به نام خدا Blood circulation dr. Radmanesh

Regulation of Peripheral Blood Flow dr. Radmanesh

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Regulation of Peripheral Blood Flow Intrinsic (Locally in the tissues) Metabolic Factors Endothelial Factors Extrinsic nervous system Humorally dr. Radmanesh

Intrinsic Control of Local Blood Flow: (Acute Control of Local Blood Flow) Metabolic Factors dr. Radmanesh

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Acute Control of Local Blood Flow Hypoxia Tissue metabolites and ions Adenosine Potassium ions Carbon dioxide Hydrogen ion Lactic acid Inorganic phosphate dr. Radmanesh

Hypoxia dr. Radmanesh

Local Changes in Metabolism (O2) (Oxygen demand theory) tissues extracellular fluid oxygen blood flow capillaries arteriole 4. O2 levels in the ECF decrease 5. ↓ [O2] causes vascular smooth muscle to relax: vasodilation dr. Radmanesh

Local Changes in Metabolism (O2) (Oxygen demand theory) tissues extracellular fluid oxygen blood flow capillaries arteriole 6. Increased blood flow 7. Increased O2 delivery dr. Radmanesh

vasomotion dr. Radmanesh

and/or Local Changes in Blood Flow Local Changes in Metabolism (Effects of CO2) and/or Local Changes in Blood Flow  [CO2]: Vasodilation Increased Blood Flow: ↓ pH; ↑ K+; ↑ lactic acid  vasodilation dr. Radmanesh

Examples of Metabolic Control of Local Bloodflow Active Hyperemia Reactive Hyperemia dr. Radmanesh

Active Hyperemia dr. Radmanesh

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Active Hyperemia dr. Radmanesh

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Autoregulation of bloood flow dr. Radmanesh Downloaded from: StudentConsult (on 14 June 2006 12:20 PM) © 2005 Elsevier

Autoregulation of blood flow Metabolic Theory Myogenic theory dr. Radmanesh

Intrinsic Control of Local Blood Flow: 2:Endothelial Factors dr. Radmanesh

The endothelium plays an active role in regulating the microcirculation Nitric Oxide (NO) Prostacyclin Endothelin dr. Radmanesh

Nitric Oxide (EDRF) endothelium derived relaxing factor Rapid flow of blood through the arteries and arterioles causes increase in the release of nitric oxide dr. Radmanesh

Synthesis of Nitric Acid dr. Radmanesh

Contd… dr. Radmanesh

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NO NO bind to Fe 2+ haem group Active Guanylate Cyclase of Guanylyl Cyclase Increased cGMP Increased intracellular Ca 2+ Relaxes muscle Dilating the vessel & lowering B.P. dr. Radmanesh

Nitric Oxide Signaling Relaxation of smooth muscle 1) Stimulated nerve releases Acetylcholine(ACh) at Nerve terminal 2) ACh binds to receptors on endothelial cells Smooth muscle cell blood vessel wall 4) NO diffuses across membranes GTP cGMP Arg NO NO 3) Activate NO synthase 5) NO binds to Guanylyl cyclase dr. Radmanesh

The Action of Nitric Oxide on Blood Vessels dr. Radmanesh

Synthesis of Nitric Oxide Kinase dr. Radmanesh

 Endotoxin (a bacterial lipopolysaccyhaaride) Bacterial Infection  Endotoxin (a bacterial lipopolysaccyhaaride)  Activates NOS in macrophages  Produces NO  vasodilation  ↓ BP  Death from Septic Shock (50-70% mortality) dr. Radmanesh

Endothelin Synthesized by endothelium Potent vasoconstrictor Other actions: Increased aldosterone secretion Increased cardiac inotropy and chronotropy Releases atrial natriuretic peptide dr. Radmanesh

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Synthesis of Endothelin dr. Radmanesh

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Signal Transduction Mechanisms regulating VSM dr. Radmanesh

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Long-Term Blood Flow Regulation dr. Radmanesh

Mechanism of Long-Term Regulation Change in “Tissue Vascularity ” Role of Oxygen in Long-Term Regulation Development of Collateral Circulation dr. Radmanesh

Angiogenesis: Sprouting of cells from mature endothelial cells of the vessel wall (secretion of proteases, resolution of Basal lamina, migration towards Chemotactic gradient, proliferation, Tube formation) VEGF is factor largely specific for endothelial cells, bFGF can also induce, not specific for EC) dr. Radmanesh

Role of Oxygen in Lon Term Regulation increased vascularity in tissues of animals that live at high altitudes, where the atmospheric oxygen is low. A second example is that fetal chicks hatched in low oxygen have up to twice as much tissue blood vessel conductivity as is normally true. This same effect is also dramatically demonstrated in premature human babies put into oxygen tents for therapeutic purposes (retrolental fibroplasia). dr. Radmanesh

vascular endothelial growth factor(VEGF) fibroblast growth factor Importance of Vascular Endothelial Growth Factor in Formation of New Blood Vessels vascular endothelial growth factor(VEGF) fibroblast growth factor angiogenin dr. Radmanesh

Hypoxia-inducible factors dr. Radmanesh

Recruitment of capillaries by an implanted tumor dr. Radmanesh Figure 13.32a The Biology of Cancer (© Garland Science 2007)

Development of Collateral Circulation When an artery or a vein is blocked , a new vascular channel usually develops around the blockage. The first stage in this process is dilation of small vascular loops that already connect the vessel above the blockage to the vessel below. both acute and long-term local blood flow control, the acute control being rapid neurogenic and metabolic dilation The most important example of the development of collateral blood vessels occurs after thrombosis of one of the coronary arteries dr. Radmanesh

B. Humoral regulation of cardiovascular system 1. Renin - angiotension system. dr. Radmanesh

Renin-angiotensin system dr. Radmanesh

Renin-Angiotensin-Aldosterone System Angiotensin II Stimulates aldosterone production Stimulates ADH secretion from pituitary Highly potent vasoconstrictor Stimulates thirst Stimulates release of catecholamines by adrenal medulla dr. Radmanesh

Renin-angiotensin vasoconstrictor mechanism for arterial pressure control. dr. Radmanesh

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Antidiuretic hormone (vasopressin) Synthesis in supraoptic nucleus and paraventricular nucleus. Store in (neurohypophysis). Release ADH to blood stream. dr. Radmanesh

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Action : V1 receptor: constriction of blood vessel increase in blood pressure. V2 receptor: reabsorption of H2O from collecting duct. Dehydration, hemorrhage:↑ADH dr. Radmanesh

The Effects of ADH on the distal collecting tubules and Collecting Ducts dr. Radmanesh Figure 26.15a, b

Formation of Water Pores: Mechanism of Vasopressin Action dr. Radmanesh

Facultative water reabsorption dr. Radmanesh

Dr. Bolliger Kanas University Medical Center 1999 The basic feedback loop is shown in this slide. An increase in ECF osmolality stimulates the osmoreceptive cells in the two hypothalmic nuclei. The cell bodies of these neurons respond to stretch and their firing rate is directly proportional to it. As we will see soon, these neuroendocrine cells are also innervated by nerve tracks coming from the medulla. These nerve tracks receive input from the baroreceptors in and around the great vessels of the heart. When firing rate of the neuroendocrine cells increase, ADH is released from the post synaptic nerve terminals in the posteriour pituitary. The half life of ADH is only about 20 min. This allows the effect of the hormone to be rapidly present and rapidly cease when it is no longer needed. This is a very tightly regulated hormone. The figure implies that ADH acts on the CCD and Medullary collecting ducts to increase water reaborption. As ADH levels increase, urine volume decreases and urine osmolality increases. http://www2.kumc.edu/ki/physiology/course/six/6_1.htm Dr. Bolliger Kanas University Medical Center 1999 dr. Radmanesh

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Atrial natriuretic peptide (ANP) Action: vasodilation, ↓cardiac output ↓HR ↓extracellular fluid volume: ↑excretion of water and Na+ ↓release of renin and aldosterone Factors of releasing ANP: ↑atrial blood volume. dr. Radmanesh

Bradykinin dr. Radmanesh

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Eicosanoid dr. Radmanesh

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Epinephrine(adrenaline EP) norepinephrine (noradrenaline NE) Origin: adrenal medulla. Secretion: EP 80%, NE 20%. dr. Radmanesh

similar to that of sympathetic nerve. Effect: similar to that of sympathetic nerve. (1)Heart: positive chronotropic and inotropic effect. (2)Blood vessels: α-adrenergic receptor: vasoconstriction. β-adrenergic receptor: vasodilation. dr. Radmanesh

nervous system dr. Radmanesh

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Continuous Partial Constriction of the Blood Vessels Is Normally Caused by Sympathetic Vasoconstrictor Tone. dr. Radmanesh

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Reflex Control of Heart Rate dr. Radmanesh

Modulation of Cardiac Contractions Figure 14-30 dr. Radmanesh

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Control of Arterial Pressure by the Carotid and Aortic Chemoreceptors The chemoreceptors are chemosensitive cells sensitive to oxygen lack, carbon dioxide excess, hydrogen ion excess dr. Radmanesh

stretch receptors called low-pressure receptors. Atrial and Pulmonary Artery Reflexes That Help Regulate Arterial Pressure stretch receptors called low-pressure receptors. dr. Radmanesh

low-pressure receptors play an important role, especially in minimizing arterial pressure change if 300 milliliters of blood suddenly are infused into a dog with all receptors intact, the arterial pressure rises only about 15 mm Hg. With the arterial baroreceptors denervated, the pressure rises about 40 mm Hg. If the low-pressure receptors also are denervated, the pressure rises about 100 mm Hg. dr. Radmanesh

Atrial Reflexes That Activate the Kidneys—The “Volume Reflex. Stretch of the atria also causes significant reflex dilation of the afferent arterioles in the kidneys glomerular capillary pressure to rise, with resultant increase in filtration of fluid into the kidney tubules And still other signals are transmitted simultaneously from the atria to the hypothalamus to decrease secretion of antidiuretic hormone. dr. Radmanesh

Atrial stretch caused by increased blood volume also elicits a hormonal effect on the kidneys— release of atrial natriuretic peptide that adds still further to the excretion of fluid in the urine and return of blood volume toward normal dr. Radmanesh

(the Bainbridge Reflex ) Atrial Reflex Control of Heart Rate (the Bainbridge Reflex ) dr. Radmanesh

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Central Nervous System Ischemic Response it can elevate the mean arterial pressure for as long as 10 minutes sometimes to as high as 250 mm Hg. The degree of sympathetic vasoconstriction caused by intense cerebral ischemia is often so great that some of the peripheral vessels become totally or almost totally occluded. The kidneys, for instance, often entirely cease their production of urine because of renal arteriolar constriction in response to the sympatheticdischarge dr. Radmanesh

it does not become significant untilthe arterial pressure falls far below normal, down to 60 mm Hg and below, reaching its greatest degree of stimulation at a pressure of 15 to 20 mm Hg dr. Radmanesh

Cushing Reaction dr. Radmanesh

Oscillation of the CNS Ischemic Response dr. Radmanesh

Abdominal Compression Reflex Increased Cardiac Output and Arterial Pressure Caused by Skeletal Muscle Contraction During Exercise dr. Radmanesh