Local & Humoral Control of Blood Flow

Local Metabolism

as blood flow increases, rate of metabolism increases

Lack of Glucose

in perfusing blood can cause local tissue vasodilation

Skin

regulated by CNS through sympathetic system

Lack of Amino Acids/Fatty Acids

same as lack of glucose but have not been studied adequately

Angiogenic Factors

-VEGF -fibroblast growth factor -angiogenin

Acute Control

-achieved by rapid changes in local vasodilation or vasoconstriction of the arterioles, metarterioles, and pre capillary sphincters, occurring within sec to minutes to provide very rapid maintenance of appropriate local tissue blood flow

Atrial Reflex

-activates kidneys -dilation of afferent arterioles of kidneyes -signals are transmitted simultaneously from atria to hypothalamus to decrease secretion of ADH (decreased afferent arteriolar resistance in kidney causes glomerular capillary pressure to rise with resultant increase in filtration of fluid into kidney tubules; diminution of ADH diminishes the reabsorption of water from tubules

Circulatory Reflex

-after baroreceptor signals have entered tracts solitaires of medulla, secondary signals inhibit the vasoconstrictor center of the medulla and excite vagal parasympathetic center -net effect: 1. vasodilation of the veins and arterioles throughout the peripheral circulatory system 2. decreased HR and strength of heart contraction

Oyxgen Availability

-as blood flow increases, arterial oxygen saturation decreases -whenever the availabilty of O2 to tissues decreases such as at a high altitude or pneumonia then blood flow through tissues increases markedly

Bainbridge Reflex

-atrial reflex control of HR -increased atrial volume>atrial pressure>stretch the sinus node> increase HR, CO, and arterial pressure

Local Tissue Blood Flow Control

-blood flow to each tissue usually is regulated at min level that will supply tissue requirements -by controlling ___ in such an exact way, tissues almost never suffer from O2 nutritional deficiency and workload on heart is kept at a min EX) blood flow is always controlled at a level only slightly more than required to maintain full tissue oxygenation BUT NO MORE THAN THIS

NO and cGMP Degradation

-degraded by phosphodiesterase-5 (PDE-5) -by inhibiting PDE-5, drugs such as Sildenafil can cause enhanced dilation of blood vessels such as in case of penile erection

Vascularity Changes

-determined by: max blood flow need, not by ave need -EX) during heavy exercise the need for the whole body blood flow often increases to six to eight times the resting blood flow. this great excess of flow may not be required for more than a few min a day but its enough to increase VEGF

Sympathetic Vasodilator

-effect is believed to be caused by epinephrine exciting specific beta-adrenergic receptors in muscle vasculature

EDCF (Endothelial-Derived Constricting Factors)

-endothelin: releases endothelin-1 (ET-1), a 21 amino acid peptide -requires only nanogram quantities to cause powerful vasoconstriction -ET-1 present in endothelial cells of all or most blood vessels but greatly increases when the vessels are injured -usual stimulus for release is damage to the endothelium such as that caused by crushing tissues or injecting a traumatizing chemical into blood vessel. after severe blood vessel damage, release of local endothelia and subsequent vasoconstriction helps to prevent extensive bleeding from arteries as large as 5mm in diameter that might have been torn open by crushing injury -increased ER-1 contribute to vasoconstriction when the endothelium is damaged by hypertension -drugs that block endothelia receptors have been used to treat pulmonary hypertension but have not generally been used for lowering blood pressure in patients with systemic arterial hypertension

Vasodilator Theory

-for acute local blood flow regulation -greater the rate of metabolism or the less the availability of O2 or some other nutrients to a tissue, the greater the rate of formation of vasodilator substances in tissue cells -___ substances then are believed to diffuse through the tissues to the pre capillary sphincters, met arterioles, and arterioles to cause dilation EX) adenosine, CO2, H+

Myogenic Theory

-for autoregulation -high arterial pressure>stretches the vessel>causes reactive vascular constriction to reduce blood flow nearly back to normal -low arterial pressure>degree of stretch of vessels is less so that the smooth muscle relaxes>reducing vascular resistance and help return blood flow to normal

Metabolic Theory

-for autoregulation -when arterial pressure becomes too great, the excess flow provides too much O2 and too many other nutrients to tissues and "washes out" the vasodilators released by tissues -these nutrients (esp O2) and decreased tissues levels of vasodilators then cause the blood vessels to constrict and flow to return nearly to normal despite the increased pressure

VEGF (Vascular Endothelial Growth Factor)

-generation of new blood vessels

Skeletal Nerves and Muscles

-increases CO and arterial pressure -abdominal compression reflex -skeletal muscle contraction during exercise -respiratory waves in arterial pressure

Baroreceptor Reflexes

-initiated by stretch receptors located at specific points in walls of several large systemic arteries -rise in arterial pressure stretches them and causes them to transmit signals into the CNS -"feedback" signals are then sent back through the ANS to the circulation to reduce arterial pressure downward toward normal level

Vasodilator Area

-located bilaterally in anterolateral portions of lower medulla -fibers from theses neurons project upward to vasoconstrictor area; they inhibit vasoconstrictor activity of this area thus causing vasodilation

Vasoconstrictor Area

-located bilaterally in anterolateral portions of upper medulla -neurons originating in this area distribute their fibers to all levels of spinal cord where they excite preganglionic vasoconstrictor neurons of the sympathetic nervous system

Sensory Area

-located bilaterally in tracts solitarius in posterolateral portions of medulla and lower pons -neurons in this area receives ___ nerve signals from circulatory system mainly through the vagus and glossophayngeal nerves and output signals from this area helps to control activities of both vasoconstrictor and vasodilator areas of the vasomotor center thus providing "reflex" control of many circulatory functions (baroreceptor reflex)

Rapid Control of Arterial Pressure

-most arterioles of systemic circulation are constricted>increases total peripheral resistance>increasing arterial pressure -veins are strongly constricted> increasing the volume of blood in heart chambers>heart to beat with far greater force>increases arterial pressure -heart itself is directly stimulated by ANS, further enhancing cardiac pumping and increase arterial pressure: increase in HR, increase contractile force of heart muscle, increasing capability of heart to pump larger volumes of blood

EDRF (Endothelial-Derived Relaxing Factors)

-nitric oxide: lipophilic gas that is released from endothelial cells in response to a variety of chemical and physical stimuli -NOS (nitric oxide sythase) enzymes in endothelial cells synthesize NO from arginine and oxygen and by reduction of inorganic nitrate -has half life in blood of 6 sec -activates soluble gauntlet cyclades in vascular smooth muscle cells, resulting in conversion of cyclic guanosine triphosphate (cGTP) to cyclase guanosine monophosphate (cGMP) -activation of cGMP-dependent protein kinase (PKG) which has several actions that cause the blood vessels to relax -when blood flow through the arteries and arterioles, this causes shear stress on endothelial cells bc of viscous drag of blood against vascular walls -this stress contorts the endothelial cells in direction of flow and causes significant increase in release of NO -NO synthesis and release from endothelial cells are also stimulated by some vasoconstrictors such as angiotensin II, which bind to specific receptors on endothelial cells. increase NO release protects against excessive vasoconstriction

Sympathetic Vasoconstrictor

-norepinephrine nerve fibers: release norepinephrine (noradrenaline) that produce vasoconstriction by acting of alpha-adrenergic receptors -adrenal medulla: release norepinephrine, epinephrine in blood to produce vasoconstriction

Long Term Control

-slow, controlled changes in flow over a period of days, weeks or even months -physiology-autonomic regulation-pathophysiology -more important when BP changes are for longer duration - days to years -metabolic demands also changes -change in "tissue vasularity" -angiogenesis: large increase in # of capillaries in a rat anterior tibias muscle that stimulated electrically to contract for short periods of time ea day for 30 days, compared with unstimulated muscle in other leg of animal

Sympathetic Innervation

-small arteries/arterioles: allows sympathetic stimulation to increase resistance to blood flow and thereby to decrease rate of blood flow through the tissues -large vessels/veins: makes it possible for sympathetic stimulation to decrease volume of these vessels; this can push blood into the heart and thereby play a major role in regulation of heart pumping

Development of Collateral Circulation

-specially critical for heart and brain -people > 60 yrs develop this and thus may survive heart attacks more frequently than young subjects

Antiangiogenc Factors

-steroids -angiostatin, fragment of protein plasminogen -endostatin, peptides

Heart

-sympathetic nerve fibers innervations: increase HR, increase force and vol of blood pumping -parasympathetic innervation through the vagus nerve or originating from brain medulla; decrease HR

ANS

-sympathetic/parasympathetic: heart, blood vessels (variable depending upon distribution of receptors in vascular bed or compartment)

Brain

-tissue, oxygen, CO2 and nutrients -acute blood flow control

Kidneys

-tubuloglomerular feedback -when too much fluid filters from blood through glomerulus into tubular system, feedback signals from macula dense cause contriction of afferent arterioles

Vitamin Deficiency

-vasodilation occurs in disease beriberi where the patient has deficiencies of vitamin B substances thiamine, niacin, and riboflavin -in this disease, the peripheral vascular blood flow almost everywhere in body often increases twofold to threefold bc all these vitamins are necessary for oxygen-induced phosphorylation, which is required to produce ATP in tissue cells

CNS Control

-vasomotor center -located bilaterally mainly in reticular substance of medulla and of lower third of pons -transmits parasympathetic impulses through vagus nerves to heart -transmits sympathetic impulses through the spinal cord and peripheral sympathetic nerves to virtually all arteries, arterioles, veins

Baroreceptor Reflex System

1. "carotid baroreceptors" are transmitted through Hering's nerves to the glossopharyngeal nerves in the high next, and then to the tracts solitaires in medullary area of brain stem; increase arterial BP, increase #of impulses 2. "aortic baroreceptors" in arch of the aorta are transmitted through vagus nerves also to the same tracts solitaires of medulla