are performed. Which of the following is the most likely set of findings of coagulation screening tests? (A) Normal bleeding time, platelet count, and thrombin time; prolonged PT and APTT (B) Normal bleeding time, platelet count, thrombin time, and APTT; prolonged PT (C) Normal bleeding time, platelet count, thrombin time, and PT; prolonged APTT (D) Normal platelet count and thrombin time; prolonged bleeding time, PT, and APTT (E) Prolonged bleeding time, PT, APTT, and thrombin time; decreased platelet count

c

A 50-year-old right-handed man with a long history of rheumatic heart disease with mitral stenosis and atrial fibrillation is brought to the emergency department after collapsing to the floor at home. He is unable to speak or walk and has right hemiplegia with a right extensor plantar response. These findings most likely result from embolism to which of the following arteries? (A) Anterior cerebral (B) Anterior communicating (C) Middle cerebral (D) Posterior communicating (E) Superior cerebellar

c

An 80-year-old woman presents with recent onset of primary hemostatic (mucocutaneous) bleeding. Questioning reveals that she has been maintaining a "tea and toast" diet for the past 4 months. Her gums are hemorrhagic and spongy in consistency, and gingival bleeding is evident. Perifollicular hyperkeratotic papules, each surrounded by a hemorrhagic halo, are scattered over the lower extremities, and each papule surrounds a twisted, corkscrew-like hair. A nutritional deficiency is suspected. Deficiency of which of the following nutrients is most likely related to the findings in this patient? (A) Vitamin A (B) Vitamin B12 (C) Vitamin C (D) Vitamin K (E) Protein

c

3 major types of shock:

cardiogenic shock hypovolemic shock septic shock