1. به نام خدا
Blood circulation
dr. Radmanesh

2. Regulation of Peripheral Blood Flow
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4. Regulation of Peripheral Blood Flow
Intrinsic (Locally in the tissues)
Metabolic Factors
Endothelial Factors
Extrinsic
nervous system
Humorally
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5. Intrinsic Control of Local Blood Flow: (Acute Control of Local Blood Flow) Metabolic Factors
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7. Acute Control of Local Blood Flow
Hypoxia
Tissue metabolites and ions
Adenosine
Potassium ions
Carbon dioxide
Hydrogen ion
Lactic acid
Inorganic phosphate
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8. Hypoxia
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9. 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
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10. Local Changes in Metabolism (O2) (Oxygen demand theory)
tissues
extracellular
fluid
oxygen
blood flow
capillaries
arteriole
6. Increased blood flow
7. Increased O2 delivery
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11. vasomotion
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12. 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
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13. Examples of Metabolic Control of Local Bloodflow
Active Hyperemia
Reactive Hyperemia
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14. Active Hyperemia
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16. Active Hyperemia
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18. Autoregulation of bloood flow
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19. Autoregulation of blood flow
Metabolic Theory
Myogenic theory
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20. Intrinsic Control of Local Blood Flow: 2:Endothelial Factors
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21. The endothelium plays an active role in regulating the microcirculation
Nitric Oxide (NO)
Prostacyclin
Endothelin
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22. Nitric Oxide (EDRF) endothelium derived relaxing factor Rapid flow of blood through the arteries and arterioles causes increase in the release of nitric oxide
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23. Synthesis of Nitric Acid
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24. Contd…
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27. 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.
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28. 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
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29. The Action of Nitric Oxide on Blood Vessels
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30. Synthesis of Nitric Oxide
Kinase
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31.  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)
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32. Endothelin Synthesized by endothelium Potent vasoconstrictor
Other actions:
Increased aldosterone secretion
Increased cardiac inotropy and chronotropy
Releases atrial natriuretic peptide
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36. Synthesis of Endothelin
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38. Signal Transduction Mechanisms regulating VSM
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43. Long-Term Blood Flow Regulation
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44. Mechanism of Long-Term Regulation
Change in “Tissue Vascularity ”
Role of Oxygen in Long-Term Regulation
Development of Collateral Circulation
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45. 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

46. 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).
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47. 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
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48. Hypoxia-inducible factors
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49. Recruitment of capillaries by an implanted tumor
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Figure 13.32a The Biology of Cancer (© Garland Science 2007)

50. 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
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51. B. Humoral regulation of cardiovascular system
1. Renin - angiotension system.
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52. Renin-angiotensin system
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53. 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
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54. Renin-angiotensin vasoconstrictor mechanism for arterial pressure
control.
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60. Antidiuretic hormone (vasopressin)
Synthesis in supraoptic nucleus
and paraventricular nucleus.
Store in (neurohypophysis).
Release ADH to blood stream.
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62. Action : V1 receptor: constriction of blood
vessel increase in blood pressure.
V2 receptor: reabsorption of H2O
from collecting duct.
Dehydration, hemorrhage:↑ADH
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63. The Effects of ADH on the distal collecting tubules and Collecting Ducts
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Figure 26.15a, b

64. Formation of Water Pores: Mechanism of Vasopressin Action
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65. Facultative water reabsorption
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66. 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.
Dr. Bolliger Kanas University Medical Center 1999
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68. 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.
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69. Bradykinin
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71. Eicosanoid
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73. Epinephrine(adrenaline EP) norepinephrine (noradrenaline NE)
Origin: adrenal medulla.
Secretion: EP 80%, NE 20%.
dr. Radmanesh

74. 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.
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75. nervous system
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80. Continuous Partial Constriction of the Blood Vessels Is Normally Caused by Sympathetic Vasoconstrictor Tone.
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83. Reflex Control of Heart Rate
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84. Modulation of Cardiac Contractions
Figure 14-30
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94. 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
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95. stretch receptors called low-pressure receptors.
Atrial and Pulmonary Artery Reflexes That Help Regulate Arterial Pressure
stretch receptors called
low-pressure receptors.
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96. 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.
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97. 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.
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98. 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
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99. (the Bainbridge Reflex )
Atrial Reflex Control of Heart Rate
(the Bainbridge Reflex )
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101. 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
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102. 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
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103. Cushing Reaction
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104. Oscillation of the CNS Ischemic Response
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105. Abdominal Compression Reflex
Increased Cardiac Output and Arterial Pressure Caused by Skeletal Muscle Contraction During Exercise
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