SouvisejÃcà obrázek BLOOD AND HEMATOPOIESIS https://static.wixstatic.com/media/f7d5d5_556b193d57884373904c39dff4f187d6~mv2.jpg/v1/fill/w_646,h_ 363,al_c,q_80,usm_0.66_1.00_0.01/f7d5d5_556b193d57884373904c39dff4f187d6~mv2.webp Department of Histology and Embryology LF MU Petr Vaňhara BLOOD Blood is body fluid •transport medium (O2, CO2, metabolites, hormones, nutrients...) •homeostasis of inner body environment (thermoregulation, acidobasic equilibrium, oncotic pressure) •integrity of cardiovascular system (clotting cascade) •immune reactions • • • • • • • • • Výsledek obrázku pro buffy coat photo formed blood elements •erythrocytes •leukocytes •thrombocytes plasma •ions, proteins, low mass organic compounds •fluid ECM Blood can be considered as a specialized connective tissue Výsledek obrázku pro erythrocyte TEM BLOOD PLAMA AND TISSUE FLUID plasma •2,8-3,5 l •pH 7.4 (± 0.05) •~ 92% water •~ 1% ions (Na+, K+, Ca+, Mg+, Cl-, HCO3-), low mass organic compounds (glucose, aminoacids, cholesterol, lipids, waste products of metabolism), respiration gases •~ 7% proteins (albumins, globulins, fibrinogen) • Výsledek obrázku pro plasma tissue fluid Venous blood Lung capillaries Arterial blood Capillaries Venous blood IONS AND LOW MASS MOLECULES OF BLOOD PLSAMA (~1%) •~ 1% ions (Na+, K+, Ca+, Mg+, Cl-, HCO3-), low mass organic compounds (glucose, aminoacids, cholesterol, lipids, waste products of metabolism), respiration gases IONS AND LOW MASS MOLECULES OF BLOOD PLSAMA (~1%) Glucose 3,3–6,1 mmol/l Aminoacids 2,3–3,9 mmol/l Urea 3,0–7,6 mmol/l Lipids 4–9 g/l Triacylglycerols 0,5–1,8 mmol/l Phospholipids 1,8–2,5 g/l Creatinine 55–110 μmol/l Cholesterol (total) 3,5–5,2 mmol/l Bilirubin 3,3–18,0 μmol/l Lactate 0,55–2,22 mmol/l COMPOSITION OF BLOOD PLASMA IS CONSTANT regulated in narrow range® essential for clinical medicine •~ 1% ions (Na+, K+, Ca+, Mg+, Cl-, HCO3-), low mass organic compounds (glucose, aminoacids, cholesterol, lipids, waste products of metabolism), respiration gases PROTEINS OF BLOOD PLASMA (7%) •oncotic blood pressure •transport •coagulation •immune response •regulatory proteins • https://pharmaceuticalintelligence.files.wordpress.com/2014/06/major_plasma_proteins2.jpg https://pharmaceuticalintelligence.files.wordpress.com/2014/06/major_plasma_proteins2.jpg PROTEINS OF BLOOD PLASMA (7%) •prealbumin -transport •albumin -68kDa -transport -osmotic pressure •a1 region -a1 lipoprotein (HDL) -a1 acid glycoprotein -a1 antitrypsin -(a1 fetoprotein) •a2 region -a2 macroglobulin -haptoglobin •b1 region -transferrin -hemopexin -b lipoprotein (LDL) -C4 (complement) •b2 region -CRP -fibrinogen -b2 microglobuin -C3 (complement) •g region -IgA, IgG, IgM Výsledek obrázku pro electrophoresis of plasma proteins Výsledek obrázku pro electrophoresis of plasma proteins Å ¡ ̶ Výsledek obrázku pro electrophoresis https://en.wikipedia.org/wiki/Reference_ranges_for_blood_tests Výsledek obrázku pro buffy coat photo •serum ≠ plasma BLOOD PLASMA AND SERUM Výsledek obrázku pro blood plasma FORMED BLOOD ELEMENTS Výsledek obrázku pro hematokrit Leukocytes 4.5-11 ´ 103/ml neutrophils 71% eosinophils 3% bazophils 1% monocytes 5% lymfocytes 20% Thrombocytes 150-450 ´103/ml Erythrocytes 4.2-6.2 ´ 106/ml 55% 44% 1% Plasma Erythrocytes HEMATOCRIT Erythrocytes 4.2-6.2 ´ 106/ml 47±5% Výsledek obrázku pro hematokrit HEMATOCRIT 42±4% Ratio of erythrocyte mass volume to volume of full blood ♂ ♀ Plasma Buffy coat Erythrocytes Norm Anemia Polycythemia ERYTHROCYTES https://upload.wikimedia.org/wikipedia/commons/thumb/7/76/Osmotic_pressure_on_blood_cells_diagram.s vg/553px-Osmotic_pressure_on_blood_cells_diagram.svg.png Size depends on osmotic pressure of environment 7,5 2,6 0,75 Výsledek obrázku pro erythrocytes sem Deviations from normal size ERYTHROCYTES •anisocytosis -macrocytes (>9 µm) -microcytes (<6 µm) Výsledek obrázku pro anisocytosis ERYTHROCYTES Erythrocyte is amazingly flexible cell Výsledek obrázku pro erythrocyte TEM Výsledek obrázku pro erythrocyte capillary Výsledek obrázku pro erythrocyte rouleaux RBC cytoskeleton Výsledek obrázku pro spectrin ERYTHROCYTES Výsledek obrázku pro erythrocyte cytoskeleton Shape of erythrocytes •integral proteins -band 3, glycoprotein A (ion transporters) •spectrin •ankyrin • •aktin a s aktinem asociované proteiny -tropomodulin, tropomyosin •hemoglobin Deviations from biconcave shape •poikilocytosis -acantocytes (irregular spikes) -codocytes („tyre “) -echinocytes (spiked membrane) -eliptocytes (elliptic) -spherocytes (spheroidal) -stomatocytes (some parts missing or other irregularities) -drepanocytes (sickle) -dacrocytes (tear drop) - ERYTHROCYTES SouvisejÃcà obrázek Výsledek obrázku pro sickle cell erythrocyte Deviations from biconcave shape ERYTHROCYTES Normal Spherocyte Echinocyte Codocyte Hereditary elliptocytosis.jpg ERYTHROCYTES Hereditary eliptocytosis Hereditary elliptocytosis.jpg ERYTHROCYTES Hereditary eliptocytosis Hereditary Spherocytosis smear 2010-03-17.JPG Hereditary spherocytosis ERYTHROCYTES Sickle cell anemia •Abnormal hemoglobin (hemoglobin S) http://www.sicklecellinfo.net/images/understanding/oxy-deoxyalias.gif http://www.sicklecellinfo.net/images/understanding/fiber5.gif http://www.sicklecellinfo.net/images/understanding/namedfiberalias.gif Sickle cell 01.jpg Výsledek obrázku pro sickle cell erythrocyte ERYTHROCYTES Sickle cell anemia Výsledek obrázku pro plasmodium erythrocyte Malaria Výsledek obrázku pro plasmodium malariae sem Výsledek obrázku pro HBS malaria •pathological genotype (heterozygote HbS/HbA) is beneficial Výsledek obrázku pro hemoglobin erythrocyte https://upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Hemoglobin_t-r_state_ani.gif/300px-Hemogl obin_t-r_state_ani.gif ERYTHROCYTES •Erythrocytes lack nucleus and organelles •Anaerobic glykolysis • •Hemoglobin Výsledek obrázku pro hemoglobin erythrocyte Výsledek obrázku pro hemoglobin oxygen exchange ERYTHROCYTES Výsledek obrázku pro erythrocyte removal spleen Výsledek obrázku pro erythrocyte removal spleen Výsledek obrázku pro erythrocyte removal spleen Výsledek obrázku pro erythrocyte removal spleen ERYTHROCYTES •Life span 120 days •Constant abrasion •No regeneration •Removal of aged or damaged erythrocytes in spleen LEUKOCYTES •immune response •morphological classification – cytoplasmic granules (does not follow hematopoesis) Granulocytes Agranulocytes Neutrophils Eosinophils Basophils Monocytes Lymphocytes https://upload.wikimedia.org/wikipedia/commons/thumb/f/f0/Hematopoiesis_simple.svg/1800px-Hematopoi esis_simple.svg.png GRANULOCYTES •Lysosomes (primary, azurophilic, nonspecific granules) •Specific (secondary) granules •Polymorphic nucleus •Terminally differentiated •Short lifespan (hours) •Reduced ER, GA, mitochondria (anaerobic glycolysis) •Apoptosis Neutrophil Eosinophil Basophil SouvisejÃcà obrázek > NEUTROPHILIC GRANULOCYTES •Neutrophils -50-70% of leukocytes in circulation -Æ >12 mm -Segmented nucleus -Barr’s body in females -Azurophilic (primary) granules -myeloperoxidase, lysozyme, proteases, defensins -Neutrophilic (secondary) granules -collagenase, bactericidal enzymes -Chemotaxis of other leukocytes -Microphages - •Neutrophilic band •Neutrophilic segment http://vet.uga.edu/ivcvm/courses/VPAT5200/03_inflammation/05_cellular/images/pmn01.JPG Neutrophil, a leukocyte phagocytoses bacteria Výsledek obrázku pro Il était une fois… la Vie globules NEUTROPHILIC GRANULOCYTES Výsledek obrázku pro neutrophils in tissue NEUTROPHILIC GRANULOCYTES Výsledek obrázku pro neutrophils in tissue •Extravasation (diapedesis) Výsledek obrázku pro diapedesis and chemotaxis Leukocyte extravasation cartoon cell migration biology EOSINOPHILIC GRANULOCYTES •Eosinophils -1-4% of leukocytes in circulation -Æ 12-15 mm -Irregular, characteristic bi-segmented nucleus -Azurophilic (primary) granules -myeloperoxidase, lysozyme, proteases, defensins -Eosinophilic (secondary) granules -bright red (eosinophilic) -major acidic protein -peroxidase -cytokines, chemokines - -Chemotaxis of other leukocytes -Phagocytosis of antibody-antigen complexes -Parasitic infections, allergic reaction -Chronic inflammation Výsledek obrázku pro eosinophil in tissue BASOPHILIC GRANULOCYTES •Basophils -<1% of leukocytes in circulation -Æ 12 mm -Irregular, bisegmented nucleus, masked by granules - -Azurophilic (primary) granules -myeloperoxidase, lysozyme, proteases, defensins -Basophilic (secondary) granules -0.5 mm -large, dark (basophilic) -heparin, histamin - vasodilatation -phospholipase A -Analogs of mast cells -Receptors for IgE -Allergy, anaphylaxis, inflammation - Výsledek obrázku pro basophil TEM Výsledek obrázku pro basophil TEM AGRANULOCYTES •Lysosomes only (azurophilic, nonspecific granules) •Specific granules absent •Non-segmented nucleus Monocytes Lymfocytes LYMPHOCYTES •Round dominant nucleus •Basophilic cytoplasm •Variable lifespan •Biologically different lymphocytes (B, T, NK) are morphologically indistinguishable •Small, medium, large •Bone marrow, thymus •BCR/TCR/Antibodies with amazing variability Výsledek obrázku pro lymphocytes classification Výsledek obrázku pro B, T lymphocytes > LYMPHOCYTES •Plasma cells Plasma cell; B cell; shooting antibodies with a sling Výsledek obrázku pro plasma cell MONOCYTES •Æ 12-15 mm •Circulating precursors of macrophages, osteoclasts, microglia, Kupfer cells and dendritic cells •Mononuclear phagocytic system •Large, oval (bean, kidney) nucleus with less condensed chromatin and 2-3 nucleoli •Basophilic cytoplasm •Azurophilic granules Výsledek obrázku pro macrophage https://www.youtube.com/watch?v=R279Cs1_Itg THROMBOCYTES •Cell fragments without nucleus •Æ 2-3 mm, discoid shape •hyalomere, granulomere •150-400 ´ 103/ml •blood clotting, repair of vessel wall • SouvisejÃcà obrázek a-granules 300-500 nm fibrinogen, PDGF d-granules 250-300 nm serotonin, CaII+ pyrophosphate ADP, ATP l-granules 175-200 nm lyzosomal enzymes THROMBOCYTES 1.Primary aggregation of platelets -collagen fibers exposed by endothelial rupture -platelet clot 2.Secondary aggregation of platelets -clotting factors, ADP from thrombocytes attracts other platelets – white thrombus 3.Coagulation – blood clotting -fibrin mesh capturing erythrocytes – red thrombus 4.Thrombus retraction -contraction of thrombus (platelet actin and myosin) 5.Thrombolysis -dissolving of thrombus (plasmin) and tissue regeneration Jak funguje sráženà krve – struÄ�nÄ›, jasnÄ›, ve tÅ™ech bodech THROMBOCYTES Výsledek obrázku pro clotting cascade Neutrophil band 4 % segment 67 % 1:17 shift to the left shift to the right more bands more segments Eosinophils 3 % Basophils 1 % Lymphocytes 20 % Monocytes 5 % ∑ = 100 % DIFFERENTIAL WHITE BLOOD CELL COUNT Norm é Increased ê Decreased Neutrophils neutrophil granulocytosis neutrophil granulocytopenia Eosinophils eosinophil granulocytosis eosinophil granulocytopenia Basophils basophil granulocytosis basophil granulocytopenia Lymphocytes lymphocytosis lymphocytopenia Monocytes monocytosis monocytopenia DIFFERENTIAL WHITE BLOOD CELL COUNT Deviations from norm DIFFERENTIAL WHITE BLOOD CELL COUNT Neutrophils bands 0-5 % segments 35-85 % Eosinopils 0-4 % Basophils 0-1 % Lymphocytes 20-50 % Monocytes 2-6 % According to: Haferlach et al. Kapesní atlas hematologie. Grada 2014 Example of population variability https://upload.wikimedia.org/wikipedia/commons/thumb/b/b5/Reference_ranges_for_blood_tests_-_white_ blood_cells.png/1920px-Reference_ranges_for_blood_tests_-_white_blood_cells.png https://upload.wikimedia.org/wikipedia/commons/thumb/b/b5/Reference_ranges_for_blood_tests_-_white_ blood_cells.png/1920px-Reference_ranges_for_blood_tests_-_white_blood_cells.png DIFFERENTIAL WHITE BLOOD CELL COUNT Wikipedia Výsledek obrázku pro leukocytes children adolescents adults DIFFERENTIAL WHITE BLOOD CELL COUNT Age dependence https://obgynkey.com/elevated-or-depressed-white-blood-cell-count/ HEMATOPOIESIS https://upload.wikimedia.org/wikipedia/commons/thumb/f/f0/Hematopoiesis_simple.svg/1800px-Hematopoi esis_simple.svg.png ERYTHROPOIESIS •2 ´ 1011 of new erythroyctes daily •proerythroblast (~14-19 µm) -mitotically active -dominant, round nucleus with 1-2 nucleoli -mildly basophilic cytoplasm • •basophilic erythroblast (~13-16 µm) -mitotically active -heterochromatic nucleus with inconspicuous nucleoli -basophilic cytoplasm (sometimes more than in proerythroblast) - •polychromatophilic erythroblast (~13-16 µm) -mitotically active -production of hemoglobin -blue-gray cytoplasm due to combined basophilic (polyribosomes) and acidophilic aspects (hemoglobin) -heterochromatic nucleus (checkerboard appearance) • •orthochromatophilic erythroblast (~8-10 µm) -mitotically inactive -small, compact, eccentric, pycnotic nucleus ® extrusion -mildly acidophilic cytoplasm with basophilic residues • •reticulocyte (polychromatophilic erythrocyte, ~ 7-8 µm) -lacks nucleus, still spheroid shape -acidophilic cytoplasm -substantia reticulofilamentosa visible by supravital staining (brilliant cresyl blue) • •erythrocyte (~7-8 µm) -anucleate, biconcave disc -acidophilic cytoplasm Výsledek obrázku pro erythropoiesis ERYTHROPOIESIS proerythroblast orthochromatophilic erythroblast erythrocytes orthochromatophilic erythroblast basophilic erythroblast polychromatophilic erythroblast reticulocyte eryhtrocytes GRANULOPOIESIS •myeloblast (~15 µm) -mitotically active -round-oval, euchromatic nucleus -2-6 apparent nucleoli -weakly basophilic cytoplasm without granules - •promyelocyte (~15-24 µm) -mitotically active -round-oval nucleus with partly condensed chromatin -basophilic cytoplasm with azurophilic granules • •neutrophilic, eosinophilic or basophilic myelocyte (~10-16 µm) -mitotically active -oval or bean-shaped nucleus with condensed chromatin -increasing number of specific granules in cytoplasm • •neutrophilic, eosinophilic or basophilic metamyleocyte (~10-12 µm) -mitotically inactive -horseshoe-like nucleus with condensed chromatin • •neutrophilic, eosinophilic or basophilic granulocyte (~10-12 µm) -segmentation of nucleus -cytoplasm rich in specific and azurophilic granules Výsledek obrázku pro granulopoiesis myeloblast promyelocyte promyelocyte neutrophilic myelocyte promyelocyte eosinophilic myelocyte neutrophilic myelocyte neutrophilic metamyelocyte neutrophilic segment polycheomatophilic erythoblast GRANULOPOIESIS Výsledek obrázku pro granulopoiesis myeloblast promyelocyte myelocyte metamyelocyte granulocyte THROMBOPOIESIS Výsledek obrázku pro megakaryoblast •megakaryoblast (up to 30 µm) -large oval, nonlobed nucleus with prominent nucleoli -basophilic cytoplasm -successive endomitoses without karyokinesis and cytokinesis •promegakaryocyte (up to 100 µm) -large cell with polyploid nucleus (8n-64n) •megakaryocyte (80-150 µm) -polyploid, multilobed nucleus (8n-64n) -azurophilic and platelet granules -multiple centrioles, ER and Golgi apparatus -numerous peripheral invaginations of plasma membrane ̶ platelet demarcation channels defining individual thrombocytes -release of thrombocytes into bone marrow sinusoids Výsledek obrázku pro megakaryocyte TEM MONOCYTOPOIESIS •monoblast (~16 µm) -round, bean shaped nucleus with 2-6 nucleoli -mildly basophilic cytoplasm •promonocyte (~16-20 µm) -mitotically active (1-2 divisions) -large nucleus with mild indentation, unapparent nucleoli -basophilic cytoplasm -azurophilic granules •monocyte -short-time in circulation, then extravasation and differentiation to tissue macrophages LYMPHOPOIESIS •lymphoblast (~18-20 µm) -round-oval nucleus with several nucleoli -mildly-basophilic cytoplasm without azurophilic granules •prolymphocyte (~12-15 µm) -morphological transition and maturation to lymphocytes •lymphocyte -further maturation and differentiation outside bone marrow MONOCYTOPOIESIS AND LYMPHOPOIESIS Výsledek obrázku pro megakaryoblast OVERVIEW OF ADULT HEMATOPOIESIS Osteoclasts CD34+ HEMATOPOIETIC STEM CELLS AND PROGENITORS •Hematopoietic stem cell ‐Quiescent, slow cell cyle ‐Transmembrane phosphoglycoprotein CD34+ - adhesion within niche ‐No expression of lineage surface markers (Lineage negative or Lin-) ‐Transplantations Výsledek obrázku pro CFU-E •Colony/Burst – Forming Unit – CFU/BFU ‐Progenitors of individual lines ‐Collonies in vitro ‒ EMBRYONIC HEMATOPOIESIS •Extraembryonic mesoblastic period (day 16-20 – week 8) -yolk sac -classical model – hemangioblasts (bipotent cells) -large, nucleated erythroid cells • •aorta-gonad-mesonephros (day 28 – week 4) - •hepatolienal period (month 1 – birth) -colonization of fetal liver and spleen - •medullary period (month 4-6. – rest of life) -bone marrow Výsledek obrázku pro fetal liver hematopoiesis •hepatolienal and bone marrow hematopoiesis •erythroblast islands HEMATOPOIETIC ISLANDS Výsledek obrázku pro erythropoietic island An external file that holds a picture, illustration, etc. Object name is nihms340340f2.jpg •Aorta-gonad-mesonephros (day 28 – week 4) -para-aortic clusters in mesoderm of splanchnopleura -source of embryonic HSCs INTRAEMBRYONIC HEMATOPOIESIS Výsledek obrázku pro aorta-gonad-mesonephros •Placenta SUMMARY OF HEMATOPOIESIS Embryonic -yolk sac -AGM -liver and spleen -bone marrow - - - - - - - - - - Adult -bone marrow (yellow, red) -extramedullar hematopoiesis rare (pathology) • Výsledek obrázku pro embryonic adult hematopoiesis http://dev.biologists.org/content/133/19/3733 Cardiovascular system •Overall concept of blood circulation •Vessels •Arteries •Microcirculation •Lymphatics •Heart E:\杨\教学\解剖学\多媒体\下载图片\血液循环途径.jpg Blood cardiovascular Lymphatic vascular system Cardiovascular system = part of circulatory system Circulatory s. = Closed tubular system (carries fluids (blood, lymph) in tubes vessle-3 Cardiovascular system – overall composition Heart PUMP •moves bloood with all its elemnents through the body Blood vessels TUBES •distribute the blood to the cells throughout the body and then back to the heart Three major types Arteries •deliver blood from the heart to the capillaries Capillaries •intimate with body cells – place of exchange between blood and tissues Veins •carry blood from body to the heart Blood vessels – several different flavours Veins ALWAYS return the blood to the heart (contain about 2/3 body's blood at any given time) Arteries ALWAYS carry blood from the heart to the periphery LARGE MEDIUM + SMALL Capillaries Anastomosing tubules among arteries and veins = microvascular bed For example At ventricular diastole: •the semilunar valves are closed •no blood enters the arteries •the blood moves forward due to the action of arteries Blood vessels – flow of blood Pulsatile to continuous Due to specific morphologies of the vessels Vessel type Diameter (mm) Blood velocity (mm/sec) Aorta 25 1 200 (systolic) Arterioles 0.02-0.05 15 Capillaries 0.005-0.009 0.4 Venules 0.02 5 Inferior vena cava 30 80 …reflected by uneven distribution of blood 20_08 65 – 70% in veins •Reservoir •Lumens are larger than in corresponding arteries Capillaries ~ 100 thousand km (estimate) & only 5% of blood volume & largest surface area (~ 600 m2) & most of the cells are no farther than 50 mm from a capillary. Blood vessels – common building plan (three-layered) Lumen Endothelium Basement membrane + Subendothelial connective tis. Internal elastic lamina External elastic lamina Muscle layer Adventitia Tunica intima Endothelial cells: •polygonal, squamous, elongated •covered by negatively charged glycocalyx (0.5 mm) •provide repellent surface for cell elements •glycocalyx - binding site for various regulators •regulate permeability •secrete regulators (e.g. interleukins, Tunica media •mainly smooth muscle (circularly arranged in layers) •collagen and elastic fibers (lamelae), reticular fibers •proteoglycans •strenghten the vessels •provide vasomotion Tunica externa •connective tissue (collagen 1 + elastin) •home for vasa vasorum and nerve fibers •continuos with stroma of the surrounding tissues Arteries Several categories accoriding to their: size + structure + function Large = conducting = elastic artery (aorta, common carotid, sabclavian a., common iliac a., pulmonary trunk) Medium-sized = distributing = muscular artery (D > 1 mm) (brachial, ulnar, femoral, renal, …) Small artery (D = 0.1 -1 mm) Arteriole (D < 0.1 mm) Large = elastic = conducting arteries Conducting •their major function is to transport blood away from the heart Elastic • •they absorb and store the contractile energy of the left ventricle and transform the pulsatile flow of blood in smooth out • •during ventricular contraction (systole), the elastic laminae of conducting arteries are stretched and reduce the pressure change • •during ventricular relaxation (diastole) ventricular pressure drops to a low level but the elastic rebound of conducting arteries helps to maintain arterial pressure • •as a consequence, arterial pressure and blood flow decrease and become less variable as the distance from the heart increases Large = elastic = conducting arteries Lumen Endothelium Nerve Basement membrane + Subendothelium Tunica media Vasa vasorum Tunica adventitia Tunica intima 100 mm Endothelium •elongated cells - along the long axis Subendothelial layer •loose connective tissue •contains many fine longitudinal elastic fibres - these gradually merge into the elastic components of t. media •some smooth muscle cells near the boundary with t. media - longitudinally arranged •place of atherosclerotic changes • • Internal elastic lamina •not clearly demarcated •elastic fibers arranged circularly as discontinuous fenestrated membranes about 2.5 mm thick - about 50 lamellae •smooth muscle cells - circularly oriented, interspersed between elastic membranes •relatively thin •loose connective tissue •some elastic fibers – longitudinally arranged, next to the t. media •vasa vasorum and lyphatics (some into t. media) •nerves Relatively thin wall as compared to their wide lumen (1/10 of the vessel diameter). Large = elastic = conducting arteries aorta 2 Tunica intima Tunica media Large = elastic = conducting arteries Tunica intima Monkey H & E x540 Tunica media transition Artery - Endothelium mc401 WP body EM Weibel-Palade bodies •organelles that are unique to endothelial cells •contain von Willebrand factor (activates coagulation factor VIII) + P-selectin Arteries - Atherosclerotic changes Endothelial injury (upon predispozing factors) Production of ROS Oxidizing of LDL Entry of monocytes Plaque formation (conversion to foam cells) (necrosis + lipid accumulation) subendothelium Arteries - Atherosclerotic changes Atheromatous plaque Artery clogging Muscular arteries = distributing arteries Distributing •distribute blood to specific destinations/organs • •size varies from centimeter down to just visibility by unaided eye Muscular •they regulate the perfusion of different parts of the body under physiological conditions Muscle arteries = distributing arteries Endothelium •elongated cells along the long axis •well developed adhesion, tight, and gap junctions •Glycocalyx Subendothelial layer •thickness increases with age •loose connective tissue •many fine longitudinal elastic fibres •some smooth muscle cells Internal elastic lamina •well developed •relatively thíck (~ ½ of the tunica media) •collagen and elastic fibers •some fibroblasts and adipocytes •vasa vasorum and lyphatics (some into t. media) •nerves – efferent – maximal in small caliber arteries •very thick •concentrically arranged smooth muscle cells •up to 50 layers of smc •ECM with elastic, collagen and reticular fibers •GAP junctions between smc (coordination) • External elastic lamina •well demarkated only in large caliber arteries Lumen Endothelium Subendothelium Tunica media Tunica adventitia Tunica intima Internal elastic lamina External elastic lamina Muscular artery Muscular arteries = distributing arteries Muscle arteries = distributing arteries Undulation - Artefact (due to postmortem contraction of smooth muscle cells) Muscle arteries = distributing arteries Elastic stain Page 139 (7 Muscle arteries = distributing arteries – small sized -peripheral resistance vessel (along with arterioles) - -internal elastic lamina is clear x external elastic lamina is not distinguished - - the tunica media contains 3 to 10 layers of smooth muscles Muscle arteries = distributing arteries – small sized Muscle arteries x Elastic arteries Elastic elements predominate in their walls Smooth muscle cells predominate in their media F11_02 Arterioles - peripheral resistance vessel (along with small-sized arteries) - part of the microcirculation (terminal circulation) - internal diameter < 0.1 mm - they regulate the flow of blood through capillary bed Endothelium •elongated cells along the long axis Subendothelial layer •non-developed Internal elastic lamina •non-developed •reduced to only sheeth of collagen fibers •NO vasa vasorum •thin (still the major part of the wall) •1 to 2 layers of smooth muscle cells External elastic lamina •non-developed Lumen Endothelium Subendothelium Tunica media Tunica adventitia Tunica intima Internal elastic lamina External elastic lamina Muscular artery Arterioles Capillaries - are the site where materials carried in the blood are unloaded and other materials are loaded into the blood - are the thinnest, simplest, largest, longest, and most widely distributed functional unit of the blood vascular system - are inserted between arterial and venous limbs of the circulation - branch extensively to form elaborate networks, the extent of which reflects the activity of an organ or tissue -are the largest part of the microcirculation (along with arterioles and venules) re-circulation1 The total length of all the capillaries of the human body = about 100 000 km Maximal distance of tissue cell from the capillary = about 50 mm The length of the capillaries usually varies between about 0.25 and 1 mm The total cross-sectional area of capillaries = about 800 x greater than of the aorta Capillaries Extensive vasculature of renal cortex (perfused by red dye) Paritubular capillaries Scarse in: tendons, ligaments Absent from: cartilage, epidermis, cornea Capillaries Capillary wall Endothelium •single layer, squamous •serrated (wavy) cell borders •zonulae occludentes + desmosomes + GAP junctions Basal lamina „Envelope“ •pericytes (+ reticular fibers and macrophages) average diameter about 8 mm Basal lamina Endothelium Pericyte Capillaries Rabbit mesentery (H+E; 600x) Arteriole Precapillary sphincter Capillary Only about 25 - 50 % of capillary volume is actively moving (containing) blood under normal conditions. 20-87 Capillaries – Regulation of blood flow Capillaries Pericyte Striated muscle Cerebellum (monkey) Capillaries According to the integrity of the endothelium and basement membrane – by TEM: •Continuous capillary • •Fenestrated capillary • •Sinusoidal 0363_0001 Capillaries - Continuous Figure 20 How ? • •non-interrupted lining •no defects in the wall (endothelium + basal lamina Where ? • •most common type •muscle, connective tissue, nerve tissue (blood-brain barrier), exocrine glands Capillaries - Fenestrated How ? • •endothelial cells perforated (diameter ~60-80 nm; diphragm 4-6 nm) •continuous basal lamina Where ? • •in tissues where rapid interchange of substances occurs between the tissue and the blood •intestinal mucosa, some endocrine glands, pankreas, choroid plexus, ciliary body, … •kidney glomeruli (no diaphragm over fenestrae) Fenestrae with diaphragm Fenestrated capillary - kidney Diaphragm Capillaries – Sinusoidal - Discontinuos How ? • •enlarged diameter (up to 40 mm) •endothelial cells with large pores without diaphragm •large clefts between endothelial cells •discontinous basal membrane (or even absent) •pericytes are absent (macrophages instead) Where ? • •liver (pores 100 nm) •hematopoietic regions (bone marrow) •endocrine glands (adenohypophysis, islets of Langerhans) C:\Documents and Settings\Sedláčková.HIST4\Dokumenty\Obrázky\prezentace, testy kardio\sinusoida a.jpg Sinusoid Capillaries – Sinusoidal - Discontinuos Bone marrow Blood vessels – several different flavours Veins ALWAYS return the blood to the heart (contain about 2/3 body's blood at any given time) Arteries ALWAYS carry blood from the heart to the periphery LARGE MEDIUM + SMALL Capillaries Anastomosing tubules among arteries and veins = microvascular bed Veins – capacitance vessels - they function as blood reservoir - greater capacity for blood containment than arteries due to thinner wall - lower blood pressure (10 mm Hg with little fluctuation) - valves aid skeletal muscles in upward blood flow (typically in lower limbs – veins with diameter > 2 mm) Three layered bulding plan = paired duplication of t. intima Endothelium •very thin Subendothelial layer •very thin Internal elastic lamina •missing or only very thin •well developed – thickest layer •often with longitudinally arranged bundles of smooth muscle cells •robust vasa vasorum (often penetrate deep to t. media) •relatively thin (except for lower limbs) •Little bundles of smooth muscle cells •collagen fibers – considerable amount External elastic lamina •non-developed General features Veins – Categories according to their diameter Postcapillary venules •endothelial cells + some pericytes •receive blood from capillaries •more porous than capillaries •larger diameter than capillaries (15-20 mm) Small- & Medium-sized veins •most have individual names •run parallel with corresponding arteries •many have valves Large veins •close to the heart •(v.cavae, pulmonary veins, internal jugular veins) •paired with elastic arteries •diameter > 10 mm •with valves •t. media is thin (muscle cells+connective tissue) •thick t. externa (with longitudinal bundles of smc; myocardial sleeves) Collecting & Muscular venules •increasing number of contractile cells •tunica media is defined in muscular venules Artery Vein Veins – Middle-sized 图片6 Veins - Large Vena cava Bundles of smooth muscle cells Veins – Valves valve6 Appearence of internal surface Histological view - bag-like protrusion of tunica intima, which prevent the blood flow from running to opposite direction - only in the veins that has low position or far away from heart Lymphatic vessels Thoracic duct Right lymphatic duct -return fluid from tissues to the circulatiory system - -depend on skeletal muscles to move fluid Lymphatic capillaries •blunt ended •very simple structure •endothelial cells + fine reticular fibres of circular orientation •the basal lamina is not developed Lymphatic vessels and ducts •thin walled tubes •resemble veins in their structure (intima+media+adventitia) •have valves Lymphatic vessels Heart - Anatomy - a hollow organ that contracts rhytmically - it functions as a pump - it is composed of two sets of chambers: Receiving atria Right Left Discharging ventricles Right Left -it is equipped by four valves (blood can travel in only one direction) Aortic semilunar Pulmonary semilunar Atrioventricular tricuspid (right) Atrioventricular bicuspid (left) Heart - Wall Endocardium •endothelium •subendothelial layer •subendocardial layer Myocardium Epicardium •mesothelium •submesothelial layer inner surface outer surface Heart - Endocardium inner surface - is continuous with the tunica intima of the large vessels entering and leaving the heart - - the endocardium of the left half of the heart is not continuous with the one on the right half as it is separated by a heart septum - valves are derivatives of endocardium - Subendothelial layer •connective tissue •collagen, elastics, solitary smc, small blood vessels, nerves Subendocardial layer •loose connective tissue •continuous with endomysium of the myocardium •nerve fibers, vessels, impuls-conducting system Purkinje fibers Endothelium •with continuous basal membrane Heart - Myocardium - its thickness varies in different parts (thickest – left ventrikle; thin in atria) - - has rich blood supply (many capillaries) - has no regenerative capacity - muscle fibers are arranged circularly around chambers - masses of connective tissue in between the muscles – cardiac skeleton (anuli fibrosi in valves, trigonum, septum membranaceum) inner surface left ventricle wall right ventricle wall interventricular septum Intercalated discs Atrial natriuretic peptide (endocrine function of contractile cells; acts on kidney) Heart - Epicardium - represents visceral layer of the pericardium inner surface Mesothelium Mesothelium •simple squamous epithelium •basal lamina •secretes pericardial fluid Submesothelial layer •loose connective tissue •elastic fibers •nerves •blood and lymphatic vessels •home of coronary vessels •adipocytes (high in obese individuals) Pericardium Fibroserous sac enveloping heart •mesothelium with basal lamina (faces epicardium) •fibrous layer (dense connective t. with vessels and nerves) Heart - Valves - composed of connective tissue layers covered by endothelium on each side Fibrosa •dense core of connective tissue Ventricularis •dense connective tissue with many elastic and collagen fibers Spongiosa •loose collagen Atrial side Ventricular side Heart – Conducting system - specially modified cardiac muscle cells (non-contracting, less myofibrils, abundant GA junctions) - generate and conduct impulses of heart contraction to various parts of myocardium - assure proper succession of beat of atria and ventricles Sinoatrial node (node of Keith-Flack) •it lies on the medial wall of the right atrium near the entrance of the superior vena cava •PRIMARY PACEMAKER Atrioventricular bundle (bundle of Hiss) • •it divides into 2 branches (for the left and right ventricles) Purkinje fibres •terminal ramifications of the AV bundle Atrioventricular node (node of Ascoff and Tawara) •it runs on the right side of the interatrial septum •SECONDARY PACEMAKER • Atrioventricular bundle Heart – Conducting system Contractile cardiomyocytes Signal-conducting Purkinje cells Heart – Coronary circulation - blood in the heart chambers does not nourish the myocardium - the heart has its own nourishing circulatory system: Coronary arteries & veins - 5-7% of blood flows through the coronary arteries - blood empties into the right atrium via the coronary sinus Dye injected into heart X-ray to examine blockages DEVELOPMENT OF CARDIOVASCULAR SYSTEM Petr Vaňhara, PhD Dept. of Histology and Embryology Faculty of Medicine, Masaryk University http://i45.tinypic.com/2vhsrqb.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM DEVELOPMENT OF CARDIOVASCULAR SYSTEM •rapid growth of embryo •insuffcient supply by diffusion •first vascularisation develops outside embryo – yolk sac, chorion and connecting stalk •bipotential (hem)angioblasts in blood islands •vasculogenesis and angiogenesis •blood cells formation • https://embryology.med.unsw.edu.au/embryology/images/c/ce/Stage5_bf11L.jpg Week 2-3 DEVELOPMENT OF CARDIOVASCULAR SYSTEM •embryonic vasculogenesis approx. 2 days later after establishment of extra-embryonic vessels •primordial blood vessels •heart primordium in cardiogenic area •embryonic hematopoiesis from para-aortic clusters in AGM • End of week 3 Image result for yolk sac vasculature DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 1 2 3 •embryonic circulation: heart tube ® truncus arteriosus ® aortal arches ® paired dorsal aorta ® caudally fuse into single aorta dorsalis ® capillary beds ® paired cardinal veins (drain pre- and postcardinal veins) ® ductus Cuvieri ® sinus venosus • •vitelinne circulation: dorsal aorta ® aa. omphalomesentericae ® fuse into single a. omphalomesenterica ® vv. omphalomesentericae + vv. umbilicales ® paired truncus vitelloumbilicalis ® sinus venosus • •umbilical circulation: dorsal aorta ® aa. umbilicales ® chorion ® vv. umbilicales + vv. omphalomesentericae ® paired truncus vitelloumbilicalis ® sinus venosus DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 6 Week 7 Week 8 Postnatal Week 4 > DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 3 •paired endothelial heart tubes (cor tubulare duplex) derived from embryonic splanchnopleura in cardiogenic area •flexion of the embryo ® medial fusion of paired tubes into simple-tubular heart (cor tubulare simplex) •visceral mesoderm constitutes myoepicardial layer: myocardium and epicardium •cardiac jelly ® subendocardial connective tissue •heart starts beating day 21-22 •blood starts flow ~week 4th • Blood cells Endocardium Myocardium Primitive heart development DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 •simple-tubular heart (cor tubulare simplex and cor tubulare sigmoideum ) •sinus venosus ® atrium ® ventriculus ® bulbus cordis® truncus arteriosus • Image result for simple tubular heart Paired dorsal aorta Truncus arterosus Bulbus cordis Ventriculus Paired atrium and sinus venosus Right auricle Left auricle Aorta Ventricle Sternocostal surface DEVELOPMENT OF CARDIOVASCULAR SYSTEM Cor tubulare simplex Cor tubulare sigmoideum Week 4 DEVELOPMENT OF CARDIOVASCULAR SYSTEM DEVELOPMENT OF CARDIOVASCULAR SYSTEM •septum primum grows from dorso-cranial wall towards endocardial cushions •incoplete closure ® foramen (ostium) primum •by apoptosis ® foramen secundum •septum secundum ® surrounds foramen ovale •valvula foraminis ovalis from septum primum • • •foramen ovale: crucial embryonic shunt •foramen ovale patens • •after atrial septation: -opening of sinus venosus shifts to the right -rest of sinus venosus ® sinus coronarius - Image result for septum primum Image result for fetal heart circulation Partitioning of atrium commune DEVELOPMENT OF CARDIOVASCULAR SYSTEM •septum interventriculorum primitivum – temporary •septum interventriculare at the end of week 4 – grows cranially •foramen interventricualre – closure linked to development of aortico-pulmonary septum • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Partitioning of ventriculus communis •5th week – ridges in bulbus and truncus from neural-crest mesenchyme •180° spiraling – spiral aortico-pulmonary septum •pulmonary trunk twists around aorta • •bulbus cordis is embedded into the definitive ventricles: •right ventricle: conus arterious (infundibulum) ® pulmonary trunk •left ventricle: aortic vestibule • • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Image result for partitioning of bulbus cordis and truncus arteriosus •Partitioning of bulbus cordis and truncus arteriosus DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 20 •semilunar valves develop by the partitioning of truncus arteriosus from three swellings of endocardial tissue •neural crest origin •AV valves (tricuspid and mitral) develop similarly at AV canals • DEVELOPMENT OF CARDIOVASCULAR SYSTEM •Development of cardiac valves https://embryology.med.unsw.edu.au/embryology/images/a/a1/Stage_22_image_178.jpg File:AV Canal Division (Superior View).jpg File:AV Valves.jpg File:Semilunar Valves.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM https://embryology.med.unsw.edu.au/embryology/images/1/1f/Basic_Heart_Development_Timeline.jpg Image result for branchial arteries fish File:Embryonic Circulations.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM DEVELOPMENT OF CARDIOVASCULAR SYSTEM Development of large arteries – aortic arches Výsledek obrázku pro aortic arches Výsledek obrázku pro aortic arches 1 mostly disappears, a. maxillaris 2 mostly disappears, a. stapedia and a. hyoidea 3 a. carotis communis, a. carotis interna 4 right: proximal part of a. subclavia dextra (distal part from dorsal aorta and 7th intersegmental artery); left: arcus aortae 5 does not develop 6 right: from proximal part: a. pulmonalis dextra, distal part disappears left: from proximal part: a. pulmonalis sinistra, from distal part: ductus arteriosus. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Aortic arches •aa. vitellinae (aa. omphalomesentericae) reduced to three principal vessels: 1truncus coeliacus 2a. mesenterica superior 3a. mesentrica inferior • • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Vitelline arteries Image result for mesenteric arteries Image result for primitive gut vascularisation •First, aa. umbilicales are ventral branches of dorsal aorta •Later, aa. umbilicales are continuations to aa. iliacae communes and aa. communes internae. • •After birth: proximal parts of aa. umbilicales form aa. iliacae internae and aa. vesicales superiores. Distal parts obliterate. • • Umbilical arteries DEVELOPMENT OF CARDIOVASCULAR SYSTEM Image result for umbilical circulation https://www.trando-med.com/Content/upload/2018253296/201810231014364855.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM •four primary segments 1hepatic segment (proximal part of the right vitelline vein = hepatic vein) 2prerenal segment (right subcardinal vein) 3renal segment (subcardinal – supracardinal anastomosis) 4postrenal segment (right supracardinal vein) •Anomalies of venae cavae • •Double SVC: persistence of left anterior cardinal vein; Abnormal CVC opens to right atrium through sinus coronarius •Left SVC: right anterior cardinal vein and v. cardinalis communis degenerate •Absence of hepatic segment of IVC: blood drained through v. azygos and hemiazygos into right atrium. Vv. hepaticae opens to right atrium individually. •Double IVC: absence of anastomoses between primitive caudal veins. Inferior vena cava DEVELOPMENT OF CARDIOVASCULAR SYSTEM Vv. omphalomesentericae •bring blood from yolk sac •septum transversum •sinus venosus (together with umbilical veins as trunci vitelloumbilicales) •growth of liver – separation of omphalomesenteric veins to proximal (yolk sac-liver) and distal parts (liver-heart) •distal parts form anastomoses and develop into v. portae •proximal parts dorm posthepatic part of IVC •begin in chorionic villi •due to liver growth lose connection with sinus venosus •proximal parts of both veins disappear •distal part of right v. umbilicalis disappears •distal part of left v. umbilicalis forms ductus venosus Vv. umbilicales DEVELOPMENT OF CARDIOVASCULAR SYSTEM Teratology •Acardia •Ectopia cordis •Dextrocardia •Atrial septal defects •Ventricular septal defects •Stenosis of truncus pulmonalis •Atresia pulmonaris •Tetra (penta)llogy of Fallot •Coartaction of aorta •Ductus arteriosus apertus • https://www.wikiskripta.eu/images/2/2d/Defekt_koarktace.png https://www.wikiskripta.eu/images/5/5c/Defekt_fallot.png https://www.wikiskripta.eu/images/1/11/Defekt_pda.png https://www.wikiskripta.eu/images/2/2e/Defekt_septum_sinove.png https://www.wikiskripta.eu/images/f/f7/Defekt_septum_komorove.png Výsledek obrázku pro primitive blood circulation Výsledek obrázku pro fetal blood circulation Fetal circulation Embryonic circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM Image result for blood circulation Image result for blood circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM Thank you for attention Questions? 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