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87 Cards in this Set

  • Front
  • Back
What is ischemia?
-Loss of blood supply - either partial or complete.
What are the 2 main physiologic dysfunctions that result from ischemia?
-Loss of both aerobic and anaerobic metabolism due to loss of metabolic substrate supply.
-Accumulation of toxic products
When is ischemia reversible?
Prior to cell membrane disruption
What is the threshold beyond which ischemic changes are irreversible?
Membrane injury
What happens when the membrane is injured?
Cell death
What can we do to detect cell injury?
Measure enzymes like CK, LDH, myoglobin, and troponin.
What do we see on an EKG that reflects ischemic myocardium?
ST elevation
What is the immediate manifestation of ischemic myocardium?
Contractility ceases
How long does it take for contractility to cease?
1 minute of ischemia
Why do we care about ischemic heart disease?
It is the leading cause of death in the U.S.
What has happened to the death rate in the past 40 years due to ischemic heart disease?
A significant decline in death rates
What is the cause of ischemic heart disease?
Atherosclerosis in the coronary arteries
What is atherosclerosis in the oronary arteries called?
CAD - coronary artery disease
What occurs in CAD to cause ischemic heart disease?
Plaque formation and disruption
When in the course of CAD does ischemia occur?
late
How many patients with IHD have CAD?
90%
When does CAD begin?
In childhood
How does CAD progress to cause IHD?
A fatty streak turns into an occlusive plaque.
What are the 7 big risk factors for CAD?
SDHHMAR
What is SDHHMAR?
-smoking
-diabetes
-hypercholesterol
-hypertension
-male
-age
-race
At what age does CAD risk increase for
-males
-females
Males: 45 yo
Females: 55 yo
What race is at increased risk for hypertension as a risk factor for CAD?
African americans
What are the 5 features of Metabolic syndrome?
Obesity
Hypertension
Impaired glucose tolerance
Dyslipidemia
Microalbuminuria
How is metabolic syndrome related to IHD?
Patients with it are at a 2-3x higher risk of developing cardiovascular disease than the rest of the population.
What are 3 risk factors for women in developing CAD?
-Elevated triglycerides
-Central obesity
-Gestational diabetes
What are 4 ways to reduce the risk of getting CAD?
-Diabetes management
-Lipid management (statins)
-Smoking cessation
-BP control
What is a female-specific way to reduce the risk of CAD?
Hormone replacement therapy
What is the problem with HRT?
The risks seem to outweigh the benefits.
What are the 4 risks of HRT?
-Stroke
-CAD
-Pulmonary embolism
-Breast cancer
What is the best way to treat dyslipidemia?
Statins
How does Statin therapy work?
-Increases HDL
-Decreases triglycerides and LDL
What is CRP?
An inflammatory marker from expanded cores of atheromatous plaques.
What are 4 types of patients in which increased CRP can be found?
-Smokers
-Obese
-Diabetics
-Metabolic syndrome patients
What is the best inflammatory marker for CAD risk?
CRP
What level of CRP indicates:
-low risk of CAD
-high risk of CAD
low risk: < 1 mg/dl
high risk: >3 mg/dl
What molecule may cause endothelial dysfunction by interfering with NO functions?
Homocysteine
What are the functions of NO that are interfered with by homocysteine?
-Vasodilation
-Antithrombogenicity
What is the process that starts of atherosclerosis?
Fatty streak propagation
How does a fatty streak develop?
By the combination of activated smooth muscle + persistent hypercholesterolemia
What are 3 stimulators of smooth muscle?
-PDGF
-FGF
-TGF-beta
What does activated smooth muscle produce?
-Collagen
-Elastin
-ECMatrix proteins
So what is the first step in forming an atherosclerotic plaque?
Injury to the endothelial lining
What happens in response to endothelial injury?
-WBCs adhere to the endothelium and migrate into the intima
-WBCs secrete chemokines that stimulate macrophages and smooth muscle cells
What do stimulated macrophages do in generating a plaque?
Secrete pro-inflammatory molecules to form a chewy center of the plaque.
What do stimulated smooth muscle cells do in generating a plaque?
Produce ECM proteins that form a covering around the plaque.
What is determined by the balance between activated macrophages and smooth muscle cells?
Whether the plaque will become stable or unstable.
What is the result of an unstable plaque?
Acute coronary syndrome
-Angina
What are the characteristics of a stable plaque?
-Fairly sturdy fibrous cap covering the pro-inflammatory center - protecting it from platelets or thrombogenic sticky things.
What happens if collagen and the proinflammatory center are revealed by an unstable fibrous cap of an unstable plaque?
Activation of the clotting cascade and thrombogenesis - occlusion of the vessel.
What is more stable; larger, more occlusive plaques, or smaller ones?
LARGER >75% occlusive
Why are larger plaques more stable?
-Less bloodflow past the occlusion
-Less hemodynamic stress
-More fibrin
What plaques are at greater risk of being unstable?
50-75% occlusive plaques
What protective mechanism is induced by stable plaques?
Collateral circulation
What does collateral circulation achieve?
Myocardial conditioning
So what plaques are at the greatest risk for acute plaque change and acute coronary syndrome?
Medium sized
50-75% occlusions
What do we term these medium sized plaques?
Vulnerable plaques
What shape are the vulnerable plaques, and what is the implication of that shape?
-Eccentric
-The long leading edges are stress points for fissure
What are 2 categories of causes of acute plaque change?
-Mechanical stress
-Hemodynamic stress
What is the main form of mechanical stress inducing acute plaque change?
Vasoconstriction due to sympathetic stimulation.
At what time do most patients present clinically with angina due to adrenergic stimulation induced vasoconstriction?
Early in the morning when they rise and shine
What are 4 things that can happen in an acute plaque change?
THER
What is THER?
-Thrombosis
-Hemorrhage
-Erosion/ulceration
-Rupture
How can a plaque HEMORRHAGE into itself?
Blood vessels can develop inside them.
So what are the 4 steps in acute plaque disruption?
1. Loss of fibrous cap integrity
2. Thrombogenic collagen exposure
3. Capillary damage in the core
4. Fragmented plaque
And what are the 2 pathologic results of fragmented plaques?
-Embolization
-Platelet activation and thrombus
What type of infarct results from a total occlusion caused by thrombosis on top of plaque disruption?
Transmural
What can result from a partial occlusion caused by thrombosis on top of plaque disruption?
-Subendothelial infarct
-Unstable angina
-Sudden death syndrome
What part of the ventricular wall is most at risk for developing ischemia?
The subendocardial tissue just under the layer that recieves nourishment from the lumen of the ventricle itself.
So the most common cause of ischemic heart disease is:
CAD
What are 3 other less common causes of IHD?
-Hypotension
-Shock
-Severe anemia
So what are 4 clinical presentations of ischemic heart disease?
-Angina
-Myocardial infarct
-Sudden death
-Ischemic cardiomyopathy (chronic)
What are the symptoms of stable angina?
-Transient
-Squeezing chest pain
-Left arm/neck/jaw pain
-Relieved with rest/nitroglyc
What does the EKG show in relation to angina?
Cell membrane instability seen by ST segment elevations.
In what sex is sudden cardiac death more common? Why?
Women - they are less symptomatic and more likely to have silent MI
What is the risk of MI in women over 60 yo?
The same as for men
In what race is IHD more common?
Whites
In what race is hypertensive heart disease more common?
African americans
What are 3 things that can cause vasoconstriction?
-Adrenergic agonists (NE)
-Activated platelet products (txA2)
-Decreased endothelial derived relaxing factors (NO)
What is vasospasm related to?
Prinzmetal's Angina
What is Prinzmetal's angina?
Angina symptoms at rest
Do patients with Prinzmetal's angina have CAD?
They may or may not
What is the general cause of sudden cardiac death?
Lethal arrythmia due to irritable myocardium
What happens when there are chronic ischemic disruptions?
Fibrosis of the myocardium
What happens as the fibrosis is replaced by scar tissue?
Loss of myocardial compliance and contractility
What is the early sign of chronic ischemia?
Diastolic dysfunction (decreased filling)
What is the later sign of chronic ischemia?
Systolic dysfunction (inability to pump it out)
What are the 4 main methods for detecting IHD?
-Risk factor profiling
-Symptoms
-Stress test
-Coronary anatomy