Week 4 Flashcards
(83 cards)
1
Q
What are the 4 things that occur in atherosclerosis?
- What forms?
- What happens to the vessel wall?
What occurs to the elasticity? - What happens to the size of the lumen and what does that lead to?
A
- Atherosclerosis
- Formation of fibro-calcific plaques
- Hardening of the vessel wall
- Decreased elasticity and strength of vascular wall
- Decrease in vascular lumen (stenosis) leading to hypertension
2
Q
How do aneurysms occur? Lay out the pathway.
A
- Atherosclerosis → decrease in elasticity and strength of vascular wall AND increase in hypertension → bulging of vascular wall proximal to stenosis → aneurysm
3
Q
What are the two types of aneurysms? One of the types has two subtypes. What are those? Have a picture in your mind.
A
- True Aneurysm – has all three layers of arterial wall involved
- Saccular – one side of vessel bulging
- Fusiform – both sides of vessel bulging
- Pseudoaneurysm – bulging with only tunica adventitia involved – interruption in vascular wall
- Bleeding into layers
4
Q
List 6 genetic or inflammatory conditions that can lead to a aneurysm and list the mutated genes in each (if applicable).
A
- Genetic and inflammatory diseases
- Marfan Syndrome Type I – defect in fibrillin-1 leads to lack of elasticity in vascular wall
- Marfan Syndrome Type II – defect in gene encoding transforming growth factor beta receptor 2 (TGFBR2)
- Ehlers-Danlos Syndrome – defect in COL3A1
- Loeys-Dietz Syndrome – defect in TGFBR1 and TGFBR2
- Giant Cell Aortitis – vasculitis that is positive for eosinophilic granulomas
- Infectious aneurysms – syphilis infection can be etiological agent beginning with tunica adventitia involving vasa vasorum
5
Q
In what age group and gender group is aortic dissection most common?
A
Males from ages 40-60 y/o
6
Q
What is an aortic dissection and what is one particular reason it is dangerous?
A
- Tear in the tunica intima that causes blood to dissect the vessel layers
- Dangerous because flap can block artery or false lumen can collapse true lumen
7
Q
What is the role of high blood pressure in aortic dissection?
A
- High blood pressure and turbulent flow leads to initial tear
8
Q
What are the clinical symptoms associated with aortic dissection?
How is it diagnosed?
A
- Clinical symptoms
- Sudden and severe tearing or crushing pain between the shoulder blades
- Mimics MI pain except that there no relief with antacids or nitroglycerin
- Associated with very high BP until rupture
- Diagnosed with CXR, which prompts for a chest CT
9
Q
What are the two types of aortic dissection?
- Where does the disection occur?
- What can it lead to?
- What are the treatments for each?
A
- Types of Dissection
- Type A – a for anything involving ascending aorta
- Cardiac tamponade – rupture into pericardium leads to blood squeezing the heart, making circulation impossible
- Rupture leads to fast death due to acute catastrophic hemorrhage
- Treatment: straight to OR
- Type B – b for anything beyond the aortic arch
- Treatment: medication to treat hypertension
- Malperfusion
- Type A – a for anything involving ascending aorta
10
Q
What are the two principal heart sounds and why do they occur?
A
- S1: closing of the AV valves; “lub”
- S2: closing of the SL valves; “dub”
11
Q
- What sound is associated with the physiologic splitting of the second sound?
- Why does it occur?
- How often doesit occur in the cardiac cycle?
A
- “Lub-didub”
- Splitting is heard near end-inspiration around every 4th cardiac cycle depending RR
- Respiration causes variation in RV filling volume, because it requires the pulmonic valve to stay open for longer to get the increased RV blood out into the pulmonary trunk
12
Q
- Define persistent splitting.
- What does it indicate and what is the mechanism?
- At what stage of breathing does it occur?
A
- Persistent splitting (A2 before P2): RBBB and pulmonary stenosis
- Happens at every stage of breathing (not just inspiration)
- RBBB: delay in RV contraction/emptying leads to later pulmonic valve closure
- PS: delay in RV contraction/emptying leads to later pulmonic valve closure
13
Q
- Define paradoxical splitting.
- What does it indicate and what is the mechanism?
- At what stage of breathing does it occur?
A
- Paradoxical splitting (P2 before A2): LBBB, aortic stenosis, R ventricular pacing
- Happens at expiration
- LBBB: delay in LV contraction/emptying leads to later aortic valve closure
- AS: delay in LV contraction/emptying leads to later aortic valve closure
- R ventricular pacing: if RV contracts before LV
14
Q
What is a gallop and what side of your stethoscope should be used to hear them? Where are they most often heard?
A
- Gallops = rushing of blood
- Low-pitched (requires use of bell) and only heard in mitral and tricuspid areas
15
Q
- What does an S3 gallop sound like?
- Why does it occur?
- What is the prognosis?
- What is it associated with?
A
- S3 = Rapid ventricular filling of LV with a high filling pressures
- “Ken-tuck-y”; S1 → S2 → S3
- Poor prognosis
- Associated with
- Heart failure, high EDP
- Volume overload –MR, AI, TR
- Can be normal in young people
16
Q
- What does an S4 gallop sound like?
- Why does it occur?
- What is it associated with?
A
- S4 = Atrial contraction against a stiff LV in late diastole
- “Tenn-ess-ee”; S4 → S1 → S2
- Associated with
- Pressure overload – HTN, AS, PS, etc.
- LVH/RVH
- Ischemia
17
Q
- What does a murmur mean?
- Is it physiologic or pathologic?
- What is the grade of the murmur determined by?
A
- Audible flow
- May be physiologic or pathologic
- Grade can be determined using location, quality, shape, radiation, thrills (palpable turbulent flow on surface of skin), and loudness
18
Q
- What are 4 physiological changes that could cause a high pitch murmur?
- What are 3 cardiac conditions that could cause a high pitch murmur?
A
- High Pitch Murmurs
- Large pressure difference
- Small defects/holes
- High velocity
- Typically systolic
- Examples:
- Aortic stenosis
- Mitral regurgitation
- Aortic insufficiency (only high pitch murmur that is diastolic)
19
Q
What are 4 physiological changes that could cause a low pitch murmur?
What is 1 cardiac condition that could cause a low pitch murmur?
A
- Low pressure difference
- Large defects/holes
- Low velocity
- Typically diastolic
- Examples
- Mitral stenosis (classic example caused by rheumatic fever)
20
Q
What is the grading scale of systolic and diastolic murmurs? WHich is harder to hear and which has thrills?
A
- Grading Scale
- Systolic: graded 1 to 6 out of 6
- Palpable thrills associated with high grades
- Diastolic: graded 1 to 4 out of 4
- Harder to hear and thrills unusual
- Systolic: graded 1 to 6 out of 6
21
Q
What are the 4 types of murmurs?
A
- Systolic ejection murmur
- Holosytolic murmur
- Diastolic murmur
- Continuous murmur
22
Q
For systolic ejection murmur:
- What condition is it most commonly associated with?
- What kind of noise pattern do you hear?
- Is S1 and S2 heard?
- Is it high or low pitch?
- Is S4 heard?
A
- Systolic ejection murmur – aortic stenosis
- “diamond-shaped” noise; crescendo-decrescendo
- S1 and S2 are heard
- High pitch
- S4 is heard
23
Q
For holosystolic murmur:
- What condition is it most commonly associated with?
- What kind of noise pattern do you hear?
- Is S1 and S2 heard?
- Is it high or low pitch?
A
- Holosystolic murmur – mitral regurgitation
- “Plateau” or uniform sound/noise
- Engulfs S1 and S2
- High pitch
24
Q
For diastolic murmur:
- What condition is it most commonly associated with?
- What kind of noise pattern do you hear?
- Is S1 and S2 heard?
- Is it high or low pitch?
A
- Diastolic murmur – mitral stenosis
- Starts with S2
- High pitch
- Pitch and and amplitude decline as diastole progresses
25
For continuous murmur:
* What condition is it most commonly associated with?
* Low or high pitch?
* Diastolic or systolic?
* Continuous murmur – patent ductus arteriosus
* Low-pitched, diastolic murmurs
26
What equation is it associated with oxygen demand of the heart? Is it used to compare consumption in one individual or used to compare different individuals?
* Rate Pressure Product (RPP) = HR x Systolic BP
* Correlates with oxygen consumption
* Is very dependent on the individual
27
What are the 5 charactersitics associated with cardiac demand?
* Wall stress
* Myocardial mass
* HR
* Contractility
* Resting cardiac metabolism and ionic fluxes – small O2 required even at resting
28
What is the equation for wall stress?
Wall stress = (Pressure \* radius) / (2 \* wall thickness)
* So, a thinner wall, larger radius or higher ventricular pressure will cause an increase in wall stress and therefore increase demand
29
What is the equation for the full pressure volume area?
30
Is HR proportional to O2 consumption?
What is the relationship between contractility and demand?
* O2 consumption is proportional with HR
* Higher contractility will increase demand
31
Supply of the heart is dependent on what two main characteristics?
* Oxygen content
* Coronary blood flow (predominantly important during diastole
* Coronary blood flow = Pressure/Resistance
32
What two things affect oxygen content?
What 4 things affect coronary blood flow?
* Oxygen content
* Hgb content
* Hgb saturation
* Coronary Blood Flow
* Coronary perfusion pressure
* Coronary vascular resistance
* HR
* External compression
33
What is the most important factor in altering coronary blood flow and what 4 things can it be controlled by?
* Coronary vascular resistance – most important factor is altering coronary blood flow
* Controlled by
* Metabolic factors
* Endothelial factors
* Neural factors
* Mechanical factors
34
How does HR affect coronary blood flow?
* HR (indirect)
* Decreasing time of diastole (due to higher HR) decreases the blood flow
* LV is able to compensate for this by dilating the coronary arteries 4x basal flow
35
What are the mediators of metabolic coronary vasodilation?
* Coronary Vasodilation
* Metabolic
* Adenosine
* Lactate
* Acetate
* H+ ions
* CO2
* Hypoxia
36
What are the mediators of endothelial coronary vasodilation?
What are the mediators of parasympathetic coronary vasodilation?
What are the mediators of sympathetic coronary vasodilation?
* Endothelial
* NO
* Prostacyclin
* Parasympathetic Activity (muscarinic)
* Ach binding
* At endothelial cells → NO release → vasodilation
* At smooth muscle → vasoconstriction
* Due to damage to endothelial cells that usually cover smooth muscle
* Sympathetic Activity (beta adrenergic)
37
What are the mediators of endothelial coronary vasoconstriction?
What are the mediators of sympathetic coronary vasoconstriction?
* Endothelial
* Endothelin-1
* Angiotensin-2
* Sympathetic Activity (alpha adrenergic)
38
What fuels do myocardium tissue use and in what progression?
* 60% of O2 consumption in the fasting state is due to oxidation of fatty acids
* The heart ultimately wants energy so it can switch to other forms of energy like carbohydrates (i.e. lactate, pyruvate and its own glycogen)
* In starvation, it can also use anaerobic respiration via breakdown of ketone bodies
39
How does the heart react to exercise?
* Exercise activate the sympathetic nervous system → increasing HR and contractility → increasing O2 demand → coronary blood flow must increase
40
Describe the structure of lipoproteins
* Structure
* Polar/hydrophilic envelope
* Apolipoprotein
* Free cholesterol
* Phospholipid
* Neutral lipid core
* Cholesteryl ester
* Triglyceride
41
Increasing density of cholesterol and decreasing size
Chylomicron → VLDL → IDL → LDL → HDL → HDL2
42
What is the function of LDL?
* LDL
* Gets cholesterol into tissues
* Gets TG into circulation
43
What is the function of HDL?
* HDL
* Gets cholesterol out of tissues
* Gets TG out of circulation
44
Explain the synthesis, absorption and clearance of cholesterol?
* Intracellular synthesis – HMG CoA Reductase
* SREBP increases transcription of HMG CoA Reductase
* Absorption from the intestine
* Clearance from the bloodstream – LDL receptors
45
Explain the role of bile in cholesterol circulation
* Bile synthesis and enterohepatic circulation
* Cholesterol is secreted as bile, but can be reabsorbed in the ileum as bile
46
Exogenous Pathway
Chylomicrons absorb triglycerides from the gut and put them into bloodstream → stripped of fatty acids/triglycerides by lipoprotein lipase at different tissue sites → chylomicron remnant → travel to the liver
47
Endogenous Pathway
Liver produces VLDL → deposits lipids into different tissue sites → IDL (E receptor on liver can reuptake) → deposits lipids into different tissue sites → LDL (B100 receptor on liver can reuptake)
48
HDL Pathway
HDL: a naïve molecule that picks up cholesterol via LCAT and takes it to the liver for recycling
49
What does Apolipoprotein E, A, C, B?
50
List some exogenous disorders of TG metabolism
* Exogenous
* Primary (genetic) hyperchylomicronemia
* Primary (genetic) hypertriglyceridemia
* Secondary hypertriglyceridemia
51
Familial Hypercholesterolemia
Mechanism
* Receptor synthesis/transport/folding
* Failed presentation of receptor
* PCSK-9 gain-of-function mutations
52
What is PCSK-9?
GOF vs. LOF mutations
PCSK-9: catalytic enzyme which degrades LDL receptors
Gain of function mutation: Increased LDL receptor degradation → familial hypercholesteremia
Loss of function mutation: Decreased LDL receptor degradation → reduced LDL levels in the blood
53
* Metabolic syndrome
* What is it?
* Criteria
* Central obesity with 2 of the following:
* high fasting glucose, high BP, high triglycerides, low HDL
* Its insulin resistance
54
Role of CETP
Effects on LDL and HDL
* CETP exchanges cholesterol from HDL/LDL with triglycerides from VLDL → triglycerides are deposited at different tissue sites via lipase activity → small density HDL/LDL particles form →
* Small density HDL particles are renally cleared
* decreases HDL concentration from body
* Small density LDL particles are very atherogenic!
* Produces smaller but more LDL molecules
55
Calculation of LDLc
* LDLc = TC – (TG/5 + HDLc)
* Must be done after fasting to get rid of the chylomicrons
* Can only be used when TG \< 400 mg/dL
* Key
* TC: Total Cholesterol
* TG = triglycerides
56
Explain the importance of assessing ventricular function
Important when the following symptoms arise: hypotension, exertional dyspnea, orthopnea, edema, syncope, arrhythmias, or unexplained organ failure
57
List some invasive techniques to access ventricular function
pulmonary artery catheter, thermodilution, ventriculography
58
Pulmonary artery catheter
* Description: Catheter balloon is inflated → static column of blood from catheter balloon to the pulmonary vein
* Gives a good estimate of left atrium pressure (wedge pressure)
59
Thermodilution
* Description: Cold saline is injected and then monitor cardiac function using PA catheter
* Temperature differences from blood and the injected saline is a function of cardiac output
* High cardiac output is correlated with fast temperature changes
* Only used in critical patients
60
Ventriculography
* Ventriculography – second to ECHO for EF analysis
* Description: Catheter-guided visualization of left ventricle
61
list noninvasive techniques to access ventricular function
fick method, cardiac hemodynamic assessment, echocadiography
62
Fick method
* ![]()SEE BELOW BC ARSH STILL DOES NOT REALIZE THAT EQUATIONS DO NOT PASTE
* In the heart, the denominator is flipped to ![](), because of the extremely high venous oxygen content and the low arterial oxygen content
63
Cardiac Hemodynamic Assessment
* Description: No tool or imaging is used. The patient is assessed based on symptoms only
* If patient is hypotensive, it can be assumed that the patient is hypovolemic
* Useful when many conditions coexsist
64
Echocardiography
* Echocardiography – most commonly used for EF analysis
* Description: ultrasound of the heart
65
List and describe the 6 main characteristics which ventricular function is assessed
* **Dimensions**: Size/volume/shapes → determines preload
* **Global systolic function (EF**) – Heart failure can be separated into two types: reduced EF and preserved EF
* **Wall motion abnormalities** – common cause for LV dysfunction
* **Hypertrophy** – increased LV mass commonly caused by diastolic dysfunction (HF with preserved EF)
* **Septal motional abnormalities:** provides info on abnormal ventricular pressure/volume
* **Diastolic function**: perturbed diastolic LV pressure-volume relationships
66
concentric vs. eccentric hypertrophy
Concentric hypertrophy: thickened wall with same volume
Eccentric hypertrophy: dilation
67
4 clinical risk factors
* Smoking → endothelial damage
* Diabetes → glycosylation of LDL
* Hypertension → increases LDL entering into tunica intima
* Hyperlipidemia → increased LDL
68
what are some other risk factors for CAD
* Traditional risk factors
* Age
* Male gender
* Family history in 1st degree relative → genetic predisposition
* Other emerging risk factors
* Greatest to least risk
* Exercise tolerance: fitness
* Smoking
* Systolic BP \> 140
* Cholesterol \> 240
* BMI \> 27
69
Diagram the mechanism of progression of CAD.
* Atherosclerotic plaque → further occlusion → plaque rupture → thrombosis
* Big thrombosis causes a myocardial infarction
* Small thrombosis causes myocardial ischemia
* Basically, CAD is the narrowing of the vessels supplying the heart (myocardial oxygen delivery is thereby reduced)
70
Sequence of events for ischemia:
* Inadequate blood flow
* Metabolic abnormality – reliance on beta-oxidation, which is not sustainable
* Abnormal wall motion – decreases contractility and wall eventually becomes akinetic
* EKG – ST depression (a little ischemia) and ST elevations (MI)
* Chest pain – late event (ischemia is silent; MI can be silent)
* Stable angina: activities requiring higher oxygen demand reproduces symptoms
* Unstable angina; less activity (or rest) reproduces symptoms
71
Relate the pathophysiology to methods to detect CAD.
* Reduced peak blood flow
* Metabolic abnormality
* Contractile abnormality
* Repolarization abnormality
* Chest Pain
* Reduced peak blood flow
* Exercise stress test (EST) with myocardial perfusion
* Metabolic abnormality
* PET scan
* Contractile abnormality
* Echocardiogram post-exercise
* Repolarization abnormality
* Standard (EKG) stress testing without imaging
* Chest Pain
* Patient says "ouch my chest hurts"
72
Explain basic treatment plan for CAD
4 parts
* Treat the risk factors. Then consider the physiology
* Ceasing smoking and initiation of exercise reduces of cardiovascular event more than drugs.
* Beta-blockers
* Decrease myocardial oxygen consumption by decreasing contractility, HR, and increasing diastole time
* Nitrates
* Venous dilation
* DHP Calcium-channel blockers
* Arterial dilation
73
Explain the central role of LDL cholesterol in cardiovascular (CV) risk management.
* High levels of LDL are correlated with higher chance of cardiovascular-related risk
* Low levels of HDL are more correlated with a higher chance of cardiovascular-related risk
74
What are the 4 clinical risk groups CVD and statin therapy options
* Clinical ASCVD (atherosclerotic cardiovascular disease)
* Tx: High/moderate intensity statin depending on age
* Hereditary Familial Hypercholesteremia
* Characteristics
* LDL-C \> 190 mg/dL
* Age \> 21 y/o
* Tx: High intensity statin
* Primary prevention – diabetes
* Characteristics
* Age 40-75
* LDL-C of 70-189 mg/dL
* Tx: High/Moderate intensity statin
* Primary prevention – no diabetes
* Characteristics:
* 10-year ASCVD risk of greater than 7.5%
* If between 5-7.5%, talk to patient about benefits/risks of statins.
* Age 40-75
* LDL-C of 70-189 mg/dL
* Tx: High/Moderate intensity statin
75
Identify the components of diet that alter CV risk.
To reduce cholesterol: eat fruits, vegetables, whole grains, nuts, and fish
Dairy and eggs have a low risk of increasing cholesterol in diet
Red meat and processed meats are high in cholesterol
76
statins vs. diet and exercise
Exercise and diet can only lower your LDL by a few percentage points. Therefore, the need for statin therapy is important because it can lower your LDL around 10-15%
77
Statins
MOA
Side effects
Utility
* MOA: HMG-CoA Reductase inhibitor; thereby increasing LDL clearance
* Adverse effects: Myalgias and rhabdomyolysis (muscle breakdown)
* Utility: Primary and secondary prevention
78
What is your body's reflex to long term statin use
* Reflex: compensation for statin therapy
* GI cholesterol absorption increases
* Cellular production of HMG CoA reductase increases
* The PCSK9 gene is activated
79
Ezetimibe
## Footnote
MOA
* MOA: inhibits cholesterol transport into enterocytes
* When given with statins, Ezetimibe has a better effect on preventing CV events
80
Bile acid sequestrants (i.e. Cholesevalam, Choleystyramine)
MOA?
* MOA: inhibit bile acid reabsorption in the ileum → more bile is secreted → more LDL is secreted → lower LDL
81
Plant stanols/sterols
MOA?
MOA: lowers reabsorption of LDL
82
PCSK-9 inhibitors (Evolocumab)
MOA?
Drawbacks?
MOA: monoclonal antibodies that bind to PCSK9 → inhibiting LDL receptor degradation → increasing LDL resorption into cells for degradation
Negative: $$$$$
83
Explain Unusual therapies for homozygous FH (HoFH)
* Lomitapide
* Mipomersen
* LDLpheresis
* Lomitapide
* MOA: blocks the apolipoprotein B from attaching to VLDL
* Mipomersen
* MOA: blocks the loading of triglycerides on apolipoprotein B
* LDLpheresis
* MOA: dialysis that removes LDL from your blood
