High Yield Weeks 1 6

Weeks 1-6

• LG 1.1 Cardiac cycle Physiology Pavlick • Objective: Define and distinguish between each of the following terms: diastole, systole, heart rate, stroke volume, cardiac output, venous return, EDV, ESV and ejection fraction. • Objective: Distinguish between the 4 basic heart sounds and explain how each of the sounds is produced.   • Objective: Explain the series of events that occur during each of the following phases of the cardiac cycle: atrial systole, isovolumetric ventricular contraction, rapid ventricular ejection, reduced ventricular ejection, isovolumetric ventricular relaxation, rapid ventricular filling, and reduced ventricular filling. – KAPLAN DISK 6-2-03

Basic Terminology  

Systole – period of contraction and emptying atrial systole and ventricular systole

Diastole – period of relaxation and filling atrial diastole and ventricular diastole

Stroke Volume (SV) – quantity of blood pumped out of the ventricles per beat @ rest - 70 ml/beat; maximum -

1/28/2009

Venous Return (VR) – quantity of blood returned to the heart per minute normally, venous return equals cardiac output

End Diastolic Volume (EDV) – quantity of blood remaining in the ventricles at the end of ventricular diastole average value is around 130 ml

End Systolic Volume (ESV) – quantity of blood remaining in

LG1.1 cardiac cycle

Cardiac cycle •

http://www.youtube.com/watch?v=Ge12P7u0aQo&feature=PlayList&p=

1/27/2009

anatomy lab

Right & Left Heart Differences Atrial Systole (contraction) begins and ends earlier in the RA than LA   Initiation of ventricular contraction • contractions start earlier on the left side • mitral valve closes before the tricuspid (timing difference is so small that a split is not heard) • pulmonary valve opens before the aortic valve (hence, duration of isovolumetric ventricular contraction is briefer for the right ventricle) Ventricular ejection •  Ejection from the right ventricle lasts longer than that from left ventricle •  The aortic valve, with higher pressure downstream, closes before the pulmonary valve • The pulmonary valve, with its lower pressure downstream, opens first and closes last Ventricular relaxation • pulmonary valve closes after the aortic valve •isovolumetric ventricular relaxation is briefer in the right ventricle •tricuspid valve opens before the mitral valve •right ventricle fills before the LG1.1 left ventricle 1/28/2009 cardiac cycle

Phases of the Cardiac Cycle

1/28/2009

LG1.1 cardiac cycle

7 phases of the CARDIAC

Phase A – Atrial Systole •

in order for this event to occur, the left atrium must FIRST be depolarized (notice the location of the P wave just before atrial systole)

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the contribution of atrial contraction to ventricular filling is usually small (approx. 15-20% of the total ventricular volume)

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after atrial systole, LVP > LAP and the mitral valve shuts

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1st heart sound (S1) is heard; may be “split” because the mitral valve closes slightly before the tricuspid valve (usually the timing difference is so small that a split is not heard)

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the volume of blood in the left ventricle at this point is the EDV

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Important Lesson: AFTER ALL IS SAID AND DONE, THERE ARE 3 PHASES OF VENTRICULAR FILLING

Phase B – Isovolumetric Ventricular Contraction •

the left ventricle develops significant pressure after initiation of QRS complex and starts contracting

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ventricular volume is constant, as all heart valves are closed

Phase C – Rapid Ventricular Ejection •

eventually, the left ventricle develops enough pressure such that LVP exceeds aortic pressure

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the aortic semilunar valve opens and blood is ejected quickly

Phase D – Reduced Ventricular Ejection •

blood is ejected at a slower rate

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the volume of blood remaining in the left ventricle after ejection is the ESV

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once blood is ejected, LVP falls below aortic pressure and the aortic semilunar valve shuts 1/28/2009 LG1.1 cardiac cycle

7 phases of the CARDIAC Phase E – Isovolumetric Ventricular Relaxation •

marks the end of ventricular systole / beginning of ventricular diastole  

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at the end of a heartbeat, all four chambers of the heart are relaxed and all of its valves are closed

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the left atrium is filling with blood that has returned from the pulmonary veins

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left ventricular pressure falls because of the blood that was previously ejected

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as left atrial volume increases, left atrial pressure (LAP) begins to exceed left ventricular pressure (LVP), resulting in opening of the mitral valve

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Important Lesson: HEART VALVES OPEN AND CLOSE DUE TO DIFFERENCES IN PRESSURE

Phase F –Rapid Passive Ventricular Filling •

blood flows quickly past the mitral valve and into the relaxed left ventricle

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there is NO contraction of any of the heart chambers

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left ventricular volume begins to increase

Phase G -- Slow Passive (Reduced) Phase or diastasis •

blood flows slowly past the mitral valve and into the relaxed left ventricle

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there is NO contraction of any of the heart chambers

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left ventricular volume continues to increase

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 once blood is ejected, LVP falls below aortic pressure and the aortic semilunar valve shuts 1/28/2009

LG1.1 cardiac cycle

Cardiac The sequence of mechanical and electrical events Cycle that repeats with every heartbeat

1/28/2009

LG1.1 cardiac cycle

EKG  

1/28/2009

LG1.1 cardiac cycle

1/28/2009

LG1.1 cardiac cycle

Overview of Heart Sounds S1: this is the first heart sound and is associated with closure of the mitral and tricuspid valves at the onset of ventricular contraction S2: the second heart sound is shorter and usually of higher frequency than S1 -- it indicates the end of ventricular systole and the beginning of diastole, which is characterized by the closure of the semilunar valves S3: the third heart sound is associated with the rapid passive filling phase of diastole; iThe third heart sound is sometimes heard in children with thin chest walls or in patients with left ventricular failure. The vibrations occur in early diastole and are caused by the abrupt cessation of ventricular distention and by the deceleration of blood entering the ventricles. S4: the fourth heart sound is associated with atrial 1/28/2009

LG1.1 cardiac cycle

• LG 1.2 Coronary circulation Physiology Pavlick • Objective: Explain how the sympathetic and parasympathetic nervous systems influence CBF.

Coronary Blood Flow (CBF) Heart Rate and CBF: •Changes in heart rate, because they affect the duration of diastole more than that of systole, also affect coronary blood flow. •During tachycardia, the fraction of the cardiac cycle spent in diastole decreases, minimizing the time available for maximal left coronary perfusion. •If the heart is healthy, the coronary vessels can adequately dilate in response to the metabolic signals generated by increased cardiac work (active hyperemia), which offsets the negative effects of the shorter diastole. •On the other hand, a high heart rate can be dangerous to a patient with severe coronary artery disease. SNS & CBF: •The primary effect of stimulation of the SNS to the coronary vessels is VASOCONSTRICTION (via 1-receptors). HOWEVER, the observed effect is a great INCREASE IN CORONARY BLOOD FLOW (via 1-receptors). 1/29/2009 LG1.2 Coronary Circulation & Myocardial Oxygen

• • • • • • • • • • • • • • • •

LG 1.6 Atherosclerosis, genetics Biochemistry Gardner Objective: Discuss the role that each of the following plays in fatty streak formation and atherosclerosis. LDLs Oxidation and Glycation Monocytes/Macrophages Scavenger receptors Foam cells Inflammation Smooth muscle cells Growth factors Calcium Fibrous cap Collagen Tissue factor Platelets Clotting factors

• Objective: Discuss the hypothesized relationship between Lp(a) and increased risk of CHD.

• • • • •

Risk Factors for CHD

Hyperlipidemia Hypertension Smoking Hyperglycemia Genetics (risk is higher if): – More affected relatives. – Female relative affected. – Early Onset (before age 55) – Genes involved in lipid metabolism and transport are major area of risk.

Additional Risk Factors for CHD: • Lp (a) is a LDL with a apoplipoprotein called apo(a). • Lp(a) is a risk factor for CHD. • Lp(a) are determined by genetics through trans fats and have been shown to increase Lp(a) levels. • Apo(a) is strucurally homologus to plasminogen. • Plasminogen is precursor to Plasmin, which cleaves fibrin to degrade clots. • α2-antiplasmin found in the blood that inactivates free plasmin. Take home message: 1/27/2009

LG1.6 Biochemistry Atherosclerosis, Clotting & Cholesterol

1/27/2009

LG1.6 Biochemistry Atherosclerosis, Clotting & Cholesterol

• Atherosclerosis – The process of build-up of materials on the inner lining of an artery. • Examples include: cholesterol, triacylglycerol, calcium, machrophages, collagen, elastin, foam cells, vascular smooth muscle and dead cells.

– Process

• Fatty streak formation  – LDL particles accumulate in the intima of arteries, if hyperglycemia is present, LDLs become glycated » Oxidation of LDL occurs in the intima » Once this LDLs are oxidized or glycated, they stimulate an inflammatory response • Monocytes migrate and are transformed into macrophages. • Macrophages (express unregulated scavenger receptors) ingest the oxidized LDLs • This leads to the formation of foam cells= fatty streak. • Foam cells release factors that stimulate smooth muscle cells to migrate to the site from the media to the intima (cytokines). • Foam cells die and release their lipid content. • Smooth muscle cells proliferate and produce ECM (eg.collagen, lipids) build-up.

– The fatty streak converts to Atheroma » It’s believed that smooth muscles play a role in the transition by changing the site from a streak to fibrous/fatty lesion • Growth factors are expressed at the site of the lesion. • PDGF, Multiple Growth factors and TGF-Beta. » Atheroma  often has core of lipid (necrotic core) released from dying foam cells » Calcium deposits from smooth muscle cell death enhances the instability of the atheroma » Atheroma has a fibrous cap which is very fragile • This thin fibrous cap surrounding the plaque can rupture (c) • This rupture can expose tissue factor and collagen (d) • Collagen stimulates platelet plug and TF stimulates fibrin clot formation.

• It is the thrombus formation that occludes the artery causing an MI—The clot is what occludes the artery not the atheroma • If it moves, then it becomes embolism. •   Accumulation and swelling in the artery walls that is

• Cardiac Cell death – Two forms of cell death • Necrosis – Occlusion of a coronary artery leads to oxygen deprivation » If it is within 20 minutes, tissue become necrotic

• Apoptosis – Cells undergo apoptosis before becoming necrotic cells » The surrounding area of necrosis undergo another type of cell death—apoptosis.

Urokinase and t-Pa convert plasminogen to plasmin

1/27/2009

LG1.6 Biochemistry Atherosclerosis, Clotting & Cholesterol

• Other Risk Factor for CHD—LIPOPROTEIN (a) or Lp(a) • Lp(a) particles are identical to LDL but have an apoliprotein called apo(a) associated with apo B-100 • Levels of Lp(a) are largely determined by genetics – Trans fat can increase them as well

• High levels of Lp(a) associated with higher risk for CHD • Mechanism – Apo is structurally homologous to plasminogen » Plasminogen is incorporated into a clot during its formation and then activated by plasminogen activators • Anti-plasmin also found in the blood inactivates plasmin » Plasminogen is converted into plasmin by plasminogen activators such as T-PA or urokinase. • Plasmin then cleaves fibrin into soluble degradation products (anticoagulant)

• LG 1.5 Cholesterol, lipids Biochemistry Gardner • Objective: List the functions of the following apolipoproteins: CII, AI, E, B-48 and B-100. • Diagram how an apo C-II or LPL deficiency could cause elevated chylomicrons and VLDLs

Lipoproteins & Lipid Transport • • • •

From least to most dense: chylomicrons, VLDL, LDL, HDL Exogenous pathway – metabolism of chylomicrons, which carry dietary fats Endogenous pathway – transports triacylglycerols synthesized from the liver to the body Elevated levels of intracellular cholesterol inhibit HMGCoA reductase and therefore reduces LDL receptor numbers on the cell surface

The apolipoproteins A1: Produced in the small intestines and liver Major component of HDL The protein promotes cholesterol efflux from tissues to the liver for excretion. B100: Synthesized in the liver Found in VLDL, IDL, LDL B48: Synthesized in the intestinal epithelium Found in chylomicrons C II: An activating cofactor for lipoprotein lipase C III: An inhibitor of lipoprotein lipase Apolipoprotein E: • Synthesized in the liver • Blocked from interacting with hepatic receptors by the C apolipoproteins • Found on chylomicrons, VLDL and HDL • When present on IDL, apolipoprotein E enhances the interaction of apolipoprotein B100 with the hepatic LDL-receptors 1/26/2009

SP1.2 Lipoproteins & Lipid Transport

– Chylomicrons • They are made in the small intestine and released in the lymphatic system and then the blood. – Contain protein, phospholipid (hydrophilic layer) and large amounts of triacyglycerol, cholesterol and cholesteryl esters (hydrophobic layer)

• In the blood HDL gives chylomicrons ApoE and ApoC-II • ApoC-II binds and activates lipoprotein lipase (LPL)-extracellular protein anchored to the capillary wall by heparan sulfate in different tissues (adipose, cardiac and skeletal muscle. • LPL degrades the triacyglycerol in the chylomicron to free fatty acids and glycerol

– Hyperchylomicronemia • People with this condition may have: – A deficiency of ApoC-II or – A deficiency of LPL or both.

• Test for deficiency of LPL or ApoC-II – Heparin competes with heparan sulfate which is bound to LPL » Adding IV heparin will lead to its binding to LPL and release from the capillary walls into the blood. • Blood is drawn to measure LPL activity • Low LPL activity=less binding therefore LPL is deficient • High LPL activity= LPL binds, but

Atherosclerosis & • Atherosclerosis is a multifactorial chronic inflammatory disease that is associated with the accumulation of LDLs in the walls of the larger arteries • Familial hypercholesterolemia generally occurs as a result of a defective (or absent) LDL receptor • Statins (HMG CoA reductase inhibitors) block cholesterol biosynthesis and consequently increase the number of LDL receptors on hepatocytes, thus reducing LDL levels in the circulation 1/26/2009

SP1.2 Lipoproteins & Lipid Transport

• LG 1.7 Coronary artery disease and complications of MI Pathology Fischione • Objective: Describe the various complications of an Acute Myocardial Infarct • Objective: Define Sudden Cardiac Death and its cause

Too many Big Macs may cause? Acute

Progressiv e Coronary Artery Disease:

•Atherosclerosis of the coronaries -> myocardial ischemia •May be chronic progressive ischemia from atherosclerosis •May be acute coronary thombosis due to a sudden occlusion Results in a MI in an anatomically defined area Acute MI cause: White thrombus forms when atherosclerotic plaque ruptures. White thrombus is mostly platelets w/ little fibrin. 1/28/09

Pathology wk1 LG1.7

Pathology of • Coronaries -> atherosclerosis -> narrowing of the lumen due CAD to fibrotic plaques and atheromas • Plaques may be covered with fibrinous clots in an acute occlusion • Granulation tissue of the plaque and thrombi in older Calcified lesions may

plaque

1/28/09

Pathology wk1 LG1.7

Myocardial Infarction

Rapid, sudden occlusion of a coronary artery • Sudden cardiac death in ~25% • Among survivors of the onset: inadequate perfusion -> multisystemic major organ failure • Cerebral ischemia most dangerous • Kidney damage most often

1/28/09

Pathology wk1 LG1.7

Causes: • Thrombosis of a

Distribution of MI’s

Anterior wall infarct Occlusion of the Left Anterior Descending (LAD) Artery – over 50% Lateral wall infarct Occlusion of the Left Circumflex Artery – 3040% Infarct of the right ventricle and posterior wall of the left ventricle

1/28/09

Pathology wk1 LG1.7

Types of MI’s

Transmu Transmural: ral

Subendocard

Subendocardial or • Most common Intramural: • All 3 layers of the heart • Infarction usually involved concentric • Free wall of the left ventricle around the and/or interventricular septum subendocardial usually involved • 1/28/09 New Q-waves develop

Pathology wk1 LG.17

Gross Pathology of MI

Gross Pathology of MI: First 1-2 days • Cannot be definitively identified • May be pallor of infarcted myocardium 3-5 days • Infarct becomes yellow • Hemorrhagic rim • Soft infarcted myocardium from hydrolytic enzymes released from neutrophils 1-2 weeks • Granulation tissue imparting a gray-pink, mottled appearance Chronic infarct • White-tan fibrosis Acute with soft yellow & hemorrhagic tissue 1/28/09

Pathology wk1 LG1.7

Subacute with deposition of granulation tissue

Myocardial COMPLICATION OF MI • Softened Rupture necrotic myocardium ruptures •

• Blood fills the pericardial sac (hemopericardium) -> cardiac tamponade (compression of the heart)

Ventricular rupture with necrosis 1/28/09

Hemopericardium due to Rupture Causing Cardiac Tamponade Pathology wk1 LG1.7

Left Ventricular Aneurysm • COMPLICATION OF MI • MI’s of the left ventricle -> granulation and fibrous tissue replacement -> bulge under pressure -> ventricular aneurysm • Fibrous tissue does not contract -> heart dilated and contracts irregularly

Ventricular Aneurysm W/ Mural Thrombus 1/28/09

Pathology wk1 LG1.7

Ventricular Aneurysm With Infarcted Myocardial Wall

Mural Thrombus • COMPLICATION OF MI • Endocardium damaged/disrupted • Blood coagulates in contact with the necrotic endocardium/exposed myocardium -> thrombus attached to the wall • Complications: – Impede blood flow – Weakens ventricular contractions – May detach giving rise to emboli -> cerebral Infarcts 1/28/09 Pathology wk1 LG1.7

• LG 1.8 Acute coronary syndrome Clinical Thomson • Objective: Recognize acute changes in an ECG associated with a myocardial infarction. • Objective: Formulate the pathophysiology of myocardial ischemia in terms of myocardial oxygen demand and supply.

Pulmonary Edema Related to Chest x-ray may show pulmonary edema. Ischemia changes myocardial stiffness, increasing the resistance to ventricular filling, elevating ventricular filling pressures, and ultimately causing symptoms of pulmonary congestion

1/28/2009

LG1.8 acute coronary syndrome, SP1.1 chest pain

Arcus Arcus senilis: also known as arcus cornealis, Senilis – gray or white arc visible above and below the outer part of – – – –

the cornea Eventually the arc may evolve into a complete ring around the cornea. common in older adults. caused by fat (lipid) deposits deep in the edge of the cornea. It can be suggestive of high cholesterol. Does not affect vision, nor does it require

1/28/2009

LG1.8 acute coronary syndrome, SP1.1 chest pain

Xanthom Xanthomas: asby accumulations of lipid-laden • lesions characterized macrophages. • can be a reflection of lipid metabolism alteration or a result of local cell dysfunction. • common manifestation of lipid metabolism disorders. • suggestive of risk factors for vascular disease (cholesterol level elevation) Tuberous xanthomas: • firm, painless, red-yellow nodules. • Tuberous xanthomas are particularly associated with hypercholesterolemia and increased levels of LDL. 1/28/2009

LG1.8 acute coronary syndrome, SP1.1 chest pain

Angina Classic symptoms of angina: – Sensation of a constriction of the chest – Radiation to the neck, jaw and both arms

Occasionally: Epigastrium or through to the back. – Pain is worse with exertion, especially in cold air; improved by rest and nitrates. – Retrosternal pain in particular (often described by patients as “pressure”) suggests that angina is the cause. – Pains that are localized elsewhere, described as sharp or stabbing, or reproduced by palpation are much less likely to be cardiac in origin.

ECG: – Development of pathological Q waves on the electrocardiogram (ECG) – ST-segment elevation or depression on the ECG

Standard Treatment for all 3 types of Angina: Morphine sulfate 1/28/2009

LG1.8 acute coronary syndrome, SP1.1 chest pain

3 Types of Angina

Stable Angina: • Most common type of Angina • Caused by coronary artery atherosclerosis w/ luminal narrowing greater than 75%. No plaque rupture • Chest pain brought on by exertion or emotional • EKG: ST segment depression (subendocardial ischemia) • Relief: Rest and Nitroglycerin Prinzmetal Variant Angina: • Caused by coronary artery vasospasm and seems to be independent of atherosclerosis • Episodic chest pain often occurring at rest • EKG: Transient ST segment elevation ( transmural ischemia) 1/28/2009

Unstable or Crescendo Angina: • Caused by formation of a nonocclusive thrombus in an area of coronary atherosclerosis. Plaque rupture w/ transient or incomplete occlusion. • Increasing frequency, intensity and duration of episodes • Occurs at rest • lasts longer than 30 minutes • not relieved by several doses of

LG1.8 acute coronary syndrome, SP1.1 chest pain

• LG 1.9 MI Biochemistry Gardner • Objective: Outline the molecular mechanism of action for each of the following therapies: Aspirin, Heparin, t-PA, Streptokinase, GP IIb/IIIa antagonist

Treatment of MI

• Immediate Goal: Reperfusion, by eliminating clot. • Accomplished with fibrinolysis (heparin) and platelet inactivation (aspirin). • Treatments – Aspirin block formation of thromboxane α2 by blocking COX-1. – Heparin (IV) – t-PA <- expensive – Streptokinase – Urokinase

1/28/2009

LG1.9 Biochemistry of MI

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Aspirin – MOA: Blocks the formation of Thromboxane A2 by inhibiting COX-1 – Reduces platelet aggregation and platelet plug formation •

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So, it would prevent the extension of the plug

Platelet glycoprotein (GP)IIb/IIIa-receptor antagonist – It prevents aggregation by binding to the platelet receptor and not allowing it to bind to the fibrinogen receptor.

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Heparin – Heparin binds to the enzyme inhibitor antithrombin (AT)causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.

•

t-PA—tissue plasminogen activator – – – –

It is only active when bound to fibrin in a clot It catalyzes the conversion of plasminogen to plasmin It degrades the clot and engages reperfusion and is faster than warfarin Plasma inhibitor activator keeps t-PA in plasma in an inactive state

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Streptokinase – Streptokinase forms a complex in the plasma with plasminogen to form an activator complex. This complex then forms plasmin from unbound plasminogen.[3] – Streptokinase is a bacterial product so the body will build up an immunity to it. It is recommended that this medication should not be used again after four days from the first administration, as it may not be as effective and can also cause an allergic reaction. For this reason, it is usually given only for a person's first heart attack

•

aPTT Test (assess clotting time)-- Why is it good for heparin therapy? – Reference range is approximately 29-41 seconds – Values below 25 seconds or over 39 s (depending on local normal ranges) are generally abnormal. Shortening of the APTT has little clinical relevance. Prolonged APTT may indicate: • •

Use of heparin hemophilia

– In other words it takes longer to clot and the test it’s good for heparin because it can monitor the fluctuation and effect of the drug in the blood. •

>39s if you’re trying to prevent clot formation especially in people who had a stroke or suffer from coronary artery syndromes.

• LG1.10 Myocarditis and Pericarditis Dr. Fischione • Objective: Identify which virus is responsible for the most cases of Viral Myocarditis • Objective: Identify the causes of Pericarditis

Myocarditis Clinical Presentation: • Mild fever • Shortness of breath • Malaise • Signs of heart failure if severe and chronic – Tachycardia – Peripheral cyanosis – Pulmonary edema

• Males > females Diagnosis & Treatment: • Diagnosis: – Endomyocardial biopsy

• Treatment: 1/28/09

– Supportive measures

Pathology wk1 LG1.10

Myocarditis Acute inflammation of the myocardium – Most often due to viral infections • Coxsackie B virus – Also can be caused by parasites • Toxoplasmosis – Can be due to a secondary disorder • Rheumatic fever – Aschoff bodies: granulomas in the myocardium – Bacteria are a rare cause • Epimyocardial microabscesses – Other causes: 1/28/09 Pathology wk1 LG1.10

Toxoplasma Myocarditis cyst

Myocardial Aschoff Bodies in Rheumatic Heart Disease

Viral Myocarditis • Viruses damage organelles -> cell death • Myocardium invaded by T-lymphocytes -> secrete interleukins, TNF -> destroy virusinfected myocardial cells • Pathology:

Viral (interstitial) myocarditis

– Tiger Effect • Pale, congested areas with mild hypertrophy • Biventricular dilatation • Generalized hypokinesis 1/28/09

Pathology wk1 LG1.10

Tiger Effect from Acute Viral Myocarditis

Acute Viral Myocarditis

• Histology: – Patchy, diffuse infiltrate of T-cells and macrophages surrounding individual myocytes – Focal or patchy acute myocyte necrosis

1/28/09

Pathology wk1 LG1.10

Pericarditis • Inflammation of the visceral or parietal pericardial layers • Most often associated with myocarditis, tuberculosis Causes of Pericarditis: • Bacteria, viruses, fungi (rarely) • Severe autoimmune diseases (SLE) • Rheumatic Heart Disease • Chronic renal failure -> metabolic waste products in the blood (uremia) • Trauma, radiation injury, and open-heart surgery 1/28/09

Pathology wk1 LG1.10

Pathology of Pericarditis

Exudation of fluid into the pericardial sac – Clear yellow with serous pericarditis (viral infections) – Purulent with bacterial infections – Serofibrinous exudate associated with more severe damage (Rheumatic fever)

Bacterial (Suppurativ 1/28/09

Serous

Pathology wk1 LG1.10

Fibrinous Pericarditis • Does not resolve as easily as a serous exudate • Fibrin bridges the space between the two layers of the pericardial sac – When separated the epicardium and pericardium resemble bread and butter taken apart • Macrophages invade exudate -> stimulate fibroblasts -> further fibrous adhesion = adhesive pericarditis • Blood vessels invade exudate -> organization = blood vessels fill space occupied by fibrin and obliterate it • Fibrous scarring may prevent expansion in diastole = constrictive pericarditis

1/28/09

Pathology wk1

Non Ischemic Causes:

Pericardit is

Sharp in quality Anterior in location Sharp in nature Non exercise related • Not relieved by NTG • • • •

1/28/2009

LG1.8 acute coronary syndrome, SP1.1 chest pain

• LG 1.11 Anticoagulants, antiplatelets, thrombolytics, antianginals Pharmacology Wendel • Objective: For each group of Antianginal drugs specify a prototypical agent and describe its mechanism of action, clinical use and adverse effects •   • Objective: For each of the seven agents (anticoagulants, antiplatelets, thrombolytics) listed previously be able to describe: Mechanism of action, Clinical

Statins/HMG-CoA reductase MOA: Inhibitors Clinical Uses: HMG-Co reductase inhibition:

– decreases synthesis of cholesterol in the liver – Therefore, LDL receptor is upregulated in expression and down regulated in clearance, thus uptake of LDL/IDL increases – Decrease in Cholesterol will also decrease VLDL synthesis

Vasoprotection: – Serves as an antioxidant or anti-inflammatory agent on blood vessels

Drug Interactions: – Substrates of P450 3A4 and 1/30/2009

Hypercholesterolemia (Type IIa): – First line choice – Used in combination with resins or niacin

Combines hyperlipidemia (Type Iib). – Used with niacin

Adverse effects: (HeMostatpinches Hepatic tissue and Muscle) – H- hepatic enzyme elevations and hepatic toxicity. – H- hypersensitivity (rare).

LG1.11, LG1.12

Bile acid-binding resins MOA • Increased bile acid excretion in the jejunum and ileum. • results in increased hepatic conversion of cholesterol to bile acids. • The resultant decrease in cholesterol leads to increased expression of LDL receptors and thus increased uptake of LDL and IDL

Clinical uses • Hypercholesterolemia (Iia) – 1st line choice

• Combined hyperlipidemia(Iib) – Used with other agents – NOT used in hypertriglyceridemia (Type 1 of IV) due to increase in VLDL

Drug interactions • Decreased absorption of certain drugs such as: Adverse effects (CoLestipol) – Aspirin • Constipation and bloating – Digitalis • Less absorption of fat – Statins soluble vitamins. – Decreased vitamin K may lead to hypoprothrombinemia 1/30/2009

– Tetracyclin – warfarin

LG1.11, LG1.12

Anti-hyperlipidemic Fibrates Fenofibrate, Gemfibrozil

Clinical uses: The GEMstone is usually worn on the 4th or the 3rd finger Hypertriglyceridemia (IV):

– This PHENOmenally • FABRICATEd GEMstone is made in BRAZIL. It fits in a HanD Large (HDL) that can hold a big Lipstick • (Lipoprotein Lipase-LPL)

– Used in severe or moderate cases.

MOA: • PPAR alpha activation • Dysbetalipoproteinemi leads to increased LPL a(III) expression, thus decreased plasma TG and VLVL levels by increasing Adverse effects: TG hydrolysis. • (The Phenomenal GEMstaone hurts) • increased plams HDL – G-gallstones due to rise in levels by increasing cholesterol hepatic expression of – E-elevated liver enzyme APoA-I and II levels

1/30/2009

LG1.11, LG1.12

Anti-hyperlipidemic drugs: sterol absorption inhibitor EZETIMIBE: Clinical uses • Has an Eze time blocking • Hypercholesterolemia. intestinal sterol absorption – Usually used with a statin MOA: • decreased sterol absorption • Decreased LDL by inhibiting intestinal absorption of cholesterol • decreased absorption of phytosterols

for synergistic action to decrease LDL

• Phytosterolemia

Adverse effects • (But no EZE time for the liver) • Hepatic dysfunction, reversible and usually minor

Drug interactions: • Plasma levels decreased by resins but increased by 1/30/2009

LG1.11, LG1.12

Niacin (nicotinc acid) • My NIECE has a very low dental line (VLDL) due to MOA: low tooth growth(TG). • Decreases Plasma VLDL Although she has small lips (Lp(a)), she likes to use a • Decreases Lp () • Increased HDL big lipstick (Lipoprotein Lipase (LPL) with a HanD large (HDL) Clinical uses: • Hypercholesterolemia(IIB) Adverse effects: • Combines hyperlipidemia – (my niece likes to FIGHT • Hypertriglyceridemia (IV) too) • Dysbetalipoproteinemia F - Flushing (III) I - Itching • Lp(a) GI upset hyperlipoproteinemia Hepatic dysfunction Hyperglycemia & Hyperuricemia 1/30/2009

LG1.11, LG1.12

Drugs used for Angina Pectoris VASODILATORS

NEGATIVE INOTROPIC DRUGS

Organic Nitrates

Beta-blockers (Bbs)

Nitroglycerin Isosorbide dinitrate

-olol

Propranolol

Isosorbide mononitrate

Nadolol

Amyl nitrite

Beta 1-selective

Calcium Channel Blockers (CCBs) dipine

Metoprolol Atenolol

Dihydopyridines – Nifedipine Amlodipine

Calcium Channel Blockers (CCBs) Verapamil

Felodipine

Diltiazem

Isradipine Nicardipine 1/30/2009

Nisoldipine

Non-selective

LG1.11, LG1.12

Drugs used for Angina Pectoris Antiplatelet Agents COX inhibitor Aspirin GPIIb/IIIa Antagonist Abciximab Eptifibatide Tirofiban Anticoagulants -parin Heparin Late Na current 1/30/2009 blocker

Mnemonic for angina drugs: A- anticoagulants B- Bbs C- vasoDilators (CCBs also) D- CCBs

LG1.11, LG1.12

Angina Pectoris & Anti-anginal Pathophysiology for angina pectoris & actions of anti-anginal drugs: • Anticoagulants & Antiplatelets prevent coagulation, platelet aggregation, and atherosclerotic plaques which in turn increases coronary blood flow • Vasodilators (venous) decrease myocardial wall tension • Negative inotropic drugs decrease HR and contractility, which in turn decreases preload • Vasodilators (arterial/arterioles prevent vasospasms and decrease peripheral 1/30/2009

LG1.11, LG1.12

Nitroglycerin MOA • Nitroglycerin will dilate veins more than arteries, – decreasing cardiac preload – leading to the following therapeutic effects during episodes of angina pectoris:

• • • •

subsiding of chest pain decrease of blood pressure increase of heart rate. orthostatic hypotension

These effects arise because: – nitroglycerin is converted to nitric oxide in the body by mitochondrial aldehyde dehydrogenase – nitric oxide is a natural vasodilator. 1/30/2009

LG1.11, LG1.12

Nitrates (Nitroglycerin, isosorbide Delivery: Adverse effects: • Administered across • Headache, syncope the buccal • Flushing, membrane palpitations, • should be used for postural acute/prophylactic hypotension angina pectoris • Rashes, – exertional, variant, or vasospasms on unstable withdrawal • Contraindicated in: MOA: – constrictive • Decreases oxygen pericarditis demand by dilating – increased veins and reducing intracranial the preload on the pressure heart 1/30/2009 LG1.11, LG1.12

Beta Blockers MOA • Propranolol (nonselective Beta Blocker) • Metoprolol (Beta 1selective Beta Blocker) • BOTH Act to decrease myocardial oxygen demand by

Clinical Use • DO NOT USE FOR PRINZMETAL (VARIANT) ANGINA • Use for chronic angina treatment (exertional and unstable)

Adverse effects ★ • Decreased tolerance for exertion ★ • Drowsiness • Increase diastolic • Rebound angina if perfusion time (increase discontinued coronary vessel • Asthma (due to the perfusion) presence of Beta receptors in the 1/30/2009 LG1.11, LG1.12 lungs as well0 ★

Decreasing HR Decreasing contractility Decreasing BP

Ca++ Channel Blockers

MOA – Verapamil (Calan) –Decrease force of myocardial contraction (decrease Ca in myocardial cells) –Decreased BP due to decreased Ca in vascular smooth muscle

Clinical Use –Chronic treatment of angina pectoris (all forms) –Alternative to beta blockers –Other uses (Arrhythmia, hypertension, migraine, myocardial infarction, etc)

Adverse effects: –Headache, dizziness –Flushing, hypotension, tachycardia, arrhythmias –Constipation, gingival hyperplasia, nausea, abdominal pain 1/30/2009

LG1.11, LG1.12

WEEK 2

• LG 2.1/2.2 Pavlick cardiac muscle excitation/pacemaker • Objective: Sketch a typical action potential in a ventricular muscle cell and a pacemaker cell, labeling both the voltage and time axes accurately. Describe how ionic currents contribute to all phases of the cardiac action potential. Use this information to explain differences in shapes of the action potentials of different cardiac cells. Describe the ion channels that contribute to each phase of the cardiac action potential. Explain how differences in channel population influence the shape of the action potential in the nodal, atrial muscle, ventricular muscle, and Purkinje fiber cardiac cells. • Objective: Define the Frank-Starling Law of the Heart.

Intercalated Discs The plasma membranes of adjacent cardiac muscle cells inter-lock at dark-staining junctions called INTERCALATED DISCS – see arrows in picture – Subdivided into two distinct structures: • Desmosomes - prevent cells from separating during contraction • Gap Junctions - allow ions to pass freely from cell to cell, directly transmitting the depolarizing current across the entire heart

Entire myocardium behaves as a single coordinated unit or FUNCTIONAL SYNCYTIUM 2/2/2009

LG2.1, LG2.2

Cardiac Action Potentials Two Types CAP: Non-Pacemaker or “Fast Response:” • Occur in atria, ventricles,

Purkinje fibers • undergo rapid depolarization (steeper slope during Phase 0)

Pacemaker or “Slow Response:” • Occur in the SA node and AV node

2/2/2009

AP Duration: • Neuron (green) – 1 msec; • Skeletal Muscle Cell – 2-5 msec; • Non-Pacemaker or “Fast Response” Cardiac LG2.1, LG2.2 Myocyte (red) – 200-400 msec

Summary of Ion Conductance & Channel Involvement

2/2/2009

LG2.1, LG2.2

Calcium Influx Key Points: • Excitation-Contraction coupling in skeletal muscle does NOT require influx through L-type Ca+2 channels, but cardiac contraction has an absolute requirement for Ca+2 influx through these channels during the action potential • The amount of calcium entering the cardiac muscle cell during an action potential is small and does NOT promote actin-myosin interaction • The influx of calcium during an action potential serves as a trigger to induce calcium release from the sarcoplasmic reticulum, which then promotes actinmyosin interaction and hence contraction • Neurotransmitters and drugs can alter calcium 2/2/2009

LG2.1, LG2.2

Calcium Extrusion Mechanisms 3 Mechanisms: • Sarcoplasmic Reticulum Ca+2 pumps (SERCA) – Utilize ATP

• Sarcolemmal Ca+2 pumps •

– Also ATP driven 3Na+/1 Ca+2 anti-

porters All 3 mechanisms 2/2/2009

LG2.1, LG2.2

Conduction Velocity

Speed at which excitation spreads throughout cardiac tissue • Depends on size of inward current during the upstroke (phase 0); • the larger the inward current, the higher the conduction velocity Purkinje fibers – fastest AV node – slowest* *Allows time for ventricular filling before

2/2/2009

LG2.1, LG2.2

The conduction system permits a rapid and organized depolarization of ventricular myocytes that is necessary for the efficient generation of pressure during systole.

Phases of Non-Pacemaker “Fast Response” Phase 0 (Rapid Depolarization) – Upstroke; – “Fast” Na+-channels open (iNa); – Several types of K+-channels closed (iK)

Phase 1 (Early/Initial Repolarization) – Transient outward current as K+ channels open (iKto); – “Fast” Na+-channels are closed

Phase 2 (Plateau Phase) – Long-lasting (L-type) Ca+2 channels open leading to inward calcium movement [iCa(L)]; – Efflux of K+ through several – types of K+-channels (iK, iK1, even iKto to a degree)

Phase 3 (Late or Final Repolarization) – Continual efflux of K+ through several channels; – Ca+2-channels eventually close 2/2/2009

LG2.1, LG2.2

Phases of Pacemaker “Slow Response” Phase 0 – Upstroke caused by an increase in Ca+2 conductance • (NOT an inward Na+ current) Phase 3 – Repolarization caused by an increase in K+ conductance; – results in an outward K+ current causing repolarization of the membrane potential Phase 4 – Slow depolarization – Accounts for the pacemaker activity of the SA node (automaticity) – Is caused by an increase in Na+ conductance, • which results in an inward current called If – If is “turned on” by 2/2/2009 LG2.1, LG2.2 repolarization of the membrane potential

Conduction Velocity Sympathetic activation –  conduction velocity (positive dromotropic effect) in nodal and non-nodal tissues by  the slope of phase 0 (more rapid depolarization of adjacent cells) – Results from NE binding to  -receptors; • drugs that block  -receptors (i.e., -blockers)  conduction velocity and can produce AV block. Parasympathetic (vagal) activation –  conduction velocity (negative dromotropy) in nodal and non-nodal tissues by decreasing the slope of phase Non-nodal 0 (slower depolarization of adjacent cells) – Ach binds to muscarinic receptors – excessive vagal activation can produce AV block – drugs such as digoxin • which increase vagal activity • used to reduce AV nodal conduction in patients that have tachycardia due to atrial flutter or fibrillation. Nodal Because CV depends on the rate of tissue depolarization (which is related to the slope of phase 0 of the AP) – conditions (or drugs) that alter phase 0 will affect conduction velocity.  – Examples • Conduction can be altered by changes in 2/2/2009 membrane potential, which LG2.1, LG2.2 during can occur myocardial ischemia & hypoxia

Cardiac EC Coupling Action potential spreads from the sarcolemma into the T-tubules During plateau phase: – Ca+2-conductance  – ECF Ca+2 enters cell Large release of Ca+2 from Sarcoplasmic Reticulum (SR) is triggered Ca+2 binds to troponin C and tropomyosin is moved out of the way – removing the inhibition of actin & myosin binding Thick and thin filaments slide past each other – myocardial cell contracts • the magnitude of the tension that develops is proportional to the ICF concentration of Ca+2 Relaxation occurs: – when Ca+2 is re-accumulated by the SR (via SERCA) – or moved to the ECF (via Sarcolemmal Ca+2 pumps and antiporters) 2/2/2009

LG2.1, LG2.2

Refractory Periods

Once a fast response has been initiated, the depolarized cell is no longer excitable until the cell is partially repolarized. EFFECTIVE (or ABSOLUTE) REFRACTORY PERIOD (c d) = a 2nd action potential absolutely cannot be initiated, no matter how large a stimulus is applied RELATIVE REFRACTORY PERIOD (d e) = a 2nd action potential may be evoked only when the stimulus is

TETA NY 2/2/2009

The electrical and mechanical events in cardiac muscle overlap (see pic →) • it is impossible to produce the summation and tetanus found in skeletal muscles during high frequency stimulation in cardiac muscles. LG2.1, LG2.2

Contractile Force Intrinsic Control of Contractile Force: – Frank-Starling Law: • within physiological limits, the more ventricles fill during diastole, the more blood they eject during systole

Extrinsic Control of Contractile Force: – INOTROPISM: • modification of cardiac contractility independent of Frank-Starling Law (“normal” curve shifts up or down) • Positive inotropism (↑ contractile force) occurs with sympathetic (NE) or hormonal (EPI) stimulation

KEY POINT • Heart is a functional syncytium; • it is NOT possible to increase the force of contraction via RECRUITMENT 2/2/2009 LG2.1, LG2.2

Contractile Force Intrinsic Control of Contractile Force: – Frank-Starling Law: • within physiological limits, the more ventricles fill during diastole, the more blood they eject during systole

Extrinsic Control of Contractile Force: – INOTROPISM: • modification of cardiac contractility independent of Frank-Starling Law (“normal” curve shifts up or down) • Positive inotropism (↑ contractile force) occurs with sympathetic (NE) or hormonal (EPI) stimulation

KEY POINT • Heart is a functional syncytium; • it is NOT possible to increase the force of contraction via RECRUITMENT 2/2/2009 LG2.1, LG2.2

• LG 2.3 Pong ECG • Objective: Describe and identify in a Lead II ECG: T wave • LG 2.4 and 2.7 EKG clinical Thomson • Objective: Distinguish among the major tachyarrhythmias and bradyarrhythmias • Objective: Recognize shockable rhythms

No r ma l

Atria l

Ventricular Fibrillation

2/2/2009

LG2.3 ECG/EKG

Atrial Fibrillation

• Multiple ectopic foci in the atria causing rate of 350-450/min • Irregular baseline without P-waves since no single impulse depolarizes the atria completely • Irregular ventricular (QRS) rhythm since only random impulses get through

Arrhythmias by Chris

A fib Ventricular rate is 75 QRS is normal. No LVH. ST and T changes could be due to digoxin effect.

EKG (LECOM)

Atrial Fibrillation

•

characterized by the presence of an irregularly irregular rhythm in the absence of P waves. 

•

Undulations in the baseline (known as "fib waves") may sometimes be seen . A Fib is therefore described as having one of the following: –

rapid ventricular response, • rate averages over 120 beats/minute.

–

controlled (moderate) ventricular response • rate averages between 70-110 beats/minute.

–

slow ventricular response • rate averages less than 60 beats/minute.

•

Common Causes: –

Hyperthyroidism

–

Alcohol use (Holiday heart)

–

Pulmonary embolism

–

Pneumonia.

–

Most commonly, atrial fibrillation occurs as a result of some other cardiac condition (secondary atrial fibrillation). • Heart valve disease • Left ventricular hypertrophy • Coronary heart disease

2/4/2009 • High blood pressure

LG2.7 Clincal EKG

Atrial Flutter Atrialflutter is like A-fib but there is a single foci that is reentrant. – That focus conducts repetitively. – The atrial rate is: • between 240 and 350 beats per minute for type I • Between 350 to 430 for type II; • this information is not very useful in the prehospital setting.

As seen here, the atrial waves are wider and move further from the isoelectric baseline. – What is the rate here?

EKG (LECOM)

Atrial Flutter

• Ectopic focus in the atria fires at 250-350 • Each P-wave looks identical to all the others – Not really P-waves = flutter waves – “Saw tooth” baseline

• Only occasional atrial stimulus will penetrate the AV node – Few flutter waves in series before a QRS

Arrhythmias by Chris

Atrial Tachycardia

Atrial tachycardia is similar to sinus tachycardia except the sinus node is not the primary focus. – The normal rate is 150 - 250 bpm for atrial tach. – We can see there is still a P wave for the QRS complexes; although small.

What is the rate here? – About 21*10 bpm.

EKG (LECOM)

Left Bundle Branch Block • Also notice the “M” pattern seen in lead V5 (or V6). • These are “left side” leads, implying LBBB;

*

EKG (LECOM)

Right Bundle Branch Block Also notice the “M” pattern seen in lead V2 (or V1). These are “right side” leads, implying RBBB;

*

EKG (LECOM)

Right Bundle Branch Block • R,R’ in V1 or V2 (right chest leads)

Arrhythmias by Chris

Conduction Issues

Conduction Block

Bundle Branch Block: • Failure in either right or left bundle branch. • Usual cause is myocardial damage. • Creates a prolonged QRS complex

*Most likely at the AV node – First degree AV block: • PR interval is prolonged, slow conduction in AV node

– 60 to 100 ms is normal – Up to 120 ms (incomplete block) – Longer than 120 ms (complete block)

– AV node becomes depressed (from anoxia etc) so the AV node cannot respond to a high rate of incoming impulses.

– Second degree AV block: • atrialexcitation does not lead to ventricular excitation. P waves but no QRS complexes. – Alternate waves can be blocked. – Ratios of waves to blocked waves can be 2:1, 3:1, 3:2, 4:1 etc.

2/2/2009

LG2.3 ECG/EKG

– Third degree or complete AV block: • AV node or common

First Degree Heart Block Here we can see that the PR interval is larger than 0.20s. – AV node is stalling for longer than it should. . the PR interval should be between 0.12 – Remember and 0.20s.

This may not cause immediate problems for the patient, but could progress to 2nd degree or 3rd degree block.

EKG (LECOM)

1st degree AV Block

• Prolongs the PR interval more than one large square (0.2s) • PR interval is prolonged the same amount in every cycle • Normal P-QRS-T • Asymptomatic

Arrhythmias by Chris

2nd degree AV Block: Mobitz I “Wenckebach” • PR interval becomes progressively longer until the final P wave does not elicit a QRS • Not pathologic

Arrhythmias by Chris

Second Degree Block Type I Type 1: Also called Wenckebach or MobitzI. Here the PR interval becomes longer and longer until a beat is eventually missed. – Notice after the 4th QRS here there is a T-wave then a pwave for the next beat. However, the ventricles are in refractory so they do not depolarize.

These patients may need treatment but it is not immediate; there is a good prognosis here.

* EKG (LECOM)

2nd degree AV Block: Mobitz II • QRS is dropped after a normal P wave • Generally there are normal, uniform PR intervals • Pathologic

Arrhythmias by Chris

Second Degree Block Type II

Type 2: Also called Mobitz II.

Here there is a dropped QRSfor a given P wave at regular intervals. – For example, there may be 4 p-waves for every 3 QRScomplexes. (4:3 block) – Here you can see 2 p-waves for every 1 QRScomplex (2:1 block). • The p-wave after the T-wave does not cause a QRS.

These patients may need treatment more quickly, which may be

EKG (LECOM)

What’s the difference? AV block 2nd degree

2/2/2009

LG2.3 ECG/EKG

3rd degree “Complete” AV

• None of the atrial depolarizations penetrate through to the ventricles • Ventricles must be paced independently by a ectopic (junctional or ventricular) focus • AV dissociation – Atrial rate independent of ventricular rate

• Usually treated with a pacemaker

Arrhythmias by Chris

Third Degree Heart Block Also called complete heart block. • Another description of this type of block would be sinus rhythm 3rd degree block with ventricular escape (or junctional escape). • This has a very poor prognosis if treatment is not given quickly. These patients will become pacemaker dependent. Here the p-waves are separate from the QRS complexes, signifying that they are not coordinated. – You can see that in the middle the p-wave occurs during the QRS and is masked.

EKG (LECOM)

Supraventricular Tachycardia Supraventricular tachycardia (SVT) can also be paroxysmal (PSVT), meaning it occurs intermittently. – – –

SVT is the same as Atrial Tachycardia (AT), except AT may use an accessory pathway. SVT uses the normal pathway (SA, AV) so QRS complexes are narrow. It looks like a box of crayons if the ECG is held upside down.

These are initially treated with vagal maneuvers: – –

having the patient bear-down (adult) ice water pack on the face (child, mammalian diving reflex)

Drugs such as adenosine may be given as well. –

Adenosine has a half-life <10 seconds so it is important to administer rapid push (RIVP) followed by a saline bolus as the drug will be metabolized quickly in the body.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common type of reentrant supraventricular tachycardia (SVT).

EKG (LECOM)

Supraventricular Tachycardia • Tachycardia that originates above the ventricles – Both atrial and junctional tachycardia

Arrhythmias by Chris

Wolff-Parkinson-White • Accessory bundle of Kent provides ventricular “preexcitation” bypassing AV node • Premature ventricular depolarization represented as a delta wave • Shortened PR interval • Lengthened QRS • Patients may have supraventricular tachycardia of 2 mechanisms: – Re-entry • Ventricular depolarization may immediately restimulate the atria in a retrograde fashion

– Rapid conduction • Supraventricular Arrhythmias by Chris tachycardia may be rapidly

Ventricular Fibrillation Blood is not circulated throughout the system and the patient will die quickly

– losing 10% chance of survival for every minute in arrest. – Along with pulseless ventricular tachycardia these rhythms are treated with drugs (epinepherine) and “Edison medicine” (shocking). – Emergency personnel follow the ABCDs for basic life support and CPR: • Airway, Breathing, Circulation, and Defibrillation

Here, multiple foci in the ventricles fire causing the heart to

EKG (LECOM)

Ventricular Fibrillation • • • •

Numerous ventricular ectopic foci producing a rate of 350-450 Erratic twitching because so many foci firing at once, each only depolarizing a small area No identifiable waves No effective cardiac pumping – A type of cardiac arrest – Fatal without CPR and defibrillation

Arrhythmias by Chris

Ventricular Flutter

• Single ventricular ectopic focus firing at 250-350 • Smooth sine wave appearance • No cardiac output -> deteriorates into ventricular fibrillation

Arrhythmias by Chris

Ventricular Tachycardia

This rhythm is marked by very wide QRS complexes occurring rapidly.

– The problem is blood cannot fill into the atria quick enough and thus is not oxygenated well. – It is important to check a pulse before defibrillating this patient. The patient will die without treatment.

Here, an irritable focus in the ventricles fires at 150 to 250bpm causing the heart to beat too quickly.

EKG (LECOM)

Torsade de Pointes Torsade de Pointes (tōr-sad’ dĕ pwant’) literally means “twisting of the points” – giving a twisted ribbon or party streamer look. – The “R on T” phenomenon occurs when a PVC R-wave lands on a T-wave, causing ventricular arrhythmia. – Ventricular fibrillation is induced in patients receiving implantable cardioverter defibrillators (ICDs) using a similar “T-Shock”. – TdP is facilitated by prolonged QT interval (QTc) due to drugs or heredity. • http://qtdrugs.org/

EKG (LECOM)

• LG 2.6 Fischione Cardiac tumors • Objective: Describe the pathologic findings of a Cardiac Myxoma

Cardiac Tumors • Rare • Usually benign and pedunculated • Three types: – Cardiac myxomas – Rhabdomyomas – Metastatic tumors

2/4/2009

LG2.6 Pathology

Cardiac Myxomas • The most common primary adult tumor (35-50%) • Most arise from the left atrium (90%) • Complications: – “Ball-valve” effect may obstruct the mitral valve orifice in over half of patients with myxomas of the left atrium • Blocks diastolic filling of the ventricle, stimulating mitral valve stenosis -> may cause syncopal episodes

– One third of these patients die of embolization of the tumor to the brain

• Dx: transesophageal Right ultrasound With

stalk

2/4/2009

LG2.6 Pathology

Histology of Cardiac Myxomas • Loose myxoid matrix • Abundant proteoglycans with stellate cells within the matrix Stellate cells and fibroblasts

2/4/2009

Amorphous extracellular matrix

LG2.6 Pathology

Rhabdomyomas • Most common primary cardiac tumor in infants and children – Major association with tuberous sclerosis

• Forms hamartomas in the myocardium • Almost all are multiple – Involve both the left and right ventricles, and the atria in 1/3 of cases – Projects into the cardiac chamber in ½ of cases

• Grossly: – Pale gray masses, up to several centimeters

• Histologically: – Derived from striated muscle cells with abundant glycogen

Grossly

2/4/2009

Striated muscle (“Spider”) cells

LG2.6 Pathology

• LG 2.8 Antiarrhythmics Pharmacology Szarek • Objective: Explain the molecular mechanism of action of antiarrhythmic drugs.

Adenosine (a-den-oh-seen) • Therapeutic class – Antiarrhythmic agent

• Pharmacologic class – Purine nucleoside

• M.O.A. – Activates adenosine receptors -> Gi coupled ↓ in cAMP = opens K channels and blocks Ttype Ca influx – ↓SA, AV nodal activity by ↓slope of phase 4

• Clinical Use

• Special Considerations – IV – Half life < 10 seconds

• Adverse Effects – Bronchospasm in asthmatics – Hypotension – Facial flushing

• Interactions – Antagonized by theophylline – Dipyridamole ↓uptake and ↑ its effects

– DOC for terminating paroxysmal supraventricular tachycardias, AV nodal arrhythmias – Emergency useCardio Drugs for BOARDS more than test

Adenosine – Transient asystole

• Antiarrhythmic • Purine nucleoside, cardiac node membrane stabilizer • Opens K channels & blocks Ca influx in SA & AV nodes • Slows AV conduction • ↑ AV refractory period Drugs

Amiodarone (am-ee-oh-darone) •

• Therapeutic class

– Antiarrhythmic agent

• Pharmacologic class – Class III antiarrhythmic – Mimics classes I, II, III, IV

• M.O.A. – Blocks K, Na, Ca and Breceptors – Slows phase 3 (repolarization), increases refractory periods, slows HR, increases PR and QT intervals = ↑APD and ERP

Adverse Effects

Pulmonary fibrosis Hypo/hyperthyroidism Hepatotoxicity Blue pigmentation of the skin (“smurf skin”) – Photosensitivity – Corneal deposits – – – –

• Interactions – ↑digoxin levels

• Clinical Use – Supraventricular and ventricular arrhythmias, including V-tach and V-fib – Oral and IV

• Special Considerations – Very long half-life (>80 days) – Safe to use in Wolff-ParkinsonCardio Drugs for BOARDS more than test White

Amidarone • Antiarrhythmic • Cardiac ion channel blocker

– – – – –

• Blocks K, Na, Ca channels & β receptors – – – –

Prolongs repolarization ↑ refractory period Slows HR ↑ PR & QT intervals

Drugs

Hypo/hyperthyroidism Photosensitivity Blue-gray skin Corneal microdeposits Pulmonary fibrosis

Atenolol (a-ten-oh-lol) •

Therapeutic class

•

– Sympatholytic; antihypertensive

• •

– Bronchoconstriction due to B2 blockade – Heart block – Bradycardia

Pharmacologic class – Selective B1 receptor antagonist – Class II antiarrhythmic

M.O.A.

•

Clinical Use – Supraventricular tachycardias via ↓ AV-conduction – Angina – Hypertension – Post-MI – Oral and IV

•

Special Considerations

Interactions – Additive hypotensive effect with nitrates and antihypertensives – Additive bradycardia with digoxin – Unopposed α-adrenergic stimulation with epinephrine and in pt’s with excess sympathetic stimulation (pheochromocytoma) = severe hypertension/arrhythmias

– Competitively blocks B1 receptors = ↓cAMP, ↓Ca currents – ↓phase 4 slope in pacemakers = ↓SA and AV nodal activity = ↑PR interval

•

Adverse Effects

•

Similar Drugs – Acebutolol – *Esmolol* (IV): used in acute SVT’s; very short half life – Metoprolol: may cause dyslipidemia

– C/I in Wolff-Parkinson-White, vasospasm, bronchospasm, and diabetes Cardio Drugs for BOARDS more than test – Less lipophilic; fewer CNS effects

Atropine (at-roe-peen) • Therapeutic class – Anticholinergic agent

• Pharmacologic class – Muscarinic receptor antagonist

• M.O.A. – Competitively blocks all muscarinic receptors

• Clinical Use – Acute MI – Bradycardia and AV block – Irritable bowel symptoms – Anticholinesterase poisoning

• Special

• Adverse Effects – – – –

Tachycardia Mydriasis Cycloplegia Delirium and hallucinations

• Interactions – Additive anticholinergic effects with antihistamines and tricyclic antidepressants – Slows absorption of other drugs by delaying gastric empying

• Similar Drugs

– Dicyclomine Cardio Drugs for BOARDS – more than test Ipratropium

Digoxin • Therapeutic class – Cardiac stimulant

• Pharmacologic class – Digitalis glycoside

• M.O.A. – Inhibits Na/K ATPase – ↑intracellular Ca and cardiac contractility from indirect inhibition of Na/Ca exchanger – ↓AV conduction

• Clinical Use – Heart failure (↑contractility) – Atrial fibrillation (↓AV conduction and depression of SA node)

• Special Considerations – Metabolized in stomach by intestinal bacteria – Most of drug is eliminated unchanged in the urine ↓dose in renal failure – C/I in Wolff-ParkinsonWhite

• Adverse Effects – Proarrhythmic – GI: nausea, vomiting, diarrhea – Blurred vision, yellow vision

• Interactions

– Amiodarone, quinidine, cyclosporine, diltiazem, Cardio Drugs for BOARDS more than verapamil test and increase

Digoxin • Cardiac stimulant • Digitalis glycoside

– Arrhythmias – N, V

• Inhibits Na/K ATPase

– Blurred vision – Yellow vision

– ↑ IC Ca & cardiac contractility – ↓ AV conduction – ↑ AV refractory period – Heart failure – Serum levels assess Drugs

Lidocaine (lye-doe-cane) • Therapeutic class

• Special Considerations

– Local anesthetic

• Pharmacologic class – Amide-type local anesthetic – Class IB antiarrhythmic

• M.O.A. – Blocks inactivated Na channels – ↓APD due to block of the slow Na “window” currents

• Clinical Use – Ventricular arrhythmias – IV because of 1st pass metabolism – Post-MI due to preference for tissues partly depolarized = ↑threshold for excitation and ↓excitability of hypoxic heart muscle – Open-heart surgery

– Rapid onset of action and immediate duration – Metabolized in liver - ↓ in liver disease – Inducers/inhibitors of liver enzymes alter metabolism

• Adverse Effects – Rarely: cross-hypersensitivity with other amide-type anesthetics – CNS toxicity: confusion, dizziness, seizures – Least cardiotoxic of conventional antiarrhythmics

• Interactions – Additive effects with other local anesthetics and class I antiarrhythmics

• Similar drugs – Mexiletine, tocainide = oral analogues

Cardio Drugs for BOARDS more than test

Magnesium • M.O.A. – Unknown

• Clinical Use – Torsades – Digoxin-induced arrhythmias

Cardio Drugs for BOARDS more than test

Procainamide • Therapeutic class – Antiarrhythmic agent

• Pharmacologic class – Class IA sodium channel blocker

• M.O.A. – Blocks Na channels in the open or activated state and K channels in cardiac tissue, slowing conduction – ↑action potential duration (APD) and the effective refractory period (ERP) – Less M2 block than Quinidine, no α1 block = less ANS side effects

•

• Special Considerations – Metabolized in liver to NAPA (N-acetylprocainamide), a K channel blocker with class III antiarrhythmic effects – NAPA and parent drug excreted by kidney = caution in pt’s with renal failure

• Adverse Effects

– Hypotension – Systemic Lupus Erythematosus (SLE)-like syndrome more likely with slow acetylators – Torsades caused by NAPA Clinical Use prolonging refractoriness than lengthening test and the QT – Supraventricular Cardio and Drugs for BOARDS more

•

Propafenone (proe-paff-enone) • Special Considerations Therapeutic class – Antiarrhythmic agent

• Pharmacologic class – Class IC sodium channel blocker

• M.O.A. – Blocks fast Na channels, especially His-Purkinje tissue = marked ↓ in slope of phase 0 – No effect on APD – No ANS effects

• Clinical Use – Supraventricular arrhythmias

– Metabolized in liver = reduce in liver disease – Monitor ECG when starting therapy; most proarrhythmic events occur in 1st 2 weeks

• Adverse Effects – Proarrhythmic: can aggravate existing arrhythmias or precipitate new ones; may prolong QT interval – Bronchospasm in asthmatics due to Bblocking effects – GI disturbances – Dizziness

• Interactions – Increases digoxin levels

Cardio Drugs for BOARDS more than test

• Similar drugs

•

Propranolol (proe-pran-ohlol)• Special Considerations Therapeutic class – Sympatholytic; antihypertensive

•

– Highly lipophilic = CNS penetration – insomnia and depression – Metabolized in liver; extensive 1st pass metabolism – C/I in Wolff-Parkinson-White, vasospasm, bronchospasm, and diabetes

Pharmacologic class – Nonselective B receptor antagonist – Class II antiarrhythmic

•

M.O.A. – Competitively and non-selectively blocks B1 and B2 receptors = ↓cAMP, ↓Ca currents – ↓phase 4 slope in pacemakers = ↓SA and AV nodal activity = ↑PR interval

•

•

– Bronchoconstriction – Cold extremities and impotence due to B2 blockade – Heart block – Bradycardia

Clinical Use – Supraventricular tachycardias via ↓ AV-conduction – Angina – Hypertension – Post-MI – Oral and IV

Adverse Effects

•

Interactions

– Additive hypotensive effect with nitrates and antihypertensives – Additive bradycardia with digoxin – Unopposed α-adrenergic stimulation with epinephrine and in pt’s with excess sympathetic stimulation (pheochromocytoma) = severe hypertension/arrhythmias Cardio Drugs for BOARDS more than test

Quinidine (kwin-i-deen) • Therapeutic class – Antiarrhythmic agent

• Pharmacologic class – Class IA sodium channel blocker

• M.O.A. – Blocks Na channels in the open or activated state and K channels in cardiac tissue, slowing conduction – ↑action potential duration (APD) and the effective refractory period (ERP)

• Clinical Use

• Adverse Effects – Proarrhythmic effects • M2 receptor blockade: ↑HR and AV conduction, prolongation of QRS and ↑QT interval • α1 receptor blockade: vasodilation with possible reflex tachycardia

– Cinchonism: GI, tinnitus, ocular dysfunction, CNS excitation due to ANS effects – Hypotension

• Interactions

– Hyperkalemia enhances effects, worsens risk of – Supraventricular and arrhythmias ventricular arrhythmias – Displaces digoxin from – Orally effective tissue binding sites, enhancing toxicity – Levels↑ by amiodarone, cimetidine, diltiazem, Cardio Drugs for BOARDS more than test

Sotalol (soe-ta-lole) • Therapeutic class – Antiarrhythmic agent

• Pharmacologic class – Class III K channel blocker – Exhibits class II actions

• M.O.A.

• Special Considerations – Excreted unchanged in urine = ↓dose,↑dosing interval in pt’s with renal failure

• Adverse Effects

– Blocks K channels in cardiac tissue, slowing phase 3 = ↑APD, ERP – Also blocks B1 receptors = ↓HR, AV conduction

• Clinical Use – Supraventricular and lifethreatening ventricular arrhythmias – Oral

– Torsades – Bronchoconstriction due to B-blockade

• Interactions – Hypotension with antihypertensives and nitrates – Bradycardia with digoxin – Myocardial depression with verapamil

• Similar Drugs – Ibutilide

Cardio Drugs for BOARDS more than test

Verapamil (ver-ap-a-mil) •

Therapeutic class

•

– Antihypertensive and antianginal agent – Class IV antiarrhythmic

• •

– – – – –

Pharmacologic class – Non-dihydropyridine Ca channel blocker

M.O.A.

•

Clinical Use – – – –

•

Supraventricular tachycardias Hypertension Angina Oral and IV

Special Considerations

Constipation Hypotension and bradycardia Peripheral edema Gingival hyperplasia AV block

Interactions – C/I in Wolff-Parkinson-White – Additive AV block with Bblockers and digoxin – Displaces digoxin from tissue binding sites – Cyclosporine, quinidine, carbamazepine, grapefruit juice ↑serum levels

– Blocks L-type cardiac Ca channels – Primarily affects nodal cells – ↓phase 0 = ↓SA, AV nodal activity

•

Adverse Effects

•

Similar Drugs – *Diltiazem*

– Metabolized in the liver = caution in liver disease – Inducers of P450 ↑metabolism – ↓P450 Cardio Drugs for BOARDS more than test – Suppresses cardiac contractility

Enalapril • •

Antihypertensive ACE inhibitor

– Cough & angioedema

•

Inhibits ACE & formation of AT II

– Hypotension – Taste disturbances

– – – – –

Vasodilation ↓ aldosterone secretion ↑ CO ↓ V remodeling ↑ survival in heart failure

– – – –

HTN Heart failure Post-MI ↓ progression of diabetic

• Inhibits bradykinin degradation

Drugs

Esmolol • • •

Antiarrhythmic Class II Selective β1 blocker

•

Blocks SNS stim. SA & AV nodes – – –

↓ HR ↓ AV conduction ↑ AV refractory period

–

Sinus tachycardia & SVT during/after surgery

–

Rapidly metabolized by plasma esterase

– Hypotension – Bradycardia

Drugs

Furosemide • •

Loop-acting diuretic Membrane ion transport inhibitor

•

Inhibits Na/K/2Cl cotransporter in ascending loop of Henle –

Blocks NaCl reabsorption

– – – –

Edema Heart failure HTN Hypercalcemia

–

↑ Ca excretion Drugs

– – – –

Hypokalemia Metabolic alkalosis Hyperuricemia Hypomagnesemia

– ↑ ototoxicity of aminoglycoside ABX

WEEK 3

• LG 3.1/3.2 Pavlick Hemodynamics/Systemic circ • Objective: Explain the relationship between pressure, flow, and resistance. • Objective: Explain how Poiseuille's Law influences resistance to flow. Use it and other equations to calculate changes in resistance.

• LG 3.3 Pong VSM control • Objective: Describe the pressure changes across the cardiovascular system.

• LG 3.4 Pavlick control of BP • Objective: Predict the mechanisms the body utilizes to restore and maintain arterial pressure under various pathological / clinical scenarios. • Objective: List all of the anatomical components of the baroreceptor reflex.

• LG 3.7 Shock Pharmacology Szarek • Objective: Explain the mechanism of action of each drug in each drug class • ..\My Documents\SOMA\Cardiopulmonary xls

• LG 3.8 Moticka Immunology • Objective: Describe the mechanism by which endotoxin can result in the pathophysiology of shock

• LG 3.9 Fischione Hemodynamics • Objective: Differentiate Cardiogenic from Hypovolemic Shock clinically   • Objective: Differentiate Acute vs. Chronic Hyperemia

• LG 3.11 Pavlick edema • Objective: Explain how edema develops in response to: venous obstruction, lymphatic obstruction, increased capillary permeability, heart failure, tissue injury or allergic reaction, malnutrition, other clinical scenarios (as discussed in the Berne & Levy assignment or

Week 4

• LG4.3 Normal Cardiovascular Control and Exercise – Dr. Pong • Objective: Describe the importance of the venous return for cardiovascular control. •  

• LG4.2 Cardiac Performance – Dr. Pavlick AND LG6.2 Compensatory Responses to CHF – Dr. Pavlick • Objective: Using key cardiac equations, calculate various parameters, including stroke volume, cardiac output, mean arterial pressure, stroke work, ejection fraction, EDV, ESV and cardiac index. Objective: Describe and predict the impact of changes in preload, afterload, and contractility in determining cardiac performance. • Objective: Draw a cardiac function curve and explain which factors cause the curve to shift. • Objective: Draw a ventricular pressure-volume loop and on

Physiology Stroke Volume: SV = EDV-ESV Cardiac Output (C0) Heart Rate X Stroke Volume CO = HR X SV Ejection Fraction: – –

the fraction of the EDV ejected in each stroke volume is an estimation of contractility is normally ~ 0.55-0.75 or 55%-75%

EF = SV / EDV

Stroke Work Stroke Work = Aortic Pressure X Stroke Volume –

fatty acids are the primary energy source for stroke work

  Cardiac Output CO = MAP / TPR 2/17/2009

LG4.2 Cardiac Performance

185

• Objective: Describe and predict the impact of changes in preload, afterload, and contractility in determining cardiac performance.

Factors Affecting Heart Rate Parasym path etic Ne r vous Syst em

Sym pa th etic ner vous sys tem

The SA node, atria, and AV node have parasympathetic vagal innervation, but the ventricles do not.

norepinephrine is the neurotransmitter, acting at b1 receptors Positive chronotropic effect

The neurotransmitter is acetylcholine (Ach) muscarinic

–

Increases HR by increasing the rate of phase 4 depolarization

–

More action potentials occur per unit time because the threshold potential is reached more quickly and, therefore, more frequently

–

The mechanism of the positive chronotropic effect is increased If, the inward Na+ current that is responsible for phase 4 depolarization in the SA node.

Negative chronotropic effect –

Decreases HR by decreasing the rate of phase 4 depolarization

–

Fewer action potentials occur per unit time because the threshold potential is reached more slowly and, therefore, less frequently

–

The mechanism of the negative chronotropic effect is decreased If, the inward Na+ current that is responsible for phase 4 depolarization in the SA node

Negative dromotropic effect –

Decreases conduction velocity through the AV node

–

Action potentials are conducted more slowly from the atria to the ventricles

Positive dromotropic effect –

Increases conduction velocity through the AV node

–

Action potentials are conducted more rapidly from the atria to the ventricles, and ventricular filling may be compromised.

–

Decreases the PR interval on ECG

–

The mechanism of the positive dromotropic effect is increased inward Ca+2 current

–

the positive dromotropic effect reinforces the positive chronotropic effect

– Increases the PR interval on ECG 2/17/2009 LG4.2 Cardiac Performance Other – The mechanism of the negative

187

Factors Affecting Stroke Volume Frank-Starling Law of the Heart Preload Describes the increases in stroke volume and cardiac output that occur in response to an increase in venous return or end-diastolic volume (preload) – Based on the length-tension relationship in the ventricle; increases in EDV cause an increase in ventricular fiber length, which produces an increase in developed tension – Is a major mechanism that matches cardiac output to venous return (particularly on a beat-by-beat basis); the greater the VR, the greater the CO – This type of control of SV is sometimes referred to as heterometric regulation – There is no single Frank-Starling curve (or “cardiac function curve”) on which the ventricle operates; there is actually a family of curves, each of which is defined by the afterload and inotropic state of the heart. – ↑ afterload or ↓ inotropy shifts the curve down and to the right, whereas ↓ afterload and ↑ inotropy shifts the curve up and to the left Key point: – ANY mechanism that raises cytosolic [Ca+2] • increases the developed force within the myocardial cells. – ANY mechanism that lowers the cytosolic [Ca+2] –

•

decreases the developed force within the myocardial cells.

2/17/2009

LG4.2 Cardiac Performance

188

Factors Affecting Stroke Volume (Contractility)

2/17/2009

LG4.2 Cardiac Performance

Inotropism

189

Factors Affecting Stroke Volume

Inotropism

Increased Heart Rate [POSITIVE INOTROPIC EFFECT] – More action potentials – more Ca+2 enters the myocardial cells during the action potential plateaus – more Ca+2 is released from the SR – greater tension is produced during contraction This phenomenon is known as: – “positive staircase” – “Bowditch staircase” – treppe. Increased HR increases the force of contraction – in a stepwise fashion

2/17/2009

LG4.2 Cardiac Performance

190

Factors Affecting Stroke Volume

Inotropism

Sympathetic stimulation via b1 receptors [POSITIVE INOTROPIC EFFECT] –

Increases the inward Ca+2 current during the plateau of each cardiac action potential

–

Increases the activity of the SERCA pumps • as a result, more Ca+2 is accumulated by the SR and thus more Ca+2 is available for release in subsequent beats

–

NE binding to b1-receptors on cardiac muscle cells activates adenylate cyclase • thereby increasing c-AMP

2/17/2009

• promoting cAMP-dependent phosphorylation of 2 important proteins: – the L-type Ca+2 channels (responsible for the “trigger” Ca+2) – Phospholamban (protein associated with SERCA) » The combined action of these phosphorylations increases the amount of Ca+2 in the SR. – The net result is that the SR releases more Ca+2 into the cytosol during the next action potential, which promotes more actin-myosin LG4.2 Cardiac Performance interactions and hence a greater 191 force of contraction.

Factors Affecting Stroke Volume

Inotropism

Cardiac glycosides (e.g., digoxin) [POSITIVE INOTROPIC EFFECT]

Increase the force of contraction: – by inhibiting Na+-K+ ATPase in the myocardial cell membranes • As a result of this inhibition – the intracellular [Na+] increases – diminishing the Na+ gradient across the cell membrane

Na+-Ca+2 exchange (a mechanism that extrudes Ca+2 from the cell):

2/17/2009

LG4.2 Cardiac Performance

192

Factors Affecting Stroke Volume Inotropism (Contractility) & Afterload

 Parasympathetic stimulation via muscarinic receptors

[NEGATIVE INOTROPIC EFFECT] – Decreases the force of contraction in the atria (NOT THE VENTRICLES) • by decreasing the inward Ca+2 current during the plateau of the cardiac action potential – control of SV via inotropism • sometimes referred to as homometric regulation. – In other words, contractile strength is independent: • of muscle stretch (Starling's Law) • the EDV – Instead, it is dependent on things like HR, SNS or ParaNS influence, and drugs. Afterload – ↑ afterload: • The ventricle must pump blood against a higher pressure, resulting in a ↓ in stroke volume 2/17/2009 LG4.2 Cardiac Performance – ↓ afterload:

193

Summary Cardiac performance is ENHANCED by: ↑ Preload ↑ Inotropy ↑ Heart rate ↓ Afterload Cardiac performance is DEPRESSED by: ↓ Preload ↓ Inotropy ↓ Heart rate ↑ Afterload 2/17/2009

LG4.2 Cardiac Performance

194

• Objective: Draw a ventricular pressure-volume loop and on it label the phases and events of the cardiac cycle.

Ventricular Pressure - Volume Loops 1

2 (isovolumetric ventricular contraction) –

The cycle begins at the very end of diastole at point 1. • The left ventricle is filled with blood from the left atrium and its volume is about 140ml (EDV).

–

Ventricular pressure is low because the ventricular muscle is relaxed.

–

On excitation, the ventricle contracts and ventricular pressure increases.

–

The mitral valve closes when left ventricular pressure is greater than left atrialpressure. • Because all valves are closed, no blood can be ejected from the ventricle (isovolumetric)

2

3 (ventricular ejection) –

The aortic valve opens at point 2 when pressure in the left ventricle exceeds pressure in the aorta. • Blood is ejected into the aorta, and ventricular volume decreases.

–

The volume that is ejected in this phase is the stroke volume. • Thus, stroke volume can be measured graphically by the width of the pressurevolume loop. – The volume remaining in the left ventricle at point 3 is the end systolic volume (ESV).

3

4 (isovolumetric ventricular relaxation) –

At point 3, the ventricle relaxes. • When ventricular pressure decreases to less than aortic pressure, the aortic LG4.2 Cardiac Performance 196 valve closes.

2/17/2009

Changes in the ventricular pressure-volume loop are caused by several factors:

A.

B.

Increased Preload – Refers to an ↑ in EDV and is the result of ↑ VR – Causes an ↑ in SV based on the Frank-Starling mechanism – The increase in SV is reflected in increased width of the pressure-volume loop

Increased Afterload – Refers to ↑ in aortic pressure (in terms of the left ventricle) – The ventricle must eject blood against a higher pressure, resulting in a ↓ in SV – The decrease in SV is reflected in decreased width of the pressure-volume loop – The decrease in SV results in Cardiac an increase in ESV 2/17/2009 LG4.2 Performance 197

• Objective: Draw a cardiac function curve and explain which factors cause the curve to shift.

Vascular Function Curves / Venous Return A vascular function or venous return curve depicts the relationship Curves between blood flow through the vascular system (or venous return) and right atrial pressure (RAP). – As RAP (or PRA) increases, venous return falls. – Venous return to the heart from the venous vascular beds is determined by a pressure gradient (venous pressure, PV, minus right atrial pressure, PRA).   Therefore, ***increases in venous pressure or decreases in right atrial pressure will lead to an increase in venous return.

Mean Systemic Filling Pressure (MSFP) – Point where the vascular function curve intersects the x-axis. – MSFP equals right atrialpressure when there is “no flow” in the cardiovascular system. – It is measured when CO and VR are zero • pressure is equal throughout the cardiovascular system. – It is often used as a reference point of sorts when looking at a SERIES of

2/17/2009

LG4.2 Cardiac Performance

199

Shifting of Vascular Function

Blood Volume –

Mean systemic pressure is increased by an increase in blood volume • shift of the vascular function curve to the right.

–

Mean systemic pressure is decreased by a decrease in blood volume • shift of the vascular function curve to the left.

Arteriolar Resistance –

The slope of the venous return curve is determined by the resistance of the arterioles.

–

Clockwise rotation: • indicates a ↓ in TPR: – When TPR is ↓ for a given right atrial pressure, there is an ↑ in venous return » i.e., vasodilaton of the arterioles “allows” more blood to flow from the arteries to the veins and back to the heart

–

Counterclockwise rotation:

• indicates an ↑ in TPR: givenCardiac right atrial 2/17/2009 – When TPR is ↑ for aLG4.2 Performance

200

Combining Cardiac Output & Venous Return Curves

Equilibrium or Steady State:

– The point at which the 2 curves intersect . – Equilibrium occurs when CO = VR.

Cardiac output can be changed by: – Altering the cardiac output curve, the venous return curve, or both curves simultaneously. – The superimposed curves can be used to predict the direction & magnitude of changes in cardiac output. CO=V R

2/17/2009

LG4.2 Cardiac Performance

201

Combining Cardiac Output & Venous Return Curves

Positive inotropic agents – e.g., digoxin – produce ↑ contractility and ↑ cardiac output. The equilibrium, or intersection, point shifts to: – a higher CO – A correspondingly lower RAP. • RAP decreases because more blood is ejected from the heart on each beat – Increased SV 2/17/2009

LG4.2 Cardiac Performance

202

Changes in Blood Volume Change the Venous Return Curve

 An ↑ in blood volume ↑ MSFP

– shifting the venous return curve to the right in a parallel fashion. – A new equilibrium, or intersection, point is established at which both cardiac output and RAP are ↑

A ↓ in blood volume (e.g., hemorrhage) has the opposite effect: – ↓ MSFP and a shift of the venous return curve to the left in a parallel fashion. – A new equilibrium is established at which both 2/17/2009

LG4.2 Cardiac Performance

203

Changes in TPR Change Cardiac Function & Venous Return Curves

 Changes in TPR alter both curves simultaneously:

–

therefore, the responses are more complicated than those noted in the previous examples.

↑ TPR: – causes a ↓ in both cardiac output and venous return

A counterclockwise rotation of the venous return curve occurs: – ↑ TPR results in ↓ VR as blood is retained on the arterial side.

A downward shift of the cardiac function curve is caused by the ↑ aortic pressure (↑ afterload) as the heart pumps against a higher pressure. – As a result of these simultaneous changes, a new equilibrium point is established at which both cardiac output and venous return are ↓. 2/17/2009

LG4.2 Cardiac Performance

RAP is unchanged

204

• LG4.5 Aortic Disease – Dr. Fischione • Objective: Describe the basic etiology of Atherogenesis

Etiology of Atherosclerosis Endothelial cell injury -> platelet, LDL deposition -> macrophage stimulation -> trapped LDL’s transformed into foam cells Platelets release growth factors -> proliferation of smooth muscle cells -> lipid accumulation within their cytoplasm -> death -> deposition of lipid as cholesterol crystals in the interstitial spaces

2/17/2009

Macrophages take up released lipids from LG4.5 & LG4.7 Pathology 206 smooth muscle death ->

Atheroma Soft core of lipids & cellular debris – covered by a fibrous cap of collagen and smooth muscle cells Major complication is vessel hardening from calcification 2/17/2009

LG4.5 & LG4.7 Pathology

Aortic atheroma with foam cells and

207

• •

•

• •

• •

Risk factors of Atherosclerosis

Age: – older age Sex: – males > females – sex differences less after menopause due to protective effect of estrogens Heredity: – i.e. Familial Hypercholesterolemia • a genetic defect of LDL receptors that does not allow lipoproteins into the liver Lipid Metabolism: – elevated serum levels of lipids Hypertension: – accelerates atherosclerosis due to: • endothelial defects • ischemic damage • damaged platelets Obesity: – causes secondary hyperlipidemia Diabetes: – hyperglycemia damages small blood vessels (microangiopathy) 2/17/2009 LG4.5 & LG4.7 Pathology 208 – accelerates atherosclerosis

Complications of Atherosclerosis Thrombus

formation: due to collagen exposure, plaque rupture, platelet activation and coagulation sequence activation

Aneurysm formation: hypertension develops as blood passes through narrower vessel -> Various forms of Aortic pressure causes Aneurysms dilatation 2/17/2009

LG4.5 & LG4.7 Pathology

– Most common 209

Dissecting Aneurysm

Aortic Dissection

Abdominal Aortic 2/17/2009 Aneurysm

Aortic Dissection between the muscle layer (tunica media)

Aortic Dissection into Media

Major danger of an aneurysm is rupture -> jet of blood dissects through wall -> forms periarterial second lumen in the media = dissecting aneurysm LG4.5 & LG4.7 Pathology

210

Cerebrovascular Disease Cerebrovascular atherosclerosis

Atherosclerosis of Circle of Willis

– Atherosclerosis of the internal carotids/circle of Willis -> strokes – 3rd most common cause of death and the most crippling disease in the U.S.

May be gradual from progressive fibrosis/calcification, or sudden from plaque rupture -> Thromboemboli from L heart to cerebral artery thrombosis 2/17/2009

LG4.5 & LG4.7 Pathology

211

Atherosclerosis of the Typically affects legs more than arms Extremities May present as intermittent claudication: chronic ischemia of the lower limbs secondary to narrowing of the femoral or popliteal artery = underperfusion of the leg muscles during walking/running – Treated with surgical plaque removal (endarterectomy)

May present as gangrene from sudden occlusion of

Atherosclerosis of the extremity causing 2/17/2009 LG4.5 & LG4.7 Pathology gangrene from diabetes

212

Atherosclerosis of Renal Arteries Reduced flow of blood through renal arteries -> hypoperfusion of the kidneys -> renal dysfunction -> increased renin release -> hypertension 2/17/2009

Renal atherosclerosis

LG4.5 & LG4.7 Pathology

213

Atherosclerosis of the Intestinal Arteries Causes ischemia of gradual onset in the intestines -> nonspecific GI symptoms (constipation, poor digestion, malabsorption)

2/17/2009

Intestinal infarction

Acute occlusion, i.e. from embolic thrombic occlusion -> intestinal

LG4.5 & LG4.7 Pathology

214

• LG4.6 Peripheral Artery Disease, Ulceration Patterns – Dr. Sharifi • Objective: Understand the importance of ABI and how to calculate it.

DIAGNOSIS • • • •

History taking Careful examination of leg Pulse evaluation Ankle-brachial index (ABI): SBP in ankle (dorsalis pedis and posterior tibial arteries) SBP in upper arm (brachial artery) Diagnostic Imaging

2/20/09

LG4.6

216

Ankle-Brachial Index Values & Clinical Classification Clinical PresentationAnkle-Brachial Index Normal

> 0.90

Claudication

0.50-0.90

Rest pain

0.21-0.49

Tissue loss

< 0.20

Values >1.25 falsely elevated; commonly seen in diabetics 2/20/09

LG4.6

217

• LG4.7 Vasculitis Leading to Skin ulcerations – Dr. Fischione • Objective: Describe the pathology and ANCA involvement in ChurgStrauss Syndrome

Pathogenesis of Vasculitis May be associated with a viral infection

C-ANCA’s seen in Wegener’s

Small vessel vasculitides – i.e. Wegener granulomatosis and Polyarteritis Nodosa – associated with ANCA (anti-neutrophil cytoplasmic antibodies) • Common patterns are:

P-ANCA’s seen in Polyarteritis 2/17/2009 LG4.5 & LG4.7 Pathology Nodosa

– perinuclear immunoflouresnce (PANCA) – cytoplasmic 219

Churg-Strauss Syndrome

Granulomatous foci around blood vessels

2/17/2009

LG4.5 & LG4.7 Pathology

Intense eosinophilic

• AKA allergic granulomatosis and angiitis • Systemic vasculitis in young people with asthma • Both C-ANCA and P-ANCA are demonstrated in 2/3 of patients • Microscopic findings: – Granulomas with intense eosinophilic infiltrate -> fibrinoid necrosis 220

• Objective: Determine which organs and tissues are involved in Kawasaki Disease

3 year old presents w/ a high fever for the past week. Physical exam reveals:

Mucocutaneous lesions

Peeling of the 2/17/2009 fingertips

R ash

Desquamation of the sole LG4.5 & LG4.7 Pathology of foot

222

Kawasaki Disease • AKA mucocutaneous lymph node syndrome • Acute necrotizing vasculitis of infancy and early childhood • Symptoms: Coronary artery with aneurysmal formations

Large coronary artery aneurysm

2/17/2009

– High fever, rash – Conjunctival, oral lesions – Lymphadenitis – Desquamation of the fingertips, soles and palms

• In 70%: affects coronary arteries -> *coronary artery aneurysms* LG4.5 & LG4.7 Pathology • Possible association 223

WEEK 5

• LG5.2 Endocarditis – Dr. Fischione • Objective: Identify the features of Endocarditis in Intravenous Drug Abusers (IVDA) • Objective: Describe characteristics of Subacute Bacterial Endocarditis (SBE) and the causative organisms

• Endocarditis in IVDA • Bacteremia from cellulitis or phlebitis at the injection site or drug contamination is the pathogenesis of this type of endocarditis • The tricuspid valve is infected in over 50% of all addicts with signs and symptoms of pulmonary emboli and abscesses leading to Pneumonia. • St. aureus is responsible

Infective endocarditis • Acute (staph aureus)

• Subacute (S. viridians)

• LG5.3 Endocarditis – Dr. Kuo • Objective: Identify and contrast the most common microbial etiologies of endocarditis in native and prosthetic valves.

COMMON MICROBIAL ETIOLOGIES OF

• Most prevalent are staphylococci, streptococci, and enterococci. • S. aureus is the most common cause. • Acute endocarditis: S. aureus accounts for 60% of cases. • Subacute endocarditis: α-hemolytic and nonhemolytic streptococci cause 60% of infection.

COMMON MICROBIAL ETIOLOGIES OF ENDOCARDITIS • First year post-op: often perioperative contamination (nosocomial); 55% staphylococci; mostly βlactam antibiotic–resistant S. epidermidis

• >1 year post-op: community acquired; streptococci, S. aureus, enterococci, and Gram-negative coccobacilli; : mostly βlactam sensitive

• LG5.4 Heart Sounds – Dr. Rios • Objective: Describe the pathophysiology of heart sound abnormalities

• LG5.5 Valvular Disease, Rheumatic Fever, Cardiomyopathies – Dr. Fischione • Objectives: Describe what Aschoff Bodies are as they relate to RHD; Define the Jones Criteria for the diagnosis of RHD

• Objective: Demonstrate the major diagnostic procedure for the diagnosis of all cardiomyopathies

• LG5.6 Embryology, Congenital Heart Disease – Dr. Fischione (2 hours) • Objective: Differentiate prenatal vs. postnatal structures in fetal circulation •   • Objective: Define rib-notching and how this characteristic occurs in Coarctation •   • Objective: Illustrate the four characteristics of a Tetralogy of Fallot

• LG5.7 Murmurs – Dr. Rios • Objective: Discuss the mechanism(s) for heart murmurs and the physiological principles.

• LG5.8 Drugs for Endocarditis – Dr. Szarek Objective: Differentiate between the uses of these drugs in treating infective • ..\My Documents\SOMA\Cardiopulmonary

WEEK 6

• LG6.3 Congestive Heart Failure – Dr. Fischione • Objective: Differentiate pathology between right and left-sided heart failure.

3/3/2009

LG6.2 Compensatory Responses to Heart Failure

264

Congestive Heart Failure • Failure of the heart as a pump • Characterized by: • forward failure • backward failure • both

3/3/2009

LG6.3 Congestive Heart Failure

265

Left Heart Failure Etiology: – Ischemic heart disease – HTN – Aortic and mitral valve disease – Non-ischemic myocardial disease Pathology: – LVH with dilation -> secondary enlargement of the left atrium -> atrial fibrillation -> blood stasis -> thromboemboli – Lungs due to backward failure: • Pulmonary congestion and edema • **Hemosiderin-laden macrophages (“heart-failure cells”)** – macrophages phagocytize RBC’s in alveolar sacs – Kidneys due to forward failure: • ↓CO -> activation of the RAS -> fluid retention -> pulmonary edema – Brain due to forward failure: • Hypoxia -> hypoxic encephalopathy -> stupor, loss of consciousness, restlessness, coma Clinical: – Dyspnea 3/3/2009

Pulmonary edema

Lung Hemosiderin-laden macrophages LG6.3 Congestive Heart Failure

266

Right Heart Failure Etiology: – Most common cause is left heart failure – If isolated: cor pulmonale Pathology: – Backward failure -> congestion of the venous Centrilobular passive system congestion of the liver (Nutmeg liver) – Hepatomegaly: • chronic passive congestion of the liver (“Nutmeg liver”) – Splenomegaly – Ascites (fluid within the abdomen) – Peripheral edema Pitting ankle (petal) • Ankle edema • Sacrum 3/3/2009 LG6.3 Congestive Heart Failure 267

• LG6.4 CHF-pharmacology Szarek • Objective: Explain the molecular mechanism of action of each drug in each drug class

• ..\My Documents\SOMA\Cardiopulmonary

• SP5.3 Syncope – Dr. Sharifi; PW5.3 Syncope – Dr. Sharifi • Objective: Recognize Diagnostic modalities: Rhythm monitoring, Head Up Tilt

• A test used to determine the cause of fainting spells. The test involves being tilted, always with the head-up, at different angles for a period of time (2 minutes at 30 degrees, then 2 minutes at 45 degrees, then up to 45 minutes at 70 degrees) . Heart rhythm, blood pressure and other symptoms are closely monitored and evaluated with changes in position. • Purpose – determine the cause of fainting spells – evaluate heart rhythm, blood pressure,