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LOCAL CONTROL OF BLOOD FLOW LEARNING OBJECTIVES: At the end of the tutorial, the student should be able to: Describe the intrinsic regulation of blood flow. Describe the vasodilator and oxygen lack theories. Tell us the mechanisms of Autoregulation. Give examples of acute metabolic control of local blood flow. LECTURE OUTLINE: LOCAL OR INTRINSIC REGULATION: OF BLOOD FLOW: Tissues and organs of the body are able to intrinsically regulate, to varying degree, their own blood supply in order to meet their metabolic and functional needs. This is termed local or intrinsic regulation of blood flow. TISSUE NEEDS FOR BLOOD FLOW INCLUDE: 1. Delivery of oxygen to the tissues 2. Delivery of nutrients, such as glucose, amino acids, and fatty acids 3. Removal of carbon dioxide and hydrogen ions from the tissues. 6. Transport of hormones and other substances to the different tissues. MECHANISMS OF BLOOD FLOW CONTROL: Local blood flow control can be divided into two phases: ACUTE CONTROL AND LONG-TERM CONTROL. ACUTE CONTROL: Achieved by rapid changes in local vasodilation/vasoconstriction of the arterioles (seconds to minutes) to provide very rapid maintenance of appropriate local tissue flow. LONG-TERM BLOOD FLOW REGULATION: Long-term control means slow, controlled changes in flow over a period of days, weeks, or even months. These changes come about as a result of an increase or decrease in the physical sizes and numbers of actual blood vessels supplying the tissues. ACUTE CONTROL OF LOCAL BLOOD FLOW: • Increases in tissue metabolism lead to increases in blood flow. • Decreases in oxygen availability to tissues increases tissue blood flow. Theories for the regulation of local blood flow: (1) VASODILATOR THEORY AND (2) OXYGEN LACK THEORY. VASODILATOR THEORY FOR ACUTE LOCAL BLOOD FLOW REGULATION: Vasodilator substances are: o Adenosine, o Carbon dioxide, o Adenosine phosphate compounds, o Histamine, o Potassium ions, and o Hydrogen tons. The greater the rate of metabolism or the less the availability of oxygen or some other nutrients to a tissue, the greater the rate of formation of vasodilator substances in the tissue cells. These then diffuse through the tissues to the precapillary sphincters to cause dilation. The vasodilator substance is released from the tissue mainly in response to oxygen deficiency OXYGEN LACK THEORY FOR LOCAL BLOOD FLOW CONTROL: In the absence of adequate oxygen, blood vessels simply relax and therefore naturally dilate. Increased utilization of oxygen in the tissues as a result of increased metabolism could decrease the availability of oxygen to the smooth muscle fibers in the local blood vessels causing location vasodilation. EXAMPLES OF ACUTE METABOLIC CONTROL OF LOCAL BLOOD FLOW: REACTIVE HYPEREMIA: When the blood supply to a tissue is blocked and then is unblocked, blood flow through the tissue usually increases immediately. Lack of flow sets into motion all of those factors that cause vasodilation. ACTIVE HYPEREMIA: When any tissue becomes highly active, the rate of blood flow through the tissue Increases. AUTOREGULATION: The capacity of the tissues to regulate their own blood is referred to as Autoregulation. TWO THEORIES: 1. MYOGENIC THEORY OF AUTOREGULATION. 2 .METABOLIC THEORY OF AUTOREGULATION. 1. MYOGENIC THEORY OF AUTOREGULATION: Muscle responds to tension in the vessel wall. LAW OF LAPLACE: o The wall tension is proportionate to the distending pressure times the radius of the vessel. 2. METABOLIC THEORY OF AUTOREGULATION: Vasodilator substances tend to accumulate in active tissues; these metabolites also contribute to Autoregulation. When blood flow decreases, they accumulate and the vessel dilates, when blood flow increases, they tend to wash away. MECHANISM FOR DILATING UPSTREAM ARTERIES WHEN MICROVASCULAR BLOOD FLOW INCREASES—The Endothelium-Derived Relaxing Factor (Nitric Oxide): o When blood flow through a microvascular portion of the circulation increases, this secondarily entrains another mechanism that dilates the larger arteries as well. o Rapid flow of blood through the arteries/arterioles causes shear stress on the endothelial cells → Contorts endothelial cells → Increase in the release of nitric oxide → Relaxation of blood vessels. LONG TERM BLOD FLOW REGULATION: • Long-term local blood flow regulation occurs by changing the degree of vascularity of tissues (size and number of vessels). • Oxygen is an important stimulus for regulating tissue vascularity. The regulatory mechanism controlling blood vessel growth according to a tissue's need for oxygen. • For example: increased vascularity in tissues of animals that live at high altitudes, where the atmospheric oxygen is low. Importance of Vascular Endothelial Growth Factor in Formation of New Blood Vessels A dozen or more factors that increase growth of new blood vessels have been found, almost all of which are small peptides. Angiogenic factors promote new vessel growth by causing new vessels to sprout from other small vessels. Blood vessels can also be made to disappear when not needed. A diagram illustrating the role of VEGF in the formation of new blood vessels that support tumor growth. Development of Collateral Circulation—A phenomenon of Long-term Local Blood Flow Regulation: • A new vascular channel usually develops around the blocked artery or vein and allows at least partial resupply of blood to the affected tissue. • E.g. development of collateral blood vessels occurs after thrombosis of one of the coronary arteries. REFERENCES: • TEXT BOOK OF MEDICAL PHYSIOLOGY GUYTON & HALL. 11TH EDITION Pg # 191-199