Fall 2024 Lecture Notes - Vascular Physiology

Lecture #26: Vascular Phys II & Special Circulations Julia M. Hum, Ph.D. Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm [email protected]  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡...

Lecture #26: Vascular Phys II & Special Circulations Julia M. Hum, Ph.D. Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm [email protected]  ↑ 𝑪𝑎𝑙𝑐𝑖𝑢𝑚 = 𝑉𝑎𝑠𝑜𝒄𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 L25 ↓ 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  Fluid Movement in Capillary Beds – Summary Slide Sudden Loss of Blood Volume Heart Failure During a sudden loss of blood, pressure preferentially drops dramatically in the venous system Decreases Pc of venous system In heart failure, fluid backs up into the venous system ∏c > Pc Fluid is ”pulled in” from the interstitium into the This raises the pressure (Pc) in the venous system Pc > ∏c throughout the whole system blood vessel to overcome the blood loss Fluid is going to be “pushed out” of the capillaries into the LO5 interstitium → edema  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?  L26: Learning Objectives 1. How does the blood brain barrier protect the brain? 2. Compare and contrast the sensory and secretory CVOs 3. Define autoregulation and relate its principle to cerebral blood flow 4. Detail the relationship of Pco2 and cerebral blood flow 5. What do regional pattern changes in cranial blood flow mean? 6. How do blood clots lead to a stroke? 7. Describe the skeletal vasculature 8. Compare and contrast local and central controls of skeletal muscle circulation 9. What’s the difference between isometric and isotonic muscle exercise and its impact on hyperemia? Unless otherwise noted, figures in today’s lecture are from: Lippincott Illustrated Reviews: Physiology 1e Wilson (Ch. 21) Circulation Needs Anatomical Considerations Relationship of blood flow to organ function Regulation of blood flow Local metabolic control Neural control Responses to pressure Autoregulatory capability “Special” Circulations Cerebral Hepatic Skeletal Muscle Coronary Splanchnic Renal  Cerebral Circulation Brain ~2% of body weight, but needs 15% of cardiac output (CO) Demand reflects the brain's high rate of metabolism Brain has few metabolic stores = brain is highly reliant on the cerebral circulation for normal function LO1  Blood Brain Barrier Characteristic feature of the brain’s vasculature Prevents solutes in the lumen of the capillaries from having direct access to the brain extracellular fluid Why many drugs that act on other organs or vascular beds have no effect on the brain LO1  Blood Brain Barrier Protects the brain from abrupt changes in the blood composition May become damaged in regions of the brain that are injured, infected, or occupied by tumors LO1  Blood Brain Barrier - Structure Cerebral capillaries deny passage by most of the ”traditional routes” used by capillaries for transport Pinocytosis – rare! Bulk flow - no fenestrations, and adjacent endothelial cells are fused together by tight junctions = blocks bulk flow and diffusion of ions and water Diffusion - Lipid-soluble molecules (O2 and CO2) can readily diffuse across the capillary wall LO1  Blood Brain Barrier - Structure Transporters - glucose, amino acids, choline, nucleotides, and fatty acids Channels, exchangers, and pumps – ions and protons Aquaporins - water to migration based on osmolarity LO1  Blood Brain Barrier – Chemical Barrier Cerebral capillary endothelial cells contain: Monoamine oxidase Peptidase Acid hydrolase Other enzymes Enzymes capable of degrading hormones, NTs, and other biologically active molecules Provide a chemical barrier to bloodborne factors LO1  Blood Brain Barrier - CVOs Six CVOs - where the BBB is interrupted to allow cerebral neurons to interact with the circulation directly Highly vascularized area with fenestrations, that allow blood to pass through more slowly Sensory CVOs - hypothalamus and brainstem Contain neuronal cell bodies that are sensitive to numerous factors (Na+, Ca2+, angiotensin II, antidiuretic hormone, sex hormones, and feeding) Axons project to hypothalamic areas Secretory CVOs – hypothalamus, posterior LO2 pituitary, pineal gland  Cerebral Blood Flow Autoregulation Protects the Brain The cerebral circulation maintains steady flow rates when mean arterial pressure is varied from ~60–150 mm Hg Much wider pressure range than in other vascular beds LO3  Cerebral Blood is Sensitive to Pco2 Cerebral resistance vessels dilate in response to the same metabolic factors that allow for local control in other circulations BUT are particularly sensitive to changes in Pco 2 Small increases in Pco 2 cause profound vasodilation Decreases in Pco 2 cause vasoconstriction LO4  Regional Changes in Cranial Blood Flow LO5 Clinical Connection: Stroke In 2018, 1 in every 6 deaths from cardiovascular disease was due to stroke Someone in the United States has a stroke every 40 seconds Every 4 minutes, someone dies of stroke About 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked Stroke is a leading cause of serious long-term disability Stroke reduces mobility in more than half of stroke survivors age 65 and over  Clinical Connection: Stroke Pathophysiology Poor blood flow to the brain causing cell death – usually caused by thrombosis or emboli Leading causes: High blood pressure Obesity High blood pressure LO6 Clinical Connection: Stroke Prevention – PREVIEW! Minimize clots Lower BP Lower cholesterol  Skeletal Muscle Circulation Skeletal muscles are highly dependent on the vasculature to deliver O2 and nutrients and to carry away heat, CO2, and other metabolic waste products Facilitated by an unusually dense capillary network LO7  Skeletal Muscle Circulation Skeletal vasculature is supplied by superficial feed arteries that branch multiple times within the muscle groups until they become terminal arterioles Each arteriole gives rise to numerous capillaries that travel parallel to individual muscle fibers Each fiber is typically associated with three or four capillaries Reduces the range over which O2 must diffuse to reach the innermost myofibrils LO7  Skeletal Muscle – Regulation: Local vs Central Local controls Resting muscle - small percentage of capillaries are perfused because the terminal arterioles (resistance vessels) are constricted Active muscle - metabolite concentrations rise, the arterioles dilate and previously inactive capillaries are filling with blood LO8  Skeletal Muscle – Regulation: Local vs Central Central controls SNS fibers - resting tone maintains flow at minimal levels When arterial pressure falls, SNS activity increases as a normal part of a reflex At rest SNS activation decreases flow to a resting muscle During exercise Local metabolites dominate vascular control Flow through the skeletal vasculature may rise to 25L/min (500% of resting CO) LO8  Skeletal Muscle – Extravascular Compression Contracting muscles compress the blood vessels that run between Active Isotonic exercises (jogging, swimming) involve rhythmic cycles of contraction and relaxation and produce a phasic flow pattern Active Hyperemia - increase in organ blood flow associated with increased metabolic activity LO9  Skeletal Muscle – Extravascular Compression Contracting muscles compress the blood vessels that run between Isometric contractions (lifting a weight) can inhibit flow for several seconds Reactive Hyperemia – temporary increase in blood volume to an area that was occluded LO9 https://thoracickey.com/wp-content/uploads/2016/12/image00403.jpeg  What’s Next? Dr. Skinner joins our course on Monday and Wednesday The topics include anticoagulants and antiplatelets If you missed Dr. Skinner’s clinical case check it out over the weekend for a terrific primer to his material next week!