Cardio-vascular.pdf

HISTOLOGY. CARDIOVASCULAR SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.16 – Cardiovascular system HIST.16.01 - List the three principal types of vessel in the blo...

HISTOLOGY. CARDIOVASCULAR SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.16 – Cardiovascular system HIST.16.01 - List the three principal types of vessel in the blood vascular system and give their function HIST.16.02 - List the components of the three layers in the walls of arteries HIST.16.03 - Describe the tunica adventitia of an elastic artery and give its function HIST.16.04 - Compare the tunica media of an elastic and a muscular artery and describe their functions HIST.16.05 - Explain the principal age change in arteries HIST.16.06 - Compare the structure of fenestrated, continuous and discontinuous capillaries HIST.16.07 - State the location and the function of the pericyte HIST.16.08 - Describe the structure and function of an arteriovenous anastomosis HIST.16.09 - Compare the structure and function of a venule and arteriole HIST.16.10 - Compare the structure and function of a vein and a muscular artery HIST.16.11 - Describe the distribution of vasa vasora in a vein and an artery & explain the differences HIST.16.12 - Describe the structure of valves in veins and explain their function HIST.16.13 - List the components of the three layers in the wall of the heart HIST.16.14 - Describe Purkinje fibers and compare their structural features to cardiac muscle fibers HIST.16.15 - Describe structure and function of the pericardium  Overview of the CVS Circulatory system (cardiovascular system - CVS) ensures the circulation of blood and lymph. It delivers nutrients to various compartments of the body and transports waste from cells to the excretory organs. It also provides for the transport of hormones to target tissues.  Overview of the CVS Blood vascular systems Lymphatic vascular systems Blood vascular system is composed of: Heart – muscular pump that maintains unidirectional flow of blood, Arteries carry the blood with nutrients and oxygen to the tissues, Capillaries where the interchange between blood and tissues takes place, Veins convey products of metabolism toward the heart. Anastomosis – direct connection of blood vessels of the same type (a+a, v+v or even a+v bypassing capillaries) that form a collateral system.  Overview of the CVS Typical connection the most common course of blood vessels in the human organism: (artery - arteriole - capillary network - venule - vein).  General structure of the blood vessel Blood vessels are usually composed of 3 layers, or tunics (tunica = coat): Tunica intima (inner layer) Tunica media Tunica adventitia (outer layer) ‘advent’ = added to  General structure of the blood vessel I. Tunica intima consists of: 1. Endothelial cells – simple squamous epithelium (inner layer), resting on a basal lamina; 2. Subendothelial layer – loose connective tissue (LCT); 3. In arteries the intima is separated from the tunica media by an internal elastic lamina, composed of elastin.  General structure of the blood vessel II. Tunica media consists of smooth muscle cells or/and elastic fibers; ! Function of vessel depend on structure of this layer; usually either smooth myocytes or elastic fibers predominate III. Tunica adventitia consists of LCT with collagen and elastic fibers; contains nerves and vasa vasorum (vessels of the vessels).  Endothelial cells Thin squamous cells Held together by occluding junctions. Cytoplasm shows numerous pinocytotic vesicles, that help transport materials from blood to the underlying tissue. Weibel-Palade granules rod-shaped granules (0.1 x 0.3 µm) contain von Willebrand's factor - important element of the coagulation cascade P-selectin - ability to increase the permeability of endothelial cells, permitting the components of the cell- mediated immune system (leukocytes) to roll, marginate, and enter the extracellular focus of inflammation (diapedesis). P-selectin also plays a role in platelet aggregation. * Patients with von Willebrand disease, an inherited disorder that results in impaired adhesion of platelets, have prolonged coagulation times and excessive bleeding at an injury site.  Endothelium Endothelium controls contraction and relaxation of vascular smooth muscle cells (myocytes) in the tunica media influencing local blood flow and pressure. Secrete types II, IV, and V collagens, laminin, endothelin, nitric oxide. Possess membrane-bound enzymes, such as angiotensin-converting enzyme (ACE), which cleave angiotensin I to generate angiotensin II. Possess enzymes that inactivate bradykinin, serotonin, prostaglandins, thrombin, and norepinephrine. Bind lipoprotein lipase that degrades lipoprotein triglycerides into glycerol and fatty acids.  Nourishment of blood vessels In small- and medium-sized blood vessels, all the layers get oxygen and nourishment by diffusion from the blood present within the lumen of the blood vessel. In large-sized blood vessels, the oxygen cannot reach the outer parts of the media and adventitia. There are small blood vessels vasa vasorum within these layers which nourish these layers. Coronary arteries are analogous to vasa vasorum for myocardium of heart.  Arteries Arteries transport blood to tissues.  resist changes in blood pressure in their initial portions  regulate blood flow in their terminal portions. Classification of arteries: Elastic (large) arteries Muscular (medium) arteries Muscular-elastic (*according to some authors)  Small arteries and arterioles  Elastic (conducting) arteries Blood is pumped from the heart into large, elastic (conducting) arteries. Examples: aorta, brachiocephalic, common carotid and subclavian arteries, pulmonary trunk, pulmonary arteries. Structure: I. Tunica intima: 1) endothelium is without folds; 2) subendothelial layer is thick and contains collagen and elastic fibers; 3) internal lamina; II. Tunica media consists of concentrically arranged perforated elastic laminae (membranae fenestratae elasticae) 40–70 layers of elastic membranes; openings in the membranes (fenestrations) are necessary due to the impermeability of elastin. III. Tunica adventitia consists of LCT+ elastic and collagen fibers, blood vessels and nerves.  Elastic artery Elastic Artery Staining: Aldehyde Fuchsin - click to open  Muscular (disturbing) arteries These arteries distribute blood to tissues; hence, also called distributing arteries Most of the arteries in the human body are muscular arteries. Examples: arteries of the limbs, brachial artery and femoral artery In muscular arteries blood passes at a reduced pressure and speed. Diameter of their lumen is controlled by contraction or relaxation of smooth muscle on their wall.  Muscular artery 1. Tunica intima forms numerous small folds: 1.1 Endothelium is simple squamous epithelium, 1.2. Subendothelial layer contains a few smooth muscle cells, 2.1 Internal elastic lamina is prominent and forms small wavy folds; 2.2 Tunica media comprises a thick layer of circumferentially arranged smooth muscle; 2.3 External elastic lamina is present in large muscular arteries; 3. Tunica adventitia consists of LCT and contains elastic and collagen fibers. Muscular artery Staining: H&E  Arterioles Less than 0,5 mm in diameter and have narrow lumen Wall of the arterioles contains: I. Tunica intima forms numerous folds; consists of: 1) endothelium is simple squamous epithelium, 2) subendothelial layer is very thin. 3) internal elastic lamina is prominent and forms small wavy folds; II. Tunica media composed of 1-2 circularly arranged layers of smooth muscle cells; external elastic lamina is absent; III. Tunica adventitia is thin. Comparison of arteries and arterioles  Clinical correlation - atherosclerosis Atherosclerosis is disease of artery that narrows lumen because of plaque – atheroma (sclerosis means hardening, in Greek). Atheroma is accumulation of lipids which protrude into the lumen of the blood vessel and obstruct them. Atherosclerosis causes narrowing of blood vessel lumen, and reduced blood supply to viscera. May lead to heart attack (myocardial infarction) or paralysis (stroke). Atheroma may rupture and cause thrombus formation; it also weakens the tunica media. This can cause localised abnormal dilation of the blood vessels, known as aneurysm. Atherosclerotic changes in coronary artery cause reduced blood supply to heart (ischemic heart disease).  Clinical correlation - Peripheral artery disease (PAD) PAD is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. PAD most commonly affects the arteries in the legs. Pathogenesis: Atherosclerosis: primary cause of PAD, plaque builds up in the arterial walls, narrowing and hardening the arteries. Diabetes: high blood sugar levels can damage blood vessels over time, contributing to the development of PAD. Smoking: nicotine constricts blood vessels and damages their inner lining, promoting atherosclerosis. Hypertension: can damage the arteries by making them less elastic, which decreases the flow of blood and oxygen. Obesity: increases the risk of developing conditions that can contribute to PAD. Symptoms: Intermittent claudication: pain and cramping in the legs that occurs during physical activity and is relieved by rest. Leg numbness or weakness due to inadequate blood flow. Coldness in lower leg or foot. Sores on toes, feet, or legs, wounds that do not heal properly due to poor blood flow. Change in leg colour: skin on the legs may become pale or bluish. Hair loss or slower hair growth on the legs and feet. Shiny skin on the legs. Weak or absent pulse in the legs or feet.  Veins Veins return blood to the heart, aided by the action of smooth muscle and specialised valves. Classification of the veins Unmuscular (atypical) Muscular: 1) with weak development of muscular elements; 2) with middle development of muscular elements; 3) with strong development of muscular elements. Venules.  Unmuscular veins Located in organs with dense walls (meninges, bones, spleen, etc.) with which they strongly fuse external tunic. The wall consists of endothelium, which is surrounded by layer of a CT. Smooth muscle cells are absent.  Muscular veins with weak development of muscular elements Located above the level of the heart on which blood goes passively owing to weight. Structure of the wall: I. Tunica intima: 1) endothelium. 2) subendothelial layer is weak-developed, 3) internal elastic lamina is absent; II. Tunica media is thin with a small amount of smooth muscle cells; external elastic lamina is absent; III. Tunica adventitia contains LCT.  Muscular veins with middle development of muscular elements Located on the level of the heart. Structure of the wall: I. Tunica intima forms the valves and consists of: 1) endothelium. 2) subendothelial layer is weak-developed, 3) internal lamina is absent. II. Tunica media consists of few layers of smooth muscle cells; external elastic lamina is absent; III. Tunica adventitia contains LCT.  Muscular veins with strong development of muscular elements Located below the level of the heart. Contain well-developed bundles of smooth muscle cells in all three tunics: in the intima and adventitia bundles have a longitudinal direction, and in the media - circular. Contain numerous valves. Valves = two semilunar folds of the tunica intima that project into the lumen, composed of elastic CT and are lined on both sides by endothelium. Venous valves  Clinical correlation – varicose veins Varicose veins are abnormally enlarged, tortuous veins usually affecting the superficial veins in the legs of older persons. This condition results from loss of muscle tone, degeneration of vessel walls, and valvular incompetence, prolonged standing. Varicose veins may also occur in the lower end of the esophagus (esophageal varices) or at the terminus of the anal canal (hemorrhoids).  Clinical correlation - deep venous thrombosis Deep venous thrombosis (DVT): in medium-sized veins, especially of lower limb, thrombus may form. It is especially seen in patients with prolonged bed rest and orthopedic cases with casts for the treatment of fractures. Part of such clots may get separated, enter pulmonary circulation and form blockage (pulmonary embolism). A 45-year-old male presents to the emergency department with sudden onset shortness of breath, pleuritic chest pain, and hemoptysis (discharge of blood or blood-stained mucus through the mouth coming from the bronchi, larynx, trachea, or lungs). He has a history of recent surgery for a fractured leg and has been relatively immobile since then. On physical examination, he has a heart rate of 110 beats per minute, a respiratory rate of 28 breaths per minute, and his oxygen saturation is 89% on room air. A chest CT angiography is performed and shows a filling defect in the pulmonary artery. What is the most likely diagnosis? A. Acute myocardial infarction B. Pneumothorax C. Pulmonary embolism D. Acute bronchitis E. Congestive heart failure  Comparison of arteries and veins Characteristics of the wall of the arteries the strongest layer is the media, which is sharply demarcated from the adventitia membrana elastica interna et externa are present Characteristics of the wall of the vein: the lumen is shattered (collapsed) the strongest layer is the adventitia, formed by collagenous CT with numerous elastic fibers small and medium veins contain valves.  Example of a muscular (distributing) artery and medium vein Artery Vein  Venules Important sites for the exchange of metabolites. Smallest venules have tunica intima and adventitia. As the size of venules increases, smooth muscles appear and form tunica media; Tunica media may contain only contractile pericytes, but a few smooth muscle cells are usually present. Venule; like capillaries, but larger venules may have smooth muscle  Postcapillary venules Normally many WBCs conveyed in the blood leave blood vessels to enter the tissues. This occurs at the level of postcapillary venules. When pathologic changes occur in the body, such as inflammatory reaction, large numbers of WBCs emigrate from these venules.  *Length of the capillaries in the whole human body Capillaries summed together is estimated to be 96,000 km. Microscopic vessels with diameter of about 8 pm. They branch and anastomose to form a network. Capillaries have a structure to permit two-directional exchange between blood and surrounding tissues.  General structure of capillary wall I. Single layer of endothelial cells, that rest on the basal lamina; II. Pericytes (also called Rouget cells or mural cells) are cells with long cytoplasmic processes that partly surround the endothelial cells; have contractile function; represent a population of undifferentiated mesenchymal stem cells. III. +- Adventitial cells. 1. Endothelium 2. Basal lamina 3. Pericyte  Types of capillaries 1. Continuous, or somatic, capillaries have uninterrupted lining of endothelial cells and basal lamina; Distribution: muscle tissue, lungs, connective tissue, exocrine glands, nervous tissue. 2. Fenestrated, or visceral, capillaries have large fenestrae (openings) that are closed by a diaphragm; continuous basal lamina is present. Distribution: endocrine glands, glomerulus of the kidney. 3. Discontinuous, or sinusoidal capillaries have wide diameter. Endothelial cells show multiple fenestrations without diaphragms; basal lamina is discontinuous. Distribution: liver, hematopoietic organs such as bone marrow and spleen. Types of capillaries Organs such as the brain and thymus have a more effective blood barrier because their blood capillaries are of which of the following types? A. Continuous type with few vesicles B. Fenestrated type with diaphragms C. Fenestrated type without diaphragms D. Discontinuous type without diaphragms In a histological specimen of a vessel, internal and external elastic membranes are well-expressed; numerous myocytes are found in the tunica media. What type of vessel is it? A. Artery of muscular type B. Vein with strong development of muscles C. Artery of elastic type D. Extraorganic lymphatic vessel E. Unmuscular vein  Variations in circulatory pathways - Portal systems Portal system („rete mirabile“) – two capillary systems arranged in series In the kidney, there is an arterial portal system, which ensures the production of urine and nutrition of the renal parenchyma. In the liver and the adenohypophysis, there is a venous portal system.  Variations in circulatory pathways – Anastomosis (shunt) Anastomoses are connections between the vessels with the same lumen, without the exchange of substances between blood and tissues.  Types of anastomoses 1. Arterio–arterial anastomoses (a-a) direct connection of artery to artery; coronary arteries, retinal arteries, circulus arteriosus cerebri Willisi in the brain, arteries of the digestive system, arches in the hand and foot 2. Veno–venous anastomoses (v-v) direct connection of veins with veins; highest number in the lower limb veins, porto-caval and cavo-caval anastomoses 3. Arteriovenous anastomoses (a-v) direct connection of arteries and veins, bypassing capillaries usually at the level of arterioles and venules; regulate blood pressure, body temperature, and also participate in the erection of erectile bodies.  Significance of anastomosis (shunt)  AVAs play a crucial role in thermoregulation, particularly in areas of the body like the skin of the hands, feet, and ears. By allowing blood to bypass capillaries, AVAs can quickly redirect blood flow to help dissipate or conserve body heat.  During cold conditions, AVAs can close, reducing blood flow to the skin and extremities to minimize heat loss. Conversely, in warm conditions, they can open, increasing blood flow to the skin to promote heat dissipation.  AVAs help in regulating blood pressure within certain tissues. By providing an alternate route for blood flow, they can help maintain proper blood pressure within capillaries and prevent damage that might be caused by high pressure.  Pathological Conditions: For instance, in diabetic patients, the dysfunction of AVAs in the skin can impair thermoregulation and wound healing, contributing to complications such as diabetic foot ulcers.  Heart Muscular organ that contracts rhythmically, pumping the blood through the circulatory system. Responsible for producing hormones called atrial natriuretic factor (ANF) and brain natriuretic factor (BNF). Heart wall consists of 3 tunics: I. Endocardium II. Myocardium III. Epicardium  Heart wall I. Endocardium Between the endocardium and the myocardium is a CT subendocardial layer, which consists of veins, nerves and branches of Purkinje cells. II. Myocardium is the thickest and consists of striated cardiac muscle tissue. III. Epicardium is the serous covering of the heart, forming the visceral layer of the pericardium. covered by simple squamous epithelium (mesothelium) supported by a thin layer of CT. + Pericardium: visceral + parietal layers  Endocardium Innermost layer of the heart wall Corresponds to the intima of the vascular wall Consists of: 1. Endothelial cells, 2. Subendothelial layer of loose collagenous CT, 3. Muscular-elastic layer, differs from the previous one by the presence of elastic fibers and myofibroblasts 4. External CT layer (sub-endocardial layer) contains the cells of the cardiac conduction system.  Cardiac valves Four valves providing a one-way flow of blood through the heart Not innervated, without vessels (nourishment via diffusion) Layers of heart valves: Fibrosa Spongiosa Ventricularis  Cardiac valves Fibrosa: Forms the core and structural support of the valve. Composed primarily of dense irregular CT (collagen type I, III, elastic fibers), providing strength and rigidity. Continuous with the fibrous rings of the cardiac skeleton, ensuring the valve's stability. Spongiosa: Located between the fibrosa and ventricularis layers, acts as a shock absorber. Consists of LCT with a high content of proteoglycans and glycosaminoglycans, making it rich in ground substance. Helps to reduce stress and wear on the valve by providing flexibility and cushioning during valve movement. Ventricularis: Found on the surface facing the ventricle and is covered with endothelium. Contains DCT with well-organised collagen fibers, elastic fibers, elastic lamilae. Elastic fibers are responsible for the smooth opening and closing of the valve. Contributes to the resilience and recoil of the valve leaflets, aiding in efficient blood flow.  Myocardium Myocardium – consisting of 2–3 layers of striated cardiac muscle Middle and widest part of the heart wall Corresponds to the tunica media of the vascular wall Bundles of cardiomyocytes are fixed to the cardiac skeleton * 3 layers of muscle tissue in the ventricles, * 2 layers in the atria (outer layer is missing) Ventricles have a stronger layer of muscle tissue when compared to the atria Myocardium in the left ventricle is 3 times stronger than in the right ventricle Inner layer – common to both heart ventricles Middle layer – predominantly circular, separate for each ventricle Outer layer – predominantly longitudinal, separate for each ventricle. Myocardium Intercalated disks  Types of cardiomyocytes 1) Contractile (typical; ordinary, working); 2) Conductive (atypical); 3) Secretory (endocrine). Contractile cardiomyocytes form the basic part of a myocardium, contain highly developed contractile system; Conductive cardiomyocytes have the ability to generate and conduct electrical impulses (impulse-generating and impulse-conducting system of heart) – less myofibrils, more glycogen deposited especially around the nucleus. Secretory (endocrine) cardiomyocytes secrete atrial natriuretic peptide.  Types of conductive cells Nodal conducting cells: located in both SA and AV nodes Pacemaker (nodal) cells or P-cells with intrinsic spontaneous pacemaker function that generate impulses; Transitional or T-cells responsible for propagating impulses into the right atrium; Cardiac conducting cells form bundle of Hiss and terminate as Purkinje fibers. Conducting cardiomyocytes: Compared to working cardiomyocytes contain less myofibrils, accumulated in the peripheral parts of the cell, Contain more glycogen deposited especially around the nucleus; Connections between individual cells of the conduction system are provided by desmosomes and gap junctions (enabling cell communication); No intercalated discs are formed.  Purkinje fibers Found in the subendocardium of the ventricles. Constitute part of the specialised impulse conducting system, which connects to the right and left bundle branches and regulates the heartbeat. Large muscular cells with a vacuolated cytoplasm due to the high glycogen content  more resistant to hypoxia. More lightly stained than typical cardiomyocytes (more glycogen, lower content of myofibrils). Purkinje fibers  Secretory cardiomyocytes Secretory (endocrine) cardiomyocytes secrete atrial natriuretic peptide. Effects of ANP: Vasodilation: ANP causes the relaxation of vascular smooth muscle, leading to vasodilation. This reduces the resistance in the blood vessels, which helps lower blood pressure. Natriuresis: ANP promotes the excretion of sodium through the urine. By increasing the renal excretion of sodium, it reduces blood volume. Diuresis: Along with sodium, water is also excreted, leading to an increased volume of urine. This further helps in reducing blood volume and, consequently, blood pressure. Inhibition of the Renin-Angiotensin-Aldosterone System (RAAS): ANP inhibits the secretion of renin from the kidneys. Renin is an enzyme that plays a crucial role in the RAAS, which typically acts to increase blood pressure. By inhibiting renin, ANP reduces the formation of angiotensin II and aldosterone, both of which contribute to blood pressure regulation and sodium retention.  Secretory cardiomyocytes B-type (or brain) natriuretic peptide (BNP) is a hormone released by ventricular myocytes in response to increased wall tension and stress, which often occur in conditions like heart failure. It has similar physiological actions to ANP but with a longer half-life, making it particularly useful in clinical settings. BNP blood test used for diagnosing heart failure (very good negative predictive value).  Important to remember Stimulation of the parasympathetic nerves decreases the heart rate. Release of the neurotransmitter acetylcholine from the terminals of postsynaptic fibers slows the heart rate (an effect known as bradycardia), reduces the force of the heartbeat, and constricts the coronary arteries of the heart. Stimulation of the sympathetic nerves increases the heart rate. Symphatetic fibers secrete norepinephrine that causes the rate of contraction to increase (an effect known as tachycardia) and increases the force of muscle contraction. Sympathetic stimulation produces dilation of the coronary arteries by inhibiting their constriction. MCQ for self-control https://forms.gle/2mKmMC8yBVCprtSaA  References Helpful videos Thieme Media Player - Vessel layers Thieme Media Player - Artery, vein, and capillary