Cardiovascular Physiology PDF

 Functional anatomy of the CVS The CVS acts as a courier system/ conveyer belt for: Average blood volume Why is the pressure higher Gasses (O2 and CO2)...

 Functional anatomy of the CVS The CVS acts as a courier system/ conveyer belt for: Average blood volume Why is the pressure higher Gasses (O2 and CO2) distribution in the CVS in in aorta than pulmonary Nutrients Metabolic waste Basics terms of percentage: artery? Electrolytes Larger blood volume pumped to systemic Hormones 2 PUMPS (7% blood volume): circulation, as oppose to the volume pumped to the Immune cells Left Heart (LH) lung at a given point in time. Heat Right Heart (RH) (Exam) Various proteins 2 CIRCULATORY SYSTEMS: (Exam) Pulmonary Circulation (9% blood volume) Functional organ - One way valves: Systemic Circulation (84% blood volume) Help the ventricles build up pressure to Cardiomyocytes: Most basic components of (Due to holding capacity-lung has less vessels than systemic) make the blood flow forward. Consists of striated muscle with intercalated disc connecting cardiomyocytes the CVS: Blood flows from a high to a low pressure What is blood pressure? Systolic Pressure (Maximum contraction Striations are caused by the regular arrangement 2 PUMPS: Blood pressure (mm Hg) is the pressure that pressure) of contractile proteins (actin and myosin). 1. Left Heart (LH) the blood exerts on the myocardium Diastolic Pressure (Lowest relaxation left atrium (LA) pressure) left ventricle (LV) 2. Right Heart (RH) Why is the left Systemic system right atrium (RA) Why is the pressure right ventricle (RV) ventricular wall thicker? It needs to pump at higher pressure, know as a lower in the atria high pressure system Functions of intercalated 2 CIRCULATORY SYSTEMS: (Exam) compared to the 1. Pulmonary Circulation disk: 2. Systemic Circulation (Exam) ventricles? 1. Acts as a connector between cardiomyocytes When the AV valves close, the ventricles build to keep them from separating during NB: up enough pressure to empty via the aortic and contraction. RH supplies pulmonary circulation. pulmonary valves. As opposed to the atria, 2. Contain gap junctions that allows LH is supplied systemic circulation. Why is pressure in where there are no “back” valves. (Exam) intercommunication between cardiomyocytes. Communication such as electrical current/ Closed loop system, in series (i.e. RH in series pulmonary system low? action potential for contraction to take place. to PC and LH in series to SC. Thus, equal Higher pressure can damage the lungs due to the blood volume present in both ventricles). lungs having small arteries with thin walls for Pressure is generated throughout the easier diffusion that can easily burst. circulatory system that drives the circulation (Exam) of blood.(To pump blood to brain the heart needs to pump with more pressure upwards.) Note: One-way valves allow blood flow in one direction through the heart Hypertrophic cardiomyopathy Cardiac pathologies (HCM) Arrhythmogenic right ventricular Peripartum cardiomyopathy: Diagnosis: increased LV wall thickness Echocardiography cardiomyopathy In healthy women, the increased strain on the heart leads to physiological Magnetic resonance imaging (e.g., late gadolinium hypertrophy. enhancement) A genetic disorder of the myocardium. However, in a proportion of women, the heart does not return to normal and Nuclear imaging ARVC is due to fatty infiltration of the right heart failure persists (postpartum cardiomyopathy). Computerized tomography ventricular free wall. Elevated left ventricular ejection fraction ≤ 45%, common symptoms of heart Genetic screening This results from the mutation of genes and can cause failure. sudden death in young people and athletes. Due to various factors: autoimmune responses, stress activated cytokines, Pathophysiology: Mutation in the intercalated disks oxidative stress and genetic factors in prolactin cleavage. Increased LV wall thickness without abnormal Blood volume 150% loading conditions Mother gets physiological hypertrophy= when baby is born; back to normal Interstitial fibrosis Some cases does not go away- to a point where the heart fails Arrhythmias Cardiomyocyte hypertrophy and disarray Disease progression: Compensatory response → Hypertrophy → Initiation of fetal gene program → Metabolic shifts (phosphocreatine → fatty acids→ glucose) → Fibrosis (interstitial and perivascular) End-stage heart failure: energy and functional imbalance Genetics: Approximately 50% of patients have mutations in one or more of >20 sarcomeric genes Mitral valve stenosis in pregnant women Pulmonary hypertension: Mitral stenosis is occasionally encountered in pregnant women, Clinical definition: elevated pulmonary artery pressures, ≥ 20 especially in developing countries, where rheumatic fever is endemic. mmHg at rest (echocardiography or right heart catheterization). Patients with mild mitral stenosis usually tolerate pregnancy and Commons causes: COPD, parenchymal lung disease, chronic delivery well. (bacteria that sits on the micro valve) thrombo-embolic disease, congenital heart disease and TB. While patients with asymptomatic moderate or severe mitral stenosis High mortality rate (up to 65% depending on several factors) and commonly develop symptoms of heart failure, especially in the 2nd increased risk of adverse cardiac outcomes, particularly at the trimester of pregnancy, when the peak haemodynamic effects take time of labour and delivery place. Systemic hypertension Fainting is a symptom Pulmonary- exclusively in the lungs Thicker right ventricle and fails and dies of right heart failure  Electrical activity of the heartThe cardiac conduction Basic knowledge: 7. Relaxation occurs when Ca unbinds from troponin. Action potential of ventricular system: Contraction of heart muscle is induced by electrical impulses initiated by the SA node. 8. Ca is pumped back into the sarcoplasmic reticulum for storage. muscle 1. Action potentials spread from the SA node Relaxation of heart muscle is induced by the 9. Ca is exchanged with Na to the AV node, causing atrial absence of electrical impulses, i.e. in between 10. Na gradient is maintained by the Na-K- depolarization. impulses ATPase. 2. Atrial depolarization, seen as the P wave, induces atrial systole. Calcium-induced calcium release:The heart Note: 3. Action potentials spread through the bundle cannot beat without calcium ions. (Exam) Tubule allows AP to move from one of His, bundle branches and Purkinje fibers, myocyte to the next. causing ventricular depolarization. Cardiac- excitation- contraction- coupling Small [Ca] moves to myocytes 4. Ventricular depolarization, seen as the QRS (Exam): More Ca is released from the complex, induces ventricular systole. An increase in electrical pulse causes increase sarcoplasmic reticulum (via ryanodine 5. As action potentials pass out of the in contraction. receptor) ventricles, ventricular diastole is induced. One can not happen without the other Why this difference in 6. Ventricular repolarization is shown by the T wave. Contraction process: Skeletal vs Cardiac: action potentials? Because the atria and ventricles can’t contract Action potential and contraction in skeletal in the same way or at the same time, muscle fiber: otherwise blood won’t be able to leave the T wave= ventricular repolarization Refractory period is shorter, i.e. muscle heart. used quickly, and relaxes shortly thereafter. Heart rate: Regulated by Action potential and contraction in cardiac muscle autonomic nerves: QT interval: represents the time it fiber: takes for both repolarization and Refractory longer, because of the slow depolarization to occur. closure of the ion channels, and all cells in ventricle or atrium contracts Phase of cardiac cycle: simultaneously. AP need to reach all of them, therefore, longer to dissipate and thus longer refractory period. 1. Action potential enters from adjacent cell. 2. Voltage-gated Ca channels open. Ca+ enters cell. 3. Ca induces Ca2+ release through ryanodine receptor-channels (RyR). 4. Local release causes Ca spark. 5. Summed Ca sparks create a Ca signal. 6. Ca ions bind to troponin to initiate contraction. (Exam) Factors that effect cardiac Heart pump regulation Positive inotropes: output: Norepinephrine is a positive inotrope = Myosin heads: increase contractility (force of contraction) Graded muscle contractions occur via Epinephrine variable calcium due to not all myosin Isoproterenol (b1-AR and B2-AR heads being involved agonist) During high preload: Dobutamine (b1-R agonist) → Muscle stretch reduces the distance Digitalis/Digoxin (Na+/K+-ATPase between thick and thin filaments inhibitor causes reverse action of Na+/ → Increase Ca2+-sensitivity of tropinin Ca2+ Exchanger) increases crossbridges Caffeine Milrinone (Phosphodieserase inhibitors) → The more crossbridges, the stronger contraction/ increase force of contraction Negative inotropes: Propranolol (beta blocker) What is the difference Atenolol (b1-AR blocker) Calcium channel blockers (Verapimil, between heart rate and Diltiazem) contractility? Beats per minute vs. forcefulness of Starling’s law of the contraction Heart: Chronotropy and Inotropy: 1. An increase in stroke volume 2. This increase is directly proportional to Chronotropes: agents that alter the rate of SA the ventricular filling (when ventricle node function and conduction through the heart filled to the maximum) 3. Increase in force due to blood pressing Positive Chronotropes: down on ventricle Norepinephrine 4. A standard contraction not all myosin Isoproterenol heads are involved, but in cardiac Milrinone contractions all heads are involved 5. This causes a more forceful contraction Negative Chronotropes: Acetylcholine Thus, increase in ventricular stretch equals Digoxin an increase in force generation. Beta blockers Calcium channel blockers Contractility: inherent ability of the heart muscle to generate force in response to electrical stimuli  Functions of Blood 1. Transportation Function Supplies oxygen to tissues, mainly carried by Blood: Edema: caused by increased secretion of fluid into the interstitial fluid or decreased removal of this fluid. Differentiation of Blood Cell Lines hemoglobin within red blood cells. Reduced pressure causes fluid Specific hematopoietic cytokines stimulate Transports nutrients like glucose, amino acids, accumulation in the interstitial space, stem cells or progenitor cells in the bone and fatty acids. resulting in edema. marrow. Removes waste such as carbon dioxide, urea, These cells differentiate into three major blood cell lines, each with its own unique and lactic acid. Acts as a messenger, transporting hormones Cellular Compartment hematopoietic cytokine. The bone marrow is red due to the presence and signals from damaged tissue. of Blood of hemoglobin and is roughly the size of the 2. Protection Function 1. Red Blood Cells (Erythrocytes) liver. Immunological function from circulating white → Responsible for oxygen transport. blood cells and antibodies in plasma. 2. Platelets (Thrombocytes) 3. Blood Clotting (Hemostasis) → Involved in clot formation Part of the body's self-repair functions. (thrombus). Regulation Function Regulates body pH with buffering systems, 3. White Blood Cells (Leukocytes) Plasma= maintaining a pH of 7.4. intravascular → Various types: lymphocytes, Regulates body temperature. fluid monocytes, neutrophils, eosinophils, Hydraulic function includes regulating colloid compartment basophils. Composition of Bone osmotic pressure. → Specific functions typically covered in 2 other compartments = intracellular and Marrow Haematology extracellular. immunology. Most developing cells in the bone marrow are The study of blood, blood organs, and blood diseases. Plasma Composition white blood cells, which have a short lifespan in circulation. Hema means blood, and ology is Mostly water, with organic molecules including In circulation, there are more red blood cells the study of blood. proteins (plasma proteins: albumin, globulins, than white blood cells. Blood is a specialized body fluid fibrinogens), glucose, nutrients, ions, New white blood cells are continually composed of blood cells suspended hormones, and respiratory gases. produced due to their short lifespan. in plasma. Albumins contribute to osmotic pressure, transport non-soluble substances, and carry bilirubin from red blood cell breakdown. Composition of Blood Globulins involved in blood clotting, act as antibodies, and play a role in transport (e.g., Obtained through venipuncture, separating plasma and blood cells via centrifugation. transferrin for iron). Fibrinogens are crucial for blood clotting. Definition of Plasma comprises 50-60% of total blood volume, while cellular compartment consists of red blood Plasma proteins are primarily produced in the liver and secreted into the blood. Hematopoiesis cells, white blood cells, and platelets. Hematopoiesis refers to the formation of In a normal adult male (70 kg), total blood blood cells. volume is about 5 liters. Colloid Osmotic Pressure "HEMA" signifies blood, and "poiesis" → Plasma: 3 liters (50-60%) Ensures water is drawn into the vasculature means formation. from tissues. In adults, blood cells are produced in the → Packed red blood cells: 2 liters (40-50%) Liver failure leads to reduced plasma protein bone marrow. → Packed red blood cells are also called production, decreasing colloid osmotic White blood cells: have nuclei hematocrit and indicate anemia if less than 40-50% pressure. Hematopoietic Process Red Blood Cell Formation Red Blood Cell Lifespan Hematopoiesis begins with hematopoietic stem (Erythropoiesis) Vitamin B12 and Folic cells that can differentiate into any of the three and Recycling cell lines. Erythropoiesis is the formation of red blood Red blood cells live for 120 days. Acid Deficiency Anemias Precursor cells are immature blood cells found in cells (erythrocytes). the bone marrow. Erythropoietin, produced in the kidney, Components of hemoglobin are recycled: vs. Iron Deficiency stimulates red blood cell production. → Globin incorporated into new proteins. Mature blood cells enter the circulation. Erythropoietin production is influenced by → Iron in heme reused for new hemoglobin. Anemia oxygen demand, with hypoxia, anemia, and → Porphyrin ring breaks down into bilirubin, Both vitamin B12 and folic acid needed Platelet Formation testosterone stimulating its production. which is excreted. HEME breakdown: for DNA synthesis in red blood cell Platelets are fragments of immature blood cells Mature red blood cells circulate for about formation. called megakaryocytes in the bone marrow. 120 days before being destroyed, indicating Deficiency in these vitamins leads to Megakaryocytes release platelet fragments into a longer lifespan Stimulated: Hypoxia, Anaemia, large and swollen red blood cells circulation. Testosterone (megaloblastic) in the hematocrit. Platelets are involved in blood clot formation. Blood Smear and Red Iron deficiency anemia: → Smaller, pale red blood cells due to White Blood Cells Blood Cells: inadequate heme and hemoglobin formation. → Result of insufficient dietary iron (Leukocytes) When observing a blood smear under a Anemias: intake There are five different types of adult white microscope: Anemia defined as a decrease in red blood cell blood cells in circulation. Red blood cells (erythrocytes) appear as count and hemoglobin, resulting in fatigue and White blood cells are the only blood cells with empty bags with no nuclei. shortness of breath. Vitamin B and folic nuclei. Five different types of white blood cells are acid deficiency anemia Interleukins and colony stimulating factors granulated and have nuclei. Gender differences in normal values: stimulate leukopoiesis, the formation and Leukocytes are nucleated, erythrocytes Hematocrit: Males 14-54%, Females differentiation of leukocytes. appear as empty bags. 37-47%. Neutrophils, the main white blood cells in Hemoglobin content: Males 14-17 g/dL, circulation, have a short lifespan of about six Erythrocyte appearance: Females 12-16 g/dL. hours. Lack of nuclei. Red blood cell count: Males higher than Biconcave shape to increase surface area for females. Iron deficiency Platelet Formation oxygen binding to hemoglobin. Flexibility for movement through small Causes of anemia: (Thrombopoiesis) capillaries. Loss of red blood cells (e.g., hemorrhage, Platelets are produced from megakaryocytes in the hemolytic anemia). Structure of red blood cells: of red blood cells bone marrow. Decreased production (e.g., bone marrow Biconcave shape. issues, dietary deficiency, inadequate Thrombopoietin, produced in the liver, stimulates Contain hemoglobin consisting of four globin platelet formation. erythropoietin). protein chains and heme groups. Platelets remain in circulation for approximately Heme groups contain iron atoms for 10 days and play a crucial role in blood clotting. Differentiating between causes: reversible oxygen binding. Hematocrit testing: Hemolytic anemia: Decreased hematocrit, increased bilirubin, smaller but normal-sized red blood cells. Iron-deficient anemia: Lower hematocrit, paler appearance, smaller red blood cells.  Haemostasis Introduction: B. Healing and Sealing (Clot Formation - Coagulation is part of the hemostasis process, which is the cessation of bleeding. Thrombus): Plasma clotting factors are involved in the Anticoagulation Mechanism: Hemostasis keeps blood within vessels while coagulation cascade. The endothelium is a barrier between blood repairing breaks without affecting blood flow. Intrinsic and extrinsic pathways converge to form circulation and body tissues. Hemostasis involves a positive feedback system, a stable clot (thrombus). Endothelial cells produce anticoagulants like different from homeostasis, which maintains internal Liver produces clotting factors, and vitamin K nitric oxide and prostacyclin. stability. and calcium are crucial for their synthesis. These anticoagulants prevent platelet aggregation and clotting. C. Removal of Clot (Thrombolysis): In vitro, anticoagulants like EDTA are used to Homeostasis vs. Hemostasis: The clot must eventually be dissolved and remove calcium and prevent clotting in test Homeostasis regulates the body's internal removed. tubes. environment despite external fluctuations, using Fibrinolysis is the process of dissolving the clot, negative feedback. involving the enzyme plasmin. Negative feedback keeps a system near its set point and counteracts stimuli to maintain stability. Hemostasis involves positive feedback, reinforcing Platelets: the stimulus and creating a cycle that requires Platelets are derived from megakaryocytes in the external intervention to stop. bone marrow. They lack nuclei but contain granules and mitochondria. negative positive Granules release chemicals like serotonin and feedback feedback thromboxane. Platelets become sticky and develop spikes when activated. They release platelet-derived growth factor for blood vessel repair. Hemostasis Analogy: Analogizes hemostasis to repairing a pothole without stopping traffic. A cut is likened to a pothole, and the goal is to close the area without obstructing blood flow. Medications and Stroke: Medications like warfarin and aspirin are Three Steps of Hemostasis: used to prevent clotting. Ischemic strokes involve blood clots and can be life-threatening. A. Temporary Plug Formation: Coagulation Cascade: Fibrinolytics dissolve clots, while Platelets are essential, and vasoconstriction reduces The cascade involves numerous plasma proteins. anticoagulants prevent clot formation. blood flow. Thrombin plays a crucial role in converting an Platelets aggregate to form a temporary plug. unstable platelet plug into a stable, insoluble clot. Thrombin is central to the process. Introduction Blood transfusions involve humans donating blood. Different blood types: A, B, O, and Rhesus blood group. Incompatible transfusions can cause severe complications Blood transfusion Importance of Cross-Matching Emphasis on avoiding transfusion reactions and future pregnancy complications. and even death. Cross-matching involves testing the donor's red blood Cross-matching blood is essential before transfusion. Rhesus Factor (D Antigen) cells against the recipient's plasma. The surface of red blood cells also has the D antigen (Rhesus Agglutination in cross-matching indicates an immune factor). response, necessitating a new donor. Blood Types and Antigens: Type O blood is the universal donor, compatible with all other blood For normal transfusions, cross-matching is essential. Red blood cells have antigens called agglutinogens, groups. In emergencies, O blood type is used, with attention to determining blood type. Type AB blood is the universal recipient, compatible with all other the Rhesus factor. Type A: A antigens, Type B: B antigens, Type AB: Both blood groups. For women planning future pregnancies, Rhesus- antigens, Type O: No antigens. Mention of the importance of preventing clumping or agglutination negative blood is preferable in emergencies. The body produces agglutinins (antibodies) when through cross-testing before transfusion. exposed to non-self agglutinogens. 1. Type A blood produces anti B antibodies when exposed to Type B antigens. Rhesus Factor and Pregnancy 2. Type B blood produces anti A antibodies when exposed People without the Rhesus factor (D antigen) can develop anti-D to Type A antigens. antibodies when exposed to blood from a person with the Rhesus 3. Type AB blood does not produce any antibodies when factor. exposed to Type A or B antigens. For the first transfusion, there won't be a reaction. 4. Type O blood produces both anti A and anti B antibodies However, after the first transfusion, the person will have anti-D when exposed to Type A or B antigens. antibodies and can react to future transfusions from Rhesus- positive donors. This is crucial during pregnancies; if a Rhesus-negative mother carries a Rhesus-positive baby, mixing of blood can occur during childbirth, leading to the mother generating anti-D antibodies. Subsequent pregnancies with Rhesus-positive babies can cause Normal Emergency immunolysis, resulting in erythroblastosis fatalis, potentially causing anemia, jaundice, and even death of the baby. First babies are generally not at risk; second and subsequent babies are at risk. Compatibility and Agglutination Blood transfusion requires compatible blood types to avoid agglutination. Incompatibility leads to clumping of incompatible red blood cells, known as agglutination. Agglutination can be life-threatening, causing hemolysis and an overwhelming immune response. 1. Type A individuals can receive Type A or Type O blood. 2. Type B individuals can receive Type B or Type O blood. 3. Type AB individuals can receive blood of any type without risk of agglutination. 4. Type O individuals can only receive Type O blood.