CVS Lecture 2 and 3 PDF

CVS topics Circulation and Lymph Circulation Blood pressure drives blood flow Arteries and Arterioles Capillaries and fluid exchange Lymphatics Venous System Blood Pressure Regulation Cardiac Output – heart rate Cardiac Output – stroke v...

CVS topics Circulation and Lymph Circulation Blood pressure drives blood flow Arteries and Arterioles Capillaries and fluid exchange Lymphatics Venous System Blood Pressure Regulation Cardiac Output – heart rate Cardiac Output – stroke volume Baroreceptor and chemoreceptor reflexes Longer-term regulation of blood pressure Humoral control Pathophysiology - Hypertension  The Vasculature All blood vessels, excluding microcirculation have the same general structure with: inner lumen: passageway for blood flow surrounded by an endothelium: tunica intima smooth muscular layer of varying thickness: tunica media an outer fibrous layer: tunica externa with a variable amount of elastic connective tissue.  Arteries & Arterioles Arteries convey blood from the heart to the capillaries. They exhibit thicker walls than veins, with lots of elastic connective tissue and more muscle than veins. They are rapid passageways. Offer little resistance to blood flow, due to their large radii. Arterial pressure fluctuates in relation to systole and diastole. But why doesn’t arterial pressure drop to 0 mmHg during diastole (no flow into arteries)? There is some specialisation (next slides).  Arteries & Arterioles Aorta Large Medium Arteries Arteries Elastic Arteries Small Capillaries Transport blood away Arteries Large lumen (1.5cm) Muscular Arteries Arterioles More elastic (elastin in tunica intima) Smaller lumen (4mm) Arterioles More smooth muscle Very small than elastin lumen (30 µm) Heart Smooth muscle Blood Pressure in Systemic Circulation Guyton Textbook of Medical Physiology BP is maintained in arteries Arterioles are the main resistance vessels = loss of BP  Arteries & Arterioles Note size here enlarged Rapid passageways and pressure reservoirs Facilitates distribution of blood - Larger radii - Small radii - Less resistance - More resistance - Elastic (& muscle some) - Elastic  The Control of Vascular Tone Radii of arterioles can be adjusted to variably distribute cardiac output among systemic organs and to help regulate MAP. Arteriolar smooth muscle imparts state of partial constriction known as vascular tone. Vasoconstriction Vasodilation The Control of Vascular Tone The Control of Vascular Tone  The Vasculature Aorta Large Medium Arteries Arteries Small Capillaries Arteries Heart Arterioles  Capillaries Smooth muscle Arterioles Venules Capillaries Metarterioles smooth muscle present as precapillary sphincters Thoroughfare channel Pre-capillary Sphincters  Capillaries Smooth muscle Arterioles Lymphatic vessels Capillaries Venules Capillaries Microscopic lumen (5 – 10 µm) Metarterioles Tissue Cells Supply blood to tissues via perfusion Only a single endothelial cell thick Interstitial fluid is between plasma & cells Fluid movement (bulk flow) is driven by 2 opposing pressure gradients Hydrostatic Pressure Oncotic Pressure = Colloid Osmotic Pressure Thoroughfare channel Pre-capillary Lymph vessels also important in fluid uptake Sphincters  3.6 L/day Lymphatic vessels for circulation Tissue Cells 20.4 24 L/day L/day NFP = + 10 Net NFP = 0 mmHg NFP = - 7 mmHg Arterioles mmHg Filtration 35 Pressure 25 mmHg 18 mmHg mmHg Venules Interstitial Fluid 25 25 25 mmHg mmHg mmHg Capillary ries Hydrostatic Capilla Pressure CHP = BCOP CHP > BCOP No net fluid CHP < BCOP Blood Colloid Fluid out movement Fluid move Osmotic of capillaries into capillaries Pressure Summary: Capillaries  Lymphatics Lymph is the fluid that flows through the lymphatic system. It is part of ECF, and is similar in ionic composition to interstitial fluid (from which it is derived). The main difference is where the fluid is located. The lymphatic system is a system of branched network of ducts which terminate in small, blind-ended capillaries, within nearly every tissue. Lymphatics Functions of lymph Returning excess fluid back to circulation Immune defence Transport of lipids from the GIT Interstitial fluid enters the lymphatic system via pores in the lymph capillaries that allow the entry of large molecules, like proteins and chylomicrons (fats). Lymph is propelled along the lymphatic system by smooth muscle contraction, and external pressure from SkM contraction squeezing the lymph vessels. Plus there are valves to prevent back-flow (like veins).  Oedema Oedema is swelling in soft tissues as a result of fluid accumulation. It occurs as a result of a shift in the balance in the capillaries. Whilst there are many pathophysiological causes of oedema the main outcome is a build up or excess of interstitial fluid. Functional consequences Elephantiasis in a leg of a young girl (WHO)  Oedema Lymphatic 1. increased blood pressure System 2. decrease oncotic pressure 3. increase permeability 4. blockade lymph Tissue Cells Arterioles more interstitial fluid 35 18 mmHg Interstitial Fluid Venules mmHg Capillary 25 25 Hydrostatic Pressure mmHg mmHg Blood Colloid ries Osmotic Capilla Pressure CHP > BCOP CHP < BCOP Fluid out Fluid move of capillaries into capillaries  The Vasculature Aorta Large Medium Arteries Arteries Arterioles Small Capillaries Arteries Heart Small Venules Veins Vena Cava Large Veins Venous System Veins act as blood reservoirs - approximately 64% of body’s blood - convey blood back to heart (R atrium) - large lumen, with thin walls - have valves prevent backflow - high volume (capacitance) - low resistance, low pressure Blood Pressure in Systemic Circulation Guyton: Medical Physiology end capillaries/start venules approx. 18 mmHg central venous pressure (right atrium) approx. 2 mmHg venous return is via low pressure  Compliance How readily a lumen of a blood vessel is able to expand Arteries Veins Thick layer of smooth muscle & elastin Less smooth muscle, little elastin. Capable of withstanding high pressure Stretchy, but no recoil. & recoils well. Readily expand when filled with blood. Lower compliance Higher compliance  Venous Return Pulmonary Venous Return The flow of blood back to heart via the veins O2 poor O2 rich CO2 rich CO2 poor blood Cardiac Output blood Directly affects Venous Return End Diastolic Volume Vol. of blood in ventricles, before contraction Stroke Volume Vol. of blood pumped out of heart Cardiac Output Vol. of blood pumped out per minute Systemic  Venous Return 1) One-way valves prevent backflow Valves prevent Blood flow caused by 2) Compression of large veins is aided backflow muscle contraction by skeletal muscle contractions Valve open These 2 points can best be exemplified by veins in our calves… Valve closed Calf muscle relaxed Calf muscle contracted  Venous Return 1) One-way valves prevent backflow 2) Compression of large veins is aided by skeletal muscle contractions 3) Respiration acts like a pump. The pressure within the chest cavity is 5 mmHg less than atmospheric pressure during inspiration. 4) Venoconstriction SNS Smooth Veins contain smooth muscle that is activation Muscle innervated by SNS z  Venous Return 1) One-way valves prevent backflow 2) Compression of large veins is aided by skeletal muscle contractions 3) Respiration acts like a pump. The pressure within the chest cavity is 5 mmHg, less than atmospheric pressure during inspiration. 4) Venoconstriction Veins contain smooth muscle that is innervated by SNS 5) “Cardiac suction” When atrial cavity enlarges during ventricular contraction (systole) atrial pressure < 0mmHg  The Vasculature Aorta Large Medium Arteries Arteries Small Capillaries Arteries Heart Arterioles  CVS topics Circulation and Lymph Circulation Blood pressure drives blood flow Arteries and Arterioles Capillaries and fluid exchange Lymphatics Venous System Blood Pressure Regulation Cardiac Output – heart rate Cardiac Output – stroke volume Baroreceptor and chemoreceptor reflexes Longer-term regulation of blood pressure Pathophysiology - Hypertension  Cardiac Output CO = SV x HR Cardiac Stroke Heart Output volume rate mL/min mL/beat beats/min 4900 ml/min 70 ml 70 bpm 5L/min at rest  ANS regulation of CO Sympathetic Parasympathetic Activation Activation ↓ Heart Rate ↑ Heart Rate Heart ↓ Force Contraction ↑ Force Contraction (Atrium) Blood Vessels Constriction Dilation (penis and clitoris) Endocrine Glands Adrenaline and noradrenaline None Adrenal Medulla  Heart Rate Heart rate is the number of heartbeats per minute, specifically ventricular contraction. Usually measured as pulse rate eg. wrist. Tachycardia is high resting heart rate. In adults > 100 bpm. When heart rate so rapid, the efficiency of pumping is an issue and blood flow can be compromised. Blood flow to heart itself is a potential issue. Bradycardia is when heart rate is too slow, defined in adults and children < 60 bpm. Athletes often have a lower than normal heart rate due to training. Resting heart rate normally decreases with age.  Cardiac Output: Heart Rate Other Factors Recall sinus rhythm is set by SA node Hormones Adrenaline Sympathetic NS Thyroid Hormones T3 and T4 Noradrenaline +ve Adrenaline +ve Body Temperature SA Fever +ve Parasympathetic NS Acetylcholine - ve Age Fetus to child to adult Ions Ca2+ hypercalcemia +ve ANS: balance of sympathetic to hypocalcemia - ve parasympathetic tone. At rest PSNS is dominant, as spontaneous activity = 110 bpm  BIOM2011 Pacemaker Activity Unstable resting membrane potential, IF (Slow inward Na+ current) Entry Ca from ECF via T (transient) channels Threshold reached à Large influx Ca via L type channels BIOM2011  Chronotropic Agents ANS Other Factors Hormones Sympathetic NS Adrenaline +ve Noradrenaline Thyroid Hormones T3 and T4 Adrenaline +ve Body Temperature SA Fever +ve Parasympathetic NS Acetylcholine - ve Ions Ca2+ hypercalcemia +ve ‘chronotropic agents’ hypocalcemia - ve include drugs affect the heart rate. Beta blockers eg. atenolol Ca channel blockers eg. verapamil slow heart rate have direct negative chronotropic effect  Cardiac Output: Stroke Volume Stroke volume (SV) is the volume of blood ejected in each ventricular contraction. SV = EDV - ESV It is the difference between ventricular end diastolic volume (EDV), the volume when relaxed and ventricular end systolic volume (ESV) the volume when fully contracted). SV is typically around 70 ml/beat at rest.  BIOM2011 Cardiac Length-Tension Relationship skeletal case The thick/thin filaments, mainly myosin and actin respectively, are similar in skeletal and cardiac muscle. For cardiac muscle contraction occurs by the sliding of the thick and thin filaments, like in skeletal muscle fibres EXCEPT note there is no descending limb on the figure for cardiac muscle  BIOM2011 Cardiac Length-Tension Relationship Normal Skeletal Operating Zone Normal Cardiac skeletal Operating Zone case In the cardiac muscle what changes length-tension? So heart failure is NOT due to too much stretch – revisit later. It relates to degree of activation! The degree of activation of cardiac muscle is variable and depends on a few factors…..  Stroke Volume There are 3 main factors that affect stroke volume: 1. Pre-load is defined as the myocardial sarcomere length, just prior to contraction. It is not measurable without removing the heart but is approximated by EDV. Pre-load is a function of: Ventricular filling intra-thoracic pressure, respiration, blood volume Ventricular and pericardial compliance reduced compliance decreases pre-load Ventricular wall thickness hypertrophy decreases pre-load  Stroke Volume Pre-load largely depends on ventricular filling and therefore venous return. The Frank-Starling Law of the heart states that the strength of cardiac contraction is dependent on initial fibre length. The additional stretch, for example as a result of venous return, increases the number of myofilament cross-bridges that can interact and the myofilament Ca2+ sensitivity. This law is represented by the "ventricular function curve" or Frank-Starling relationship and is based on length-tension relationship in cardiac muscle. It is an intrinsic ability of cardiac myocytes. ↑ tension is a result of ↑ length ↑ contractility is proportional to ↑ end-diastolic volume (EDV)  Stroke Volume 2. After-load is the force against which the ventricles must act in order to eject blood. It is the sum of the elastic and kinetic forces. Often terms such as "resistance" or "impedance" are used to describe after-load. The main forces that oppose ventricular ejection are arterial blood pressure and vascular tone. For example, with increased arterial resistance (atherosclerosis) stroke volume will initially decrease, but over time will increase via compensatory mechanisms to maintain blood flow.  Stroke Volume 3. ‘Contractility’ there are other factors, including pharmacological agents, that affect stroke volume and therefore cardiac output. Thes factors change the ventricular function curve. Shift to right = negative inotropy Shift to left = positive inotropy The dashed line indicates where maximal contractility has been exceeded “descending limb" of the F-S curve. Contractility = the inherent vigour of contraction of the heart muscle during systole.  Inotropic Agents Modulation of Cardiac Contractility An inotrope is an agent which increases or decreases the force of muscular contraction (nervous and hormonal input, drugs). Negative inotropic agents weaken the force of contraction. Positive inotropic agents increase the strength of contraction. (both positive and negative inotropes are used in the management of various cardiovascular conditions) Positive inotropic agents Cardiac Glycosides : Digitalis (blocks Na-K ATPase) Catecholamines : Epinephrine or Norepinephrine (activates beta Adrenergic Receptors) Isoproterenol (also activates beta Adrenergic Receptors) Negative inotropic agents Beta blockers (blocks beta Adrenergic Receptors) Diltiazem (blocks DHPR Ca channels) Verapamil (also blocks DHPR Ca channels) BIOM2011  Autonomic Regulation of Cardiac Contractility Parasympathetic Sympathetic ACh NE DHPR Ca Pacemaker KACh Channel (If) Channel Adenylyl M2 Cyclase b1 G G + - + + + ATP cAMP Inactive PKA + SR Ca Pump The available intracellular Ca determines Activated MYOCARDIAL CONTRACTILITY. PKA Therefore, all the factors that modulate intracellular [Ca] affect cardiac contractility. Note: the cell displayed is neither distinctly pacemaker nor contractile. BIOM2011