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BIO 250 – Patho II – Cardiac – Lewis 32-35 & 37, Braun 14

Cardiovascular system: Lewis chapter 32 – on your own. There will be exam questions from this chapter.

I. Cardiovascular system:a. Trace a drop of blood through the heart – include all the valves. Lewis fig 32-1, b. Trace the electrical impulse through the muscle fibers of the heart – what actions

correlate to ECG tracings? Lewis fig 32-4c. What are the differences between arteries/arterioles, capillaries, veins/venules? Lewis

fig 32-5i. What role do arterioles have?

d. What impacts cardiac output (CO)?i. How is cardiac output calculated?

ii. What is preload, afterload, contractility?e. What regulates cardiovascular system?

i. What role do baro and chemo receptors play?

II. Requirements for adequate perfusion:a. _______________________ and _______________________ – as discussed last week –

we must exchange oxygen/CO2 which requires both ventilation and diffusion.i. This also require adequate circulation to the pulmonary system

b. Blood _____________________ and ____________________ – must have enough volume to maintain blood pressure AND RBCs to carry oxygen from lungs to tissue and waste products (CO2) from tissue to lungs.

i. If needed review the Hematology unitc. Adequate heart _______________________:

i. Strong enough contraction to move the blood – 1. Stroke volume – Blood moved with each contraction2. Heart rate/rhythm – number of contractions and if they are coordinated

impact perfusion3. Control center must be functioning. This impacts rate and the force of

the contractions.4. ANS must be intact – again this impacts rate and force of contractions

based on body needs.5. Cardiac conduction – the electrical signal to contract must move

through the cardiac muscle fibers in a specific and organized manner to optimize CO.

d. Intact _______________________ circulation – if heart tissue is not being supplied with adequate oxygen it will stop working. Coronary arteries must be free from blockage (coronary artery disease). During which part of the coronary process does the coronary circulation occur?

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e. Intact ____________________ circulation – Even if the heart is working just fine if the systemic circulation has blockages the oxygen and nutrients won’t reach the tissues.

III. __________________ _________________ (33) – pressure or tension of blood within the systemic arteries. Force of the blood against the walls of the arteries. Lewis fig 33.1 One of the best tools to assess fluid volume (hemodynamic stability)!a. Maintained by:

i. Contraction of the left ventricleii. Peripheral (systemic) vascular resistance (SVR) – force against the movement of

blood. The radius (size of the lumen) of the small arteries and arterioles are main factor in determining vascular resistance.

1. Small change in the radius of these creates a major change in the SVR.iii. Elasticity of the arterial wallsiv. Viscosity and volume of blood

b. Changes in BP occur in response to: (Mechanisms that regulate BP impact either CO or SVR)

i. ___________receptors and _____________________receptors in the arteries1. SNS reacts within seconds to a decrease sensed by baroreceptors by

increasing HR and contractility and increasing vasoconstriction. Release of norepinephrine binds to different receptors in heart and smooth muscles in the vessels.

a. Example is moving from lying to standing – this system responds rapidly to perfuse the brain. If doesn’t work the result is dizziness or syncope.

ii. Renin-angiotensin system – (RAAS)1. In response to a ____________________ in perfusion to the kidneys

they (juxtaglomerulus) release _________________. This converts the plasma protein angiotensin to angiotensin I. Then an enzyme from the lungs (angiotensin converting enzyme) converts this to angiotensin II.

2. Angiotensin II acts on:a. Arteries/arterioles and causes _________________________b. The ___________________ glands which then release

_____________________ which tells the kidneys to keep Na+ and water. This increase volume which increase BP.

iii. The kidneys – in response to chemicals released by the body (such as aldosterone) the kidneys participates via sodium and water retention or excretion.

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1. When there is too much volume the cardiac endothelium releases ANP and BNP which antagonize ADH and aldosterone (tells the kidney to release water/sodium which decreases blood volume.

c. ________________________ = persistent SBP ≥ 140 mm Hg or DBP ≥90 mm Hg. Lewis table 33-2 Hallmark of HTN is persistently increased SVR.

i. 90-95% of cases have no known cause (_________________). However contributing factors are known: Risk factors are listed in Lewis table 33-4

1. Increase in _________ activity – anger, fear, pain – results may persistent even when event is no longer present. Chronic high stress lead to HTN more often than those with minimal stress.

2. Overproduction of sodium-retaining hormones (eg. Aldosterone) and vasoconstricting substances (eg. RAAS system)

3. Increased ________________ intake – 1 in 3 HTN will decrease with decrease in salt intake.

4. Overweight/obesity – leads to insulin resistance and hyperinsulinemia.a. Stimulates SNS activity and impairs nitric oxide (vasodilator),

leads to vascular hypertrophy, and renal sodium reabsorption.5. Diabetes mellitus – the presence of glucose in the vascular space leads

to the same results as the presence of too much insulin.6. Excessive alcohol consumption

ii. 5-10% of cases have a known cause – Lewis table 33-3 lists those causes.

iii. Usually _________________________________ – “silent killer” until heart, vessels, and organs are damaged – then see:

1. Fatigue, activity intolerance, dizziness, palpitations, angina, dyspnea. (most related to Left ventricular hypertrophy)

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2. Organs damaged include: Lewis table 33-5a. _____________ – CAD (coronary artery disease – the thinking is

the constant high pressure results in chronic inflammation….), Left ventricular hypertrophy, and heart failure.

b. _________________ – cerebrovascular disease – Stroke. Again related to the presence of athrosclerosis in the blood vessels.

c. ___________________ vascular disease – hypertension increases the presence of athrosclerosis.

d. __________________ – nephrosclerosis – HTN is one of the leading causes of end-stage renal disease. Narrowing intrarenal vessel lumens result in ischemia. Leads to atrophy of tubules, destroy glomerulus, death of nephrons.

e. __________ – retinal damage – The damage to retinal vessels indicates the extent of damage to the heart, brain, and kidney.

IV. Coronary Artery Disease (34) – Most common type of cardiac disease. Early on it is asymptomatic with stable angina (chest pain). Late manifestations include unstable angina and myocardial infarction (MI). This is termed acute coronary syndrome (ACS).

a. Leading cause of CAD is __________________________ – “hardening of the arteries”. Steps to the formation of atherosclerosis include: Lewis Fig 34.1

i. __________________ to the vessel endothelium. This can occur from smoking, hyperlipidemia, hypertension, diabetes, infections, and immune reactions.

1. Injury results in elevated C-reactive proteins which oxidize LDL’s and trigger macrophages to consume the oxidized LDL’s and take it into the endothelial lining.

ii. ________________ _____________ forms from the accumulation of these fat filled macrophages in the smooth muscle cells.

1. Lowering the overall LDL levels can reverse this.

iii. Fibrous __________________ with smooth muscle cell proliferation1. The presence of the fatty streak stimulates platelets to release growth

factors. This causes the smooth muscle in the vessel to grow resulting in a thickened vessel wall.

2. Collagen covers the fatty streak – fibrous plaqueiv. ___________________________ ______________ – most dangerous stage

1. Continuous inflammation can lead to instability of the plaque, ulceration, and rupture.

2. Platelets accumulate which create a thrombus (clot) which further narrows the vessel (can occlude it completely)

a. Platelets attract more platelets causing thrombus to continue to grow.

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Pathophysiology of atherosclerosis

Endothelial Injury

Inflammation abnormal vasoconstriction

Abnormal Macorphages adhered to and HYPERLIPIDEMIAVasoconstriction migrate below the injured

endothelium

Ischemia Lipoproteins (LDL) migrate below the endothelium

Oxidization of LDL by macrophages

Formation of the ‘fatty streak’ in tunica media of vessel wall

progressive damage to vessel wall

scar tissue deposition results in formation of the fibrous plaque

Narrowing of vessel lumenEventually plaque calcifies rupture

Rough plaque surface promotes clot

Obstruction worsens……

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Endothelium stops making normal antithrombic and vasodilatory substances

(nitric acid and prostaglandins)

Growth factors are released which stimulates smooth muscle hyperplasia

Release of enzymes and oxygen free radicals


b. Collateral circulation can occur – see Lewis fig 34-2 – if enough time is allowed. So with slow progression of disease most people create new paths to bypass the blockage.

i. With rapid-onset – or faster progression- there is not enough time for vessels to grow to bypass – (or if there is coronary spasms). This results in severe ischemia or infarction.

c. See Lewis table 34-1 for both modifiable and non-modifiable risk factors – KNOW THESE.

d. Chronic _________angina – chest pain that occurs with the same pattern (same trigger), onset, duration, intensity. Pain is described as pressure, ache, squeezing, heaviness, and lasts only a few minutes. This is a warning sign of CAD and needs to be addressed.

i. This pain is from _____________________ of the myocardium either from increased demand or decreased supply.

1. Lactic acid builds up and trigger pain sensors

e. Acute coronary Syndrome (ACS): Stable angina changes to unstable and patient experiences an MI –

i. Unstable angina is new pain, worsening pain, or pain that occurs at rest.ii. Myocardial infarction (MI) – aka: heart attack. Death/necrosis of cardiac muscle

tissue occurs due to sustained ischemia.1. First damaged is the innermost layer (20 minutes) – the entire muscle

thickness can be damaged if blood flow is not restored in 4-6 hours.

f. Sudden Cardiac Death (SCD) – unexpected cardiac arrest.i. CPR, defibrillation (AED use), and advanced cardiac life support have greatly

improved outcomes for witnessed arrest.ii. Ventricular dysrhythmias cause majority of cases.

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V. Heart ___________________________ (35) – impaired cardiac pumping and/or filling. a. Most often occurs due to:

i. Long-standing HTNii. CAD (and age)

iii. MI

b. Alterations in preload, afterload, contractility, and HR lead to HFi. Ventricular Failure –

1. ___________________ – Left ventricle in unable to generate enough force to move blood through the aorta. Usually due to:

a. Impaired contractile functions (MI, dysrhythmias…)b. Increased afterload (HTN)c. Cardiomyopathy (Left ventricular hypertrophy…..)d. Valvular diseases

2. __________________– Ventricles cannot relax - they do not fill with blood. This is because they are stiff and noncompliant. Leads to venous engorgement in both pulmonary and systemic systems.

a. Left ventricular hypertrophy from chronic HTN is leading causeb. Aortic stenosis

3. Mixed – seen most often in dilated cardiomyopathy. (Enlarged heart chambers that cannot relax). Common causes include:

a. Acute: MIb. Chronic: HTN

c. Compensatory Mechanisms:i. SNS - first trigger but least effective. Epi/norepi released = increase HR,

contractility, and vasoconstriction. If the heart is sick how well will this work?1. It increases cardiac oxygen demands2. Immediately increases afterload

ii. Neurohormonal response – 1. Lack of ___________________ to the kidney triggers release of renin.

This results in: angiotensinogen II which causes vasoconstriction and adrenal release of aldosterone which tells kidneys to keep salt/water.

2. Lack of perfusion to _____________ tells the post pit to release ADH which tells the kidneys to keep water.

3. These result in HTN, and increased vascular volume. How well will the sick heart respond to this extra work?

a. Leads to ventricular remodeling (hypertrophy). So the ventricle muscle mass enlarges but this lead to impaired pumping, increased tension, and increased oxygen demand.

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iii. Ventricular __________________ – this occurs due to increased blood volume from the RAAS, SNS, ADH release. Eventually the ventricles enlarge to where the muscles cannot contract well enough to eject the blood. Frank-Starling law -

iv. Ventricular ______________________ – enlarged heart muscle from overwork. Eventually this leads to inability to contract, huge oxygen demands, and poor cardiac perfusion.

d. Counter measures – our body attempts to find a balancei. Atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP)

1. These are present in the atrial (ANP) and ventricle (BNP) and respond to changes in volume and pressures.

a. They promote ________________________ (decrease both preload and afterload)

b. They are aldosterone antagonistsc. They enhance diuresisd. They block RAASe. They inhibit hypertrophyf. They are anti-____________________ mediators

2. Prolonged cardiac distention (volume and pressure) depletes these factors.

ii. Nitrous oxide (NO) – released from vascular endothelium – promotes vasodilation.

e. Types of HF include Left sided and Right sided: (Eventually both sides become involved but it can start in one side) See concept map/flow chart in Lewis fig 35-2

i. ___________________– most common form. It is left ventricular dysfunction and leads to a back-up of blood into the left atria and from there into the pulmonary capillaries leading to pulmonary congestion and edema. (think about the hydrostatic pressures forcing the fluid from the vascular beds into the interstitial spaces – what will this result in as far as pulmonary function? How will gas exchange be impacted?)

ii. ____________________ – Failure of R ventricle causes blood to back-up into R atria and vena cava – and the venous system resulting in jugular distention, hepatomegaly, splenomegaly, vascular congestion in GI tract, peripheral edema. What impact does this have on pulmonary? How is gas exchange impacted? (think about perfusion versus ventilation)

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VI. Cardiac _____________________________ disorders (37) – a. ____________________ defects – basically these are holes that exist between the atria

or the ventricles. They are part of normal fetal circulation and fail to close at birth. i. These allow blood movement where it should not be.

b. Defects of the great vessels – Either transposition or narrowingi. _______________________________ is where the aorta comes off the R

ventricle (remember the R ventricle has a much weaker contraction as it’s made to pump against a low pressure environment (pulmonary). The pulmonary artery comes off the L ventricle which has a strong contractility.

ii. _________________ or narrowing of either aorta or pulmonary artery cause the heart to work harder (increased afterload)

c. Patent ductus arteriosis – again – from fetal development; a hole remains between the aorta and the pulmonary artery allowing un-oxygenated blood into the aorta

d. _________________ defects – There are four valves that control unidirectional blood flow. Problems with these include stenosis (narrowed opening) or regurgitation (valve does not close). You will hear a murmur as blood flows the wrong way or through a tight opening.

i. In children these are congenital (there are a variety of causes in older adults)

ii. M________________________ ____________: 1. _______________________ – most common cause is rheumatic heart

disease (from incomplete or untreated strep throat). This causes scarring of the leaflets and chordae tendineae which results in a tight valve (or one that won’t close – that’s next).

a. Can also be from Rheumatic diseases (rheumatic arthritis or Lupus)

b. Results in increased volume in L atrium and thus into the pulmonary arteries (system).

2. __________________________ – valve fails to close! Causes can include rheumatic heart disease, MI, prolapse.

a. Blood flows back into the L atrium during systole. Results in L atrial dilation and L ventricular hypertrophy. Decreased CO

3. ___________________ – The leaflets buckle back into the atrium during systole allowing regurgitation. Fairly common – usually asymptomatic.

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iii. A_______________________ ____________________:1. Stenosis – Usually caused by rheumatic heart disease or fibrocalcific

degeneration (plaque buildup on the valve).a. Obstructed flow from L ventricle through aortic valve leads to L

vent hypertrophy, increased myocardial oxygen demand, decreased CO, decreased tissue perfusion, pulmonary hypertension, HF.

2. Regurgitation – Aortic valve allows backflow of blood into the L ventricle during diastole. Caused by rheumatic heart disease, congenital, syphilis, chronic rheumatic conditions.

a. Results in volume overload (preload)- L vent dilates, hypertrophies, contractility decreases, pulmonary HTN, R vent failure.

VII. Inflammatory diseases of the heart (37) – Due to some type of pathogen

a. ____________________________ – infection/inflammation of the innermost lining of the heart. This is continuous with valves – so valves can be damaged.

i. Most common pathogens are Staph and Strep (Lewis table 37-1). Rheumatic heart disease used to be leading cause but now:

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1. Aging2. IVDA – intravenous drug abuse3. Prosthetic valves4. Intravascular devices (hospital acquired)5. Renal dialysis

ii. Vegetations form on the valves, endocardium. These can break off as emboli.1. Consist of: fibrin, leukocytes, platelets, microbes

b. _________________________________ – Inflammation of the pericardial sac. This includes the inner serous membrane that is attached to the heart, the space, and the outer fibrous layer. Usually there is fluid in the space which decrease friction as the heart beats.

i. Inflammation results in: influx of neutrophils, increased permeability, increased vascularity (vasodilation), eventually fibrin deposits.

ii. Caused by – see Lewis table 37-4iii. Pt. complains of sharp chest pain that worsens with a deep breath. You will

hear a friction rub.iv. Complication is cardiac tamponade – this is where so much fluid fills this space

that the heart becomes compressed. Decreased filling occurs leading to decreased CO, muffled heart sounds, tachypnea, tachycardia, neck veins become distended…

c. ___________________________ – inflammation of the myocardium (cardiac muscle). i. Many causative agents – pathogens, radiation therapy, chemicals, drugs

ii. Agent invades myocytes causing cellular damage and death – this triggers the immune/inflammatory response. Eventually an autoimmune response occurs resulting in extensive myocyte destruction leading to dilated cardiomyopathy.

1. Dilated cardiomyopathy is where the chambers in the heart increase in size while the muscle decreases.

a. Loss of contractility and large blood volume lead to loss of CO

d. Rheumatic fever/heart disease – results from an abnormal immune response to group A-streptococcal antigens. Can impact heart, skin, joints, CNS. Has declined since effective use of antibiotics.

i. Results in:1. Swelling and erosion of valve leaflets

a. Thickening of valve leaflets leading to stenosis2. Vegetation formation

a. Reduction in valve mobility leads to regurgitation.

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RAAS system: Angiotensinogen (present in the serum)

NaCl ReninBlood pressure

Angiotensin I

Angiotensin-convertingEnzyme (ACE)

Angiotensin II Arterial SVR

Vasoconstriction BP

Aldosterone

Na+/water reabsorption BV and BP

Manifestations of heart failure:

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