Lecture #23: Vascular Physiology PDF

Lecture #23: Vascular Physiology Julia Hum, PhD Primary Course Instructor Course Meets: Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm (317B or WebEx)  L23: Learning Ob...

Lecture #23: Vascular Physiology Julia Hum, PhD Primary Course Instructor Course Meets: Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm (317B or WebEx)  L23: Learning Objectives 1. Compare and contrast the different vessels within the vasculature 2. Relate vessel structure to its role in blood flow 3. What determines blood flow through the vasculature and what are the various parameters that impact vessel resistance? 4. Summarize the four mechanisms of exchange between blood and tissue 5. How do pressure changes across the capillary bed promote fluid exchange? 6. Compare and contrast the local mediators of vascular control 7. Describe the function of the endothelium in regulating blood flow Unless otherwise noted, figures in today’s lecture are from: Lippincott Illustrated Reviews: Physiology 1e Wilson (Ch. 19) L23: ”Take Home” Slide  Vasculature Anatomy Common structure of blood vessels: 1. Endothelial cells – single layer ”Tunica intima” 2. Vascular smooth muscle cells ”Tunica media” 3. Elastic fibers Not present capillaries and venules 4. Collagen fibers 5. Outer layer of connective tissue “Tunica externa” The degree to which these are all LO1 present are different  Vasculature Organization Arteries: High Pressure Thick, muscular walls Elastic layers – limit expansion Narrow Lumen Veins: Low Pressure Thin muscle layer in the wall Wide Lumen ~50% blood volume in the venous system Blood reservoir LO1,2  Blood velocity & vessel cross-sectional area across the systemic vasculature In capillaries, the cross-sectional area is the highest, but the velocity the blood is moving is the lowest Why? This is the site of exchange! LO1,2  Vessel Compliance Principle Compliance: The degree to which something can expand Arteries: Low compliance, very rigid with thick musculature Veins: High compliance, can deform as needed to allow changes in blood volume REMEMBER! The venous system is a blood reservoir General Rule: More muscle and more elastin = lower compliance LO2  Vessels – Large Arteries Arteries carry blood at high pressure = thick and lumens narrow - limits arterial system capacity Walls of the larger arteries (“elastic arteries”) contain smooth muscle layers and elastin fibers Muscle layers have a resting tone, which limits arterial distensibility and helps maintain the pressure of the blood within them LO1,2  Vessels – Small Arteries & Arterioles Walls mostly smooth muscle layers “Resistance vessels”- act points of control of blood flow to capillaries Small arteries and arterioles have more control over local blood flow than large arteries Controlled by the SNS (major driver of vasoconstriction and vasodilation) Receptors: a1 – vasoconstriction LO1,2 B2 - Vasodilation  Vessels – Capillaries Sites of exchange - designed to keep blood contained within the vasculature during exchange of materials between blood, interstitium, and tissues Walls are the thickness of a single endothelial cell plus the basal lamina Pores (fenestrations) – direct communication between blood and cells Clefts – direct communication between adjacent cells LO1,2  Exchange between blood and tissue Primary function of CV system is to deliver O2 and nutrients to all cells of the body Capillaries are the site of this action Blood moves through capillaries at a very slow rate (~1mm/s) LO1,2  Four Mechanisms of Exchange Between Blood and Tissue 1. Pinocytosis Large Molecules 2. Bulk Flow Driven by pressure Via junctions and fenestrations 3. Diffusion via fenestrations and pores Larger molecules Concentration gradient 4. Diffusion across endothelial cells “Classic” diffusion O2 and CO2 LO4  Fluid Movement in Capillary Beds - Normal Hydrostatic pressure gradient across the length of a capillary Pc – mean capillary hydrostatic pressure Usually a positive pressure that drives fluid out of the capillary and into the interstitium Pressure “pushing out” on the capillary walls πc – plasma colloid osmotic pressure Pressure “pulling” fluid back INTO the capillary LO5  Fluid Movement in Capillary Beds - Normal Hydrostatic pressure gradient across the length of a capillary Pc – mean capillary hydrostatic pressure Starling Equilibrium πc – plasma colloid osmotic pressure If Pc > ∏c, fluid will move out of the capillary and into the interstitium If ∏c > Pc, fluid will move from the interstitium and into the capillary FYI: Lymphatics hold “extra” fluid LO5  Fluid Movement in Capillary Beds - Examples Sudden Loss of Blood Volume Heart Failure During a sudden loss of blood, pressure preferentially drops In heart failure, fluid backs up into the venous system dramatically in the venous system This raises the pressure (Pc) in the venous system Decreases Pc of venous system Pc > ∏c throughout the whole system ∏c > Pc Fluid is going to be “pushed out” of the capillaries into the interstitium Fluid is ”pulled in” from the interstitium into the blood vessel to LO5 → edema overcome the blood loss  Vessels – Venules & Veins Low-pressure system for blood to make its way back to the heart Venules widen and fuse with each other as they progress toward the heart Larger venules contain VSMCs within their walls, but far fewer than in the arterial system Walls are thin and highly distensible = accommodate large volumes of blood Larger veins contain valves that help maintain unidirectional flow Low pressure system going against gravity Valves help prevent backflow LO1,2  Venous Pump Possible for large volumes of blood to become trapped in lower extremity due to high capacity of veins Normally blood pooling is prevented by a venous pump Aid in ensuring continued vascular resistance LO1,2  Venoconstriction Vascular smooth muscle is tethered to collagen Low pressure = folded collagen High pressure = unfolded collagen Smooth muscle contraction is stimulated by the SNS This will limit the veins ability to distend LO1,2  What determines blood flow through the vasculature? RESISTANCE Resistance: A measure of how “resistant” vasculature is to blood flow. Why is it important? It ensures proper blood flow Blood is not going to move through the vasculature unless forced to by applied pressure LO3  What is the source of the resistance? Poiseuille Law FLOW 1. Vessel Radius (r) Primary determinant of vascular resistance 2. Vessel Length (L) Inversely related to blood flow 3. Blood Viscosity (n) - constant Measured relative to water Major impact: RBC Electrolytes http: //www. ca i.md. chula. ac. th/l ess on/le sson4711/ima ge s/1poi seuil le_ la w.jpg Proteins - Plasma proteins LO3  Why is maintaining steady blood flow important? Clinical Connection: RBC will aggregate in the vasculature if flow is inappropriately slowed Perfusion issues, Atrial Fib, Heart Valve replacement Aggregates lead to thrombosis formation – blood clots that adhere to the vessel wall Thrombi can break loose to form emboli, which can get stuck in small vasculature https://up lo ad.wi kim edi a.org/wi kip edi a/co mmon s/th umb /2/21 /Deep _ve in _throm bosi s_o f_ the_ rig ht_l eg.jpg/12 00p x-Deep _ve in _throm bosi s_o f_ the_ rig ht_l eg.jpg Deep Vein Thrombosis Pulmonary Embolism  Acute Control of Blood Flow – Summary Slide How do local mediators impact vascular flow? Vasoconstrictors Vasodilators Receptor: a1 Receptor: B2 1. Ach 1. Nitric Oxide 2. NE 2. EDHF 3. Endothelins 3. Increase in tissue metabolism 1. Why? 1. Increase waste/nutrients need to be removed from the area 4. Decreased O2 LO6  Local Mediators of Vascular Control Two broad classes of local control mechanisms – Metabolic and Myogenic 1. Metabolic Metabolic byproducts released by cells include: Adenosine, Lactate, K+, H+, CO2 Byproducts increased as activity of tissue increases Ultimately results in increased blood flow LO6  Local Mediators of Vascular Control Two broad classes of local control mechanisms – Metabolic and Myogenic 2. Myogenic (***Not Intuitive***) Resistance vessels constrict reflexively to increases in intraluminal pressures Mediated by VSMC Ca++ channels activated by stretching ht tp:/ /www.au stin cc.edu/ apreview/N urs ingPics /V ascularPics/ Pict ure24.jpg LO6  Local Mediators of Vascular Control: Role of Endothelium Endothelium is a thin layer of cells that lines the interior (luminal) side of all blood vessels Importance of the endothelium: Maintain vascular permeability (barrier function) Regulate blood flow and vascular reactivity Numerous vasoregulatory factors Inflammation and Immunity are produced by endothelium Regulate Coagulation ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Cell growth Serves as an intermediary for a number of vasoactive compounds LO6,7  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: NO Highly localized effect due to short half-life Raises cGMP, causes cGMP- dependent kinase to phosphorylate and inhibit myosin light-chain kinase Phosphorylates SERCA to increase activity – causing intracellular Ca++ to fall Mediates the response of many vasodilators LO6,7  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: NO *note role of Ach LO6,7 http://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-14/14_14A.jpg  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: Prostaglandins Endothelium is an important source of Prostaglandins Family of both vasodilators and vasoconstrictors Depends on which PG type and which receptor LO6,7  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: Prostaglandins PGE (PGE1, PGE2, PGE3 ) PGF (PGF1, PGE2A, PGF3A ) PGI2 FYI ONLY LO6,7 http://physiologyonline.physiology.org/content/nips/26/3/156/F1.large.jpg  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: EDHF “Endothelium-Derived Hyperpolarizing Factor” Vasodilator Opens K+ channels in the PM of VSMC Leads to hyperpolarization that limits Ca++ permeability Intracellular Ca++ falls LO6,7 http://clinicalgate.com/wp-content/uploads/2015/06/c00004_f004-004-9781455753048.jpg  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 ↓ 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 Endothelial Control of Blood Flow: Endothelins Potent vasoconstrictor Synthesized and released by endothelial cells in response to numerous factors: Ang-II Trauma Hypoxia Binds ETA receptors on VSMC Triggers intracellular Ca++ release via IP3 pathway LO6,7  What’s Next? How does the blood flow to the brain remain constant despite changes in blood pressure? What’s the principle of autoregulation of blood flow?