Review Q's Week 4 Flashcards
1. biochem artherosclerosis (1-32) 2. pharma anti angina (33-46) 3. physio hemodynamics (47-71) 4. patho atherosclerosis (72-88) 5. patho IHD (89-108) 6. nuclear cardiology (109-124) 7. physio seminar ECG leads (125-171) 8. clinical med acute coronary syndromes (172-197)
What are four things plaques are made up of?
cholesterol
lipids
inflammatory cells
Ca deposits
What occurs if the femoral artery gets occluded due to atherosclerosis?
intermittent claudication (condition in which cramping pain in the leg is induced by exercise)
What occurs if the internal carotid artery gets occluded due to atherosclerosis?
ischemia and cerebral infarction
What is the predominant cell in early atherosclerotic lesions?
macrophages
Where dos lipid accumulate in the arteries?
tunica intima
What are foam cells? Where can they be found?
Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
Where are smooth muscle cells located in the blood vessels?
in the tunica media
What occurs to the smooth muscle cells (SMC) of blood vessels during atherosclerosis?
foam cells release cytokines and growth factors that induce the SMCs to move to the tunica intima (they’re also changed to a repair phenotype instead of a contractile phenotype)
early atherosclerotic lesions are also called
fatty streaks/fatty dots (the first grossly visible lesion in the development of atherosclerosis)
Which lipoprotein reduces risk of atherosclerosis? Why?
LDL or HDL
HDL; it moves the lipids from the body back to the liver, this is why its called the good cholesterol.
LDL moves lipids to the body
What are the two ways cholesterol inflex is regulated?
too much free cholesterol inhibits the main cholesterol synthesis enzyme (HMG-CoA reductase) and it can also inhibit the DNA transcription of LDL receptors
What occurs to the cell if ACAT enzyme is defective?
the cell would get damaged. The ACAT enzyme acts to esterify and store free cholesterol, without it the free cholesterol would build up and cause damage to the cell (its toxic)
What are the receptors that uptake cholesterol via regulated versus unregulated pathway?
regulated= LDL receptors (they uptake native LDL)
unregulated= SR-A, CD36, oxLDL receptor (they uptake modified LDL’s!!)
What are the three uses for free cholesterol in the cell?
make steroids
make cell membrane
esterify and store it
Which of the following is a full transporter?
a. ABCA1: ATP-Binding Cassest Transporter A1
b. ABCG1: ATP-Binding Cassest Transporter G1
a. ABCA1: ATP-Binding Cassest Transporter A1
(ABCA1 gives both phospholipids and cholesterol esters to form the small HDL; ABCG1 only gives cholesterol esters to make the HDL bigger)
Where/Which receptor do the full HDL lipoproteins bind to?
the SR-B1 receptor in the liver
(it takes the lipids from the fat HDL and returns it to the circulation as a skinny legend)
How do modified LDL’s lead to inflammation?
by binding to toll like receptors (those activate inflammation)
(these modified/oxidized LDL’s get consumed by the macrophages by the unregulated scavenger receptors, but they also bind to the toll-like receptors on these macrophages and activate inflammation)
How does adaptive immunity play a role in atherosclerosis? explain.
dendritic cells (antigen-presenting) uptake the oxidized LDL, go to lymph, and present them to naive T cells. The naive T cells differentiate and go to the plaque to kill the oxidized LDL- this causes inflammation
What can be used biomarkers in coronary vascular disease?
inflammatory mediators
(use to diagnose)
What are the two hypotheses that explain how atherosclerosis develops?
1- response to injury (injury to endothelium caused the lipoproteins to go into the vessel wall and oxidize)
2- lipid retention (hyperlipidemia causes a the lipoproteins to go into the vessel wall and bind to matrix protein, aggregating and oxidizing) (…but why does it go into the vessel wall? because it’s going from the high lipid concentration in the blood to low lipid concentration on the vessel wall)
T/F: once the atherosclerotic plaque ruptures, occlusion is imminent
false, it doesn’t have to cause an occlusion, it can heal and cause stenosis instead
What can reduce the size of plaques?
efferocytosis (when dying cells are removed by phagocytic cells) or when cells migrate out of the plaque
Explain how plaques initiate
LDL accumulates in tunica intima and they get oxidized
oxidized LDL makes endothelial cells make adhesion receptors (ICAM, VCAM)
adhesion receptors attract monocytes and transform them into macrophages
macrophages express the scavenger receptors to uptake the oxidized LDL and transform to foam cells
What are four harmful effects of oxidized LDL?
- proliferation and migration of smooth muscle cells
- inducing endothelial cells to make adhesion molecules
- inducing MCP-1 (macrophage chemotactic factor protein-1) so monocytes get attracted to the site
- increase MCSF (macrophage colony-stimulating factor) so monocytes can differentiate into macrophages
Which cells mainly aid in producing the fibrous cap? how?
vascular smooth muscle cells; they are the ones that migrate into the tunica intima and produce extracellular matrix, collagen, elastin, etc. This forms the fibrous cap while the inner portion is filled with foam cells/macrophages.
Which plaque enzyme acts to degrade the fibrous cap?
metalloprotease
How does the necrotic/lipid core of the plaque form?
the macrophages that have lots of free cholesterol die first (they die because the free cholesterol is toxic), and release the free cholesterol into the plaque killing cells and forming the core (lipids and debris)
T/F: thrombosis symptoms appear as soon as the lipid core is formed
false; the lipid core doesn’t cause any symptoms when its under the fibrous cap, but when the plaque ruptures and the core interacts with the circulation, symptoms appear
T/F: apoptosis of macrophages is good for the atherosclerotic plaque development
false; apoptosis of macrophages can be both good and bad for the atherosclerotic plaque development. In the early lesion the apoptotic debris gets cleared, so it hinders plaque development. But later on when the plaque is bigger, the debris doesn’t get cleared, thus making the plaque bigger.
What plays a physical role in disrupting the continuity of the fibrous cap?
the free cholesterol makes sharp crystals that can mechanically/physically pierce the fibrous cap open
After a plaque ruptures and a thrombus is formed, what process can result in stenosis?
constrictive remodeling
What’s the difference between M1 and M2 macrophages?
M1= proinflammatory, initiate the plaque formation
M2= antiinflammatory, reduce plaque size and help tissue remodeling (matrix synthesis)
Patient feels severe chest pain when playing soccer, what kind of angina is this?
stable/classic/typical angina
What is Prinzmetal’s Angina?
Caused by coronary artery spasm (vasospastic angina) which reduces coronary blood flow leading to reduction of blood flow to the myocardium
Which administration method allows Nitroglycerin to reach a therapeutic dose faster?
a. Oral route
b. Transdermal route
c. Sublingual
c. Sublingual
What location does Nitroglycerin have the biggest effect on?
large veins (affected at lower doses)
Mechanism of action of Nitroglycerin. How does it reduce angina?
dilate veins, which decreases preload and venous return causing the oxygen consumption of myocardial muscle to be reduced
dilate arteries, which decreases resistance and afterload causing the oxygen consumption of myocardial muscle to be reduced
Explain how organic nitrates increase the blood supply to the heart.
Organic nitrates increase NO, which increase cGMP synthesis, which then relaxes vascular smooth muscle. This dialates coronary muscles and allows the blood supply to the heart to increase.
What drugs are contraindicated when organic nitrates are taken? why?
PDE5 inhibitors EX/sildenafil
it enhances the action of nitric oxide (NO) and cGMP and severely lowering blood pressure
How do beta 1-receptor Antagonists work to treat angina?
Reduce heart rate and force of contraction, thus reducing work done and oxygen demand.
When are beta 1-receptor Antagonists contraindicated?
in variant (vasospastic/Prinzmetal’s) angina (they man worsen symptoms)
Which Ca channel blockers is cardioselective?
a. Nifedipine
b. Verapamil
c. Amlodipine
d. Diltiazem
b. Verapamil
(a nondihydropyridine)
Side effect of Calcium Channel Blockers?
constipation
What kind of anti-anginal drug is Ranolazine? Where is it metabolized?
Sodium Channel Blocker; Extensively metabolized in the liver by CYP enzymes
Patient comes in with unstable angina, what can you prescribe?
aspirin
heparin
clopidogrel
What’s the long term effect of aspirin? explain.
reduced platelet aggregation; aspirin selectively inhibits thromboxane synthesis by inhibiting COX-1 (COX is the precursor to thromboxane)
thromboxane= hypertensive agent that facilitates platelet aggregation
platelets do not possess a cell nucleus and are therefore unable to resynthesize COX
Describe the relationship between blood flow and resistance versus blood flow and pressure gradient
↑Resistance= ↓ blood flow
↑pressure gradient= ↑ blood flow
What is the normal value of Pulse pressure?
40mmHg
Pulse pressure is the difference between systolic and diastolic; so the difference between them 120/80 mmHg
An increase in which of the following increases resistance?
a. viscosity of blood
b. radius of vessel
c. length of vessel
d. A+B
e. A+C
e. A+C
In a healthy patient, in which location can the blood flow become turbulent during exercise?
ascending aorta
What are four things that facilitate turbulent flow?
large blood vessels diameters
high velocities
low blood viscosity
stenotic cardiac valves
T/F: the total cross sectional area of capillaries are higher than the aorta
true
What’s the major mechanism of regulating blood flow and blood pressure?
Vascular tone (the degree of contraction of vascular smooth muscle cells)
(for the record, both vascular tone and CO regulate BP)
Describe the role of the arterioles in regulating the blood pressure and the blood flow
They use vascular/arterial tone to regulate each of the following; its a war between increasing the pressure and allowing the blood flow, they’re opposite forces
What occurs if the arterioles were fully dilated?
anaphylactic shock; we don’t have enough blood to fill all the arteries, that’s partly why they’re always constricting
How do extrinsic factors affect arteriole contraction?
extrinsic factors mostly constrict the arterioles
(they’re selfish and want a higher blood supply, so they constrict to get more.)
How do the intrinsic factors affect arteriole contraction? Where do these factors come from?
They usually dilate the arteries, they’re selfish and only care about the blood they’re getting, not about any other organ’s blood supply.
These factors come from the endothelial cells of the arterioles and from the surrounding tissue autocrine/paracrine.
In theory, when blood pressure increases the blood flow would also increase, this doesn’t happen in the body, why?
because the vessels contract to compensate
When the pressure increases, the diameter of the vessels increases with it- this causes a blood flow increase. However, right after, the vascular smooth muscles constrict to reduce the diameter and bring blood flow back to normal.
How do the vascular smooth muscle cells know when to contract?
(they contact when the blood pressure increases abruptly)
There are pressure/tension receptors that sense these changes and start the cation influx which leads into contraction.
TRPC6 receptors (Transient receptor potential cation channel)
After running for 5 minutes, the blood flow to skeletal muscle increased drastically. What do you call this? Explain the mechanism.
active hyperemia
This occurs due to tissue hypoxia and the generation of vasoactive metabolites
What is passive/reactive hyperemia?
higher blood flow after a period of ischemia
How will endothelial damage affect vessels? Would it cause vasoconstriction or vasodilation? Why?
vasoconstriction, because endothelial damage causes decreased secretions of Nitric oxide and Prostacyclin (which are both vasodilators) so the substances that cause constriction go unchallenged.
What are four endothelium produced substances that cause vasodilation?
Nitric oxide
Prostacyclin
Endothelium derived hyperpolarization factor
Acetylcholine (when endothelium is intact, it causes dilation. if not, then constriction)
How do bradykinin and histamine affect both arterioles and veins? What can this lead to?
they dilate arterioles and constrict veins
this causes the blood to easily leave the heart (low afterload) and get stuck in the dilated veins- leading to edema
Describe the vessel constriction/dilation from point A to point B. How is the relationship between the pressure and blood flow in this interval?
vessels maximally dilated, so the resistance is as low as possible.
pressure and blood flow are linearly proportional
Describe the vessel constriction/dilation from point B to point C. How is the relationship between the pressure and blood flow in this interval?
During this stage, the vessels are constricting to neutralize the pressure changes, so when you increase the pressure you don’t see as much change in the blood flow. The resistance is increasing
Describe the vessel constriction/dilation from point C to point D. How is the relationship between the pressure and blood flow in this interval?
The vessels in this area are maximally constricted and the resistance is as high as it can be. So the vessels did what they could do, but the relationship between pressure and blood flow is linearly proportional.
Explain the long term pressure increase. In what ways to the vessels adapt to the higher pressure?
the pressure changes have very low effect on the blood flow (because it occurs slower and the body has time to adapt)
Adaption occurs by the proliferation of vascular smooth muscle cells of the vessels, so they become thicker and the diameter decreases. This allows them to withstand higher pressure.
Explain how an acute increase in pressure (and thus blood flow) is counteracted by metabolic responses.
As the pressure increases, it initially dilates the vessels and increases flow (occurs before the muscles contract in response) This flow of blood dilutes the dilatory substances, causing the vessels to constrict.
What organs have the highest autoregulation? lowest?
highest= brain, kidney, heart
lowest= skin
What are the autoregulation range? (the pressures that the body can successfully regulate) Explain why these limitations exist.
around 50-120mmHg or 60-180mmHg
we can’t regulate below 50mmHg because at that pressure the vessels are fully dilated
We can’t regulate above 180/200mmHg because the vessels are fully contracted (what else do you want them to do? they’re trying their best!)
arteriosclerosis vs arteriolosclerosis
differentiate between them
arteriosclerosis= in arteries (large and medium sized)
arteriolosclerosis= in arterioles (small sized)
Which of the following does atherosclerosis mostly affect?
a. tunica intima
b. tunica media
c. tunica adventitia
a. tunica intima
(tunica media indirect affect)
Which hormone has a protective effect from atherosclerosis?
estrogen
What are a few things that can result in endothelial dysfunction?
high BP, fungi, toxins, nicotine, oxidized LDL, homocysteine
What attracts smooth muscle cells from the tunica media to intima?
monokines made by macrophages
What induces smooth muscle cell proliferation?
platelet-derived growth factors and other cytokines
T/F: thrombosis is the initial step of atherogenesis
false, its a complication of atherogenesis
What is a mural thrombus?
a thrombus that adheres to the wall of a blood vessel. They occur in large vessels such as the heart and aorta, and can restrict blood flow but usually do NOT block it entirely.
Explain what happened to this vessel.
layering of many mural thrombi, which then resulted in stenosis over time
What is the blue circle highlighting?
calcification
Describe the fibro/fatty proportions of this plaque.
it’s a fibrous plaque
What process does this picture show? (wall very thick and to the side)
remodeling of lesion
the lesion invaded the tunica adventitia and grew into it instead of growing into the lumen of the vessel
Eccentric coronary stenosis
What kind of thrombus is “M”?
intramural thrombus
What kind of thrombus is this?
occlusive/luminal thrombosis
What can you seen near the lumen of the vessel? What does this indicate?
you can see cholesterol crystals (white and pointy) so that means that there was a rupture nearby and that’s how they ended up in the lumen. Its an atheromatous embolus, which is due to the fragmentation of cholesterol crystals or atheromatous debris from atherosclerotic vessels.
What are the two types of acute MI?
transmural (due to a complete occlusion)
subendocardial (due to partial thrombus that causes low perfusion, leading the endocardium of the heart to die)
What can you see in this myocardial tissue?
contraction band necrosis (happens because myocytes die while contracting)
there’s also fewer nuclei present
*early myocardial necrotic changes
Describe the state of the myocardial tissue.
advanced necrosis and neutrophilic infiltration
identify cells
blue arrow= macrophages
yellow arrow= fibroblasts
*this is granulation tissue
describe the state of the myocardial tissue
fibrous tissue formation
What is Myocardial rupture? When does it occur?
Its when an area of the muscular wall of the heart weakens and ruptures (it ruptures because of the high pressure in the heart, like a baloon with no contracitlity). If this happens, then blood from witlhin the heart can leak into the pericardium.
This usually because of a heart attack; after the MI inflammation occurs and polymorphonuclear cells are trying to digest the dead tissue causing the area to be less rigid and more liquefactive, leading to rupture.
This is a heart of a hypertensive patient with a previous MI. explain what happened.
the previous MI may have weakened his heart (and dilated it) causing the ejection fraction to decrease. This would cause a build-up of blood in the ventricle that would coagulate and form a mural thrombus (it can also be pumped and become a systemic embolism)
Diagnose.
The short axis (one on top) is different during rest and exercise, the inferolateral wall of the ventricle doesn’t have enough circulation during exercise. This reversible quality means that it’s ischemia (change during stress, not permanent)
Diagnose.
Block appears in rest and during stress so it’s infarct/blocked artery. Scarring is what caused this result.
diagnose the scintigraphy image.
dilated left ventricle (bad prognosis)
diagnose
MI (regions of necrosis, which have a bad supply at rest and in stress)
Describe the viability of the tissue. explain.
The tissue is not viable (scar tissue) because the blood flow and the metabolism are absent, meaning that the tissue is fully dead- irreversible damage.
Describe the viability of the tissue. explain.
The tissue is hybernating and viable. The blood flow is not reaching some regions, but they still have active metabolic processes. So if you reperfuse the tissue it will still function.
Which of the following leads have the highest reaction to this vector?
a. lead 1
b. lead 2
c. lead 3
c. lead 3
T/F: unipolar chest leads have one pole
false, they have the positive pole and a null/near-zero pole (created by averaging out three electrodes- this average acts like it’s in the center of the heart)
Which of the following chest leads are anteroseptal leads?
V1, 2, 3, 4
(picture= V1+2 detect septal changes while V3+4 detect anterior changes.)
How to classify chest leads:
based on their location
VS
based on electrical changes they see
(you can ignore this if you want, I got this info from Dr.Najeeb)
based on their location:
V1+2= over the right side of heart (right leads)
V3+4= over the septum of heart (septal leads)
V5+6= over the left side of heart (left leads)
based on electrical changes:
V1+2= see septal changes (septal leads)
V3+4= see anterior changes ( anterior leads)
V5+6= see left changes (left leads)
name
qRs
name
Qr
name
qR
name
rS
name
QS
name
rsR’
If the initial deflection is positive = an R wave
A negative deflection following an R wave = an S wave
A second positive deflection (Another R) = an R’ wave
name
Rs
During left bundle branch, what can you seen in the V1 chest lead? how about V6?
V1= W pattern
V6= M pattern
how does K concentration affect T wave?
hypokalemia= low T wave
hyperkalemia= high T wave
Which kind of MI causes ST segment elevation/deep Q waves?
a. Transmural MI
b. Subendocardial MI
a. Transmural MI
T wave inversion is associated with
myocardial ischemia (increased cardiac death)
(we also said that some leads go through T wave inversion during ventricular hypertrophy)
What is the J point?
The point between the end of the QRS complex and the ST segment
Which of the following shows J point depression only? (not ST-segment depression)
E
(Up-sloping depression of less than 1 mm at 80 ms beyond the J point (E) is simply J point depression)
What is a Q wave MI?
myocardial infarctions that in a Q wave forming on the 12-lead ECG once the infarction is completed. Many Q-wave infarctions are often non-transmural, and conversely, transmurality may occur in the absence of Q-waves.
