Cardiovascular system Brno, May 2024 • Overall concept of blood circulation • Vessels • Arteries • Microcirculation • Veins • Lymphatics • Heart Lecture Blood cardiovascular Lymphatic vascular system Cardiovascular system = part of circulatory system Circulatory s. = Closed tubular system (carries fluids (blood, lymph) in tubes Cardiovascular system – overall composition Heart PUMP • moves bloood with all its elements 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 Microvasculature–<0.1mmMacrovasculature–diameter>0.1mm 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 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 0.15mm2mm 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 Tunica intima Tunica media Large = elastic = conducting arteries Tunica intima Monkey H & E x540 Tunica media transition Artery - Endothelium 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 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 wallsSmooth muscle cells predominate in their media 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) 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. 20-30 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 Capillaries - Continuous 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) 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 Microvasculature–<0.1mmMacrovasculature–diameter>0.1mm 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 Veins - Large Vena cava Bundles of smooth muscle cells Veins – Valves 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 Purkinje fibers Sinoatrial node Atrioventricular node 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 Thank you for your attention ! Questions and comments at: ahampl@med.muni.cz