Blood Vessels 2024 PDF

Topic 3 Blood Vessels November 2024  Objectives Topic 3 Describe the three layers (or tunics) of arteries/arterioles. Describe and give examples of the following factors which effect arteriolar diameter: Neural, Humoral, Tissue Metabolites Describe the actions of no...

Topic 3 Blood Vessels November 2024  Objectives Topic 3 Describe the three layers (or tunics) of arteries/arterioles. Describe and give examples of the following factors which effect arteriolar diameter: Neural, Humoral, Tissue Metabolites Describe the actions of noradrenaline and adrenaline on vascular smooth muscle. Explain what distinguishes the regulation of coronary and cerebral blood flow from the regulation of peripheral arterial blood flow (say to that of the gut or kidney). Briefly describe the cause of chest pain (angina)  Mini Case (Katherine) While waiting to board a bus this winter you notice an older woman rushing up toward the bus stop. All of a sudden she clutches her chest and sinks to her knees. She is diaphoretic, dyspneic and she looks terrified. You take her pulse and she is tachycardic. Basic vessel architecture primarily endothelium lumen (intima) connective tissue / fat (adventitia) smooth muscle & elastic tissue (media) lumen: the small central space in a vessel through which blood/fluid flows. Arterioles lumen Smooth Muscle smooth muscle for vasoconstriction and vasodilation also called “resistance” vessels have a critical role in controlling blood pressure  Maintaining Blood Pressure Blood is pumped from the heart into a closed loop of collapsible tubes. Pressure in this circuit is determined largely by two things: 1. volume of blood in the arterioles 2. how relaxed (dilated) or contracted (constricted) the arterioles are. Called: Systemic Vascular Resistance (SVR)  Arterioles Fig 10-10 S&K At rest partially constricted. Blood flow determined by constriction or dilation from nerves and hormones. FLEXIBILITY in blood pressure control  What determines vasoconstriction and vasodilation? Neural control of Arteriolar Diameter SNS: Noradrenaline Adrenaline PSNS: insignificant Ca2+ - Calmodulin Activates MLCK MLCK phosphorylates MLC heads leads to cross-bridge formation (Actin & Myosin) which produces contraction MLCK – Myosin Light Chain Kinase MLC - Myosin Light Chain PL-C – Phospholipase C DAG – DiAcylGlycerol PK-C – Protein Kinase C IP3 –Inositol TriPhosphate – -adrenergic receptor SR – Sarcoplasmic Reticulum  Adrenaline adrenaline acts at β2 receptors  adenyl cyclase & cAMP, Protein Kinase A (PKA) Phosphorylating and inhibiting MLCK and causes vasodilation Gs, Gq – GTP-binding Proteins PIP2 – Phosphatidylinositol 4,5-bisphosphate b2 –b2 adrenergic Receptor AC – Adenylyl Cyclase Epinephrine Adrenaline Nice to know Noradrenaline fibres Scherbakova et al, JCB 176, 521-33, 2007 Nice to know..... b1 adrenergic Receptor with Adrenaline Ring et al, Nature, 502, 575-579 October, 2013 Nice to know..... Cryo-EM structure of the human GLP-1–rabbit GLP-1R–Gs complex Y Zhang et al. Nature 1–6 (2017) doi:10.1038/nature22394  Nodal Cells Ventricular Vascular Muscle Cells Smooth Muscle cells SNS Noradrenaline β1 receptors Phase 4 slope HR Adrenaline β1 receptors Phase 4 slope HR PSNS Acetylcholine Muscarinic receptors Phase 4 slope HR  Nodal Cells Ventricular Vascular Muscle Cells Smooth Muscle cells SNS Noradrenaline β1 receptors α1 receptors Phase 4 slope Ca++ VC HR Adrenaline β1 receptors B2 receptors Phase 4 slope MLCK activity HR VD PSNS Acetylcholine Muscarinic Limited direct receptors action Phase 4 slope HR  Vasoactive Hormones: Constrictors: From the kidney! Angiotensin II (AII) Arginine Vasopressin (AVP) From the brain! Dilator: Atrial Natriuretic Peptide (ANP) From the heart! Useful Charts in Boron: Medical Physiology Table 46-3 Peptide Hormones and Signal Transduction Other vasoactive mechanisms Tissue metabolites released by active cells and cause local vasodilation e.g.  O2,  CO2,adenosine, K+ This is called Metabolic Regulation of Blood Flow Regulation of Coronary Circulation Metabolic Regulation of Blood Flow Coronary BF diminished in systole** ** More in left ventricle than right Ensuring a constant supply of Oxygen to cardiac muscle is critical.  What happens when there is insufficient blood supply to the cardiac muscle? Causes: – coronary artery spasm (drugs/alcohol) – coronary artery narrowing (plaque formation) Result is CHEST PAIN (called Angina) Ischemia Afferent Brain Perceived as (O2) nerve endings Painful stimuli Heart Attack Regulation of Cerebral Circulation Metabolic Regulation of Blood Flow* Regional cerebral BF linked to brain activity * Very responsive to low O2 tension Writing Phyl 301 Exam We hope! Writing CAPS 301 Exam We hope!  Mini Case (Katherine) While waiting to board a bus this winter you notice an older woman rushing up toward the bus stop. All of a sudden she clutches her chest and sinks to her knees. She is diaphoretic, dyspneic and she looks terrified. You take her pulse and she is tachycardic.  an older woman rushing she clutches her chest diaphoretic and dyspneic (labored breathing) feels like something is squeezing her chest and it hurts Symptoms are associated with exertion Sweating (diaphoretic) could be due to exercise or increased Symp. NS (anxiety) Chest pain due to Cramped chest muscle? Lung problem? Heart problem?  What has Katherine’s problem got to do with Blood Vessels?  It’s all about balance… blood supply = tissue demand In Katherine’s case: Coronary blood flow = heart muscle demand During Exertion!!! Genesis of a Plaque: Fibrous plaques develop in the intima with a necrotic core of cholesterol. Plaque may project into the lumen, reducing blood flow (a) It can rupture sending an embolus downstream resulting in complete occlusion (b) (b) (a) embolus In Katherine’s case, Narrowed coronary arteries limited coronary artery blood supply. At rest blood supply = demand (no pain) mild exertion supply < demand = angina (heart pain).  What will happen to Katherine? She will have a “Stress Test”. the doctor may recommend either: – Angioplasty (Percutaneous Intervention “PCI”)/Stenting (opening a narrowed vessel) – Coronary Artery Bypass Graft (CABG) (replacing narrowed or blocked artery)  Case 3 Objective Given the case of Katherine, the older woman who collapses while running to the bus, relate her symptoms to their underlying physiological mechanism, briefly describe the genesis of an atherosclerotic plaque and differentiate between the terms angioplasty and coronary artery bypass graft. Nice to know…..ECG changes in the ischemic heart during a stress test. Nice to know…..ECG changes in the ischemic heart during a stress test. Nice to know…. Rates of CABG and PCI per 100,000 people in Canada Hassan et al, American Heart Journal, 2010  PCI CABG 1994 2005 1994 2005 British Columbia 96 183.3 60.4 54.1 Alberta 119 114.4 67.4 58.7 Saskatchewan 100.4 208.8 64.6 90.6 Manitoba 75.9 137.3 62.4 76.6 Ontario 53.3 179.8 72.6 74.2 Quebec 118.1 229.1 90.6 68.5 New Brunswick 95.5 172 70.1 67.8 Nova Scotia 81.3 177.9 94.8 71.1 Prince Edward Island 72.2 132.7 98 66.9 Newfoundland 55.5 136.3 80.3 113.6 Total 85.6 186.7 75.6 70.8 Rates of CABG and PCI per 100,000 people Hassan et al, American Heart Journal, 2010  Nice to know…. “Percutaneous coronary intervention (PCI) is associated with a lower 5-year stroke rate than CABG surgery in patients with multivessel and left main coronary artery disease, according to a pooled analysis of individual patient data from 11 randomized clinical trials including a total of 11,518 patients.“ Nature Reviews Cardiology In Brief 2018 Head, S. J. et al. Stroke rates following surgical versus percutaneous coronary revascularization. J. Am. Coll. Cardiol. 72, 386–386 (2018)