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, sgreid@utsc.utoronto.ca http://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 questions from 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 2007 Lab 5 (Cardiovascular Dynamics): June 13 2007 Lab 7 (Respiratory System Mechanics): June 27 2007 Lab 9 (Renal System Physiology): July 18 2007 Lab 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 Output 3 (May 23): Regulation of Cardiac Output; Blood Flow Regulation; Heart Failure 4 (May 30): Blood Pressure Regulation; Pulmonary Mechanics 5 (June 6): Pulmonary Mechanics; Gas Exchange 6 (June 13): Gas Transport; Ventilation-Perfusion Matching; Control of Breathing 7 (June 20): Control of Breathing; EEG and Sleep-Related Breathing Disorders; Glomerular Filtration 8 (June 27): Glomerular Filtration; Tubular Reabsorption and Secretion; Clearance Reading Week (July 2-6) 9 (July 11): Water, Na+, K+ and Ca2+ Balance 10 (July 18): Acid-Base Balance 11 (July 25): Digestive Physiology I 12 (August 1): Digestive Physiology II

Cardiovascular System
Pacemaker Potential / Cardiac Action Potential Electrocardiogram (ECG) Cardiac Cycle Cardiac Output (CO); volume of blood pumped per minute Blood Flow Blood Pressure (BP)

CO = HR X SV

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

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

Heart Valves and Major Blood Vessels

Aorta (to the systemic circulation) Pulmonary Arteries (to lungs) Semilunar valves (aortic & pulmonary) RA Tricuspid (AV) Valve Inferior Vena cava RV
apex

Superior Vena cava

LA

Pulmonary Veins (from lungs) Bicuspid (AV; mitral) Valve

LV

interatrial septum interventricular septum

ventricular muscle

RA: right atria LA: left atria RV: right ventricle LV: left ventricle

Patterns of Blood Flow

Lungs

Pulmonary artery

3.

4.

Pulmonary vein

Vena cavae 1. 2. RV 5. LV

Aorta

6.

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

Systemic Circulation

The Conduction System of the Heart

(pacemaker conduction fibres contractile fibres )
conduction fibres: larger diameter atria ventricles: separated by fibrous bundles

2. Internodal pathways 1. Sinoatrial (SA) node 3. Atrioventricular (AV) node 4. AV bundle (Bundle of His)

6. Purkinje fibres 5. Right and left bundle branches coordinated contraction RV

LV
gap junctions

Cardiac Muscle Cells are Electrically Connected via Gap Junctions

desmosome (protein fibres)

Cardiac Muscle Cells

intercalated disk

Gap Junction
desmosome resist stretching important as it occurs every time the heart fills (cardiac cycle) gap junction passage of current Plasma membrane

hypertrophy: reduced contraction steps in conduction

a. AP is initiated in the SA node

a. AP is initiated in the SA node

b. AP are conducted throughout the atria very rapid large cells

a. AP is initiated in the SA node

b. AP are conducted throughout the atria very rapid large cells

fibrous septum

c. Conduction slows at the AV node small cells

SA node versus AV node

(frequency and refractory period)

Allows full ventricular filling before contraction

a. AP is initiated in the SA node

b. AP are conducted throughout the atria very rapid large cells c. Conduction slows at the AV node small cells d. AP travel rapidly through the bundle of His and the branch bundles

a. AP is initiated in the SA node

e. AP spread through the ventricles (bottom to top)

b. AP are conducted throughout the atria very rapid large cells contraction: apex to top c. Conduction slows at the AV node small cells d. AP travel rapidly through the branch bundles

a. AP is initiated in the SA node

f. rest

e. AP spread through the ventricles (bottom to top) Ectopic (idioventricular) Pacemakers

b. AP are conducted throughout the atria very rapid large cells c. Conduction slows at the AV node small cells d. AP travel rapidly through the branch bundles

Artificial Pacemakers

First Battery Powered Pacemaker

Line Powered Pacemaker (failed during power outages)

Older models: stimulate at a fixed rate

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

lithium batteries hybrid circuit

Pulse Generator

left atria

left ventricle right atria

right ventricle

Sense and Stimulate

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

V
normal ecg

V A A

V A

V A

V A

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

ECG during third degree heart block

Ectopic Pacemakers

Neuronal Action Potential

AP Na+ permeability

K+ permeability

Na+ channels open

K+ channels Open (delayed rectifier)

Pacemaker Potential

intracellular

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

extracellular fluid

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

Pacemaker cells do not have a steady resting potential. Equilibrium potentials EK = -94 mV ENa = +60 mV ECa = +123 mV

1. PK; PNa
Closure of K+ channels. Opening of funny channels (Na+ and K+)

Pacemaker Potential 1.

intracellular

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

extracellular fluid

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

K+

K+

Na+

1. PK; PNa
Closure of K+ channels. Opening of funny channels

1.

2.

2. PCa
Opening of voltagegated Ca++ channels (T-type channels) Closure of funny channels (at ~ -55mV; 15 mV short of threshold)
T channel

Ca+

K+ Na+

1. PK; PNa
Closure of K+ channels. Opening of funny channels

1.

2. 3.

2. PCa
Opening of voltagegated Ca++ channels (T-type channels) Closure of funny channels
T channel

3. PCa
Opening of voltagegated Ca++ channels (L-type channels)
some Na+ enters through these

Ca+

K+ Na+ Ca+ L channel

Closure of T- type Ca++ channels

1. PK; PNa
Closure of K+ channels. Opening of funny channels

1.

2. 3. 4.

2. PCa
Opening of voltagegated Ca++ channels (T-type channels) Closure of funny channels

T channel

4. PK; PCa
Opening of voltagegated K+ channels Closure of voltagedependent Ca++ channels (L-type) K+

Ca+

3. PCa
Opening of voltagegated Ca++ channels (L-type channels) Closure of T- type Ca++ channels

Na+
L channel Ca+

sympathetic/parasympathetic influences: later

a. AP is initiated in the SA node

FROM THE 2006 FINAL EXAM 1. Which changes in ionic conductance (permeability) occur in zone 1?

3. 4. 2. 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

Cardiac Action Potential

(differ from cell to cell: size

and channel numbers)

Length Plateau Ca++ (Em and contraction) K+ channel closure

Cardiac contractile cells have a stable resting potential

Time (msec)

Cardiac Action Potential: Phase 0

PNa

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

Depolarisation Na+ channel opening cascade

Cardiac Action Potential: Phase 1

PNa PCa PK

Deactivation of Na+ channels ; PNa ; Em

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)

PCa PK

Inward rectifier K+ channels remain closed ; PK ; Em

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

Cardiac Action Potential: Phase 3

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

Cardiac Action Potential: Phase 4

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++ permeability b) A reduction in K+ permeability c) Incomplete Na+ channel inactivation d) An increase in K+ permeability e) None of the above contributes to the plateau phase of the cardiac action potential.

ECG: Electrocardiogram

Electrical Activity Surface Electrodes Diagnostic Tool

Bipolar ECG limb leads record the voltage between electrodes placed on the wrists and the arms Equilateral triangle surrounding the heart (Einthovens triangle)

Right Arm (RA)

Left Arm (LA)

II

III

Standard Bipolar Limb Lead

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

Left Leg LL)

Imaginary equilateral triangle surrounding the heart.

Einthovens Law
In the electrocardiogram, at any given instant, the potential of any wave in lead II is equal to the sum of the potentials in lead I and III.
Right Arm Left Arm

Lead I = ELA- ERA Lead II = ELL- ERA Lead III = ELL- ELA
E = electrical potential

II

III

Left Leg

EI + EIII = EII
Nobel Prize, 1924

II

III

180

Lead I

Lead III
Lead II

120

60

ECG Waves
An ECG recording is very similar to a compound AP

R P Q S T

Isoelectric Line

ECG Waves
An ECG recording is very similar to a compound AP Stimulating + Electrodes
Compound Action Potential + + =

Nerve containing many axons

nerve recording chamber

Recording electrodes

ECG Waves
An ECG recording is very similar to a compound AP

R P Q S T

Isoelectric Line

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

Right Side of the Heart

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

Right Atria

Left Atria

Left Side of the Heart Left Ventricle

Right Ventricle

Phases of the ECG relate to the waves of depolarisation and repolarisation during a heart beat.

Phases of the ECG relate to the waves of depolarisation and repolarisation during a heart beat.

Amount of electrical activity is proportional to the amount of tissue being depolarised.

Left and right ventricles Disease (hypertrophy) Electrical axis

Pacemaker Potential

Pacemaker Potential

mV

Time (sec)

Conduction through the atria

mV

Time (sec)

P Wave: Atrial Depolarisation

mV P

Time (sec)

Delay at the AV node and beginning of conduction through the branch bundles and Purkinjie fibres

mV P

Time (sec)

QRS Complex: Ventricular Depolarisation (and atrial repolarisation)

mV P

Q
S Time (sec)
Q wave also represents some of the branch bundle / PF depolarisation.

P Wave: Ventricular Repolarisation

mV P T

Q
S Time (sec)

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

Instantaneous heart rate

R
P

Q S

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

Sinus (i.e., SA node) Bradycardia

R P T P Q S T

Exercise or atropine* always increase the rate to normal.

Sympathetic and parasympathetic effects Cardiac Output lecture

Physiological bradycardia occurs in healthy individuals (usually athletes) with increased vagal tone. K+ conductance Na+/Ca++ conductance *, atropine blocks muscarinic acetylcholine receptors

Rhythm

Segments of the ECG Trace Normal Rhythms Abnormal Rhythms

Irregular Rhythms Early / Late Beats Flutter / Fibrillation Heart Block Palpitations Sensation of your heart beating. Caffeine Nicotine Alcohol Cocaine Stress Sleeplessness

Rhythm
P-(Q)R Distance start of P wave until the start of the QRS complex
time of conduction through the AV node

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

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

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

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

R
P

Q S

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

Normal Sinus Rhythm

R P T P Q S T

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

Rhythm
Beat Originates from SA or AV Node QRS Complex: normal, narrow SA node AV node

Internodal Pathways
Bundle of His Purkinje Fibres

Beat Originates from the Ventricle QRS Complex: Abnormal, wide Bundle Branches

Arrhythmia: abnormal rhythm

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 Distances are the same (atrial origin) 5 P P
P Q

4.5
P

4.0
P

5 P

Disappears with exercise or breath holding

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

Four Types of Arrhythmia

1. Irregular Rhythms
e.g. Wandering Atrial Pacemakers
P Q

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

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

Four Types of Arrhythmia

2. Premature and Late Beats
The rhythm is generally normal but there are occasional early or late beats. Premature atrial contraction (normal QRS)
P Q

Premature ventricular contraction (Abnormal QRS)

Four Types of Arrhythmia

3. Flutter and Fibrillation
P Q

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.

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

220 and 300/min. The AV-node and, thereafter, the ventricles are generally activated
by every second or every third atrial impulse. SA node AV node

conduction to the ventricles

Atrial Fibrillation Extremely chaotic electrical

activity in the atria. 500 action potentials per minute.

elderly patients valve disease coronary artery disease

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

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.

Ventricular Fibrillation

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)

unidirectional block

conduction both ways dead cells normal cells

conduction one way only

Ventricular Fibrillation

Ventricular fibrillation leads to death within a few minutes.

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

Four Types of Arrhythmia

4. AV Heart Block (First Degree Heart Block)
R P Q Normal Rhythm S T

1. irregular rhythms 2. early/late beats 3. flutter fibrillation

Slow conduction through the AV node. Prolonged PR interval (> 0.2 sec). No treatment; highly-trained athletes Enhanced vagal tone; AV node disease; electrolyte imbalance

Four Types of Arrhythmia

4. AV Heart Block (Second Degree AV Block)

Missing QRS

Impulses are intermittently blocked at the AV junction.

Not all P waves are followed by a QRS complex.

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

Four Types of Arrhythmia

4. AV Heart Block (Third Degree AV Block)

Complete lack of conduction through the AV node 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

right bundle branch

left bundle branch

The Electrical Axis of the Heart

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

The Electrical Axis of the Heart

Lead I

+ 0

180 Lead II Lead III

120

60

 The mean electrical axis is the average of all the instantaneous

mean electrical vectors occurring sequentially during depolarization of the ventricles.
4 Left 1 3 2 3
R

Right

Lead II

Q S

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

Lead I

180
Lead II

Lead III
225

270
315

120

60

180 135 45 90

Less than 0: Left Axis Deviation Greater than 90: Right Axis Deviation

270 225 315

180 135 90 45

Less than 0: Left Axis Deviation Greater 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 Hearts Electrical Axis

Deviation to the Right

Increased Right Ventricular Mass

Chronic obstructive lung disease Pulmonary embolism Congenital heart defects Severe pulmonary hypertension Deviation to the Left Increased Left Ventricular Mass Hypertension Aortic stenosis Ischemic heart disease

Calculating the Mean Electrical Axis

Look at the lead I ECG. Calculate the isoelectric line to R distance. This equals a Look at the lead I ECG. Calculate the isoelectric line to S distance. This equals b Add a plus b. Note that b is a negative value. Do the same for the lead II and II ECG traces to find c, d, e and f. Calculate c + d and e + f Draw an equilateral triangle. 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. 1. 2. 3. 4. 5. 6. 7.

Follow these instructions while looking at the following slide.

2 mV
R

Lead I

Calculating the Mean Electrical Axis

I a+b

a
Q - 2 mV II

b
S

2 mV
R c Q - 2 mV

Lead II

c+d
2 mV Lead III R e f Q S

e+f
III

d
S

- 2 mV

Use the following information and diagrams to calculate the mean electrical axis of the heart. Each division on the leads equals 1.
Magnitude of the QRS complex in lead I = 2 Magnitude of the QRS complex in lead II = 5 Magnitude of the QRS complex in lead III = 3 a) Approximately 33 b) Approximately 43 c) Approximately 67 d) Approximately 90 e) Approximately 115
225

270 315

180

135 90

45

270 225 315

180 135 90 45

Use the following information and diagrams to calculate the mean electrical axis of the heart. Each division on the leads equals 1.
Magnitude of the QRS complex in lead I = 2 Magnitude of the QRS complex in lead II = 5 Magnitude of the QRS complex in lead III = 3 a) Approximately 33 b) Approximately 43 c) Approximately 67 d) Approximately 90 e) Approximately 115
225

270 315

180

135 90

45

270 225 315

Step 1: Plot the QRS complex magnitude on the appropriate lead.

180 135 90 45

Use the following information and diagrams to calculate the mean electrical axis of the heart. Each division on the leads equals 1.
Magnitude of the QRS complex in lead I = 2 Magnitude of the QRS complex in lead II = 5 Magnitude of the QRS complex in lead III = 3 a) Approximately 33 b) Approximately 43 c) Approximately 67 d) Approximately 90 e) Approximately 115
225

270 315

180

135 90

45

270 225 315

Step 2: Draw perpendicular lines from the end of the drawn vector into the triangle. They should all meet.

180 135 90 45

Use the following information and diagrams to calculate the mean electrical axis of the heart. Each division on the leads equals 1.
Magnitude of the QRS complex in lead I = 2 Magnitude of the QRS complex in lead II = 5 Magnitude of the QRS complex in lead III = 3 a) Approximately 33 b) Approximately 43 c) Approximately 67 d) Approximately 90 e) Approximately 115
225

270 315

180

135 90

45

270 225 315

Step 3: Draw perpendicular lines from the middle of each lead into the triangle. They will meet at the centre.

180 135 90 45

Use the following information and diagrams to calculate the mean electrical axis of the heart. Each division on the leads equals 1.
Magnitude of the QRS complex in lead I = 2 Magnitude of the QRS complex in lead II = 5 Magnitude of the QRS complex in lead III = 3 a) Approximately 33 b) Approximately 43 c) Approximately 67 d) Approximately 90 e) Approximately 115
225

270 315

180

135 90

45

270 225 315

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

180 135 90 45

The Stages of the Cardiac Cycle

1

2 Isovolumetric Contraction

3 Ventricular Ejection

4
Isovolumetric Relaxation

Atrial Contraction

Ventricular Filling

Isovolumetric: constant volume

1 AV Valves Semilunar Valves

Aortic Pressure

Overview of the Pressure and Volume Changes in the Cardiac Cycle (Details to come)

Ventricular Pressure Atrial Pressure

Ventricular Volume