Beruflich Dokumente
Kultur Dokumente
iv.
v.
vi.
to the endothelium, causing endothelial cell loss and exposure of the subendothelial
tissue to blood components. This leads to platelet adhesion and aggregation and fibrin
deposition.
Activated macrophages also ingest the oxidized LDL (by uptake through the
scavenger receptor) to become foam cells, which are present in all stages of
atherosclerotic plaque formation.
Platelets and activated macrophages release various factors that are thought to
promote growth factors that modulate the proliferation of smooth muscle cells and the
deposition of extracellular matrix in the lesions.
Lipids released from necrotic foam cells accumulate to form the lipid core of unstable
plaques.
Unstable plaques typically are characterized histologically by a large central lipid core, an
inflammatory infiltrate, and a thin fibrous cap. These vulnerable plaques are at risk of rupture,
often at the shoulder of the plaque where the fibrous cap is thinnest and the mechanical stresses
highest
Pathophysiology of Thrombosis
Thrombosis is inappropriate activation of blood clotting in uninjured vasculature or thrombotic
occlusion of a vessel after relatively minor injury. There are three primary influences on
thrombus formation, called Virchows triad:
1. Endothelial injury is dominant and can independently cause thrombosis (e.g.,
endocarditis or ulcerated atherosclerotic plaque). Injury can be due to hemodynamic
stresses (e.g., hypertension or turbulent), endotoxin, radiation, or noxious agents (e.g.,
homocystinuria, hypercholesterolemia, or cigarette smoke). Thrombosis results from
exposed subendothelial ECM, increased platelet adhesion or procoagulant production
(i.e., tissue factor, PAI), or reduced anticoagulant activity (i.e., PGI2, thrombomodulin, tPA).
2.
Alterations in normal blood flow can promote thrombosis. Normal blood flow is laminar
(i.e., cellular elements flow centrally in the vessel lumen, separated from endothelium by
a plasma clear zone). Stasis and turbulence disrupt laminar flow and bring platelets into
contact with the endothelium. Stasis causes thrombosis in the venous circulation, cardiac
chambers, and arterial aneurysms; turbulence causes thrombosis in the arterial circulation
as well as endothelial injury. Hyperviscosity syndromes (e.g., polycythemia) or deformed
erythrocytes (e.g., sickle cell anemia) result in small vessel stasis and also predispose to
thrombosis.
3.
Pathophysiology of Embolism
Embolism refers to any intravascular solid, liquid, or gaseous mass carried by blood flow to a
site distant from its origin. Most (i.e., 99%) arise from thrombi, hence the term
thromboembolism. Emboli lodge in vessels too small to permit further passage, resulting in
partial or complete vascular occlusion and ischemic necrosis (infarction).
1. Pulmonary Embolism
Pulmonary emboli (PE) occur in 0.2% to 0.4% of hospitalized patients and cause about 200,000
deaths annually in the United States. Greater than 95% of PE originate from DVT, although DVT
occur roughly 3-fold more commonly than PE. PE can occlude the main pulmonary artery,
impact across the bifurcation (saddle embolus), or pass into smaller arterioles.
Rarely, emboli pass through atrial or ventricular defects into the systemic circulation
(paradoxical embolism). Most PE (60% to 80%) are small and clinically silent. They eventually
organize and get incorporated into the vessel wall or leave a delicate, bridging fibrous web.
Sudden death, right-sided heart failure (cor pulmonale), or cardiovascular collapse occurs when
60% or more of the pulmonary circulation is obstructed with emboli.
2. Systemic Thromboembolism
Systemic thromboembolism refers to emboli in the arterial circulation. Approximately 80% arise
from intracardiac mural thrombi; two thirds are secondary to myocardial infarcts, and 25% arise
in the setting of dilated left atria and fibrillation. Systemic emboli can also originate from aortic
aneurysms, thrombi on ulcerated atherosclerotic plaques, or valvular vegetations; they rarely
originate from paradoxical emboli (venous emboli that pass through an atrial or ventricular septal
defect, including patent foramen ovale); 10% to 15% are ofunknown origin. Major sites for
arteriolar embolization are the lower extremities (75%) and brain (10%); intestines, kidneys,
spleen, and upper extremities are less frequent. The consequences of arterial emboli depend on
collateral vascular supply, tissue vulnerability to ischemia, and vessel caliber; most arterial
emboli cause tissue infarction.
3. Fat and Marrow Embolism
Pulmonary embolization of microscopic fat globules (with or with- out hematopoietic marrow
elements) occurs after fractures of long bones or, rarely, after burns or soft tissue trauma. Fat
embolism occurs in 90% of severe skeletal injuries; less than 10% have any clinical findings.
4. Air Embolism
Air embolism refers to gas bubbles within the circulation that obstruct vascular flow and cause
ischemia. Small amounts in the coronary or cerebral circulation (introduced following surgery)
can be catastrophic. Generally, in the pulmonary circulation, more than 100 cc is required to have
a clinical effect; such volumes can be introduced during obstetrical procedures or after chest wall
injury. Decompression sickness is a special form of air embolism caused by sudden changes in
atmospheric pressure; deep-sea divers and individuals in unpressurized aircraft during rapid
ascent are at risk. Air breathed at high pressure causes increasing amounts of gas (particularly
nitrogen) to be dissolved in blood and tissues. Subsequent rapid ascent (depressurization) allows
the dissolved gases to expand and bubble out of solution to form gas emboli. Formation of gas
bubbles in skeletal muscles and joints causes painful bends. In lungs, edema, hemorrhage, and
focal emphysema lead to respiratory distress, or chokes. Gas emboli may also cause focal
ischemia in a number of tissues, including brain and heart.
5. Amniotic Fluid Embolism
Embolization of amniotic fluid into the maternal pulmonary circulation is a serious (mortality
rate 80%) but uncommon (1 in 40,000 deliveries) complication of labor and postpartum period.
The syndrome is characterized by sudden severe dyspnea, cyanosis, and hypotensive shock,
followed by seizures and coma.
.