Department of Bioengineering

Imperial College London

MEng in Biomedical Engineering

MEng in Biomolecular Engineering

BIOE 40010 Medical and Biological Sciences 1

BIOE 40007 Medical and Biochemical Sciences 1

AUTUMN TERM

CARDIOVASCULAR & RESPIRATORY SYSTEMS

Professor P D Weinberg

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 Contents

Recommended textbooks ………………………………………………………………………… 3

Lecture outlines ………………………………………………………………………………………… 4

Lecture slides ………………………………………………………………………………………………… 9

Study group questions ………………………………………………………………………………… 29

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 Recommended Textbooks

Vander's Human Physiology

by Eric P. Widmaier, Hershel Raff, Kevin T. Strang
McGraw-Hill Higher Education; 15th edition (2019)
ISBN13: 9781260231526

Levick’s Introduction to Cardiovascular Physiology (Arnold Publication)

(Paperback)
by Neil Herring, David J Paterson
CRC Press; 6th edition (2018)
ISBN-13: 9781498739849

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Lecture Outlines

Lecture 1

Explanation of the course content, timetable and assessment methods; advice

on note taking, buying textbooks, how to study at university; suggestions for
those who haven’t studied A-level biology

Lecture 2

I. Introduction to the Circulation

a) Why have a circulation?
Nature of diffusion; characteristic diffusion times; bulk flow.
b) Components of the circulation.
Systemic and Pulmonary; 2 sides of heart; series and parallel architectures;
anomalies; generalised vessel structure; Laplace’s law and wall thickness;
specific vessel types, functions and structures

Lecture 3

II. Lung Structure and Mechanics

a) Thoracic arrangement.
Pleural membranes and fluid; Elasticity; Movement of chest and diaphragm;
Intrapleural pressure.
b) Ventilation.
Inspiration and expiration; Q=(P1-P2)/R; Sequence of events in ventilation;
Volumes and capacities – terminology.
c) Resistance.
d) Compliance.
Surfactant; Respiratory distress syndrome.
e) Airway structure.
Conducting and exchange vessels; Protective function.
f) Alveoli.
Surface area; Transport pathway; Types I and II cells; Pores.

Lecture 4

III. The Heart: Structure, and Mechanics of the Cardiac Cycle

a) Heart Structure.
i. Cross section: chambers; wall; vessels in and out; valves.
ii. Arrangement: Fibrotendinous ring; position in thorax.
iii. Pumping action: Left and Right.

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b) Pressures and volumes during the cardiac cycle
Diastole; atrial contraction; isovolumetric ventricular contraction; ventricular
ejection; isovolumetric ventricular relaxation: Pressures and Volumes in atria
and ventricles; valve action; heart sounds; Right versus left side.

Lecture 5

IV. Gas Transport and Exchange

a) Gas exchange.
Respiratory quotient; General exchange arrangement; Partial pressures and
solubilities of gases – theory; Partial pressures in lung, blood and tissue;
Alveolar exchange.
b) Oxygen transport in blood.
Dissolved oxygen and oxyhaemoglobin; Indirect effect of haemoglobin on
diffusion; % saturation; oxygen-haemoglobin dissociation curve;
Consequences for high altitude, hyperventilation and exchange in tissue and
lung; Effect of Pco2, [H+] and temperature; Consequences for exchange.
c) Carbon dioxide transport in blood.
Dissolved, amino groups (incl. on Hb) and bicarbonate; Effect on pH;
Pathways for CO2 exchange in tissue and lung.

Lecture 6

V. The Heart: Electrics of the Cardiac Cycle

a) Resting Potential.
Donnan Equilibrium; K+ channels; Na+ channels; Na/K Pump; Ca++ channels
and pump in myocardial cells.
b) Action Potential.
Polarity; Threshold; Voltage-sensitive Na channels; +ve feedback; 2nd inward
current (Ca++); Refractory period; Repolarisation; Different cell profiles.

Lecture 7

V. The Heart: Electrics of the Cardiac Cycle contd.

c) Spreading of Action Potentials.
Local currents; Directionality
d) Excitation-Contraction Coupling.
Linkage of electrical and mechanical events through [Ca]i
e) Initiation and Co-ordination.
Spontaneous action potentials; Pacemaker cells; SA node; AV node; Bundles.
f) The electrocardiogram
Idealised ECG waves and their origins; Einthoven’s triangle; ventricular dipoles
and the QRS complex

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Lecture 8

VI. Control of Ventilation and Perfusion

a) Role of Medulla.
Skeletal musculature; Medullary inspiratory neurones.
b) Control of frequency.
Role of Po2, Pco2 AND [H+]; Flow chart; Peripheral and central
chemoreceptors and their responses to each factor; Effect of Po2; No effect of
HbO2; Major role of CO2; Lactic acid; Plasma pH control.
c) Other factors.
Pain, emotion and voluntary control.
d) Control of ventilation-perfusion ratios.
i. Cases of: normal ventilation and perfusion; blocked ventilation; blocked
perfusion
ii. Possible values for Pco2 and Po2 and effect of change in V / Q
iii. Local metabolic demands insignificant: local control of blood flow is
paradoxical; local control of ventilation

Lecture 9

VII. Cardiac Output and its Regulation

a) Cardiac Output.
b) Control of Heart Rate.
Parasympathetic and sympathetic effects on SA and AV nodes; Ionic
mechanisms; Other effects of catecholamines.
c) Control of Stroke Volume.
Starling's Law of the Heart; Starling curve; Left and Right heart balance;
Sarcomere mechanism.
Contractility; Catecholamines; Actin-myosin cross-bridges.

VIII. Introduction to Haemodynamics

a) Flow in Pipes.
Pressure drop along a pipe; Entrance region; Fully developed flow; Turbulence;
Q=(P1-P2)/R; Resistance in laminar flow; Parallel and series arrangements.

Lecture 10

VIII. Introduction to Haemodynamics contd.

b) Flow in the body.
Entrance lengths; Blood cells; Pulsatility; Resistance in the arterial tree;
Dominance of arteriolar resistance.

IX. Control of Arteriolar Tone

a) Role of resistance vessels.

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b) Local controls.
Local metabolites (active hyperaemia); Pressure autoregulation; Reactive
hyperaemia; Temperature; Injury; Endothelium.
c) Extrinsic controls.
Sympathetic nerves; Parasympathetic nerves; Hormones.

Lecture 11

X. Capillaries, Interstitium and Lymph: Solute Exchange and Fluid Balance

a) Capillary structure.
Capillary module; Distribution of smooth muscle; Sphincters. Continuous
capillary structure; Intercellular junctions; Vesicles; Glycocalyx; Basal lamina;
Other types of capillary.
b) Solute exchange
Diffusion and convection; Lipid soluble molecules; Small lipid-insoluble
molecules and water; Large lipid-insoluble molecules.

Lecture 12

X. Capillaries, Interstitium and Lymph: Solute Exchange and Fluid Balance

contd.
Exceptions – blood brain barrier, fenestrated and discontinuous capillaries.
c) Modification of exchange (e.g. exercise): concentration gradients altered by
metabolism; increased flow rate (flow-limited and diffusion-limited exchange);
capillary recruitment - Krogh cylinders, altered exchange area and distance.
d) Movement of water
i. Depends on hydrostatic pressure in capillaries and interstitium, oncotic
pressure in capillaries and interstitium, capillary permeability to water and
macromolecules:
Jv = Lp S [ ( Pc - Pi ) - rc ( Pip - Pii ) ]
consider each factor:
ii. Membrane properties: hydraulic conductivity, area, reflection coefficient.
iii. Capillary pressure measurement (cannulation).

Lecture 13

X. Capillaries, Interstitium and Lymph: Solute Exchange and Fluid Balance

contd.
iv. Plasma oncotic pressure: no effect of ions; non-ideality; role of albumin.
v. Interstitial oncotic pressure: defined to include only effects of plasma
proteins; measurement; concentration of plasma proteins.
vi. Interstitial pressure: controversial; anatomy - collagen, proteoglycans; high
charge density and resistance to flow; evidence for negative pressure; role of
proteoglycans and lymphatic pumping.
e) Lymphatic system

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i. Functions: water return; large particle return; fat transport; defence.
ii. Anatomy: lymphatic capillaries; valves and smooth muscle.
iii. Driving force for flow: intrinsic pumping; extrinsic pumping.
f) Starling balance
i. Original theory: water out at arterial end, in at venous end.
ii. Modern modification: not tenable; role of vasomotion.

Lecture 14

X. Capillaries, Interstitium and Lymph: Solute Exchange and Fluid Balance

contd.
iii. Effect of posture: swelling of lower limb; arteriolar resistance - changes Pc
and filtration.
iv. Exercise and muscle swelling.
g) Oedema
i. Causes: high Pc - thrombosis, venous failure; low Pip - malnutrition, poor
protein absorption, synthesis or retention; high capillary permeability -
inflammation; low lymph flow - developmental, damage, parasites.
ii. Characteristics: subcutaneous and pulmonary oedema.

XI. Return of Water and Solutes to the Heart

a) Venous System.
Anatomy; Capacitance; Compliance and its control; Muscular and respiratory
pumping.
b) Lymphatic system.
Vessels entering heart

XII. Control of Blood Pressure

a) Short-term
Baroreceptors; Medullary cardiovascular centre; Flow chart of integrated reflex.
b) Long-term
Blood volume control

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 Study Group Questions

STUDY GROUP 1

Overview of the Circulation

1. What functions do the following blood vessels have in addition to

transporting blood, and what structural adaptations enable them to carry out
these functions?
a. Elastic arteries
b. Muscular arteries
c. Arterioles
d. Capillaries
e. Veins

2. Give the Law of Laplace

3. Output of the right heart is what percentage of the left heart?

a. 25%
b. 50%
c. 75%
d. 100%
e. 125%

Cardiac Mechanics

4. TRY THIS ONE WITHOUT NOTES/TEXTBOOKS: Show on the x- (time-)

axis of the following diagram the points at which the aortic and mitral
(atrioventricular) valves open and close, and the isovolumetric contraction and
isovolumetric relaxation phases.

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5. Aortic pressure reaches a high of ~__ mm Hg, also called the ___
pressure, and a low of ~__ mm Hg, also called the ___ pressure.

6. True or False? End diastolic volume is equal to about 130 ml, and end
systolic volume is about 0 ml, so the stroke volume equals 130 ml.

7. Give an equation relating the stroke volume, heart rate and cardiac output.
What are the approximate values at rest?

Ventilation

8. If a person suffered a stab injury and air entered the intrapleural space
(pneumothorax), the most likely response would be for the

a. lung to expand outward and the chest wall to spring inward

b. lung to expand outward and the chest wall to spring outward
c. lung to collapse inward and the chest wall to collapse inward
d. lung to collapse inward and the chest wall to spring outward
e. lung volume to be unaffected and chest wall to spring outward

9. A patient has an inability to produce surfactant. In order to inhale a normal

tidal volume, will her intrapleural pressure have to be more or less
subatmospheric during inspiration, relative to a normal person?

10. Why must a person floating on the surface of the water and breathing
through a snorkel increase his tidal volume and/or breathing frequency if
alveolar ventilation is to remain normal?

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STUDY GROUP 2

Cardiac Electrics

11. TRY THIS ONE WITHOUT NOTES/TEXTBOOKS: Show on the first diagram
the equilibrium potentials in a cardiac myocyte of Na + and K+ and give the
value for Ca2+. What does the arrow at -65 mV signify?

+51

12. Label the diagram, including the y-axis.

13. Explain the term “voltage-gated Na channel.” Why does it lead to a very
rapid depolarisation of the cardiac myocyte during an action potential?

Gas Exchange

14. How many layers of plasma membrane must an alveolar oxygen molecule
traverse to reach hemoglobin?

a. 2
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 b. 3
c. 4
d. 5
e. 6

15. A normal person breathing room air voluntarily increases their alveolar
ventilation twofold and continues to do so until new steady-state alveolar partial
pressures for oxygen and carbon dioxide are reached. Are the new values for
(a) oxygen and (b) carbon dioxide higher or lower than normal?

16. A person has an alveolar PO2 of 105 mmHg and an arterial PO2 of 80 mmHg.
Could hypoventilation, say, due to respiratory muscle weakness, produce these
values?

17. At which of the following sites is the partial pressure of carbon dioxide
(Pco2) highest?
A. exhaled gas
B. alveolar gas
C. systemic arterial blood
D. systemic venous blood
E. about the same in all of the above (40 mmHg)

18. At which of the following sites is the partial pressure of oxygen (Po 2)
highest?
A. exhaled gas
B. anatomical dead space at the end of expiration
C. anatomical dead space at the end of inspiration
D. alveolar gas
E. about the same in all of the above (100 mmHg)

19. Consider the Po2 and Pco2 in the following locations: alveoli, pulmonary
vein, systemic arteries, systemic veins, pulmonary artery. Which pairs of
locations have the same partial pressures, and why?

STUDY GROUP 3

Cardiac Electrics (contd.)

20. Which of the following statements about the heart is false?

a. Contraction is initiated by a nerve impulse
b. Impulses are conducted from one muscle cell to the next
c. The heart contains a number of cells with an unstable membrane
potential
d. The heart contains a number of cells with a stable membrane
potential
e. The ventricles are inexcitable for most of the contraction period

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21. The sinoatrial node is the pacemaker for the heart because the SA node
a. is the most richly innervated structure in the heart
b. is the only structure in the heart capable of generating action
potentials
c. has the highest rate of automatic discharge
d. has the most stable transmembrane potential
e. is the cardiac cell least sensitive to catecholamines

22. The physiological function of the relatively slow conduction through the
AV node is to allow sufficient time for
a. run-off of blood from the aorta to the arterioles
b. venous return to the atria
c. filling of the ventricles
d. contraction of the ventricles
e. repolarization of the ventricles

ECG

23. Which of the following events is represented on the ECG?

a. SA node depolarization
b. AV node depolarization
c. His Bundle depolarization
d. Repolarization of the atria
e. Ventricular muscle depolarization

24. An independence of the P waves and the QRS complexes of the ECG
indicates
a. an early repolarization of ventricular fibers
b. a failure of the AV node to conduct
c. slowed firing of the sinoatrial node
d. slowing of conduction at the atrioventricular node
e. a conduction block in the left bundle branch

25. A person with a heart rate of 40 has no P waves but normal QRS complexes
on the ECG. What is the explanation?

Gas Transport

26. A person is breathing 100 percent oxygen. How much will the oxygen
content (in milliliters per liter of blood) of the arterial blood increase compared
to when the person is breathing room air?

27. What is the % saturation of haemoglobin after passing through a lung with
a Po2 of 100 mmHg? How far will the saturation fall if Po2 drops to 60 mmHg? If
Po2 in the lungs is normally 100 mmHg and in tissue is normally 40 mmHg, can
tissue Po2 fall low enough so that the haemoglobin delivers 5 times as much
oxygen? If not, how can oxygen delivery to tissue increase by this amount
during exercise?

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28. As blood passes through systemic capillaries, what happens to the affinity
of hemoglobin for oxygen and what happens to the Hb-O2 dissociation curve?

A. Hb affinity for O2 increases and the dissociation curves shifts to the

left
B. Hb affinity for O2 increases and the dissociation curves shifts to the
right
C. Hb affinity for O2 decreases and the dissociation curves shifts to the
left
D. Hb affinity for O2 decreases and the dissociation curves shifts to the
right
E. neither Hb affinity for O2 nor the Hb-O2 dissociation curve change

29. Compared with systemic venous blood, pulmonary arterial blood has a
higher
A. oxygen content
B. pH
C. bicarbonate ion concentration
D. Hb concentration
E. none of the above

STUDY GROUP 4

Regulation of Cardiac Output

30. If the end-diastolic ventricular volumes are increased (within physiologic

limits)
a. the stroke volume would be increased
b. cardiac output would be decreased
c. venous pressure would be decreased
d. the force of cardiac contraction would be decreased
e. the stroke volume would be decreased

31. The effect of parasympathetic nervous stimulation on the heart is

a. slowing of the heart
b. increased activity of the SA node
c. increased activity of the AV node
d. increased force of contraction
e. all of the above

32. Which of the following best describes conditions consistent with

increased contractility?
a. Increased cardiac output for a given end-systolic volume
b. Increased cardiac output for a given end-diastolic volume
c. Decreased cardiac output for a given end-systolic volume
d. Decreased cardiac output for a given end-diastolic volume

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 e. The ventricles are inexcitable for most of the contraction period

33. What role does the Frank-Starling relationship play in normal physiology
of the heart? How is it altered by sympathetic nerves?

34. True or False? Cutting the parasympathetic nerve to the heart (the
vagus nerve) causes the heart to speed up. Explain your answer.

Arterioles

35. Give: Darcy’s Law, Poiseuille's law. How do resistances combined in series
and in parallel?

36. The greatest pressure drop in the circulation occurs across the arterioles
because
a. they have the greatest surface area
b. they have the smallest diameters
c. there are many of them running in parallel
d. they are the shortest vessels
e. they have the greatest resistance

Gas Transport (contd.)

37. As blood passes through systemic capillaries, the enzyme carbonic

anhydrase catalyzes
A. conversion of dissolved CO2 to carbonic acid
B. conversion of carbonic acid to bicarbonate ion
C. conversion of gaseous CO2 to dissolved CO2
D. binding of carbon dioxide to hemoglobin, thus displacing oxygen
E. all of the above

38. An oxyhemoglobin saturation of mixed systemic venous blood of 25%

for a person at rest is
A. above normal
B. below normal
C. within the normal range

STUDY GROUP 5

Arterioles (contd.)

39. Which would cause a greater increase in resistance to flow—a doubling of

blood viscosity or a halving of tube diameter?

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40. A person is given a drug that doubles the blood flow to their kidneys but
does not change the mean arterial pressure. What must the drug be doing?

41. Which of the following locally regulate arteriolar tone?

a. Metabolite concentration in plasma
b. Blood pressure
c. Blood flow rate
d. Temperature
e. Inflammation
f. Blood clotting

42. Do arterioles receive a supply of sympathetic nerve fibers? What

neurotransmitter is released? Are arterioles innervated by parasympathetic
nerves? What effect is observed when the sympathetic neurotransmitter binds
to the alpha receptor in most vascular beds?

43. Name three organs in which the hormone adrenaline causes

vasodilatation. What is the adaptive advantage of this response? What type of
receptors does adrenaline interact with to cause this effect?

Control of Ventilation

44. If the spinal cord were cut where it joins the brain stem, what would
happen to respiration?

45. The nerves connecting the peripheral chemoreceptors to the brain are cut
in an experimental animal, and the animal then breathes a gas mixture
containing 10 percent oxygen. What changes occur in the animal’s ventilation?
What changes occur when this denervated animal is given a mixture of air
containing 21 percent oxygen and 5 percent carbon dioxide to breath?

46. Patients with severe, uncontrolled diabetes mellitus produce large

quantities of certain organic acids. Can you predict their ventilation pattern and
whether their arterial PO2 and PCO2 increase or decrease?

47. What happens to Po2 and Pco2 in the blood leaving a region of the lung
shortly after (a) ventilation is decreased or (b) perfusion is decreased?

STUDY GROUP 6

Structure of blood capillaries

48. Which of the following is not found in blood capillaries?

a. smooth muscle
b. valves
c. endothelial cells
d. basal lamina

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 e. elastin
f. tight junctions

49. Give values in nm for the following:

a. the width of a normal intercell junction over most of its length
b. the width of a tight junction
c. the diameter of a vesicle
d. the diameter of the neck of an open surface vesicle
e. the diameter of a low-density lipoprotein particle

Exchange of solutes

50. By what route would you expect the following to cross the endothelium
of a continuous capillary?
a. carbon dioxide
b. glucose
c. low-density lipoprotein (give three possibilities)

51. Is the transport of the following across the endothelium of a continuous

capillary primarily by diffusion, by advection or by neither mechanism?
a. carbon dioxide
b. glucose
c. low-density lipoprotein (give two possibilities)

52. Where would you expect to find (a) a fenestrated capillary and (b) a
discontinuous capillary. What roles do they serve?

53. Name three structural adaptations that give rise to the blood-brain
barrier. Why do they not stop you from getting drunk?

Exchange of water

54. Explain the following statement: total osmotic pressure of plasma is

much larger than the colloid osmotic pressure.

55. Give Starling’s equation for water flux across the capillary wall and
explain the terms in it.

56. What are typical values for the four pressures in Starling’s equation?
Given these pressures, if the reflection coefficient of a capillary wall is 0.9,
would you expect flow out of the capillary (Jv>0) or into the capillary (Jv<0)?

STUDY GROUP 7

Modification of exchange of solutes and water.

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57. What happens to capillary fluid pressure when the terminal arteriole
controlling blood flow into the capillary bed undergoes vasodilatation?

58. Which of the following is/are important in determining flux of oxygen from
capillaries to muscles?
a. oxygen concentration in the muscles
b. oxygen concentration in the capillaries
c. carbon dioxide concentration in the muscles
d. colloid osmotic pressure of plasma
e. hydrostatic pressure of the capillaries
f. rate of blood flow through the capillaries
g. distance from capillary to the muscle cells

Oedema

59. The tendency to form oedema will be increased by

a. arteriolar constriction
b. increased venous pressure
c. increased plasma protein concentration
d. dehydration

60. A person is accumulating oedema throughout the body. Average capillary

pressure is 25mmHg, and lymphatic function is normal. What is the most likely
cause of the oedema?

61. Which of the following might be expected to lead to pulmonary edema?

a. decrease pulmonary arterial pressure (pulmonary hypotension)
b. decrease in systemic arterial pressure (systemic hypotension)
c. decrease volume of blood in the pulmonary circulation (as in
hemorrhage)
d. increase systemic venous pressure (as in right heart failure)
e. increase pulmonary capillary permeability to plasma proteins (as in
pulmonary inflammation)

Veins

62. List 3 types of extrinsic pumping that, in combination with valves, assist
venous blood to return to the heart from parts of the body below the heart in
a walking person.

Lymph

63. What structures and pressures are involved in causing lymph flow from
the feet to return to the veins?

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Regulation of Blood Pressure

64. How do we apply the equation Q = (P 1 - P2)/R to the systemic circulation

as a whole?

65. The following data are obtained for an experimental animal before and
after a drug. Before: Heart rate = 80 beats/min and stroke volume = 80
mL/beat. After: Heart rate = 100 beats/min, and stroke volume = 64 mL/beat.
Total peripheral resistance remains unchanged. What has the drug done to
mean arterial pressure?

P D Weinberg

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