Chapter IV Flashcards
Refers to one of the fate of thrombus where additional platelet and fibrin accumulates.
Propagation
Refers to one of the fate of thrombus where the thrombi get dislodged and travel to other sites in the vasculature
Embolization
Refers to one of the fate of thrombus where dissolution of the thrombus occurs due to fibrinolysis
Dissolution
Refers to one of the fate of thrombus where older thrombi become
organized by the ingrowth of endothelial cells, smooth
muscle cells, and fibroblasts
Organization and recanalization
Site of venous embolization
Lungs
Where does superficial venous thrombi typically occur?
Saphenous veins
What type of venous thrombosis that more often embolize to the lungs and give rise to pulmonary infarction?
Deep Vein Thrombosis
What type of thrombosis is asymptomatic in 50% of cases and is associated with hypercoagulable states?
Deep Vein Thrombosis
What is a
major cause of arterial thromboses due to its association
with loss of endothelial integrity and with abnormal blood
flow?
Atherosclerosis
This disease may engender atrial mural thrombi by causing atrial dilation and fibrillation.
rheumatic heart
Can predispose
to cardiac mural thrombi by causing dyskinetic myocardial
contraction and endocardial injury.
Myocardial infarction
What are the components of the Virchow Triad?
- Endothelial injury
- Abnormal Blood Flow
- Hypercoagulability
Give three (3) disorders of primary hypercoagulability states?
- Factor V Leiden
- Increased prothrombin synthesis
- Antithrombin III deficiency
Give five (5) disorders that cause secondary hypercoagulability states?
- bed rest
- tissue damage
- malignancy
- development of aPL antibodies [antiphospholipid antibody syndrome]
- antibodies against PF4/heparin complexes [heparin-induced thrombocytopenia]
Widespread thrombosis within the microcirculation which is a complication of a large number of conditions associated with systemic activation of thrombin.
Disseminated Intravascular Coagulation (DIC)
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
Embolus
What are the most
common form of thromboembolic disease?
Pulmonary Embolism (PE)
Embolus that is lodged in the pulmonary artery bifurcation.
Saddle Embolus
Venous embolus passes through an
interatrial or interventricular defect and gains access to the
systemic arterial circulation.
paradoxical embolism
A condition where cardiovascular collapse occurs when emboli obstruct 60% or more of the pulmonary circulation
Cor pulmonale
Where does most systemic emboli arise from?
intracardiac mural thrombi
Is characterized by pulmonary insufficiency, neurologic symptoms, anemia, and thrombocytopenia, and is fatal in 5% to 15% of cases.
Fat embolism syndrome
Refers to the presence of microscopic fat
globules in the vasculature after fractures of long bones.
Fat Embolism
These substances in the circulation coalesce to form frothy masses that obstruct vascular flow and cause distal
ischemic injury
Gas bubbles (Air Embolism)
Introduction of what amount of air in the circulation may be fatal?
300-500 ml at 100ml/sec
What type of gas comes out of solution in the tissues and the blood in decompression sickness?
Nitrogen
Pertains to a painful condition caused by rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints.
The bends
Pertains to the presence of gas bubbles in the lung vasculature that cause edema, hemorrhage, and focal atelectasis or emphysema, leading to a form of respiratory distress
Chokes
Pertains to a disease characterized by persistence of gas emboli in the skeletal system leads to multiple foci of ischemic necrosis; the more common sites are the femoral heads, tibia, and humeri.
Caisson disease
Is a complication of labor characterized by sudden severe dyspnea, cyanosis, and shock, followed by neurologic impairment ranging from headache to seizures and coma, and by DIC.
Amniotic Fluid Embolism
Is an event that causes ischemic necrosis due to occlusion of either the arterial supply or the venous drainage.
Infarction
What underlies the vast majority of infarctions?
Arterial thrombosis or arterial embolism
Give three (3) organs that produce white infarcts when occluded.
Heart
Spleen
Kidney
Give two (2) organs that produce red infarcts when occluded.
Lungs
Small Intestines
How many hours does it take for dead tissue to show microscopic evidence of necrosis?
4-12 hours
This type of infarction occurs when infected cardiac valve vegetations
embolize or when microbes seed necrotic tissue.
Septic Infarction
What is the most important determinant
factor of whether vessel occlusion will cause tissue damage after an infarction?
Availability of an
alternative blood supply is
Is a state of circulatory failure that impairs tissue
perfusion and leads to cellular hypoxia.
Shock
Shock that results from low cardiac output due to
myocardial pump failure.
Cardiogenic Shock
Shock that results from low cardiac output due
to low blood volume,
Hypovolemic Shock
Is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
Sepsis
is a sepsis-like condition associated with systemic inflammation that may be triggered by a variety of nonmicrobial insults, such as burns, trauma, and/or
pancreatitis.
Systemic inflammatory response syndrome (SIRS)
What are the likely initiators of inflammation in sepsis?
Signaling pathways that lie downstream of Toll-like receptors
What are the microbe-derived substances that Toll-like receptors (TLRs) recognize?
- Pathogen associated molecular pattern (PAMPs)
- Damage-associated molecular pattern (DAMPs)
What are the cytokines and inflammatory mediators involved in septic shock?
- TNF
- IL1
- IL12
- IL18
- Interferon-y
- High-mobility group box 1 (HMGB1)
Complement system that are Anaphylatoxin
C3a, C5a
Complement system that is a Chemotactic fragment
C5a
Complement system responsible for Opsonization
C3b
What coagulation factor can microbes directly activate?
Factor XII
What are the anticoagulants that decrease in septic shock?
Tissue Factor Pathway Inhibitor, Protein-C, Thrombomodulin
Is a serine protease inhibitor that is the principal inhibitor of tPA that is increased in septic shock which dampens fibrinolysis.
PAI-1 (Plasminogen Activator Inhibitor-1)
Which transporter is impaired by proinflammatory cytokines in septic shock leading to suppression of insulin release while simultaneously promote insulin resistance?
Glucose Transporter-4 (GLUT-4)
Is a rare but life-threatening disorder associated with bilateral adrenal hemorrhage, caused by fulminant meningococcemia.
Waterhouse-Friderichsen syndrome
Are polyclonal T-lymphocyte activators that induce the release of high levels of cytokines that result in a variety of clinical manifestations, ranging from a diffuse rash to vasodilation, hypotension, shock, and death.
Superantigens
Refers to fluid accumulation in the tissues
Edema
Refers to fluid accumulation in the body cavities
Effusion
Where does fluid drained into the lymphatic vessels pass to return to the bloodstream?
Thoracic duct
This type of fluid accumulates in the interstitial space due to increase in vascular permeability caused by inflammatory mediators.
Exudate (protein-rich)
What is the main cause of increased hydrostatic pressure?
Disorders that impair venous return
This condition is an important cause of albumin loss in which albumin leaks into the urine through abnormally permeable glomerular capillaries.
Nephrotic Syndrome
Is microscopically, appreciated as clearing and separation of the extracellular matrix (ECM) and subtle cell swelling.
Edema
This type of edema can be
diffuse or more conspicuous in regions with high hydrostatic
pressures. Its distribution is often influenced by gravity
Subcutaneous Edema
This type of edema yields a frothy, blood-tinged fluid—a mixture of air, edema, and extravasated red cells
Pulmonary Edema
Are typically protein-poor,
translucent, and straw colored.
Transudative effusions
Are peritoneal effusions
caused by lymphatic blockage, which may be
milky due to the presence of lipids absorbed from the gut
Chylous Effusion
Are protein-rich and often cloudy due to the presence of white cells.
Exudative Effusion
What are the causes of edema?
- Increased hydrostatic pressure
- Decreased colloid osmotic pressure
- Increased vascular permeability
- Lymphatic obstruction
- Sodium and water retention
Is an active
process in which arteriolar dilation (e.g., at sites of inflammation
or in skeletal muscle during exercise) leads to
increased blood flow. Affected tissues turn red (erythema)
because of increased delivery of oxygenated blood.
Hyperemia
Is a passive process resulting from reduced venous
outflow of blood from a tissue. It can be systemic, as in cardiac failure, or localized, as in isolated venous obstruction.
Congested tissues have an abnormal blue-red color (cyanosis)
that stems from the accumulation of deoxygenated hemoglobin in the affected area.
Congestion
Microscopically , is marked by engorged alveolar capillaries, alveolar septal edema, and focal intra-alveolar hemorrhage.
acute pulmonary congestion
Is often caused by congestive heart failure, the septa are
thickened and fibrotic, and the alveoli often contain numerous
macrophages laden with hemosiderin
chronic pulmonary congestion
the central vein and sinusoids are distended. Because the centrilobular
area is at the distal end of the hepatic blood supply, centrilobular hepatocytes may undergo ischemic necrosis, and the periportal hepatocytes—better oxygenated because of proximity to hepatic arterioles—may only develop fatty change.
acute hepatic congestion
the centrilobular regions are grossly redbrown
and slightly depressed (because of cell death) and are accentuated against the surrounding zones of uncongested tan
liver (nutmeg liver)
chronic passive
hepatic congestion
Microscopically, there is centrilobular congestion and hemorrhage, hemosiderin-laden macrophages, and variable degrees of hepatocyte dropout and necrosis
chronic passive
hepatic congestion
Is a precisely orchestrated 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.
Hemostasis
What are the events leading to hemostasis?
- Arteriolar Vasoconstriction
- Primary Hemostasis: platelet plug
- Secondary Hemostasis: fibrin deposition
What mediates the immediate arteriolar vasoconstriction after injury?
Endothelin
Are disc-shaped anucleate cell fragments that are shed from megakaryocytes in the bone marrow into the bloodstream.
Platelets
What type of platelet granules have the
adhesion molecule P-selectin on their membranes
α-Granules
What platelet granules contain adenosine diphosphate
(ADP), adenosine triphosphate, ionized calcium, serotonin,
and epinephrine.
Dense (or δ) granules
What receptors mediate platelet adhesion?
- GpIb (platelet) to
vWF (subendothelial matrix) - GpIa/IIa (platelet) to subendothelial collagen
Which glycoprotein increases platelet affinity to fibrinogen on cell surface?
GpIIb/IIIa
What bleeding disorder has a deficiency in GpIb?
Bernard-Soulier Syndrome
What bleeding disorder has a deficiency in GpIIb/IIIa?
Glandzmann Thrombasthenia
Thrombin activates platelets through which G-protein coupled receptor?
Protease activated receptor-1 (PAR-1)
ADP binds to which G-protein coupled receptors?
P2Y1 and P2Y12
a large bivalent plasma polypeptide that forms bridges between
adjacent platelets, leading to their aggregation and allows binding of fibrinogen to platelets.
GpIIb/IIIa
What are the vitamin K dependent coagulation and anticoagulation factors?
IX, X, VII, II
Protein C and S
What is the anti-coagulation action of warfarin
Inhibition of y-carboxylation of vitamin k dependent coagulation factors though blocking the functions of vitamin k epoxide reductase complex in the liver
What is the cofactor of factors IXa-X + Ca?
Factor VIIIa
What is the cofactor of factors Xa-II?
Factor Va
What is the anticoagulation action of coumadin?
Antagonizes y-carboxylated glutamic acid use of vitamin K.
What coagulation factors do Prothrombin Time assess?
Factors VII, X, V, II (prothrombin), and fibrinogen
What are added to the plasma to measure Prothrombin time
Tissue Factor, phospholipids and calcium
APTT measures which coagulation factors?
XII, XI, IX, VIII, X, V, II and fibrinogen
Deficiency with this/these coagulation factor/s are/is associated with moderate to severe bleeding disorders
Factors V, VII, VIII, IX, X
Deficiency with this/these coagulation factor/s are/is associated with mild bleeding disorders
Factor XI
Deficiency with this/these coagulation factor/s are/is incompatible with life
Prothrombin
Deficiency with this/these coagulation factor/s do not bleed and may be susceptible to thrombosis.
Factor XII
What complex is the most important activator of factor IX?
Tissue factor/Factor VIIa complex
What complex is the most important activator of factor X?
Factor IXa/Factor VIIIa
What breaks down fibrin and interferes with its polymerization?
Plasmin
What activates plasminogen to plasmin?
factor XII–dependent pathway or by plasminogen activators (tPA)
Which factor/s is/are inactivated by active protein C and protein S
Factor Va and VIIIa
What are the substances are secreted by the endothelial cells that prevent platelet aggregation?
Prostacyclin, Nitric Oxide and adenosine diphosphate
What are the substance is secreted by the endothelial cells that binds and subsequently inactivates thrombin, factors IXa and Xa?
Anti-thrombin III
Anti-thrombin binds with heparin-like molecules to inactivate which coagulation factors?
Factor IXa, Xa, XIa, XIIa
Most common inherited cause of hypercoagulability.
Point mutations in factors V gene and prothrombin gene
Is an autosomal dominant mutation that renders factor V resistant to cleavage and inactivation by protein C.
Factor V Leiden
A single nucleotide change (G20210A) in the 3′-untranslated region of the prothrombin gene is another common mutation
Prothrombin gene mutation
Affected individuals typically present with venous thrombosis
and recurrent thromboembolism beginning in adolescence
or early adulthood.
deficiencies of anticoagulants such as antithrombin III, protein C, or protein S
Elevated levels of homocysteine may
be inherited or acquired. Marked elevations of homocysteine
may be caused by an inherited deficiency of this enzyme.
Cystathione B-synthetase
Acquired causes of homocysteinemia included deficiency in the following vitamins:
Vitamin B6, B12, folic acid
is a serious, potentially life-threatening disorder that occurs following the administration of unfractionated heparin
Heparin-Induced Thrombocytopenia (HIT) Syndrome
is an autoimmune disorder characterized by:
* Presence of one or more antiphospholipid (aPL) autoantibodies
* Venous or arterial thromboses, or pregnancy complications
such as recurrent miscarriages, unexplained fetal death, and
premature birth.
Antiphospholipid Antibody Syndrome (APS)
Proteins that are recognized by APL antibodies
cardiolipin and B2-glycoprotein I
Lupus antigen
Thrombi often have grossly and microscopically apparent
laminations which are pale platelet and fibrin deposits alternating with darker red cell–rich layers
lines of Zahn,
are gelatinous and have a dark-red dependent portion where red
cells have settled by gravity and a yellow “chicken fat” upper
portion, and are usually not attached to the underlying vessel
wall.
Postmortem clots
sterile verrucous
endocarditis that can occur in the setting of systemic lupus erythematosus
Libman-Sacks endocarditis
