cardiovascular function

normal endothelium

• smooth

• very tight junctions in between individual cells

how can endothelium be damaged

• smoking

• mechanical stress caused by HTN

• elevated LDL

• mechanisms of the immune system

where do athlerosclerotic lesions form

where vessels branch or in areas of turbulent blood flow

what is the meaning of turbulent blood flow contributing to atherosclerosis

suggests that hemodynamic factors play a role in endothelial injury

when endothelium is damaged or LDL is high

• monocytes become stick

• attach themselves to the endothelium in response to adhesion molecules

result of monocytes sticking to endothelium

endothelium loses some of its ability to produce antithrombotic and vasodilating cytokines

monocyte emigration

• an early response to endothelial injury

• the movement of monocytes into the intimal layer of the endothelium squeezing through cell junctions

after monocyte emigrates to intimal layer

• continue emigration into subendothelial space

• monocytes are transformed into macrophages

• free radicals released

what do the monocytes turn into

macrophages

what do macrophage do in atherosclerosis

consume the oxidized LDL and form foam cells

foam cells

release growth factors, inflammatory cytokines that worsen endothelial injury and further the process of atherogenesis

LDL oxidation

• LDL make their way through the intact endothelium and are quickly oxidized into proinflammatory lipids

• oxidized LDLs act as an attractant to monocytes in the endothelium causing further migration

smooth muscle proliferation

• when the platelets in the blood are exposed to the subendothelium, they adhere to the site of injury

• followed by proliferation of smooth muscle

  • causing endothelial layer to pouch out making the lumen of the vessel smaller

formation of fatty streak

• Think, flat, yellowing discolourations that enlarge over time occluding the vessel lumen

what is the fatty streak made from

macrophages and smooth muscle cells that are distended with no lipid to form foam cells

formation of lipid core

• Lipids accumulate beneath the endothelial layer and form a hard lipid core

• The atherosclerotic plaque becomes vulnerable to rupture as enzymes eat away at the protective fibrous cap

plaque hemorrhage

• Prothrombogenic mediators are released as the plaque begins to fissure or rupture

• Platelets floating by adhere to the lesion with the help of procoagulant factors and a thrombus is formed 

  • Blood flow to the coronary artery and myocardium can be compromised leading to infarction

steps/sequence of atherosclerosis

• endothelial cell injury

• monocyte emigration

• LDL oxidation

• smooth muscle proliferation

• formation of fatty streak

• formation of lipid core

• plaque hemorrhage

more causes of endothelial injury

• HTN

• smoking

• hyperlipidemia

• hyperhomocysteinemia

• hemodynamic factors

• toxins

• immune reactions

myocardial ischemia

restriction of blood supply that results from an imbalance between myocardial oxygen supply and demand

factors in oxygen supply and demand from the heart

• coronary vessel patency

• ventricular wall compression

• diastolic filling time (heart rate)

• myocardial contractility

• heart rate

• wall stress (preload, afterload)

diastole

the portion of the cardiac cycle when the ventricle is in a relaxed state, stretching as it fills with blood from the atrium

what is oxygen supply regulated by

• the patency or size of the lumen of the coronary vessel

• The ability of the ventricular wall to compress

• The amount of time the ventricle spends in diastole

what is oxygen demand dependent on

• Myocardial contractility

• Heart rate

• Vascular wall stress

• preload and afterload

what if preload or afterload is too high or low?

added stress to the heart → higher oxygen demand

in normal heart how is increased demand of oxygen met?

increasing supply of oxygen

*may not occur in non healthy heart

supply ischemia

an abrupt or acute reduction in blood flow to the myocardium caused by thrombus, coronary vasospasm or platelet aggregation

demand ischemia

an increase in need for oxygen and nutrients due to exercise or stress

what happens in coronary artery disease with oxygen supply and demand

With coronary artery disease increased demand causes an imbalance

potential outcomes of cell injury

• reversible injury, cell recovery, and return to normal function

• apoptosis and programmed cell removal

• cell death and necrosis

common causes of ischemia

• Blockage or coronary artery, thrombus 

• Spasm of coronary artery

• Coronary artery obstruction (formation of plaque)

cellular effects of ischemia

• inadequate supply of oxygen and nutrients

• accumulation of waste

• inadequate

how long does it take for myocardial cells to become ischemic and decrease contractility

within 10 seconds of blood flow being interrupted adn contractility is depresses within minutes

how long for ischemia to progress into necrosis

20 minutes if blood flow is not resolved

what happens when oxygen not available

• shift to anaerobic processes

• only 2 ATP molecules and lots of pyruvic and lactic acids which are toxic to our cells

why is it bad to have anaerobic metabolism

without ATP our NaK pump becomes inefficient and electrical impulses in the heart and nervous system become uncoordinated, which can lead to dysrhythmias

what happens in accumulation of waste

• Inflammatory mediators are released

• Granulocyte activation 

• Free radical accumulation

what is the result of inadequate supply and accumulation of waste

• Alteration of cell membrane

• Cell edema

• Arrhythmias

• Cell death

• Failure of contraction

hemodynamic effects of ischemia

• reduced contractility

• abnormal wall motion and changes in compliance

• decreased cardiac output

• reduced ventricles emptying

• compensatory stimulation of the SNS

why is there reduced contractility with ischemia

• the larger the area of ischemia, injury or infarct, the less ventricular muscle available to contract

abnormal wall motion and changes in compliance in ischemia

• hypokinesis or akinesis

• leads to ventricular walls losing their elasticity so they can no longer stretch to accomodate incoming volume

hypokinesis

poor contraction of the heart

akinesis

full loss of ability of heart to contract

what is decreased cardiac output in ischemia a result of

low stroke volume

when is there reduced ventricle emptying in ischemia

at the end of systole

how are compensatory stimulation of the SNS happen when there is ischemia

• senses a drop in cardiac output

• initiates increased HR and BP to compensate

what is acute coronary syndrome

• Spectrum of ischemia diseases 

• A continuum that begins with plaque rupture within a coronary artery and results in infarction of myocardial tissue if perfusion is not restored

3 phases of acute coronary syndrome

• unstable angina

• NSTEMI

• STEMI

process of acute coronary syndrome

1. normal artery and vessel wall

2. asymptomatic

3. stable angina

4. unstable angina

5. thrombus

6. acute STEMI

what happens in a normal artery and vessel wall

blood flows easily through the vessel

asymptomatic acute coronary syndrome

• some development of atherosclerosis

• because the lumen in not significantly narrowed the blood flows through providing enough oxygenated blood to prevent symptoms

stable angina

• lumen has significant amount of narrowing from plaque

• patient will have some symptoms when demand for oxygenated blood increases

unstable angina

• atherosclerotic plaque has been disrupted and platelets travelling by begin to stick to it

• the plaque is unstable or vulnerable

• patient develops symptoms without warning and is not able to control symptoms with medications and rest

thrombus/NSTEMI

• plaque has ruptured with hemorrhage

• the lumen becomes even more occluded with clot and the patient suffers some infarction to a part of the myocardium

• because the damage does not involve the full thickness of the ventricle the patient has suffered a “non ST elevated MI” or NSTEMI

acute STEMI

• the clot continues to build and the entire lumen is occluded

• the myocardium suffers significant infarct and changes on ECG are notes

normal ECG deflections

what is the relationship of the ST wave

between S and T wave

what does ST segment represent

end of ventricular depolarization and beginning or repolarization

how should ST segment look

flat on ECG

what finding is concerning of ST segment

elevation or depression of 1 mm or more

unstable angina

• Atherosclerotic plaque disruption exposing injured endothelium to platelets and coagulant factors leading to clot formation 

• Leads the transient episodes of vessel occlusion at the site of plaque disruption

• Thrombus is labile and vulnerable but perfusion is restored before necrosis can occur 

• Can occur at rest

• Pain is persistent and severe

• Difficult to relieve 

what are common findings for the ST segment during unstable angina

• ST segment depression

• T wave inversion

when are the ST changes in unstable angina found

during pain

labs in unstable angina

cardiac enzymes:

• creatinine kinase

• lactic dehydrogenase

• troponin

all negative

contractility during unstable angina

may be abnormal

what is an NSTEMI

• Necrosis of myocardial tissue occurs but does not involve full thickness of the ventricular wall (inner ½-⅓ of ventricular wall)

• Necrosis is limited to subendocardial area

NSTEMI ECG changes

• ST-segment depression

• T-wave inversion

NSTEMI patient experience

severe abrupt pain and no relief

NSTEMI diagnosis

• history

• pain

• biomarkers

  • increased myocardial enzymes creatinine kinase and troponin

what is creatinine kinase

enzyme found in heart, brain, and muscle adn is released when the cells are damaged

creatinine kinase isoenzymes

• CK-BB

• CK-MB (myocardial muscle)

CK-MB levels of infarction

• levels rise 3-6 hours post infarction

• peak in 12-24 hr

• return to normal after 12-48 hours

CK-MB normal value

0-4% of total CK

troponin

protein found in skeletal and cardiac muscle

troponin levels in MI

• with MI troponin-T and troponin-I levels rise very quickly

• rise in 6-10 hours

• peak at 18-24 hours

• falls at 5-6 days

downfalls of troponin

prolonged period for diagnosis

preferred biomarker for MI diagnosis

troponin, specifically Troponin I because it is the most specific

what is occuring in a STEMI

arterial occlusion is complete resulting in necrosis of full thickness of the ventricle altering electrical condition

symptoms of STEMI

pain is abrupt with no relief

ECG changes in STEMI

ST elevation

cardiac biomarkers for STEMI

elevated

zones of tissue damage during infarction

• zone of infarction (inner most)

• zone of injury

• zone of ischemia (outer most)

zone of infarction

• Cell death and necrosis had occurred

• Seen as pathological Q waves on ECG

• Cells replaced with scar tissue 

zone of injury

• Blood flow is interrupted causing injury but potential viable tissue surrounding area of infarct

• Seen as ST segment elevation on ECG

zone of ischemia

• Perfusion to area decreased but no damage occurs as long as blood flow is restored

• Outer region of infarcted area

• Cells still viable

• Manifest as T wave inversion on ECG

worst care scenario of impaired muscle perfusion

myocardial infarction

what happens to overcome ischemia

• new blood vessels form through angiogenesis to form a detour around the blockage

• these are to bypass the occlusion restoring blood flow to tissue (collateral circulation)

• some people with collateral circulation never know they have significant heart disease

what happens if reperfusion is not obtained

• necrosis of full ventricle can occur

• necrotic cells can never participate in contraction so the ventricle is either hypokinetic or akinetic- some ventricular function si then lost

pathological process of myocardial infarction

1. once an infarct has occurred the area becomes bruised and cyanotic and cardiac enzymes are released from the damaged cells

2. infiltrates by neutrophils and cytokines and complement and coagulation cascades begins

3. inflammation and angiogenesis occur

4. ventricular remodelling due to inflammation and angiogenesis

5. inflammation → recruitment of stem cells which differentiate into endothelium leading to regeneration of myocardial tissue

6. catecholamines are released

7. coronary vasoconstriction occurs in the area of the infarct along with embolization of thrombi

8. location of infarct depends on vessels involved

purpose of catecholamine release

neurotransmitters increase blood glucose for energy

purpose of coronary vasoconstriction

death of myocytes may stimulate production of toxic free radicals that further plug coronary capillaries decreasing blood flow

possible locations of MI

• right coronary artery

• left anterior descending artery

• left circumflex artery

*knowing helps to determine what clinical manifestations we might see

right coronary artery MI

• supplies right ventricle

• occlusion of this artery causes right ventricular infarct

left anterior descending artery MI

• supplies anterior portion of the left ventricle

left circumflex artery MI

• supplies the lateral part of the left ventricle

ECG changes at the zones of MI

• Ischemia and non stemi: flipped or inverted T wave 

• Transmural MI: elevated ST segment 

• Infarction: pathological Q wave

how do some people find out they had an infarction

• symptomatic is a possibility

• accidentally discover at routine checkup

• pathological Q wave persists forever on ECG

clinical presentation of symptomatic MI/CAD

• pain (may radiate)

• pallor, dyspnea, anxiety, diaphoresis

• dysrhythmias

• nausea and vomiting

• denial of infarct

cause of pain

from lactic acid during ischemic episode or by myocardial stretching irritating nerve fibres

cause of pallor, dyspnea, anxiety, diaphoresis

From catecholamines diverting blood flow to priority areas