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Layers of a blood vessel Tunica Intima (Innermost) -Thin, single layer- tight junctions to prevent leaks, releases vasoactive substances Tunica Media (Middle)- Smooth muscle and connective tissue (elastin and collagen), adds to the strength of the vessels, contains internal/external elastic lamina,...

Layers of a blood vessel Tunica Intima (Innermost) -Thin, single layer- tight junctions to prevent leaks, releases vasoactive substances Tunica Media (Middle)- Smooth muscle and connective tissue (elastin and collagen), adds to the strength of the vessels, contains internal/external elastic lamina, sympathetic innervation, important for blood pressure control. Tunica externa (outer)- Connective tissue (collagen and elastin), contains nerves, fibroplasts, adipocytes, control of overexpansion/collapse, vasa-vasorum in some large vessel Types of Blood Vessels- Elastic conducting arteries, muscular distributing arteries, arterioles, capillaries, venules, veins Arteries- thicker outer wall, small lumen, thick layer of muscle and elastic fibres Veins- thin outer wall, large lumen, thin layer of muscles and elastic fibres Capillaries- Wall made of a single layer of cells, very small lumen Large arteries are elastic (e.g., aorta), they absorb pressure generated by cardiac contractions to reduce peak systolic pressure and ensure better flow. Large arteries also have a narrow lumen but thick muscular walls, they dilate or constrict in a regulated manner to regulate and help direct blood flow to active organs. Small arteries/arterioles are small and act as resistance vessels. They have limited elasticity but do contain smooth muscle, they also regulate blood pressure and blood flow through capillaries. Diameter of blood vessels is regulated by many mediators also released by inner lining endothelial cells; these are: Vasodilators: e.g., histamine, nitric oxide, prostaglandins, bradykinin and adenosine Vasoconstrictors: endothelin, thromboxane, noradrenalin (α), adrenalin (α) Venules: Narrow diameter and no tunica media Medium diameter veins: thin tunica media, few smooth muscle cells Larger diameter veins: thicker tunica externa; relatively thick tunica media Large veins also contain valves to assist the one-way flow of blood back to the heart. Muscle contraction aids venous return Varicose veins from in valves. Arterioles Tissue blood flow is controlled by vasoconstriction or dilation of small arteries/arterioles supplying the tissue. Arterioles and their precapillary sphincters control blood flow. Smooth muscle contraction/relaxation precapillary sphincters are regulated by a range of local (metabolic) and extrinsic (neural) mechanisms During exercise skeletal muscle blood flow increases but flow to the intestines decreases Capillaries Endothelium: Single cell layer, no tunica media or externa, controls fluid Continuous capillaries are the most common type of capillaries Fenestrated capillaries are permeable/leaky (renal) Discontinuous capillaries form sinusoids in liver/spleen/bone. Site of gas diffusion (O2 and CO2) Respond to vasoactive growth factors, mediators and cytokines Each arterioles provides blood to many capillaries. Flow is slow allowing better gas and nutrient exchange. As blood flows through capillaries there is a net loss of fluid to interstitial fluid leading toa fall in blood pressure. Plasma proteins generate osmotic pressure (against capillary) these fluids form urine in the kidney and lymph elsewhere Lymphatic vessels Plasma-like lymph is derived from fluids that leak from the arterial ends of capillaries due to blood pressure. Lymph capillaries are found in all tissues except the CNS, bone marrow and epidermis. Fluid enters tiny lymph capillaries and is returned to blood to prevent oedema and help maintain normal blood volume and pressure. Lymphatic fluid contains white blood cells but no red cells. Lymph flows, via lymph nodes, to the subclavian vein. Valves in the larger lymphatic vessels prevent backflow. Smooth Muscle Contraction -Increase in intracellular Ca2+ concentrations initiate contraction -Ca2+ combines with acid protein “calmodulin” -Ca2+/Cal complex activates Myosin Light chain The heart is part of the cardiovascular system. It is a physiological pump which contributes to overall pressure maintenance (total peripheral resistance, blood flow, heart rate, cardiac output) Heart oversees the perfusion of organs (delivers and removes) The approximate cardiac output of a healthy 20-year-old person is ~5-6 litres/min Structures The pericardium is a protective sac surrounding the heart. The pericardial cavity (the space in-between) is filled with pericardial fluid which consists of 40-50ml of ultraclean plasma, the pericardial fluid acts as a lubricant. The fibrous (outermost layer) is attached to the blood vessels and diaphragm (sometimes) The heart has 4 cardiac chambers There are 4 valves in the heart which are: the tricuspid atrioventricular valve, the mitral atrioventricular valve, the pulmonary semi-lunar valve (which leads to pulmonary artery) and the aortic semi-lunar valve (which leads to the aorta) The sinoatrial (SA) node is a spontaneously depolarising pacemaker, located in the right atrium (at the junction of the superior vena cava), responsible for atrial contraction. The atrioventricular (AV) node is in the right-posterior portion of inter-atrial septum, responsible for ventricular contraction. Myocardial cells are branched, striated, (lines visible through cells which indicate the sarcomere edges) and mononucleated, rich in mitochondria Z disc- edge of sarcomere M line- centre of sarcomere I band- contains only LIGHT myofilaments (actin) H zone- contains only HEAVY myofilaments (myosin) A band- contains heavy myofilaments and overlapping region with actin Pattern of electrical activity in the heart P wave- Atrial depolarisation (contraction) QRS interval- Ventricular depolarisation (contraction) and atrial repolarisation (relaxation) Q wave- Septal depolarisation R wave- Depolarisation of the majority of ventricular mass S wave- Depolarisation of the Purkinje fibres T wave- Ventricular repolarisation (relaxation) U wave- Rare! Late repolarisation ( of Purkinje fibres and some ventricular myocytes) Heart rate: How fast the heart is contracting Heart rhythm: The way the heart is beating Breathing in: Decrease in vagus nerve activity, and increase in heart rate Breathing out: Increase in vagus nerve activity, and decrease in heart rate Blood pressure is the pressure of circulating blood against the walls of blood vessels. Types of Blood Pressure Systolic: blood pressure is the pressure when the ventricles (bottom chambers of the heart) contract to eject blood forward. For systemic circulation this is the pressure generated by the left ventricle. Diastolic: blood pressure is the pressure on the blood vessels when the heart muscle relaxes. Mean blood pressure is calculated in multiple ways. Most common calculation used is the sum of two-third of diastolic and one-third of systolic pressure. Another common calculation used is diastolic pressure + one-third of pulse pressure Pulse pressure: difference between systolic and diastolic blood pressure. Systemic circulation: Left ventricle pumps at a higher pressure (80-120mmHg). Above 140mmHg at rest is abnormal. Pulmonary circulation: Right ventricle pumps blood at lower pressure (8-20mmHg) to lungs. Above 25mmHg at rest is abnormal. What is the use of blood pressure? Blood pressure is the driving force for blood flow Pressures decrease throughout the vascular system: ~Arteries>Arterioles>Capillaries>Venules>Veins Flow is proportional to the pressure gradient divided by the resistance to flow (Poiseuille’s Law): ~ if pressure gradients reduce the flow reduces ~ if resistance increases the flow will reduce Regulators of Blood Pressure Cardiac Output (Heartrate and stroke volume) Total peripheral resistance Renin-angiotensin aldosterone system Antidiuretic hormone (ADH)/ Vasopressin Natriuretic peptides (ANP) Baroreflex Other factors (metaboreflex, mechanoreflex, chemoreflex, central command, pain, temp, gravity) Pressure generated by the heart and its cardiac output are the main sources of blood pressure. Cardiac output (heartrate x stroke volume) Stroke volume is affected by the size of the heart and also by the force of cardiac contraction (inotropy) Flow is proportional to the pressure gradient divided by the resistance to flow (Poiseuille’s Law) ~if pressure gradients reduce the flow reduces ~if resistance increases the flow will reduce Small arteries/arterioles are the most important resistance vessels. No single set point for blood pressure regulation. Diuresis: production of urine, extraction of volume Natriuresis: excretion of sodium in urine Renin is a proteolytic enzyme secreted by kidneys in response to fall in sodium, acts on angiotensinogen to produce angiotensin 1. Angiotensin 1 (an inactive peptide) which with the help of angiotensin converting enzyme, converts angiotensin 1 to angiotensin 2 (active form) in lungs Angiotensin 2 is a potent vasoconstrictor Angiotensin 2 also leads to the production on aldosterone from adrenal cortex which increases reabsorption of salt and water from distal tubules (increased volume). Regulators of blood pressure: Antidiuretic hormone (vasopressin) Vasopressin is released from posterior pituitary in response to decreased volume and reduced blood pressure. Vasopressin is generally a vasoconstrictor in the body (particularly skin and splanchnic circulation) Vasopressin also leads to bradycardia (slows heartrate) In kidneys: Reabsorbs water from the final third of the distal tubules and collecting ducts through increased permeability >>> increase in blood volume>>> decrease in urine output Increased sodium reabsorption>>>increases osmotic pressure gradient >>> fluid retention>>>concentrated urine with low volume Regulators of blood pressure: Natriuretic peptides ANP: atrial natriuretic peptide is a short-lived peptide, released from atrial myocytes in response to increased pressures within the area. BNP: brain natriuretic peptide is also a short-lived peptide, released from ventricular myocytes (mainly left ventricle) in response to increased pressures within the ventricles. Natriuretic peptides inhibit renin and reduce angiotensin 2 concentrations to inhibit vasoconstriction. They also inhibit aldosterone and promote salt and water uresis (reduced volume). Natriuretic peptides also directly cause some vasodilation. They increase cGMP and NO (vasodilator). And decrease sympathetic tone and noradrenaline. Baroreceptors: short-term acute regulators, not long-term controllers of blood pressure. Autoregulation is the intrinsic ability of an organ to maintain a constant blood flow despite the changes in blood pressure. Autoregulation of flow through blood vessels, particularly arterioles, occurs in response to changes in blood pressure. Autoregulation is very important in brain, heart and kidney. Autoregulation is mediated by metabolic products (e.g., CO2 alongside extrinsic factors like neural tone to the blood vessels) that auto-regulate flow via vasodilation like active hyperaemia. Autoregulation promotes vasoconstriction when flow is fast due to the removal of the local controls (e.g., CO2)

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