Cardiovascular System Part II PDF

Cardio-vascular system Part II A L I CE YI P Cardio-vascular System Homeostasis is the body's Let us find how long it took way of maintaining a your heart rate to return to constant state in its internal its state of homeostasis. environment, such as...

Cardio-vascular system Part II A L I CE YI P Cardio-vascular System Homeostasis is the body's Let us find how long it took way of maintaining a your heart rate to return to constant state in its internal its state of homeostasis. environment, such as What might cause temperature or heart rate. So differences in the time it took when we exercise, that for different people? For disturbs our body's instance, athletes typically homeostasis. What evidence have a quicker recovery time shows that homeostasis was in their heart rate compared disturbed in this activity? to the average person.  Review of Cardio-vascular ( Circulatory ) System Regulation of Blood Pressure and Hemostasis Topics Diseases of Circulatory System – Causes and Clinical Impact Prevention of Heart Disease Review One Heart Systemic circulations Two closed Circulations of blood Pulmonary circulations Arteries Three types of Blood Vessels Veins Capillaries Right Atrium and Right Ventricle with the tricuspid valve Four chambers and valves in the heart Left Atrium and Left Ventricle with the mitral valve Aortic valve and pulmonary valve Summary of Circulatory System Main functions of the Circulatory System Maintain constant body temperature and fluid balance within the body Transport nutrients, hormones, electrolytes, oxygen and carbon dioxide Removes metabolic waste to excretory organs for disposal Protects the body against disease and infection Clotting stops bleeding after injury Blood Circulation Two closed circuits of blood flow 1) S​ ystemic Circulation – send O2 rich blood and nutrients to all body cells and remove wastes 2) Pulmonary Circulation – send O2 poor blood to lung and pick up O2 and unload CO2 Exception : blood in the pulmonary veins is oxygenated whereas blood in the pulmonary arteries is deoxygenated The systemic and pulmonary circulations Heart ( side and top view) Cardiac Cycle Arrows indicate the flow of pressure. Valves kept to closed to prevent backward flow of blood during isovolumetric ventricular contraction and relaxation. Systole Cycle All AV and semilunar valves closed Blood flow into the ventricle and no back flow Then when the pressure built up to open the semilunar valves, blood ejected to the aorta and pulmonary veins Volume of ventricle remains no change  Diastole Cycle All AV and semilunar valves closed as the ventricle contraction stopsand relaxation starts. No blood enter or flow away from the ventricle. This is isovolumetric ventricular relaxation without change of ventricle volume. Next, the AV valves open and ventricular filling occurs as blood flows in from the atria. Atrial contraction occurs at the end of diastole, after most of the ventricular filling has taken place. Absolute Refractory Period of Heart Occur during and following an action potential when an excitable membrane cannot be re-excited Incapable of undergoing summation of contractions Function as a pump ventricles can only filled up while they are relaxed Relationship between membrane potential changes and contraction in a ventricular muscle cell​  Properties of cardiac ion channels Heart Rhythm. 2010 Jan;7(1):117-26. Selectivity: they are only permeable to a single type of ion based on their physical configuration. Voltage-sensitive gating: a specific TMP range is required for a particular channel to be in open configuration; at all TMPs outside this range, the channel will be closed and impermeable to ions. Therefore, specific channels open and close as the TMP changes during cell depolarization and repolarization, allowing the passage of different ions at different times. Time-dependence: some ion channels (importantly, fast Na+ channels) are configured to close a fraction of a second after opening; they cannot be opened again until the TMP is back to resting levels, thereby preventing further excessive influx. Action potential in cardiomyocytes ( 0-4 phases) Phase 4: The resting phase −90 mV due to a constant outward leak of K+ through inward rectifier channels. Na+ and Ca2+ channels are closed at resting TMP. Phase 0: Depolarization An action potential triggered in a pacemaker cell causes the TMP to rise above −90 mV. Na+ leaks into the cell, further raising the TMP to −70mV, and then rapidly depolarizes the TMP to 0 mV and slightly above 0 mV for a transient period of time called the overshoot Ca2+ channels open when the TMP is greater than −40 mV and cause a small but steady influx of Ca2+ down its concentration gradient. Action potential in cardiomyocytes ( 0-4 phases) Phase 1: Early repolarization TMP is now slightly positive. Some K+ channels open with an outward flow of K+ and returns the TMP to approximately 0 mV. Phase 2: The plateau phase Ca2+ channels are still open and there is a small, constant inward current of Ca2+. This becomes significant in the excitation-contraction coupling process. K+ leaks out down its concentration gradient through delayed rectifier K+ channels. These two countercurrents are electrically balanced, and the TMP is maintained at a plateau just below 0 mV throughout phase 2. Action potential in cardiomyocytes ( 0-4 phases) Phase 3: Repolarization Ca2+ channels are gradually inactivated. Persistent outflow of K+, now exceeding Ca2+ inflow, brings TMP back towards resting potential of −90 mV to prepare the cell for a new cycle of depolarization. Normal transmembrane ionic concentration gradients are restored by returning Na+ and Ca2+ ions to the extracellular environment, and K+ ions to the cell interior. The pumps involved include the sarcolemmal Na+-Ca2+ exchanger, Ca2+-ATPase and Na+-K+-ATPase. Refractory period in the cardiac cycle Flow Rate Flow Rate = Pressure Difference / Resistance Flow rate is directly proportional to the pressure difference between two points and inversely proportional to the resistance. Calculation of Resistance: 90 mmHg ÷ 10 mL/min = 9 mmHg/mL/min Circulatory System Consists of two Circulations to provide adequate circulation of blood throughout all parts of body. Pulmonary circulation provide oxygenation of blood Systemic circulation provide oxygenated blood and nutrition to the body By Starling Law, Cardiac output ( CO ) = Stroke Volume (SV) x Heart Rate (HR ) CO is the volume of blood ejected from the left ventricle of the heart and is equal to venous return in Litres per min Stroke volume is the amount of blood pumped out of the heart after one contraction of the ventricle and thus is the difference of End diastole volume ( EDV ) and End systole volume ( ESV) in mL HR is the number of heart beats in one minute Circulatory System By Poiseuille Equation, Flow Rate (FR) = Change of Pressure ( ΔP )/ Resistance (R) In systemic circulation, ΔP = Mean Arterial Pressure MAP- Right arterial pressure ( zero ) FR = Cardiac Output (CO); R = Total Peripheral Resistance ( TPR) MAP = CO x TPR In pulmonary circulation, Mean pulmonary arterial pressure = CO x Total pulmonary vascular resistance  Short term and Long term control Regulation of Control of BP in hypertension Blood Pressure ( BP) Control of BP in Haemorrhage Sudden fall in BP - Shock Regulation of Arterial Blood Pressure Short term regulation ( nervous) : Intermediate and long term regulation : 1) Baroreceptors reflex Cooperate with urinary system to maintain the blood volume and pressure in the body. 2) Chemoreceptors reflex 1) Renin-Angiotensin- Aldosterone mechanism 3) Vasomotor center 2) Antidiuretic hormone ( ADH ) Regulation of Arterial Blood Pressure A human biological system for self regulating process and feedback mechanism to maintain balance for blood pressure. Receptor : baroreceptor, chemoreceptor, blood volume, salt level Effector : nervous system, heart, blood vessel Regulation of Arterial Blood Pressure in Hypertension Baroreceptors respond quickly to changes of BP When the arterial baroreceptors increase their rate of discharge in hypertension, the result is a decrease in sympathetic neuron activity and an increase in parasympathetic neuron activity and vise versa for hypotension but for short term regulation only. Chemoreceptors are in 2 types: 1) Peripheral one respond to O2 and CO2 levels and pH of the blood 2) Central one measures pH and CO2 changes of cerebral spinal fluid  Regulation of Arterial Blood Pressure in Hemorrhage In hemorrhage when there is significant blood loss, homeostatic reflexes will be elicited to change the cardiac output and peripheral resistance to minimize the change of arterial blood pressure. Such adjustment is controlled by the nervous system with help of baroreceptors and chemoreceptors, both located in the carotids and aortic arch. Change of arterial blood pressure in Hemorrhage (↑ Sympathetic and ↓ Parasympathetic ) 1)The discharge rate of the arterial baroreceptors also decreases inducing increase in HR for the heart 2) Increased ventricular contractility and venous constriction for the vein 3) arteriolar constriction for the arterioles The compensatory mechanisms increase HR and SV as well as TPR and return BP near to normal. But the fact that plasma angiotensin II and vasopressin are also reflexively increased and help constrict arterioles is not shown. Change of arterial blood pressure in Hemorrhage Chemoreceptors provide sensory input to the cardiovascular system Detect for chemical changes of oxygen, carbon dioxide and pH in the blood level Enhance the cardiac sympathetic response to increase heart rate and elevate the arterial pressure The resulting chemoreflex is a potent regulator of blood pressure Regulation of Arterial Blood Pressure Renin-angiotensin-aldosterone system (RAAS) Antidiuretic hormone In response to Sympathetic stimulation, RAAS reduced ( ADH ) sodium-chloride delivery to the distal convoluted ADH is also known as tubule and decreased blood flow to the kidney, renin is vasopressin and is released from the kidney. It facilitates the conversion of made by cell bodies angiotensinogen to angiotensin I. which is then located in the converted to angiotensin II using angiotensin- hypothalamus and converting enzyme (ACE). released from the Angiotensin II is a potent vasoconstrictor which adjacent posterior increase salt reabsorption and promotes release of pituitary. aldosterone which further promotes salt and water retention It acts by increasing water absorption in ACE also breaks down bradykinin which is a potent vasodilator and thus increasing blood pressure. the kidney. Regulation of Arterial Blood Pressure Causal relationships between arterial pressure and blood volume (a) (b) An increase in arterial pressure due to an An increase in blood volume due to increased increased cardiac output induces a decrease in fluid ingestion induces an increase in arterial blood volume by promoting fluid excretion by pressure. the kidneys. This tends to restore blood volume to its This tends to restore arterial pressure to its original value by promoting fluid excretion by original value. the kidneys. Because of these relationships, blood volume is a major determinant of arterial pressure. Effect of Gravity on Blood Pressure The pressure increases in any vessel below the level of the heart while it decreases in any vessel above the level of the heart due to the effect of gravity Gravitational effect = 0.77 mmHg/cm at the density of normal blood In adult of upright position, if mean arterial pressure (MAP) at heart level is 100mmHg, MAP in an artery at the height above heart = 100- ( 0.77 x 50) = 62mmHg CO falls during standing because rapid loss of blood volume into the legs reduce the cardiac preload and venous return which leads to lower SV CO increases normally during exercise because HR and SV increases greater and venous return is greater until the heart rate close to the maximal are attained Baroreceptors Reflex Mechanism during changes in body posture Immediately on standing, arterial pressure in the head and upper part of the body tends to fall which can out of consciousness Falling pressure at the baroreceptors elicits an immediate reflex, resulting in strong sympathetic discharge throughout the body This minimizes the decrease in pressure in the head and upper part of the body by increasing heart rate and peripheral resistance Circulatory System Circulatory system controls velocity ( flow rate ) and amount of blood in the vessel so as to provide enough blood supply throughout the body Heart and the blood vessels control the amount of blood flow to the body parts so as to provide adequate blood flow Blood vessels control the amount of blood flow to the body parts by contraction and relaxation to regulate the blood flow together with the valves in the blood vessels to prevent back flow of the blood so that the blood pressure can be maintained upon change of body posture Shock It denotes any situation in which a sudden decrease in blood flow to the organs and tissues damages them because lack of blood flow means the cell and tissues do not get enough oxygen and nutrients to function well. Arterial pressure is usually decreased in shock. Any damage to the heart can be irreversible after prolonged shock. It can be life threatening medical emergency and get worse rapidly. Shock Hypovolemic shock Caused by a decrease in blood volume secondary to hemorrhage or loss of fluid other than blood Low-resistance shock Caused by excessive release of vasodilators, as in allergy and infection resulted in a decrease in total peripheral resistance Cardiogenic shock Caused by any of a variety of factors (for example, during a heart attack) resulted in an extreme decrease in cardiac output  Primary Haemostasis Secondary Haemostasis Haemostasis Fibrinolysis Risk if Haemostasis not work Hemostasis Hemostasis is the body’s natural reaction to an injury that stops bleeding and repairs the damage. “hemo” (meaning “blood”) “stasis” (meaning “standing still”). This capability is usually for the benefit of conserving blood and preventing infections. Cause problems in the circulatory system if too much or too little clotting. Hemostasis Composes of a series of processes occurred simultaneously to form a blood clot for stop of bleeding in the body ◦ Vasoconstriction ◦ Primary hemostasis (platelet clotting) ◦ Secondary hemostasis (coagulation cascade) ◦ Fibrin clot remodelling ( fibrinolysis ) Vasoconstriction The wall of blood vessel “shrink” to reduce the size of area that the blood flow through. The muscle surrounding the vessel will contract shrinking the vessel Endothelial cells stop secretion of coagulation and aggregation inhibitors and instead secrete von Willebrand factor, which causes platelet adherence during the initial formation of a platelet plug Primary hemostasis (platelet clotting) When endothelial cells are damaged, revealing subendothelial collagen proteins from the extracellular matrix, thromboxane causes platelets to swell, grow filaments, and start clumping together, or aggregating Von Willebrand factor causes them to adhere to each other and the walls of the vessel This process results in a platelet plug that seals the injured area If the injury is small, the platelet plug may be able to form within several seconds Primary hemostasis (platelet clotting) Platelets that circulate in the blood stick to the damaged tissue More platelets are activated and released to the damaged area to form a temporary plug That clot works much like a cork or bottle stopper, keeping blood in and debris or germs out May also involve constriction (narrowing) of the damaged blood vessel, which can happen because of substances that activated platelets release. Video demonstration : https://www.youtube.com/watch?v=gZnjCT17bHM Secondary hemostasis (coagulation cascade) When blood vessels are damaged, vessels and nearby platelets are stimulated to release a substance called prothrombin activator, which in turn activates the conversion of prothrombin, a plasma protein, into an enzyme called thrombin. This reaction requires calcium ions. Thrombin facilitates the conversion of a soluble plasma protein called fibrinogen into long, insoluble fibers or threads of the protein, fibrin. Fibrin threads wind around the platelet plug at the damaged area of the blood vessel, forming an interlocking network of fibers and a framework for the clot. This net of fibers traps and helps hold platelets, blood cells, and other molecules tight to the site of injury, functioning as the clot. This temporary fibrin clot can form in less than a minute and slows blood flow before platelets attach. Secondary hemostasis (coagulation cascade) Involves molecules of “coagulation factors” in the blood Activate the coagulation factors in sequence according to the “coagulation cascade,” which amplifies clotting effects Form a substance called fibrin which further form a solid stable clot together with the platelet plug Video demonstration : https://www.youtube.com/watch?v=cy3a__OOa2M https://www.sunsmedic.com/knowledge-base/kb-role-of-hemostasis-plays-in-thrombosis-and-bleeding/ Fibrinolysis ( Fibrin clot remodeling ) Comes to the last stage of hemostasis in the body Remodels the existing temporary clot into a fibrin clot ( permanent ) Involves a process called fibrinolysis during which the body remodels the clot into the same kind of tissue that was there before the injury Involves plasminogen which becomes entrapped within the clot when it formed Gives rise to production of fibrin degradation products (FDPs ) which compete with thrombin, and thus slow down clot formation by preventing the conversion of fibrinogen to fibrin. Fibrinolysis ( Fibrin clot remodeling ) Plasminogen was slowly activated by tissue plasminogen activator ( t-PA) and urokinase which are released into the blood by the damaged endothelium of the blood vessels after several days (when the bleeding has stopped), fibrinolysis occurs and the clot is broken down. Plasmin breaks down fibrin into soluble parts called fibrin degradation products (FDPs). https://www.researchgate.net/figure/Interplay-of-enzymes-in-the-process-of-fibrinolysis-Abbreviations-used-are-FDPs-fibrin_fig3_284717812 Potential Risk if Haemostasis not work Thrombophilia (hypercoagulability or too much clotting) Blood clots too much or too easily developed or got stuck in different places in the body resulted in severe, life-threatening problems. Most medications include antiplatelet, anticoagulant and fibrinolytic (fibrin-breaking or clot- busting) drugs. Common examples of diseases related to too much blood clotting: ◦ Deep Vein Thrombosis ( DVT) ◦ Heart Attack ◦ Stroke Potential Risk if Haemostasis not work Hypocoagulability (not enough clotting) Without proper clotting, even minor injuries can lose a lot of blood including risk of internal bleeding. Treatment involves boosting up ability to make platelet ( or platelet transfusion ) or that add more of clotting factors to the blood ) Common examples of diseases related to insufficient blood clotting: ◦ Hemophilia ◦ Thromobocytopenia ◦ Von Willebrand Disease Deep Vein Thrombosis Deep vein thrombosis occurs when a thrombus (blood clot) develops in veins deep in the body because veins are injured or the blood flowing through them is too sluggish The blood clots may partially or completely block blood flow through your vein, usually in lower leg, thigh or pelvis Can cause life-threatening pulmonary embolism when the traveling blood clots (emboli) become lodged in the blood vessels of your lung Hemophilia A rare inherited bleeding disorder in which blood cannot clot normally at the site of a wound or injury. Cause extensive external bleeding from a cut or wound or internal bleeding inside the body, especially in muscles and in joints like the hips and knees. Two main types of inherited hemophilia: Type A (most common) caused by a deficiency of factor VIII ( Classic Hemophilia ) Type B caused by a deficiency of factor IX( Christmas disease) Acquired hemophilia A (AHA) can be acquired later in life if the body begins to produce antibodies that attack and destroy clotting factors (Autoimmune hemophilia) Von Willebrand Disease A common blood disorder that keeps the blood from clotting because the platelets cannot stick well without von Willebrand factor and it takes longer for platelets to help form blood clots Treat with different medications: Desmopressin: This hormone boosts the levels of von Willebrand factor in the bloodstream. Von Willebrand factor infusions: to stop bleeding episodes especially before surgery or severe type of disease. Antifibrinolytics: to keep blood clots from breaking down before dental surgery or during heavy period. Birth control pills: to help people with menstrual bleeding and the pill contains estrogen that increases von Willebrand factor levels in the bloodstream.  Vascular Diseases Common Heart Diseases Diseases of Circulatory System Hypertension Prevention of Heart Disease Common Diseases of Circulatory System Any conditions that affect the heart or blood vessels May come on suddenly or develop gradually over years Examples of Vascular Disease ◦ Myocardial Ischaemia ◦ Abdominal Aortic Aneurysm (AAA) Examples of Disease of the Heart ◦ Hypertension ◦ Coronary Artery Disease ( CAD) ◦ Myocardial Infarction ( heart attack ) ◦ Arrhythmia ( abnormal heart rhythms ) Myocardial Ischemia Myocardial ischemia (or cardiac ischemia) means the heart muscle is not getting enough blood (which contains oxygen and nutrients) to work as it should. If this lack of blood from the coronary arteries is severe or goes on for more than a few minutes, it can damage your heart muscle. Then it becomes a myocardial infarction. Treatments may include medications or procedures to improve blood flow to the heart muscle depending on the causes. Abdominal Aortic aneurysm (AAA) ◦ A disease of aorta - potentially life-threatening condition ◦ Abnormal dilatation of aortic wall that supplies blood to the belly, pelvis and legs. ◦ A weak spot in the blood vessel wall, at risk for rupturing (breaking open) and causing a hemorrhage (severe internal bleeding) if not treated earlier enough. ◦ Sometimes call AAA a stomach aneurysm ◦ Symptoms of abdominal / back pain or awareness of pulsation or no symptoms until the aneurysm ruptures ◦ Treated by open surgery or medication to lower blood pressure if the size is not critical Coronary Artery Disease ( CAD) A narrowing or blockage of your coronary arteries, usually due to plaque buildup. Plaque buildup in these arteries limits the blood supply of oxygen-rich blood to the heart. A so called “ silent killer” because of no symptoms Two main forms: ◦ Stable Ischemic heart disease – chronic, coronary arteries gradually narrow over years and the heart receives less oxygen rich blood but live with the condition day to day ◦ Acute coronary syndrome – emergency, sudden rupture and formation of blood clots in the coronary artery which blocks blood flow to the heart ( heart attack ) Treatment for CAD often includes lifestyle changes, risk factor management and medications. Myocardial Infarction ( heart attack) ◦ Always due to the formation of the occlusive thrombosis at the site of rupture or erosion of an atheromatous plaque in a coronary artery ◦ Extremely dangerous condition caused by a lack of blood flow to the heart muscle. Without blood flow, the affected heart muscle will begin to die. If blood flow isn’t restored quickly, a heart attack can cause permanent heart damage and death. ◦ Diagnosed by ECG, repolarization and depolarization become abnormal relative to the surrounding myocardium ◦ ECG show ST segment depression and / or T wave inversion in myocardial infarction Arrhythmia ( Abnormal heart rhythms) An irregular heartbeat, faster or slower than normal Different types of arrhythmias induced from the lower chambers of the heart or slow heart rhythms caused by disease in the heart’s conduction system Treated by different types of drugs such as anti- arrhythmic drugs, heart rate control drugs or anticoagulant or anti-platelet drugs depending on the causes Arrhythmia ( Abnormal heart rhythms) Tachycardia Beating fast (>100 beats/m) e.g. Atrial fibrillation, ventricular fibrillation Bradycardia Beating slow ( < 60 beats /m) e.g. sick sinus syndrome, conduction block Premature heartbeats Beat irregularly Arrhythmia ( Abnormal heart rhythms) In case of heart problem with heart beating, a small battery operated device ( pacemaker) can be implanted under the skin to control the irregular heart beat and consists of:- 1) The generator contains the battery and the information to control the heartbeat. 2) The leads which are wires that connect the heart to the generator and carry the electrical messages to the heart. Hypertension Blood Pressure recorded as Systolic pressure / Diastole pressure 145/92 means Systolic pressure is 145 and Diastole pressure is 92 Blood Pressure varies with excitement, stress and environment ◦ Hypertension in elderly - No symptom but if untreated, it can lead to death or morbidity from heart disease, cerebrovascular accident or renal failure ◦ Hypertension in the young – Sweating, vomiting or headaches due to secondary causes, treated by taking beta-blocking agents / Calcium channel , an ACE inhibitor with a diuretic for those ventriculr dysfunction Prevention of Circulatory system problems Some risk factors such as family history, sex or age cannot be changed but the following ways can reduce some risk factors:- 1) Physical activity daily 2) Eat heart-healthy diet 3) Ease stress 4) Sleep well 5) Maintain a healthy weight 6) Manage conditions such as diabetes, high blood pressure and cholesterol 7) Quit smoking Prevention of Circulatory system problems RISK FACTORS FOR HYPERTENSION: RISK FACTORS FOR VASCULAR DEFECT 1) Hereditary factor 1) Cigarette smoking 2) Obesity 2) High level of saturated fat 3) Lack of exercise 3) High blood cholesterol 4) Diet high in salt 4) Diabetes 5) Heavy drinking 5) Certain drugs 6) Kidney disease 6) Aging 7) Some types of stress Prevention of Circulatory system problems 1) At least 150 mins of physical activity every week -Physical activity helps control your weight 2) Eat heart-healthy diet ( rich in vegetable and fiber but low in saturated fat)- help protect the heart, improve blood pressure and cholesterol, and reduce the risk of type 2 diabetes. 3) Ease stress- Some people cope with stress in unhealthy ways such as eating a lot or drinking 4) Get good quality sleep - People with not enough sleep have a higher risk of obesity, high blood pressure, heart attack, diabetes and depression. Prevention of Circulatory system problems 5) Maintain a healthy weight- Excess weight can increase the chances of developing high blood pressure, high cholesterol and type 2 diabetes. 6) Manage conditions such as diabetes, high blood pressure and cholesterol- Regular screening and control 7) Quit smoking - Chemicals in tobacco can damage the heart and blood vessels. Cigarette smoke reduces the oxygen in the blood, which increases blood pressure and heart rate Reference Widmaier, E.P., Raff, H., Strang, K.T. (2019) Vander’s Human Physiology: The mechanisms of body function, 15th Ed. McGrawHill Education. https://my.clevelandclinic.org/health/symptoms/21999-hemostasis Thank You Because of this my heart is glad, and my glory is full of joy: while my flesh takes its rest in hope. (Psalms 16:9)