cardiovascular physiology based on Ganong's

CVS physiology, all details with explanation easy to recall physiology of cardiovascular system. based on Ganong's Review of Medical Physiology. all the high-yield facts are there.

1. Cardiovascular system

2. Rt Atrium Rt.Vent T.C P.V P.A L. Atrium L. Vent Aorta Mitral v Aortic v Valves open and close in response to pressure gradients across the leaflets If proximal P > distal P → valve opens If distal P > proximal P → valve closes

3. Cardiac Cycle

4. Late diastole The ventricles are relaxed – Filled – blood Mitral valve had open allow ventricular filling But Vent. End diastolic P low 2-10 end diastolic volume 130ml Still the Aortic P is greater than vent. pressure - So Aortic valve remained closed

5. Needs building up of aortic pressure A - V valve close - First Ht sound Isovoluemic contraction The energy of ventricular contraction is used to raise intraventricular pressure. From a low filling pressure to a high ejection pressure Systole The rising intraventricular pressur , Eventually equals aortic pressure AV opens and end the isovoluemic contraction →Blood is ejected in to the outflow tract Rapid ejection phase and Slower later →About 70ml of blood is ejected – Stroke Volume

6. Iso volumic relaxation Ventricle relaxation remits in a rapid fall intra luminal pressure. Aortic pressure falls but elastic result ensures it falls more slowly. Arterial pressure exeeds ventricular pressure and the aortic valve closes. ---- 2 nd Ht sound Aortic valve closure results in a ware of pressure down the arterial free – diacrotic notch. Ventricular again closed → and it relaxes- Isovolumic relaxation.

7. Early diastole Atrial systole Small transient rise of left atrial pressure and left ventricle pressure Small amount of blood = 5 ml ejected into the left ventricle Atrial systole is not important cause of ventricular filling on the bulk of filling has already occurred

8. Heart sound 1 st sound – associated with Isovolumic contraction 2 nd sound – associated with Isovolumic relaxation Cardiac murmurs Abnormal 1 sounds – either with stenosi or incompetence Systolic murmur - Aortic / Palm . Stenosis mitral / T C reg. Diastolic murmur – Mitral / T C - stenosis Aortic/ palm - regurg

9. Cardiac Cycle Note the 7 phases separated by vertical lines. The ECG is used in general as an event marker

10. Cardiac Cycle Atrial systole Is preceded by the P wave (electrical activation of atria) Contributes to ventricle filling Produce the a wave of the JVP 2. Isovolumetric contraction Begins after the onset of the QRS of the ECG When ventricle pressure exceeds that of the atria, AV valves close producing the 1 st heart sound Ventricular pressure increases isovolumetrically while all four valves are closed c wave of the JVP occurs due to high ventricular pressure

11. Cardiac Cycle 3. Rapid ventricular ejection When ventricle pressure exceeds aortic pressure, aortic valve open Rapid ejection of blood to aorta occurs Most of the stroke volume is ejected during this phase Same time, atrial filling begins. T wave of the ECG occurs and the ventricles start repolarising Reduced ventricular ejection Blood continues to be ejected slowly Both ventricular and aortic pressure starts dropping Atrial filling continues

12. Cardiac Cycle 5. Isovolumetric ventricular relaxation Repolarisation of ventricle is now complete Semilunar valves close and the 2 nd heart sound occur All 4 valves are closed while the ventricle relaxes – causing a rapid drop in pressure Dicrotic notch in the aortic pressure occur When ventricle pressure becomes lower than the atrial pressure mitral valve opens v wave of the JVP occur at the end due to atrial filling 6. Rapid ventricular filling Mitral valve open and ventricle fill from the atria rapidly

13. Cardiac Cycle Reduced ventricular filling (diastasis) Longest phase of the cardiac cycle Ventricle fill at a slower rate The time for this varies with the heart rate

14. Jugular venous pulse 3 pulsation – Pressure changes in Right a tria a - A trial systole. c - onset of ventricular sys. – cusp bulging. v - the end of ventricular systole

15. Vascular system

16. Humans have Parallel vascular arrangement which is important. Flow in different capillary beds can be selectively altered Flow to vital organs can maintained at expense of other organs Constriction of a significant fraction of capillary bed can Increase total peripheral resistance This is not possible if the pumps are in series

17. Arteries Thick walled, extensive elastic tissue & smooth muscle Under high pressure The blood volume contained in them are called the stressed volume Arterioles Smallest branches of the arteries Site of highest resistance in the cardiovascular system Have smooth muscle walls which have extensive autonomic innervation  1 adrenergic - in the skin and splanchnic arterioles Β 2 adrenergic – in the skeletal muscle arterioles Components of the vasculature

18. Capillaries Have the largest cross sectional surface area Consist of a single layer of cells – thin walled Are the site of exchange of nutrients, water & gases Venules Are formed from merged capillaries Components of the vasculature

19. Veins Progressively forms larger and larger veins Are thin walled Are under low pressure Contains the highest proportion of the blood in the cardiovascular system Blood volume in the veins is called the unstressed volume Are innervated by autonomic fibres Components of the vasculature

20. Cross sectional profile of the vessels Cross sectional area is greatest in capillaries Arteries – Pressure varies bet. Sys. and diastole Largest –pressure drop recorded at - arterioles Site where flow can be regulated

21. Velocity of blood flow Can be expressed by: V = Q / A v = velocity (cm/sec) Q = blood flow (ml/min) A = cross sectional area (cm 2 ) Therefore, velocity is higher in the aorta (smaller cross sectional area) is lower in all the capillaries – Why ?

22. Mean velocity of blood flow – lowest on the capillaries To maximize the exchange of substances

23. Blood flow Can be expressed by: Q = ∆P / R Q = blood flow (ml/min) ∆P = pressure gradient (mmHg) R = resistance Δ P = Mean arterial pressure MAP and Right atrial pressure –CVP Cardiac Mean arterial Right atrial output = pressure - pressure Total peripheral resistance

24. Cardiac Output Is the volume of blood ejected from each ventricle per minute Expressed by the following: CO = SV x HR Cardiac output of a 70 kg man is about 5L

25. Stroke volume Is the volume of blood ejected from each ventricle on each beat Expressed by the following: Stroke volume = EDV – ESV Normally is about 70 ml (as EDV = 140 ml & ESV = 70 ml) SV = (~2 x pulse pressure)

26. Cardiac Index Expressed by the following: cardiac index = CO / body surface area Gives a correct estimation of the cardiac output depending on the size of the person

27. Ejection fraction Is the fraction of end-diastolic volume ejected in each stroke volume Is normally 0.55 or 55% Is expressed by the following equation: Ejection fraction = SV End-diastolic volume

28. Stroke work Is the work the heart performs on each beat Is expressed by; Stroke work = Aortic pressure x Stroke volume Fatty acids are the primary energy source for stroke work

29. Myocardial oxygen consumption Is directly related to the amount of tension developed by the ventricles It is increased by: increased afterload (aortic pressure) Increased size of the heart (Laplace’s law) Increased contractility Increased heart rate

30. Control of cardiac output Cardiac output Heart Rate Pre Load Myocardial contraction After load 4 factors determine cardiac output

31. Staring law of the heart “ The energy of cardiac contraction is depended on the resting length of the cardiac muscle fibre” “ When stretch more contract more” Explains how heart matches input ( VR) to output (C.O) Also how Cardiac output of Right and Left Ht are equalized to p revent congestion This is an intrinsic function of the heart But alsoThis leads to increase or decrease cardiac function at constant diastolic volumes

32. Frank-Starling relationship describes the increase in stroke volume that occurs in response to an increase in venous return (or end-diastolic volume) Length-tension relationship in the ventricles Force of contraction Left Ventricular End diastolic Volume

33. Preload is equivalent to end-diastolic volume It is related to the right atrial pressure Increase will increase the force of contraction (Frank-Starling relationship) 2. Afterload For the left ventricle = aortic pressure For the right ventricle = pulmonary arterial pressure Increase of these pressures will increase the afterload Length-tension relationship in the ventricles

34. Venous return: ΔP = flow x Resistance Rise of the venous Pressure leads to more Venous Return Right Atrial pressure Veins

35. Venous Return RAP

36. MSFP is increased by – increased blood volume or decreased venous compliance MSFP is decreased by – decreased blood volume or increased venous compliance Cardiac & vascular function curves Mean systemic filling pressure (MSFP) is at the point where venous return curve intersects the x axis (normally ~7 mmHg)

37. Control of cardiac output 2 relationships Between Venous Return and Rt atrial pressure Between cardiac output and preload (Starling's law)

38. Cardiac & vascular function curves Its a simultaneous plot of cardiac output and venous return as a function of right atrial pressure or end diastolic volume

39. The point at which the two curves intersect is the equilibrium point or steady state point Cardiac output can be changed by altering The cardiac output curve The venous return curve Or both curves simultaneously Combining cardiac output & venous return curves

40. There can be different equilibrium conditions With increase contractility cardiac output is raised but CVP is lower: With decreased contractility cardiac output is reduced but CVP is raised eg - C.C.F

41. Inotropic agents changes the cardiac output curve intersection point shifts to a higher cardiac output corresponding to a lower right atrial pressure Combining cardiac output & venous return curves

42. 2. Changes in blood volume or venous compliance change In this case both cardiac output and right atrial pressure will increase or decrease

43. Changes in TPR changes both the cardiac output and venous return Increased TPR – decrease both CO and VR Decrease in TPR – increases both CO and VR

44. Pressures in the vasculature & heart

45. Velocity of blood flow Can be expressed by: v = Q / A where v = velocity (cm/sec) Q = blood flow (ml/min) A = cross sectional area (cm 2 ) Therefore, velocity is higher in the aorta (smaller cross sectional area) is lower in all the capillaries

46. Blood flow Can be expressed by: Q = ∆P / R where Q = blood flow (ml/min) ∆P = pressure gradient (mmHg) R = resistance Or Cardiac Mean arterial Right atrial output = pressure - pressure Total peripheral resistance

47. Resistance According to Poiseuille’s equation: R = 8 η l π r 4 where R = resistance η = viscosity of blood l = length of blood vessel r = 4 th power of the radius of blood vessel

48. Resistance Resistance could be in parallel or series Parallel resistance: Illustrated by the systemic circulation Each organ is supplied by an artery that branches off the aorta  the resistance of this arrangement is given by 1 = 1 + 1 + 1 ....... 1 R total R 1 R 2 R 3 R n The total resistance is less than the resistance of any of the individual arteries

49. Resistance Series resistance: Illustrated by the arrangement of blood vessels within a given organ Since an organ is supplied by a large artery, small arteries, arterioles, capillaries arranged in series R total = R artery + R arterioles + R capillaries The largest proportion of resistance is contributed to by arterioles

50. Blood flow – laminar vs turbulent Laminar flow is in a straight line and turbulent flow is not. Reynold’s number predicts whether blood flow is turbulent or laminar. When Reynold’s number is increased, there will be turbulence and audible vibrations (bruits) ` Reynold’s number is increased by: reduced viscosity (low haematocrit, anaemia) increased velocity (narrowing of a vessel)

51. C = Capacitance (compliance) Describes the distensibility of blood vessels Is inversely related to elastance Capacitance is given by: C = V / P where C = capacitance (ml/mmHg) V = volume (ml) P = pressure (mmHg) Describes how volume changes in response to changes in pressure

52. C = Capacitance is much greater for veins than for arteries Changes in venous capacitance changes the venous blood volume Eg: decrease in venous capacitance decreases the unstressed volume (venous volume) and increases the stressed volume (arterial volume) Capacitance of arteries decreases with age. Arteries become stiffer and less distensible

53. Pressure profile in vessels As the blood flow through the systemic circulation, pressure decreases because of the resistance

54. C = Pressure is highest in the aorta and lowest in the venae cavae The largest decrease in pressure occurs across the arterioles (site of highest resistance) Mean pressures: aorta - 100 mmHg end of arterioles - 30 mmHg vena cava - 4 mmHg Pressure profile in vessels

55. Is pulsatile Varies during the cardiac cycle Systolic pressure Diastolic pressure Arterial pressure

56. C = Pulse Pressure SBP – DBP difference The most important determinant is stroke volume Decrease in capacitance due to aging can cause an increase of pulse pressure Generally ~ 40 mmHg Mean Arterial Pressure It is actually the average arterial pressure with respect to time Is equal to DBP + 1/3 pulse pressure

57. C = Venous pressure Is very low Has a high capacitance Able to hold a large volume without an increase in pressure

58. Atrial pressure Even lower than venous pressure Right atrial pressure – generally similar to CVP Left atrial pressure is estimated by pulmonary capillary wedge pressure Catheter inserted into the smallest pulmonary artery branch, very close to pulmonary capillaries. Pulmonary capillary pressure is only a little higher than the left atrial pressure

59. C = Venous pressure Is very low Has a high capacitance Able to hold a large volume without an increase in pressure

60. Atrial pressure Even lower than venous pressure Right atrial pressure – generally similar to CVP Left atrial pressure is estimated by pulmonary capillary wedge pressure Catheter inserted into the smallest pulmonary artery branch, very close to pulmonary capillaries. Pulmonary capillary pressure is only a little higher than the left atrial pressure

61. Most important mechanisms are: the fast neurally mediated baroreceptor mechanism the slower hormonally mediated renal mechanisms Other mechanisms include; Atrial stretch receptors local vasoconstrictors and dilators Regulation of arterial blood pressure

62. Most of the vasculature is innervated by sympathetics Sympathetic noradrenergic fibres terminate on resistant vessels – mediates vasoconstriction Exceptions: - Skeletal muscle vessels undergo vasodilatation via β 2 due to circulating adrenaline - parasympathetic innervation is seen in some erectile tissue of reproductive organs, uterine vessels some facial vessels blood vessels in the salivary glands Sympathetic innervation of veins cause a reduction in capacitance and an increase in venous return Innervation of blood vessels

63. There are pressure receptors located in the cardiovascular system Those that monitor arterial pressure: In the carotid sinus & aortic arch Low-pressure receptors (cardiopulmonary receptors) In walls of right atria at vena caval entrance wall of left atria pulmonary circulation Baroreceptors Located within the walls of the carotid sinus near the bifurcation of the common carotid artery and aortic arch Baroreceptor reflex

64. Baroreceptor reflex

65. Baroreceptor reflex

66. Increased baroreceptor discharge - inhibits the tonic discharge of sympathetic nerves and - excites the vagal innervation of the heart. These neural changes produce vasodilation, venodilation, hypotension, bradycardia and a decrease in cardiac output. Baroreceptor reflex

67. There are two types of stretch receptors in the atria Those discharging in atrial systole & In late diastole during atrial filling Effect of increase discharge from the include; vasodilatation & a fall in BP But, an increase in heart rate Cardiopulmonary receptors

68. Peripheral chemoreceptors found in the; Aortic & carotid bodies Have a very high blood flow Activated by: low P a O 2 , PCO 2 and pH Stimulated by hypoxic hypoxia Main effects are on respiration, but also leads to vasoconstriction Direct effect of chemoreceptor activation is hypoxia, increased catecholamines from medulla which increases HR and BP Peripheral chemoreceptor reflex

69. When intracranial pressure increases, The pressure on the VMC and the local hypoxia and hypercapnia , increases its discharge. Results in the rise of systemic blood pressure Accompanied by reflex reduction in heart rate (through baroreceptor reflex) Therefore, Increased ICP – Hypertension and bradycardia Central chemoreceptors

70. The capacity of tissues to regulate their own blood flow is referred to as autoregulation. Most vascular beds have an intrinsic capacity to compensate for moderate changes in perfusion pressure by changes in vascular resistance, so that blood flow remains relatively constant. Seen in mainly kidney . Also in mesentery, skeletal muscle, brain, liver, myocardium. Two theories for this: Myogenic autoregulation Metabolic theory of autoregulation Autoregulation

71. Local Factors Factors affecting blood vessel calibre Vasoconstriction Vasodilatation Decreased temperature Increased CO 2 & decreased O 2 Autoregulation Increased K + , adenosine, lactate Decreased local pH increased temperature

72. Endothelial products Factors affecting blood vessel calibre Vasoconstriction Vasodilatation Endothelin - 1 Nitric oxide Locally released platelet serotonin Kinins Thromboxane A 2 Prostacyclin

73. Circulating neurohormonal agents Factors affecting blood vessel calibre Vasoconstriction Vasodilatation Epinephrine (except in skeletal muscle and liver) In skeletal muscle & liver Norepinephrine Calcitonin-G related protein ADH (vesopressin) Substance P Angiotensin II Histamine Endogenous digitalis like substances Atrial natriuretic peptide Neuropeptide Y Vasoactive intestinal polypeptide

74. Stimulators Inhibitors Angiotensin II Nitric oxide Catecholamines ANP Growth factors PGE2 Hypoxia Prostacyclin Insulin Oxidized LDL HDL Shear stress Thrombin Regulation of Endothelin-I secretion

75. Many circulating substances affect the vascular system The vasodilator regulators include kinins VIP & ANP Circulating vasoconstrictor hormones include vasopressin norepinephrine epinephrine & angiotensin II Systemic regulation by neurohormonal agents

76. C = Neurohormonal mechanisms of regulating blood pressure Associated with volume regulation Volume regulation is closely related to Na + regulation The main controller are: Renin – angiotensin – aldosterone system ANP and natriuretic substances

77. C = Renin – angiotensin – aldosterone system Renin Referred to as an enzyme / hormone Synthesised as prorenin Secreted from the JG cells of the kidney as renin or prorenin The active form is renin and only kidney can produce this Only known function is to cleave angiotensinogen and form angiotensin-I Angiotensinogen Alpha-2 globulin blood level increase by - glucocorticoids, thyroid hormones, estrogens, several cytokines and angiotensin II.

78. C = Angiotensin Converting Enzyme & Angiotensin II ACE is formed by endothelial cells and happens in many parts of the body Conversion of Angiotensin I happens mainly when blood passes through the lungs Same ACE inactivates bradykinin Angiotensin-II has a very short half life of 1-2 min The active substance is Angiotensin-II

79. C = Actions of Angiotensin II Potent vasoconstrictor. Acts on AT 1 receptors. Constricts arterioles and elevate SBP & DBP Directly acts on adrenal cortex to increase aldosterone secretion Facilitation of release of NE from sympathetic postganglionic neurones Contraction of mesangial cells with a decrease in GFR A direct effect on the renal tubules to increase Na + reabsorption . Acts on the brain to reduce the sensitivity of baroreflex Increase thirst Increase ADH and ACTH secretion

80. C = Juxtaglomerular apparatus Comprise of JG cells, Lacis cells and macula densa Renin is produced by JG cells – located in the media of afferent arterioles Renin is also found in lacis cells that are located in the junction between the afferent & efferent arterioles – functional importance of this renin? Macula densa – modified efferent arteriolar cells in close proximity to JG cells

81. C = Regulation of renin secretion Occur due to the balance of many factors 1. Intrarenal baroreceptor mechanism that decrease renin when pressure in the JG cells increase 2. Increased Na + and Cl - amount delivered to the macula densa cells decrease renin secretion 3. Angiotensin-II has a direct feedback inhibition on JG cells 4. ADH also has an inhibitory effect on renin secretion

82. C = Regulation of renin secretion 5. Increased sympathetic activity Increase renin secretion by - increased circulating catecholamines acting on β 1 receptors on the JG cells - stimulation of renal sympathetic nerves 6. Reduced renal artery pressure (due to renal artery constriction or aorta) produce increased renal sympathetic nerve stimulation and that increase renin secretion

83. Navar L G et al. Physiology 1998;13:170-176 ©1998 by American Physiological Society

84. Navar L G et al. Physiology 1998;13:170-176 ©1998 by American Physiological Society

85. Hormones of the heart & other natriuretic factors Secreted from the muscle cells in the atria and, to a much lesser extent in the ventricles Contain secretory granules The granules increase in number when ECF expands due to increased Na + in the body The other hormones BNP – Brain and heart CNP - brain, pituitary, kidneys, and vascular endothelial cells (acts in a paracrine fashion) Causes natriuresis ANP

86. Hormones of the heart & other natriuretic factors Actions: Increase GFR by dilating afferent arteriole & relaxing mesangial cells Acts on the renal tubule to inhibit Na + reabsorption An increase in capillary permeability, leading to extravasation of fluid and a decline in blood pressure. Relax vascular smooth muscle in arterioles and venules. CNP has a greater dilator effect on veins Inhibit renin secretion and Counteract the pressor effects of catecholamines ANP

87. Microcirculation Blood flow through the tissues is regulated by contraction and relaxation of the arterioles and pre-capillary sphincters

88. C = Microcirculation Passage of substances across capillary walls 1. Lipid soluble substances – by simple diffusion 2. Small water soluble substances – across water filled clefts between endothelial cells. Brain – clefts exceptionally tight (BBB) Liver & intestine – clefts are very wide, allow passage of proteins too. 3. Large water soluble substances – by pinocytosis

89. C = Starling’s equation for fluid movement across capillaries J v = K f [(P e – P i ) – ( π e – π i )] Where: J v - fluid movement (ml/min) K f - hydraulic conductance (ml/min . mm Hg) P e - capillary hydrostatic pressure (mm Hg) P i - interstitial hydrostatic pressure (mm Hg) π e - capillary oncotic pressure (mm Hg) π i - interstitial oncotic pressure (mm Hg)

90. Control of blood flow Autoregulation Active hyperaemia Reactive hyperaemia Local control of blood flow Mechanisms of local control of blood flow Myogenic theory Metabolic theory Extrinsic control of blood flow Sympathetic innervation Other vasoactive hormones

91. Other vasoactive hormones Histamine Causes arteriolar dilatation & venous constriction Resulting in local oedema due to increased P e Released in response to tissue trauma Bradykinin Exactly like histamine Serotonin Causes arteriolar constriction released in response to vessel damage to prevent blood loss

92. Other vasoactive hormones Prostaglandins Prostacyclin is a vasodilator in several vascular beds E-series prostaglandins are vasodilators F-series prostaglandins are vasoconstrictors Thromboxane A 2 is a vasoconstrictor

93. Special circulations Coronary Circulation Is controlled almost entirely by local metabolic factors – most important factors are hypoxia & adenosine Exhibits autoregulation Exhibits active and reactive hyperaemia Active hyperaemia: contractility increase will create an increase demand for oxygen. To meet this demand, vasodilatation of coronaries occur increasing oxygen delivery Reactive hyperaemia: during systole, mechanical compression of coronaries, cause increase of flow after systole Sympathetic nerves play a minor role

94. Special circulations Cerebral Circulation Is controlled almost entirely by local metabolic factors – most important local vasodilator is CO 2 Exhibits autoregulation Exhibits active and reactive hyperaemia Sympathetic nerves play a minor role Vasoactive substances in the systemic circulation has little or no effect as they cannot cross the BBB

95. Special circulations Skeletal muscle Is controlled by sympathetic nerves of blood vessels & by local metabolic factors Sympathetic innervation: Primary regulator of flow at rest There are both  1 and β 2 receptors in vessels  1 – cause vasoconstriction β 2 – cause vasodilatation Vasoconstriction of skeletal muscle vessels is the major contributor to TPR at rest

96. Special circulations Skeletal muscle Local metabolic control: Exhibits autoregulation, active and reactive hyperaemia Local vasodilatory substances are lactate, adenosine and K + Mechnical occlusion during exercise can occlude arteries temporarily and cause an oxygen debt producing a reactive hyperaemia later

97. Special circulations Skin Sympathetic nerves play a Major role Temperature regulation is the principal function of cutaneous sympathetics trauma produce the triple response with a red line, flare and a wheal

98. CVS changes in a haemorrhage Arterial Baroreceptors Cardiopulmonary receptors Chemoreceptors Central nervous system cardiovascular centres Hypovolaemia Sympathetic output increased Parasympathetics output reduced Reduced CVP Reduced CO Reduced MAP HR increased Heart contractility increased Arterial constriction Venous constriction increased Fluid absorption increased Capillary hydrostatic Pressure reduced raised CO raised TPR Blood pressure restored

99. Valsalva manoeuvre

100. Are constructed by combining systolic and diastolic pressure curves. It is a cycle of contraction, ejection , relaxation and refilling Ventricular pressure-volume loops

101. Change in Preload Refers to a change in end diastolic volume Relates to the width of the pressure-volume loop Changes in the ventricular pressure-volume loops

102. 2. Change in Afterload Refers to an increase in aortic pressure Ventricle must eject blood against a higher pressure, resulting in a smaller stroke volume Therefore, the end systolic volume would be more

103. 3. Increased Contractility Ventricle develops greater tension than usual and contracts more forcefully Stroke volume increases End systolic volume decreases

104. Atria, ventricles and Purkinje system Resting membrane potential is determined by the conductance to K + Close to the K + equilibrium potential. Around -90 mV Cardiac action potentials Phase 1, Initial repolarization K+ efflux and the reduction of Na+ conductance Phase 4, Resting membrane potential. Approaches the K+ equilibrium potential

105. Sinoatrial (SA) node Does not have a constant resting membrane potential Exhibits phase 4 depolarization or automaticity Phases 1 & 2 are absent in the SA node action potential Cardiac action potentials

106. Conduction velocity Fastest in the Purkinje system Slowest in the AV node Absolute refractory period (ARP) – No action potential could be initiated Relative refractory period (RRP) – more than the usual inward current is required to initiate an action potential Cardiac action potentials Refractory period

107. Autonomic effects on the heart & vessels Innate rate of the SA node is about 100/min Both sympathetics and parasympathetics have effects on the rate If parasympathetics are blocked, the rate rises to 150-180 /min Chronotropic effect – producing changes in the heart rate Dromotropic effect – producing changes in conduction velocity mainly in the AV node Inotropic effect – produce an effect on the contractility of the heart

108. Parasympathetic effect on heart SA node, atria and AV node has parasympathetic innervation Neurotransmitter is Ach. Acting on muscarinic receptors Effects are: Decreasing heart rate (threshold potential is reached slowly) Decrease conduction velocity through the AV node Increase the PR interval (decreased inward Ca ++ current)

109. Sympathetic effect on heart Neurotransmitter is Norepinephrine. Acting on β 1 receptors Effects are: Positive chronotropic effect (threshold potential is reached faster Increase conduction velocity through the AV node Decrease the PR interval (increase inward Ca ++ current) Positive inotropic effect

110. Cardiac muscle fibres Large number of mitochondria – for supply of constant energy

111. Cells contain myosin, actin, troponin and tropomyosin Gap junctions are present at the intercalated disks  Entire heart behaves as an electrical syncytium Mitochondria are more numerous in cardiac muscles than in skeletal muscles T tubules – invaginations in the cell membrane. Carry action potentials into the cell interior Sarcoplasmic reticulum – sites of storage of Ca ++ needed for excitation-contraction coupling Myocardial cell structure

112. Action potential spreads from the cell membrane through the T tubules During the plateau phase of the AP, Ca ++ enter the cell from the ECF This Ca ++ entry trigger the release of more Ca ++ from the SR (Ca ++ induced Ca ++ release) – amount released depends on the amount stored and the size of the inward current Intracellular Ca ++ increase – actin and myosin interaction and contraction occurs The magnitude of tension developed depends on the amount of Intracellular Ca ++ Relaxation occurs when Ca ++ is pumped back into SR by Ca ++ -ATPase pump Steps in excitation-contraction coupling

113. P wave Represents atrial depolarization PR interval Is the interval between the beginning of P wave to beginning of Q wave Increases with problems in conduction velocity (heart blocks) Varies with heart rate. QRS complex Represents ventricular depolarization Electrocardiogram (ECG)

114. QT interval From beginning of QRS to end of T wave Represents entire ventricular depolarization and repolarisation ST segment Is the segment from the end of S wave to the beginning of T wave Is isoelectric Represents the period when the ventricle is depolarized T wave Represents ventricular repolarisation Electrocardiogram (ECG)

115. Atria, ventricles and Purkinje system Resting membrane potential is determined by the conductance to K + Close to the K + equilibrium potential. Around -90 mV Cardiac action potentials Phase 1, Initial repolarization K+ efflux and the reduction of Na+ conductance Phase 4, Resting membrane potential. Approaches the K+ equilibrium potential

116. Explain the physiological determinants of ejection fraction. (40 % marks Importance of Ca ++ in cardiac muscle contraction. (30% marks)  Explain the physiological basis of the following : 4.2. Tachycardia in shock. (25 marks) 4.3 . Low urine output in a patient who has lost IL of blood. (25 marks ) 3. 3.1 . Explain how variations in arteriolar resistance affect the arterial blood flow. (50 marks) Outline the factors that determine the blood flow to an organ (15 marks) Explain the autoregulation of cerebral blood flow. (35 marks) Describe the baroreceptor reflex regulation of blood pressure. (50 marks )     Give the physiological mechanisms that facilitate the venous return from the extremities to the heart.

117. 1 . Explain the physiological basis of the following , 1.1 A drop in systolic blood pressure when standing from supine position (30 marks) 1.2 Low urine output following a haemorrhage (40 marks ) 1.1. What biophysical factors determine the blood pressure? 1.2. Explain with examples how blood pressure is increased when these factors are altered by diseases.