Supply (perfusion) and demand of oxygenated blood.

Most Ischemic heart disease is secondary to reduced blood flow through sclerosed coronary arteries.

Coronary artery occlusion (thrombus, embolism, atherosclerotic plaque)

Anemia, decreased HCT and oxygen carrying capacity

Pulmonary disease, hypoxemia

tachycardia --too much time spent in systole and not enough in diastole (when blood is distributed to heart)

Tachycardia -- faster beating is metabolically expensive

Left ventricular Hypertrophy -- more muscle mass requires more O2.

Hypertension -- increased wall tention and effort to pump increase need for metabolism...causes LV hypertrophy

Physical exertion, emotional excitement

low supply can create situations of increased demand...ex. anemia (low supply of O2) caused the heart to beat faster (increased demand) to circulate more blood.

What are the four clinical syndromes of Ischemic Heart Disease?

That is to say, what clinical issues are underlayed by ischemia?

Myocardial infarction -- local cell death

Angina pectoris -- chest pain from heart cell hypoxia (nerves reacting to metabolites and panic signals)

Chronic Ischemic Heart Disease with Heart Failure

Sudden Death...not so much a syndrome as a final outcome.

Angina can be an acute or chronic issue. If angina is chronic and predictable it is considered ______.

If it is acute and not predicted/lasting longer than 20 minutes, it is considered ________.

Stable

Unstable (emergency...forewarns of an MI)

What can convert stable angina to unstable angina?

Ischemic heart disease is the leading cause of death in males and females in the US. IHD is caused, if you recall, by an imbalance between supply and demand of oxygenated blood of myocardial tissue -- generally from occlusion to the coronary arteries.

What level of occlusion can cause symptoms of ischemia (angina, perhaps) with exertion?

What level of occlusion can cause symptoms at rest?

75%

90%

A larger lipid core that can exert more pressure on the fibrous cap (between core and endothelium) and cause the fibrous cap to become thinner and more likely to:

Rupture/fissure

Erode/ulcerate

Hemorrhage

The answer is: Large lipid core with Thin fibrous cap

What is the common pathophysiological basis among the acute coronary syndroms of angina, acute MI, sudden death?

Provide a summary sentence describing the following acute coronary syndromes?

Angina

Unstable angina

MI

Sudden cardiac Death

Angina -- decreased O2 supply (notes indicate increased demand) due to stenosis (occlusion) of the vessel. Stable, no plaque disruption. Depending on % occlusion, causes transient myocardial ischemia (<90%)

Unstable Angina -- Sudden change in the plaque morphology (erosion, fissuring, hemorrage) that can severely but transiently alter coronary flow.

MI -- Total thrombotic occlusion of vessel due to acute plaque change (unstable angina can foretell)

Sudden cardiac Death -- complications such as disrupted plaque and partial thrombus/embolus can cause fatal arrhythmias -- inadequate blood flow.

Stable Angina, the most common form of angina.

Why is it called stable?

Stable because it is a predictable syndrome. With greater than 75% coronary vessel occlusion it can be induced by exertion, but dissipates in less than 15 minutes with rest and/or vasodilators such as nitroglycerine

Typical feeling of "squeezing, choking, constricting" the chest. Also common is neck or left arm pain (referred)

What are the characteristics of unstable angina?

The onset of symptoms breaks with previous patterns/frequency/severity.

Caused by disrupted plaques that can cause paroxysmal platelet aggregation and thrombus formation. Paroxysmal because these thrombi can form, be removed, form again, etc...

Can indicate an oncoming MI because these prothrombotic events are likely to set up conditions for an MI.

episodic angina, happens at rest.

usually without coronary stenosis

Caused by occlusion due to vasospasm (sympathetic stimulation/circulating agonist)

responds quickly to vasodilators (Fenoldepam, Minoxidil, Hydralazine, nitroglycerine as examples)

-----> may see elevated ST segment

Sudden death from cardiac causes usually occurs within an hour of symptom onset. May be the first clue you have. Ischemia is the most common cause (recall a partial thromus may initiate arrhythmias and cause inadequate blood pumping leading to ischemia). Of course Atherosclerosis likely underlies this. But there are also non  AS causes.

Name some non-AS causes

Electrolyte abnormalities (K+), valular disease, myocarditis, condction disorders, Hypertrophic Cardiomyopathy.

Likewise, these issues may cause fatal arrhythmias or make it difficult for blood to be pumped mechanically

What are some general risk factors for acute myocardial infarctions?

Simmilar to those for Coronary Artery Disease (CAD):

Older age

HTN

smoking

diabetes

hyperlipidemia, esp. hypercholesterolemia (cholesterol is what's in plaques)

Maleness

Two general types of MI, Transmural (across the wall) and Subendocardial.

What distinguishes the two?

Transmural MI's, as most MI's are, are necrosed the entire thickness of the wall. Represents the distribution of a single coronary artery.

Subendothelial MI's show necrosis limited to about 1/3 - 1/2 the wall thickness. Can extend laterally because of collateral circulation derived from parent artery. This may be cause by plaque disruption (like the transmural) or from global hypoperfusion -- remember heart blood flow is from epicardium to endocardium. Subendothelial can progress to transmural.

What are the sequential steps that occur in ischemia of the heart?

Within seconds:

within 2 minutes:

within 40-50 minutes:

taking hours:

within seconds, ATP is drastically reduced.

Within 2 minutes, there is a loss of contractility

Within 40 - 50 minutes, ATP is completely depleted

(irreversible damage happens after 20-40 minutes)

Microvascular injury occurs within hours, becoming leaky

What are the gross morphologica features of an MI?

<12 hrs

12-14hrs

10+ days

weeks

Less than 12 hours, no apparent changes (TTC stain makes infarct area pale)

Just over 12 hours the heart may appear reddish-blue, caused by vessels becoming leaky and blood seeping into tissues

10 days and beyond, the necrotic tissue is yellow/tan with a red, hyperemic border (inflammation and granulation tissue)

within weeks there has been scar formation, which appears white...you know, like a scar.

Describe the histologic appearance of an MI

4-12 hours

2-3 days

5-10 days

2-4 weeks

6-8 weeks

4-12 hours, myocardial fibers appear wavy, with spaces between. This is characteristic of coagulative necrosis.

2-3 days, there is acute inflammation with infiltration with neutrophils to destroy the dead cells

5-10 days, Macrophages replace the neutrophils to phagocytize the cellular debris left by the neutrophils (they are part of the debris)

2-4 weeks, granulation tissue is replaces by fibrosis

6-8 weeks, infarcted area is fully fibrosed

What methods might be available to try and reperfuse and area of tissue undergoing infarction (try to do this within 20 - 40 minutes to prevent irreversible cellular damage)?

Thrombolysis (Tissue plasminogen activator)

balloon angioplasty

PTCA (percutaneous transluminal coronary angioplasty)

A reperfused area of tissue has a red appearance from leakage of blood throught the inflamed vessel walls.

Reperfusion may cause some damage (reperfusion injury) and leave some stunned myocardium

Rapid, weak pulse

diaphoresis

Crushing chest pain (angina)

dyspnea

nausea

*diabetics may have "silent MI" possibly due to diabetic neuropathy

What are the laboratory markers used to detect and monitor MI's?

mention their relative importance/sensitivity

Myoglobin, elevated in MI, but not necessarily specific. Cleared relatively quicly.

Lactate dehydrogenase, elevated, not specific at all.

CK-MB, relatively heart-specific fraction of creatinin kinase -- but can be found in other tissues. Sensitive only for 72 hours. Begins rising within 2-4 hours, peak at 24, back to normal in 72.

Troponin T and I -- very MI specific (diagnostic). Rises within 2-4 hours and peaks in 48, remaining elevated for 7-10 days.

CK-MB and troponin are used in conjuction to monitor and define when a heart attack happened.

Free wall rupture (most likely 7-10 days post) ---> temponade, hemopericardium

Spetal rupture ---> left to right shunt, can cause right heart failure

papillary muscle rupture ---> severe mitral regurg. life threatening.

Dressler's Syndrome

Pericarditis that occurs weeks after an MI. Likely involves the immune system.

Otherwise, pericarditis is a normal finding within days due to inflammation.

Progressive heart disease following ischemic myocardial events (usually MI)

Compensatory mechanisms are exhausted (hypertrophy, dilation, colateral circulation)

up to half of pts may require heart transplant.