Thrombosis, Embolism, Infarction Flashcards
LO #1: Define thrombosis, differentiate hemostatic versus pathologic thrombosis,
and summarize the 3 major predisposing factors.
Thrombosis is formation of a blood clot (thrombus) within a
blood vessel in response to vessel wall damage. Recall from the
“Introduction to Blood” lecture that the hemostatic system consists of
multiple independent, but closely related, components that function to
maintain blood fluidity and to promote localized, temporary thrombus
formation at sites of vascular injury (hemostatic thrombus). Pathologic
thrombosis occurs when this balance is lost and a clot forms at a site with
only minimal endothelial injury or the thrombus is not localized.
LO #2: Describe the features that differentiate a true thrombus from a postmortem
clot.
Thrombi can be differentiated from post-mortem blood clots. A postmortem clot usually lacks the tissue-like consistency of a thrombus and
has a more gelatinous appearance. In addition, true thrombi fill or distend
the vessel, may be attached to the vessel wall and have lines of Zahn.
Lines of Zahn are laminations produced by alternating pale layers of
platelets admixed with fibrin and darker layers of RBCs. Lines of Zahn are
most apparent in the heart or aorta, and not so apparent in veins or
smaller arteries where blood flow is more sluggish.
LO #3: Describe the mechanism whereby factor V Leiden and the prothrombin gene
mutation lead to hypercoagulability.
Factor V Leiden Mutation - A point mutation in factor V results in
replacement of arginine by glutamine at amino acid residue 506,
resulting in a mutated factor V, known as factor V Leiden (FVL).
FVL is the most commonly identified cause of inherited
thrombosis. This mutated Factor V is resistant to inactivation by
activated protein C (activated protein C resistance), resulting in
loss of one of the major coagulation system inhibitors.
• Prothrombin Gene Mutation - A point mutation in the
prothrombin gene results in increased levels of prothrombin
that results in increased fibrin formation.
LO #4: Describe the potential fates of a thrombus and their clinical significance.
If a patient survives the initial vascular obstruction
caused by the thrombus, thrombi will undergo some combination of the
following events:
1) Dissolution – Cleared by the fibrinolysis
2) Embolization – Portions of the thrombus dislodge and travel
through the vasculature to other sites of the body. Emboli lodge in
small vessels and cause partial or complete occlusion; this may
cause ischemic necrosis (infarction) of distal tissue.
3) Propagation – Accumulation of more platelets and fibrin leads to
growth of the thrombus.
4) Organization and recanalization – Thrombus undergoes fibrosis
(organization) and may eventually be recanalized (reestablish
blood flow).
LO #5: Define embolism and describe different types (thromboemboli, fat, air,
amniotic fluid) and their causes/risk factors
Intravascular material (solid, liquid, or gas) that is carried
through the vascular system from its site of origin to a distant site, where
it typically lodges, resulting in occlusion of a vessel. The majority of
emboli are thromboemboli, a detached fragment of a thrombus. Other
rare forms of embolism include globules of fat, gas (air, nitrogen) and
amniotic fluid.
Systemic Thromboembolism:
These are thromboemboli within the arterial circulation. Most arise from
thrombi in the cardiac chambers in the setting of myocardial infarcts and
atrial fibrillation. Other sources include aortic aneurysms and thrombi on
ulcerated atherosclerotic plaques. The major sites for arterial
embolization are the lower extremities (75%) and the brain (10%).
Fat Embolism: These emboli are due to release of fatty marrow into damaged blood
vessels. They are most frequently seen after blunt trauma with bone
fractures; other less common causes include acute pancreatitis,
pathologic fractures, and joint reconstruction. In most cases, these are
asymptomatic. Rarely, patients will experience respiratory distress,
neurologic symptoms, anemia and thrombocytopenia (fat embolism
syndrome).
Air Embolism:
Air may gain entry into the vascular system during medical procedures
(central venous catheter placement – most common), trauma, diving
(decompression sickness, “the bends”), and child birth. Small air bubbles
may coalesce and obstruct flow of blood in the right heart, pulmonary
circulation and cerebral vessels. The severity of symptoms depends on
the location and amount of air entering the circulation.
Amniotic Fluid Embolism:
Rare, catastrophic complication of pregnancy in which amniotic fluid, fetal
squamous cells, and/or hair enter the maternal circulation causing
cardiovascular collapse. In addition, the contents of amniotic fluid activate
coagulation resulting in a consumptive coagulopathy called disseminated
intravascular coagulation (widespread clotting organ ischemia;
consumption of clotting factors and platelets bleeding). Characterized
by sudden onset of severe difficulty breathing (dyspnea), cyanosis, and
shock; followed by neurological symptoms (headache, seizures, coma).
5th most common cause of maternal mortality worldwide; mortality is up to
80%. Estimated to occur in 1/8,000-1/80,000 pregnancies.
LO #6: Describe the pathophysiologic consequences and potential outcomes of
pulmonary embolism.
Incidence data for PE vary from study to study. Studies have estimated
that one million people in the U.S. are affected by PE each year, with
100,000-200,000 of these being fatal. PE is the cause of death in 10-15%
of hospitalized patients. In most (95%) cases, the emboli originate from a
DVT. Depending on the size of the embolus, it may occlude the main
pulmonary artery, the pulmonary artery bifurcation (saddle embolus) or
pass out into the smaller vessels.
Pathophysiologic consequences:
1) Ventilation of a non-perfused segment of lung leads to
respiratory compromise
2) Increased resistance to pulmonary blood flow as a result of
vascular obstruction leads to hemodynamic compromise
Outcomes:
1) Most are small and clinically silent (60-80%).
2) Sudden death, right heart failure (cor pulmonale) or
cardiovascular collapse occurs when >60% of the pulmonary
circulation is obstructed with emboli.
3) Embolic obstruction of medium-sized arteries may result in
pulmonary hemorrhage but usually does not cause infarction
because of the dual blood flow from the bronchial circulation.
Infarction may occur in patients with impaired bronchial circulation
due to poor cardiovascular function
4) Pulmonary hypertension (2-3%) - usually multiple episodes of
small thromboemboli
Clinical symptoms: acute onset of chest pain, cough, shortness of
breath, rapid heart rate (tachycardia) and rapid respirations
(tachypnea)
LO #7: Define infarction and describe the clinical significance.
An infarct is an area of ischemic necrosis caused by occlusion
of either the arterial supply or the venous drainage. More than half of all
deaths In the U.S. are caused by infarction, particularly myocardial and
cerebral infarction. Most (~99%) result from thrombotic or embolic events
involving arteries. Other, less common causes include vasospasm,
twisting of vessels (torsion), compression of blood supply, or traumatic
rupture of a vessel.
LO #8: Compare and contrast the gross and microscopic features of red and white
infarcts; explain why they occur in different organs
Infarcts are classified based on their color, which is a
reflection of the amount of hemorrhage into the affected tissue.
1) White (pale) infarcts occur with arterial occlusion in organs with
end-arterial circulation (no/minimal collaterals, no dual blood
supply): heart, kidney, spleen.
2) Red infarcts occur in the following settings:
a) venous occlusion (e.g., ovarian or testicular torsion)
b) tissues with dual circulation (lung, small intestine) that allow
blood flow from an unobstructed parallel supply into a necrotic zone. Blood flow from this secondary circulation is not
sufficient to keep the tissue alive.
c) loose tissues (such as lung), which allow blood to collect in the
infracted zone
d) flow is re-established to a site of previous necrosis due to
arterial occlusion (re-perfusion)
LO #9: Summarize the factors that influence the development of an infarct
Not every tissue that suffers a cessation of
blood flow will undergo necrosis. What factors influence development
of an infarct?
1) Nature of vascular supply. The availability of an alternative
blood supply is the most important factor in determining
whether occlusion of a vessel will result in infarction. Lungs
and liver, for example, have dual circulation. These organs are
therefore relatively insensitive to small occlusions if the
alternative blood supply is intact.
2) Rate of development of occlusion. Slowly developed
occlusions allow time for collateral circulation to develop and
are less likely to cause infarction as a result. For example,
small connections exist between the 3 major coronary arteries;
they normally have minimal flow, but in the setting of a slowly
developing narrowing of the coronary artery, flow within this
collateral circulation may increase enough to prevent
infarction.
Vulnerability to hypoxia. Tissues that are particularly
sensitive to hypoxia are more likely to infarct.
a. Neurons undergo irreversible change within 3-4 min
b. Cardiac myocytes die after 20-30 min. of ischemia
c. Fibroblasts in myocardium can last several hours
4) Oxygen content of blood. Patients with anemia or pulmonary
disease (low oxygen delivery to blood) are more susceptible to
even partial flow obstructions of a small vessel that under
normal circumstances would be without effect.
