02-19-07, Anatomy and Physiology - Cardiovascular System

Lippincott medical physiology 2nd edition has a good chapter on cardiovascular physiology. Most cardiac myocytes have only one nucleus, sometimes two, which is not like the skeletal myocytes that are multinucleated.

Blood flows through the network of capillaries and veins, arteries and so on throughout the human body. Blood is a type of connective tissue. The blood carries stuff throughout the body and serves as a transportation system, it connects far away places together. Blood is composed of erythrocytes, leukocytes, platelets (thrombocytes) and platelets.

The structure of the blood vessel allows for blood vessel spasm. Cutting a blood vessel causes the muscle in its wall to contract reflexively, and this reflex lasts only for a few minutes. The reflex lasts long enough, however, to initiate the second and third steps of hemostasis, which means the steps that involve the formation of the thrombocytes plug and the general coagulation process. The vasoconstriction is long enough to cause the second and third steps of the hemostasis process to continue and proceeds.

The blood is usually 45% cells and 55% plasma. Blood plasma is 90% water. If you put the cells into a centrifuge and spin it at high speed, you are going to find that the cells are going to be gathering at the bottom of the test tube that you are swishing them around in.

Plasma is a mixture of water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes and cellular wastes. The blood provides for the transportation of nutrients and wastes throughout the body.

So in the plasma there is going to be water, which is a solvent for carrying other substances, and ions (blood electrolytes) such as sodium, potassium, calcium, magnesium, chloride, and bicarbonate which provide for the osmotic balance, pH buffering, and regulation of membrane permeability. Also in plasma are plasma proteins, such as albumin, fibrinogen, immunoglobulins (antibodies), which provide for osmotic balance, pH buffering, clotting and immunological defense. Substances transported by the blood nutrients include glucose, fatty acids, vitamins, and waste products of metabolism and respiratory gases like O₂ and CO₂ and hormones are also transported in the plasma.

The type of leukocytes are the basophils, neutrophils, eosinophils, lymphocytes, and monocytes which eventually grow up into a macrophage and live in the tissues of target sites.

The erythrocytes have biconcave disks. They are like donuts. Each microliter of blood is going to have roughly five to six million erythrocytes. The erythrocytes contain one-third oxygen-carrying hemoglobin by volume. Hemoglobin is a very important molecule. Hemoglobin is an iron-containing protein that carries oxygen atoms. Oxygen binds to hemoglobin. Nitrates also bind to hemoglobin. Nitrates in your drinking water will dissolve into your blood. A hemoglobin molecule can hold four oxygen molecules and the problem is that nitrate will not leave from hemoglobin, so over time you can develop serious problems. Infants will start to turn blue if their well-water has nitrates in it. Erythrocytes discard their nuclei during development. That means that mature erythrocytes do not have nucleus. So they're not producing proteins. This also means they cannot reproduce.

Nitrates come from poop and fertilizers. So having a well next to the septic tank is a bad idea. Marrow is where the erythrocytes are reproduced. The average life span of the erythrocyte is 120 days (four months). One erythrocyte has roughly 120 million hemoglobin molecules. Nitric oxide (NO) allows for the easier diffusion of oxygen gas into the erythrocytes from the lungs.

Leukocytes are the white blood cells. These are the monocytes, neutrophils, basophils, eosinophils, and lymphocytes. The leukocytes fight infections and help defend the body against disease. Monocytes and neutrophils are phagocytes, which means that they will engulf bacteria. Leukocytes can squeeze between the cells of the blood vessels (the walls) and attack bacteria, debris and fragments, foreign materials, etc.

Lymphocytes can develop into either B cells or T cells. The leukocytes largely remain outside of the blood, and instead run through the lymphatic system and patrol tissues and so on - that's where most pathogens are fought. In one microliter of blood, there is going to be five to ten thousand lymphocytes, but this increases when the body is fighting an infection.

Thromobocytes are known as blood platelets and are maybe two to three micrometers in diameter. Thromobocytes function in blood clotting. These are “cell fragments”. Thromobocytes help repair damaged blood vessels by adhering to their broken edges. The blood platelet counts are very important, so per millimeter volume there is going to be from 130,000 to 360,000 thrombocytes. The precursor of the thrombocytes is the megakaryocytes. As the number of thrombocytes in the blood stream falls, megakaryocytes release the hormone thromboprotein. Coagulation is the process where thrombocytes do their jobs.

Thrombocytes lack the nucleus that other cells contain, and the importance of this is that normally you would suspect that they cannot manufacture proteins—but apparently they can some enzyme manufacturing jobs, which is important in their functioning especially in coagulation and maintaining hemostasis.

The plasma is the clear, straw-colored fluid portion of the blood. Plasma enables most of the functions of the blood to occur. Erythrocytes and leukocytes would not really be able to go anywhere if they were not suspended in the plasma. The plasma transports nutrients, gases, regulates fluid and electrolyte balance, and maintains a favorable pH. Depending on the number of ions, you're going to have different pH levels. When the pH is out of range, then the kidneys start to dump certain compounds into the blood stream.

There are various proteins in the plasma of the blood. Proteins are the most abundant dissolved substances in the plasma. The proteins maintain the osmotic pressure of the blood. The plasma transports lipids and fat-soluble vitamins. There is osmosis going on with the cells of the blood, and that means that there is going to be varying concentrations of nutrients and substances and so on.

Hemostasis is maintained largely by the thrombocytes. This is largely the stoppage of bleeding. Hemostasis is blood fixation. Following injury to a vessel, three steps occur in hemostasis.

The thrombocytic response is 1) adherence, 2) aggregation, and 3) secretion. Collagen and laminin can support the thrombocytes in their response. Integrins are also important. The cells that pass by release serotonin, ADP, thromboxane A2 which promotes degranulation, vasoconstriction, etc. This promotes the formation of a thrombocytes plague.

Thrombin, fibrinogen, fibrin,

The structure of the blood vessel allows for blood vessel spasm. Cutting a blood vessel causes the muscle in its wall to contract reflexively, and this reflex lasts only for a few minutes. The reflex lasts long enough, however, to initiate the second and third steps of hemostasis, which means the steps that involve the formation of the thrombocytes plug and the general coagulation process. The vasoconstriction is long enough to cause the second and third steps of the hemostasis process to continue and proceeds.

So, after vasoconstriction, the thrombocytes (platelets) stick to the exposed edges of damaged blood vessels. This is the start of the formation of the thrombocytes plug. The thrombocytes form a net with spiny pieces protruding from their membranes.

“To a large extent, the interaction of coagulation factors occurs on the surfaces of platelets and endothelial cells. While plasma can eventually clot in the absence of surface contact, localization and assembly of coagulation factors on cell surfaces amplifies reaction rates by several orders of magnitude.”

The thrombocyte plug formation is better done in short, small areas or something like that, and it takes longer with the larger the cut on the vessel, so it's not really effective for huge gaping holes in the circulation networks.

Coagulation is the most effective means of maintaining hemostasis (which is a subset of homeostasis). Hemostasis is the operative balance of the blood and all of its contents. You do not want blood leaking out of your body extensively, that's really not good at all. The process of coagulation is very complex and involves many factors. The major event in blood clot formation is the conversion of soluble fibrinogen into insoluble fibrin. Fibrin is going to be what makes the most of the clot in general.

“Granulation tissue contains numerous newly formed blood vessels. As discussed previously, VEGF promotes angiogenesis but is also responsible for a marked increase in vascular permeability (VEGF was first named vascular permeability factor).[107] The latter activity leads to exudation and deposition of plasma proteins, such as fibrinogen and plasma fibronectin, in the ECM and provides a provisional stroma for fibroblast and endothelial cell ingrowth. Migration of fibroblasts to the site of injury and their subsequent proliferation are triggered by multiple growth factors, including TGF-b, PDGF, EGF, FGF, and the cytokines IL-1 and TNF (see Table 3-5 ). The sources of these growth factors and cytokines include platelets, a variety of inflammatory cells (notably macrophages), and activated endothelium. Macrophages are important cellular constituents of granulation tissue, clearing extracellular debris, fibrin, and other foreign material at the site of repair. These cells also elaborate TGF-b, PDGF, and FGF and there-fore promote fibroblast migration and proliferation.[108] If the appropriate chemotactic stimuli are present, mast cells, eosinophils, and lymphocytes may also accumulate. Each of these cells can contribute directly or indirectly to fibroblast migration and proliferation. Of the growth factors involved in inflammatory fibrosis, TGF-b appears to be the most important because of the multitude of effects that favor fibrous tissue deposition. TGF-b is produced by most of the cells in granulation tissue and causes fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM by metalloproteinases (discussed later). TGF-b is also chemotactic for monocytes and causes angiogenesis in vivo, possibly by inducing macrophage influx. TGF-b expression is increased in tissues in a number of chronic fibrotic diseases in humans and experimental animals.”

http://www.mhhe.com/biosci/esp/2002_general/…. Damage to small blood vessels

Go through all of the steps of blood clot formation.

Coagulation process from Lippincott medical physiology second edition book.

The sequential activation of coagulation factors provides for the regulation of coagulation or blood clotting. These coagulation factors are proteins that are synthesized in the liver of the human body and they circulate in the plasma in an inactive state. They are named via Roman numerals in the order in which they were discovered, so it's not necessarily the order in which they act in the situation of coagulation.

The coagulation cascade is an excellent example of metabolic cascading, which is where there is the sequential activation of a series of inactive molecules resulting in a biological response. The cascade in coagulation is the conversion of fibrinogen to fibrin (fibrin is going to mean clotting). Deletion of any of the steps in the cascade has drastic consequences. For example, factor VIII (antihemophilic factor) when reduced provides for prolonged bleeding time on tissue injury due to delayed clotting, or those who lack factor VIII who therefore have the disease hemophilia (severe coagulation defects result from hemophilia).

Tissues can release proteins known as thromboplastin or tissue factor (factor III) that provides for the activation of blood clotting in the region, even if the buildup of factors was not specifically caused by the blood or in order for that matter. At any rate, either method of the activation of coagulation is going to require phospholipids, which provide a surface for the efficient interaction of several factors.

Arteries and Arterioles

Arteries and arterioles carry blood from the heart to capillaries and the rest of the body, walls of arteries are generally thicker than those of veins. Smooth muscle cells and elastic fibers that make up the walls help to make arteries tough and flexible. This enables the arteries to withstand the high pressure of blood as it is pumped from the heart. Arteries can handle high blood pressures, otherwise if not they would rupture. The force that blood exerts on the walls of blood vessels is known as blood pressure.

Except for the pulmonary arteries, all arteries carry oxygen-rich blood. The artery that carries oxygen-rich blood from the left ventricle to all parts of the body, except the lungs, is the aorta. The artery that carries blood to the lungs is the pulmonary artery, and the pulmonary artery does not carry oxygen-rich blood, so the heart is pumping the blood towards the lung to drop off waste carbon dioxide and to pick up some more molecular oxygen on the hemoglobin molecules which number in the thousands or millions per each erythrocyte cell that we examine.

The aorta is the largest artery in the body with the diameter of 2.5 centimeters (this is about one inch). The anatomical structure of the artery is going to branch off very quickly like a tree trunk.

Usually you are going to have to amputate for clots, and you could add some sort of anticoagulation agent (blood thinner) to help not thin the blood. You have to reverse the clotting of the blood, and then you bleed out. Unless you can specifically identify it and get it, that's a very small percentage by the way, and so you have to go do the amputation.

The aorta “travels” away from the heart, it branches into small arteries which the arteries then branch into arterioles so that all parts of the body are supplied. It is exactly the same as a highway system: a super-mega highway, and then you get smaller highways that branch from that, and then they branch into streets, roads, neighborhoods, and the houses can almost represent cells like that. The I-35 highway is like the main super-artery, where 290 (the highway) is the smaller branching arteries with the arteriole offshoots and so on.

Capillaries

Arterioles branch into networks of very small blood vessels called capillaries. From the arterioles, we branch further down into capillaries, and those are the smallest of the structures for the artery subset of the system. Capillaries are so small that you can't see them. They are very small. How small? It is so small that blood has to go through it in “single file”. It is thin-walled and it is one cell in thickness. What type of epithelial tissue is going to be there? Simple squamous epithelial tissue is going to be what's making up the capillaries. Simple squamous allows it for gases to quickly move between the cells and to move into the blood and then into the tissue. They are flat, thin, and it's one layer. The problem with this is that they break easily, they potentially break easily.

Most of the heat lost is going to be in the capillaries. Capillaries give off a lot of heat. There is something called a capillary bed, where it goes through a specific group of tissues or something, and then it fades into the veins. Once it goes through the capillary beds, most of its hemoglobin is going back to the heart. Blue veins are going to be carrying deoxygenated blood. You will never see blue blood.

Forces of diffusion drive carbon dioxide and waste products from the tissue into the capillaries and then to the veins and the veins return erythrocytes and other substances back to the heart to go to the pulmonary artery eventually to the lungs to exchange carbon dioxide and get some oxygen for the hemoglobin molecules in the erythrocytes.

Capillaries are extremely narrow because of the diffusion of substances back and forth. Blood cells moving through capillaries must move single file. That's going to be kind of important and definitely a test question.

Blood vessels include arteries, capillaries and veins. With the exception of capillaries and tiny veins, blood vessels have walls made of 3 layers of tissue, providing a combination of …. The inner layer of the arteries and veins are going to be epithelial tissues, and the middle layer is smooth muscle, and the outer layer is going to be connective tissue.

(from Robbins pathological basis of disease)

Forces of diffusion drive CO₂ and waste products from the tissue into the capillaries. The capillaries are extremely narrow. Blood cells moving through the capillaries must pass in single file, because it's so very narrow.

Veins - The pulmonary vein is the only one that brings deoxygenated blood away from the heart. In between the vein and the capillary is going to be the venule. Veins form a system that collects blood from every part of the body and these veins carry the blood back to the heart so that the heart can pump it through the chambers and then into the pulmonary vein which then brings it to the lungs and then back to the heart eventually and then to the arteries so that the oxygenated blood can be moved throughout the rest of the body.

There are three layers to the vein, just like there are the three layers to the artery. Veins are lined with smooth muscle, this is why there are vasoconstrictors and vasodilators that you all know about. Vein walls are thinner and less elastic than arteries but more flexible. Arteries have much more pressure in terms of blood because it's coming right out of the heart. There's less direct pressure in the veins, coming towards the heart. You don't want to have a lot of resistance with the flow of blood in veins for that reason. Flexibility reduces the resistance that the flow of blood encounters on its way back to the heart.

The majority of your blood in your body is going up, fighting gravity, because the majority of your body is below your heart. Valves prevent the backflow of blood. The blood is going to go forward anyway, so if you are upside down, and suddenly you reverse the process, the places that have the valves don't really need them, and then suddenly the chambers that need the valves don't have them - that's why you don't want to stand on your head for too long.

Large veins contain valves that maintain the one direction flow of blood. This is important where blood must flow against the force of gravity. The flow of blood in veins is helped by contractions of skeletal muscles (in the legs and arms). When muscles contract, they squeeze against veins and help force blood toward the heart.

There are patterns of circulation. Blood moves through the body in a continuous pathway in one of two ways, that means that there are two circuits that are made going out of the heart and going back to the heart, there is going to be 1) the pulmonary circuit and 2) the systemic circuit.

The pulmonary circuit is the one where it goes from the heart and goes to the lungs and then back (at the pulmonary veins from the left lung, or the pulmonary veins from the right lung). The systemic circuit goes from the heart to the rest of the body through the arteries and then it goes back to the heart, this is the main circulation pathway that we all know of.

[pulmonary circuit] -> heart <- [systemic circuit]

The pulmonary circulation carries blood between the heart and the lungs. It begins at the right ventricle and ends at the left atrium. Pulmonary: right ventricle and ends up at the left atrium. Oxygen-poor blood pumped out of the right ventricle of heart into lungs through the pulmonary arteries. Then from the lungs the blood is pumped to the pulmonary veins, which move the blood to the left atrium, thus completing the pulmonary circulation circuit.

Pulmonary arteries are the only arteries to carry deoxygenated blood. Blood returns to the heart (from the right and left lungs) through the pulmonary veins. The pulmonary veins are the only veins to carry oxygen-rich blood (they move the blood back to the heart). The pulmonary artery and pulmonary vein are the only ones that are switched throughout the entire human circulatory system, they're going to be the odd balls.

The lungs are the only organs that are directly connected to both of the two chambers of the heart. See http://www.childrenheartinstitute.org/kidsonly/hearthse.htm

The systemic circulation goes the systems of the body (there is a very obvious connection here in terms of name/function orientation). The systemic circulation starts at the left ventricle and ends at the right atrium through the inferior venacava and superior vencava from the lower and upper body respectively. The left ventricle moves blood to the aortic valve and then into the aorta which pumps blood to the lower part of the body.

Oxygen-rich blood leaving the Heart passes through the Aorta, into many arteries that supply blood to all parts of the body. Eventually, the blood will flow into the superior vencava if it is from the top of the body, and then eventually the blood in the lower parts of the body will flow from veins into the inferior venacava, which eventually gets all of the de-oxygenated blood into the left ventricle. The systemic circulation supplies each major organ of the body with blood, including the heart itself.

The heart receives its blood from a pair of coronary arteries leading from the aorta (where blood goes after it reaches the left ventricle and is passed through the aortic valve). Blood enters into capillaries that lead to the veins through which blood returns to the right atrium (the veins feed into the superior venacava from the upper boddy, and the inferior venacava from the lower parts of the body).