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Figure Legend:
Chronic endothelial injury, inflammation, and oxidative stress arecentral to the development of atherosclerosis. Endothelial injury
resultsfrom a variety of factors including tobacco use, hypercholesterolemia, interventionaltherapies with angioplasty or coronary
stents, and from ulceration or fissuringof atherosclerotic plaques. At sites of endothelial injury, production ofendothelial-derived
substances (nitric oxide [NO], tissue plasminogen activator[tPA], and prostacyclin [PGI2]) is decreased, creating a
prothromboticenvironment characterized by increased platelet
Copyright © 2012 and leukocyte
American adhesion, increasedpermeability to plasma
Medical
Date of download:
lipoproteins, 3/11/2013
myointimal hyperplasia, and vasoconstriction.Ulceration
Association. All rights reserved. of the atherosclerotic plaque results from
or fissuring
degradationof collagen matrix in the fibrous cap by metalloproteases released from macrophages.Exposure of the subendothelium
after plaque ulceration or fissuring leadsto platelet adhesion and aggregation and local accumulation of largely platelet-
derivedmediators (thromboxane A2, serotonin, adenosine diphosphate [ADP],thrombin, platelet activating factor [PAF], oxygen-
derived free radicals,tissue factor, and endothelin) that promote thrombus growth, fibroproliferation,and vasoconstriction. LDL
indicates low-density lipoprotein.
Endothelial Injury
Normal blood flow is laminar such that the platelets (and other
blood cellular elements) flow centrally in the vessel lumen,
separated from endothelium by a slower moving layer of plasma.
Stasis and turbulence therefore:
http://www.oocities.org/venkatej/mech/fluid_mechanics/LaminarFlowProfile.gif
http://www.phlebolymphology.org/2009/07/recent-findings-in-the-pathogenesis-of-venous-wall-degradation/
http://content.onlinejacc.org/data/Journals/JAC/23086/02059_gr4.jpeg
Alterations in Normal Blood Flow
Aortic and arterial dilations called aneurysms result in local stasis and are
therefore fertile sites for thrombosis.
http://www.doctortipster.com/wp-content/uploads/2011/08/Deep-
venous-thrombosis-causes.jpg
http://www.stoptheclot.org/images/natt_other_ar
t/acute%20left%20leg%20DVT;%20postthormb
otic%20syndrome%20right%20leg.jpg
http://www.aafp.org/afp/2012/1115/afp20121115p913-f1.gif
Hypercoagulability
http://ars.els-cdn.com/content/image/1-s2.0-S0268960X08000362-gr1.jpg
PRIMARY (GENETIC)
Common
http://www.nature.com/nrcardio/journal/v11/n3/full/nrcardio.2013.211.html?WT.ec_id=NRCARDIO-201403
http://www.practical-haemostasis.com/images/Images-2/Thrombophilia%20Tests/pc_ps_pathway.jpg
http://www.med4you.at/laborbefunde/lbef2/atIII_anim3.gif
Thrombomodulin (TM)
http://hcp.obgyn.net/image/image_gallery?img_id=2082561&t=1339545353297
Among the acquired thrombophilic states, two that are
particularly important.
beta2 Glycoprotein 1
http://www.nature.com/nrrheum/journal/v7/n6/images/nrrheum.2011.52-f1.jpg
Thrombi can develop anywhere in the cardiovascular system
(e.g., in cardiac chambers, on valves, or in arteries, veins, or
capillaries).
http://i48.tinypic.com/2vmvqcj.jpg
http://811699.net/wp-content/uploads/2011/03/LUNG065.jpg
Organized arterial thrombus
http://www.geocities.ws/m4pathology/Osce/Slides/histsch03.jpg
Recanilizatuion
http://farm3.static.flickr.com/2791/4337748744_3a92ba6583.jpg
Aortic thrombi from electrical injury
Lung hilum thromboembolus with lines
of Zahn
Right atrial mural thrombus with lines
of Zahn
Clinical Consequences.
Neurons: 3 – 4 minutes
Myocardial cells: 20 – 30 minutes
Fibroblasts, skeletal muscle: hours
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
Disorders ranging from obstetric complications to advanced
malignancy can be complicated by DIC, the sudden or insidious onset
of widespread fibrin thrombi in the microcirculation.
Although these thrombi are not grossly visible, they are readily
apparent microscopically and can cause diffuse circulatory
insufficiency, particularly in the brain, lungs, heart, and kidneys.
https://www.meducation.net/encyclopedia/29623
Extra Stuff
Nature of the vascular supply. The availability of an alternative
blood supply is the most important determinant of whether vessel
occlusion will cause damage.