Exam 4

What are the functions of the circulatory system?

Transportation of respiratory gases, nutrients, and wastes. Hormonal and temperature regulation. Protection via clotting and immunity.

Cardiovascular System Major Components

The heart is a four chambered pump to the pulmonary and systemic circulations. Blood vessels include arteries (away from heart), arterioles, capillaries, venules, and veins (toward the heart). Blood contains cells and plasma.

What are the two major components of the circulatory system?

Cardiovascular and lymphatic systems

What are the major components of the lymphatic system?

Lymphatic vessels, lymphoid tissues, and lymphatic organs (spleen, thymus, tonsils, and lymph nodes). Lymph is the fluid of the lymphatic system that originates from blood and returns to blood.

Four Chambers of the Heart

Right atrium receives deoxygenated blood from the body. Left atrium receives oxygenated blood from the lungs. Right ventricle pumps deoxygenated blood to the lungs. Left ventricle pumps oxygenated blood to the body.

Oxygen Poor vs Rich Blood Flow

Oxygen poor blood flows from the systemic capillaries to the superior vena cava, right atrium, and lungs. CO2 is diffused out. Oxygen rich blood flows to the left side through the aorta to reach the tissue cells and capillaries.

Septum

Muscular wall separating the right and left sides. Prevents the mixing of oxygen rich and poor blood.

Fibrous Skeleton

Separates atria from ventricles. Allows atria to work as one unit (myocardium), while the ventricles work as a separate unit. Forms the annuli fibrosi rings which support the heart valves.

Atrioventricular Valves

Located between the atria and ventricles and prevents backflow. There are two AV valves. Tricuspid is between the right atrium and ventricle. Bicuspid/mitral is between the left atrium and ventricle. Papillary muscles and chordae tendineae prevent the valves from everting.

Semilunar Valves

Located between the ventricles and arteries leaving the heart and prevents backflow. There are two SL valves. Pulmonary is between the right ventricle and pulmonary trunk. Aortic is between the left ventricle and aorta. Papillary muscles and chordae tendineae prevent valves from everting.

Heart Sounds

Produced by closing valves. Lub occurs at ventricular systole during the closing of AV valves. Dub occurs at ventricular diastole during the closing of SL valves.

Stethoscope Positions for Heart Sounds

Aortic area, tricuspid area, pulmonary area, and bicuspid area.

Heart Murmur

Abnormal heart sounds produced by abnormal blood flow through the heart. Many are caused by defective heart valves. Can be congenital or from rheumatic endocarditis.

Mitral Stenosis

Mitral valve calcifies and impairs flow between left atrium and ventricle. May result in pulmonary hypertension.

Incompetent Valves

Don’t close properly. May be due to damaged papillary muscles or mitral valve prolapse.

Septal Defects

Holes in interventricular or interatrial septa which allows blood to cross sides.

Pulmonary Circulations

Circulates between heart and lungs. Blood pumps to lungs via pulmonary arteries. Blood returns to heart via pulmonary veins.

Systemic Circulation

Circulates between heart and body tissues. Blood pumps to body tissues via aorta. Blood returns to heart via superior and inferior vena cava.

What are cardiac muscle cells interconnected by?

Gap junctions called intercalated discs.

In smooth muscle, what does calcium bind to?

Calmodulin, forming a complex that activates MLCK.

Why can smooth muscle contract no matter the stretch, while skeletal and cardiac muscle decrease tension after 2.25uM?

It’s based on the arrangement of actin and myosin. Cardiac and skeletal muscle have sarcomeres, while smooth muscle doesn’t.

What arteries do NOT contain oxygen rich blood?

Pulmonary artery.

Cardiac Cycle Contraction/Relaxation

During systole, the ventricles contract and the atria are relaxed. During diastole, the ventricles relax and fill while the atria contract.

During isovolumetric relaxation of ventricles, what happens to pressure in the ventricles?

It is falling.

What electrically separates the atria and ventricles?

Fibrous skeleton.

Electrical Activity of Heart

Sinoatrial node is the pacemaker located in right atrium. AV node and purkinje fibers are secondary/ectopic pacemakers. They have a slower rate compared to the normal sinus rhythm.

Automaticity

Automatic nature of the heartbeat.

Steps of Cardiac Action Potential

Rapid depolarization causes VG sodium channels to open and sodium enters cell. Initial repolarization causes potassium channels to open, potassium leaves and sodium channels close. Plateau occurs when slow calcium channels open and calcium enters. Rapid repolarization causes calcium channels to close and potassium channels open and potassium leaves. Then, cell reaches RMP.

Cardiac AP through Heart Tissue

AP spreads via intercalated discs between right and left atria. Travels from SA node to AV node to stimulate atrial contraction. AV node at the base of right atrium and bundle of His conduct the AP towards ventricles. In the interventricular septum, the bundle of His divides into right and left bundle branches. Bundle branches become purkinje fibers, which stimulate ventricular contraction upwards.

Conduction of Impulses

AP from the SA node spreads rapidly, about 1 m/s. At the AV node, things slow down to about 0.05 m/s. This accounts for half of the time delay between atrial and ventricular contraction. The speed picks up in the bundle of His, reaching 5 m/s in purkinje fibers. Ventricles contract 0.1-0.2 seconds after atria.

Excitation-Contraction Coupling in Cardiac Muscle

Ca2+ stimulated Ca2+ release occurs. AP is conducted along sarcolemma and T tubules. They open VG Ca2+ channels. Ca2+ diffuses into cells and stimulates the opening of Ca2+ release channels of the SR. Ca2+ binds to troponin to stimulate contraction. This all occurs at signaling complexes on the sarcolemma where it’s close to SR.

Calcium Channels in Cardiac Muscle

Unlike skeletal muscle, the VG Ca2+ channels aren’t directly connected to Ca2+ channels in the SR. Instead, Ca2+ acts as a second messenger to open SR channels. It’s called calcium induced calcium release. Excitation contraction coupling is slower.

Cardiac Muscle Relaxation

Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ is pumped back into the sarcoplasmic reticulum for storage. Ca2+ is exchanged with Na+ via the NCX antiporter. Na+ gradient is maintained by the Na+-K+-ATPase.

Cardiac Muscle Refractory Periods

Since the atria and ventricles contract as single units, they can’t sustain a contraction. The AP of cardiac cells is long, so they have long refractory periods before they are able to contract again.

Where are the cells that have the fastest rate of spontaneous diastolic depolarization located?

SA node

Electrocardiogram Waves and Intervals

P wave is atrial depolarization. P-Q interval is atrial systole. QRS wave is ventricular depolarization. S-T segment is the plateau phase and ventricular systole. T wave is ventricular repolarization.

ECG Pressures and Heart Sounds

Lub occurs after the QRS wave, as the AV valves close. Dub occurs at the beginning of the T wave, as the SL valves close. Intraventricular pressure rises as ventricles contract during systole. Pressure falls as ventricles relax in diastole.

Examples of Abnormal Heart Rhythms

Bradycardia, tachycardia, abnormal tachycardia, ventricular tachycardia, and paroxysmal supraventricular tachycardia.

Bradycardia

Slow heart rate, below 60 bpm.

Tachycardia

Fast heart rate, above 100 bpm.

Abnormal Tachycardia

Can occur due to drugs or fast ectopic pacemakers.

Ventricular Tachycardia

Occurs when pacemakers in the ventricles contract out of sync with atria. Can be very dangerous and lead to ventricular fibrillation.

Paroxysmal Supraventricular Tachycardia

SVT is sporadic tachycardia that originates in the atria and produces a fast ventricular rate. Is treated with intravenous adenosine.

Flutter

Extremely fast (200-300 bpm) but coordinated contractions.

Fibrillation

Uncoordinated pumping between the atria and ventricles.

Types of Blood Vessels

Arteries, arterioles, capillaries, venules, and veins.

Tunics of Blood Vessels

Tunica interna is the inner layer, composed of simple squamous endothelium and elastic fibers. Tunica media is the middle layer, composed of smooth muscle. Tunica externa is the outer layer, composed of connective tissue.

Types of Arteries

Elastic arteries are closer to the heart, allow stretch, and recoil when ventricles relax. Muscular arteries are farther from the heart, have more smooth muscle, and have more resistance due to smaller lumina. Arterioles provide the greatest resistance and control blood flow via vasoconstriction and vasodilation.

Capillaries

Smallest blood vessel. Has a single layer of simple squamous epithelium tissue. It is where gases and nutrients are exchanged between the blood and tissues. Blood flow to capillaries is regulated by precapillary sphincters and vasoconstriction/vasodilation of arterioles.

Types of Capillaries

Continuous capillaries are adjacent cells found in muscle, adipose tissue, or CNS. Fenestrated capillaries have pores in the vessel wall and are found in kidneys, intestines, and endocrine glands. Discontinuous capillaries have gaps between cells and are found in bone marrow, liver, and spleen. Discontinuous capillaries allow for the passage of proteins.

Veins

Low pressure, thin walls with no elastin or collagen, and a larger lumen. Veins are compliant, they stay stretched out when stretched. They are the capacitance vessel because they take on the shapes that we force them into.

Ways to Return Blood to Heart

Valves keep blood flowing in one direction. Peristalsis is alternating waves of smooth muscle contraction and relaxation. Skeletal muscle pump is muscle around veins massaging the veins to move blood forward. Breathing increases pressure in abdomen and decreases pressure in thorax due to diaphragm contraction. Blood wants to move from high to low pressure, increasing blood flow to heart. Sympathetic nervous system goes to smooth muscle layer, causing a tonic/general contraction at all times.

How much blood does the average adult have?

5 liters

Arterial Blood

Leaving the heart, is bright red, and is oxygenated except for blood going to the lungs.

Venous Blood

Entering the heart, is dark red, and is deoxygenated except for blood coming from the lungs.

Plasma

Makes up 55% of blood volume. Is made of water and dissolved Na+ and K+ ions.

Plasma Proteins

Albumin creates osmotic pressure, drawing water into blood vessels. Alpha and beta globulins transport lipids and vitamins. Gamma globulins produce antibodies. Fibrinogen causes zymogen (inactive protein) to become fibrin, which helps with blood clotting. Serum is plasma without fibrinogen. Transferin is an iron transport protein.

Formed/Cellular Elements

Make up 45% of blood volume. Includes erythrocytes, leukocytes, and platelets.

Erythrocytes

Life span of about 120 days ensures they carry oxygen efficiently. They don’t have mitochondria so they won’t use the oxygen they carry. Have no nuclei, allowing more room to carry oxygen. Their job is to carry oxygen via hemoglobin. Hemoglobin contains 4 heme groups with iron at the center, which binds and releases oxygen.

Leukocytes

Have nuclei and mitochondria. Their job is to help fight infections. Granular leukocytes include neutrophils, eosinophils, and basophils. Agranular leukocytes contain monocytes and lymphocytes (B and T cells).

Platelets/Thrombocytes

Platelets have no nuclei and are short lived. Their job is to help with blood clotting.

Hematopoiesis

Process of making new blood cells. Erythropoiesis forms new RBCs. Leukopoiesis forms new WBCs. Cytokines stimulate the production of different WBC subtypes. Thrombopoiesis makes new platelets.

Blood Typing

Antigens are found on the surface of cells to help immune system recognize self cells. Antibodies are proteins secreted by lymphocytes in response to foreign cells that bind to antigens. Type A blood has anti-B antibodies. Type B has anti-A antibodies. Type AB has no antibodies (universal receiver). Type O has both anti-A and anti-B antibodies.

Rh Factor

Has another antigen on RBC (antigen D). Rh positive have antigen D and Rh negative doesn’t. Can cause issues in pregnancy.

Transfusion Reaction

If we receive the wrong blood type, antibodies bind foreign RBC and cause agglutination (clumping). Type A blood has transfusion reactions to Type B or AB blood. Type B blood has a reaction to Type A or AB blood. Type AB blood rarely has transfusion reactions. Type O blood has a reaction to Type A, B, or AB blood.

Blood Clotting

Hemostasis is the cessation of bleeding. Healthy, intact blood vessel endothelium secretes prostacyclin PGI2, which causes vasodilation. NO CD39 cleaves ADP into AMP and Pi, inhibiting platelet aggregation. Damaged blood vessels expose collagen. Platelets bind collagen using Von Willebrand factor.

Platelet Release Reaction

Occurs when platelets secrete ADP, thromboxane A2, and serotonin. TxA2 and serotonin cause vasoconstriction and decrease blood flow to the wound. ADP and TxA2 increase platelet stickiness, which increases platelet release reaction and increases platelets via positive feedback. Process continues until platelet plug forms. Platelet plug is reinforced with fibrin. Plug contracts, becomes more compact, and stops bleeding.

Intrinsic Pathway of Forming Fibrin

Occurs in vitro (out of body). Blood collected at the drs binds glass, activating clotting factor XII. Activates a series of clotting factors, which will combine with Ca2+ and phospholipids. Then it starts the common pathway. Activates clotting factor X, which cleaves prothrombin into thrombin. Thrombin cleaves fibrinogen into fibrin, which infiltrates platelet plug and stops bleeding.

Extrinsic Pathway of Forming Fibrin

Occurs in vivo (in body). Damage to blood vessel causes release of thromboplastin, which activates clotting factor VII. This activates clotting factor X, starting the common pathway. Clotting factor X is activated, which cleaves prothrombin into thrombin. Thrombin cleaves fibrinogen into fibrin, which infiltrates the platelet plug and stops bleeding.

Dissolving Clots

Plasminogen is cleaved into plasmin, which digests fibrin via Kallikrein.

Functions of Lymphatic System

Transports excess interstitial fluid from tissues to veins. Produce/store lymphocytes for the immune response (B and T cells). Transports absorbed fats from intestines to blood.

Cardiac Output

Volume of blood pumped each minute by ventricles. CO=SVxHR.

Regulation of Heart Rate Components

Looking at chronotropic effects, positive is an increase in HR and negative is a decrease. HCN channels are hyperpolarization cyclic nucleotide channels that are activated by hyperpolarization or cAMP/cGMP to produce pacemaker potential.

What Regulates Heart Rate

Sympathetic nervous system releases NE and epi to keep HCN channels open, so we fire more cardiac APs and increase HR. Parasympathetic nervous system releases ACh to keep K+ channel open, so we fire less cardiac APs and decrease HR. These are both controlled by the cardiac control center in the medulla oblongata (brainstem).

What is the major determinant of resting heart rate?

Parasympathetic nervous system

Ways to Increase HR

Decreased vagal input causes decreased parasympathetic input. Add sympathetic input.

What Regulates Stroke Volume

SV=EDV-ESV. End diastolic volume (preload) is how much the heart is stretched. Increased EDV causes increased SV. Total peripheral resistance (afterload) is the sum of all resistance in arteries or impedance of blood flow. It’s the resistance the heart has to overcome to pump blood. Increased TPR causes decreased SV. Contractility is the strength of ventricular contraction. Increased contractility causes increased SV.

Intrinsic Control of Heart

Intrinsic means within the heart, sometimes called the Frank-Starling Law of the Heart. Increased EDV means our heart has more stretch, so we have increased contractility, increasing SV. What goes into the heart must come out. Principle is all due to stretch with increased cross bridges and increased sensitivity to Ca2+. Right before filling have lots of actin overlap, decreasing contraction. Increased interactions between actin and myosin allow increased contractility. Stretch increases sensitivity of SR Ca2+ channels, increasing release of Ca2+, allowing for increased contractility.

How does the heart adjust to increased TPR?

Increased TPR causes decreased SV, which results in less blood leaving the heart. Increased EDV increases stretch, which increases contractility, which increases SV.

Extrinsic Control of Heart

Sympathetic nervous system releases NE and epi, which have a positive ionotropic effect, increasing contractility by increasing available Ca2+ for the sarcomere. Parasympathetic nervous system releases ACh that decreases HR, which increases EDV, which increases stretch, which increases contractility, which increases SV. This all depends on how much the HR drops.

Venous Return

Returning blood back to the heart influences EDV. It’s determined by vein factors such as valves, peristalsis (caused by sympathetic NS), skeletal muscle pump, total blood volume, and pressure difference. Pressure difference is due to breathing and arteries vs. veins. Veins are highly compliant (capacitance vessels) and hold more blood at a lower pressure, while arteries aren’t compliant (resistance vessels) and have high pressure.

Atrial Stretch Reflex

Increased venous return increases EDV, which increases atrial stretch. Increased HR is called reflex tachycardia. Decreased ADH causes an increase in urine and decreased blood volume. Increased atrial natriuretic peptide causes increased Na+ and H2O excretion, decreasing blood volume.

Blood Volume Percents

67% of blood volume is in intracellular fluid. 33% is in extracellular fluid. Within the extracellular compartment, 20% of blood volume is in plasma and 80% is in interstitial fluid.

Hydrostatic Pressure

Hydrostatic pressure is due to an existing fluid and acts due to capillaries and interstitial fluid. Capillary pressure is due to blood in capillaries being pushed out, forcing water into interstitial space. Interstitial fluid pressure is due to ISF pushing on capillaries from outside, which wants to move fluid into capillaries.

Colloid Osmotic Pressure

Due to existing proteins that can’t move, so water does. Acts due to capillaries/plasma and interstitial fluid. Capillary/plasma pressure is due to protein in plasma drawing water into the capillary. Interstitial fluid pressure is due to protein drawing water out of capillaries, but is a small contribution, often none.

Starling Forces

Hydrostatic pressure of capillaries and ISF and colloid osmotic pressure of capillaries/plasma and ISF. They affect blood volume.

Fluid Movement in Capillary

Fluid out-fluid in. Hydrostatic capillary pressure moves fluid out. Hydrostatic ISF pressure moves a little fluid in. Colloid osmotic capillary/plasma pressure moves a lot of fluid in. Colloid osmotic ISF pressure moves a tiny bit of fluid out, if any. Veins can’t catch everything coming out, so lymphatic system absorbs the leftover and returns it to blood. Increased venous return increases cardiac output.

Blood Flow Equation

Q=change in pressure/resistance. Pressure difference between two ends of the vessel is the driving force of blood flow. Increased change in pressure increases blood flow and vice versa. Increased resistance decreases blood flow and vice versa. Resistance= the length of vessel times thickness of fluid, divided by radius. Radius makes the biggest impact. Increased radius (VD) causes decreased resistance. Decreased radius (VC) causes increased resistance.

Poiseuille’s Law

Q=change in P x r4 (radius) x pi / n (thickness) x L x 8. Length and thickness have little variation. Change in pressure and radius have a big impact.

What happens if radius of blood vessel decreases?

If vasoconstriction of a blood vessel occurs, resistance increases, so blood flow decreases.

What happens if the radius of a blood vessel increases.

If vasodilation of a blood vessel occurs, resistance decreases, so blood flow increases.

Parallel Blood Flow to Organs

When we change resistance in one organ, the change in blood flow doesn’t impact other organs. Structure is stacked instead of a line so it doesn’t cause a cascade.

Mean Arterial Pressure

The average pressure in arteries during one cardiac cycle. MAP=COxTPR. Cardiac output is impacted by stroke volume and heart rate. Total peripheral resistance comes from the vasoconstriction of arterioles. BP increases upstream of the vasoconstriction, so the arteries leading to arterioles has increased BP. BP decreases downstream of the vasoconstriction, so the capillaries have decreased BP.

MAP and Surface Area

MAP is inversely proportional to surface area (total cross section area). Increased surface area causes decreased blood pressure, like in capillaries. Decreased surface area causes increased blood pressure, like in arteries. Veins have the same surface area as arteries, but low blood pressure because they are compliant and take the shape of the blood.

Blood Pressure Regulation

Long term regulation: kidney controls blood volume and thus stroke volume. Short term regulation (beat to beat): sympathetic nervous system increases heart rate which increases cardiac output, increasing MAP. Controls vasoconstriction of arterioles impacting TPR.

Baroreceptor Reflex

Baroreceptors are stretch receptors in the aortic arch and carotid sinus. They send sensory information to medulla oblongata control centers. Vasomotor control center regulates VC and VD, regulating TPR. Cardiac control center regulates heart rate.

Baroreceptors and Blood Pressure

Increased BP stretches baroreceptors and increases APs to control centers, which increases parasympathetic NS and decreases sympathetic NS. This decreases heart rate and TPR, causing decreased BP. Decreased BP causes less stretch in baroreceptors and decreases APs to control centers, which decreases parasympathetic NS and increases sympathetic NS. This increases heart rate and TPR, causing increased blood pressure. Baroreceptors are more sensitive to a drop in BP.

Pulse Pressure

Taking pulse measures heart rate. Your pulse is every time your arteries stretch due to increased BP at systole before snapping back. Pulse pressure is the difference in BP at systole and diastole. Pulse pressure=SBP-DBP. If BP is 120/80, pulse pressure is 40 mmHg. Pulse pressure is a reflection of stroke volume. MAP=DBP+1/3(pulse pressure).

Cardiac Cycle and Pressure Phases

Isovolumetric Contraction Phase: Ventricles are starting to contract, increasing pressure in ventricles. Pressure in ventricles becomes greater than pressure in atria. AV valve closes (lub). Ejection Phase: Ventricular pressure increases greatly. Pressure in ventricles is greater than pressure in arteries. SL valves open and blood enters vessels. Isovolumetric Relaxation Phase: Ventricular pressure decreases. Pressure in ventricles is less than pressure in arteries. SL valves close (dub). Rapid Filling Phase: Ventricular pressure continues decreasing. Pressure in ventricles is less than pressure in atria. AV valve opens and ventricles fill with blood. Atrial Contraction Phase: atria contracts.

How do Starling forces affect blood pressure?

By determining fluid movement between blood vessels and tissues, balancing hydrostatic pressure (pushing fluid out) and osmotic pressure (pulling fluid in).