Hemodynamic Disorders, Thromboembolic Disease, and Shock Flashcards
(169 cards)
1
Q
How is edema different from effusion?
A
Edema is the abnormal accumulation of fluid in the interstitial space; effusion is the abnormal accumulation of fluid in a body cavity/ potential space
2
Q
What are some examples of body cavities/potential spaces where fluid can accumulate?
A
pericardial space, peritoneal space, pleural space, and joint space
3
Q
what is it called when fluid accumulates in the peritoneal space?
A
ascites
4
Q
What 4 things are the direct causes of edema/effusions?
A
Increased hydrostatic pressure, decreased colloid osmotic pressure, increased vascular permeability, and lymphatic obstruction
5
Q
What is hyperemia, what color is it, and is it physiologic or pathologic?
A
Hyperemia is when too much blood is arriving, red/arterial, physiologic
6
Q
what is congestion, what color is it, and is it physiologic or pathologic?
A
Congestion is when not enough blood is leaving, blue/venous, pathologic
7
Q
What does congestion usually result in and why?
A
edema- due to increased hydrostatic pressure
8
Q
why does heart failure lead to edema?
A
there is an increased hydrostatic pressure, which directly leads to edema; there is also a decrease in renal blood flow, which activates the RAAS system, which causes retention of Na+ and H2O, which causes there to be an increase in blood volume- this causes increased hydrostatic pressure and decreased colloid osmotic pressure, which directly causes edema
9
Q
what are the pulmonary findings associated with heart failure?
A
pulmonary edema and pulmonary effusions
10
Q
what is the mechanism of heart failure that leads to edema/effusions?
A
there is decreased “pumping activity”- this leads to a “back up” of pulmonary venous circulation (aka congestion); there is also retention of Na+ and H2O- this causes there to be increased blood volume, which causes a decrease in plasma colloid osmotic pressure
11
Q
what are 2 examples of edema associated with heart failure?
A
pitting edema and pulmonary edema
12
Q
what are 2 signs of liver failure?
A
ascites and edema
13
Q
what are the mechanisms of edema/ascites associated with liver failure?
A
there is a decrease in the production of albumin (this causes there to be a decreased in colloid osmotic pressure); there is also portal hypertension, which leads to congestion
14
Q
what are the two ways that renal failure can result in edema?
A
there is increased retention of Na+ and H2O (this increases intravascular pressure); nephrotic syndrome, which causes there to be excessive loss of proteins in the urine (this causes there to be decreased colloid osmotic pressure)
15
Q
What is Kwashiorkor?
A
a protein deficiency that results in insufficient production of albumin- this leads to a decreased colloid osmotic pressure
16
Q
When might you have a protein deficiency that leads to decreased plasma osmotic pressure?
A
protein deficiency (Kwashiorkor), decreased synthesis of proteins (liver failure) or excessive protein loss of proteins in urine (renal disease with nephrotic syndrome)
17
Q
What could cause localized edema?
A
lymphedema
18
Q
What are some causes of lymphedema?
A
infection, inflammation, trauma, tumors, surgery, or malformations
19
Q
What effect does the parasite filariasis have on the body?
A
the organism induces obstructive fibrosis of lymphatic channels and lymph nodes (this could lead to edema of the external genitalia and lower limbs)
20
Q
What is the difference between exudate and transudate?
A
exudate has a high protein concentration and contains cell debris; transudate has a low protein concentration and no cellular debris, and has a low specific gravity
21
Q
what does the presence of transudate imply?
A
that there is an increase in hydrostatic pressure (congestive heart failure) or a decreased in colloid osmotic pressure (decreased protein synthesis –> liver failure or increased protein loss–> kidney disease with nephrotic syndrome)
22
Q
What does the presence of exudate imply?
A
the existence of an inflammatory process that has increased the permeability of small blood vessels
23
Q
what could cause an increase in capillary permeability?
A
sepsis, infection, and burns
24
Q
what could chronic congestion lead to?
A
edema–>hemosiderosis–>tissue damage
25
What is the morphology/pathology of heart failure caused (chronic) pulmonary edema?
pulmonary edema from left heart failure results in the accumulation of fluid in the alveolar spaces; chronic congestion shows increased hemosiderin-laden macrophages (aka heart failure cells)
26
where do you see obstruction of blood flow in cases of hepatic congestion?
central vein
27
what is hepatic congestion most often caused by?
advanced heart failure
28
what is the pathology/morphology of acute hepatic congestion?
the central vein and sinusoids are distended--> centrilobular hepatocytes may undergo ischemic necrosis
29
what is the pathology/morphology of chronic hepatic congestion?
the centrilobular regions are grossly red-brown and slightly depressed (because of cell death) and are accentuated against the surrounding zones of uncongested tan liver (nutmeg liver)
30
What is the initial step in hemostasis?
vasoconstriction
31
how does the initiating step of hemostasis-vasoconstriction- occur?
it is a reflexive neurogenic process that is further mediated by endothelin
32
what is the purpose of the initiating step of hemostasis- vasoconstriction?
it reduces the surface area affected and it reduces the blood flow
33
What are the steps of primary hemostasis?
adhesion, activation, and aggregation
34
what does the subendothelial surface have that allows platelets to bind?
von Willebrand Factor
35
what do the platelets have that allow them to bind to the subendothelial surface?
GpIb
36
What is a significant source of von willebrand factor?
Weibel Palade bodies
37
What does lack of functional vWF cause?
von Willebrand disease
38
what does lack of GpIb receptor cause?
Bernard-Soulier Syndrome
39
what do the platelets look like in Bernard Soulier syndrome?
they are giant
40
what 2 things occur during platelet activation?
conformational change and secretion
41
during the stage of activation what is there a conformational change of?
the actual platelet- makes it a negatively charged surface, and the GpIIb-IIIa changes shape
42
during the stage of activation, what is there secretion of? and what is this secretion initiated by?
secretion of ADP and Thromboxane A2; secretion is initiated by thrombin
43
what does secretion of ADP cause?
more activation of platelets
44
what does secretion of Thromboxane A2 cause?
more aggregation of platelets
45
what is the effect of administration of aspirin?
aspirin is going to inhibit thromboxane A2 (so there will not be aggregation of platelets)
46
what does the conformational change of the GpIIb-IIIa in activated platelets allow for?
bivalent binding of fibrinogen, which leads to cross linking of platelets
47
what do you get if there is a deficiency in GpIIb-IIIa complex?
disorder of platelet aggregation- Glanzmann thrombasthenia
48
How do we know if something is wrong with primary hemostasis clinically?
Mucocutaneous bleeding
49
What are some common clinical signs of someone with a disorder of primary hemostasis/mucocutaneous bleeding?
petechiae, ecchymoses, purpura, hemorrhagic bullae
50
symptoms of disorders of primary hemostasis depends on platelet levels. What symptoms do you get if you have 20-50k platelets?
petechiae and ecchymoses following mild trauma
51
symptoms of disorders of primary hemostasis depends on platelet levels. What symptoms do you get if you have less than 10k platelets?
risk for intracranial hemorrhage and spontaneous generalized mucocutaneous bleeding
52
symptoms of disorders of primary hemostasis depends on platelet levels. What symptoms do you get if you have less than 2k platelets?
widespread ecchymoses, hemorrhagic bullae, and retinal hemorrhage
53
How do we know if something is wrong with primary hemostasis in the laboratory?
platelet quantity (CBC); platelet quality (function)
54
what are some modern techniques to test platelet function?
flow cytometry and PFA-100
55
What is the mechanism of disease in thrombocytopenia?
loss or impaired production of platelets
56
what is the platelet count for thrombocytopenia?
low
57
Is there still platelet adhesion in cases of thrombocytopenia?
Is there still platelet aggregation in cases of thrombocytopenia?
yes and yes
58
what is the mechanism of disease in Von Willebrand disease?
inherited lack of vWF
59
What is the platelet count in cases of von willebrand disease?
normal
60
is there platelet adhesion in cases of von willebrand disease?
Is there platelet aggregation in cases of von willebrand disease?
no platelet adhesion
| yes platelet aggregation
61
what is the mechanism of disease for bernard-soulier disease?
abnormal GpIb
62
What is the platelet count for bernard-soulier disease?
low-normal
63
is there platelet adhesion in cases of bernard-soulier disease?
Is there platelet aggregation in cases of bernard-soulier disease?
no platelet adhesion
| Yes platelet aggregation
64
what is the mechanism of disease for Glanzmann's thrombasthenia?
abnormal GpIIb-IIIa
65
what is the platelet count in cases of Glanzmann's thrombasthenia?
normal
66
is there platelet adhesion in cases of Glanzmann's thrombasthenia?
is there platelet aggregation in cases of Glanzmann's thrombasthenia?
Yes platelet adhesion
| No platelet aggregation
67
What is secondary hemostasis?
the coagulation cascade
68
What is the overall purpose of the coagulation cascade?
to form the fibrin clot
69
where does the coagulation cascade start for the intrinsic pathway?/ what kicks off the intrinsic pathway?
a negatively charged surface
70
where does the coagulation cascade start for the extrinsic pathway?/ what kicks off the extrinsic pathway?
tissue factor (factor III)
71
What is reflected in the laboratory for the intrinsic pathway?
aPTT
72
what is reflected in the laboratory for the extrinsic pathway?
PT
73
What factors are involved in the intrinsic pathway?
XII, XI, IX, VIII
74
What factors are involved in the extrinsic pathway?
VII
75
What factors are involved in the common pathway?
X
76
what happens once thrombin binds to the heparin-like molecule?
it inactivates thrombin (and factors IXa and Xa)
77
What is another name for factor II?
prothrombin
78
what is another name for factor VIII?
Antihemophilic A Factor (AHF)
79
What are the prothrombotic functions for thrombin?
it stabilizes fibrin, it activates platelets, and it activates receptors on inflammatory cells and endothelium
80
What are the vitamin K dependent factors?
II, VII,IX, X
81
what is the function of Coumadin (warfarin)?
it blocks the vitamin K dependent carboxylation- so the factors II, VII, IX, X remain inactive
82
What are the clinical signs of a defect in hemostasis? (most common in platelet dysfunction)
dermatologic manifestations--> petechiae, purpura, and ecchymosis
83
what type of problem with hemostasis might you have if there is visceral and intracranial bleeding?
factor deficiencies or profound thrombocytopenia
84
what should a normal aPTT be?
32-45 seconds
85
what should a normal PT be?
10-14 seconds
86
if there is a prolonged aPTT what might you have?
factor deficiency in VIII, IX, XI, or XII
87
if there is a prolonged PT what might you have?
factor VII deficiency
88
if there is a combined abnormal aPTT and PT, what might you have?
taking anticoagulants, DIC, liver disease, vitamin K deficiency, massive transfusion, or a factor X, V, and II defect
89
what is the function of plasmin?
it breaks apart fibrin (the fibrin clot duh)
90
where do we get t-PA?
the non-injured endothelial cells release the t-PA
91
what is the function of t-PA?
it is going to activate plasmin (from plasminogen)
92
how does intact endothelium have an antithrombotic effect?
there is no exposed tissue factor; there is also platelet inhibition
93
what molecules are platelet inhibitors?
adenosine diphosphatase, prostacyclin, nitric oxide
94
what enzyme is responsible for fibrinolysis?
plasmin
95
what does thrombin bind to on uninjured endothelial cells?
thrombomodulin
96
what happens once thrombomodulin binds thrombin?
it activates protein C
97
what happens once protein C is activated?
it inactivates factors Va and VIIIa
98
what happens once thrombin binds to the heparin-like molecule?
it inactivates thrombin (and factors IXa and Xa)
99
What are the primary mechanisms that lead to thrombosis?
endothelial injury, abnormal blood flow, and hypercoagulability of the blood
100
What section of virchow's triad would you place hypercholesterolemia or inflammation?
under endothelial injury
101
what section of virchow's triangle would you place stasis (a fib or bed rest) or turbulence (atherosclerotic vessel narrowing)?
abnormal blood flow
102
what section of virchow's triangle would you place factor V Leiden or disseminated cancer?
under hypercoagulability
103
What is the result of endothelial dysfunction?
decreased nitric oxide activity; which leads to endothelial activation, causing an increase in adhesion molecules
104
what are the prothrombotic changes that occur with endothelial activation?
there is a down regulation of both thrombomodulin and activated protein C; there is also an elaboration of plasminogen activator inhibitors (PAIs)
105
what is the effect of plasminogen activator inhibitor (PAIs)?
they will limit fibrinolysis
106
when might there be alterations in blood flow?
normal bifurcations, dilated vessels (aneurysms or hemorrhoids), internal obstruction, external compression, or inadequate heart chamber function
107
how can hypercoagulability be divided?
primary (genetic) or secondary (acquired)
108
What are the 3 most common causes of primary (genetic) hypercoagulability?
factor V mutation, prothrombin mutation, or increased levels of factors VIII, IX, XI, or fibrinogen
109
what are the 3 rare primary (genetic) causes of hypercoagulability?
antithrombin III deficiency, Protein C deficiency, protein S deficiency
110
what are 2 very rare primary (genetic) causes hypercoagulability?
fibrinolysis defects or homozygous homocystinuria
111
who is at strong risk for a secondary (acquired) hypercoagulability?
those on prolonged bed rest, MI, A fib, tissue injury, cancer, prosthetic cardiac valves
112
What are some other risks factors for secondary (acquired) hypercoagulability?
hyperestrogenic states (pregnancy and postpartum), oral contraceptive use, smoking, sickle cell anemia
113
What happens if the deep vein thrombosis dislodges?
it becomes an embolus and will lodge itself in the pulmonary arterial circulation
114
when might you suspect a primary hypercoagulable state?
if there is an initial event (DVT or PE) with no provoking factors, they have young age (40-50), and a strong family history
115
what tests might you run if you want to rule out a primary hypercoagulable state?
ATIII levels, Protein C levels, Protein S levels, Factor V Leiden mutation
116
In the coagulation cascade, what does calcium bind to?
the gamma-carboxylated glutamic acid residues that are present in factors II, VII, IX, and X
117
the enzymatic reactions that produce gamma-carboxylated glutamic acid uses what as a cofactor?
vitamin K
118
What is found to be more common in factor deficiencies rather than primary hemostasis issues?
hemarthrosis (hemophilia)
119
Following secondary hemostasis: the coagulation cascade, what is the final step of hemostasis?
fibrinolysis and limitation of clot formation
120
What are the ways our body limits coagulation?
through blood flow (blood washes away activated clotting factors); there is no more platelet surface; and through plasmin
121
What is the most common genetic cause of thrombosis?
a factor V Leiden mutation
122
what population is more susceptible to a factor V leiden mutation?
Caucasian/ Europeans
123
what is the mechanism of action of a factor V Leiden mutation?
the mutated factor V makes it essentially unable to be cleaved by activated protein C
124
What are two ways you can see if a patient has a factor V Leiden mutation?
by doing a direct genetic test or by using the functional test: APC resistance (APCR) testing
125
How do you perform the APCR test?
you give samples of activated protein C to a patient; the patient should have an elevated clot time; however, if they have a factor V Leiden mutation, they will continue to thrombose
126
What are two common acquired (secondary) hypercoagulable states?
1) Heparin-induced thrombocytopenia and 2) antiphospholipid antibody syndrome
127
what is the prothrombotic state caused by in heparin-induced thrombocytopenia?
antibodies to PF4 heparin
128
what does heparin bind to when administered?
to PF-4
129
what type of antibodies are produced against the heparin-PF4 complex in some people?
IgG
130
what do the anti-heparin + PF-4 IgG bind to?
platelet Fc receptors
131
what happens once the antibody complex binds to the platelet Fc receptors?
there is going to be activation and aggregation of the platelets leading to a thrombotic event; but there is also going to simultaneously be dropping out of the platelets from circulation, which leads to thrombocytopenia
132
what does a patient scenario with heparin-induced thrombocytopenia typically look like?
we put a patient on heparin and then a few days later their platelet count drops, they might even have a thrombotic event
133
how do we test to see if a patient has heparin-induced thrombocytopenia?
we test for PF-4 Antibodies
134
what is a common sign in patients if HIT is not treated quickly?
digital gangrene
135
what population of people are more susceptible for antiphospholipid antibody syndrome?
it is a relatively common situation especially in younger-middle aged women in the US
136
what can antiphospholipid antibody syndrome occur in the presence of?
systemic lupus erythematosis
137
what occurs in antiphospholipid antibody syndrome?
you get antibodies against plasma proteins that bind to phospholipids
138
What are the various presentations for a patient with antiphospholipid antibody syndrome?
Vascular: arterial or venous thrombosis (stroke, pulmonary emboli, digital gangrene); obstetric: unexplained miscarriage/stillbirth
139
What are the four fates of the thrombus?
propagation, embolization, dissolution, or organization/recanalization
140
What is propagation of a thrombus?
the growth of the thrombus and eventually it is going to occlude and create symptoms
141
What are the 5 different types of emboli?
Thromboemboli, amniotic fluid emboli, fat emboli, air emboli, and septic emboli
142
What is it called when a thromboemboli lodges itself right at the bifurcation of the pulmonary arteries?
saddle pulmonary embolus: INSTANTANEOUSLY LETHAL
143
How might a patient with a medium sized pulmonary emboli present?
SOB and decreased oxygen saturation
144
what causes the instantaneous death during a saddle pulmonary emboli?
acute right heart failure
145
How can you tell if a thrombus/embolus occurred during active blood flow (when the patient was still alive)?
lines of Zahn
146
What leads to a fat emboli?
fracture or trauma to bones (think recent ortho surgery or chest compressions that broke ribs)
147
What are the symptoms of a fat embolism determined by? and what are some examples?
As the marrow lodges it creates a situation that manifests based on where it is lodged; respiratory distress or mental status changes
148
What are two causes of air emboli?
cardiac catheterization and decompression sickness
149
An amniotic fluid embolism is caused when?
there is introduction of fetal material into maternal circulation; when these cells and materials get introduced it creates a shock situation
150
When might a septic emboli occur?
in endocarditis (valve vegetations break off and manifest in other sites)
151
what are the microemboli associated with endocarditis/ septic emboli?
skin microemboli, retinal microemboli, and vascular damage in the nail bed
152
Where do white thrombi occur and what are they rich in?
arterial vessels; rich in platelets
153
A lot of these white thrombi are occurring in a setting of what?
atherosclerosis
154
when you think about white thrombi, what arteries should you think of?
coronary arteries and cerebral arteries (carotid artery)
155
what type of drugs are good for treating CAD?
anti-platelet drugs
156
where do red thrombi occur and what are they rich in?
venous vessels; red cell rich
157
a lot of these red thrombi are occurring in the setting of what?
stasis
158
when you think of red thrombi, what should you think of?
DVT
159
Infarctions are typically occurring because of what?
arterial thromboembolic disease
160
What determines if an infarct is going to be red versus white?
the anatomy of the vascular supply
161
what is an example of an organ that would have a white infarct?
the spleen
162
What are some examples of an organ that would have a red infarct?
lungs and the intestines
163
Why does the rate of an occlusion matter?
because if a thrombus grows slowly enough, collateral blood vessel formation may occur
164
What are 3 different factors that influence infarcts?
anatomy of the vascular supply, rate of the occlusion, and the tissue vulnerability to hypoxia
165
what is shock?
when tissue oxygen and nutrient delivery is inadequate to meet physiologic needs
166
What are the 5 different types of shock?
cardiogenic, hypovolemic, shock associated with systemic inflammation (SIRS), neurogenic, and anaphylactic
167
what happens when PAMPs on the pathogenic bacteria/fungi interact with TLRs on innate immune cells?
there will be a release of inflammatory mediators and activation of complement
168
What is the final result of septic shock?
hypotension, hypovolemia, thrombosis; decreased tissue oxygenation
169
as septic shock progresses, how does it manifest?
manifestations of hypoxic tissue injury
