13.4 Lecture Blood Flow and Oxygen Availability

• Blood flow varies greatly depending on the tissue and its needs.
• Kidneys receive 1100 ml/min of blood.
• Active muscles receive 750 ml/min of blood, despite having a greater mass than kidneys.
• The heart can't supply enough blood to all tissues maximally.
• Blood flow is regulated to supply tissues' minimal needs.
• Acute control of blood flow involves vasodilation or constriction of arterioles and pre-capillary sphincters.
• Long-term control (over days, weeks, or months) involves changes in the number and size of blood vessels.

Oxygen Availability and Blood Flow

• When oxygen availability decreases, blood flow increases to compensate.
• Vasodilator theory: Decreased nutrient supply or increased metabolism leads to greater formation of vasodilator substances, such as adenosine, carbon dioxide, histamine, potassium, and hydrogen.
• These substances diffuse to capillaries, pre-capillary sphincters, and arterioles, causing dilation.
• Oxygen demand theory: Oxygen is needed to cause constriction and contraction of muscles in the arterioles.
• Absence of oxygen causes blood vessels to relax and dilate.

Pre-capillary Sphincters

• These are either completely open or closed.
• The number of open or closed sphincters is proportional to the requirement for tissue nutrition.

Reactive Hyperemia

• This is the increase of blood flow to an area after blood supply is restored.
• The extra blood flow lasts long enough to repay the tissue oxygen deficit.

Active Hyperemia

• It is the increased tissue blood flow in response to activity (e.g., increased blood flow in skeletal muscle during exercise).

Blood Flow Auto-regulation

• Occurs between arterial pressures of 70 to 175.
• Blood flow increases only 20-30% even with a 150% increase in arterial pressure.
• Metabolic theory: Excess flow washes out vasodilators, causing arterioles to constrict.
• Myogenic theory: Stretching of small blood vessels causes vascular smooth muscle to contract decreasing blood flow back to normal.
• Stretch rapidly increases calcium ion entry into cells, causing contraction.
• The myogenic mechanism prevents excess stress on blood vessels.
• Metabolic factors can override the myogenic mechanism when metabolic demands increase, such as during exercise.

Blood Flow Auto-regulation in Specific Areas

• Kidneys: Controlled by tubuloglomerular feedback.
• If too much fluid enters the tubular system, the macula densa causes afferent arterioles to constrict, decreasing blood flow and fluid into the tubules.
• Brain: Increased carbon dioxide or hydrogen causes cerebral vasodilation and increased blood flow.
• Skin: Blood flow is closely linked to body temperature.

Nitric Oxide

• Most important endothelial-derived relaxing factor.
• It is a lipophilic gas released in response to chemical and physical stimuli (including shear stress).
• It has a short half-life (about six seconds).
• It activates soluble guanylate cyclase, converting cyclic guanosine triphosphate to cyclic guanosine monophosphate.
• Resulting in blood vessel relaxation.
• Release is stimulated by some vasoconstrictors, like angiotensin II, to prevent excessive vasoconstriction.
• Impaired synthesis due to damaged endothelial cells (from chronic hypertension or atherosclerosis) can contribute to excessive vasoconstriction and worsening hypertension.

Endothelin

• It is a powerful vasoconstrictor released by damaged endothelium after local vessel damage.
• Helps prevent excessive bleeding.
• Believed to contribute to vasoconstriction caused by hypertension.

Angiogenesis

• If arterial pressure remains high, new blood vessels grow over hours, days, or weeks.
• Blood flow to the tissue returns to normal.
• Occurs rapidly in new tissue or cancerous tissue, but slowly in old, established tissues.
• Vascularity is determined by the maximum level of blood flow, not the average need.
• Even a few minutes of heavy exercise daily can cause angiogenesis.
• Angiogenesis can occur in response to a blockage.
• Initially, collateral vessels dilate, allowing some collateral blood flow.
• Over weeks or months, collateral vessels grow, forming other small channels.
• Example: Collateral growth in response to partial destruction of coronary vessels.

Norepinephrine and Epinephrine

• Vessel constrictors with a dual system of control.
• Epinephrine is less powerful due to preference causing beta one stimulation.
• The sympathetic nervous system releases norepinephrine from nerve endings.
• The adrenal medulla secretes more epinephrine into the blood.

Angiotensin II

• Acts on many arterioles simultaneously.
• Increases total peripheral resistance.
• Decreases sodium and water excretion by the kidneys, increasing arterial pressure.

Vasopressin

• One of the body's most potent vascular constrictor substances.
• Formed in nerve cells in the hypothalamus and transported to the posterior pituitary gland for secretion into the blood.
• Causes massive vasoconstriction and increases water reabsorption in the renal tubules.
• Secreted in minute amounts, so it plays a small role in vascular control.

Kinins

• Including bradykinin.
• Cause powerful vasodilation and increased capillary permeability.
• They Have a short duration due to quick inactivation.

Histamine

• Released in almost every tissue when damaged, inflamed, or subject to an allergic reaction.
• Derived from mast cells in tissue and basophils in blood.
• Powerful vasodilator and increases capillary permeability.

Vasodilators and Vasoconstrictors

• Have little effect on long-term blood flow due to auto-regulation.