6 Cardiology High Yield

CA01.1- CA01.1-

Introduction Cardiovascular System Lecture I

Stephen Bagley, M.D. Resident Physician University of Pennsylvania

1

CA01.1- CA01.1-

To understand the following topics and how they may be

tested on USMLE Step 1 – Cardiac physiology

• Fluid dynamics • The cardiac cycle • Electrophysiology

– Heart sounds – Biochemistry of lipids – Ischemic heart disease and cardiomyopathies – Congenital heart disease – Vasculitis

Cardiovascular System Course Objectives:

2

CA01.1- CA01.1-

– Beta and alpha adrenergic receptors and

their role in the cardiovascular system – Cardiac output – Resistance, pressure, and flow – Cardiac function curve

Learning Objectives

3

CA01.2-

Kaplan Pharmacology 2011 : Table II-3-2

FA 2012: 263.1 • FA 2011: 236 • FA 2010: 232 • ME 3e: 169 1

CA01.3-

KNOW THE FICK PRINCIPLE

CO = O2 Consumption / (Arterial O2 – Venous O2)

• O2 Consumpsion Æ often given • Arterial O2 = [Hgb] x [1.34] x [Arterial O2 Saturation] • Venous O2 = [Hgb] x [1.34] x [Venous O2 Saturation]

FA 2012: 280.2 • FA 2011: 254.2 • FA 2010: 250 • ME 3e: 249

1

CA01.3-

Mean Arterial Pressure (MAP)… MAP = (CO) X (TPR) MAP = (2/3 Diastolic Pressure) + (1/3 Systolic Pressure) When heart rate increases, so does the cardiac output and the mean arterial pressure, all things being equal.

FA 2012: 280.2 • FA 2011: 254.2 • FA 2010: 250 • ME 3e: 248

2

CA01.3-

What changes cardiac output... By changing:

Contractility

Preload

Afterload

FA 2012: 281.1 • FA 2011: 255.1 • FA 2010: 251 • ME 3e: 243

3

CA01.3-

Kaplan Pharmacology 2011 : Figure III-4-2

FA 2012: 281.1 • FA 2011: 255.1 • FA 2010: 251 • ME 3e: 271

Ca2+ +

(SERCA)

4

CA01.4-

Kaplan Physiology 2011 : Figure IV-1-9

FA 2012: 281.1 • FA 2011: 255.1 • FA 2010: 251 • ME 3e: 251

1

CA01.4-

PRELOAD = Left Ventricular EDV

FA 2012: 281.2 • FA 2011: 255.2 • FA 2010: 251 • ME 3e: 242

2

CA01.4-

AFTERLOAD = Mean Arterial Pressure (MAP)

FA 2012: 281.2 • FA 2011: 255.2 • FA 2010: 251 • ME 3e: 242

3

CA01.4-

Kaplan Physiology 2011 : Figure VI-1-1

FA 2012: 281.2 • FA 2011: 255.2 • FA 2010: 251 • ME 3e: 242

4

CA01.4-

Bitzblitz, commons.wikimedia.org, Used With Permission

Frank-Starling Curve

Increased Contractility

Decreased Contractility

SV

(uL)

LVEDP (mmHg)

Normal

FA 2012: 281.3 • FA 2011: 255.3 • FA 2010: 251 • ME 3e: 242

5

CA01.4-

NEED TO KNOW !

EF tells us about the heart’s contractility EF = SV / EDV = (EDV-ESV) / EDV A decrease in EF is seen in heart failure Echocardiograms are often used to diagnose heart failure by measuring ejection fraction!

FA 2012: 282.1 • FA 2011: 255.4 • FA 2010: 251 • ME 3e: 242

6

CA01.5-

Resistance (R) = 8(viscosity) x Length π r 4

As viscosity increases, resistance increases Examples: Polycythemia, multiple myeloma

As radius (r) increases, resistance decreases The aorta has less resistance to flow than a capillary

FA 2012: 282.2 • FA 2011: 256.1 • FA 2010: 252 • ME 3e: 248

1

CA01.5-

FA 2012: 282.2 • FA 2011: 256.1 • FA 2010: 252 • ME 3e: 248

2

CA01.5-

Kaplan Physiology 2011 : Figure V-1-5

FA 2012: 282.2 • FA 2011: 256.1 • FA 2010: 252 • ME 3e: 249

Velocity = Q/CSA Q = flow

CSA = cross sectional area

3

CA01.5-


FA 2012: 282.2 • FA 2011: 256.1 • FA 2010: 252 • ME 3e: 249

4

CA01.5-

Cardiac and Vascular Function Curves

commons.wikimedia.org Used with permission

FA 2012: 282.3 • FA 2011: 256.2 • FA 2010: 252 • ME 3e: 243

filling pressure

5

CA02.1- CA02.1-

Lecture II • Cardiac cycle • Maintenance of MAP


The Cardiac Cycle

1

CA02.1-

Kaplan Physiology 2011 : Figure VI -1-6

FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 245 2

CA02.1- FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 245 3

CA02.1-


FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 245 4

CA02.1-

Bitzblitz, commons.wikimedia.org, Used With Permission

Increased Contractility

Decreased Contractility

SV

(uL)

LVEDP (mmHg)

Normal

Frank-Starling Curve

FA 2012: 281.3 • FA 2011: 255.3 • FA 2010: 251 • ME 3e: 243 5

CA02.1-

Points: – Greater pressure needed to

open aortic valve – Smaller stroke volume – An example of this would be Æ increased in systemic blood pressure

FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 246 6

CA02.1-

Points: – Phase 4 longer – Larger EDV – Wider curve – Increased PVL area – Increased SV and CO

FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 245 7

CA02.1-

Increasing Afterload Increasing Preload

FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 246 8

CA02.1-


FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 245 9

CA02.2-

Kaplan Physiology 2011 : Figure VI -1-1 & Figure VI -1-3

FA 2012: 283.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 244 1

CA02.3-

Lecture II continued Cardiac cycle Maintenance of MAP

Cardiology

1

CA02.3-

Lecture II continued

Maintenance of MAP

Cardiology

2

CA02.3-

Kaplan Physiology 2011 : Fig V-1-18

FA 2012: n/a • FA 2011: 265.1 • FA 2010: 261 • ME 3e: 253 3

CA02.3-

Kaplan Physiology 2011 : Fig X-4-9

FA 2012: n/a • FA 2011: 265.1 • FA 2010: 261 • ME 3e: 253 4

CA02.3-

Atrial Natriuretic Peptide

FA 2012: n/a • FA 2011: 265.1 • FA 2010: 261 • ME 3e: 316 5

CA02.3-

Return to this chart later for review…

FA 2012: 290.3 • FA 2011: 265.2 • FA 2010: 261 • ME 3e: 253 6

CA02.3-

Kaplan Pathology 2011 : Fig 5-5

FA 2012: 290.3 • FA 2011: 265.2 • FA 2010: 261 • ME 3e: 253 7

CA02.3-

Return to this chart later for review…

FA 2012: 290.3 • FA 2011: 265.2 • FA 2010: 261 • ME 3e: 253 8

CA02.3-

Kaplan Physiology 2011 : Fig VII-3-8

FA 2012: 290.3 • FA 2011: 265.2 • FA 2010: 261 • ME 3e: 288 9

CA02.3-

Don’t get tricked with Cushing’s Triad…

ICP Via sympathetic NS Hypertension Via sympathetic NS

Inappropriate response

Appropriate response

Bradycardia

TRIAD = Hypertension + Bradycardia + Respiratory Depression

FA 2012: 290.3 • FA 2011: 265.2 • FA 2010: 261 • ME 3e: 288 10

CARDIO3.1- CARDIO3.1-

Lecture III • Autoregulation of blood flow • Capillary fluid exchange • Sympathomimetic drugs

Regulation of blood flow and fluid exchange


1

CARDIO3.1-

Nevit Dilmen, commons.wikimedia.org, Used With Permission

FA 2012: 291.1 • FA 2011: 265.3 • FA 2010: 261 • ME 3e: 252

2

CARDIO3.1-

FA 2012: 291.3 • FA 2011: 266.2 • FA 2010: 262 • ME 3e: 252

Autoregulation


What factors control local blood flow?

• Heart: O2, adenosine, NO

• Brain: arterial pCO2/pH

• Kidney: tubuloglomerular feedback

• Lungs: hypoxic vasoconstriction (next slide)

• Skeletal muscle: lactate, adenosine, potassium

3

CARDIO3.1-

Pneumonia = No Oxygen

Nevit Dilmen, commons.wikimedia.org, Used With Permission

FA 2012: 291.3 • FA 2011: 266.2 • FA 2010: 262 • ME 3e: 252

4

CARDIO3.1-

Skin • Temperature influences local

blood flow

Kaplan Pharmacology 2011 : Figure V-2-4

FA 2012: 291.3 • FA 2011: 266.2 • FA 2010: 262 • ME 3e: 252

5

CARDIO3.1-

FA 2012: 291.4 • FA 2011: 266.3 • FA 2010: 262 • ME 3e: 250

6

CARDIO3.2-

DIRECT SYMPATHOMIMETICS

Norepinephrine

Dobutamine

Dopamine

Epinephrine

Isoproterenol Phenylephrine

FA 2012: n/a • FA 2011: 240 • FA 2010: 236 • ME 3e: 193

1

CARDIO3.2-

Kaplan Pharmacology 2011 : Figure II-3-5c

FA 2012: n/a • FA 2011: 240 • FA 2010: 236 • ME 3e: 193

2

CARDIO3.2-

Kaplan Pharmacology 2011 : Figure II-3-4

FA 2012: n/a • FA 2011: 240 • FA 2010: 236 • ME 3e: 193

3

CARDIO3.2-

Beta Agonists/Dopamine

• β1 and β2 agonists: isoproterenol • β1 agonists: dobutamine • β2 agonists: albuterol, metaproterenol, terbutaline, salmeterol

• Dopamine: – Does dependent effect:

– Causes vasoconstriction via action upon α1 receptors (dose

dependent) – Causes cardiac stimulation via B1 receptor stimulation

FA 2012: 266.3 -267.1 • FA 2011: 240 • FA 2010: 236 • ME 3e: 193

Β1 effects α1 effects (low doses) (high doses)

4

CARDIO3.2-

Kaplan Pharmacology 2011 : Figure II-3-2

FA 2012: 266.3 • FA 2011: 240 • FA 2010: 236 • ME 3e: 193 5

CARDIO3.2-

FA 2012: 267.1 • FA 2011: 240 • FA 2010: 236 • ME 3e: 194

• Both amphetamines and cocaine are indirect sympathomimetics.

• Both increase endogenous norepinephrine in the synapse.

6

CARDIO3.3-

Clinical Pearls… Clonidine often used to treat opiate withdrawal

– Dampens the sympathetic response that occurs during opiate withdrawal

α-methyldopa indicated in hypertension in pregnancy

FA 2012: 267.2 • FA 2011: 241.1 • FA 2010: 237 • ME 3e: 193

1

CARDIO3.4-

Chikumaya, commons.wikimedia.org, Used With permission

FA 2012: 291.2 • FA 2011: 266.1 • FA 2010: 262 • ME 3e: 249

1

CA04.1 - CA04.1 -

Lecture IV • Normal electrophysiology

Cardiac Electrophysiology


1

CA04.1 -


FA 2012: n/a • FA 2011: 260.1 • FA 2010: 256 • ME 3e: 232

2

CA04.1 -

Ventricular Action Potential


FA 2012: 286.1 • FA 2011: 260.2 • FA 2010: 256 • ME 3e: 237

3

CA04.1 -

EM of Intercalated Disk with

Gap Junction (arrow). Adjacent to an Adhering Junction with Intracellular Density


FA 2012: n/a • FA 2011: 260.1 • FA 2010: 256 • ME 3e: 232

4

CA04.1 -

Cardiac Action Potentials in Fast-Response Fibers


FA 2012: 286.1 • FA 2011: 260.2 • FA 2010: 256 • ME 3e: 237

5

CA04.1 -

Mechanism of Action of Voltage-Gated Na+ Channels

FA 2012: 286.1 • FA 2011: 260.2 • FA 2010: 256 • ME 3e: 237

6

CA04.1 -



FA 2012: 286.1 • FA 2011: 260.2 • FA 2010: 256 • ME 3e: 237

7

CA04.1 -

Cardiac Action Potentials in Slow-Response Fibers – SA and AV Nodes

FA 2012: 287.1 • FA 2011: 261.1 • FA 2010: 257 • ME 3e: 237

8

CA04.1 -

Sympathetic Effects

Parasympathetic Effects


FA 2012: 287.1 • FA 2011: 261.1 • FA 2010: 257 • ME 3e: 237

9

CA04.1 -

Cardiac Action Potentials in Slow-Response Fibers – SA and AV Nodes

FA 2012: 287.1 • FA 2011: 261.1 • FA 2010: 257 • ME 3e: 237

10

CA04.2 -

Glenlarson, commons.wikimedia.org, Used With permission

Normal ECG Demonstrating Sinus Rhythm

FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 258 • ME 3e: 239

1

CA04.2 -

EKG Leads

FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 258 • ME 3e: 241

2

CA04.2 -

commons.wikimedia.org Used with permission

FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 258 • ME 3e: 241

3

CA04.2 -

Normal Pattern of an ECG


FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 258 • ME 3e: 238

4

CA05.1- CA05.1-

Arrhythmias

Lecture V – Arrhythmias – Antiarrhythmic drugs


1

CA05.1-

Lecture V Arrhythmias

Cardiovascular System

2

CA05.1-

TORSADES DE POINTES

Long QT Interval

Congenital Causes Jervell and Lange-Nielsen syndrome

Arrhythmogenic Drugs Class Ia and III Antiarrhythmics Antipsychotics

Metabolic Disturbances Hypokalemia, hypomagnesia,

FA 2012: 288.2 • FA 2011: 262.2 • FA 2010: 258 • ME 3e: 240 3

CA05.1- FA 2012: n/a • FA 2011: 263.1 • FA 2010: 259 • ME 3e: 236

DeltaWave09.jpg, commons.wikimedia.org, Used With Permission

Delta Waves

WPW.jpeg, commons.wikimedia.org, Used With Permission

Two-way

Shortened PR interval

Two-way accessory pathway

4

CA05.1- FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 259 • ME 3e: 236

Arrhythmias Atrial fibrillation:

Atrial flutter:

5

CA05.1-

Arrhythmias: AV Block 1st Degree

2nd Degree

3rd Degree

Progressive prolongation of the PR interval

A blocked beat is not preceded by a change in PR interval

FA 2012: 288.1 • FA 2011: 264.1 • FA 2010: 260 • ME 3e: 236

•Slowed conduction through the AV node

•Some impulses are not transmitted through the AV node

•No impulses are conducted from the atria to ventricles

6

CA05.1-

Arrhythmias: Ventricular Ventricular fibrillation :

FA 2012: 288.1 • FA 2011: 262.1 • FA 2010: 259 • ME 3e: 236 7

CA05.2-

Lecture V

Antiarrhythmic drugs


1

CA05.3- 1



FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 237

CA05.3-

Mechanism of Action of Voltage-Gated Na+ Channels


FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 267 2

CA05.3-



• Class IA drugs block Na+ channels and increase AP duration

• Examples: quinidine, procainamide, disopyramide

• Should not be used in patients with a long QT interval

FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 237 3

CA05.3-

TORSADES DE POINTES

Long QT Interval

Congenital Causes Jervell and Lange-Nielsen syndrome

Arrhythmogenic Drugs Class Ia and III Antiarrhythmics Antipsychotics

Metabolic Disturbances Hypokalemiae Hypomagnesemia

FA 2012: 288.2 • FA 2011: 262.2 • FA 2010: 258 • ME 3e: 240 4

CA05.3-

Antiarrhythmic toxicities are heavily tested on

USMLE Step 1…

Class Ia Class Ib Class Ic • Thrombocytopenia • Torsades de pointes • Reversible lupus-like syndrome (procainamide) • Cinchonism (quinidine)

• CNS stimulation • CV depression

• Proarrhythmic • Contraindicated after myocardial infarction

The toxicity is increased in all class I antiarrhythmics with HYPERkalemia.

FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 267 5

CA05.3-



• Class IB drugs decrease AP duration; lidocaine, mexiletine, phenytoin

• Class IC drugs have no effect on AP duration; flecanide, encainide, propafenone; pro-arrhythmic

FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 237 6

CA05.3-

Antiarrhythmic toxicities are heavily tested on

USMLE Step 1…

Class Ia Class Ib Class Ic • Thrombocytopenia • Torsades de pointes • Reversible lupus-like syndrome (procainamide) • Cinchonism (quinidine)

• CNS Stimulation • CV depression

• Proarrhythmic • Contraindicated after myocardial infarction

The toxicity is increased in all class I antiarrhythmics with HYPERkalemia.

FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 267 7

CA05.4- FA 2012: 311.1 • FA 2011: 285.1 • FA 2010: 281 • ME 3e: 269

Hypertension Angina Chronic heart failure (carvedilol, labetalol, metoprolol) Arrhythmia (propranolol, acebutolol, esmolol) Glaucoma (timolol) Migraine, tremor, thyrotoxicosis (propranolol)

Decreased libido

1

CA05.4-

Cardiac Action Potentials in Slow-Response Fibers

FA 2012: 311.1 • FA 2011: 285.1 • FA 2010: 281 • ME 3e: 237 2

CA05.4-

• Beta Blockers – Clinical Uses:

• Supraventricular tachycardia • Atrial fibrillation • Atrial flutter

– Toxicities:

• Impotence in men • Exacerbation of asthma with use of non-selective -blockers • Can mask signs of hypoglycemia in diabetics

FA 2012: 311.1 • FA 2011: 285.1 • FA 2010: 281 • ME 3e: 269 3

CARDIO5_5 - 1



• Class III drugs block K+ channels; sotalol, amiodarone

FA 2012: 310.1 • FA 2011: 284.1 • FA 2010: 280 • ME 3e: 237

CARDIO5_5 - 2

Amiodarone toxicity is commonly tested

Remember to check…

LFTs = Liver Function Tests

PFTs = Pulmonary Function Tests

TFTs = Thyroid Function Tests

commons.wikimedia.org, Used With permission

FA 2012: 311.2 • FA 2011: 285.2 • FA 2010: 281 • ME 3e: 268

CA05.6

Cardiac or Vascular Selectivity of Major Ca2+-Channel Blockers

FA 2012: 312.1 • FA 2011: 286.1 • FA 2010: 282 • ME 3e: 268

(Ca channel blockers which are not used as anti-arrhythmics)

1

CA05.7- FA 2012: 312.2 • FA 2011: 286.2 • FA 2010: 282 • ME 3e: 268

• Clinical Pearls… • Adenosine increases K+ efflux from cells Æ Causes hyperpolarization

• K+ is provided to patients suffering from diabetic ketoacidosis because they are grossly hypokalemic and at risk for arrhythmias.

• Mg+ is used to treat and prevent cardiac arrhythmias and seizures in pre-eclampsia!

1

CARDIO06_1a- CARDIO06_1-

Heart Sounds


1


CARDIO6_2c- 1

Abnormal Splitting of the Second Heart Sound (S2)

FA 2012: 284.1 • FA 2011: 258.1 • FA 2010: 254 • ME 3e: 254

CARDIO6_2c- 2

COMMON FORMS OF ACYANOTIC CONGENITAL HEART DISEASE

FA 2012: 284.1 • FA 2011: 258.1 • FA 2010: 254 • ME 3e: 254

CARDIO6_2c- 3

Abnormal Splitting of the Second Heart Sound (S2)

FA 2012: 284.1 • FA 2011: 258.1 • FA 2010: 254 • ME 3e: 255

CARDIO6_3- 1

Projection of Heart Valve Sounds on Anterior Chest Wall

FA 2012: 284.2 • FA 2011: 258.2 • FA 2010: 254 • ME 3e: 234

CARDIO6_4- 1

Auscultation of Heart Murmurs

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 234

CARDIO6_6- 1 FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 234

Auscultation of Aortic Stenosis Features: - Systolic ejection murmur - Crescendo-decrescendo

- Best heard: upper right sternal border

- Radiates to: carotid arteries

- Sign: pulsus parvus et tardus

CARDIO6_7a- 1

Forms of Acyanotic Congenital Heart Disease

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 231

CARDIO6_8a- 1

National Institute of Health, commons.wikimedia.org, Used With permission

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 231

CARDIO6_9a- 1

Aortic Insufficiency (Regurgitation)

Features: - Diastolic flow murmur

- Best heard: lower left sternal border

- Wide pulse pressure

- Bounding pulses

- Causes: HTN (most common), RF, IE

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 247

CARDIO6_10a- 1

Mitral Stenosis

Features: - Diastolic murmur

- Best heard: at the cardiac apex

- Opening snap

- Cause: Rheumatic heart disease

(most common)

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 247

CARDIO6_10a- 2

Features: - Diastolic murmur

- Best heard: at the cardiac apex

- Opening snap

- Cause: Rheumatic heart disease

(most common)

Mitral Stenosis

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 247

CARDIO6_11a- 1

Ductus Arteriosus

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 254

CARDIO6_12- 1

S3

FA 2012: 285.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 244

CARDIO6_12c- 1

S4

FA 2012: 285.1 • FA 2011: 257.1 • FA 2010: 253 • ME 3e: 244

CARDIO6_12e- 1

Auscultation of Heart Murmurs

FA 2012: 285.1 • FA 2011: 259.1 • FA 2010: 255 • ME 3e: 247

CARDIO7.1- CARDIO7.1-

Lecture VII – Hypertension and antihypertensive

medications

Hypertension


1

CARDIO7.1-

Hypertension Basics

1. Majority of HTN is “essential” = idiopathic

2. Risk factors affect not only the risk of HTN, but affect the first-

line treatment

3. HTN is a problem because of its long-term consequences Æ stroke, LVH, retinopathy, etc.

FA 2012: 294.2 • FA 2011: 269.2 • FA 2010: 265 • ME 3e: 265 2

CARDIO7.2-

Angiogram of Renal Artery Stenosis

FA 2012: 294.2 • FA 2011: 269.2 • FA 2010: 265 • ME 3e: 265 1

CARDIO7.2- FA 2012: 294.2 • FA 2011: 269.2 • FA 2010: 265 • ME 3e: 265 2

CARDIO7.3-

What’s Happening in Hypertension

1. Decreased number of arterioles

2. Increased arteriolar wall thickness

3. Increased total peripheral resistance

FA 2012: 294.2 • FA 2011: 269.2 • FA 2010: 265 • ME 3e: 265 1

CARDIO7.4-

Patrick J. Lynch, commons.wikimedia.org, Used With Permission

Left Ventricular Hypertrophy Secondary To Longstanding HTN

FA 2012: 294.2 • FA 2011: 269.2 • FA 2010: 265 • ME 3e: 265 1


Arteriolosclerosis and Onion-Skinning

Note the grossly thickened wall of this arteriole

Tdvorak; commons.wikimedia.org, Used With Permission

CARDIO7_5-

FA 2012: 294.4 • FA 2011: 269.4 • FA 2010: 265 • ME 3e: 264 2

CARDIO7_6-

Location of Aneurysms

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 1

CARDIO7_6-

KGH, commons.wikimedia.org, Used With Permission

This is a section of aorta that contains myxomatous

degeneration that led to an aortic dissection

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 2

CARDIO7_6-

J Heuser, commons.wikimedia.org, Used With Permission

Widened mediastinum seen on Chest x-ray in aortic dissection

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 3

CARDIO7_7-

When treating Hypertension, the USMLE often asks, “What’s the drug of choice…”

• Essential hypertension? •Diuretics (1st ine) •ACE Inhibitors or ARBs •Calcium channel blockers

•The Hypertensive CHF patient? •: Diuretics (e.g. furosemide, hydrochlorothiazide)

• Potassium-sparring diuretics (e.g. spironolactone) • Nesiritide: an analogue of brain natriuretic peptide (BNP) • ACE inhibitors or ARBs: decrease BP and cardiac remodeling • -blockers: used in compensated (not acute) CHF

• The Hypertensive Diabetic? •ACE inhibitors or ARBs (1st line): are reno-protective, slowing progression to nephropathy •2nd line agents:

• Diuretics • Calcium channel blockers • Beta-Blockers

•Notable side effect: •Dyslipidemia (metoprolol, HCTZ,)

FA 2012: 306.1 • FA 2011: 280.1 • FA 2010: 276 • ME

3e: 269 1

CARDIO7_7- FA 2012: 306.2 • FA 2011: 280.2 • FA 2010: 276 • ME 3e: 269 2

CARDIO7_7-

Selectivity of Major Ca2+-Channel Blockers

FA 2012: 306.3 • FA 2011: 280.3 • FA 2010: 277 • ME 3e: 269 3


CARDIO7_7- FA 2012: 268.1 • FA 2011: 241.2 • FA 2010: 237 • ME 3e: 269

α1-antagonist: Nonselective Selective

Phentolamine (reversible) Phenoxybenzamine (irreversible) α1 - prazosin,terazosin,doxazosin α2 - mirtazapine

Blocks α1 receptors on arterioles and venules and/or α2 receptors in the CNS

α2 antagonists: used to treat depression

Non-selective antagonists: used to treat pheochromocytoma

α1 antagonists: used to treat benign prostatic hyperplasia

Side effects: α1 blockade: reflex tachycardia, orthostatic hypotension and syncope α2 blockade:

α2-agonists:

Clonidine

Methyldopa

Decrease sympathetic outflow by stimulating α2 receptors in the CNS

Rebound hypertension, dry mouth, sedation, bradyarrhythmias

Sedation, positive Coombs test: it is a prodrug that is converted to α-methyl norepinephrine

5


Characteristics of Some Beta Blockers

6

CARDIO8_1- CARDIO8_1-

Lecture VIII – Biochemistry of lipids – Primary dyslipidemias – Lipid-lowering agents

Lipid metabolism

1


CARDIO8_2- 1

Overview of Lipoprotein Metabolism

FA 2012: 120.1 • FA 2011: 114.1 • FA 2010: 114 • ME 3e: 53


Composition water, bilirubin (bile pigments), bile salts, phospholipids, cholesterol

Function Form micelles around dietary lipids to facilitate absorption of fats, cholesterol, and fat-soluble vitamins

Synthesis

primary bile salts

primary bile salts

glycine / taurine conjugation liver

hepatocytes

Brief Review of Bile:

cholesterol primary bile acids

secondary bile salts

gut bacteria

CARDIO8_2- 3

Dietary Lipids

Lipid breakdown by enterocytes at the brush border:

Triglycerides

Cholesterol esters

Phospholipids

pancreatic lipase 2-monoglyceride + fatty acids

cholesterol esterase cholesterol + fatty acid

Absorbable Lipids

lysolecithin + fatty acid phospholipase A2

FA 2012: 120.1 • FA 2011: 114.1 • FA 2010: 114 • ME 3e: 51

CARDIO8_2- 4


FA 2012: 120.1 • FA 2011: 114.1 • FA 2010: 114 • ME 3e: 53

CARDIO8_2- 5

Enzyme Triglycerides (TGs) degraded Pancreatic lipase Dietary TGs in small intestine Lipoprotein lipase TGs circulating in chylomicrons and VLDL Hepatic triglyceride lipase TGs that remain in IDL Hormone-sensitive lipase TGs stored in adipocytes (most active

during fasting)

Lipase enzymes catalyze breakdown of triglycerides into free fatty acids

FA 2012: 120.1 • FA 2011: 114.1 • FA 2010: 114 • ME 3e: 51

CARDIO8_2- 6


FA 2012: 120.1 • FA 2011: 114.1 • FA 2010: 114 • ME 3e: 53

CARDIO8_3- 1

Apoproteins Function

apoA-1 Activates lecithin cholesterol acyltransferase (LCAT) to produce cholesterol esters

apoB-100 Binds LDL receptor to facilitate uptake by the liver Mediates VLDL secretion

apoC-II Cofactor for lipoprotein lipase

apoB-48

Mediates chylomicron secretion from intestinal enterocytes into lymphatic vessels

apoE Mediates remnant uptake

FA 2012: 120.2 • FA 2011: 114.2 • FA 2010: 114 • ME 3e: 53

CARDIO8_4- 1

Classes of Lipoproteins and Important Apoproteins

FA 2012: 121.1 • FA 2011: 115.1 • FA 2010: 115 • ME 3e: 53

CARDIO8_5-

Type

Deficiency

Lipid Elevated in Blood

Lipoprotein Elevated in Blood

Comments

I Familial lipoprotein lipase (rare) apoC-II (rare) Autosomal recessive

Triglyceride Chylomicrons Red-orange eruptive xanthomas (eyelids) Fatty liver Acute pancreatitis Abdominal pain after fatty meals

IIa Familial hypercholesterolemia Autosomal dominant (Aa 1/500, AA 1/106) LDL-receptor deficiency

Cholesterol LDL High risk of atherosclerosis and coronary artery disease Homozygous condition, usually death <20 years Xanthomas of Achilles tendon Tuberous xanthomas on elbows Xanthelasmas Corneal arcus

IV Hepatic overproduction of VLDL

VLDL TG Pancreatitis

1

Primary Hyperlipidemias

FA 2012: 121.2 • FA 2011: 115.2 • FA 2010: 115 • ME 3e: 53

CARDIO8_5- 2

Deficiency

Lipid Lowered in Blood

Comments

Inability to synthesize lipoproteins due to lack of ApoB-100 and ApoB-48. Autosomal recessive.

Triglycerides Cholesterol

Symptoms in first months of life Intestinal biopsy – lipid accumulation in enterocytes. Poor absorption of vitamins A and E Failure to thrive Steatorrhea Acanthocytosis Ataxia Night blindness

Abetalipoproteinemia (a hypolipidemia)

FA 2012: 121.3 • FA 2011: 115.3 • FA 2010: 115 • ME 3e: 53

CARDIO8_6- 1

Statins

FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 52

CARDIO8_6- 2

Drug Class/Agent Mechanisms Side Effects/Comments

HMG-CoA Reductase Inhibitors (“-statins”: lovastatin, atorvastatin, fl uvastatin pravastatin, simvastatin, rosuvastatin,)

Inhibit rate-limiting step in cholesterol synthesis

-receptor

expression

• Myalgia, myopathy (check creatine kinase) • Rhabdomyolysis • aminotransferases • Teratogenic • P450 inhibitors can risk of hepatotoxicity, myopathy

Lipid-Lowering Drugs

FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 52

CARDIO8_6- 3


Niacin Liver: Adipose tissue:

Flushing (and over time), pruritus, hepatotoxicity


FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 53

CARDIO8_6- 4


Bile Acid Sequestrants (cholestyramine, colestipol, colesevelam)

Enterohepatic recirculation of bile salts, leading to:

salts by liver

-receptor expression

• GI disturbances • Malabsorption of lipid- soluble vitamins • (e.g., warfarin, thiazides, digoxin, pravastatin, fluvastatin)


FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 53

CARDIO8_6- 5


Ezetimibe Blocks intestinal absorption of cholesterol

Possible hepatotoxicity with reductase inhibitors


FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 53

CARDIO8_6- 6


Fibrates (gemfibrozil, clofibrate, bezafibrate, fenofibrate)

Ligands for PPAR-αactivation of lipoprotein lipases

Modest

• Gallstones • Myopathy (especially when combined with reductase inhibitors) • Can patients, so often combined with other cholesterol-lowering agents • Hepatotoxicity (rare)


FA 2012: 308.1 • FA 2011: 282.1 • FA 2010: 278 • ME 3e: 53


Lecture IX Atherosclerosis Ischemic heart disease

Atherosclerosis


1

CARDIO9_1-

Arterial Supply to the Heart

FA 2012: 280.1 • FA 2011: 254.1 • FA 2010: 250 • ME 3e: 233 2

CARDIO9_1-

Structures of the Mediastinum

FA 2012: 280.1 • FA 2011: 254.1 • FA 2010: 250 • ME 3e: 232 3

CARDIO9_2-

Atheromatous Plaque

FA 2012: 295.1 • FA 2011: 270.1 • FA 2010: 266 • ME 3e: 265 1

CARDIO9_3-

Location of Aneurysms

FA 2012: 295.1 • FA 2011: 270.1 • FA 2010: 266 • ME 3e: 265 1

CARDIO9_3-

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265

J Heuser, commons.wikimedia.org, Used With Permission A B

Different criteria are used to classify aortic dissections. “Stanford Criteria” is one example: Stanford “A” dissection: involves the Ascending aorta, but can also include the descending aorta. Requires surgical intervention Stanford “B” dissection: exclusive to descending aorta – does not require surgery.

2

CARDIO9_3-

KGH, commons.wikimedia.org, Used With Permission

Notice the tear between the two layers that has resulted in the formation of a "false lumen".

True lumen

False lumen

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 3

CARDIO9_3-

J Heuser, commons.wikimedia.org, Used With Permission A B

Different criteria are used to classify aortic dissections. “Stanford Criteria” is one example: Stanford “A” dissection: involves the Ascending aorta, but can also include the descending aorta. Requires surgical intervention Stanford “B” dissection: exclusive to descending aorta – does not require surgery.

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 4

CARDIO9_3-

J Heuser, commons.wikimedia.org, Used With Permission

Widened mediastinum seen on Chest x-ray in aortic dissection

FA 2012: 295.3 • FA 2011: 270.2 • FA 2010: 265 • ME 3e: 265 5


Ischemic Heart Disease

– Angina • Stable • Unstable • Prinzmetal’s

– Myocardial infarction – Sudden cardiac death – Chronic ischemic heart disease

1


Lecture X Myocardial infarction Antianginal therapy

Ischemic Heart Disease

1


CARDIO10_1- 2

FA 2012: 297.1 • FA 2011: 271.1 • FA 2010: 267 • ME 3e: 257

Time Gross Histologic Complications

1 day Dark mottling. Pale after tetrazolium stain

First 2-4 hours: No visible changes 4-24 hours: Early coagulative necrosis Contraction bands (>4 hrs)

Arrhythmia

2 - 4 days Hyperemia Acute inflammation: Dilated vessels Neutrophils Loss of myocyte nuclei

Arrhythmia

5 - 10 days Yellow-brown softening with hyperemic border

Macrophages Granulation tissue

Free wall rupture Tamponade Papillary muscle rupture Septal rupture

Weeks to months

Gray-white scar Contracted scar Ventricular aneurysm

Tissue Changes in Myocardial Infarction


Diagnosis of MI

Troponin I first 4 hours 7-10 days

CK-MB 24 hours

cardiac specific

non-specific; released by all muscle injury

Peak Duration

2-3 days

LDH 48 hours

AST non-specific; released by all muscle injury and liver injury

7-10 days

24 hours 2-3 days


MI

Transmural ST Elevation MI (STEMI)

Subendocardial Non-ST Elevation MI (NSTEMI)

Involves entire thickness of cardiac wall Usually complete occlusion of blood supply (i.e. atherosclerosis of coronary artery) Q Waves at the affected ECG leads

Smaller regions of subendocardial tissue (only innermost layer of wall affected) Affects areas that are highly susceptible to ischemia (high output, low perfusion) Left ventricle, ventricular septum, papillary muscle

CARDIO10_2- 2

Orange = ST elevations in anterolateral leads Blue = ST depressions in inferior leads

ST Elevation Myocardial Infarction

commons.wikimedia.org, Used With Permission

FA 2012: 298.2 • FA 2011: 272.2 • FA 2010: 268 • ME 3e: 256

CARDIO10_2- 3

FA 2012: 298.3 • FA 2011: 272.3 • FA 2010: n/a • ME 3e: 233

Artery Affected

LAD

Left Main/LCX

RCA

Infarct Location

Relevant Leads (look for ST segment changes and Q waves)

V1-V4

V1-V2

Anterior Wall

Anteroseptal

Anterior Leads

Septal Leads

Lateral Leads Anterolateral

Lateral Wall

Inferior Wall Inferior Leads

V4-V6

I, aVL

II, III, aVF

LCX


Post-MI Complications – Immediate Risk

Cardiac arrhythmia Ventricular tachycardia/fibrillation Causes sudden cardiac death in 25% of patients with MI Congestive heart failure LV failure with pulmonary edema most common Cardiogenic shock Complete pump failure and hypoperfusion of all organs

Note: These risks are immediate but can persist for months or years.

CARDIO10_3- 2

Post-MI Complications – Delayed Risk

Ventricular rupture 5-10 days post-MI Free wall rupture → tamponade Septum rupture → severe left-to-right shunt via VSD Papillary muscle rupture → severe mitral insufficiency Ventricular aneurysm several weeks to months later Increased risk of mural thrombus (embolism and stroke) Increased risk of arrhythmia

FA 2012: 298.4 • FA 2011: 272.4 • FA 2010: 268 • ME 3e: 256

CARDIO10_3- 3

Post-MI Complications – Pericarditis

Friction rub may be heard in both types.

Post-infarction fibrinous pericarditis Due to inflammation secondary to ischemia Can occur 3-5 days post-MI Dressler’s syndrome (autoimmune pericarditis)

Also fibrinous pericarditis, but due to autoimmune process Can occur 2-10 weeks post-MI

FA 2012: 298.4 • FA 2011: 272.4 • FA 2010: 268 • ME 3e: 256

CARDIO10_3b- 1

Loading…

FA 2012: 298.4 • FA 2011: 272.4 • FA 2010: 268 • ME 3e: 256

This interaction is unavailable on the iPad. To engage with this part of the lesson, please

access this presentation on a Mac or PC that has Adobe Flash installed.


Antianginal Therapy - Goals

Decrease myocardial oxygen consumption

Primary Goal

Secondary Goal Increase oxygen delivery to myocardium by increasing perfusion

By decreasing: End diastolic volume (preload) Blood pressure (afterload) Heart rate Contractility

CARDIO10_4- 2

Antianginal Therapy – Nitrates

Nitrates

End diastolic volume (preload)

Blood pressure Heart Rate

Contractility

reflex reflex

FA 2012: 307.1 • FA 2011: 281.1 • FA 2010: 277 • ME 3e: 271

CARDIO10_4- 3

Beta Blockers

Antianginal Therapy – Beta Blockers

Nitrates


Blood pressure Heart Rate

Contractility

reflex reflex

FA 2012: 307.1 • FA 2011: 281.1 • FA 2010: 277 • ME 3e: 271

CARDIO10_4- 4

Net Effect

Large decrease in myocardial O2 consumption

Beta Blockers

Antianginal Therapy – Nitrates & Beta Blockers

Nitrates


Blood pressure (afterload)

Heart Rate

Contractility

reflex reflex

FA 2012: 307.1 • FA 2011: 281.1 • FA 2010: 277 • ME 3e: 271

CARDIO10_4- 5

Antianginal Therapy – Calcium Channel Blockers

Do not use beta blockers in patients with reactive airway disease (asthma, COPD)

Instead use:

Nifedipine

Diltiazem Verapamil

(similar to nitrates)

(similar to beta blockers)

End diastolic volume (preload) and Blood pressure (afterload)

Heart rate and Contractility

FA 2012: 307.1 • FA 2011: 281.1 • FA 2010: 277 • ME 3e: 271

CARDIO10_4- 6

FA 2012: 296.1 • FA 2011: 270.3 • FA 2010: 266 • ME 3e: 256

Prinzmetal’s Angina

• Vasospasm causes decreased blood flow through coronary arteries

• Occurs at rest or even wakes patient at night

• Diagnosed with ergonovine test – induces vasospasm

• Transient ST elevations on ECG

• Treated with calcium channel blockers


Congestive heart failure and cardiomyopathies

1


Lecture XI Cardiomyopathies Congestive heart failure


Dilated Cardiomyopathy

Insult or Injury to

Myocardium

Contractility

Cardiac output

Compensatory neuro-hormonal

signaling

Cardiac remodeling

e.g. Renin- Angiotensin- Aldosterone System

sarcomeres added in

series


CARDIO11_1- 3


Chronic alcohol abuse

Wet Beriberi (thiamine/B1 deficiency)

Viral myocarditis (Cocksackie B)

Chronic cocaine use

Chagas’ disease (trypanosomes)

Doxorubicin toxicity

Hemochromatosis

Peripartum cardiomyopathy

Important Causes

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_1- 4

Dilated Cardiomyopathy - Signs & Symptoms

• Point of maximal impulse laterally displaced (at axilla)

• S3 heart sound: rapid filling and expansion of ventricle

• Enlarged heart on chest x-ray: cardiac silhouette > ½ chest cavity

• Cavitary dilation of heart on echocardiogram

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_1- 5

Copyright James Van Rhee. Used with permission.

Chest X-Ray

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_2- 1

Cardiac output

Asymmetric septal

thickening

actin/myosin synthesis

concentric hypertrophy:

Sarcomeres added in parallel

Genetic (50% cases) Autosomal dominant

Idiopathic etiology

or Decreased compliance

Poor diastolic

filling

Hypertrophic Cardiomyopathy

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_2- 2

Hypertrophic Cardiomyopathy

Complications

• Decreased compliance diastolic dysfunction (S4 heart sound)

left ventricle outflow obstruction (systolic murmur, exertional syncope)

• Asymmetric septal hypertrophy + Mitral valve anterior leaflet motion

• Arrhythmia sudden cardiac death

Treatments: myomectomy, beta-blockers

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_3- 1

Restrictive Cardiomyopathy

Infiltrative processes can cause stiffening of ventricles, diastolic dysfunction

Causes Sarcoidosis

Amyloidosis

Post-radiation fibrosis

Löffler’s syndrome (endomyocardial fibrosis eosinophilic infiltrate)

Hemochromatosis

FA 2012: 299.1 • FA 2011: 273.1 • FA 2010: 269 • ME 3e: 260

CARDIO11_4- 1

The Failing Heart

FA 2012: 300.1 • FA 2011: 274.1 • FA 2010: 270 • ME 3e: 258

CARDIO11_4- 2

Heart Failure - Signs & Symptoms

• Dyspnea on exertion

• Pulmonary edema → orthopnea, paroxysmal nocturnal dyspnea → hemosiderin-laden macrophages in lungs

• Hepatomegaly, central venous congestion (“nutmeg liver”)

• Peripheral edema (ankles, sacrum) • Jugular venous distention (after right heart failure)

FA 2012: 300.1 • FA 2011: 274.1 • FA 2010: 270 • ME 3e: 258


Cardiac Tamponade

Compression of heart by fluid in pericardium (blood, effusion)

Signs & Symptoms

• Diastolic pressure equal in all four heart chambers

• Hypotension, jugular venous distention, increased heart rate

• Distant heart sounds

• Pulsus paradoxus (Kussmaul’s pulse): pulse strength during inspiration

CARDIO11_6- 1

Mechanism of Action of Inotropes

FA 2012: n/a • FA 2011: 283.1 • FA 2010: 279 • ME 3e: 271


Mechanism Effects Uses Toxicities

Inhibits Na+/K+ ATPase

+ + gradient +/Ca2+ exchange

2+

• Increased myocardial Ca2+ increased contractility • Delayed conduction at AV node.

• CHF (contractility) • Atrial fibrillation (to conduction)

Yellow vision, nausea, vomiting, diarrhea, anorexia, hallucination, life-threatening arrhythmias

Notes: • Hypokalemia enhances toxicity • Quinidine • Digoxin antibodies (Fab fragments) used in overdose • Digitalis does not improve survival following MI

Cardiac Glycosides - Digoxin & Digitalis


Lecture XII Embryology of the heart Congenital Heart Disease

Congenital heart disease

1


CARDIO12_1- 2

Fate: (A) Ascending aorta / pulmonary

trunk

(B) Smooth part of L and R ventricles (outflow tracts)

(C) Trabeculated L and R ventricle

(D) Trabeculated L and R atrium

(E) Left horn: coronary sinus Right horn: smooth right atrium

A

B

C

D

E

Heart tube from lateral plate mesoderm

FA 2012: 130.1 • FA 2011: 123.1 • FA 2010: 123 • ME 3e: 230

Inflow

Outflow

Gray476.png, commons.wikimedia.org. Used with permission.

Venous system during cardiac development

CARDIO12_1- 3

Truncus Arteriosus

Migrate into truncal/bulbar

region

Neural crest cells

Spiral and fuse: form

aorticopulmonary septum

(days 27-33)

FA 2012: 130.2 • FA 2011: 123.2 • FA 2010: 123 • ME 3e: 231

Arterial outflow

CARDIO12_1- 4

Interventricular Septum

FA 2012: 130.3 • FA 2011: 123.3 • FA 2010: 123 • ME 3e: 230

Kaplan Anatomy: Figure III-2-16.

CARDIO12_2- 1

Endocardial Cushion Defects

Failure of dorsal and ventral endocardial cushions to fuse → persistent common AV canal

Ebstein’s anomaly • Weak, under-developed right ventricle (“atrialized” right ventricle) • Associated with lithium use by the mother Tricuspid atresia • Tricuspid valve does not form completely • Under-developed right side of heart

FA 2012: 130.3 • FA 2011: 123.3 • FA 2010: 123 • ME 3e: 230


Eisenmenger’s Syndrome

Uncorrected Left-to-Right

Shunt

(e.g. ASD,VSD,PDA)

Pressure in pulmonary vasculature

Hypertrophy of pulmonary vasculature

and Resistance

Pressure in R side of

heart

L-to-R shunt reverses, becomes

R-to-L shunt

Late Cyanosis

CARDIO12_4- 1

Formation of Atrial Septum

FA 2012: 131.1 • FA 2011: 124.1 • FA 2010: 124 • ME 3e: 230


CARDIO12_4- 2

Secundum and Primum Atrial Septal Defect


FA 2012: 131.1 • FA 2011: 124.1 • FA 2010: 124 • ME 3e: 230


Fetal Erythropoiesis

Fetal hemoglobin: α2γ2 Adult hemoglobin α2β2

3-8 weeks Yolk sac

6-30 weeks Liver and Spleen

> 28 weeks Bone marrow

CARDIO12_5- 2

Fetal Circulation and Shunts

FA 2012: 132.1 • FA 2011: 125.1 • FA 2010: 125 • ME 3e: 232

Kaplan Anatomy: Figure III-2-12

CARDIO12_6a- 1 FA 2012: 292.1 • FA 2011: 267.1 • FA 2010: 263 • ME 3e: 231

Congenital Heart Disease

Cyanotic (Right-to-Left Shunts) Non-cyanotic (Left-to-Right Shunts)

Tetralogy of Fallot

Transposition of great vessels

Truncus arteriosus

Tricuspid atresia

Total anomalous pulmonary venous return (TAPVR)

Ventricular septal defect (VSD)

Atrial septal defect (ASD)

Patent ductus arteriosus (PDA)

(late cyanosis)

CARDIO12_6a- 2

Persistent Truncus Arteriosus


FA 2012: 292.1 • FA 2011: 267.1 • FA 2010: 263 • ME 3e: 231

CARDIO12_6a- 3

Tricuspid Atresia

Kaplan Pathology: Figure 14-3

Aorta

Atrial Septal defect

Closed tricuspid valve

Under- developed right ventricle

C. Tricuspid Atresia

FA 2012: 292.1 • FA 2011: 267.1 • FA 2010: 263 • ME 3e: 231

CARDIO12_6a- 4

1. Ventricular septal defects 2. Atrial septal defect 3. Patent ductus arteriosus

FA 2012: 292.1 • FA 2011: 267.1 • FA 2010: 263 • ME 3e: 230

CARDIO12_6a- 5

Tetralogy of Fallot

FA 2012: 292.3 • FA 2011: 267.3 • FA 2010: 263 • ME 3e: 231


CARDIO12_6a- 6

Transposition of the Great Vessels

FA 2012: 293.1 • FA 2011: 268.1 • FA 2010: 264 • ME 3e: 231


CARDIO12_6a- 7

Coarctation of the Aorta

FA 2012: 293.2 • FA 2011: 268.2 • FA 2010: 264 • ME 3e: 231

Kaplan Pathology: Figure 14-2.

CARDIO12_6a- 8

Ductus Arteriosus

FA 2012: 293.3 • FA 2011: 268.3 • FA 2010: 264 • ME 3e: 232


CARDIO12_6b- 1

Loading…

FA 2012: 293.3 • FA 2011: 268.3 • FA 2010: 264 • ME 3e: 232


Congenital Heart Disease - Associations

22q11 syndromes

Down syndrome

Congenital rubella

Turner syndrome

Marfan’s syndrome

Infant of diabetic mother

Truncus arteriosus, Tetralogy of Fallot

ASD, VSD, endocardial cushion defect

PDA, septal, pulmonary artery stenosis

Coarctation of aorta (preductal)

Aortic insufficiency

Transposition of great vessels


Lecture XIII – Endocarditis and associated bacteria – Rheumatic heart disease – Syphilitic heart disease

Infection-related heart disease

1



Manske, commons.wikimedia.org, Used With Permission

Gram positive bacteria have this thick outer peptidoglycan layer which retains a blue crystal violet stain Also note the absence of the outer cell membrane seen in gram negative bacteria.

Inne

r cel

l m

embr

ane

Pept

idog

lyca

n la

yer

2

CARDIO13_1-

Huckfinne, commons.wikimedia.org, Used With Permission

3

Streptococcus Staphylococcus

S.epidermis

Novobiocin sensitive

S. saprophyticus

Novobiocin resistant

S. pyogenes Group A, bacitracin sensitive

S. agalactiae Group B, bacitracin resistant

Enterococcus

E. faecalis, E. faecium

S. pneumoniae optochin sensitive, bile soluble, capsule (quellung +)

S. viridans, S.mutans, S.sanguis optochin resistant, not bile soluble no capsule

FA 2012: 155.1 • FA 2011: 144.1 • FA 2010: 146 • ME 3e: 533

Corynebacterium

CARDIO13_1-

Bill Branson, commons.wikimedia.org, Used With Permissio

Plain Agar Plate Beta - Hemolysis

4 FA 2012: 155.1 • FA 2011: 144.1 • FA 2010: 146 • ME 3e: 116

CARDIO13_1- FA 2012: n/a • FA 2011: 145.1 • FA 2010: 147 • ME 3e: 533

Huckfinne, commons.wikimedia.org, Used With Permission

5

Streptococcus Staphylococcus

S. epidermis

Novobiocin sensitive

S. saprophyticus

Novobiocin resistant

pyogenesGroup A, bacitracin sensitive

agalactiaeGroup B, bacitracin resistant

Enterococcus

E. faecalis, E. faecium

Pneumoniae optochin sensitive, bile soluble, capsule (quellung +)

Viridans mutans, sanguis optochin resistant, not bile soluble no capsule

CARDIO13_1- 6 FA 2012: n/a • FA 2011: 145.1 • FA 2010: 147 • ME 3e: 533

CARDIO13_2-

Intracellular Killing in CGD

1 FA 2012: n/a • FA 2011: 145.1 • FA 2010: 147 • ME 3e: 98

CARDIO13_3- 1 FA 2012: n/a • FA 2011: 145.1 • FA 2010: 147 • ME 3e: 533


Gram positive cocci in clusters

Y tambe, commons.wikimedia.org, Used With Permission

1

S. aureus

CARDIO13_4-

Superantigen Activation Superantigen activation: Notice that

there is no complementarity between the TCR and the MHC/peptide complex.

2 FA 2012: 156.2 • FA 2011: 145.2 • FA 2010: 147 • ME 3e: 92

CARDIO13_5-

Staphylococcus aureus

1 FA 2012: 156.2 • FA 2011: 145.2 • FA 2010: 147 • ME 3e: 259

CARDIO13_5-

FA 2012: 156.3 • FA 2011: 145.3 • FA 2010: n/a • ME 3e: 259

Mirko Junge M.D., commons.wikimedia.org, Used With Permission

Prosthetic Valves Catheters

Staphylococcus epidermidis seeds prosthetic devices …

2


Mike Miller M.D., commons.wikimedia.org, Used With Permission

Streptococcus viridans

Endocarditis!

Cavities!

1

CARDIO13_6-

• Enterococci are inherently resistant to penicillins

– Initial treatment is vancomycin – This has led to Vancomycin-Resistant-Enterococci (VRE) – Treat VRE with linezolid

• Streptococcus bovis – Endocarditis in colon cancer patients !!! (USMLE pearl)

FA 2012: 157.3 • FA 2011: 146.3 • FA 2010: 148 • ME 3e: 534

BOTH are group D streptococci Differentiating test Æ Plate with 6.5% NaCl Enterococci will grow; Bovis will not grow

2

CARDIO13_7-

FA 2012: 301.1 • FA 2011: 275.1 • FA 2010: 271 • ME 3e: 259

© Richard Usatine, M.D. Used with permission.

Roth Spots Janeway lesions

1

CARDIO13_7- 2

users

FA 2012: 301.1 • FA 2011: 275.1 • FA 2010: 271 • ME 3e: 259


CARDIO13_9-

Mitral

Tricuspid

More frequently affected

Commonly affected in IV drug abuse

1 FA 2012: 301.1 • FA 2011: 275.1 • FA 2010: 271 • ME 3e: 259

CARDIO13_10-

Libman-Sacks Endocarditis

FA 2012: n/a • FA 2011: 275.2 • FA 2010: 271 • ME 3e: 259

Sterile vegetations

Usually benign

Vegetations on both sides of valve

Can attack both tricuspid and mitral valves.

1


Stages of Syphilis

1


Jones Criteria of Rheumatic Fever

1


Lecture XIV Vasculitis Cardiac and vascular tumors

Vasculitis and cardiovascular tumors

1


CARDIO14_1-

Varicose Veins

• Dilated torturous superficial veins

• Associated with prolonged standing or sitting, and pregnancy

• Occur in areas of high venous pressure (lower extremities)

• Rarely a source of thromboembolism

2 FA 2012: 303.2 • FA 2011: 277.2 • FA 2010: 273 • ME 3e: 265


Jamclaassen. commons.wikimedia.org. Used with permission

Raynaud Disease

Small artery vasospasm

Blanching/cyanosis of fingers/toes Triggered by cold or stress

Note called Raynaud phenomenon when secondary to systemic disease e.g. SLE, scleroderma

1


Wegener’s granulomatosis

Necrotizing granulomatous inflammation

Vasculitis (small vessels)

Glomerulonephritis lung upper airway

Signs and symptoms:

• Hemoptysis

• Cavitary lung lesions

• Hematuria

• Chronic sinusitis

• Nasal septum perforation

• Otitis media

• Mastoiditis

• Cough, dyspnea

1

CARDIO14_3-

Malittle. commons.wikimedia.org. Used With Permission

2 FA 2012: 304.1 • FA 2011: 277.4 • FA 2010: 274 • ME 3e: 263

CARDIO14_3-

FA 2012: n/a • FA 2011: 277.5 • FA 2010: 274 • ME 3e: 262

Malittle. commons.wikimedia.org. Used With Permission

3

CARDIO14_3-

Wegener’s granulomatosis

• Associated with c-ANCA

• Treated with cyclophosphamide (for renal disease) & corticosteroids

4 FA 2012: 304.1 • FA 2011: 277.4 • FA 2010: 274 • ME 3e: 263

CARDIO14_4-

Other ANCA-associated vasculitides

Microscopic Polyangiitis

Primary pauci-immune crescentic glomerulonephritis

Churg-Strauss syndrome

(all small vessel diseases)

(p-ANCA)

(p-ANCA)

• Affects small vessels in multiple organs but without granulomas

• Fever, malaise, myalgia, weight loss (skin rash in 50%)

• Vasculitis limited to kidney

• Granulomatous vasculitis with eosinopilia - can also involve kidneys, heart, lung

• Asthma, sinusitis, skin lesions, peripheral neuropathy (wrist drop/foot drop)

1 FA 2012: n/a • FA 2011: 277.5 • FA 2010: 274 • ME 3e: 262


Sturge-Weber disease (capillary-sized vessels)

Congenital capillary malformations

Signs and Symptoms • Port-wine stain (nevus flammeus) on face

• Leptomeningeal angiomatosis (intracerebral AVM)

• Seizures

• Early-onset glaucoma

Gaillard. commons.wikimedia.org. Used With Permission


Henoch-Schönlein Purpura (small vessels)

Signs and Symptoms

• Most common childhood systemic vasculitis

• IgA-mediated vasculitis, circulating IgA complexes

• Linked to parvovirus

• Typically develops after URI

• “Palpable purpura” skin rash (buttocks and legs)

• Arthralgia (wrists, ankles)

• Intestinal involvement: hemorrhage, melena

• Nephritis – IgA nephropathy

• Normal complement levels

1

CARDIO14_6-

Crescent formation in rapidly progressive glomerulonephritis, as seen with trichrome stain


2 FA 2012: 305.1 • FA 2011: 278.1 • FA 2010: 274 • ME 3e: 262


Buerger’s disease - thromboangiitis obliterans (small and medium vessels in the extremities)

Signs and Symptoms • Heavy smokers

• Rapidly progressive thrombosing vasculitis

• Claudication (vascular insufficiency)

• Cold sensitivity (Raynaud’s phenomenon)

• Ulceration, gangrene, autoamputation

Treatment: improves rapidly with smoking cessation

Geirunited. commons.wikimedia.org. Used With Permission

1


Kawasaki disease (small and medium vessels)

Signs and Symptoms

• Acute, segmental necrotizing vasculitis

• Commonly affects infants/children (<4 yo)

• Associated with Japanese heritage

• Fever

• Conjunctivitis

• Erythema of oral mucosa (“strawberry tongue”)

• Lymphadenopathy

• Desquamative skin rash

• Risk of coronary aneurysms

Treatment: IV immunoglobulin and aspirin Soo Kim. commons.wikimedia.org. Used With Permission

1

CARDIO14_9-

FA 2012: 304.1 • FA 2011: 278.4 • FA 2010: 275 • ME 3e: 263

Polyarteritis Nodosa (small and medium arteries)

Signs and Symptoms

• Immune complex-mediated transmural vasculitis

• Lesions at different stages (acute, healing, healed) - ”beads on a string”

• Abdominal pain, diarrhea, GI bleeding

• Fever, weight loss, malaise

• Hematuria, renal failure, hypertension

• Important association with Hepatitis B antigen

• Sometimes associated w/ p-ANCA

1


Ly. commons.wikimedia.org. Used With Permission

1

Takayasu’s arteritis (medium and large arteries, aortic arch and major branches)

Signs and Symptoms

• Granulomatous vasculitis with heavy intimal thickening

• Often affects young to middle-aged Asian women

• Fever, night sweats, myalgias/arthralgias, weight loss

• Weak pulse in upper extremities (pulseless disease)

• Visual loss or other neurologic abnormalities

• Increased ESR

Ly. commons.wikimedia.org. Used With Permission

CARDIO14_11-

FA 2012: 305.1 • FA 2011: 278.1 • FA 2010: 275 • ME 3e: 263

Temporal arteritis (giant cell arteritis)

Multinucleated giant cell Destroyed artery from giant cell arteritis

Marvin and Nguyen. commons.wikimedia.org. Used With Permission

1

CARDIO14_11-

Temporal arteritis (giant cell arteritis) (medium and large arteries)

Signs and Symptoms

• Most common large-vessel vasculitis (granulomatous)

• Commonly affects branches of carotid artery

• Patient > 50 yo and ESR > 50

• Unilateral headache

• Unilateral jaw claudication (pain on chewing)

• Unilateral visual disturbance

• Associated with polymyalgia rheumatica (proximal muscles)

Treatment: corticosteroids

2 FA 2012: 305.1 • FA 2011: 278.1 • FA 2010: 275 • ME 3e: 263


Hemangioma


1

CARDIO14_13-

Cystic Hygromas

• Most commonly associated with Turner Syndrome

• Usually found in the posterior aspect of the neck


1 FA 2012: 305.2 • FA 2011: 279.2 • FA 2010: 276 • ME 3e: 266

CARDIO14_14-

KGH. commons.wikimedia.org. Used With Permission

Angiosarcoma Kaposi’s Sarcoma

1 FA 2012: 305.2 • FA 2011: 279.2 • FA 2010: 276 • ME 3e: 266

CARDIO14_15-

FA 2012: 303.1 • FA 2011: 277.1 • FA 2010: 273 • ME 3e: 261

James Moon. commons.wikimedia.org. Used With Permission

Atrial Myxoma

Myxoma

Mitral valve

ventricle

(Ball valve obstruction)

1

CARDIO14_15-

Nephron. commons.wikimedia.org. Used With Permission

Atrial Myxoma

• Stellate cells

• Myxoid background

2 FA 2012: 303.1 • FA 2011: 277.1 • FA 2010: 273 • ME 3e: 261

CARDIO14_16-

Rhabdomyoma

• Most common primary cardiac tumor in children

• Patients with tuberous sclerosis often develop these tumors

1 FA 2012: 303.1 • FA 2011: 277.1 • FA 2010: 273 • ME 3e: 261

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6 Cardiology High Yield

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