Cardiovascular Physiology 31.1.23. or pptx

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1. Cardiovascular Physiology

2. CARDIAC VOLUMES Stroke Volume: The volume of blood pumped with each heartbeat it is determined by Preload: gives the volume of blood that the ventricle has available to pump Contractility : the force that the muscle can create at the given length Afterload : the arterial pressure against which the muscle will contract. SV=EDV-ESV EDV (End Diastolic Volume)- amount of blood collected in a ventricle during diastole ESV(End Systolic Volume)- amount of blood remaining in a ventricle after contraction Ejection fraction: the fraction of EDV pumped with each heart beat EF=SV/EDV

3. Preload Preload is the ventricular load at the end of diastole, before contraction has started. First described by Starling, a linear relationship exists between sarcomere length and myocardial force.

4. Frank-Starling Relationship Frank-Starling relationship. The relationship between sarcomere length and tension developed in cardiac muscles is shown. In the heart, an increase in end-diastolic volume is the equivalent of an increase in myocardial stretch; T herefore, according to the Frank-Starling law, increased stroke volume is generated.

5. Frank-Starling Relationship The Frank-Starling relationship is an intrinsic property of myocardium by which stretching of the myocardial sarcomere results in enhanced myocardial performance for subsequent contractions Heart muscle expands to maximum during filling. Maximal length produces maximum tension on the muscle, resulting in forceful contraction. Therefore, greater filling (more volume entering the heart) produces greater ejection (more volume leaving).

6. FRANK STARLING PRINCIPLE CONT… A family of Frank-Starling curves is shown. A leftward shift of the curve denotes enhancement of the inotropic state, whereas a rightward shift denotes decreased inotropy

7. LAPLACE LAW σ =P×R/2h σ- wall stress P- Pressure R- radius of the ventricle h – thickness of the ventricle Wall stress and heart rate are probably the two most relevant factors that account for changes in myocardial oxygen demand Ellipsoid shape is responsible for the least amount of stress,therefore when the shape changes to spherical during contraction, the wall stress increases.

8. In response to aortic stenosis , left ventricular (LV) pressure increases. To maintain wall stress at control levels, compensatory LV hypertrophy develops. Therefore, the increase in wall thickness offsets the increased pressure, and wall stress is maintained at control levels

9. CARDIAC OUTPUT Cardiac output is the amount of blood pumped by the heart per unit of time. It determined by four factors: Two factors that are intrinsic to the heart heart rate and myocardial contractility Two factors that are extrinsic to the heart preload and afterload

10. Measurement of cardiac output Invasive methods Fick’s method Dye dilution method

11. Cardiac output in a living organism can be measured with the Fick’s principle If the oxygen (O2) concentration in pulmonary arterial blood (CpaO2), the O2 concentration of the pulmonary vein (CpvO2), and the O2 consumption are known, then cardiac output can be calculated. pa, Pulmonary artery; pv , pulmonary vein

12. The Fick principle is based on the concept of conservation of mass such that the O2 delivered from pulmonary venous blood (q3) is equal to the total O2 delivered to pulmonary capillaries through the pulmonary artery (q1) and the alveoli (q2).

13. The amount of O2 delivered to the pulmonary capillaries by way of the pulmonary arteries (q1) equals total pulmonary arterial blood flow (Q) times the O2 concentration in pulmonary arterial blood (CpaO2): q1 =Q × CpaO2 The amount of O2 carried away from pulmonary venous blood (q3) is equal to total pulmonary venous blood flow (Q) times the O2 concentration in pulmonary venous blood (CpvO2): q3 =Q × CpvO2

14. q1+q2=q3 Q(CpaO2)+q2=Q(CpvO2) q2=Q{CpvO2-CpaO2) Q=q2/(CpvO2-CpaO2) Thus, if the CpaO2, CpvO2, and O2 consumption (q2) are known, then the cardiac output can be determined.

15. Indicator Dilution Method for Measuring Cardiac Output A dye is injected into a large systemic vein or, preferably, into the right atrium. This passes rapidly through the right side of the heart, then through the blood vessels of the lungs, through the left side of the heart, and, finally, into the systemic arterial system . The concentration of the dye is recorded as the dye passes through one of the peripheral arteries

16. Extrapolated dye concentration curves  used to calculate two separate cardiac outputs by the dilution method. ( The rectangular areas are the calculated average concentrations of dye in the arterial blood for the durations of the respective extrapolated curves.)

17. A total of 5 mg of dye had been injected at the beginning.  A verage concentration of dye was 0.25 mg/dl of blood Duration of this average value was 12 seconds. CO= 5X60/ 0.25X12 =10L/min

18. EXTRINSIC INNERVATION OF THE HEART Afferents: SYMPATHETIC - the paired superior, middle and inferior cardiac nerves from the cervical ganglia and those originating from the upper 4-5 thoracic ganglia PARASYMPATHETIC - the paired vagi Form the cardiac plexus Efferents : Through the C fibres , to the white rami , to bulbar center Responsible for perception of cardiogenic pain. Through Glossopharyngeal and Vagus nerves

19. NEURAL REGULATION OF CARDIAC FUNCTION The two limbs of the autonomic nervous system provide opposing input to regulate cardiac function.

20. The neurotransmitter of the parasympathetic nervous system is acetylcholine . Parasympathetic innervation of the heart is through the vagal nerve . The principal parasympathetic target neuroeffectors are the muscarinic receptors in the heart. Activation of muscarinic receptors reduces pacemaker activity, slows AV conduction, directly decreases atrial contractile force, and exerts inhibitory modulation of ventricular contractile force

21. The neurotransmitter of the sympathetic nervous system is norepinephrine . Norepinephrine released from sympathetic nerve terminals stimulates adrenergic receptors located in the heart. The two major classes of ARs are α and β Sympathetic receptors: All types of β receptors are found in the human heart. β 1 receptors are the predominant subtype in heart(both atria and ventricles) β 2 – atria>ventricles β 3- ventricles β-AR stimulation increases both contraction and relaxation

22. The two major subpopulations of α-ARs are α1 and α2. - α₁ receptors- α₁ A, α₁ B, and α₁ D subtypes Both α₁ A and α₁ B are positive inotropic Cardiac hypertrophy is primarily mediated by α₁ A ARs - α₂ receptors- Three subtypes α₂ A, α₂B and α₂C . Presynaptic inhibition of NE release

23. HORMONAL REGULATION Cardiac hormones: Polypeptides secreted by cardiac tissues Natriuretic peptides Adrenomedullin Angiotensin II Aldosterone Natriuretic peptides: Atrial natriuretic protein- secreted from the atria B-type natriuretic peptide- from the venttricles Generate cGMP Cardiac endocrine response to pressure or volume overload Organogenesis of the embryonic heart and CVS In patients with chronic heart failure, increases of serum ANP and BNP levels are a predictor of mortality

24. Adrenomedullin is a recently discovered cardiac hormone that was originally isolated from pheochromocytoma tissue. Positive inotropic and positive chronotropic Increase NO- potent vasodilator Angiotensin II- key modulator of cardiac growth and function Two receptors- AT₁ and AT₂ AT₁ Predominant subtype Positive chronotropic and inotropic Cell growth and proliferation of myocytes and fibroblasts Activation of AT1 receptors is directly involved in the development of cardiac hypertrophy and heart failure AT₂ Antiproliferative Most abundant in fetal heart Upregulated in response to injury and ischemia

25. CARDIAC REFLEXES Cardiac reflexes are fast-acting reflex loops between the heart and the central nervous system (CNS) that contribute to -Regulation of cardiac function and - M aintenance of physiologic homeostasis. Specific cardiac receptors elicit their physiologic responses by various pathways.

26. Cardiac receptors are linked to the CNS by myelinated or unmyelinated afferent fibers that travel along the vagus nerve. Cardiac receptors are in the atria, ventricles, pericardium, and coronary arteries. Extracardiac receptors are located in the great vessels and carotid artery.

27. Reflexes Baroreceptor Reflex Chemoreceptor Reflex Brain Bridge Reflex Bezold-Jarisch Reflex Valsalva Maneuver Cushing Reflex Occulocardiac Reflex

28. Baroreceptor Reflex (Carotid Sinus Reflex) The baroreceptor reflex is responsible for maintenance of arterial blood pressure. Changes in arterial blood pressure are monitored by circumferential and longitudinal stretch receptors located in the carotid sinus and aortic arch . The nucleus solitarius , located in the cardiovascular center of the medulla, recieves the impulse from these stretch receptors through afferent glossopharyngeal and vagus nerves.

29. The cardiovascular center in medulla consists of two functionally different areas; LATERALLY & ROSTRALLY - This area is responsible for increasing blood pressure CENTRALLY & CAUDALLY - This area is responsible for lowering arterial blood pressure. Typically, the stretch receptors are activated if systemic blood pressure is greater than 170 mm of Hg

30. The response from depressor system includes decreased sympathetic activity, leading to decrease in cardiac contractility, heart rate and vascular tone. In addition, activation of the parasymapathetic system further decreases the heart rate, myocardial contractility. Reverse effects are elicited with the onset of hypotension

31. The baroreceptor reflex plays an important beneficial role during acute blood loss and shock. However, the reflex arch loses its functional capacity when arterial blood pressure is less than 50 mm Hg

32. CHEMORECPTOR REFLEX Chemosensitive cells are located in the carotid bodies and the aortic body. These cells respond to changes in pH status and blood O2 tension

33. At PaO2 < 50 mm Hg or in acidosis Chemoreceptors send impulses along the sinus nerve of Hering (a branch of the glossopharyngeal nerve) and the tenth cranial nerve to the chemosensitive area of the medulla. This area responds by S timulating the respiratory centers and thereby increasing ventilatory drive. A ctivation of the parasympathetic system ensues and leads to a reduction in heart rate and myocardial contractility .

34. Bainbridge Reflex

35. BEZOLD- JARISCH REFLEX The Bezold-Jarisch reflex responds to noxious ventricular stimuli

36. Because it invokes bradycardia , the Bezold-Jarisch reflex is thought of as a cardioprotective reflex. This reflex has been implicated in the physiologic response to a range of cardiovascular conditions such as myocardial ischemia or infarction, thrombolysis , or revascularization and syncope.

37. Valsalva Maneuver

38. Cushing Reflex

39. Oculocardiac Reflex

40. The incidence of this reflex during ophthalmic surgery ranges from 30% to 90%. Administration of an antimuscarinic drug such as glycopyrrolate or atropine reduces the incidence of bradycardia during eye surgery

41. THE CARDIAC MUSCLE Myocardium has three types of muscle fibers : Cardiac muscles forming the walls of the atria and ventricles (contractile unit of the heart). Muscle fibres forming the pacemaker which is the site of origin of cardiac impulse . Muscle fibres forming the conducting system which transmits the impulse to the various parts of the heart

42. Muscle Fibres which Form the Contractile unit Cardiocytes are 10-20 micrometers in diameter and 50-100 micrometers in length. Cardiac muscle fibers are striated and involuntary Sarcomere of the cardiac muscle has all the contractile proteins, namely actin , myosin, troponin and tropomyosin . Cardiocytes have a single nucleus and are short, thick, and branched.

43. Exhibit branching Adjacent cardiac cells are joined end to end by specialized structures known as - intercalated discs Within intercalated discs there are two types of junctions — Desmosomes - to provide additional support and stability for the cardiac muscle fibers. — Gap junctions that allow action potential to spread from one cell to adjacent cells

44. Contain Large Mitochondria Mechanism of contraction is similar to skeletal muscle cells. Cardiac muscle is oxygen dependant, receives oxygen from blood in coronary arteries. Can use various organic fuels; fatty acids, glucose, ketones , and lactic acid. Fatigue resistant- beats continuously from early embryonic stage to death.

45. Heart function as syncytium When one cardiac cell undergoes an action potential, the electrical impulse spreads to all other cells that are joined by gap junctions so they become excited and contract as a single functional syncytium. Atrial syncytium and ventricular syncytium

46. Orientation of cardiac muscle fibres: Unlike skeletal muscles, cardiac muscles have to contract in more than one direction. Cardiac muscle cells are striated, meaning they will only contract along their long axis. In order to get contraction in two axis, the fibres wrap around.

47. Cardiac Action Potential Action potential in heart initiated by group of specialized cells called SA node. Cardiac action potential is a brief changes in voltage(membrane potential) across the cell membrane of the heart cells. This is caused by movement of charged ions between the inside and outside of the cell through protein called ion channels.

48. SPREAD OF ACTION POTENTIAL THROUGH CARDIAC MUSCLE Action potential spreads through cardiac muscle very rapidly because of the presence of gap junctions between the cardiac muscle fibers. Gap junctions are permeable junctions and allow free movement of ions and so the action potential spreads rapidly from one muscle fiber to another fiber.

49. ii) Muscle fibres forming the pacemaker Some of the muscle fibres of heart are modified into a specialized structure known as pacemaker. These muscle fibres forming the pacemaker have less striation. They are named pacemaker cells or P cells. Sino-atrial (SA) node forms the pacemaker in human heart.

50. Action Potential Depolarization starts very slowly and the threshold level of –40 mV is reached very slowly. After the threshold level, rapid depolarization occurs up to +5 mV. It is followed by rapid repolarization . Once again, the resting membrane potential becomes unstable and reaches the threshold level slowly

51. Depolarization When the negativity is decreased to –40 mV, which is the threshold level, the action potential starts with rapid depolarization. The depolarization occurs because of influx of more calcium ions

52. Repolarization After rapid depolarization, repolarization starts. It is due to the efflux of potassium ions from pacemaker fibers. Potassium channels remain open for a longer time, causing efflux of more potassium ions. It leads to the development of more negativity, beyond the level of resting membrane potential. It exists only for a short period. Then, the slow depolarization starts once again, leading to the development of pacemaker potential, which triggers the next action potential.

53. CONTRACTILITY CONTRACTILITY „- Contractility is ability of the tissue to shorten in length (contraction) after receiving a stimulus. Following are the contractile properties: ALL-OR-NONE LAW „ STAIRCASE PHENOMENON „ SUMMATION OF SUBLIMINAL STIMULI „ REFRACTORY PERIOD

54. ALL-OR-NONE LAW According to all-or-none law , when a stimulus is applied, whatever may be the strength, the whole cardiac muscle gives maximum response or it does not give any response at all. Below the threshold level, i.e. if the strength of stimulus is not adequate, the muscle does not give response Cause for All-or-none law All-or-none law is applicable to whole cardiac muscle. It is because of syncytial arrangement of cardiac muscle.

55. First, one stimulus is applied with a strength of 1 volt and the contraction is recorded. Then, after 20 seconds, the strength is increased to 2 volt and the contraction is recorded. The procedure is repeated by increasing the strength every with an interval of 20 seconds Amplitude of all contractions remains same , irrespective of increasing the strength of stimulus. This shows that cardiac muscle obeys all-or-none law

56. STAIRCASE PHENOMENON or TREPPE PHENOMENON When the ventricle is stimulated at a interval of 2 seconds, without changing the strength, the force of contraction increases gradually for the first few contractions and then it remains same. Gradual increase in the force of contraction is called staircase phenomenon.

57. SUMMATION OF SUBLIMINAL STIMULI When a stimulus with a subliminal strength is applied, the quiescent heart does not show any response. When few stimuli with same subliminal strength are applied in succession, the heart shows response by contraction, due to the summation of stimuli.

58. REFRACTORY PERIOD Refractory period is the period in which the muscle does not show any response to a stimulus. It is of two types: 1. Absolute refractory period 2. Relative refractory period.

59. Absolute Refractory Period Absolute refractory period is the period during which the muscle does not show any response at all, whatever may be the strength of the stimulus. It is because, the depolarization occurs during this period. So, a second depolarization is not possible. Relative Refractory Period Relative refractory period is the period during which the muscle shows response if the strength of stimulus is increased to maximum. It is the stage at which the muscle is in repolarizing state.

60. Refractory Period in Cardiac Muscle Cardiac muscle has a long refractory period compared to skeletal muscle. Absolute refractory period extends throughout the contraction period of cardiac muscle and its duration is 0.27 sec. Relative refractory period extends during first half of relaxation period, which is about 0.26 sec. So, the total refractory period is 0.53 sec.

61. Refractory period in beating heart When the stimulus is applied during systole, the heart does not show any response. It is because the absolute refractory period extends throughout systole

62. When a stimulus is applied during diastole, the heart contracts because, diastole is the relative refractory period. This contraction is called extrasystole or premature contraction . Extrasystole is followed by the stoppage of heart in diastole for a while. Temporary stoppage of the heart before it starts contracting is called compensatory pause.

63. Refractory period in quiescent heart When two stimuli are applied successively in such a way that the second stimulus falls during contraction period , the heart contracts only once. It is because of the first stimulus. There is no response to second stimulus because systole is the absolute refractory period .

64. However, when a second stimulus is applied during diastole, the heart contracts again and second contraction superimposes over the first one. This shows that the relative refractory period extends during diastole

65. Frank-Starling Relationship The Frank-Starling relationship is an intrinsic property of myocardium by which stretching of the myocardial sarcomere results in enhanced myocardial performance for subsequent contractions Heart muscle expands to maximum during filling. Maximal length produces maximum tension on the muscle, resulting in forceful contraction. Therefore, greater filling (more volume entering the heart) produces greater ejection (more volume leaving).