Intensive Course For Emergency Medicine Phase I

(MMed Professional Exam 2010)

KS Chew

School of Medical Sciences

Universiti Sains Malaysia

Cardiovascular Physiology Review: Cardiac Output

• Stroke volume = End diastolic volume – End systolic volume = 135 – 65 = 70 ml

• At rate of 70 beats/min, CO = 70 * 70 = 4900 ml

• Ejection fraction (EF) is the ratio of stroke volume to end-diastolic volume (EDV), expressed as a percentage:

• EF = (SV/EDV) * 100

Schematic Representation Of The Frog-heart Preparation Used By Otto Frank

Frank-Starling Law

Effects On Stroke Volume Of Stimulating The Sympathetic Nerves To The Heart

The pressure-volume cycle of the human left ventricle. The area bounded by the pressure-volume curve gives the stroke work of the heart. The lower confine of the pressure-volume loop shown by the dotted line is defined by the passive stretch of the relaxed ventricular muscle by the returning blood.

Increased Preload

Increased Afterload

Increased Contractility

Vascular Function and Cardiac Function Curve

Vascular Function and Cardiac Function Curve

Relationship Between End-diastolic Ventricular Volume and Stroke

Volume

Pathophysiology of Acute Coronary Syndrome

Chronology of the interface between the patient and the clinician through the progression of plaque formation and the onset of complications of STEMI.

Management Before STEMI

41 2 3 4 5 6

Onset of STEMI- Prehospital issues- Initial recognition and management in the Emergency Department (ED)- Reperfusion

Hospital Management- Medications- Arrhythmias- Complications- Preparation for discharge

Secondary Prevention/Long-Term Management

Presentation

Working Dx

ECG

Cardiac Biomarker

Final Dx

UA

NQMI QwMI

No ST Elevation

NSTEMI

Ischemic DiscomfortAcute Coronary Syndrome

UnstableAngina

Myocardial Infarction

ST Elevation

Modified from Libby. Circulation 2001;104:365, Hamm et al. The Lancet 2001;358:1533 and Davies. Heart 2000;83:361.

Pathophysiology of ACS

Fuster V et al NEJM 1992;326:310–318Davies MJ et al Circulation 1990;82(Suppl II):II–38, II–46

Lipid poolLipid pool

MacrophagesMacrophages

Stress, tensile,Stress, tensile,internalinternal

Shear forces,Shear forces,externalexternal

FissureFissure

LargeLargefissurefissure

SmallSmallfissurefissure

Mural thrombusMural thrombus(unstable angina/(unstable angina/non-Q-wave MI)non-Q-wave MI)

Occlusive thrombusOcclusive thrombus(Q-wave MI)(Q-wave MI)

AtheroscleroticAtheroscleroticplaqueplaque

PlaquePlaquedisruptiondisruption

ThrombusThrombus

One example of atherothromboticdisease progression

Atherothrombosis: a Generalized and Progressive Process

NormalNormalFattyFattystreakstreak

FibrousFibrousplaqueplaque

Athero-Athero-scleroticscleroticplaqueplaque

PlaquePlaquerupture/rupture/fissure &fissure &thrombosisthrombosis MIMI

IschemicIschemicstroke/TIA stroke/TIA

Critical Critical

leg leg ischemiaischemiaClinically silentClinically silent

CardiovascularCardiovasculardeathdeath

Increasing ageIncreasing age

Stable anginaStable anginaIntermittent claudicationIntermittent claudication

UnstableUnstableanginaangina}}ACSACS

ACS, acute coronary syndrome; TIA, transient ischemic attack

Platelet Inhibition With GP IIb/IIIa Inhibitors

Reproduced with permission from Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Engl J Med. 2000;342:101-114. Copyright © 2000, Massachusetts Medical Society. All rights reserved.

Mechanism of Action of Aspirin in Acute Coronary Syndrome

Prostacyclin is produced by endothelial cells and thromboxane A2 by platelets from their common precursor arachidonic acid via the cyclooxygenase pathway.

Thromboxane A2 promotes platelet aggregation and vasoconstriction, whereas prostacyclin inhibits platelet aggregation and promotes vasodilation.

The balance between platelet thromboxane A2 and prostacyclin fosters localized platelet aggregation and consequent clot formation while preventing excessive extension of the clot and maintaining blood flow around it.

Mechanism of Action of Aspirin in Acute Coronary Syndrome

The thromboxane A2–prostacyclin balance can be shifted toward prostacyclin by administration of low doses of aspirin. Aspirin produces irreversible inhibition of cyclooxygenase.

Although this reduces production of both thromboxane A2 and prostacyclin, endothelial cells produce new cyclooxygenase in a matter of hours whereas platelets cannot manufacture the enzyme, and the level rises only as new platelets enter the circulation. This is a slow process because platelets have a half-life of about 4 days.

The thrombus in STEMI is RBC & fibrin rich and often called a red clot or red thrombus

Unstable angina and NSTEMI often precedes STEMI (preinfarction angina). During this phase blood flow in the coronary artery becomes sluggish gradually, and therefore the platelets get trapped within the plaque. Hence in NSTEMI, thrombus is predominantly a white thrombus (platelet rich). Often, a central platelet core is seen over which fibrin clot may also be formed.

Fibrinolytics

• Why is streptokinase not used in treating UA/ NSTEMI?

• All available thrombolytic agents act basically as a fibrinolytic agents, therefore it is difficult to lyse the platelet rich clot.

• There is also a risk of these agents lysing the fibrin cap and exposing underlying platelet core and trigger a fresh thrombus (TIMI IIIb trial)

STEMI, NSTEMI and UA

• STEMI - occlusive thrombus - ST elevation (and Q waves) - Cardiac Enzyme elevation - Fibrinolytics beneficial

• NSTEMI - non-occlusive thrombus - NO ST/Q - Cardiac Enzyme elevation present - Fibrinolytics not beneficial

• UA - non-occlusive thrombus - NO ST/Q - Cardiac Enzyme elevation absent - Fibrinolytics not beneficial

Electrophysiological Changes During Cardiac Ischemia

• Ischemia/hypoxia causes an elevation in extracellular K+. This occurs because K+ leaks out through K+ - ATP channels and because of decreased activity of the Na+/K+-ATPase pump

Pathophysiology of Asthma and COPD

• A chronic inflammatory disorder of the airways

• Many cells and cellular elements play a role• Characterized by airway hyperresponsiveness

that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing

• Widespread, variable, and often reversible airflow limitation

YYYYYY

Mast cellMast cell

CD4+ cellCD4+ cell(Th2)(Th2)

EosinophilEosinophil

AllergensAllergens

Ep cellsEp cells

ASTHMAASTHMA

BronchoconstrictionBronchoconstrictionAHRAHR

Alv macrophageAlv macrophageEp cellsEp cells

CD8+ cellCD8+ cell(Tc1)(Tc1)

NeutrophilNeutrophil

Cigarette smokeCigarette smoke

Small airway narrowingSmall airway narrowingAlveolar destructionAlveolar destruction

COPDCOPD

Reversible IrreversibleAirflow LimitationAirflow Limitation

Source: Peter J. Barnes, MD