Hemodynamics/Hemostasis Flashcards
(112 cards)
1
Q
What are elastic vessels?
A
Those with great ability to expand/contract because of systolic pulse.
- ex. aorta, common carotid A
2
Q
Describe the layers of muscular AA.
A
All arteries start with an intima that’s one cell lining thick.
- Underneath that is a basement membrane.
- Underneath that is an internal elastic lamina.
- Between the two elastic lamina (internal and external) is the tunica media that contains smooth MM fibers that allows constriction or dilation.
- Outside of that is the tunica adventitia which is continuous with the subQ tissue.
3
Q
Describe the pressure in small arteries/arterioles and venules.
A
The vessel is under much lower pressure, therefore they don’t have much smooth muscle.
4
Q
Do lymphatic channels have muscle?
A
No, they are a single layer thick. They rely on surrounding skeletal muscle and subcutaneous tissues pressing on the skin to move the lymph.
5
Q
How wide is a capillary?
A
1 RBC wide - 7 microns
6
Q
Why do sickle cell patients get joint pain?
A
Sickle cells get trapped in capillaries around the joint capsule.
7
Q
What is the importance of tight junctions in epithelial cells?
A
They don’t allow movement between intravascular space and extravascular space.
*think of BBB and barriers in testes and ovaries.
8
Q
Fenestrated capillary
A
Spaces between the endothelial lining that allow movement of water and ions between the intra and extravascular space.
9
Q
Where are fenestrated capillaries seen?
A
In the kidneys.
10
Q
Can albumin move in fenestrated capillaries?
A
No, its molecular weight is too large.
11
Q
In sinusoids, what moves in/out of fenestra?
A
RBCs
12
Q
Thrombus
A
Intravascular blood coagulum.
“Blood clot”
13
Q
What are the 3 sizes of thrombi?
A
- Petechiae- 1-2mm often seen in epithelia
- Purpura => 3mm
- Ecchymosis > 1-2cm subcutaneous
14
Q
Postmorten intravascular coagulum
A
Forms only from the plasma coagulation factors (no cellular factors at play)
15
Q
Hemostasis
A
Involuntary mechanism that forms an intravascular blood coagulum (thrombus)
16
Q
What is happening at the site of hemorrhage?
A
- Vasoconstriction (occurring immediately)
- Formation of platelet plugs (hemostasis mechanisms into play, primary + secondary)
- Fibrinolysis (dissolution of the clot)
17
Q
Vasoconstriction functions (2)
A
- It slows the bleeding.
2. It hemoconcentrates the blood so that the clotting factors pile up at the site because of the reduced blood flow.
18
Q
Which vessels have smooth muscle coat?
A
Arteries, arterioles, and large veins.
19
Q
Which vessels do not have muscular coat?
A
Venules and small veins.
20
Q
Steps to vasoconstriction.
A
Upon injury, the neurogenic and humoral stimuli cause transient vasoconstriction of the vessel lumen, thereby reducing blood flow.
21
Q
Platelets are produce from…
A
Megakaryocytes
22
Q
Where are platelets found?
A
Circulating in the blood.
23
Q
Step after vasoconstriction.
A
Primary hemostasis.
24
Q
What occurs in primary hemostasis?
A
- Receptor-mediated platelet adhesion to ECM
- Change in shape/activation
- Release of ADP by EC help change shape
- Thromboxane A2 helps to stimulate platelets and recruits more
- Platelets are stacking up - this is the formation of hemostatic plug.
25
What occurs in secondary hemostasis?
- endothelial cells are releasing tissue factors (factor 3, thromboplastin, and pro-coagulant glycoprotein acting with factor 7 as an initiator of coagulation)
- this results in thrombin generation
- thrombin cleaves fibrinogen to form fibrin
26
Formation of the permanent plug
- polymerized fibrin and platelet aggregates form the solid plug
- now anticoagulant activities begin
27
Anticoagulant activities s/p permanent plug formation
- t-PA (tissue plasminogen activator) is released to break down polymerized fibrin and start to limit the progression of the permanent plug
- thrombomodulin changes thrombin to anticoagulant factor
28
Plasminogen activator (t-PA) function
It takes fibrin and starts to digest it. These chopped up threads re-enter the circulation and can be measured.
29
D-Dimer
Measures the fibrin splits in circulation. Elevated D-Dimer can signify a clot.
30
Steps in Platelet Adhesion and Aggregation
- Platelet GpIb receptor attaches to vWF (von willebrand factor) in the extracellular matrix
- Fibrinogen links GpIIb-IIIa receptors on the platelets
- ADP from endothelial cells stimulates conformational changes
31
What does Plavix inhibit?
ADP, thus preventing coagulation (used in MI, stent, CABG patients)
32
What makes vWF?
Megakaryocytes in endothelial cells.
33
Where is factor VIII made?
Liver and kidney
34
von Willebrand-Factor VIII complex
Is circulating and can activate factor X
35
Fibrinolysis function
- Opposes and counteracts coagulation
| - Prevents coagulation of blood in areas where it's not needed
36
Steps in fibrinolysis
- Thrombin activates plasminogen to plasmin
- Plasmin degrades fibrin into fibrin-split products
- Split products can be measured in the blood (D-Dimer) to detect presence of "clot"
37
The most important PA...
t-PA (tissue plasminogen activator)
38
Functions of plasmin (3)
1. Breaks down fibrin
2. Interferes with fibrinogen polymerization to fibrin
3. Is inactivated by plasmin activator inhibitor (PAI)
39
Activation of Factor 10
Continues the clotting cascade to the formation of fibrin.
40
2 pathways that get you to Factor 10
Intrinsic + extrinsic
41
Coagulation pathway
Is a cascade of amplified enzymatic reactions.
42
What factors require vitamin K as cofactor?
2, 7, 9, 10
43
Plavix vs. Coumadin
Plavix is anti-platelet.
| Coumadin is an anti-coagulant, meaning it interferes with the clotting cascade.
44
Which pathway involves factor 7?
Extrinsic
45
How is factor 10 activated?
Thromboplastin converts factor 7 to factor 7a.
| In the presence of calcium, factor 7a will convert factor 10 to factor 10a.
46
PT (Prothrombin time) asses function of...
7, 10, 2, 5, and fibrinogen
47
How is PT run?
Adding tissue factor and phospholipid to chelated serum, then adding calcium.
48
Which pathway requires exposure of factor 12?
Intrinsic pathway
49
PTT (Partial Thromboplastin time) tests for...
12, 11, 9, 8, 10, 5, 2 and fibrinogen (I)
50
What delays the intrinsic pathway?
Heparin
51
Define hemorrhage
Site of uncontrolled blood loss
52
Direct methods of hemorrhage control
- pressure on site of bleeding
- application of tourniquets
- suturing of damaged vessels
- burning the blood vessel with cautery
- vasoactive drugs (like epinephrine)
53
You never use ________ with epinephrine when suturing up appendages.
Lidocaine
| fingers, toes, penis, nose, ears
54
Congenital coagulopathies
- Hemophilia A & B
| - von Willebrand Disease
55
Hemophilia A is deficiency in what factor?
Factor 8
56
Hemophilia A facts
- sex-linked with high rate of spontaneous mutation (30%)
| - Males >>> females
57
Hemarthrosis
Bleeding into joint space, common with hemophilia A.
| - can lead to crippling arthropathy
58
Platelet count, PT, and PTT in Hemophilia A
- Platelet count: normal
- PT: normal
- PTT: increased
59
Hemophilia A is deficiency in what factor?
Factor 9
60
Hemophilia B factors
- sex-linked
| - less common
61
von Willebrand Disease facts
- autosomal dominant disease
- affecting a coagulation factor produced by the endothelial cells
- characterized by easy bruising
- easy bleeding
62
Using hemarthrosis to differentiate Hemophilia A and VWD
little to no bleeding into joints with VWD due to location of vWF
63
Acquired bleeding disorders
- vitamin K deficiency
| - severe liver disease
64
Coumadin interferes with...
Vitamin K, thus interfering with factors 2, 7, 9, 10
65
Which factors are synthesized in the liver?
2, 7, 9, 10
66
Sources of vitamin K deficiency
- malnutrition due to ETOH
- malabsorption
- biliary obstruction
- drug therapy
67
Thrombocytopenia
Decrease in platelets
68
Thrombocytopenia characteristics
Petechial bleeding into the skin, GI tract, mucous membranes, urinary tract, and/or brain.
69
What platelet count impedes coagulation?
< 50,000/mL
70
What platelet count may result in spontaneous hemorrhage?
< 20,000/mL
71
How does aspirin interfere with function of platelets?
Inhibition of thromboxane A2
72
Thrombosis
Formation of blood "clots"
73
Virchow's Triad
1. Alteration of vascular endothelium
2. Alteration of blood flow
3. Alterations of blood components
74
How does alteration of blood flow affect thrombi formation?
Stasis or turbulence will disrupt the normal laminar flow of blood, bringing platelets in direct contact with the endothelium.
75
What contributes to disrupted vascular flow?
- Atherosclerosis
- Diabetes
- Hypertension
- Bacterial toxins
- Chemical agents
- Immunologic reaction
76
Causes of hypercoagulability and inappropriate thrombosis.
1. Excessively viscous blood
- Polycythemia
- Hyperproteinemia
2. Abnormal presence of procoagulants
- Systemic lupus
- Various neoplasms
3. Deficiencies of anticoagulants (Protein C, Protein S, Factor V Leiden)
77
Arterial Thrombi
- Form mostly in areas of atherosclerotic damage to the vessel wall
- Also seen in the heart wall over areas of previous myocardial infarction
78
Mural thrombus
A clot attached to the underlying chamber wall (generally nonocclusive).
79
Occlusive arterial thrombi
In smaller arteries (coronary, cerebral, femoral).
80
White (Arterial) Thrombi
- Develop in alternating layers
| - Particularly those in the heart and large arteries where there is high blood flow
81
Lines of Zahn
Seen as layers of fibrin and aggregated platelets which grossly gives the thrombus a grey laminated appearance
82
Red (Venous) Thrombi
- These usually form in areas of blood stasis (less tendency to develop line of Zahn)
- Typically found in the deep leg veins
- Frequently occlusive
83
Capillary Thrombi
- usually due to local endothelial damage.
| - generally consist of platelets and fibrin and are not grossly visible
84
Postmortem clots
- form a perfect cast of the vessel in which they form
- Do not contain lines of Zahn
- are not firmly attached to the vessel wall
- have a “currant-jelly” and/or “chicken fat” appearance
- do not break apart easily because they are mostly fibrous without cellular elements
85
Thrombolysis
Neutrophils and monocytes trapped in a thrombus will degrade and phagocytize fibrin and cell debris
86
Lysosomal enzymes from neutrophils and platelets function to...
Digest the coagulum and lead to softening
87
Fibroblast & endothelial cell roles in thrombolysis.
- Fibroblasts and endothelial cells from the underlying vessel will infiltrate the thrombus, and initiate fibrinolytic activity
- Endothelial proliferation may reestablish vascular flow (recanalization) through an occlusive thrombus.
88
Final step of thrombolysis
Eventually fibroblastic contraction will shrink the thrombus and it may become incorporated into the wall of the vessel
89
Thromboembolus
- During thrombolysis a thrombus may fragment or become completely detached from its place of origin
- As it tumbles through the circulation it is referred to as a thromboembolus (because it started as an intravascular coagulum - thrombus)
- Or just plane embolus (may be many kinds)
90
Clinical manifestations of thrombosis
Depend on several factors:
- The size
- Number
- Location
- Rapidity of development
- Availability of collateral circulation
91
Infarction
- refers to the process of tissue necrosis secondary to an abrupt reduction in tissue oxygenation.
- brain infarctions result in liquefactive necrosis
- tissues that are more highly specialized and/or are more metabolically active, are most sensitive to the effects of hypoxia/anoxia
92
Infarctions are usually the result of...
sudden interference with the arterial blood supply to a tissue
- in some instances, they may be due to obstruction of venous drainage or to conditions that decrease the oxygen carrying capacity of blood
- slowly developing vascular occlusions are LESS prone to cause infarction since collateral circulation may develop around the obstruction
93
Which tissues are somewhat protected against abrupt hypoxia?
Small bowel (rich anasmotic blood supply), lung, and liver (due to dual blood supply).
94
Where do red infarcts occur?
Any time you have 2 different circulations.
95
Infarction appearance
Grossly, infarcts due to arterial occlusion tend to be wedge-shaped with the apex located close the point of obstruction
- initially, somewhat ill-defined but become progressively demarcated with time
96
White or pale infarction
- occlusion of an artery will result in coagulation necrosis in those tissues that have a single blood supply without significant anastomoses (kidney, spleen, heart, etc.)
- since blood profusion of the tissue is interrupted, the tissue becomes white/pale
97
Infarction - Clinical Significance
- effects of an infarct depends on the location and size.
- A small infarct of the myocardium may be clinically insignificant, while one of the brainstem may be fatal.
- Conversely, a large infarct of the cerebral cortex may result only in neurologic deficits, while a large infarct of the myocardium may cause sudden death
98
3 kinds of emboli
Fat, air, and blood
99
Define embolus
A free-floating mass that is carried through the vascular system to a point distant to its site of origin or entry.
- often a fragment of pre-existing thrombus (thromboembolus)
100
Embolization
Emboli will impact and occlude vessels when the diameter of the vessel becomes smaller than the diameter of the embolus.
101
Systemic (arterial) emboli
80-85% arise from thrombi that form on the wall of the atria or ventricle (mural thrombi) on the left side of the heart – potentiated by dysfunctional heart rhythms - A-fib
102
Other sources of systemic (arterial) emboli
- Valve infections with “vegetations”
- Aortic mural thrombi
- Fragments of atherosclerotic plaque
103
What tissues are affected by systemic (arterial) emboli?
Tissues with high metabolic needs (brain, kidney, heart, intestines)
- others: lower extremities, intestines, spleen
104
Pulmonary embolism from venous thrombus
- Third most common cause of sudden death (after myocardial infarct and stroke)
- 95% arise from thrombi in the deep LE veins (popliteal, femoral, iliac), travel through enlarging venous channels, through the right heart, and into the pulmonary arteries
105
Pulmonary embolism clinical significance
- depends on size, number and cardiovascular status of the patient
- Presence should prompt investigation of underlying cause: hypercoagulability or malignancy
106
Fat/Marrow Emboli
- Occur after long-bone trauma when marrow fat is exposed to the venous circulation
- Fat emboli >20 µm are filtered in the lung
- Smaller aggregates may pass through the lung and lodge in brain and/or kidneys
107
Fat/Marrow Emboli Clinical Syndrome
1-3 days after trauma:
- progressive respiratory distress
- CNS impairment (restlessness, confusion, incontinence, and coma)
- possible renal dysfunction related to the mechanical and chemical effects of the fat
108
Air Emboli
May result from trauma or procedures that access large veins:
- Pelvic fracture
- Gynecological procedures including delivery
- Pneumothorax
- COPD with emphysema
109
Define Disseminated Intravascular Coagulation (DIC)
- Can be acute, subacute or chronic
| - Thrombus formation in microvascular channels throughout the body
110
When does DIC occur and from what sites?
- Can occur with sepsis, eclampsia, trauma, multisystem organ failure
- Bleeding at multiple sites can occur
111
DIC Mechanism
- The coagulations use up platelets, fibrin and coagulation factors
- Thrombolytic/fibrinolysis factors are triggered
- Thrombin/thrombomodulin creates anticoagulant effect.
* Coagulation gone wild
112
How do you treat DIC?
With platelets and clotting factors.
