Circulatory System + Blood and Hematopoiesis PDF

Circulatory system + Blood and hematopoiesis Dr.Mohammad Omran, MD Arab American University Faculty of medicine Blood and hematopoiesis  Composition of blood Blood is a specialized connective tissue with its typical components as the followin...

Circulatory system + Blood and hematopoiesis Dr.Mohammad Omran, MD Arab American University Faculty of medicine Blood and hematopoiesis  Composition of blood Blood is a specialized connective tissue with its typical components as the following: 1. Extracellular matrix as in plasma 2. Proteins/fibers as proteins dissolved in plasma like alpha and beta globulin, albumin, fibrinogen. 3. Cells as erythrocytes, leukocytes and platelets. Composition of blood  Composition of blood After centrifugation: 44% of the tube contents are erythrocytes lies in the bottom half of the tube called sediment and represents what is called hematocrit. In the upper half, there will be a straw colored translucent slightly viscous material compromising around 55% of the whole volume called the plasma. In between these two layers there is thin gray-white layer called the buffy coat (leukocytes and platelets) represent around 1% of the total volume.  Plasma composition Blood smear(blood film)  Blood cells Erythrocytes (red blood cells RBCs) Shape : biconcave (provide large surface Life span:120 days. to volume, and gas exchange) These are well differentiated cells. Normal count : Lack nucleus. 3.9-5.5 million per microliter in females Filled with a protein to carry O2 called hemoglobin. 4.1-6.0 million/μL in males. The only cells that their function does not require them to leave vasculature. Erythrocytes (red blood cells RBCs)  Erythrocytes (red blood cells RBCs) During its terminal differentiation, RBCs lose all its organelles including its nucleus, even its cytoplasm is almost totally replaced by hemoglobin (O2 carrying protein) Due to its lack of mitochondria, RBCs undergoes anaerobic glycolysis.  Leukocytes Leukocytes are divided based on the density of their cytoplasmic granules into two major groups: Granulocytes (neutrophils, eosinophils, basophils) Agranulocytes (lymphocytes, monocytes). There are two types of cytoplasmic granules: 1- Lysosomes (often called azurophilic granules in blood cells). 2- Specific granules that bind neutral, basic, or acidic stains and have specific functions.  Leukocytes (granulocytes) Granulocytes have polymorphic nuclei with two or more distinct (almost separated) nuclear lobes. Includes: eosinophils, neutrophils and basophils. Have few mitochondria and poorly developed Golgi apparatus and rER. Depends on glycolysis for energy production. Its apoptotic cell death does not elicit an inflammatory response.  Leukocytes (agranulocytes) Do not have specific granules, but they do contain azurophilic granules (lysosomes), with affinity for the basic stain azure A (azurophilic). The nucleus of agranulocyte is spherical or indented (uneven edges) but not lobulated (mononuclear). Includes : lymphocytes and monocytes.  Leukocytes a-Color with routine blood smear stains. There are typically 4500-11,000 total leukocytes/μL of blood in adults, higher in infants and young children. b-The percentage ranges given for each type of leukocyte are those used by the US National Board of Medical Examiners. The value for neutrophils includes 3%-5% circulating, immature band forms.  Types of leukocytes Neutrophils (Polymorphonuclear Leukocytes) Most abundant type of leukocytes. Size : 12-15 μm in diameter. Life span:6-8 hours in blood and a life span of 1-4 days in connective tissues. Nucleus : having two to five lobes linked by thin nuclear extensions,females has drumstick-like appendage representing the inactive X chromosome. Cytoplasm : has a faint pink granules contains (Myeloperoxidase,Lysozyme,Defensins) plays major role in both killing and degrading engulfed microorganisms. Neutrophils (Polymorphonuclear Leukocytes)  Eosinophils Size : almost same as neutrophils. Nucleus: bilobed nuclei. Cytoplasm: contains large, acidophilic-specific granules typically staining pink or red contains contains major basic proteins (MBP), and peroxidases that play a major role in parasitic worms or helminths destruction, and plays a role in allergy. Eosinophils are particularly abundant in connective tissue of the intestinal lining and at sites of chronic inflammation, such as lung tissues of asthma patients. Eosinophils Basophils  Lymphocytes By far the most numerous type of agranulocyte. Nucleus : spherical with highly condensed chromatin Size: 9-18 μm in diameter. Cytoplasm :a thin scanty rim. Divided into subclasses by the “cluster of differentiation” or CD markers these are: 1. B lymphocytes. 2. Helper and cytotoxic T lymphocytes (CD4+ and CD8+, respectively). 3. Natural killer (NK) cells. Lymphocytes Monocytes  Platelets Very small non-nucleated, membrane-bound cell fragments Life span: 10 days. Cytoplasm:marginal bundle of actin filaments, alpha and delta granules and an open canalicular system of membranous vesicles Origin : megakaryocytes of the bone marrow. Function : 1. promote blood clotting. 2. help repair minor tears or leaks in the walls of small blood vessels. 3. preventing loss of blood from the microvasculature. Platelets  Hemopoiesis Hematopoietic Stem Cells All blood cells arise from a single type of pluripotent hematopoietic stem cell in the bone marrow that can give rise to all the blood cell types. Give rise to two major lineages of progenitor cells with restricted potentials (committed to produce specific blood cells): lymphoid cells myeloid cells (lymphocytes) 1. Granulocytes. Progenitor cells migrate from the 2. Monocytes. bone marrow to the thymus or the 3. Erythrocytes. lymph nodes, spleen. 4. megakaryocytes. Hematopoietic Stem Cells and differentiation Major hematopoietic cytokines (growth factors or colony-stimulating factors).  Bone marrow Bone marrow is found in the medullary canals of long bones and in the small cavities of cancellous bone. There are two types of bone marrow that are recognized grossly: red bone marrow yellow bone marrow blood-forming. filled with adipocytes that color is produced by an exclude most hematopoietic abundance of blood and cells. hematopoietic cells.  Red Bone marrow Contains adipocytes but is primarily active in hematopoiesis. It can be examined histologically in sections of bones or in biopsies, but its cells can also be studied in smears. Marrow consists of capillary sinusoids running through a stroma of specialized, fibroblastic stromal cells and an ECM meshwork with reticular fibers. Stromal cells produce the ECM; both stromal and bone cells secrete various CSFs, creating the microenvironment for hematopoietic stem cell maintenance, proliferation, and differentiation.  Maturation of erythrocytes Erythrocyte maturation is an example of terminal cell differentiation involving hemoglobin synthesis and formation of a small, enucleated, biconcave corpuscle. Major changes take place during erythropoiesis : 1. Cell and nuclear volumes decrease. 2. nucleoli diminish in size and disappear. 3. Chromatin density increases until the nucleus presents a pyknotic appearance and is finally extruded from the cell. 4. There is a gradual decrease in the number of polyribosomes (basophilia), with a simultaneous increase in the amount of hemoglobin (a highly eosinophilic protein). 5. Mitochondria and other organelles gradually disappear.  Maturation of erythrocytes Erythropoiesis requires approximately a week and involves three to five cell divisions. The responsible growth factor is erythropoietin. Maturation of granulocytes  Agranulocyte maturation The monoblast is a committed progenitor cell that is virtually identical to the myeloblast morphologically. Further differentiation leads to the promonocyte, with basophilic cytoplasm and a large, slightly indented nucleus Monocytes maturation develops into monocytes which have fine azurophilic granules at maturity. Monocytes circulate in blood for several hours and enter tissues where they mature as macrophages.  Lymphocyte progenitor cells originate in the bone marrow then migrate to the thymus acquire the properties of T lymphocytes. While B lymphocytes migrate to the peripheral lymphoid organs Lymphocyte The first identifiable progenitor of lymphoid cells is the lymphoblast, a large cell capable of dividing two or three maturation times to form lymphocytes. As lymphocytes develop, their nuclei become smaller, nucleoli disappear, and cell size decreases.  Origin of platelets It is small, membrane-enclosed formed elements called platelets or thrombocytes originate by fragmentation from mature megakaryocytes. Megakaryocytes which in turn differentiate from megakaryoblasts in a process driven by thrombopoietin. Origin of platelets Heart and circulatory system The cardiovascular system The cardiovascular system consists of The heart, arteries, veins, and microvascular beds. Moves blood throughout the body along two routes: The systemic circulation The pulmonary circulation. The Heart  The internal endocardium Layers of The middle myocardium the wall of the heart The external epicardium.  The endocardium The endocardium consists of: 1. The lining endothelium 2. Its supporting layer of fibroelastic connective tissue with scattered fibers of smooth muscle 3. A deeper layer of connective tissue (continuous with that of the myocardium and often called the subendocardial layer) a. The endocardium, includes the surface endothelium (En). The surrounding variable numbers of subendocardial layer of connective tissue (SEn) in the ventricles surrounds Purkinje fibers (P) of the heart’s impulse conducting modified cardiac muscle fibers that network. Purkinje fibers typically are paler staining than contractile muscle fibers (M). comprise the heart’s impulse b. In the atria, Purkinje-like fibers (P) often occupy most of the conducting system subendocardial layer, lying close to the endothelium (En), and merging with the contractile fibers of the myocardium (M), which is organized into many partially separated bundles and muscles. (Both X200; H&E). The myocardium The myocardium consists mainly of typically contractile cardiac muscle fibers arranged spirally around each heart chamber. Because strong force is required to pump blood through the systemic and pulmonary circulations, the myocardium is much thicker in the walls of the ventricles than the atria. The wall of the left ventricle is about three times thicker than that of the right ventricle because the left side must produce sufficient force to propel blood through the much larger systemic circulation with its multiple capillary beds The epicardium The epicardium is a simple squamous mesothelium supported by a layer of loose connective tissue containing blood vessels and nerves. The epicardium corresponds to the visceral layer of the pericardium, the membrane surrounding the heart. Where the large vessels enter and leave the heart, the epicardium is reflected back as the parietal layer lining the pericardium During heart movements, underlying structures are cushioned by deposits of adipose tissue in the epicardium and friction within the pericardium is prevented by lubricant fluid produced by both layers of serous mesothelial cells. Tissues of the vascular wall Walls of both arteries and veins have three tunics: 1. The intima 2. The media 3. The adventitia (or externa). An artery has a thicker media and relatively narrow lumen. A vein has a larger lumen, and its adventitia is the thickest layer. The intima of veins is often folded to form valves. Capillaries have only an endothelium, with no subendothelial layer or other tunics.  Comparison between the vascular walls Simple squamous endothelial cells (arrows) line the intima (I) that also has subendothelial connective tissue and in arteries is separated from the media by an internal elastic lamina (IEL), a structure absent in all but the largest veins. The media (M) contains many elastic lamellae and elastic fibers (EF) alternating with layers of smooth muscle. The media is much thicker in large arteries than veins, with relatively more elastin. Elastic fibers are also present in the outer tunica adventitia (A), which is relatively thicker in large veins. Vasa vasorum (V) are seen in the adventitia of the aorta. (a) Aorta (b) vena cava. Vasa vasorum large vessels usually have vasa vasorum (“vessels of the vessel”): arterioles (A), capillaries, and venules (V) in the adventitia and outer part of the media. The vasa vasorum are required to provide metabolites to cells in those tunics in larger vessels because the wall is too thick to be nourished solely by diffusion from the blood in the lumen. Luminal blood alone does provide the needs of cells in the intima. Because they carry deoxygenated blood, large veins commonly have more vasa vasorum than arteries. The adventitia of larger vessels also contains a network of unmyelinated autonomic (sympathetic) nerve fibers (N), the vasomotor nerves, which release the vasoconstrictor norepinephrine. The density of this innervation is greater in arteries than in veins. Vessel classification:  Elastic arteries The aorta, the pulmonary artery, and their largest branches. These large vessels are also called conducting arteries because their major role is to carry blood to smaller arteries. Have thick tunica media (M) in which elastic lamellae alternate with layers of smooth muscle fibers. During ventricular contraction (systole), blood is moved through the arteries forcefully and the elastin is stretched, distending the wall within the limit set by the wall’s collagen. When the ventricles relax (diastole), ventricular pressure drops to a low level, but the elastin rebounds passively, helping to maintain arterial pressure. A transverse section through part of a large elastic artery(X200 Muscular arteries Called distributing arteries; distribute blood to organs. With distance from the heart, arteries gradually have relatively less elastin and more smooth muscle in their walls. Multiple layers of smooth muscle (SM) in the media are thicker than the elastic lamellae and fibers with which they intersperse. Vasa vasorum (V) are seen in the adventitia. (X100; H&E) The microvasculature Microvasculature: Arterioles (A), capillaries (C), and venules (V). Where, in almost every organ, molecular exchange takes place between blood and the interstitial fluid of the surrounding tissues. Capillaries Lack Media and adventitia tunics and with diameters of only 4-10 μm. Not all interstitial fluid formed at capillary beds is drained into venules; the excess is called lymph and collects in thin-walled, irregularly shaped lymphatic vessels (L)  Arterioles a) Arterioles are microvessels with an intima (I) consisting only of endothelium (E), in which the cells may have rounded nuclei. They have media (M) tunics with only one or two layers of smooth muscle, and usually thin, inconspicuous (not clearly visible) adventitia (Ad).  Capillaries: The vessels between arterioles and venules (a) Continuous capillaries, the most common type, have tight, occluding junctions sealing the intercellular clefts between all the endothelial cells. Molecules exchanged must cross the cells by diffusion or transcytosis. (b) Fenestrated capillaries also have tight junctions, but perforations (fenestrations) through the endothelial cells allow greater exchange across the endothelium. The basement membrane is continuous in both these capillary types. Fenestrated capillaries are found in organs where molecular exchange with the blood is important, such as endocrine organs, intestinal walls, and choroid plexus. (c) Sinusoids, or discontinuous capillaries, usually have a wider diameter than the other types and have discontinuities between the endothelial cells, large fenestrations through the cells, and a partial, discontinuous basement membrane. Sinusoids are found in organs where exchange of  Capillaries Capillaries consist only of an endothelium rolled as a tube, across which molecular exchange occurs between blood and tissue fluid. (a) Capillaries are normally associated with perivascular contractile cells called pericytes (P). The more flattened nuclei belong to endothelial cells. Venules The transition from capillaries to venules occurs gradually. Postcapillary venules are similar to capillaries with pericytes but larger, ranging in diameter from 15 to 20 μm. Postcapillary venules converge into larger collecting venules that have more distinct contractile cells.  Veins Veins usually travel as companions to arteries. Classified as small, medium, or large based on size and development of the tunics. The wall of a small vein is very thin, containing only two or three layers of smooth muscle (a) Micrograph of small vein (V) shows a relatively large lumen compared to the small muscular artery (A) with its thick media (M) and adventitia (Ad). (X200; H&E) (b) Micrograph showing valve in an oblique section of a small vein (arrow). Valves are thin folds of intima projecting well into the lumen, which act to prevent backflow of blood.  Veins (c) Micrograph of a medium vein (MV) shows a thicker wall but still less prominent than that of the accompanying muscular artery (MA). (d) Micrograph of a medium vein contains blood and shows valve folds (arrows). (X200; Masson trichrome) An important feature of large and medium veins are valves, which consist of thin, paired folds of the tunica intima projecting across the lumen, rich in elastic fibers and covered on both sides by endothelium LYMPHATIC VASCULAR SYSTEM A system of very thin-walled channels, the lymphatic capillaries. Function: Collect excess interstitial fluid from the tissue spaces as lymph and return it to the blood. Like the interstitial fluid, lymph is usually rich in lightly staining proteins but does not normally contain red blood cells, although lymphocytes and other white blood cells may normally be present. Most tissues with blood microvasculature also contain lymphatic capillaries (or lymphatics), except the bone marrow and CNS. (a) Micrograph shows a lymphatic capillary filled with this fluid called lymph (L). Lymphatics are blind-ended vessels with a wall of very thin endothelial cells (E). (X200; Mallory trichrome)  LYMPHATIC VASCULAR SYSTEM Lymphatic capillaries originate locally as tubes of very thin endothelial cells. Lack tight junctions and rest on a discontinuous basal lamina. Specific domains of adjacent endothelial cells also lack hemidesmosome connections to the basal lamina and extend into the lumen to form leaflets of valves facilitating fluid entry and preventing most backflow of lymph. Lymph vessels Lymphatic capillaries converge into larger lymphatic vessels with thin walls and increasing amounts of connective tissue and smooth muscle that never form clearly distinct outer tunics. Like veins, lymphatic vessels have valves comprised of complete intimal folds. lymph nodes, where lymph is processed by cells of the immune system. Lymphatic vessels normally do not contain red blood cells, which provide another characteristic distinguishing them from venules. (a) Cross section shows a lymphatic vessel (LV) near a venule (V), whose wall is thick by comparison. (X200; Mallory trichrome) Lymph vessels Lymphatic vessels ultimately converge as two large trunks: the thoracic duct and the right lymphatic duct, which empty lymph back into the blood. The thoracic duct connects with the blood circulatory system near the junction of the left internal jugular vein with the left subclavian vein. The right lymphatic duct enters near the confluence of the right subclavian vein and the right internal jugular vein. The structure of these largest lymphatic vessels is similar to that of small veins. The adventitia is (b) Lymphatic vessel (LV) in muscle cut longitudinally shows a relatively underdeveloped, but contains vasa valve, the structure responsible for the unidirectional flow of lymph. The solid arrow shows the direction of the lymph flow, vasorum and a neural network. and the dotted arrows show how the valves prevent lymph backflow. The lower small lymphatic vessel is a lymphatic capillary with a wall consisting only of endothelium. (X200; PT)