Flashcards in Exam #2: Hemodynamics IV Deck (50):
What is Virchow's Triad?
Virchow's Triad outlines the three primary abnormalities that lead to thrombus formation:
1) Endothelial Injury
3) Hypercoaguable state
What is the dominant influence on thrombosis formation?
Why is endothelial injury especially important for thrombus formation in the heart & arterial circulation?
High flow rates impede platelet adhesion & washout clotting factors; thus, endothelial injury is the major factor leading to thrombus formation in these high flow areas
List the difference sources of endotheial injury & dysfunction.
4) Oxidtive stress
5) LDL cholesterol
6) Homocysteine ADMA
List the consequences of endothelial dysfunction.
2) Increased leukocyte adhesion & infiltration
3) Platelet aggregation & thrombosis
4) Vascular smooth muscle cell proliferation
5) Lipid accumulation
What is the difference between primary and secondary hypercoaguable states?
Primary= genetic mutation leading to hypercoagulation
- Factor V Leiden
Secondary= acquired alterations leading to hypercoagulation i.e.
- bed rest
What is a Factor V Leiden deficiency?
- Factor V is a clotting factor
- Normally broken down by protein C
- Mutation in Factor V prevents the removal of Factor V by protein C-->hypercoaguable state
Specifically, a glutamine residue is substituted for arginine in the 506 position, and prevents cleavage by protein C
What is the typical presentation of Factor V Leiden deficiency?
Recurrent DVTs without secondary risk factors
- More common in caucasians
What is antiphospholipid antibody syndrome?
Serum antibody directed against anionic phospholipid
- In vitro there is INHIBITION of clotting due to interference with assembly of phospholipid complexes
- In vivo= HYPERCOAGUABLE state
What is antiphospholipid antibody syndrome associated with?
Autoimmune diseases, especially, SLE
What are the clinical manifestations of antiphospholipid antibody syndrome?
- Recurrent venous or arterial thrombi
- Repeated miscarriage
- Cardiac valve vegetations
What is the effect of turbulence in the vasculature?
Disruption of normal laminar flow
- In normal laminar flow, platelets flow centrally & are separated from the endothelium by slower moving plasma
- Stasis & turbulence:
1) Disrupts laminar flow & brings platelets in contact with endothelium
2) Prevents dilution of clotting factors
3) Promotes endothelial cell activation
List the causes of turbulence in the vasculature?
- Ulcerated atherosclerotic plaque
- Mitral valve stenosis
- Hyperviscosity syndrome i.e. polycythemia
- Sickle cell anemia
Describe the morphology of thrombi. What is the difference between aterial & venous thrombi?
Arterial= usually occur at sites of endothelial cell injury
- Grey-white and friable
Venous= more commonly caused by stasis/ low-flow
- Red, slower blood flow= higher accumulation of RBCs
What are the complications of arterial thrombi?
May cause local obstruction or distant embolization leading CVA, MI, and PAD
- Rheumatic heart disease
What are arterial thrombi composed of?
Describe the relative incidence of arterial thrombi i.e. where do they occur most commonly?
Where does rupture of a thrombis typically occur?
What is an abdominal aortic aneurysm?
Outpouching of the wall of the abdominal aorta that is at risk for rupture
- Layered thrombus is in the lumen
What are "Lines of Zahn?"
Alternating layering of pale platelets & fibrin with darker erythrocytes
*****Note that these are important for distinguishing between antemortem & postmortem thrombosis
Where are venous thrombi most commonly seen?
90% involve LE veins, but other less common sites include:
Ovarian & periuterine veins
Where do venous thrombi typically form?
In valve pockets of the deep veins
What is phlebothrombosis?
Superficial thrombi that rarely embolize
In what percentage of patients are DVTs asymptomatic?
****This is important! In roughly 50% of affect patients, collateral circulation may mask symptoms of a DVT i.e. the patient is asymptomatic.
What are the risk factors for venous thrombosis?
What is Trousseau Syndrome?
This is a "migrating thrombophlebitis" caused by a serine protease released by malignant tumors that activates Factor X
- Tumor cells release plasma membrane vesicles exhibiting procoagulant activity
- Tissue thromboplastin is released from a necrotic tumor e
What are the different fates of a thrombus?
3) Organization and incorporation into the wall
4) Organization & recannulization
What is an embolus?
A detached intravascular solid, liquid, or gas that is carried by the blood to a distant site from its point or origin
- Lodge is vessels that are too small for migration to continue
- Unless otherwise specified, embolus is assumed to be a "THROMBOEMBOLUS"
List the sources of aterial emboli.
- Mitral stenosis
- Mural thrombi in heart or aorta*
- Paradoxical emboli
What is the most common source of emboli that migrate within the arterial circulation?
Intracardiac mural thrombi
What is a paradoxical emboli?
Rare condition in which an embolus originating from the VENOUS circulation passes through a VSD and into the systemic circulation
E.g. a DVT that causes a stroke
What is the most common cause of a pulmonary thromboembolism?
95% arise from deep leg vein thrombi ABOVE THE KNEE
Where can a pulmonary thromboembolism occlude?
- Main pulmonary artery
- Saddle= across vessel bifurcation
- Smaller braching arterioles
*Can cause sudden death via acute RVH
What is cor pulmonale?
Chronic/ recurrent pulmonary embolism that leads to pulmonary HTN
How are pulmonary embolism diagnosed?
- 2D echo
- V/Q scan
- CT chest
What causes a fat embolism?
Long bones contain fatty marrow. In 90% of long bone fractures/ skeletal trauma, there is embolism of this fatty marrow, leading to a fat embolism. However, on 10% of patients actually develop clinical findings i.e. most are ASYMPTOMATIC
What is fat embolism syndrome?
This is the term applied to the minority of patients with a fat embolism that become symptomatic. Typically 1-3 s/p injury:
1) Dyspnea, tachypnea, & tachycardia
2) Irritability & restlessness
3) Progression to delirium & coma
What is an air embolism?
Coalesced gas bubbles in the circulation-->obstruction of vascular flow
Outline the pathophysiology of decompression sickness or the Bends.
- Sudden change in atmospheric pressure i.e. diving
- Nitrogen inspired at high pressure (deep under water) dissolves in blood
- Rapid decrease in pressure i.e. rapid ascent, nitrogen comes out of solution & forms gas bubbles in the circulation
What is the difference between "the bends" and "the chokes?"
Bends= dissolution of nitrogen in muscles, bones, and joints leads to a painful condition called, "the bends"
Chokes= dissolution of nitrogen in the lung vasculature leading to edema, hemorrhage, and focal atelectasis-->respiratory distress
What is the treatment for decompression sickness?
Hyperbaric oxygen therapy=
- Forces gas back into solution
- Allows for slow & controlled decompression
What is an amniotic fluid embolism?
Breach of the placental membranes & uterine veins causes infusion of amniotic fluid into maternal circulation. This is a very ominous diagnosis and leads to:
- Sudden severe dyspnea
- Neurologic impairment (headache, seizures-->coma)
IF the patient survives the initial crisis, pulmonary edema and DIC follow.
Describe the pathophysiology of an amniotic fluid embolism.
Tear in the placental membranes or rupture of the uterine veins leads to amniotic fluid or fetal tissue into the maternal circulation
List the contents of an amniotic fluid embolism. What is important about the contents?
Squamous cells from fetal skin
Fat from vernix caseosa
Mucin from fetal respiratory or GI tract
*****All are procoagulative
What is the definition of infarction?
Death of tissue due to the interruption in blood supply
What can cause infarction besides thrombosis & emboli?
- Vasopasm e.g. cocaine-->MI
- Hemorrhage within athersclerotic plaque
- Extrinsic compression of vessel
- Twisting of a vessel e.g. testicular torsion or intestinal volvulus
What is the major factor in tissue damage from infarction?
Availability of alternative blood supply
What cells are the most vulnerable to hypoxia?
Neurons= 3-4 min
Myocardium= 20-30 min
Describe the general morphology of an infarct.
- Poorly defined
- Over time delineated by a rim of hyperemia