Lecture 1 Summer 2007 WEB

Description: This course will cover the cardiovascular, respiratory, renal and digestive systems.

Pre-Requisites: BGYB30H or an equivalent. Students who have not taken BGYB30H but have taken an equivalent course should contact me to avoid being removed from the course.

Instructor: Dr. Stephen Reid; Office, S526; e-mail, [email protected]://www.utsc.utoronto.ca/~sgreid/

Office hours: Wednesday 11:00 to 11:45 and 2:15 to 3:15

Teaching Assistant: Jeff Knight (e-mail will be available on the course intranet site)

Lectures: Wednesday, 12:00 to 2:00; Room SW128

Recommended (not required) Textbook:

“Human Physiology” by D.U. Silverthorn (used in BGYB30 in 2006, 2007)

“Human Physiology” by R. Rhodes and R. Pflanzer (used in BGYB30 in 2004/2005 and BGYC33/C34 in 2005/2006/2007; available in the bookstore)

“Principles of Human Physiology” by W.J. German and C.L. Stanfield (used in BGYC33 in 2004)

Required Lab Book and Software PhysioEx. 6.0 For A & P. Laboratory Simulations in Physiology

Course Web Site: http://www.utsc.utoronto.ca/~sgreid/bgy%20C34%20Summer%202007.htm

Lecture Notes: Lecture notes (the Power Point slides and PDF files)will be posted on the course web site in advance of the lecture.

Study Guides: Study guides, complete with sample exam questionsfrom previous years, are available on the course web site.

Evaluation

Midterm Exam, 30%Simulated Lab Reports, 20%Final Exam, 50%

THE FINAL EXAM IS CUMULATIVE.

Exams are Multiple Choice

BGYC34: Schedule of Assignments (Simulated Labs: PhysioEx 6.0)Summer 2007

Lab 6 (Cardiovascular Physiology): June 6 2007Lab 5 (Cardiovascular Dynamics): June 13 2007Lab 7 (Respiratory System Mechanics): June 27 2007 Lab 9 (Renal System Physiology): July 18 2007Lab 10 (Acid-Base Balance): August 1 2007

The PhysioEx. 6.0 Software is (or will be) available for purchase in the bookstore.

Complete the computer-simulated lab exercises on your own time (and computer) and submit the lab reports (within the manual) and additional questions on the given due date.

Lecture Schedule

1 (May 9): Electrical Activity of the Heart; Electrocardiograms (ECG) 2 (May 16): The Electrical Axis of the Heart; The Cardiac Cycle;

Regulation of Cardiac Output3 (May 23): Regulation of Cardiac Output; Blood Flow Regulation; Heart Failure4 (May 30): Blood Pressure Regulation; Pulmonary Mechanics5 (June 6): Pulmonary Mechanics; Gas Exchange6 (June 13): Gas Transport; Ventilation-Perfusion Matching; Control of Breathing7 (June 20): Control of Breathing; EEG and Sleep-Related Breathing Disorders; Glomerular Filtration8 (June 27): Glomerular Filtration; Tubular Reabsorption and Secretion; Clearance

Reading Week (July 2-6)

9 (July 11): Water, Na+, K+ and Ca2+ Balance10 (July 18): Acid-Base Balance11 (July 25): Digestive Physiology I12 (August 1): Digestive Physiology II

Cardiovascular System

Pacemaker Potential / Cardiac Action PotentialElectrocardiogram (ECG)Cardiac Cycle Cardiac Output (CO); volume of blood pumped per minuteBlood FlowBlood Pressure (BP)

CO = HR X SV

BP = CO X PRBP = (HR X SV) X Peripheral Resistance

HR = heart rateSV = stroke volume (volume of blood pumped per beat)

Semilunar valves(aortic & pulmonary)

Tricuspid (AV) Valve

Bicuspid (AV; mitral) Valve

LA

LV

RV

RA

Heart Valves and Major Blood VesselsHeart Valves and Major Blood Vessels

Aorta (to the systemiccirculation)Superior

Vena cavaPulmonary Arteries(to lungs)

Pulmonary Veins(from lungs)

InferiorVena cava RA: right atria

LA: left atriaRV: right ventricleLV: left ventricle

• interatrial septum• interventricular septum

apex

• ventricular muscle

Patterns of Blood Flow

Pulmonaryartery

Pulmonaryvein

AortaVena cavae

RV LV

Systemic Circulation

Lungs

Oxygenated blood (red)De- Oxygenated blood (blue)

1. 2.

3. 4.

6.5.

The Conduction System of the Heart(pacemaker → conduction fibres →contractile fibres )

1. Sinoatrial (SA) node

3. Atrioventricular (AV) node 4. AV bundle(Bundle of His)

LV

RV

5. Right and left bundle branches

6. Purkinje fibres

2. Internodal pathways

coordinated contraction gap junctions →

conduction fibres: larger diameter atria – ventricles: separated by fibrous bundles

Gap Junction

Plasma membrane

Cardiac Muscle Cells are Electrically Connected via Gap Junctions

Cardiac Muscle Cells

desmosome(protein fibres)

desmosome – resist stretching important as it occurs every time the heart fills (cardiac cycle)

gap junction – passage of current steps in conduction →

intercalated disk

sarcomers

hypertrophy: reduced contraction

a. AP is initiated in the SA node


b. AP are conductedthroughoutthe atria• very rapid• large cells


c. Conduction slows at the AV node• small cells

SA node versus AV node(frequency and refractory period)


fibrousseptum

Allows full ventricular fillingbefore contraction


d. AP travel rapidlythrough the bundle of His and the branch bundles




d. AP travel rapidlythrough the branchbundles



e. AP spreadthroughtheventricles(bottom to top)

contraction: apex to top


d. AP travel rapidlythrough the branchbundles

f. rest b. AP are conductedthroughoutthe atria• very rapid• large cells


e. AP spreadthroughtheventricles(bottom to top)

Ectopic (idioventricular) Pacemakers

Line Powered Pacemaker(failed during power outages)

First Battery Powered Pacemaker

Artificial Pacemakers

Older models: stimulate at a fixed rate


• implantable• computer programmable• sense heart rate and stimulate as appropriate (e.g. during complete heart block; next lecture)

Pulse Generator

lithium batteries

hybrid circuit

left atria

left ventricle

right atria

right ventricle

Sense and Stimulate



A

V

A

V

A

V

A

V

A

V

A

Vnormal ecg



V V V V V

Ectopic Pacemakers

A A A A A A A A A

ECG during third degree heart block

Neuronal Action Potential

Na+ permeability

K+ permeability

AP

K+ channelsOpen (delayed rectifier)

Na+ channelsopen

Pacemaker Potential

[Na+]e high[K+]e low[Ca2+]e high

[Na+]i low[K+]i high[Ca2+]i low

extracellularfluid

intracellular Pacemaker cells do not have a steady resting potential.

Equilibrium potentialsEK = -94 mVENa = +60 mVECa = +123 mV

Pacemaker Potential1. ↓ PK; PNa

• Closure of K+ channels.• Opening of “funny” channels (Na+ and K+)

[Na+]e high[K+]e low[Ca2+]e high

[Na+]i low[K+]i high[Ca2+]i low

1.

extracellularfluid

intracellular

K+

Na+

K+

1. ↓ PK; PNa

• Closure of K+ channels.• Opening of “funny” channels

2. PCa

• Opening of voltage- gated Ca++ channels (T-type channels)

1. 2.

K+

Na+

Ca+

• Closure of funny channels (at ~ -55mV; 15 mV short of threshold)

T channel

1. ↓ PK; PNa


2. PCa

•Opening of voltage- gated Ca++ channels (T-type channels)

3. PCa

•Opening of voltage- gated Ca++ channels (L-type channels)

1. 2. 3.

K+

Ca+

Ca+

• Closure of funny channels

Na+

T channel

L channel• Closure of T- type Ca++ channels

some Na+ entersthrough these

1. ↓ PK; PNa


2. PCa

•Opening of voltage- gated Ca++ channels (T-type channels)

1. 2. 3. 4.

4. PK; ↓ PCa

•Opening of voltage- gated K+ channels

• Closure of voltage- dependent Ca++ channels (L-type)

K+

Ca+

Ca+

• Closure of funny channels

Na+

3. PCa

•Opening of voltage- gated Ca++ channels (L-type channels)

• Closure of T- type Ca++

channels sympathetic/parasympathetic influences: later

T channel

L channel


FROM THE 2006 FINAL EXAM

1. Which changes in ionic conductance (permeability) occur in zone 1?

a) A decrease in PK and an increase in PNa

b) A decrease in PK and an increase in PCa

c) An increase in PNa and no change in PK

d) A decrease in PK and no change in PNa

e) An increase in PK and an increase in PCa

1.2.

3.4.

Cardiac Action Potential(differ from cell to cell: size

and channel numbers)

LengthPlateauCa++ (Em and contraction)K+ channel closure

Cardiac contractile cells have a stableresting potential

Time (msec)

Cardiac Action Potential: Phase 0

• Opening of voltage-gated Na+ channels ; PNa ; Em

↑PNa

Depolarisation Na+ channel opening cascade


• Deactivation of Na+ channels ; ↓ PNa ; ↓ Em

↓PNa ↑PCa ↓PK

Countered by:

Closing of voltage-gated (inward rectifier) K+ channels ; ↓ PK ; Em

Opening of voltage-gated (L-type) Ca++ channels ; PCa ; Em

Cardiac Action Potential: Phase 2 (Plateau)

• Inward rectifier K+ channels remain closed ; ↓ PK ; Em

• Voltage-gated (L-type) Ca++ channels remain open; PCa ; Em

↑PCa ↓PK


• Delayed rectifying K+ channels open ; PK : ↓ Em

• Inward rectifying K+ channels begin to open ; PK : ↓ Em

• Voltage-gated Ca++ channels close ; ↓ PCa ; ↓ Em

↓PCa ↑PK


Resting membrane potential

FROM THE 2006 FINAL EXAM

2. Which of the following does not contribute to the plateau phase of the cardiac action potential?

a) An increase in Ca++ permeabilityb) A reduction in K+ permeabilityc) Incomplete Na+ channel inactivationd) An increase in K+ permeabilitye) None of the above contributes to the plateau phase of the cardiac action potential.

ECG: Electrocardiogram

• Electrical Activity• Surface Electrodes• Diagnostic Tool

I

II III

RightArm (RA)

LeftLeg LL)

• Equilateral triangle surrounding the heart (Einthoven’s triangle)

• Bipolar ECG limb leads record the voltage between electrodes placed on the wrists and the arms

Lead I: right arm (-) to left arm (+)Lead II: right arm (-) to left leg (+)Lead III: left arm (-) to left leg (+)

Standard Bipolar Limb Lead

LeftArm (LA)

Imaginary equilateral trianglesurrounding the heart.

I

II III

RightArm

LeftArm

LeftLeg

Einthoven’s Law

In the electrocardiogram, at any given instant, the potential of any wave in lead II is equal to the sum of the potentialsin lead I and III.

Lead I = ELA- ERA

Lead II = ELL- ERA Lead III = ELL- ELA

E = electrical potential

EI + EIII = EII

Nobel Prize, 1924

Lead II

Lead III

0

60120

I

II III

180Lead I

ECG Waves

• An ECG recording is very similar to a compound AP

Isoelectric Line

P T

Q

R

S

ECG Waves


StimulatingElectrodes

Recording electrodes

+

+

+……

=

Nervecontainingmany axons

nerve recording chamber

Compound Action

Potential

ECG Waves

P Wave: Atrial depolarisationQRS Complex: Ventricular Depolarisation (phase 0)T Wave: Ventricular Repolarisation


Isoelectric Line

P T

Q

R

S

Left Side ofthe Heart

Right Side ofthe Heart

Left VentricleRight

Ventricle

Right Atria

LeftAtria

Orientation (left; right) of the heart is based on the assumption that youare looking at the person (heart)from a frontal view.

Phases of the ECG relateto the waves of depolarisationand repolarisation during a heart beat.

Amount of electricalactivity is proportional tothe amount of tissue beingdepolarised.

Left and right ventriclesDisease (hypertrophy)Electrical axis

Phases of the ECG relateto the waves of depolarisationand repolarisation during a heart beat.

Pacemaker Potential

Time (sec)

mV

0

Pacemaker Potential

Time (sec)

mV

Conduction through the atria

Time (sec)

mVP

P Wave: Atrial Depolarisation

Time (sec)

mVP

Delay at the AV node andbeginning of conduction through the branch bundlesand Purkinjie fibres

Time (sec)

mVP

Q

R

S

QRS Complex: VentricularDepolarisation (and atrialrepolarisation)

Q wave also represents some of the branchbundle / PF depolarisation.

Time (sec)

mVP

Q

R

S

T

P Wave: VentricularRepolarisation

ECG Interpretation

• Rate• Rhythm• Axis• Hypertrophy• Infarct

Rate

< 60 beats per minute: Bradycardia> 100 beats per minute: Tachycardia

Rate

R-R Distance• time between 2 heat beats• 60/R-R interval = heart rate

P

Q

R

S


• Instantaneous heart rate

• Exercise or atropine* always increase the rate to normal.

Sinus (i.e., SA node) Bradycardia

• Physiological bradycardia occurs in healthy individuals (usually athletes) with increased vagal tone.

PT

Q

R

S

P T

Sympathetic and parasympathetic effects Cardiac Output lecture

*, atropine blocks muscarinic acetylcholine receptors

↑ K+ conductance↓ Na+/Ca++ conductance

-

Rhythm

• Segments of the ECG Trace• Normal Rhythms• Abnormal Rhythms

Irregular Rhythms Early / Late Beats Flutter / Fibrillation Heart Block

Palpitations

Sensation of yourheart beating.

CaffeineNicotineAlcoholCocaineStressSleeplessness

P-(Q)R Distance • start of P wave until the start of the QRS complex

• time of conduction through the AV node


Rhythm

Rhythm

Q-T Distance• Onset of QRS complex until the end of the T wave• Ventricular systole (contraction time)


T-Q Distance• End of the T wave until the start of the QRS complex• Ventricular diastole (relaxation time)

P

Q

R

S


Rhythm

• Each P followed by QRS with resulting P:QRS ratio 1:1.

Normal Sinus Rhythm

• Impulses originate in the SA node regularly at a rate of 60-100 per minute in adults.

• P waves upright and of uniform size and contour from beat to beat.

PT

Q

R

S

P T

RhythmSA node

AV node

Bundleof His

Bundle Branches

Purkinje Fibres

Internodal Pathways

• Arrhythmia: abnormal rhythm

Beat Originates from SA or AV Node

QRS Complex: normal, narrow

Beat Originates from the Ventricle

QRS Complex: Abnormal, wide

Four Types of Arrhythmia

1. Irregular Rhythms

The QRS Complex is not evenly spaced; total irregularity of the beat

e.g. Sinus Arrhythmia

P-Waves and PR Distancesare the same (atrial origin)

P

Q

R

S

T

Disappears with exercise or breath holding

5 4.5 4.0 5

P-R(Q) Distance:conduction timethrough the AV node

P P P P P


1. Irregular RhythmsP

Q

R

S

T

P-R(Q) Distance:conduction timethrough the AV node

e.g. Wandering Atrial Pacemakers

• Pacemaker activity from different locations within the atria.• P Waves and PR distance vary.

P P P P P P P P


2. Premature and Late BeatsP

Q

R

S

T

The rhythm is generally normal but there are occasionalearly or late beats.

Premature atrial contraction (normal QRS)

Premature ventricular contraction (Abnormal QRS)


3. Flutter and FibrillationP

Q

R

S

T

• Very rapid rates of electrical excitation and contraction in either the atria or the ventricles can produce flutter or fibrillation.

Flutter: rapid 200-300 per minute; contractions are coordinated.

• 220 and 300/min.

Atrial Flutter

• Heart rate is so fast that the isoelectric interval between the end of the T wave and the beginning of the P wave disappears

• The AV-node and, thereafter, the ventricles are generally activated by every second or every third atrial impulse.

AV node

SA node

Atrial Fibrillation

• Extremely chaotic electricalactivity in the atria. 500 actionpotentials per minute.

• elderly patients• valve disease• coronary artery disease

• wandering re-entry loop (becomes pacemaker at any given time)

conduction to the ventricles

atria as an accessory pump

Atrial Fibrillation

Ventricular Fibrillation

• Fibrillation: contraction of different groups of muscle fibres occurs at different times; coordinated pumping action is impossible.

• Caused by continuous recycling of electrical activity through the myocardium.


• Recycling is normally prevented due to the myocardium refractory period (post-contraction).

• However, if some cells emerge from their refractory period before others, electrical waves can be continuously regenerated and conducted leading to uncoordinated contraction and impotent pumping.

Ventricular Fibrillation (Re-entry circuits)

unidirectionalblock

normal cells

dead cells

conduction both ways conduction one way only


• Ventricular fibrillation leads to death within a few minutes.

• Fibrillation can be stopped (sometimes) by a strong electrical shock delivered to the chest.

• Slow conduction through the AV node. • Prolonged PR interval (> 0.2 sec).

P

Q

R

S

T


4. AV Heart Block (First Degree Heart Block)

Normal Rhythm

• No treatment; highly-trained athletes• Enhanced vagal tone; AV node disease; electrolyte imbalance

1. irregular rhythms2. early/late beats3. flutter fibrillation

• Impulses are intermittently blocked at the AV junction.

• Not all P waves are followed by a QRS complex.

Missing QRS


4. AV Heart Block (Second Degree AV Block)

• Progressive increase in delay until a beat is skipped (Type I).• 2-4 P waves for every QRS complex (Type II)

• Complete lack of conduction through the AV node


4. AV Heart Block (Third Degree AV Block)

•“Escape QRS Complex”: Generated in the ventricle

Above the Bundle of His: Narrow QRS complex (stable heart) Below the Bundle of His: Wide QRS complex (unstable heart)

• heart attack; increased vagal tone; drug intoxication• pacemaker required

Bundle Branch Block (BBB)

• Impulses originate in the SA node and spread normally through the atria and AV junction, however, the conduction through the right (R) or left (L) branch bundles is blocked.

• In LBBB the left ventricle is activated late; in RBBB the right ventricle is activated late

left bundlebranchright bundle

branch

The Electrical Axis of the Heart

• Definition• Vectoral Analysis of the Axis• Diagnostic Uses• Calculating the Mean Electrical Axis

- +

Lead I

Lead II

-

+

Lead III

-

+

0

60120

180

The Electrical Axis of the Heart

2

1

4

3

1

2

3

4

• The mean electrical axis is the average of all the instantaneous mean electrical vectors occurring sequentially during depolarization of the ventricles.

1. Conduction down the branch bundles → interventricular septum depolarises from left to right (Q wave; negative; away from the positive lead II electrode).

Left

Right

2. 20 msec later: Depolarisation towards the apex (vector 2)

3. 20 msec later: Depolarisation towards the left arm (vector 3)

4. S Wave (vector 4)

QS

R

Lead II

Lead I

Lead II

Lead III

0

60120

180

0

90

180

270

45135

225 315

Less than 0°: Left Axis DeviationGreater than 90°: Right Axis Deviation

0

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Less than 0°: Left Axis DeviationGreater than 90°: Right Axis Deviation

What factors affect the mean electrical axis of the heart? How can it be used as a diagnostic tool?

Diagnostic Use of the Heart’s Electrical Axis

Deviation to the Right

Increased Right Ventricular Mass

Chronic obstructive lung diseasePulmonary embolismCongenital heart defectsSevere pulmonary hypertension

Deviation to the Left

Increased Left Ventricular Mass

HypertensionAortic stenosisIschemic heart disease

Calculating the Mean Electrical Axis

1. Look at the lead I ECG. Calculate the isoelectric line to R distance. This equals “a” 2. Look at the lead I ECG. Calculate the isoelectric line to S distance. This equals “b”3. Add “a” plus “b”. Note that “b” is a negative value.4. Do the same for the lead II and II ECG traces to find “c”, “d”, “e” and “f”.5. Calculate “c + d” and “e + f”6. Draw an equilateral triangle. 7. Starting at the centre of each line (which represent leads I, II and II) measure the distance represented by “a + b”, “c + d” and “e + f” (right is positive).8. Draw a perpendicular line from the end of these vectors into the middle of the triangle.9. Determine the centre of the triangle.10. Draw a line from the centre of the triangle to the point at which the perpendicular lines (from the end of a + b, c + d and e + f meet).11. The line from the centre of the triangle the meeting point of these lines represents the mean electrical axis of the heart.

Follow these instructions while lookingat the following slide.

Q

R

S

2 mV

- 2 mV

Q

R

S

2 mV

- 2 mV

Q

R

S

2 mV

- 2 mV

a

b

c

d

e

f

a+b

c+de+f

Calculating the Mean Electrical AxisLead I

Lead II

Lead III

I

II

III

Use the following information and diagrams to calculate the mean electricalaxis of the heart. Each division on the leads equals 1.

Magnitude of the QRS complex in lead I = 2Magnitude of the QRS complex in lead II = 5Magnitude of the QRS complex in lead III = 3

a) Approximately 33°b) Approximately 43°c) Approximately 67°d) Approximately 90°e) Approximately 115°

0

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0

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0

90

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0

90

180

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Step 1: Plot the QRS complexmagnitude on the appropriatelead.




0

90

180

270

45135

225 315

0

90

180

270

45135

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Step 2: Draw perpendicular linesfrom the end of the drawn vectorinto the triangle. They shouldall meet.




0

90

180

270

45135

225 315

0

90

180

270

45135

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Step 3: Draw perpendicular linesfrom the middle of each lead intothe triangle. They will meet at thecentre.




0

90

180

270

45135

225 315

0

90

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270

45135

225 315

Step 4: Draw a line from the centre of the triangle to the point at which the three lines perpendicular to the ends of thevectors meet. This is the axis.

VentricularFilling

AtrialContraction

IsovolumetricContraction

VentricularEjection

IsovolumetricRelaxation

1

2 3

4

The Stages of the Cardiac Cycle

Isovolumetric: constant volume

2 3 4

AV Valves

Semilunar Valves

1

Aortic Pressure

Atrial Pressure

Ventricular Pressure

VentricularVolume

Overview ofthe Pressureand Volume

Changes in theCardiac Cycle

(Details to come)

Documents

Lecture 1 Summer 2007 WEB