1. Cardiovascular System
Physiology
Cardiovascular System

2. Blood Flow
Mechanistic: Because the contractions of the heart produce a hydrostatic pressure gradient and the blood wants to flow to the region of lesser pressure. Therefore, the Pressure gradient (P) is main driving force for flow through the vessels
Blood Flow Rate  P/ R

3. Pressure Blood Flow Rate  P/ R
Hydrostatic pressure is in all directions
Measured in mmHg: The pressure to raise a 1 cm column of Hg 1 mm
Sphygmomanometer
Flow is produce by Driving Pressure
Pressure of fluid in motion decreases over distance because of energy loss due to friction
Blood Flow Rate  P/ R

4. Plumbing 101: Resistance Opposes Flow
3 parameters determine resistance (R):
Tube length (L)
Constant in body
Tube radius (r)
Can radius change?
Fluid viscosity ( (eta))
Can blood viscosity change??
Poiseuille’s law
R =
r4
8L 
 R  1 / r4
Blood Flow Rate  P/ R

5. Velocity (v) of Flow v = Q / A
Depends on Flow Rate and Cross-Sectional Area:
Flow rate (Q) = volume of blood passing one point in the system per unit of time (e.g., ml/min)
If flow rate   velocity 
Cross-Sectional area (A) (or tube diameter)
If cross sectional area   velocity 
v = Q / A

6. Cardiac Muscle & Heart Review heart and circulatory system anatomy
One way flow in heart is ensured by ?
Heart muscle cells:
99% contractile
1% autorrhythmic

8. Cardiac Muscle and the Heart
Myocardium
Heart muscle
Sits in the media stinum of the thoracic cavity
Left Axis Deviation
May have a right axis deviation with obesity and/or pregnancy
May hang in the middle of the thoracic cavity if the individual is very tall

10. The Heart The heart has four chambers Right and left atrium
Atria is plural
Right and left ventricle

12. Blood Flow Through the Heart
Deoxygenated blood enters the right atrium of the heart through the superior and inferior vena cava
Deoxygenated blood
Has less than 50% oxygen saturation on hemoglobin

14. Hemoglobin Quaternary Structure Four Globin proteins
Globin carries CO2, H+, PO4
Four Heme attach to each Globin
Heme binds O2 and CO
Heme contains an Iron ion
About 1 million hemoglobin molecules per red blood cell
Oxygen carrying capacity of approximately 5 minutes

15. Heart Valves Ensure One-Way Flow of Blood in the Heart
Atrioventricular Valves
Located between the atria and the ventricle
Labeled Right and Left
Right Valve is also called Tricuspid
Left Valve is also called Bicuspid or Mitral

16. Heart Valves Papillary muscles are attached to the chordae tendinae
Chordae tendinae are also connected to the AV valves
Just prior to ventricular contraction the papillary muscles contract and pull downward on the chordae tendinae
The chordae tendinae pull downward on the AV valves
This prevents the valves from prolapsing and blood regurgitating back into the atria.

17. Follow Path of Blood through Heart

18. Blood Flow
Due to gravity deoxygenated blood enters the right/left atrium (by way of the pulmonary veins) and flows through the open AV valve directly into the ventricles
The filling of the ventricles with blood pushes the AV valve upward
They are held in place by the chordae tendinae
Right before the valves shuts completely the atria contract from the base towards the apex of the heart in order to squeeze more blood into the ventricle
The AV valves snapping shut creates the “Lub” sound of the heart beat

19. Blood Flow
When the AV valves are shut the Pulmonary and Aortic semi-lunar valves are also shut
Diastole
Quiescence of the heart

20. Myocardial Contraction (Systole)
After Diastole occurs the ventricles begin to contract from the apex towards the base of the heart
The deoxygenated blood on the right side of the heart is pushed through the pulmonary trunk after opening the semi-lunar valve to the pulmonary arteries into the lungs to become oxygenated.
The oxygenated blood on the left side of the heart is pushed through the aorta after opening the semi-lunar valve into the systemic circulation

21. Blood Flow
The Ventricles do not have enough pressure to push all of the blood out of the pulmonary trunk and aorta
The blood falls back down due to gravity
The semi-lunar valves snap shut
The “Dup” sound of the heart beat

22. Blood Flow
Blood is always flowing from a region of higher pressure to a region of lower pressure

23. Atrial and Ventricular Diastole
The heart at rest
The atria are filling with blood from the veins
The ventricles have just completed contraction
AV valves are open
Blood flow due to gravity

24. Atrial Systole: Completion of Ventricular Filling
The last 20% of the blood fills the ventricles due to atrial contraction

26. Early Ventricular Contraction
As the atria are contracting
Depolarization wave moves through the conducting cells of the AV node down to the Purkinje fibers to the apex of the heart
Ventricular systole begins
AV Valves close due to Ventricular pressure
First Heart Sound
S1 = Lub of Lub-Dup

27. Isovolumic Ventricular Contraction
AV and Semilunar Valves closed
Ventricles continue to contract
Atrial muscles are repolarizing and relaxing
Blood flows into the atria again

28. Ventricular Ejection
The pressure in the ventricles pushes the blood through the pulmonary trunk and aorta
Semi-lunar valves open
Blood is ejected from the heart

29. Ventricular Relaxation and Second Heart Sound
At the end of ventricular ejection
Ventricles begin to repolarize and relax
Ventricular pressure decreases
Blood falls backward into the heart
Blood is caught in cusps of the semi-lunar valve
Valves snap shut
S2 – Dup of lub-dup

32. Isovolumetric Ventricular Relaxation
Semilunar valves close
AV valves closed
The volume of blood in the ventricles is not changing
When ventricular pressure is less than atrial pressure the AV valves open again
The Cardiac Cycle begins again

34. Cardiac Circulation
Blood flowing through the heart has a high fat content
Curvature as well as diameter of the arteries is important to blood flow through the heart
Vasoconstriction due to sympathetic nervous system input
Norepinephrine/Epinephrine
Alpha Receptors not Beta

35. Myocardial Infarction
Heart Attack
Due to plaque build up in the arteries
Decrease in blood flow to myocardium
Depolarization of muscle cannot occur due to myocardial death
Myocardium doesn’t work as a syncytium any longer
Destruction of gap junction or “connexons”

36. Atherosclerosis Plaque in the arteries
Elevated Cholesterol in the blood
Cholesterol is cleared by the liver
HDL – High Density Lipoprotein
H for healthy
LDL – Low Density Lipoprotein
L for Lethal
Omega 3 fatty acids
“Rotorooter” for the arteries

37. If a Patient Has a Left Atrial Infarction Then
What happens to heart contraction and blood flow through the heart?
What type of outward problems might your patient have?
What recommendations might you give the patient to live a better life?
There are some things they better not do or they will die. What are these things (in general)?

38. Angioplasty/Open Heart Surgery

39. Unique Microanatomy of Cardiac Muscle Cells
1% of cardiac cells are autorhythmic
Signal to contract is myogenic
Intercalated discs with gap junctions and desmosomes
Electrical link and strength
SR smaller than in skeletal muscle
Extracelllar Ca2+ initiates contraction (like smooth muscle)
Abundant mitochondria extract about 80% of O2

40. Cardiac Muscle Cells Contract Without Nervous Stimulation
Autorhythmic Cells
Pacemaker Cells set the rate of the heartbeat
Sinoatrial Node
Atriventricular Node
Distinct from contractile myocardial cells
Smaller
Contain few contractile proteins

41. Excitation-Contraction (EC) Coupling in Cardiac Muscle
Contraction occurs by same sliding filament activity as in skeletal muscle
some differences:
AP is from pacemaker (SA node)
AP opens voltage-gated Ca2+ channels in cell membrane
Ca2+ induces Ca2+ release from SR stores
Relaxation similar to skeletal muscle
Ca2+ removal requires Ca2 -ATPase (into SR) & Na+/Ca2+ antiport (into ECF)
[Na+] restored via?

42. Cardiac Contraction Action Potentials originate in Autorhythmic Cells
AP spreads through gap junction
Protein tunnels that connect myocardial cells
AP moves across the sarcolemma and into the t-tubules
Voltage-gates Ca +2 channels in the cell membrane open
Ca +2 enters the cell which then opens ryanodine receptor-channels
Ryanodine receptor channels are located on the sarcoplasmic reticulum and Ca +2 diffuses into the cells to “spark” muscle contraction
Cross bridge formation and contraction occurs

43. Myocardial Contractile Cells
In the myocardial cells there is a lengthening of the action potential due to Ca +2 entry

44. AP’s in Contractile Myocardial Cells
Phase 4: Resting Membrane Potential is -90mV
Phase 0: Depolarization moves through gap junctions
Membrane potential reaches +20mV
Phase 1: Initial Repolarization
Na+ channels close; K + channels open
Phase 2: Plateau
Repolarization flattens into a plateau due to
A decrease in K + permeability and an increase in Ca +2 permeability
Voltage regulated Ca +2 channels activated by depolarization have been slowly opening during phases 0 and 1
When they finally open, Ca +2 enter the cell
At the same time K + channels close
This lengthens contraction of the cells
AP = 200mSec or more
Phase 3: Rapid Repolarization
Plateau ends when Ca +2 gates close and K + permeability increases again

45. Myocardial Autorhythmic Cells
Anatomically distinct from contractile cells – Also called pacemaker cells
Membrane Potential = – 60 mV
Spontaneous AP generation as gradual depolarization reaches threshold
Unstable resting membrane potential (= pacemaker potential)
The cell membranes are “leaky”
Unique membrane channels that are permeable to both Na+ and K+

46. Myocardial Autorhythmic Cells, cont’d. If-channel Causes Mem. Pot
Myocardial Autorhythmic Cells, cont’d. If-channel Causes Mem. Pot. Instability
Autorhythmic cells have different membrane channel: If - channel
If channels let K+ & Na+ through at -60mV
Na+ influx > K+ efflux
slow depolarization to threshold
allow current
(= I ) to flow
f = “funny”:
researchers didn’t
understand initially

47. AP Myocardial Autorhythmic Cells, cont’d.
“Pacemaker potential” starts at ~ -60mV, slowly drifts to threshold AP
Heart Rate = Myogenic
Skeletal Muscle contraction = ?

48. Channels involved in APs of Cardiac Autorhythmic Cells
Myocardial Autorhythmic Cells, cont’d.
Channels involved in APs of Cardiac Autorhythmic Cells
Slow depolarization due to If channels
As cell slowly depolarizes: If -channels close & Ca2+ channels start opening
At threshold: lots of Ca2+ channels open  AP to + 20mV
Repolarization due to efflux of K+

49. Autorhythmic Cells No nervous system input needed
Unstable membrane potential
-60mV
Pacemaker potential not called resting membrane potential
At -60mV If (funny) channels permeable to K + and Na + open
Na + influx exceed K + efflux
The net influx of positive charge slowly depolarizes the autorhythmic cells
As the membrane becomes more positive the If channels gradually close and some Ca +2 channels open
The influx of Ca +2 continues the depolarization until the membrane reaches threshold
At threshold additional Ca +2 channels open
Calcium influx creates the steep depolarization phase of the action potential
At the peak of the action potential Ca +2 channels close and slow K+ channels open
Repolarization of the autorhythmic action potential is due to the efflux of K +

50. Cardiac Muscle Cell Contraction is Graded
Skeletal muscle cell: all-or-none contraction in any single fiber for a given fiber length. Graded contraction in skeletal muscle occurs through?
Cardiac muscle:
force  to sarcomere length (up to a maximum)
force  to # of Ca2+ activated crossbridges (Function of intracellular Ca2+: if [Ca2+]in low  not all crossbridges activated)

51. Length Tension Relationship

53. Autonomic Neurotransmitters Modulate Heart Rate
The speed at which pacemaker cells depolarize determines the rate at which the heart contracts
The interval between action potentials can be altered by changing the permeability of the autorhythmic cells to different ions
Increase Na + and Ca +2 permeability speeds up depolarization and heart rate
Decrease Ca +2 permeability of increase K + permeability slow depolarization and slows heart rate

55. Autonomic Neurotransmitters Modulate Heart Rate
The Catecholamines: norepinephrine and epinephrine increases ion flow through If and Ca+2 channels
More rapid cation entry speeds up the rate of the pacemaker depolarization
Β1-adrenergic receptors are on autorhythmic cells
cAMP second messenger system causes If channels to remain open longer

56. Autonomic Neurotransmitters Modulate Heart Rate
Parasympathetic neurotransmitter (Acetylcholine) slows heart rate
Ach activates muscarinic cholinergic receptors that
Increase K+ permeability and
Decrease Ca+2 permeability

57. Electrical Conduction in the Heart Coordinates Contraction
Action potential in an autorhythmic cell
Depolarization spread rapidly to adjacent cells through gap junctions
Depolarization wave is followed by a wave of contraction across the atria from the sinoatrial node on the right side of the heart across to the left side of the heart and then from the base to the apex
From AV nodes to the atrioventricular bundle in the septum (Bundle of His)
Left and right bundle branches to the apex
Purkinje Fibers through the ventricles branches from apex to base and stopping at the atrioventricular septum

58. Pacemakers Set the Heart Rate
SA Node is the fastest pacemaker
Approximately 72 bpm
AV node approximately 50 bpm
Bundle Branch Block
Complete Heart Block

60. Electrocardiogram Einthoven’s triangle
Electrodes are attached to both arms and left leg to form a triangle
Lead I- negative electrode attached to right arm
Lead II – positive electrode attached to left arm
Lead III – Ground attached to the left leg

62. Electrocardiogram ECG (EKG)
Surface electrodes record electrical activity deep within body - How possible?
Reflects electrical activity of whole heart not of single cell!
EC fluid = “salt solution” (NaCl)  good conductor of electricity to skin surface
Signal very weak by time it gets to skin
ventricular AP = ? mV
ECG signal amplitude = 1mV
EKG tracing =  of all electrical potentials generated by all cells of heart at any given moment

63. ECG P wave QRS complex T wave Depolarization of the atria
Atrial contraction begins almost at the end of the P wave
QRS complex
Ventricular depolarization
Ventricular contraction begins just after the Q wave and continues through the T wave
T wave
Ventricular repolarization

64. ECG PQ or PR segment Q wave R wave
Conduction through AV node and AV bundle
Q wave
Conduction through bundle branches
R wave
Conduction beginning up the Purkinje Fibers
S wave Conduction continue up half way
ST segment
Conduction up the second half of Ventricles

65. ECG
When an electrical wave moving through the heart is directed toward the positive electrode, the ECG waves goes up from the baseline
If net charge movement through the heart is toward the negative electrode, the wave points downward

67. Einthoven’s Triangle and the 3 Limb Leads:RA LA LL I II
III – +

68. Why neg. tracing for depolarization ?? - electrode EKG tracing goes
Net electrical current
in heart moves towards
+ electrode
EKG tracing goes
up from baseline
Net electrical current in
heart moves towards
- electrode
EKG tracing goes
Down from baseline

69. Info provided by EKG: HR Rhythm Relationships of EKG components
each P wave followed by QRS complex?
PR segment constant in length? etc. etc.

70. For the Expert:
Find subtle changes in shape or duration of various waves or segments.
Indicates for example:
Change in conduction velocity
Enlargement of heart
Tissue damage due to ischemia (infarct!)

71. Prolonged QRS complex
Injury to AV bundle can increase duration of QRS complex (takes longer for impulse to spread throughout ventricular walls).

72. Heart Sounds (HS)
1st HS: during early ventricular contraction  AV valves close
2nd HS: during early ventricular relaxation  semilunar valves close

73. Gallops, Clicks and Murmurs
Turbulent blood flow produces heart murmurs upon auscultation