Hemodynamic Disorders Part 2 Flashcards
What causes thrombosis?
- Endothelial Injury
- Abnormal Blood Flow
- Hypercoagulability
What are the effects of endothelial injury?
Procoagulant changes and antifibrinolytic effects
What are the procoagulant changes of endothelial injry?
Downregulates expression of thrombomodulin
Down regulation of protein C and tissue factor inhibitor
What are the antifibrinolytic effects of endothelial injury?
Plasminogen Activator Inhibitors (PAI) are secreted
What are causes that can lead to endothelial injury?
Hypertension
Bacterial products
Radiation Injury
Hypercholesterolemia
Toxins from cigarette smoke
What are the effects of turbulence and stasis?
- Endothelial Activation
- Disruption of laminar flow
- Washout and dilution of activated clotting factors are prevented
- Prevents inflow of clotting factor inhibitors
What does abnormal blood flow cause?
Turbulence and Stasis
What happens when endothelial activation is promoted?
- Procoagulant changes
- Increase in leukocyte adhesion
What happens when laminar flow is disrupted?
Platelets get in contact with endothelium causing clotting
What causes abnormal blood flow? And is it due to turbulence or stasis?
Aneurysms (Stasis)
Atherosclerotic plaque (turbulence)
Myocardial infarctions (Stasis)
Rheumatic Mitral Valve Stenosis (Stasis)
Sickle cell anemia (Stasis)
What is the difference between turbulence and stasis?
Both are alterations in normal blood flow which cause endothelial injury
Turbulence: Damage to lining of BV and is aterial
Stasis: Anticlog factors can enter here and is usually venous in nature
What are examples of Stasis?
Atrial fibrillation
Bed Rest
Aneurysms
Myocardial Infarctions
Rheumatic Mitral Valve Stenosis
Sickle cell anemia
What are examples of turbulence?
Atherosclerotic plaque
Vessel Narrowing
What can endothelial injury cause?
Thrombosis, Hypercoagulability, and abnormal blood flow
What does hypercoagulability cause?
Thrombosis
What does abnormal blood flow cause?
Endothelial injury, thrombosis, and hypercoagulability
What is hypercoagulability (Thrombophilia)?
Disorder of blood that predisposes to thrombosis
Which types of disorders arise from hypercoagulability?
Primary (genetic)
Secondary (aquired)
What arises from a genetic etiology of hypercoagulability?
Factor 5 mutation
Prothrombin mutation
Increased levels of factors 8,9,11 or fibrinogen
What arises from a secondary etiology of hypercoagulability?
Bed rest
Atrial fibrillation
Malignancy
Development of antiphospholipid antibodies
What are antiphospholipid antibodies?
The antibody binds to phospholipid then glycoprotein is unveiled which leads to more blood clots.
- Phospholipid is needed to form thrombomodulin
What is the factor V leiden?
Single nucleotide mutation of (Arg-> Glu)
- The mutation makes factor V resistant to cleavage and inactivation from protein C (which is needed to inactivate factor V for inhibition of thrombosis)
What is antiphospholipid antibody syndrome (Lupus anticoagulant syndrome)?
Binding of antibodies to epitopes on proteins that are induced or “unveiled” by phospholipids -> more clotting
What are the effects of lupus anticoagulant syndrome?
Recurrent thromboses, repeated miscarriages, cardiac valve vegetations, and thrombocytopenia (low blood platelet count)
What are examples of effects from hypercoagulability of the blood?
Factor V mutation
Prothrombin Mutation
Protein C deficiency
Protein S deficiency
What is homocysteine?
An amino acid derived from methionine which leads to more blood clots forming due to elevated levels of homocysteine
What are the effects of elevated levels of homocysteine?
More prone to heart disease and strokes
What are the effects of thrombosis?
Tissue injury by local vascular occlusion or by distal embolization
What are the different paths thrombi may do?
- Propagate- get larger
- Resolve
- Become organized- blood clot will integrate into the lining of the BV wall
- Embolize- Break away to other body sites
What are the different forms of thormbosis?
Venous Thrombosis and Arterial/ Cardiac Thrombosis
What are the different forms of venous thrombosis and where is it mostly found?
Found mainly in the veins of legs and can be:
1. Superficial veins
2. Deep veins
What are the effects of superficial veins?
Local congestion, swelling, pain, and tenderness but rarely embolization
What are the effects of deep veins?
Can embolize to the lung and eventually affect the heart
What causes arterial thrombosis?
Atherosclerosis
What causes a cardiac mural thrombus and where does it occur?
Myocardial infarction (obstruction of blood supply to heart)
- The thrombus will form on the lining of the heart
What are cardiac and aortic mural thrombi prone to?
Embolization to anywhere in the body with tissue thus it can cause tissue infarctions and organ infarctions
What is embolism?
Intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin
Give examples of a solid, liquid and gas embolism.
- Dislodged thrombus
- Fat droplets
- Bubbles of air or nitrogen
- Atherosclerotic debris (cholesterol emboli)
- Tumor Fragments
- Bits of bone marrow
- Amniotic Fluid
Where is pulmonary thromboembolism derived from and what are its effects/ consequences?
- Derived from lower extremity deep vein thrombi
- Effects depend mainly on size of the embolus and the location it lodges
- Consequences include: Right sided heart failure, pulmonary hemorrhage, pulmonary infarction, or sudden death
What is systemic thromboembolism derived from and what does it cause?
- Derived from cardiac mural or valvular thrombi, aortic aneurysms, or atherosclerotic plaques
- Causes ischemic (blood flow/ oxygen restriction) necrosis (infarction) of downstream tissues which is dependent on site of embolization and the presence or absence of collateral circulation
What can happen if you have pulmonary thromboembolism of the lungs?
Since the lungs have dual blood supply you can still get blood supply depending on the location of the embolism
What is a saddle blood clot?
It affects the right and left sides of the lungs thus size and location matter
What is cholesterol emboli derived from, what can it cause, and what it it also known as?
AKA “Hollenhorst Plaque”
It is derived from the carotid artery thus it affects the retina
It can cause heart disease (atherosclerosis) which leads to stroke/ heart attack
Not as close to the optic nerve
What is Calcific Embolus, what is it derived from, what is its location, and which test would you run?
It is made of calcium and from calcification of vales or arteries (aorta) in the heart it breaks away and goes to the retina
You would run an echocardiogram test
It is close to the central retinal artery and OPTIC NERVE
What is Fibrin- Platelet Embolus, what is its shape, what is its origin, and where is it located?
It is elongated and closer to the optic nerve
It is similar to a blood clot but with large platelet collection
It’s origin is the Carotid Artery
What is the most likely consequence of deep vein thrombosis?
Pulmonary Thrombombolus
What is an infarction?
An area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue
What are causes of an infarction?
- Arterial Thrombosis
- Arterial Embolism
- Venous outflow obstruction (rare)
What are features of an infarction caused by venous occlusion? Which type of tissue are they in?
They can occur in spongy tissues and are typically hemorrhagic (red)
What are the features of an infarction caused by an arterial occlusion? Which type of tissue are they in?
They can occur in compact tissues and are typically pale (white)
What influences infarct devolpment?
- Anatomy of vascular supply
- Rate of occlusion (slow is good so tissue can have collateral blood supply)
- Tissue Vulnerability to ischemia
- Blood oxygenation
What is ischemia?
When blood flow is restricted to certain body parts
- Neurons: 3-4 mins to die
- Heart: 30 mins to die
What does branch retinal artery occlusion result in? What does it look like?
It is localized and results in superior vision loss thus inferior retina is affected
What does central retinal artery occlusion result in? What does it look like?
The entire retina is affected and there is no vision
- All retina in pale
What does branch retinal vein occlusion result in? What does it look like?
It has many hemorrhages on the veins of the retina
What does central retinal vein occlusion look like?
The entire retina is full of hemorrhages
Identify the infarction
Coagulative Necrosis
Identify the infarction
Hemorrhagic in the lungs
Identify the infarction
Coagulative Necrosis
What is shock?
Systemic hypoperfusion of tissues
Hypoperfusion: Reduced amount of blood flow aka ischemia
What are the causes of shock?
- Diminished cardiac output
- Reduced effective circulating blood volume
What are the results of shock?
- Inadequate tissue perfusion
- Global cellular hypoxia
- Fatality
What are the three types of shock?
- Cardiogenic
- Hypovolemic
- Shock associated with systemic inflammation
What is the mechanism of cardiogenic shock? What are examples?
Failure of myocardial pump due to intrinsic myocardial damage, obstruction to outflow, and extrinsic compression
Heart attack
Arrhythmia
What is the mechanism of hypovolemic shock? What are examples?
Inadequate blood or plasma volume
Hemorrhage
Vomiting
Diarrhea
What is the mechanism of systemic inflammation shock? What are examples?
Cytokine cascades, peripheral vasodilation, endothelial activation/ injury, leukocyte-induced damage
Microbial infections ie: septic shock
What is septic shock? What does it derive from?
Most severe complication of sepsis (systemic inflammation with infectious source)
- Gram +/- bacteria
- Fungi
What are early signs of systemic inflammation?
- Fever
- Tachycardia (inc. heart rate)
- Tachypnea (inc. breathing)
- Leukocytosis (wbc elevated)
What is the pathogenic pathway of septic shock?
What is the starting factor of septic shock?
PAMPs from microbial products
What does PAMPs lead to?
- Intrinsic pathway with Factor XII (12)
- Complement activation
- Endothelial activation
- Neutrophil/ monocyte activation
What is the result of factor 12 activation?
- Procoagulant -. fibrin blood clots ->
- Increase: tissue factor
- Decrease: TFPI, thrombomodulin, proteinC
What does Procoagulant lead to?
Microvascular Thrombosis (DIC): Little blood clots everywhere -> tissue ischemia -> multiorgan failure
What is the result of endothelial activation
Anti-fibrinolytic: Increase in PAI-1 which prevents blood clot breakdown
What is the result of neutrophil and monocyte activation?
Systemic effects or immunosuppression via secondary anti-inflammatory mediators
What are the 3 stages of shock?
- Nonprogressive
- Progressive
- Irreversible
What is nonprogressive shock?
-Compensatory mechanisms activated -> vital organ perfusion is maintained
What is progressive shock?
Hypoperfusion -> circulatory and metabolic derangement
What is irreversible shock?
Severe cellular and tissue injury -> hemodynamic corrections are of no use
What are the symptoms of septic shock?
- Altered mental status
- Oliguria/ anuria (decreased urine due to kidney failure)
- Hypoxia
- Cyanosis
- Death
What are 3 deficiencies that could lead to thrombosis?
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
