Highlights lecture 4.1 Flashcards
Explain why the following can cause edema when they have issues:
1) Venous return
2) Oncotic pressure
3) Lymphatic obstruction
4) Sodium retention
5) Inflammation
1) Too much pressure
2) Solute is gone
3) Drain is broken
4) Water follows salt
5) Leaky vessels
What does myocardium release (for BP regulation)?
Natriuretic peptides
Name two things that compound each other in a cyclical manner
Heart failure & Renal failure
What is another factor in pts with both HF and kidney failure?
Change in oncotic force (an issue with albumin)
Petechia is caused by a deficiency in what?
platelets
Why do ecchymoses (bruises) change color?
Hemoglobin goes from blue > bilirubin (blue-green) > hemosiderin (golden brown)
Massive hemorrhage may lead to hypovolemic ___________.
shock
What is the worst case scenario for a hematoma?
Compartment syndrome
Chronic hemorrhages can cause slow blood loss, which can lead to what?
Iron deficiency anemia
Primary hemostasis: platelet plug
1) What happens when the endothelium is broken?
2) What does do to the platelets?
3) What do the platelets do next?
4) What do all these steps lead to?
1) Von Willebrand factor (vWF) is released
2) Promotes platelet activation; shape change!
3) Release granules that recruit more platelets
4) Platelet aggregation/ primary plug
Step 3 of hemostasis: Secondary hemostasis: fibrin clot
1) What is exposed to cause the clotting cascade?
2) What is ultimately the result of this cascade?
1) Tissue factor
2) Thrombin turns fibrinogen into a fibrin clot
Step 4 of hemostasis: Clot stabilization and resorption
1) Fibrin makes a solid, permanent scaffolding that stops what?
2) Counterregulatory mechanisms come into play to ________ too much clotting; specifically ________________.
3) ______________ breaks down fibrin.
1) Further clotting
2) limit; tissue plasminogen activator tPA
3) Plasmin
Explain the 4 steps of hemostasis very briefly
1) Arteriolar vasoconstriction
2) Primary hemostasis: vWF release, platelet activation, release of granules, then aggregation.
3) Secondary hemostasis: Tissue factor + clotting cascade; thrombin turns fibrinogen into fibrin clot
4) Clot stabilization + reabsorption: Fibrin scaffolding, tissue plasminogen activator tPA, plasmin breaks down fibrin
slide 22
1) PT/INR addresses __________ pathway
2) PTT addresses the ______________ pathway
3) Note there are several “____________” that amplify the sequences
1) PT/INR extrinsic
2) PTT intrinsic
3) “feedback loops”
Heparin-Like Molecule does what for clotting inhibition?
Activates antithrombin!
Endothelial cells become anticoagulant by releasing _________________ complexes that block ________ activity
tissue factor VIIa; VII
Protein C and its cofactor protein S are what?
Anticoagulants that disrupt the clotting pathway
What would deficiency of protein C and protein S do?
Make you clot [taking away the anticoagulant will make you clot]
1) What does the endothelium make for clotting inhibition?
2) List 3 other clotting inhibitor products
1) tPA
2) Prostacyclin (PGI2), nitric oxide, adenosine diphosphatase
What acts by inhibiting vitamin K and depletes its reserves in the body?
Warfarin (anticoagulant)
Heparin (anticoagulant): Activates ___________; inhibits ______________
antithrombin; thrombin
What act directly on Xa clotting factor?
Xa inhibitors: Novel Oral Anticoagulants (anticoagulant)
What drug binds irreversibly to platelets?
Aspirin (antiplatelet)
What drugs block the receptor for ADP on platelets?
P2Y12 inhibitors (antiplatelet)
Why “bridge to Warfarin?” by giving Heparin?:
Because warfarin inhibits production of __________________ causing a temporary _______________ state, before ___________________ is fully blocked
Protein C and S; procoagulant; clotting cascade
A sign that clotting has been going on occurs when breakdown products of fibrinogen appear in the blood (called “fibrin-split products”), the measurable one of these is called what?
D-dimer
What are 4 examples of clotting/ clotting inhibition gone wrong?
1) Factor V Leiden Mutation
2) Protein C and S deficiency
3) Antithrombin III deficiency
4) Von Willebrand’s disease
To Tx Blood Clots and Cardiovascular Disease:
1) _______________ with heparin or NOAC now called (DOAC)
2) Use ASA or P2Y12 inhibitors for ____________ therapy
3) ________________ clot with tPA
1) Anticoagulate
2) antiplatelet
3) Lyse
______________ (friable) portion of a thrombus growth is poorly attached and prone to fragmentation, leading to ____________
Propagating; embolus
Describe the inheritance pattern of Factor V Leiden
Autosomal dominant with incomplete penetrance
What does Factor V do?
Accelerate clotting
Heparin induced thrombocytopenia (HIT):
1) Autoantibodies bind to complexes of heparin and platelet membrane protein and endothelial surfaces, this leads to a ______________ state.
2) What do you need to do bc of this condition?
1) PROTHROMBOTIC
2) Always get PT/INR PTT baseline before starting heparin
Disseminated Intravascular Coagulation (DIC):
1) What is it?
2) What happens simultaneously?
3) What does this lead to?
1) Wide-spread clotting in the microcirculation all over the body
2) Fibrinolytic mechanisms are activated
3) Profuse bleeding
Sepsis alters the expression of clotting factors, and it _____________ coagulation
favors
Septic Shock Hypercoagulation: Cytokines inhibit tissue factor pathway inhibitor, thrombomodulin, and protein C, causing what kind of state?
Hypercoagulable
Septic Shock & metabolic derangement:
As the cells continue bearing the brunt of shock (inadequate perfusion) they become increasingly hypoxic, and lactic acid is produced, leading to lactic acidosis; what does this do to blood pH?
Blood pH drops
Septic Shock and organ dysfunction: systemic hypotension, interstitial edema and small vessel thrombosis all decrease what?
Oxygen and nutrients to tissues
Septic Shock and organ dysfunction:
1) What happens to the heart?
2) What does this do?
1) Myocardial contractility starts to diminish
2) Reduce cardiac output
Septic Shock and organ dysfunction:
1) What leads to ARDS?
2) What are all eventually catastrophically effected, leading to death?
1) Increased vascular permeability
2) Kidneys, liver, lungs, heart
True or false: severe shock by other means still leads to poor perfusion which can cause most of the organ effects of septic shock to occur
True
Normal blood vessels are organized into 3 concentric layers (more apparent in larger arteries); what are they?
Intima
Media
Adventitia
In ___________ shock, skin may be warm and flushed secondary to peripheral vasodilation
septic
The 3 main forms of vascular disease are as follows:
1) Clog the pipe
2) Weaken the pipe
3) Born with bad pipes
Where do each of the following fit in those categories?:
a) Congenital anomalies
b) Hypertension
c) Atherosclerosis
d) Aneurysms and Dissections
e) Vasculitis
f) Tumors
1) Clog the pipe: Hypertension, atherosclerosis, vasculitis, tumors
2) Weaken the pipe: Hypertension, aneurysms and dissections
3) Born with bad pipes: Congenital anomalies
Give 3 examples of congenital anomalies of vasculature
1) Berry aneurysms
2) Arteriovenous fistulas
3) Fibromuscular dysplasia
1) What are arteriovenous fistulas? Are they always dangerous?
2) Are they ever intentional?
1) Abnormal connections between arteries and veins that bypass capillaries
-May be benign, may cause abnormal shunting of blood into venous system
2) Done intentionally for dialysis
Atherosclerosis: what are the 3 localized types and what might each cause?
1) Cerebral: stroke
2) Coronary: MI
3) Aortic: Aneurysm rupture
List 3 potential clinical consequences of AAAs
1) Obstruction of branch vessel
2) Compression of adjacent structure
3) Rupture into peritoneal cavity (usually fatal)
True or false: Hypertension is a major risk factor for aortic dissection
True
1) Marfan syndrome affects what system that predisposes them to aortic dissections?
2) What gene? What is this gene important for?
1) Cardiovascular system
2) The fibrillin 1 (FBN1) gene; scaffold for elastin
Marfan syndrome does what cardiovascularly?
Weakens connective tissue around the base of the aorta
______________ resistance is mostly controlled by arterioles through ____________ and _____________ factors
Peripheral; neural and humoral
1) 90% to 95% of cases of hypertension are essential hypertension which is ______________.
2) What are 2 contributing factors to HTN?
3) List the 4 major sequalae of HTN
1) Idiopathic
2) Salt + obesity
3) Cardiac hypertrophy
Heart failure
CVA
Dissection
Thrombangitis Obliterans (Buerger Disease):
1) What size arteries does it affect? Especially which two arteries?
2) It occurs almost exclusively who? When?
1) Medium and small arteries; tibial and radial
2) Almost exclusively in heavy smokers, usually before 35
Thrombangitis Obliterans (Buerger Disease):
1) Is there a cure?
2) Thrombus typically contains what?
1) Smoking cessation can be curative
2) Microabscesses
Raynaud Phenomenon:
1) What is it?
2) Who is it often seen in?
1) Vasoconstriction of digital arteries and arterioles
2) Young women
Raynaud Phenomenon: What are the two types and their causes?
1) Primary: usually benign
2) Secondary: caused by other autoimmune disease
Define hemangioma
Increased numbers of normal or abnormal vessels
1) Define hemangioma
2) Kaposi Sarcoma is most frequently associated with what?
1) Increased numbers of normal or abnormal vessels
2) AIDs
Familial hypercholesterolemia (FH) is a disorder of cholesterol and lipid metabolism caused by what?
Mutations in the low-density lipoprotein receptor (LDLR) gene
Familial Hypercholesterolemia:
1) Hepatic LDL receptors clear half of what?
2) Hepatic LDL receptors clear up to 80% of what from circulation by endocytosis?
3) Mutations occur through combination of large ______________/ _____________ and recombination involving _________ repeats
4) Mutations in the LDLR gene disrupt what? What does this cause?
1) Intermediate-density lipoproteins
2) LDL
3) insertions/ deletions; Alu repeats
4) Production of LDL receptor; accumulation of plasma LDL
_____________________ FH (Familial Hypercholesterolemia) presents in the first decade of life with arcus corneae and tendon xanthomas.
Homozygous
Familial Hypercholesterolemia:
1) What is required to reduce the risk of CAD?
2) What kind of diet can give an insufficient 10-20% reduction in LDL?
1) Aggressive normalization of LDL cholesterol concentration is required
2) Low-fat, high-carbohydrate
Familial Hypercholesterolemia: Heterozygous patients receive what 3 things?
1) Bile acid sequestrants
2) Statin drugs that inhibit hepatic cholesterol synthesis
3) LDL apheresis (where LDL is filtered from the blood using a machine)
Hypercoagulability causes:
1) Which condition turns up the thing that makes you clot?
2) Which two conditions turn down the thing that stops clotting?
3) Which 3 reasons cause hypercoagulability because of internal damage?
1) Factor V Leiden mutation
2) Anti-thrombin III deficiency
Protein C and S deficiency
3) Surgery, tissue injury, anti-phospholipid antibody syndrome (attack against blood vessels)
Hypercoagulability causes:
1) Which two conditions cause sticky blood?
2) Which two reasons involve estrogen’s sticky nature?
3) Why can cancer and prosthetic valves both lead to hypercoagulability?
1) Immobility + atrial fibrillation (afib)
2) Pregnancy and postpartum + Oral contraceptives (esp. if smoking over 35)
4) Both are sticky
